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33519678

Cognitive Dysfunction and Mortality After Carotid Endarterectomy.

Background: Carotid endarterectomy (CEA) has been associated with both postoperative cognitive dysfunction (POCD) and improvement (POCI). However, the prognostic significance of postoperative cognitive changes related to CEA is largely unknown. The aim of this study was to examine the associations between postoperative cognitive changes after CEA and long-term survival. Methods: We studied 43 patients 1 day before CEA as well as 4 days and 3 months after surgery with an extensive neuropsychological test array, and followed them for up to 14 years. POCD and POCI relative to baseline were determined with the reliable change index derived from 17 healthy controls. Associations between POCD/POCI and mortality within the patient group were studied with Cox regression analyses adjusted for confounders. Results: POCD in any functional domain was evident in 28% of patients 4 days after surgery and in 33% of patients 3 months after surgery. POCI was shown in 23% of patients at 4 days and in 44% of patients at 3 months. POCD at 3 months was associated with higher long-term mortality (hazard ratio 5.0, 95% CI 1.8-13.9, p = 0.002) compared with patients with no cognitive decline. Conclusions: Our findings suggest that POCD in a stable phase, 3 months after CEA predicts premature death. Evaluation of postoperative cognitive changes is essential, and POCD in a stable phase after CEA should prompt scrutiny of underlying factors and better adherence to therapies to prevent recurrences and to promote early intervention in imminent deterioration.

['Relander|Kristiina|K|', 'Hietanen|Marja|M|', 'Nuotio|Krista|K|', 'Ijäs|Petra|P|', 'Tikkala|Irene|I|', 'Saimanen|Eija|E|', 'Lindsberg|Perttu J|PJ|', 'Soinne|Lauri|L|']

2020

32889481

Review: Strategies for using satellite-based products in modeling PM2.5 and short-term pollution episodes.

Short-term air pollution episodes motivate improved understanding of the association between air pollution and acute morbidity and mortality episodes, and triggers required mitigation plans. A variety of methods have been employed to estimate exposure to air pollution episodes, including GIS-based dispersion models, interpolation between sparse monitoring sites, land-use regression models, optimization models, line- or area-dispersion plume models, and models using information from imaging satellites, often including land-use and meteorological variables. There has been increasing use of satellite-borne aerosol products for assessing short-term air quality events. They provide better spatial coverage, but currently at the price of low temporal coverage and rather crude spatial resolution. This is a brief review on using satellite data for modeling short-term air quality and pollution events. The review can be pursued as a practical guide for modeling air quality with satellite-based products, as it includes important questions that should be considered in both the study design as well as the model development stages. Progress in this field is detailed and includes published models and their use in environmental and health studies. Both current and future satellite-borne capabilities are covered. It also provides links to access and download relevant datasets and some example R code for data processing and modeling.

['Sorek-Hamer|Meytar|M|', 'Chatfield|Robert|R|', 'Liu|Yang|Y|']

2020

33806596

Properties of WC-10%Co-4%Cr Detonation Spray Coating Deposited on the Al-4%Cu-1%Mg Alloy.

One of the methods of local improvement of the wear resistance of aluminum alloy parts is the deposition of hard tungsten carbide-based coatings on the surfaces subjected to intense external influence. This paper is devoted to the characterization of the WC-10Co-4Cr (wt.%) coating deposited on an Al-4Cu-1Mg (wt.%) alloy by the detonation spray method. In comparison with the common thermal spray techniques like High Velocity Oxygen Fuel (HVOF) or Atmospheric Plasma Spraying (APS), the heat input delivered to the substrate during detonation spray is significantly lower, that is especially important in case of coating deposition on aluminum alloys. The paper presents the results of morphology investigation, microstructure, phase composition, microhardness, and cohesive strength of deposited carbide-based detonation spray coating. Results showed that the coating has a porosity less than 0.5% and the carbide grain refinement down to the submicron size during coating deposition was detected. According to the investigation, the variation of spraying distance from 270 to 230 mm does not influence on the coating microstructure and composition.

['Samodurova|Marina|M|', 'Shaburova|Nataliya|N|0000-0001-8339-8293', 'Samoilova|Olga|O|', 'Moghaddam|Ahmad Ostovari|AO|0000-0002-5316-3773', 'Pashkeev|Kirill|K|', "Ul'yanitckiy|Vladimir|V|", 'Trofimov|Evgeny|E|']

2021

23702104

Health outcomes and related effects of using social media in chronic disease management: a literature review and analysis of affordances.

Whilst the future for social media in chronic disease management appears to be optimistic, there is limited concrete evidence indicating whether and how social media use significantly improves patient outcomes. This review examines the health outcomes and related effects of using social media, while also exploring the unique affordances underpinning these effects. Few studies have investigated social media's potential in chronic disease, but those we found indicate impact on health status and other effects are positive, with none indicating adverse events. Benefits have been reported for psychosocial management via the ability to foster support and share information; however, there is less evidence of benefits for physical condition management. We found that studies covered a very limited range of social media platforms and that there is an ongoing propensity towards reporting investigations of earlier social platforms, such as online support groups (OSG), discussion forums and message boards. Finally, it is hypothesized that for social media to form a more meaningful part of effective chronic disease management, interventions need to be tailored to the individualized needs of sufferers. The particular affordances of social media that appear salient in this regard from analysis of the literature include: identity, flexibility, structure, narration and adaptation. This review suggests further research of high methodological quality is required to investigate the affordances of social media and how these can best serve chronic disease sufferers. Evidence-based practice (EBP) using social media may then be considered.

['Merolli|Mark|M|', 'Gray|Kathleen|K|', 'Martin-Sanchez|Fernando|F|']

2013

26708384

Wnt5a-Ror2 signaling in mesenchymal stem cells promotes proliferation of gastric cancer cells by activating CXCL16-CXCR6 axis.

Wnt5a-Ror2 signaling has been shown to play important roles in promoting aggressiveness of various cancer cells in a cell-autonomous manner. However, little is known about its function in cancer-associated stromal cells, including mesenchymal stem cells (MSCs). Thus, we examined the role of Wnt5a-Ror2 signaling in bone marrow-derived MSCs in regulating proliferation of undifferentiated gastric cancer cells. Coculture of a gastric cancer cell line, MKN45, with MSCs either directly or indirectly promotes proliferation of MKN45 cells, and suppressed expression of Ror2 in MSCs prior to coculture inhibits enhanced proliferation of MKN45 cells. In addition, conditioned media from MSCs, treated with control siRNA, but not siRNAs against Ror2, can enhance proliferation of MKN45 cells. Interestingly, it was found that expression of CXCL16 in MSCs is augmented by Wnt5a-Ror2 signaling, and that recombinant chemokine (C-X-C motif) ligand (CXCL)16 protein can enhance proliferation of MKN45 cells in the absence of MSCs. In fact, suppressed expression of CXCL16 in MSCs or an addition of a neutralizing antibody against CXCL16 fails to promote proliferation of MKN45 cells in either direct or indirect coculture with MSCs. Importantly, we show that MKN45 cells express chemokine (C-X-C motif) receptor (CXCR)6, a receptor for CXCL16, and that suppressed expression of CXCR6 in MKN45 cells results in a failure of its enhanced proliferation in either direct or indirect coculture with MSCs. These findings indicate that Wnt5a-Ror2 signaling enhances expression of CXCL16 in MSCs and, as a result, enhanced secretion of CXCL16 from MSCs might act on CXCR6 expressed on MKN45, leading to the promotion of its proliferation.

['Takiguchi|Gosuke|G|', 'Nishita|Michiru|M|', 'Kurita|Kana|K|', 'Kakeji|Yoshihiro|Y|', 'Minami|Yasuhiro|Y|']

2016

34022515

Influence of adjuvants on the amount, specificity and functional activity of antibody response to human influenza vaccine in mice.

It's been almost a century since immunologists started using adjuvants as tools to develop more effective vaccines. Despite the rising number of adjuvanted vaccines in the last decades, we still lack knowledge of the adjuvants' effects on antibody response. This study was aimed to test the effect of immunizing mice with the human Inactivated Influenza vaccine (IIV), either alone or combined with different widely used adjuvants on the specific antibody response induced. Differential levels of IgM and IgG subclasses were found with the different adjuvants tested. Higher levels of antibodies did not always correspond with a higher efficacy to interfere with the virus infectivity. Differences in neutralization properties are possibly mediated by the specificity of the repertoire of antibodies induced. The repertoire was studied using a phage display 7-mer peptide library to screen for epitopes/mimotopes recognized by serum pools from vaccinated mice. The selected phage clones included peptides that corresponded to conformational mimotopes since they have no homology with lineal sequences of the Influenza strains' proteins. Five peptides were identified as recognized by sera from mice immunized with the IIV vaccine alone, including peptides from the hemagglutinin stalk domain, and by sera from mice immunized with the vaccine plus the different adjuvants employed. Adjuvants elicited a more diverse repertoire of epitope-recognizing antibodies that recognized epitopes of the HA recombinant globular head. Mimotopes were theoretically located at the neutralizing antigenic sites of the globular head of Influenza A H1N1pdm09, Influenza A H3N2, and Influenza B hemagglutinin. This study illustrates how different adjuvants can modify the extent and quality of humoral immunity against the IIV vaccine and the effectiveness of vaccination.

['Voutssas-Lara|Juan|J|', 'Cervantes-Torres|Jacquelynne|J|', 'Hernández|Marisela|M|', 'Bobes|Raúl J|RJ|', 'Lamoyi|Edmundo|E|', 'Vázquez-Ramírez|Ricardo A|RA|', 'Mendoza|Luis|L|', 'Reyes-Barrera|Karen L|KL|', 'López-Martínez|Rogelio|R|', 'Alpuche-Solís|Ángel G|ÁG|', 'Rosales-Mendoza|Sergio|S|', 'Huerta|Leonor|L|', 'Fragoso|Gladis|G|', 'Sciutto|Edda|E|']

2021

34215539

New Zealand maternity and midwifery services and the COVID-19 response: A systematic scoping review.

PROBLEM COVID-19 guidance from professional and health organisations created uncertainty leading to professional and personal stress impacting on midwives providing continuity of care in New Zealand (NZ). The COVID-19 pandemic resulted in massive amounts of international and national information and guidance. This guidance was often conflicting and not suited to New Zealand midwifery. AIM To examine and map the national and international guidance and information provided to midwifery regarding COVID-19 and foreground learnt lessons for future similar crises. METHODS A systematic scoping review informed by Arksey and O'Malley's five-stage framework. A range of sources from grey and empirical literature was identified and 257 sources included. FINDINGS Four categories were identified and discussed: (1) guidance for provision of maternity care in the community; (2) guidance for provision of primary labour and birth care; (3) Guidance for midwifery care to women/wāhine with confirmed/suspected COVID-19 infection, including screening processes and management of neonates of infected women/wāhine (4) Guidance for midwives on protecting self and own families and whānau (extended family) from COVID-19 exposure. CONCLUSION Guidance was mainly targeted and tailored for hospital-based services. This was at odds with the NZ context, where primary continuity of care underpins practice. It is evident that those providing continuity of care constantly needed to navigate an evolving situation to mitigate interruptions and restrictions to midwifery care, often without fully knowing the personal risk to themselves and their own families. A key message is the need for a single source of evidence-based guidance, regularly updated and timestamped to show where advice changes over time.

['Crowther|Susan|S|', 'Maude|Robyn|R|', 'Zhao|Ivy Y|IY|', 'Bradford|Billie|B|', 'Gilkison|Andrea|A|']

2021

26939739

Autonomic nervous system activity and anxiety and depressive symptoms in mothers up to 2 years postpartum.

INTRODUCTION We investigated the association between autonomic nervous system (ANS) activity and symptoms of anxiety and depression for the first 2 years postpartum. METHODS A total of 108 participants within 2 years postpartum underwent physiological measurements of ANS activity using the heart rate variability (HRV) power spectrum and self-reported questionnaires (14-item Hospital Anxiety and Depression Score). The cutoff points for anxiety and depressive symptom scores in this questionnaire were as follows: 7 or less, non-cases; 8-10, doubtful cases; 11 or more, definite cases. This study was conducted from 2012 to 2014 at University Hospital in Kyoto Prefectural University of Medicine and a nearby obstetrics and gynecology department clinic in Japan. RESULTS Anxiety and depression non-cases accounted for 67.6% (n = 73) of subjects, anxiety non-cases and depression doubtful and definite cases 7.4% (n = 8), anxiety doubtful and definite cases and depression non-cases 8.3% (n = 9), and anxiety and depression doubtful and definite cases 16.7% (n = 18). Findings were similar for women with anxiety or depression, with total power (TP), low-frequency (LF) and high-frequency (HF) components of HRV among doubtful and definite cases significantly lower than among non-cases for both anxiety (p = 0.006, 0.034, 0.029, respectively) and depression (p = 0.001, 0.004, 0.007). Significant correlations were observed between TP, LF and HF and anxiety and depression scores (respective values for anxiety: rs = -0.331, p <0.001; rs = -0.286, p = 0.003; rs = -0.269, p = 0.005; and depression: rs = -0.389, rs = -0.353, rs = -0.337, all p <0.001). DISCUSSION The present study demonstrated that mothers with anxiety or depressive symptoms had significantly lower HRV (HF, LF and TP) than those without.

['Izumi|Mie|M|', 'Manabe|Emiko|E|', 'Uematsu|Sayo|S|', 'Watanabe|Ayako|A|', 'Moritani|Toshio|T|']

2016

31125491

A safety, pharmacokinetic, pharmacogenomic and population pharmacokinetic analysis of the third-generation EGFR TKI, olmutinib (HM61713), after single oral administration in healthy volunteers.

The main objective of this phase I trial was to investigate pharmacokinetics (PKs) of olmutinib in three racial subjects. We also evaluate safety/tolerability and a population PK and pharmacogenomic analysis were performed for explorative purposes. A dose escalation study was conducted in 56 Korean, Japanese and Caucasian subjects. The food effect was assessed in the 300 mg Korean group. Individual PK parameters were calculated by non-compartmental methods and presented by dose and race. Genotype analysis was performed using DMET® plus to identify genotypes which affect PK characteristics. A population PK model was developed to explore inter-individual variability and to evaluate the influence of possible covariates using NONMEM® . Tmax was 2-3 hour, regardless of race. The mean terminal half-life ranged from 4.8 to 7.4 hour, with no significant differences between dose or racial groups. Dose-normalized Cmax and AUClast were not significantly different between race groups. PK parameters were similar between the fasting and fed conditions. A single-nucleotide polymorphism in the GSTM3 gene (rs4783) and a copy number variation in the GSTM1 gene were significantly related to AUC. A one-compartment model with first-order absorption adequately described the observed olmutinib data. Thirty adverse events were observed in 15 subjects, of which 26 events, all mild, were possibly related to olmutinib. A single oral dose of olmutinib 100-300 mg was safe and well tolerated. PK parameters were dose-proportional and did not differ by race. Food intake did not affect olmutinib absorption. Pharmacogenomic analysis indicated that glutathione S-transferase might be involved in olmutinib metabolism.

['Noh|Young Su|YS|', 'Yoon|Seonghae|S|', 'Kim|Suk Ran|SR|', 'Lee|Kyung-Tae|KT|', 'Jang|In-Jin|IJ|']

2019

23470614

Ultrasound mapping of the long saphenous vein in coronary artery bypass graft surgery.

Long saphenous vein is the most common conduit utilized for surgical coronary revascularization. Ultrasound-assisted vein assessment is superior to traditional clinical examination of the long saphenous vein in discerning path and suitability for use as a conduit. Preoperative ultrasound mapping of the long saphenous vein is easy and rapidly accomplished allowing optimal surgical site selection, avoiding unnecessary surgical dissection and potential wound complications. We describe the technique of ultrasound mapping of the long saphenous vein and its application to conduit harvest in coronary artery bypass graft (CABG) surgery.

['Soo|Alan|A|', 'Noel|Dennis|D|', 'MacGowan|Simon|S|']

2013

33262737

Effects of Apolipoprotein E Polymorphism on Cerebral Oxygen Saturation After Traumatic Brain Injury.

Objective: To investigate the effects of the apolipoprotein E gene (APOE) on the cerebral oxygen saturation of patients after traumatic brain injury (TBI). Methods: Clinical data of 114 patients with TBI and 54 normal people were collected. The APOE genotypes of all subjects were determined by quantitative fluorescent polymerase chain reaction (QF-PCR). The regional cerebral oxygen saturation (rScO2) of TBI patients and normal people were monitored by near-infrared spectroscopy (NIRS). Results: The mean rScO2 of patients was (55.06 ± 7.60)% in the early stage of TBI, which was significantly lower than that of normal people (67.21 ± 7.80)% (P < 0.05). Single-factor and multifactor logistic regression analyses showed APOEε4 was an independent risk factor that caused the early decline of rScO2 in TBI patients. Furthermore, in the TBI group, the rScO2 of APOEε4 carriers (52.23 ± 8.02)% was significantly lower than that of non-ε4 carriers (60.33 ± 7.12)% (P < 0.05). But in the normal group, no significant differences in rScO2 were found between APOEε4 carriers and non-carriers. Conclusion: The rScO2 may be significantly decreased after TBI, and APOEε4 may be a risk factor for decreased rScO2 in the early stage of TBI.

['Wu|Zhimin|Z|', 'Xiong|Senjie|S|', 'Sun|Xiaochuan|X|', 'Shi|Quanhong|Q|', 'Dan|Wei|W|', 'Zhan|Yan|Y|', 'Xie|Yanfeng|Y|', 'Jiang|Li|L|']

2020

30709074

Climate Change: A Review of a Public Health Opportunity for the Northeast.

[Full article available at http://rimed.org/rimedicaljournal-2019-02.asp].

['Salas|Renee N|RN|']

2019

34598691

Suppressor of variegation 3-9 homologue 1 impairment and neutrophil-skewed systemic inflammation are associated with comorbidities in COPD.

BACKGROUND Systemic manifestations and comorbidities are characteristics of chronic obstructive pulmonary disease (COPD) and are probably due to systemic inflammation. The histone methyltransferase SUV39H1 controls the Th1/Th2 balance. We previously reported that reduced SUV39H1 expression contributed to abnormal inflammation in COPD. Here, we aimed to determine whether impaired SUV39H1 expression in COPD patients associated with neutrophilic/eosinophilic inflammation responses and comorbidities. METHODS A total of 213 COPD patients and 13 healthy controls were recruited from the Shuang Ho Hospital, Taipei Medical University. SUV39H1 levels in peripheral blood mononuclear cells (PBMCs) from 13 healthy and 30 COPD participants were measured by immunoblotting. We classified the patients into two groups based on low (fold change, FC < 0.5) and high SUV39H1 expression (FC ≥ 0.5) compared to normal controls. Clinical outcomes including neutrophil or eosinophil counts associated with SUV39H1-related inflammation were evaluated by Chi square analyses or Mann-Whitney U test. The correlations between the percentage of neutrophils and number of COPD comorbidities or Charlson Comorbidity Index (CCI) scores were performed by Spearman's rank analysis. RESULTS Low SUV39H1 expression group had high neutrophil counts relative to high SUV39H1expression group. In the COPD cohort, the high comorbidity group (≥ 2 comorbidities) had higher counts of whole white blood cell (WBC) and neutrophil, and lower proportion of eosinophil and eosinophil/neutrophil, as compared with low comorbidity group (0 and 1 comorbidities). The quantity of neutrophils was associated with COPD comorbidities (Spearman's r = 0.388, p < 0.001), but not with CCI scores. We also found that the high comorbidity group had more exacerbations per year compared with low comorbidity group (1.5 vs. 0.9 average exacerbations, p = 0.005). However, there were no significant differences between groups with these non-frequent (0-1 exacerbation) and frequent exacerbations per year (> 1 exacerbation) in numbers of WBC and proportion of neutrophils, eosinophils or eosinophil/neutrophil. Finally, patients with high comorbidities had lower SUV39H1 levels in their PBMCs than did those with low comorbidities. CONCLUSION Blood neutrophil counts are associated with comorbidities in COPD patients. Impaired SUV39H1 expression in PBMCs from COPD patients are correlated with neutrophilic inflammation and comorbidities.

['Chen|Tzu-Tao|TT|', 'Wu|Sheng-Ming|SM|', 'Chen|Kuan-Yuan|KY|', 'Tseng|Chien-Hua|CH|', 'Ho|Shu-Chuan|SC|', 'Chuang|Hsiao-Chi|HC|', 'Feng|Po-Hao|PH|', 'Liu|Wen-Te|WT|', 'Han|Chia-Li|CL|', 'Huang|Erick Wan-Chun|EW|', 'Yeh|Yun-Kai|YK|', 'Lee|Kang-Yun|KY|http://orcid.org/0000-0003-4705-5802']

2021

32516076

An International Collaborative Approach to Developing Training Guidelines for Veterinary Paraprofessionals.

Veterinary paraprofessionals (VPPs) are engaged worldwide in animal health management, disease surveillance and food safety control. In many countries, particularly developing countries, VPPs are critical to national veterinary services provision. Until recently, there were no globally recognized training requirements for VPPs. Recognition of VPPs' qualifications and roles, and requirements for registration, vary greatly between jurisdictions. To address these issues, the World Organisation for Animal Health (OIE) has developed competency and curricular guidelines for VPPs. A collaborative approach was essential to this mission. Extensive consultation with individuals and agencies representing various countries, animal health and veterinary sectors, and forms of expertise, was undertaken. Collaborative methods included the formation of a guidelines development ad hoc group whose diversity reflected project needs, the use of existing OIE Member Country data to understand roles of VPPs globally, conducting stakeholder surveys to collate VPP competency expectations and solicit feedback on draft guidelines, and in-country missions to validate draft curricular models. The initial deliverable from this work was publication of Competency Guidelines for VPPs. This document provides recommendations on the knowledge, skills, attitudes, and aptitudes that could be expected of VPPs following effective training. The companion document, OIE Curricular Guidelines for VPPs, provides recommendations on coursework structure and content to achieve these competencies. These guidelines will assist countries worldwide in more effectively training and qualifying VPPs so that they can contribute positively to the provision of veterinary services. Another potential impact is to catalyze the review of educational and regulatory standards regarding the respective work rights and activities of veterinarians and VPPs.

['Cobbold|Rowland N|RN|https://orcid.org/0000-0002-5560-4237', 'Simmons|Heather L|HL|', 'Cargill|Jessica|J|', 'Lasley|Jennifer|J|', 'Oosthuizen|Johan|J|', 'Sherman|David M|DM|']

2020

29522678

π-Cation Interactions in Molecular Recognition: Perspectives on Pharmaceuticals and Pesticides.

The π-cation interaction that differs from the cation-π interaction is a valuable concept in molecular design of pharmaceuticals and pesticides. In this Perspective we present an up-to-date review (from 1995 to 2017) on bioactive molecules involving π-cation interactions with the recognition site, and categorize into systems of inhibitor-enzyme, ligand-receptor, ligand-transporter, and hapten-antibody. The concept of π-cation interactions offers use of π systems in a small molecule to enhance the binding affinity, specificity, selectivity, lipophilicity, bioavailability, and metabolic stability, which are physiochemical features desired for drugs and pesticides.

['Liang|Zhibin|Z|http://orcid.org/0000-0002-8855-1696', 'Li|Qing X|QX|http://orcid.org/0000-0003-4589-2869']

2018

33650388

Induction of labor at 39 weeks and risk of cesarean delivery among obese women: a retrospective propensity score matched study.

OBJECTIVES To evaluate if induction of labor (IOL) in obese women at 39 weeks of gestation decreases the risk of cesarean delivery (CD). METHODS We conducted a retrospective propensity score matched study using the Center for Disease Control's (CDC's) Period Linked Birth-Infant Death data. The study population consisted of cephalic singleton births to women with BMI greater or equal to 30.0 kg/m2 who delivered at or beyond 39 weeks between 2013 and 2017. Women with prior CD were excluded. Women who underwent IOL at 39 weeks were propensity score matched 1:5 on the basis of CD risk factors to women who did not undergo IOL at 39 weeks but may have had an IOL at a later gestational age. Conditional logistic regression compared CD rates and maternal outcomes between obese women induced at 39 weeks with those not induced at 39 weeks. RESULTS Our cohort consisted of 197,343 obese women induced at 39 weeks and 986,715 obese women not induced at 39 weeks. Overall, the risk of CD among women who had an IOL at 39 weeks was lower than those without an IOL at 39 weeks, 0.59 (0.58-0.60). The decrease in CD risk was more pronounced in multiparas, 0.47 (0.46-0.49) than nulliparas, 0.81 (0.79-0.83). When stratified by BMI, the effect of IOL on lowering CD risk was similar across all obesity classes. Aside from an increased risk of instrumental deliveries, morbidities were comparable in both groups. CONCLUSIONS IOL at 39 weeks among obese women appears to lower the risk of CD, without compromising maternal outcomes.

['Eberle|Alexa|A|', 'Czuzoj-Shulman|Nicholas|N|', 'Azoulay|Laurent|L|', 'Abenhaim|Haim Arie|HA|']

2021

31399257

Early Adversity and the Neotenous Human Brain.

Human brain development is optimized to learn from environmental cues. The protracted development of the cortex and its connections with subcortical targets has been argued to permit more opportunity for acquiring complex behaviors. This review uses the example of amygdala-medial prefrontal cortex circuitry development to illustrate a principle of human development-namely, that the extension of the brain's developmental timeline allows for the (species-expected) collaboration between child and parent in co-construction of the human brain. The neurobiology underlying affective learning capitalizes on this protracted timeline to develop a rich affective repertoire in adulthood. Humans are afforded this luxuriously slow development in part by the extended period of caregiving provided by parents, and parents aid in scaffolding the process of maturation during childhood. Just as adequate caregiving is a potent effector of brain development, so is adverse caregiving, which is the largest environmental risk factor for adult mental illness. There are large individual differences in neurobiological outcomes following caregiving adversity, indicating that these pathways are probabilistic, rather than deterministic, and prolonged plasticity in human brain development may also allow for subsequent amelioration by positive experiences. The extant research indicates that the development of mental health cannot be considered without consideration of children in the context of their families.

['Tottenham|Nim|N|']

2020

32943060

CLPTM1L induces estrogen receptor β signaling-mediated radioresistance in non-small cell lung cancer cells.

INTRODUCTION Radioresistance is a major challenge in lung cancer radiotherapy, and new radiosensitizers are urgently needed. Estrogen receptor β (ERβ) is involved in the progression of non-small cell lung cancer (NSCLC), however, the role of ERβ in the response to radiotherapy in lung cancer remains elusive. In the present study, we investigated the mechanism underlying ERβ-mediated transcriptional activation and radioresistance of NSCLC cells. METHODS Quantitative real-time PCR, western blot and immunohistochemistry were used to detect the expression of CLPTM1L, ERβ and other target genes. The mechanism of CLPTM1L in modulation of radiosensitivity was investigated by chromatin immunoprecipitation assay, luciferase reporter gene assay, immunofluorescence staining, confocal microscopy, coimmunoprecipitation and GST pull-down assays. The functional role of CLPTM1L was detected by function assays in vitro and in vivo. RESULTS CLPTM1L expression was negatively correlated with the radiosensitivity of NSCLC cell lines, and irradiation upregulated CLPTM1L in radioresistant (A549) but not in radiosensitive (H460) NSCLC cells. Meanwhile, IR induced the translocation of CLPTM1L from the cytoplasm into the nucleus in NSCLC cells. Moreover, CLPTM1L induced radioresistance in NSCLC cells. iTRAQ-based analysis and cDNA microarray identified irradiation-related genes commonly targeted by CLPTM1L and ERβ, and CLPTM1L upregulated ERβ-induced genes CDC25A, c-Jun, and BCL2. Mechanistically, CLPTM1L coactivated ERβ by directly interacting with ERβ through the LXXLL NR (nuclear receptor)-binding motif. Functionally, ERβ silencing was sufficient to block CLPTM1L-enhanced radioresistance of NSCLC cells in vitro. CLPTM1L shRNA treatment in combination with irradiation significantly inhibited cancer cell growth in NSCLC xenograft tumors in vivo. CONCLUSIONS The present results indicate that CLPTM1L acts as a critical coactivator of ERβ to promote the transcription of its target genes and induce radioresistance of NSCLC cells, suggesting a new target for radiosensitization in NSCLC therapy. Video Abstract.

['Li|Hang|H|', 'Che|Jun|J|', 'Jiang|Mian|M|', 'Cui|Ming|M|', 'Feng|Guoxing|G|', 'Dong|Jiali|J|', 'Zhang|Shuqin|S|', 'Lu|Lu|L|', 'Liu|Weili|W|', 'Fan|Saijun|S|']

2020

34681029

ABA and Bud Dormancy in Perennials: Current Knowledge and Future Perspective.

Bud dormancy is an evolved trait that confers adaptation to harsh environments, and affects flower differentiation, crop yield and vegetative growth in perennials. ABA is a stress hormone and a major regulator of dormancy. Although the physiology of bud dormancy is complex, several advancements have been achieved in this field recently by using genetics, omics and bioinformatics methods. Here, we review the current knowledge on the role of ABA and environmental signals, as well as the interplay of other hormones and sucrose, in the regulation of this process. We also discuss emerging potential mechanisms in this physiological process, including epigenetic regulation.

['Pan|Wenqiang|W|', 'Liang|Jiahui|J|0000-0002-0106-1193', 'Sui|Juanjuan|J|', 'Li|Jingru|J|0000-0002-0946-0201', 'Liu|Chang|C|', 'Xin|Yin|Y|', 'Zhang|Yanmin|Y|', 'Wang|Shaokun|S|', 'Zhao|Yajie|Y|', 'Zhang|Jie|J|', 'Yi|Mingfang|M|', 'Gazzarrini|Sonia|S|', 'Wu|Jian|J|0000-0001-8582-302X']

2021

31295532

Elimination of hepatitis C virus has limited impact on the functional and mitochondrial impairment of HCV-specific CD8+ T cell responses.

BACKGROUND & AIMS Hepatitis C virus (HCV)-specific CD8+ T cells are functionally impaired in chronic hepatitis C. Even though HCV can now be rapidly and sustainably cleared from chronically infected patients, the repercussions of HCV clearance on virus-specific CD8+ T cells remain elusive. Here, we aimed to investigate if HCV clearance by direct-acting antivirals (DAAs) could restore the functionality of exhausted HCV-specific CD8+ T cell responses. METHODS HCV-specific CD8+ T cells in peripheral blood were obtained from 40 patients with chronic HCV infection, during and 6 months following IFN-free DAA therapy. These cells were analyzed for comprehensive phenotypes, proliferation, cytokine production, mitochondrial fitness and response to immune-checkpoint blockade. RESULTS We show that, unlike activation markers that decreased, surface expression of multiple co-regulatory receptors on exhausted HCV-specific CD8+ T cells remained unaltered after clearance of HCV. Likewise, cytokine production by HCV-specific CD8+ T cells remained impaired following HCV clearance. The proliferative capacity of HCV multimer-specific CD8+ T cells was not restored in the majority of patients. Enhanced in vitro proliferative expansion of HCV-specific CD8+ T cells during HCV clearance was more likely in women, patients with low liver stiffness and low alanine aminotransferase levels in our cohort. Interestingly, HCV-specific CD8+ T cells that did not proliferate following HCV clearance could preferentially re-invigorate their proliferative capacity upon in vitro immune-checkpoint inhibition. Moreover, altered mitochondrial dysfunction exhibited by exhausted HCV-specific CD8+ T cells could not be normalized after HCV clearance. CONCLUSION Taken together, our data implies that exhausted HCV-specific CD8+ T cells remain functionally and metabolically impaired at multiple levels following HCV clearance in most patients with chronic hepatitis C. Our results might have implications in cases of re-infection with HCV and for HCV vaccine development. LAY SUMMARY Direct-acting antiviral therapy results in cure of hepatitis C virus (HCV) in almost all treated patients. However, the impacts of HCV cure on immune responses remain controversial. Whether immune responses to HCV recover is important in cases of re-exposure, or for the resolution of extrahepatic manifestations. The main finding of our study was that HCV-specific T cells remain functionally impaired despite HCV clearance. This finding could explain the fact that HCV cure does not lead to protective immunity and that re-infections have frequently been observed.

['Aregay|Amare|A|', 'Owusu Sekyere|Solomon|S|', 'Deterding|Katja|K|', 'Port|Kerstin|K|', 'Dietz|Julia|J|', 'Berkowski|Caterina|C|', 'Sarrazin|Christoph|C|', 'Manns|Michael Peter|MP|', 'Cornberg|Markus|M|', 'Wedemeyer|Heiner|H|']

2019

33786400

Influence of poly(N-isopropylacrylamide) (PIPAAm) graft density on properties of PIPAAm grafted poly(dimethylsiloxane) surfaces and their stability.

A previous report shows that poly(N-isopropylacrylamide) (PIPAAm) gel grafted onto poly(dimethylsiloxane) (PDMS) (PI-PDMS) surfaces with large PIPAAm graft density (Lar-PI-PDMS), is prepared by using electron beam irradiation, demonstrating that applied mechanical stretching affects properties of the Lar-PI-PDMS surface. However, the influence of PIPAAm graft density on the properties of PI-PDMS surfaces and their stability are not understood. To provide insight into these points, the properties of PI-PDMS surfaces with low PIPAAm graft density (Low-PI-PDMS) surfaces with stretched (stretch ratio = 20%) and unstretched states were examined as stretchable temperature-responsive cell culture surface using contact angle measurement and cell attachment/detachment assays, compared to those with Lar-PI-PDMS, as previously reported. Long-term contact angle measurements (61 days) for unstretched Low-PI-PDMS and Lar-PI-PDMS surfaces indicated that the cross-linked structure of the grafted PIPAAm gel suppressed hydrophobic recovery of the basal PDMS surface. The cell attachment assay revealed that the stretched Low-PI-PDMS surface was less cell adhesive than that of the unstretched Low-PI-PDMS surface despite of a larger amount of adsorbed fibronectin (FN). The lower cell adhesiveness was possibly explained by denaturation of adsorbed FN, which was induced by the strong hydrophobic property of the stretched Low-PI-PDMS surface. The cell detachment assay revealed that dual stimuli, low temperature treatment and mechanical shrinking stress applied to the stretched Low-PI-PDMS surface promoted cell detachment compared to a single stimulus, low temperature treatment or mechanical shrinking stress. These results suggested that the PIPAAm gelgrafted PDMS surface was chemically stable and did not suffer from hydrophobic recovery. External mechanical stretching stress not only strongly dehydrated grafted PIPAAm chains, but also denatured the adsorbed FN when the grafted PIPAAm layer was extremely thin, as in Low-PI-PDMS surfaces. Thus, PI-PDMS may be utilized as a stretchable temperature-responsive cell culture surface without significant hydrophobic recovery.

['Akiyama|Yoshikatsu|Y|']

2021

30009399

S100A10, a novel biomarker in pancreatic ductal adenocarcinoma.

Pancreatic cancer is arguably the deadliest cancer type. The efficacy of current therapies is often hindered by the inability to predict patient outcome. As such, the development of tools for early detection and risk prediction is key for improving outcome and quality of life. Here, we introduce the plasminogen receptor S100A10 as a novel predictive biomarker and a driver of pancreatic tumor growth and invasion. We demonstrated that S100A10 mRNA and protein are overexpressed in human pancreatic tumors compared to normal ducts and nonductal stroma. S100A10 mRNA and methylation status were predictive of overall survival and recurrence-free survival across multiple patient cohorts. S100A10 expression was driven by promoter methylation and the oncogene KRAS. S100A10 knockdown reduced surface plasminogen activation, invasiveness, and in vivo growth of pancreatic cancer cell lines. These findings delineate the clinical and functional contribution of S100A10 as a biomarker in pancreatic cancer.

['Bydoun|Moamen|M|', 'Sterea|Andra|A|', 'Liptay|Henry|H|', 'Uzans|Andrea|A|', 'Huang|Weei-Yuarn|WY|', 'Rodrigues|Gloria J|GJ|', 'Weaver|Ian C G|ICG|', 'Gu|Hong|H|', 'Waisman|David M|DM|']

2018

33740355

Simplicity Radiofrequency Ablation Demonstrates Greater Functional Improvement Than Analgesia: A Prospective Case Series.

BACKGROUND Pain originating from the posterior sacroiliac complex is notoriously difficult to effectively treat due to its complex anatomy and variable innervation. Data on radiofrequency ablation (RFA) is limited. The Abbott Simplicity probe creates 3 monopolar lesions along the medial aspect of the sacroiliac joint and 2 bipolar lesions between the active portions of the probe. This device has been studied previously with improvement of pain-associated disability and pain reduction, but insufficient data is present to determine its utility at this time. Using the most recent literature for the potential innervation of the posterior sacroiliac joint, it is reasonable to explore this novel device and its ability to treat sacroiliac joint pain. OBJECTIVES Identify the percentage of improved posterior sacroiliac complex pain and improved function in patients who completed posterior sacroiliac complex radiofrequency ablation using the Simplicity probe. STUDY DESIGN Prospective case series. SETTING A single outpatient pain clinic. METHODS This prospective case-series occurred at an outpatient pain clinic. Data were analyzed after completion of follow-up appointments. Inclusion criteria included 2 successful lateral branch blocks. Fourteen patients with posterior sacroiliac complex pain were examined and completed sacroiliac ablation with the Simplicity probe. The numeric rating scale and the Modified Oswestry Disability Index were used as outcome measures for pain and function, respectively. The primary outcome measures were improvement in the numeric rating scale score by a reduction of 2.5 points and an improvement in Modified Oswestry Disability Index by 15% based upon previous studies demonstrating these values as the minimal clinical important difference . Patients were followed at a 3 to 6 month interval and 12 month interval (an average of 88 and 352 days, respectively). RESULTS In total, 14 patients were examined. At the first follow-up, 29% of patients had analgesia and 38% functionally improved. At the second follow-up, 15% of patients had analgesia and 31% functionally improved. LIMITATIONS Considering data were collected retrospectively, this study relied on completed charts. Therefore, data points of interest were limited to what was previously documented, which included multiple answers or the absence of numerical data points. In addition, patients were disproportionately female (71.4%). Data were also affected by patients lost to follow-up. Also, this study examined a relatively small number of patients, therefore the results should be carefully considered. CONCLUSIONS Radiofrequency ablation of the posterior sacroiliac complex with the Simplicity probe resulted in more functional improvement than analgesia. This study provides more data for clinicians to utilize in managing posterior sacroiliac complex pain. IRB: Protocol number 20170342HU. Not registered in clinical trials.

['Brennick|Caroline|C|', 'Bickelhaupt|Brittany|B|', 'Boies|Brian|B|', 'Nagpal|Ameet|A|']

2021

33549686

Intermittent fasting promotes anxiolytic-like effects unrelated to synaptic mitochondrial function and BDNF support.

Anxiety disorders are linked to mitochondrial dysfunction and decreased neurotrophic support. Since anxiolytic drugs target mitochondria, non-pharmacological approaches to improve mitochondrial metabolism such as intermittent fasting (IF) may cause parallel behavioral benefits against anxiety disorders. Here, we investigated whether a chronic IF regimen could induce anxiolytic-like effects concomitantly to modulation in mitochondrial bioenergetics and trophic signaling in mice brain. A total of 44 Male C57BL/6 J mice (180 days old) were assigned to two dietary regimens: a normal, ad libitum diet (AL group) and an alternate-day fasting (IF group), where animals underwent 10 cycles of 24 h food restriction followed by 24 h ad libitum access. Animals underwent the open field test, dark/light box and elevated plus maze tasks. Isolated nerve terminals were obtained from mice brain and used for mitochondrial respirometry, hydrogen peroxide production and assessment of membrane potential dynamics, calcium handling and western blotting. We showed that IF significantly alters total daily food intake and food consumption patterns but not body weight. There were no differences in the exploratory and locomotory parameters. Remarkably, animals from IF showed decreased anxiety-like behavior. Mitochondrial metabolic responses in different coupling states and parameters linked with H2O2 production, Ca2+ buffering and electric gradient were not different between groups. Finally, no alterations in molecular indicators of apoptotic death (Bax/Bcl-2 ratio) and neuroplasticity (proBDNF/BDNF and synaptophysin were observed). In conclusion, IF exerts anxiolytic-like effect not associated with modulation in synaptic neuronergetics or expression of neurotrophic proteins. These results highlight a potential benefit of intermittent fasting as a nutritional intervention in anxiety-related disorders.

['Carteri|Randhall B|RB|', 'Menegassi|Lizia Nardi|LN|', 'Feldmann|Marceli|M|', 'Kopczynski|Afonso|A|', 'Rodolphi|Marcelo Salimen|MS|', 'Strogulski|Nathan Ryzewski|NR|', 'Almeida|Amanda Staldoni|AS|', 'Marques|Daniela Melo|DM|', 'Porciúncula|Lisiane O|LO|', 'Portela|Luis Valmor|LV|']

2021

33233249

Microbial community in Chinese traditional fermented acid rice soup (rice-acid) and its correlations with key organic acids and volatile compounds.

Rice-acid is a unique Chinese traditional fermented acid rice soup and its microbial community plays an important role in the formation of flavour compounds. In the study, rice-acid products from high-temperature and low-temperature fermentation methods were selected to analyze the microbial community, organic acids, and volatile flavour compounds (VFCs). The main bacterial and fungal phyla in Chinese traditional fermented rice-acid were determined to be Firmicutes and Ascomycota, including 62 bacterial genera and 57 fungal genera. The dominant bacterial genera were Lactobacillus, Acetobacter, and Prevotella and the dominant fungal genera were Naumovia, Pichia, Candida, and Saccharomyces. Among organic acids in rice-acid, L-lactic acid had the highest concentration, followed by malic acid, acetic acid, citric acid, oxalic acid, and tartaric acid. Volatile flavour compounds had a high contribution to the flavour, including ethyl acetate, ethanol, acetic acid, propanoic acid, 1-octen-3-ol, 2-nonanol, 2-undecanol, propyl propionate, ethyl propanoate, propyl propionate, and 2,3-butanedione. The microorganisms which were closely correlated with key organic acids in rice-acid included Lactobacillus, Acetobacter, Pichia, Candida, Kluyveromyces and Meyerozyma. The microorganisms which were correlated with VFCs included Acetobacter, Prevotella, Kluyveromyces and Saccharomyces. In particular, Lactobacillus, Pichia, Malassezia, Clavispora, Rhizopus and Cystofilobasidium were significantly positively correlated with lactic acid in rice-acid. Kluyveromyces, Saccharomyces and Emericella were significantly positively correlated with ethanol and ethyl acetate. The study provides the basis for improving the quality of rice-acid.

['Liu|Na|N|', 'Pan|Jihong|J|', 'Miao|Song|S|', 'Qin|Likang|L|']

2020

28784588

Probing the interaction of the p53 C-terminal domain to the histone demethylase LSD1.

The p53 transcription factor plays a central role in the regulation of the expression of several genes, and itself is post-translationally regulated through its different domains. Of particular relevance for p53 function is its intrinsically disordered C-terminal domain (CTD), representing a hotspot for post-translational modifications and a docking site for transcriptional regulators. For example, the histone H3 lysine demethylase 1 (LSD1) interacts with p53 via the p53-CTD for mutual regulation. To biochemically and functionally characterize this complex, we evaluated the in vitro interactions of LSD1 with several p53-CTD peptides differing in length and modifications. Binding was demonstrated through thermal shift, enzymatic and fluorescence polarization assays, but no enzymatic activity could be detected on methylated p53-CTD peptides in vitro. These experiments were performed using the wild-type enzyme and LSD1 variants that are mutated on three active-site residues. We found that LSD1 demethylase activity is inhibited by p53-CTD. We also noted that the association between the two proteins is mediated by mostly non-specific electrostatic interactions involving conserved active-site residues of LSD1 and a highly charged segment of the p53-CTD. We conclude that p53-CTD inhibits LSD1 activity and that the direct association between the two proteins can contribute to their functional cross-talk.

['Speranzini|Valentina|V|', 'Ciossani|Giuseppe|G|', 'Marabelli|Chiara|C|', 'Mattevi|Andrea|A|']

2017

30558917

The relationship between acute pain and dynamic postural stability indices in individuals with patellar tendinopathy.

BACKGROUND Patellar tendinopathy is a common condition resulting in persistent pain, frequently reported during physical activity. The relationship between dynamic postural stability and pain in these individuals is unclear and how it may affect postural stability. RESEARCH QUESTION Is there a relationship between acute pain and dynamic postural stability indices in individuals with patellar tendinopathy? METHODS Twenty-two recreationally active individuals with patellar tendinopathy participated. Participants performed a two-legged jump and landed on a single test-limb on a force platform. They completed 100 mm visual analogue scales (VAS) before and after landing trials. Anterior-posterior (APSI), medial-lateral (MLSI), vertical (VSI), and composite (DPSI) stability indices were calculated from ground reaction force data. The relationship between stability indices and VAS for pain as well as pain change scores were assessed via non-parametric Spearman's rho (ρ) rank correlations (p≤.05). RESULTS Baseline pain was not significantly correlated with any stability indices. Post-landing pain was significantly correlated with MLSI (ρ = 0.540, p = 0.004) while, VSI (ρ = 0.353, p = 0.053) and DPSI (ρ = 0.347, p = 0.057) had moderate, yet insignificant correlations. Pain change scores demonstrated a large correlation with MLSI (ρ = 0.598, p = 0.002). SIGNIFICANCE As pain increased in individuals with patellar tendinopathy, dynamic postural stability indices values increased, indicating more difficulty transitioning from a dynamic to static state. Although balance deficits are not typically associated with patellar tendinopathy, it appears pain and dynamic postural stability may be related in these individuals.

['Rosen|Adam B|AB|', 'Ko|Jupil|J|', 'Brown|Cathleen N|CN|']

2018

27713914

ATRX, IDH1-R132H and Ki-67 immunohistochemistry as a classification scheme for astrocytic tumors.

Recurrence and progression to higher grade lesions are key biological events and characteristic behaviors in the evolution process of glioma. Malignant astrocytic tumors such as glioblastoma (GBM) are the most lethal intracranial tumors. However, the clinical practicability and significance of molecular parameters for the diagnostic and prognostic prediction of astrocytic tumors is still limited. In this study, we detected ATRX, IDH1-R132H and Ki-67 by immunohistochemistry and observed the association of IDH1-R132H with ATRX and Ki-67 expression. There was a strong association between ATRX loss and IDH1-R132H (p<0.0001). However, Ki-67 high expression restricted in the tumors with IDH1-R132H negative (p=0.0129). Patients with IDH1-R132H positive or ATRX loss astrocytic tumors had a longer progressive- free survival (p<0.0001, p=0.0044, respectively). High Ki-67 expression was associated with shorter PFS in patients with astrocytic tumors (p=0.002). Then we characterized three prognostic subgroups of astrocytic tumors (referred to as A1, A2 and A3). The new model demonstrated a remarkable separation of the progression interval in the three molecular subgroups and the distribution of patients' age in the A1-A2-A3 model was also significant different. This model will aid predicting the overall survival and progressive time of astrocytic tumors' patients.

['Cai|Jinquan|J|', 'Zhang|Chuanbao|C|', 'Zhang|Wei|W|', 'Wang|Guangzhi|G|', 'Yao|Kun|K|', 'Wang|Zhiliang|Z|', 'Li|Guanzhang|G|', 'Qian|Zenghui|Z|', 'Li|Yongli|Y|', 'Jiang|Tao|T|', 'Jiang|Chuanlu|C|']

2016

31976138

The Efficiency of SNP-Based Microarrays in the Detection of Copy-Neutral Events at 15q11.2 and 11p15.5 Loci.

Prader-Willi, Angelman, Beckwith-Wiedemann, and Russell-Silver are imprinting syndromes. In this study, we aimed to compare the efficiency of single nucleotide polymorphism (SNP) microarray analysis with methylation-specific Multiplex ligation-dependent probe amplification (MS-MLPA) in the detection of uniparental disomy in these syndromes. The patient samples with regions of loss of heterozygosity (LOH), covering 15q11.2 and 11p15.5 critical loci, were analyzed with MS-MLPA to demonstrate the efficiency of SNP microarray in the detection of uniparental disomy (UPD). In a total of seven patients, LOH covering 15q11.2 and 11p15.5 critical loci was detected. Two (28.6%) of these seven patients showed aberrant methylation (suggesting UPD) in MS-MLPA. SNP microarray is a useful tool in the detection of LOH; however, it should be used with caution, since false-positive or false-negative LOH results can be obtained. Although methylation analysis is recommended as the first tier test in the diagnosis of most of the imprinting disorders, combining methylation analysis with SNP microarray can enhance our evaluation process.

['Ozyilmaz|Berk|B|', 'Kirbiyik|Ozgur|O|', 'Ozdemir|Taha R|TR|', 'Kaya|Ozge Ozer|OO|', 'Kutbay|Yasar B|YB|', 'Erdogan|Kadri M|KM|', 'Guvenc|Merve Saka|MS|', 'Koc|Altug|A|']

2020

25913391

Flexible cystourethroscopy in the follow-up of posturethroplasty patients and characterisation of recurrences.

BACKGROUND Urethral strictures can be difficult to diagnose at an early stage because the urinary flow rate does not diminish until the urethral calibre is ≤3mm. In the past, posturethral surgery follow-up has relied upon flow rates and contrast imaging. OBJECTIVE To evaluate the role of flexible urethroscopy in the follow-up of patients undergoing urethroplasty. DESIGN, SETTING, AND PARTICIPANTS Prospective flexible urethroscopy follow-up of 144 male patients who underwent urethroplasty by a single surgeon over a 10-yr period at a tertiary referral centre. INTERVENTION Flexible urethroscopy at 3, 6, and 12 mo postoperatively, and annually thereafter. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS Type of recurrence, based on urethroscopy findings, and further interventions were measured. Actuarial analysis was performed using Kaplan-Meier curves and a log-rank test. RESULTS AND LIMITATIONS All 144 patients underwent flexible urethroscopy follow-up over a median postoperative follow-up of 22 mo (range: 1-96 mo). No further intervention was required for 117 patients (81.25%); 27 (18.75%) developed recurrences that required further treatment. Recurrences included diaphragms (13 patients) or significant restenosis (14 patients). Diaphragms were treated by urethrotomy, gentle dilatation, or a short course of intermittent self-dilatation. Restenosis required repeated simple procedures or surgical revision. Most recurrences (26 of 27, 96%) were detected within the first year. Urinary peak flow-rate data were available for 11 of 27 of these recurrences; 7 patients had flow rates >15ml/s. Anastomotic procedures had greater success than augmentation urethroplasty (p=0.0136); there was no significant difference in outcomes between redo and non-redo surgery (p=0.2093) CONCLUSIONS: Endoscopic follow-up of patients after urethroplasty enables earlier identification and treatment of recurrences compared to the use of urinary flow rates alone. It also enables the identification of two different morphologic recurrence patterns that require different types of intervention. PATIENT SUMMARY Endoscopy detects most stricture recurrences within 1 yr after urethroplasty and is more sensitive than using urinary flow rates alone.

['Goonesinghe|Satish K|SK|', 'Hillary|Christopher J|CJ|', 'Nicholson|Timothy R|TR|', 'Osman|Nadir I|NI|', 'Chapple|Christopher R|CR|']

2015

34243709

A machine learning approach for accurate and real-time DNA sequence identification.

BACKGROUND The all-electronic Single Molecule Break Junction (SMBJ) method is an emerging alternative to traditional polymerase chain reaction (PCR) techniques for genetic sequencing and identification. Existing work indicates that the current spectra recorded from SMBJ experimentations contain unique signatures to identify known sequences from a dataset. However, the spectra are typically extremely noisy due to the stochastic and complex interactions between the substrate, sample, environment, and the measuring system, necessitating hundreds or thousands of experimentations to obtain reliable and accurate results. RESULTS This article presents a DNA sequence identification system based on the current spectra of ten short strand sequences, including a pair that differs by a single mismatch. By employing a gradient boosted tree classifier model trained on conductance histograms, we demonstrate that extremely high accuracy, ranging from approximately 96 % for molecules differing by a single mismatch to 99.5 % otherwise, is possible. Further, such accuracy metrics are achievable in near real-time with just twenty or thirty SMBJ measurements instead of hundreds or thousands. We also demonstrate that a tandem classifier architecture, where the first stage is a multiclass classifier and the second stage is a binary classifier, can be employed to boost the single mismatched pair's identification accuracy to 99.5 %. CONCLUSIONS A monolithic classifier, or more generally, a multistage classifier with model specific parameters that depend on experimental current spectra can be used to successfully identify DNA strands.

['Wang|Yiren|Y|', 'Alangari|Mashari|M|', 'Hihath|Joshua|J|', 'Das|Arindam K|AK|', 'Anantram|M P|MP|']

2021

23798341

Highly efficient asymmetric additions of diethylzinc to aldehydes triply activated by chiral phosphoramide-Zn(II) complexes derived from cinchona alkaloids.

New chiral phosphoramide ligands derived from cinchona alkaloids were developed, which react with diethylzinc to form chiral phosphoramide-Zn(II) complexes containing two Lewis bases and one Lewis acid. These trifunctional complexes can serve as highly efficient chiral catalysts for triple activation of enantioselective addition reactions of diethylzinc with aldehydes to give desired alcohol products with excellent yields and enantiomeric excess (ee) values up to 99%.

['Shen|Bin|B|', 'Huang|Huayin|H|', 'Bian|Guangling|G|', 'Zong|Hua|H|', 'Song|Ling|L|']

2013

30520204

Neurodevelopmental outcome of children with spina bifida aperta repaired prenatally vs postnatally: systematic review and meta-analysis.

OBJECTIVE To assess the neurodevelopmental outcome of children with spina bifida aperta (SBA) treated prenatally as compared to those treated postnatally. METHODS We performed a systematic review of the literature in PubMed/MEDLINE, EMBASE, Web of Science and The Cochrane Library, comparing the neurological outcome of infants with SBA treated prenatally vs postnatally. Only randomized controlled trials (RCTs) and non-randomized prospective controlled studies were included. The primary outcome assessed was neurodevelopmental impairment at the age of 1 year or later. Secondary outcomes were preterm birth, need for ventriculoperitoneal (VP) shunt by 12 months of age, absence of signs of hindbrain herniation at the first postnatal magnetic resonance imaging (MRI) evaluation and independent ambulation evaluated at 30 months. RESULTS Of 11 359 studies identified through the electronic search, six met the inclusion criteria and were assessed in full text and two, one RCT and one prospective cohort study, were ultimately included in the meta-analysis. Sensitivity analysis did not show any difference between the outcomes of the RCT alone and those of the pooled RCT and prospective cohort study. This allowed neurodevelopmental assessment of 213 children between 14 and 53 months of age. Neurodevelopment was assessed by the Bayley Scales of Infant Development II (BSID-II) mental development index corrected for chronological age, with a cut-off of ≥ 70 (representing no more than 2 SD below the mean). The presence of neurodevelopmental impairment was similar between children who underwent prenatal (25/105 (23.8%)) and those who had postnatal (30/108 (27.8%)) repair of SBA (odds ratio (OR), 0.82 (95% CI, 0.43-1.56); P = 0.54), although the risk of prematurity was higher in the prenatal-repair group (OR, 17.62 (95% CI, 7.60-40.87); P < 0.0001). For every two fetuses operated on before birth, there was, compared with those operated on after birth, one additional premature birth (number needed to harm = 2 (95% CI, 1-3)). The need for VP shunt placement by 12 months of age was lower in the prenatal-repair group (45/109 (41.3%)) than in children that had postnatal repair (93/112 (83.0%); OR, 0.14 (95% CI, 0.08-0.26); P < 0.0001). Data on neurodevelopmental impairment in children with a shunt were available only for patients from the prenatal-surgery group of the RCT; in this subgroup, the likelihood for impairment was similar between children who did (7/39 (17.9%)) and those who did not (4/48 (8.3%)) have shunt placement (P = 0.21). At first postnatal MRI evaluation, no signs of hindbrain herniation were detected in 28/88 (31.8%) children who were operated on prenatally compared with 4/89 (4.5%) who had postnatal repair (OR, 9.45 (95% CI, 3.12-28.64); P < 0.0001). Independent ambulation at 30 months was achieved by 41/109 (37.6%) children who underwent prenatal repair compared with 21/111 (18.9%) who had postnatal repair (OR, 2.59 (95% CI, 1.39-4.86); P = 0.003). CONCLUSION The risk of neurodevelopmental impairment in infants with SBA was similar between those who underwent prenatal and those who had postnatal surgical repair, despite an increased risk of prematurity in the prenatally repaired group. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

['Inversetti|A|A|https://orcid.org/0000-0001-8655-9427', 'Van der Veeken|L|L|', 'Thompson|D|D|', 'Jansen|K|K|', 'Van Calenbergh|F|F|', 'Joyeux|L|L|https://orcid.org/0000-0001-7331-6354', 'Bosteels|J|J|', 'Deprest|J|J|https://orcid.org/0000-0002-4920-945X']

2019

26957917

Broncho-Pleural Fistula with Hydropneumothorax at CT: Diagnostic Implications in Mycobacterium avium Complex Lung Disease with Pleural Involvement.

OBJECTIVE To determine the patho-mechanism of pleural effusion or hydropneumothorax in Mycobacterium avium complex (MAC) lung disease through the computed tomographic (CT) findings. MATERIALS AND METHODS We retrospectively collected data from 5 patients who had pleural fluid samples that were culture-positive for MAC between January 2001 and December 2013. The clinical findings were investigated and the radiological findings on chest CT were reviewed by 2 radiologists. RESULTS The 5 patients were all male with a median age of 77 and all had underlying comorbid conditions. Pleural fluid analysis revealed a wide range of white blood cell counts (410-100690/µL). The causative microorganisms were determined as Mycobacterium avium and Mycobacterium intracellulare in 1 and 4 patients, respectively. Radiologically, the peripheral portion of the involved lung demonstrated fibro-bullous changes or cavitary lesions causing lung destruction, reflecting the chronic, insidious nature of MAC lung disease. All patients had broncho-pleural fistulas (BPFs) and pneumothorax was accompanied with pleural effusion. CONCLUSION In patients with underlying MAC lung disease who present with pleural effusion, the presence of BPFs and pleural air on CT imaging are indicative that spread of MAC infection is the cause of the effusion.

['Yoon|Hyun Jung|HJ|', 'Chung|Myung Jin|MJ|', 'Lee|Kyung Soo|KS|', 'Kim|Jung Soo|JS|', 'Park|Hye Yun|HY|', 'Koh|Won-Jung|WJ|']

2016

28783523

A case of sclerosing angiomatoid nodular transformation of the spleen with increased accumulation of fluorodeoxyglucose after 5-year follow-up.

INTRODUCTION Sclerosing angiomatoid nodular transformation (SANT) of spleen is a new entity defined as a benign pathologic lesion. Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) shows weak accumulation, thereby ruling out the malignancy in preoperative diagnosis is difficult. Herein, we reported a case of shrinking SANT with increased FDG accumulation during a 5-year follow-up period, which was treated by laparoscopic splenectomy. PRESENTATION OF CASE A 64-year-old female had been referred to our hospital for the evaluation of a splenic tumor. Initial contrast-enhanced computed tomography (CT) showed a well-defined, and ovoid hypoattenuating lesion, measuring 52mm in diameter in the spleen. Initial PET/CT revealed accumulation of FDG in the tumor (maximum standardized uptake value [SUVmax]: 2.8). The mass was diagnosed as SANT, and the patient was followed-up every 6-12 months for 5 years. Follow-up PET/CT revealed increased accumulation of FDG (SUVmax: 3.5). As it was suspicious considering the differential diagnosis, including malignant lymphoma and inflammatory pseudotumor, she underwent laparoscopic splenectomy. The pathological results showed three types of vessels including capillaries, ectatic small veins, and sinusoids-like vessels, consistent with the features of SANT. DISCUSSION A SANT may have features that resemble those of malignancy, including the growing mass and the increase of FDG accumulation. CONCLUSION Although the preoperative diagnosis of SANT is difficult, it is necessary to make a diagnosis of SANT comprehensively, even when accumulation of FDG increased slightly during the follow-up period and suggested the possibility of malignant diseases.

['Matsubara|Keiso|K|', 'Oshita|Akihiko|A|', 'Nishisaka|Takashi|T|', 'Sasaki|Tamito|T|', 'Matsugu|Yasuhiro|Y|', 'Nakahara|Hideki|H|', 'Urushihara|Takashi|T|', 'Itamoto|Toshiyuki|T|']

2017

30965554

Differences in Eysenck's Personality Dimensions between a Group of Breast Cancer Survivors and the General Population.

Cancer may influence personality in patients and survivors. However, the possible relations between the treatments that the patients have undergone and the personality in survivors are not clear. This study aimed to establish the differences in personality between a group of breast cancer survivors and a control group, and to test the predictive utility of the treatments on the personality traits in survivors. Thirty breast cancer survivors and thirty participants from the general population completed the Eysenck personality questionnaire-revised (EPQ-R) and a socio-demographic questionnaire. Survivors had lower scores on extraversion and higher scores on neuroticism than the control group, but these differences were not significant. However, differences in psychoticism were significant, with higher scores in the survivor group. Breast-conserving therapy predicted extraversion while breast reconstruction predicted psychoticism. These results suggest that the physical consequences of surgery may lead to social and psychological impairments in this group of patients.

['García-Torres|Francisco|F|0000-0002-5129-6951', 'Castillo-Mayén|Rosario|R|0000-0001-8599-2368']

2019

24132468

In-office imaging capabilities among procedure-based specialty practices.

BACKGROUND Stark law's in-office ancillary services exception permits physicians to furnish designated health services in the office, including advanced imaging. OBJECTIVES To determine whether arrangements tailored to fit this loophole spur utilization. RESEARCH DESIGN Cross-sectional. SUBJECTS Procedure-based specialty clinics participating in the National Ambulatory Medical Care Survey. MEASURES Using restricted data files (2006-2008), we identified specialty practices with on-site advanced imaging capabilities (ie, computed tomography, magnetic resonance imaging, and/or positron emission tomography). We then characterized these practices and the physicians who worked in them over a variety of factors. Finally, we performed multivariable regression to evaluate the association between imaging use and the availability of in-office imaging. RESULTS Fourteen percent of practices performed advanced imaging on site. While this proportion remained stable over the study period for most specialties, it rose significantly among orthopedic surgery clinics from 13.6% to 31.3% (P = .023 for the temporal trend). The availability of advanced imaging varied by practice organization and size. For instance, 32.6% of large single-specialty groups provided in-office imaging as compared to only 10.1% of solo/partnership practices. While less than a quarter of specialty visits were made to practices that offered advanced imaging, these locations generated a third of all advanced imaging studies. In fact, 1 in 11 visits (9.0%; 95% confidence interval = 6.8% to 11.6%; P = .030) to them resulted in advanced imaging. CONCLUSIONS The availability of in-office advanced imaging is associated with increased imaging use.

['Hollingsworth|John M|JM|', 'Sakshaug|Joseph W|JW|', 'Zhang|Yun|Y|', 'Hollenbeck|Brent K|BK|']

2014

28559210

Cinnamaldehyde in diabetes: A review of pharmacology, pharmacokinetics and safety.

Cinnamaldehyde, one of the active components derived from Cinnamon, has been used as a natural flavorant and fragrance agent in kitchen and industry. Emerging studies have been performed over the past decades to evaluate its beneficial role in management of diabetes and its complications. This review highlights recent advances of cinnamaldehyde in its glucolipid lowering effects, its pharmacokinetics, and its safety by consulting the Pubmed, China Knowledge Resource Integrated, China Science and Technology Journal, National Science and Technology Library, Wanfang Data, and the Web of Science Databases. For the inquiries, keywords such as Cinnamon, cinnamaldehyde, property, synthesis, diabetes, obesity, pharmacokinetics, and safety were used in various combinations. Accumulating evidence supports the notion that cinnamaldehyde exhibits glucolipid lowering effects in diabetic animals by increasing glucose uptake and improving insulin sensitivity in adipose and skeletal muscle tissues, improving glycogen synthesis in liver, restoring pancreatic islets dysfunction, slowing gastric emptying rates, and improving diabetic renal and brain disorders. Cinnamaldehyde exerts these effects through its action on multiple signaling pathways, including PPARs, AMPK, PI3K/IRS-1, RBP4-GLUT4, and ERK/JNK/p38MAPK, TRPA1-ghrelin and Nrf2 pathways. In addition, cinnamaldehyde seems to regulate the activities of PTP1B and α-amylase. Furthermore, cinnamaldehyde has the potential of metalizing into cinnamyl alcohol and methyl cinnamate and cinnamic acid in the body. Finally, there is a potential toxicity concern about this compound. In summary, cinnamaldehyde supplementation is shown to improve glucose and lipid homeostasis in diabetic animals, which may provide a new option for diabetic intervention. To this end, further scientific evidences are required from clinical trials on its glucose regulating effects and safety.

['Zhu|Ruyuan|R|', 'Liu|Haixia|H|', 'Liu|Chenyue|C|', 'Wang|Lili|L|', 'Ma|Rufeng|R|', 'Chen|Beibei|B|', 'Li|Lin|L|', 'Niu|Jianzhao|J|', 'Fu|Min|M|', 'Zhang|Dongwei|D|', 'Gao|Sihua|S|']

2017

24563548

Singular perturbation theory for predicting extravasation of Brownian particles.

Motivated by recent studies on tumor treatments using the drug delivery of nanoparticles, we provide a singular perturbation theory and perform Brownian dynamics simulations to quantify the extravasation rate of Brownian particles in a shear flow over a circular pore with a lumped mass transfer resistance. The analytic theory we present is an expansion in the limit of a vanishing Péclet number (P), which is the ratio of convective fluxes to diffusive fluxes on the length scale of the pore. We state the concentration of particles near the pore and the extravasation rate (Sherwood number) to O(P1/2). This model improves upon previous studies because the results are valid for all values of the particle mass transfer coefficient across the pore, as modeled by the Damköhler number (κ), which is the ratio of the reaction rate to the diffusive mass transfer rate at the boundary. Previous studies focused on the adsorption-dominated regime (i.e., κ → ∞). Specifically, our work provides a theoretical basis and an interpolation-based approximate method for calculating the Sherwood number (a measure of the extravasation rate) for the case of finite resistance [κ ~ O(1)] at small Péclet numbers, which are physiologically important in the extravasation of nanoparticles. We compare the predictions of our theory and an approximate method to Brownian dynamics simulations with reflection-reaction boundary conditions as modeled by κ. They are found to agree well at small P and for the κ ≪ 1 and κ ≫ 1 asymptotic limits representing the diffusion-dominated and adsorption-dominated regimes, respectively. Although this model neglects the finite size effects of the particles, it provides an important first step toward understanding the physics of extravasation in the tumor vasculature.

['Shah|Preyas|P|', 'Fitzgibbon|Sean|S|', 'Narsimhan|Vivek|V|', 'Shaqfeh|Eric S G|ES|']

2014

23961485

Prevalence of gestational diabetes mellitus and its outcome in western Rajasthan.

BACKGROUND Gestational diabetes mellitus (GDM) is a metabolic disorder defined as glucose intolerance with the onset or first recognition during pregnancy. Women with GDM are at increased risk for adverse obstetric and perinatal outcome. Hence, it is imperative that an early detection and management of the disease is done to ensure better maternal and fetal outcomes. AIMS This study was done to evaluate the prevalence of gestational diabetes using diabetes in pregnancy Study Group India (DIPSI) criteria and further assess its feto-maternal outcome in western Rajasthan. MATERIALS AND METHODS This study was carried out in 500 patients between 24 and 28 weeks of gestation, attending the antenatal outdoor. These patients were given 75 g oral glucose irrespective of the meals and their plasma glucose was estimated at 2 h. Patients with plasma glucose values ΃140 mg/dl were labeled as GDM and the rest as the control or the non-GDM group. All GDM patients were followed up and treated with diet and/or insulin therapy till delivery to know maternal and fetal outcomes. RESULTS The prevalence of GDM in this study was 6.6%. Maternal and fetal complications in the GDM group were much higher than in the non-GDM group. Hypertension, vaginal candidiasis, and abruptio placentae were the common maternal complications, while macrosomia and stillbirths occurred in the fetuses. CONCLUSION GDM as a disease entity adversely affects maternal and fetal outcomes. This also builds a strong case for following DIPSI guidelines in diagnosis and management of GDM.

['Kalra|Priyanka|P|', 'Kachhwaha|Chetan Prakash|CP|', 'Singh|Hilda Victoria|HV|']

2013

32087367

Carbon dots as versatile nanoarchitectures for the treatment of neurological disorders and their theranostic applications: A review.

The development of novel methods plays a fundamental role in early diagnosis and controlling of neurological disorders (NDs). Blood-brain barrier (BBB) is the most challenging barrier for the development of neuro drug delivery systems due to its inhibiting ability to enter drugs and agents into central nervous system (CNS). Carbon dots (CDs) have shown to be very promising and outstanding agents for various biomedical applications (bio imaging studies, treatment of NDs and brain tumors). They exhibit remarkable properties such as biocompatibility, small size (less than 10 nm, enabling penetration into BBB), tunable optical properties, photostability and simple synthetic procedures, allowing them to act as ideal candidates in various fields of science. Therefore, the objective of this review is to overview the recent studies on CDs for the development of neuro drug delivery systems to reach CNS via crossing of BBB. Primarily, this review briefly outlines the unique optical properties and toxicity of CDs. The development of novel neuro drug delivery systems for various neurological disorders using CDs as carriers is described. This review also covers the potential applications of CDs in brain tumors imaging and treatment of neurodegenerative diseases. Finally, the sensing applications and future prospects of CDs are summarized.

['Ashrafizadeh|Milad|M|', 'Mohammadinejad|Reza|R|', 'Kailasa|Suresh Kumar|SK|', 'Ahmadi|Zahra|Z|', 'Afshar|Elham Ghasemipour|EG|', 'Pardakhty|Abbas|A|']

2020

32210102

DNA Methylation in Neurodegenerative and Cerebrovascular Disorders.

DNA methylation is an epigenetic mechanism by which methyl groups are added to DNA, playing a crucial role in gene expression regulation. The aim of the present study is to compare methylation status of healthy subjects with that of patients with Alzheimer's, Parkinson's or Cerebrovascular diseases. We also analyze methylation status of a transgenic Alzheimer's disease mouse model (3xTg-AD). Our results show that both global methylation (n = 141) and hydroxymethylation (n = 131) levels are reduced in DNA samples from buffy coats of patients with neurodegenerative disorders and age-related cerebrovascular disease. The importance of methylation and hydroxymethylation reduction is stressed by the finding that DNMT3a mRNA levels are also downregulated in buffy coats of patients with Dementia (n = 25). Global methylation is also reduced in brain, liver and serum samples of 3xTg-AD vs. wild type mice, such as DNMT3a mRNA levels that are also decreased in the brain of 3xTg-AD (n = 10). These results suggest that the use of global methylation and hydroxymethylation levels, together with the study of DNMT3a expression, could be useful as a new diagnostic biomarker for these prevalent disorders.

['Martínez-Iglesias|Olaia|O|', 'Carrera|Iván|I|', 'Carril|Juan Carlos|JC|0000-0002-3159-3545', 'Fernández-Novoa|Lucía|L|', 'Cacabelos|Natalia|N|', 'Cacabelos|Ramón|R|']

2020

34715110

Sources and composition of chemical pollution in Maritime Antarctica (King George Island), part 1: Sediment and water analysis for PAH sources evaluation in the vicinity of Arctowski station.

The paper presents a study regarding the identification of polycyclic aromatic hydrocarbons (PAHs) in fresh waters and surface sediments on the western shore of Admiralty Bay over four sampling seasons from 2017 to 2018. The results were compared to literature data from 2016 to provide a more comprehensive image of the environmental fate of PAHs over the years. The highest value of Σ PAHs was 82.9 ng/L and 445 ng/g dw in water and sediment samples, respectively. The analysis of PAH indicator ratio values showed that pyrogenic or mixed sources contribute to the PAH pollution in Antarctic sediments and water more than does petroleum. The main source is the combustion of biomass (e.g. as a result of fires) and coal, and PAHs are mostly associated with the activity of stations or are transported to a lesser extent by long-range atmospheric transport (LRAT) from South America. The values of the ΣLMW/ΣHMW ratio in sediments indicate that petrogenic sources contribute to PAH contamination, but among the six PAH ratios tested, petrogenic sources were identified as dominant in approximately 17-19% of cases. Lack of coherence in the obtained results confirms the mixed origin of PAHs in the studied samples. Although the differentiation of PAHs sources is still ambiguous, caution is recommended in light of the Antarctic system's evident and rapid response to global and local PAH emissions, and the dependency of accumulation and release cycle processes on weather conditions. A reduction in petrol usage in favour of renewable energy sources, and restriction of tourism are strongly recommended for better preservation of the pristine Antarctic environment.

['Potapowicz|Joanna|J|', 'Szopińska|Małgorzata|M|', 'Szumińska|Danuta|D|', 'Bialik|Robert Józef|RJ|', 'Polkowska|Żaneta|Ż|']

2021

33673381

CRISPR/Cas9 Mediated Knock Down of δ-ENaC Blunted the TNF-Induced Activation of ENaC in A549 Cells.

Tumor necrosis factor (TNF) is known to activate the epithelial Na+ channel (ENaC) in A549 cells. A549 cells are widely used model for ENaC research. The role of δ-ENaC subunit in TNF-induced activation has not been studied. In this study we hypothesized that δ-ENaC plays a major role in TNF-induced activation of ENaC channel in A549 cells which are widely used model for ENaC research. We used CRISPR/Cas 9 approach to knock down (KD) the δ-ENaC in A549 cells. Western blot and immunofluorescence assays were performed to analyze efficacy of δ-ENaC protein KD. Whole-cell patch clamp technique was used to analyze the TNF-induced activation of ENaC. Overexpression of wild type δ-ENaC in the δ-ENaC KD of A549 cells restored the TNF-induced activation of whole-cell Na+ current. Neither N-linked glycosylation sites nor carboxyl terminus domain of δ-ENaC was necessary for the TNF-induced activation of whole-cell Na+ current in δ-ENaC KD of A549 cells. Our data demonstrated that in A549 cells the δ-ENaC plays a major role in TNF-induced activation of ENaC.

['Shabbir|Waheed|W|', 'Topcagic|Nermina|N|', 'Aufy|Mohammed|M|', 'Oz|Murat|M|']

2021

33195283

Construction of a Five-Super-Enhancer-Associated-Genes Prognostic Model for Osteosarcoma Patients.

Osteosarcoma is a malignant tumor most commonly arising in children and adolescents and associated with poor prognosis. In recent years, some prognostic models have been constructed to assist clinicians in the treatment of osteosarcoma. However, the prognosis and treatment of patients with osteosarcoma remain unsatisfactory. Notably, super-enhancer (SE)-associated genes strongly promote the progression of osteosarcoma. In the present study, we constructed a novel effective prognostic model using SE-associated genes from osteosarcoma. Five SE-associated genes were initially screened through the least absolute shrinkage and selection operator (Lasso) penalized Cox regression, as well as univariate and multivariate Cox regression analyses. Meanwhile, a risk score model was constructed using the expression of these five genes. The excellent performance of the five-SE-associated-gene-based prognostic model was determined via time-dependent receiver operating characteristic (ROC) curves and Kaplan-Meier curves. Inferior outcome of overall survival (OS) was predicted in the high-risk group. A nomogram based on the polygenic risk score model was further established to validate the performance of the prognostic model. It showed that our prognostic model performed outstandingly in predicting 1-, 3-, and 5-year OS of patients with osteosarcoma. Meanwhile, these five genes also belonged to the hub genes associated with survival and necrosis of osteosarcoma according to the result of weighted gene co-expression network analysis based on the dataset of GSE39058. Therefore, we believe that the five-SE-associated-gene-based prognostic model established in this study can accurately predict the prognosis of patients with osteosarcoma and effectively assist clinicians in treating osteosarcoma in the future.

['Ouyang|Zhanbo|Z|', 'Li|Guohua|G|', 'Zhu|Haihong|H|', 'Wang|Jiaojiao|J|', 'Qi|Tingting|T|', 'Qu|Qiang|Q|', 'Tu|Chao|C|', 'Qu|Jian|J|', 'Lu|Qiong|Q|']

2020

24374856

Single-dose pharmacokinetic studies of abiraterone acetate in men with hepatic or renal impairment.

Three open-label, single-dose studies investigated the impact of hepatic or renal impairment on abiraterone acetate pharmacokinetics and safety/tolerability in non-cancer patients. Patients (n = 8 each group) with mild/moderate hepatic impairment or end-stage renal disease (ESRD), and age-, BMI-matched healthy controls received a single oral 1,000 mg abiraterone acetate (tablet dose); while patients (n = 8 each) with severe hepatic impairment and matched healthy controls received 125- and 2,000-mg abiraterone acetate (suspension doses), respectively (systemic exposure of abiraterone acetate suspension is approximately half to that of tablet formulation). Blood was sampled at specified timepoints up to 72 or 96 hours postdose to measure plasma abiraterone concentrations. Abiraterone exposure was comparable between healthy controls and patients with mild hepatic impairment or ESRD, but increased by 4-fold in patients with moderate hepatic impairment. Despite a 16-fold reduction in dose, abiraterone exposure in patients with severe hepatic impairment was about 22% and 44% of the Cmax and AUC∞ of healthy controls, respectively. These results suggest that abiraterone pharmacokinetics were not changed markedly in patients with ESRD or mild hepatic impairment. However, the capacity to eliminate abiraterone was substantially compromised in patients with moderate or severe hepatic impairment. A single-dose administration of abiraterone acetate was well-tolerated.

['Marbury|Thomas|T|', 'Lawitz|Eric|E|', 'Stonerock|Robert|R|', 'Gonzalez|Martha|M|', 'Jiao|James|J|', 'Breeding|Jim|J|', 'Haqq|Christopher|C|', 'Verboven|Peter|P|', 'Stieltjes|Hans|H|', 'Yu|Margaret|M|', 'Molina|Arturo|A|', 'Acharya|Milin|M|', 'Chien|Caly|C|', 'Tran|NamPhuong|N|']

2014

31155778

Seeing the light: urban stream restoration affects stream metabolism and nitrate uptake via changes in canopy cover.

The continually increasing global population residing in urban landscapes impacts numerous ecosystem functions and services provided by urban streams. Urban stream restoration is often employed to offset these impacts and conserve or enhance the various functions and services these streams provide. Despite the assumption that "if you build it, [the function] will come," current understanding of the effects of urban stream restoration on stream ecosystem functions are based on short term studies that may not capture variation in restoration effectiveness over time. We quantified the impact of stream restoration on nutrient and energy dynamics of urban streams by studying 10 urban stream reaches (five restored, five unrestored) in the Baltimore, Maryland, USA, region over a two-year period. We measured gross primary production (GPP) and ecosystem respiration (ER) at the whole-stream scale continuously throughout the study and nitrate (NO3 - -N) spiraling rates seasonally (spring, summer, autumn) across all reaches. There was no significant restoration effect on NO3 - -N spiraling across reaches. However, there was a significant canopy cover effect on NO3 - -N spiraling, and directly comparing paired sets of unrestored-restored reaches showed that restoration does affect NO3 - -N spiraling after accounting for other environmental variation. Furthermore, there was a change in GPP : ER seasonality, with restored and open-canopied reaches exhibiting higher GPP : ER during summer. The restoration effect, though, appears contingent upon altered canopy cover, which is likely to be a temporary effect of restoration and is a driver of multiple ecosystem services, e.g., habitat, riparian nutrient processing. Our results suggest that decision-making about stream restoration, including evaluations of nutrient benefits, clearly needs to consider spatial and temporal dynamics of canopy cover and trade-offs among multiple ecosystem services.

['Reisinger|Alexander J|AJ|0000-0003-4096-2637', 'Doody|Thomas R|TR|', 'Groffman|Peter M|PM|', 'Kaushal|Sujay S|SS|', 'Rosi|Emma J|EJ|']

2019

33428881

Determining the effects of nutrition on the reproductive physiology of male mosquitoes.

Nutrition affects multiple aspects of insect physiology such as body size and fecundity, but we lack a detailed understanding of how nutrition influences the reproductive physiology of male insects such as mosquitoes. Given that female mosquitoes are vectors of many deadly diseases and can quickly proliferate, understanding how male nutrition impacts female fecundity could be of critical importance. To uncover the relationship between nutrition in adult male mosquitoes and its impacts on reproductive physiology, we reared larvae of the Northern house mosquito, Culex pipiens, on a standard lab diet and divided adult males among three different dietary treatments: low (3%), moderate (10%), and high (20%) sucrose. We found that although overall body size did not differ among treatments, one-week-old males raised on the 3% sucrose diet had significantly smaller male accessory glands (MAGs) compared to males that consumed the 10% and the 20% sucrose diets. Diet affected whole-body lipid content but did not affect whole-body protein content. Using nuclear magnetic resonance (NMR) spectroscopy, we found that diet altered the metabolic composition of the MAGs, including changes in lactic acid, formic acid, and glucose. We also observed changes in protein and lipid abundance and composition in MAGs. Females who mated with males on the 3% diet were found to produce significantly fewer larvae than females who had mated with males on the 10% diet. Taken together, our results demonstrate that the diet of adult male mosquitoes clearly affects male reproductive physiology and female fecundity.

['Huck|Derek T|DT|', 'Klein|Matthias S|MS|', 'Meuti|Megan E|ME|']

2021

26188438

Intimate partner violence in neighborhood context: The roles of structural disadvantage, subjective disorder, and emotional distress.

Most theoretical treatments of intimate partner violence (IPV) focus on individual-level processes. Some researchers have attempted to situate IPV within the larger neighborhood context, but few studies have sought to link structural- and individual-level factors. The current analyses fill a research gap by examining the role of anger and depression in the association between neighborhood disadvantage and IPV. Using data from the Toledo Adolescent Relationships Study (TARS) and the 2000 Census, this study focuses on structural indicators of disadvantage as well as subjective disorder, and highlights the complex associations between neighborhood conditions, emotional distress, and IPV. Findings indicate that anger and depressive symptoms partially explain the association between neighborhood disadvantage and IPV. Additionally, the associations between disadvantage, disorder, and IPV depend on respondent's level of anger. Results underscore the need to further consider the role of neighborhood factors (both objective and subjective) in relation to IPV, and also suggest the utility of introducing individual-level emotional measures to assess the circumstances under which neighborhoods matter most.

['Copp|Jennifer E|JE|', 'Kuhl|Danielle C|DC|', 'Giordano|Peggy C|PC|', 'Longmore|Monica A|MA|', 'Manning|Wendy D|WD|']

2015

30007711

Effect of mitochondrial cytochrome c release and its redox state on the mitochondrial-dependent apoptotic cascade reaction and tenderization of yak meat during postmortem aging.

We aim to investigate the effect of mitochondrial cytochrome c release and its redox state on the mitochondrial-dependent apoptotic pathway and yak meat tenderization during postmortem aging. Results indicated that the internal environment factors considerably decreased, whereas mitochondrial dysfunction increased in the early stage (0-72 h). Moreover, the release of mitochondrial cytochrome c into the cytosol, which was an apoptotic early event and the apoptosome elements in the cytoplasm changed remarkably with the increase of aging time. Meanwhile, N,N,N',N'-tetramethylphenylene-1, 4-diamine (TMPD) inhibited the mitochondrial apoptotic process and postmortem meat tenderization by influencing the redox state of cytochrome c and apoptotic factors. These findings confirmed that the internal environment factors in the muscles provided essential conditions for mitochondrial cytochrome c, which activated the mitochondrial apoptotic pathway by forming apoptosome complexes. The reduction state of cytochrome c produced by TMPD plays a negative role in the activation of the mitochondrial apoptotic cascade reaction and meat tenderization during postmortem aging. We conclude that mitochondrial cytochrome c release and oxidized cytochrome c plays a significant role in yak meat tenderization by regulating the mitochondrial apoptotic pathway.

['Wang|Linlin|L|', 'Ma|Guoyuan|G|', 'Zhang|Yubin|Y|', 'Shi|Xixiong|X|', 'Han|Ling|L|', 'Yu|Qunli|Q|', 'Zhao|Suonan|S|', 'Ma|Junyi|J|']

2018

32766770

The IBD-F Patient Self-Assessment Scale Accurately Depicts the Level of Fatigue and Predicts a Negative Effect on the Quality of Life of Patients With IBD in Clinical Remission.

BACKGROUND Fatigue is highly prevalent among patients with inflammatory bowel disease (IBD) and may have an unfavorable impact on quality of life (QoL). The IBD-Fatigue scale (with components SCORE1 and SCORE2) is a recently developed disease-specific questionnaire. We sought to validate a Greek version of IBD-F and use it to assess the severity and characteristics of fatigue and its effect on QoL in our study population. METHODS The IBD-F scale was validated and used to obtain fatigue-related data from patients with IBD attending a tertiary care hospital. Correlations with other fatigue and QoL instruments were performed. RESULTS The Greek IBD-F showed high internal consistency and test-retest reliability (Cronbach's alpha = 0.901/0.966 and intraclass correlation coefficient = 0.876/0.895 for SCORE1/SCORE2, respectively). A SCORE1 >7.5 suggested "significant" fatigue. In a cohort of 157 patients (mean age = 35.8 y; male patients = 52.2%; patients with Crohn disease = 65.6%), both SCORE1 and SCORE2 were significantly associated with Crohn disease (odds ratio [OR] = 4.17; 95% confidence interval [CI], 2.05-8.47; b = 8.5; 95% CI, 2.8-14.1, respectively), female sex (OR = 7.27; 95% CI, 3.19-16.6; b = 15.3; 95% CI, 9-21.6), and Harvey-Bradshaw Index/Simple Clinical Colitis Activity Index score (OR = 1.22; 95% CI, 1.06-1.39; b = 1.8; 95% CI, 0.9-2.8). A SCORE1 >7.5 was present in 46% of patients in remission, and 82% of patients with a baseline SCORE1 >7.5 remained fatigued at serial measurements. The SCORE1 was significantly associated with impaired QoL (P < 0.001). CONCLUSIONS The validated IBD-F scale is a useful and applicable instrument for use in the IBD population. A large proportion of patients have significant fatigue, which is maintained longitudinally, independent of inflammatory activity. Fatigue impairs QoL, thus necessitating interventions that may lead to its amelioration in the IBD population.

['Varbobitis|Ioannis|I|', 'Kokkotis|Georgios|G|', 'Gizis|Michael|M|', 'Perlepe|Nikoletta|N|', 'Laoudi|Efrosini|E|', 'Bletsa|Maria|M|', 'Bekiari|Despoina|D|', 'Koutsounas|Ioannis|I|', 'Kounadis|Georgios|G|', 'Xourafas|Vassileios|V|', 'Lagou|Stilliani|S|', 'Kolios|George|G|', 'Papakonstantinou|Ioannis|I|', 'Bamias|Giorgos|G|']

2021

24137297

Use of a calcium tracer to detect stone increments in a rat calcium oxalate xenoplantation model.

The majority of urinary stones have been observed to grow by circular increments in the clinic and in animal studies. However, the mechanism of stone formation has not yet been elucidated. Marking the stone at specific time-points during the growth of the stone is likely to enable the clarification of the mechanisms behind lithogenesis. The objective of this study was to evaluate the role and efficacy of calcium-tracing fluorescence in the labeling of stone lamination in a rat calcium oxalate xenoplantation model. In the rat calcium oxalate xenoplantation model, human renal stone particles, extracted by percutaneous nephrolithotomy, were xenoplanted into the bladders of Wistar rats in a sterile manner. The rats received 1% ethylene glycol in their drinking water, starting from the day following the stone xenoplantation. Two weeks subsequent to this, three calcium-tracing fluorochromes, alizarin complexone, calcein and xylenol orange were administered by intraperitoneal injection. The newly-formed bladder stones were cut into slices and examined using light and fluorescence microscopy. The newly-formed bladder stones had a large variance in size, and circular increments were observed in the sections of the stones. The stones were successfully labeled with calcein and alizarin complexone, although calcein labeling provided superior results. However, the use of xylenol orange did not result in clear labeling. The calcium-tracing fluorochromes, calcein and alizarin complexone may be effectively used to label stone lamination in rat models.

['Wang|Shuo|S|', 'Xu|Qingquan|Q|', 'Huang|Xiaobo|X|', 'Lin|Jingxing|J|', 'Wang|Jinxing|J|', 'Wang|Xiaofeng|X|']

2013

33367713

Brugada syndrome and syncope: a practical approach for diagnosis and treatment.

Syncope in patients with Brugada electrocardiogram pattern may represent a conundrum in the decision algorithm because incidental benign forms, especially neurally mediated syncope, are very frequent in this syndrome similarly to the general population. Arrhythmic syncope in Brugada syndrome typically results from a self-terminating sustained ventricular tachycardia or paroxysmal ventricular fibrillation, potentially leading to sudden cardiac death. Distinguishing syncope due to malignant arrhythmias from a benign form is often difficult unless an electrocardiogram is recorded during the episode. We performed a review of the existing literature and propose a practical approach for diagnosis and treatment of the patients with Brugada syndrome and syncope.

['Mascia|Giuseppe|G|', 'Bona|Roberta Della|RD|0000-0003-4146-7099', 'Ameri|Pietro|P|0000-0001-7167-7287', 'Canepa|Marco|M|0000-0001-9063-5576', 'Porto|Italo|I|0000-0002-9854-5046', 'Parati|Gianfranco|G|0000-0001-9402-7439', 'Crotti|Lia|L|', 'Brignole|Michele|M|0000-0002-1845-5607']

2021

33585337

Gitelman Syndrome: A Rare Case of Hypokalaemia and a Novel Mutation.

Gitelman syndrome (GS) is a hereditary renal tubulopathy caused by mutations in the SLC12A3 gene which encodes the thiazide-sensitive apical sodium-chloride cotransporter. GS is characterized by hypokalaemia, hypomagnesaemia and metabolic alkalosis. Treatment is based on potassium and magnesium replacement ad eternum. We present the case of a young man with palpitations and persistent hypokalaemia, who was diagnosed with GS. Genetic testing revealed 2 mutations in the gene SLC12A3 of combined heterozygosity, both considered pathological. Interestingly, 1 of these mutations was not yet described in the literature or in the reviewed databases. We also discuss the clinical approach and the specificities of managing this rare hereditary renal tubulopathy.. LEARNING POINTS Gitelman syndrome is a rare cause of persistent hypokalaemia.A definitive diagnosis is determined by the identification of mutations in the SLC12A3 gene.Management consists of chronic potassium and magnesium supplementation aimed at symptom control.

['Matos|Clara|C|', 'Correia|Fábio|F|', 'da Silva|Inês Nunes|IN|', 'Carola|Sofia|S|', 'Órfão|Ana|A|', 'Ferreira|Maria|M|', 'Branco|Teresa|T|']

2021

34171987

Comparative insights into genome signatures of ferric iron oxide- and anode-stimulated Desulfuromonas spp. strains.

BACKGROUND Halotolerant Fe (III) oxide reducers affiliated in the family Desulfuromonadaceae are ubiquitous and drive the carbon, nitrogen, sulfur and metal cycles in marine subsurface sediment. Due to their possible application in bioremediation and bioelectrochemical engineering, some of phylogenetically close Desulfuromonas spp. strains have been isolated through enrichment with crystalline Fe (III) oxide and anode. The strains isolated using electron acceptors with distinct redox potentials may have different abilities, for instance, of extracellular electron transport, surface recognition and colonization. The objective of this study was to identify the different genomic signatures between the crystalline Fe (III) oxide-stimulated strain AOP6 and the anode-stimulated strains WTL and DDH964 by comparative genome analysis. RESULTS The AOP6 genome possessed the flagellar biosynthesis gene cluster, as well as diverse and abundant genes involved in chemotaxis sensory systems and c-type cytochromes capable of reduction of electron acceptors with low redox potentials. The WTL and DDH964 genomes lacked the flagellar biosynthesis cluster and exhibited a massive expansion of transposable gene elements that might mediate genome rearrangement, while they were deficient in some of the chemotaxis and cytochrome genes and included the genes for oxygen resistance. CONCLUSIONS Our results revealed the genomic signatures distinctive for the ferric iron oxide- and anode-stimulated Desulfuromonas spp. strains. These findings highlighted the different metabolic abilities, such as extracellular electron transfer and environmental stress resistance, of these phylogenetically close bacterial strains, casting light on genome evolution of the subsurface Fe (III) oxide reducers.

['Guo|Yong|Y|', 'Aoyagi|Tomo|T|', 'Hori|Tomoyuki|T|']

2021

30036952

Protection of Anthocyanin from Myrica rubra against Cerebral Ischemia-Reperfusion Injury via Modulation of the TLR4/NF-κB and NLRP3 Pathways.

Myrica rubra (MR) is rich in anthocyanins, and it has good anti-cancer, anti-aging, antioxidant, and antiviral effects. The proportion of disability and death caused by ischemic stroke gradually increased, becoming a major disease that is harmful to human health. However, research on effects of anthocyanin from MR on cerebral ischemia-reperfusion (I/R) injury is rare. In this study, we prepared eight purified anthocyanin extracts (PAEs) from different types of MR, and examined the amounts of total anthocyanin (TA) and cyanidin-3-O-glucoside (C-3-G). After one week of PAE treatment, the cerebral infarction volume, disease damage, and contents of nitric oxide and malondialdehyde were reduced, while the level of superoxide dismutase was increased in I/R mice. Altogether, our results show that Boqi¹ MR contained the most TA (22.07%) and C-3-G (21.28%), and that PAE isolated from Dongkui MR can protect the brain from I/R injury in mice, with the mechanism possibly related to the Toll-like receptor 4 (TLR4)/ nuclear factor-κB (NF-κB) and NOD-like receptor pyrin domain-containing 3 protein (NLRP3) pathways.

['Cui|Hong-Xin|HX|', 'Chen|Ji-Hong|JH|', 'Li|Jing-Wan|JW|', 'Cheng|Fang-Rong|FR|', 'Yuan|Ke|K|']

2018

28484551

Self inflicted stab with a knife: An unusual mode of penetrating brain injury.

Self-inflicted penetrating injuries have been very rarely described in the medical literature. We describe a middle-aged woman, who had driven a long knife inside her skull with the help of a brick. She had done this to get relief from chronic headache, which was troubling her for 10 years. Patient was hemodynamically stable and had Glassgow Coma scale score of 15. She was immediately operated to remove the knife and evacuate the acute subdural hematoma. Patient made a steady postoperative recovery. Psychiatric and neurological evaluation in the postoperative period revealed features of mixed anxiety and depressive disorder with migraine, for which she was started on treatment. Management of such cases needs a team approach with inputs from neurosurgeon, neurophysician and psychiatrist.

['Qazi|Zeeshan|Z|', 'Ojha|Bal Krishna|BK|', 'Chandra|Anil|A|', 'Singh|Sunil Kumar|SK|', 'Srivastava|Chhitij|C|', 'Verma|Nishant|N|', 'Patil|Tushar B|TB|']

2017

30134543

Core-Shell Nanofibrous Scaffold Based on Polycaprolactone-Silk Fibroin Emulsion Electrospinning for Tissue Engineering Applications.

The vast domain of regenerative medicine comprises complex interactions between specific cells' extracellular matrix (ECM) towards intracellular matrix formation, its secretion, and modulation of tissue as a whole. In this domain, engineering scaffold utilizing biomaterials along with cells towards formation of living tissues is of immense importance especially for bridging the existing gap of late; nanostructures are offering promising capability of mechano-biological response needed for tissue regeneration. Materials are selected for scaffold fabrication by considering both the mechanical integrity and bioactivity cues they offer. Herein, polycaprolactone (PCL) (biodegradable polyester) and 'nature's wonder' biopolymer silk fibroin (SF) are explored in judicious combinations of emulsion electrospinning rather than conventional electrospinning of polymer blends. The water in oil (W/O) emulsions' stability is found to be dependent upon the concentration of SF (aqueous phase) dispersed in the PCL solution (organic continuous phase). The spinnability of the emulsions is more dependent upon the viscosity of the solution, dominated by the molecular weight of PCL and its concentration than the conductivity. The nanofibers exhibited distinct core-shell structure with better cytocompatibility and cellular growth with the incorporation of the silk fibroin biopolymer.

['Roy|Trina|T|', 'Maity|Priti Prasanna|PP|', 'Rameshbabu|Arun Prabhu|AP|', 'Das|Bodhisatwa|B|', 'John|Athira|A|', 'Dutta|Abir|A|', 'Ghorai|Sanjoy Kumar|SK|', 'Chattopadhyay|Santanu|S|', 'Dhara|Santanu|S|']

2018

29052999

Impulsivity and compulsivity in Internet gaming disorder: A comparison with obsessive-compulsive disorder and alcohol use disorder.

Background and aims Internet gaming disorder (IGD) is characterized by a loss of control and a preoccupation with Internet games leading to repetitive behavior. We aimed to compare the baseline neuropsychological profiles in IGD, alcohol use disorder (AUD), and obsessive-compulsive disorder (OCD) in the spectrum of impulsivity and compulsivity. Methods A total of 225 subjects (IGD, N = 86; AUD, N = 39; OCD, N = 23; healthy controls, N = 77) were administered traditional neuropsychological tests including Korean version of the Stroop Color-Word test and computerized neuropsychological tests, including the stop signal test (SST) and the intra-extra dimensional set shift test (IED). Results Within the domain of impulsivity, the IGD and OCD groups made significantly more direction errors in SST (p = .003, p = .001) and showed significantly delayed reaction times in the color-word reading condition of the Stroop test (p = .049, p = .001). The OCD group showed the slowest reading time in the color-word condition among the four groups. Within the domain of compulsivity, IGD patients showed the worst performance in IED total trials measuring attentional set shifting ability among the groups. Conclusions Both the IGD and OCD groups shared impairment in inhibitory control functions as well as cognitive inflexibility. Neurocognitive dysfunction in IGD is linked to feature of impulsivity and compulsivity of behavioral addiction rather than impulse dyscontrol by itself.

['Kim|Yeon-Jin|YJ|', 'Lim|Jae A|JA|', 'Lee|Ji Yoon|JY|', 'Oh|Sohee|S|', 'Kim|Sung Nyun|SN|', 'Kim|Dai Jin|DJ|', 'Ha|Jong Eun|JE|', 'Kwon|Jun Soo|JS|', 'Choi|Jung-Seok|JS|']

2017

34694067

Delivery of MiR335-5p-Pendant Tetrahedron DNA Nanostructures Using an Injectable Heparin Lithium Hydrogel for Challenging Bone Defects in Steroid-Associated Osteonecrosis.

Corticosteroids-induced Dickkopf-1 (DKK1) upregulation and Wnt signaling inhibition result in bone metabolism disorder and steroid-associated osteonecrosis (SAON). Implanting biomaterials to regulate the Wnt pathway is a promising method to repair challenging bone defects associated with SAON. Here, tetrahedral DNA nanostructures (TDNs) are fabricated as gene carriers to deliver MiR335-5p, which targets DKK1 translation. Heparin lithium hydrogel (Li-hep-gel) is synthesized to act as a lithium and MiR@TDNs delivery agent. Finally, the repair effects on challenging bone defect in SAON using a MiR@TDNs/Li-hep-gel composite are assessed in vivo. The results reveal that MiR@TDNs are absorbed by bone mesenchymal stem cells (BMSCs) and increase cell viability and reduce apoptosis. Moreover, MiR@TDNs promote alkaline phosphatase expression and calcium nodular deposition, decrease lipid droplet expression of BMSCs, and improve vascular endothelial growth factor secretion and vascular-like structure formation in vitro. After MiR@TDNs/Li-hep-gel is implanted into the SAON model, the internal bone defect of osteonecrosis is repaired with a large area of new bone accompanied with neovascularization and reduced empty lacunae. In conclusion, MiR@TDNs/Li-hep-gel can provide dual delivery of lithium and MiR@TDNs, which synergistically upregulate the Wnt signaling pathway, enhancing bone regeneration in challenging bone defects, and can be potentially used in SAON repair.

['Li|Donghai|D|', 'Yang|Zhouyuan|Z|', 'Luo|Yue|Y|', 'Zhao|Xin|X|', 'Tian|Meng|M|', 'Kang|Pengde|P|https://orcid.org/0000-0002-6474-440X']

2021

30309564

Effect of hulling methods and roasting treatment on phenolic compounds and physicochemical properties of cultivars 'Ohadi' and 'Uzun' pistachios (Pistacia vera L.).

The aim of this study was to identify phenolic compounds and measure the physicochemical properties of two pistachio (Pistacia vera L.) cultivars ('Uzun' and 'Ohadi'). For this purpose, the pistachios were subjected to four different hulling methods (wet hulling-WT, brine hulling-BR, wet-dry hulling-WD, and dry-dry hulling-DD) and a standard roasting treatment. Phenolic compounds were analyzed by HPLC-DAD-ESI-MSn. Twelve phenolics were identified and quantified in the samples, 10 of which were flavonoid and two non-flavonoid phenolic acids. In both cultivars, the major compounds were found to be gallic acid and catechin followed by eriodictyol-7-O-glucoside and eriodictyol. The dry-dry hulling method treated sample had higher antioxidant capacity, total phenol content, and phenolic compounds than the other hulling methods in both pistachio cultivars. After the roasting treatment, the antioxidant capacity, phenolic content, and a∗ value increased while the L∗ and b∗ values decreased.

['Sonmezdag|Ahmet Salih|AS|', 'Kelebek|Hasim|H|', 'Selli|Serkan|S|']

2019

29501474

Factors associated with non-participation in cervical cancer screening - A nationwide study of nearly half a million women in Denmark.

Cervical cancer occurs most often in under-screened women. In this nationwide register study, we described differences in sociodemographic characteristics between passive and active non-participants and examined socio-demographic characteristics, reproductive history, and mental and physical health as potential determinants for passive non-participation compared with participation in the Danish cervical cancer screening program. Screening history in women aged 23-49 years invited for cervical cancer screening in 2008-2009 was retrieved from the Danish Pathology Databank with information about dates of invitation and unsubscription. We identified participants (n = 402,984), active non-participants (n = 10,251) and passive non-participants (n = 63,435) within four years following baseline invitation and retrieved data about the study population from high-quality registries. We examined differences in socio-demographic characteristics of passive and active non-participants, and used multiple logistic regression analyses to identify potential determinants of passive non-participation. We found that active and passive non-participants differed in relation to socio-demography. When compared with screening participants, the odds of passive non-participation was increased in women who originated from less developed countries; were unmarried; had basic education or low income; had four or more children; smoked during pregnancy; had multiple induced abortions; or had a history of obesity, intoxicant abuse or schizophrenia or other psychoses. In conclusion, in this nationwide, prospective, population-based study, differences in socio-demographic characteristics between passive and active non-participants were found. Furthermore, sociodemography, reproductive history, and mental and physical health were determinants for passive non-participation. Addressing inequalities in screening attendance may help to further decrease the incidence of and mortality from cervical cancer.

['Harder|Elise|E|', 'Juul|Kirsten E|KE|', 'Jensen|Signe M|SM|', 'Thomsen|Louise T|LT|', 'Frederiksen|Kirsten|K|', 'Kjaer|Susanne K|SK|']

2018

32742984

Effects of prostaglandin E combined with continuous renal replacement therapy on septic acute kidney injury.

BACKGROUND The effects of prostaglandin E (PGE) combined with continuous renal replacement therapy (CRRT) on renal function and inflammatory responses in patients with septic acute kidney injury (SAKI) remain unclear. AIM To investigate the effects of PGE combined with CRRT on urinary augmenter of liver regeneration (ALR), urinary Na+/H+ exchanger 3 (NHE3), and serum inflammatory cytokines in patients with SAKI. METHODS The clinical data of 114 patients with SAKI admitted to Yichang Second People's Hospital from May 2017 to January 2019 were collected. Fifty-three cases treated by CRRT alone were included in a control group, while the other 61 cases treated with PGE combined with CRRT were included in an experimental group. Their urinary ALR, urinary NHE3, serum inflammatory cytokines, renal function indices, and immune function indices were detected. Changes in disease recovery and the incidence of adverse reactions were observed. The 28-d survival curve was plotted. RESULTS Before treatment, urinary ALR, urinary NHE3, blood urea nitrogen (BUN), serum creatinine (SCr), CD3+ T lymphocytes, CD4+ T lymphocytes, and CD4+/CD8+ T lymphocyte ratio in the control and experimental groups were approximately the same. After treatment, urinary ALR and NHE3 decreased, while BUN, SCr, CD3+ T lymphocytes, CD4+ T lymphocytes, and CD4+/CD8+ T lymphocyte ratio increased in all subjects. Urinary ALR, urinary NHE3, BUN, and SCr in the experimental group were significantly lower than those in the control group, while CD3+ T lymphocytes, CD4+ T lymphocytes, and CD4+/CD8+ T lymphocyte ratio were significantly higher than those in the control group (P < 0.05). After treatment, the levels of tumor necrosis factor-α, interleukin-18, and high sensitivity C-reactive protein in the experimental group were significantly lower than those in the control group (P < 0.05). The time for urine volume recovery and intensive care unit treatment in the experimental group was significantly shorter than that in the control group (P < 0.05), although there was no statistically significant difference in hospital stays between the two groups. The total incidence of adverse reactions did not differ statistically between the two groups. The 28-d survival rate in the experimental group (80.33%) was significantly higher than that in the control group (66.04%). CONCLUSION PGE combined with CRRT is clinically effective for treating SAKI, and the combination therapy can significantly improve renal function and reduce inflammatory responses.

['Lei|Li|L|', 'Wang|Ming-Jun|MJ|', 'Zhang|Sheng|S|', 'Hu|Da-Jun|DJ|']

2020

27041274

Colorimetric Glucose Assay Based on Magnetic Particles Having Pseudo-peroxidase Activity and Immobilized Glucose Oxidase.

Magnetic particles (MPs) are currently used as a suitable alternative for peroxidase in the construction of novel biosensors, analytic and diagnostic methods. Their better chemical and thermal stabilities predestine them as appropriate pseudo-enzymatic catalysts. In this point of view, our research was focused on preparation of simply and fast method for immobilization of glucose oxidase onto surface of MPs with peroxidase-like activity. Spectrophotometric method (wavelength 450 nm) optimized for glucose determination using modified MPs has been successfully developed. Concentration curve for optimization of method was assayed, and Michaelis-Menten constant (K m) calculated, maximum reaction rate (V max), limit of detection, and correlation coefficient were determined to be 0.13 mmol/l (2.34 mg/dl), 1.79 pkat, 3.74 µmol/l (0.067 mg/dl), and 0.996, respectively. Interferences of other sugars such as sucrose, sorbitol, deoxyribose, maltose, and fructose were determined as well as effect of substances presenting in plasma (ascorbic acid, reduced glutathione, trolox, and urea). Results in comparison with positive and negative controls showed no interferences of the other sugars and no influence of plasma substances to measuring of glucose. The constructed method showed corresponding results with linear dependence and a correlation coefficient of 0.997. Possibility of repeated use of modified MPs was successfully proved.

['Martinkova|Pavla|P|', 'Opatrilova|Radka|R|', 'Kruzliak|Peter|P|', 'Styriak|Igor|I|', 'Pohanka|Miroslav|M|']

2016

28764014

Generation of bioactive peptides from duck meat during post-mortem aging.

The objective of this study was to investigate the endogenous release of bioactive peptides in duck meat during 7days of post-mortem aging. The degradation of muscle proteins led to release of small peptides (<5kDa). The peptides formed in the samples after 3days post-mortem exhibited highest DPPH radical scavenging, oxygen radical scavenging (ORAC) and ferric reducing antioxidant power (FRAP). By using size-exclusion chromatography, the initial extract was purified into three fractions (A-C) in which fraction C exhibited the highest antioxidant activity. In total 18 peptides were sequenced and identified in the fractions by nano LC-MS/MS. Among these peptides, the peptides of fraction C possessed the lowest molecular weight and consisted of the highest amount of hydrophobic amino acid, which might be responsible for the antioxidant property of aged duck meat. The present findings provide an insight into the release of bioactive peptides in duck meat during post-mortem aging.

['Liu|Dongmei|D|', 'Chen|Xing|X|', 'Huang|Jichao|J|', 'Huang|Ming|M|', 'Zhou|Guanghong|G|']

2017

26572851

Factors associated with peritoneal dialysis catheter complications in children.

BACKGROUND/PURPOSE Peritoneal dialysis (PD) is a common method of renal replacement therapy for children. However, placement of PD catheters has risk, and some are never used. METHODS We conducted a retrospective chart review of children with a PD catheter placed between 2000 and 2014. Logistic regression analyses were used to identify covariates associated with complications. RESULTS We identified 175 children with PD catheters. 110 complications developed in 80 children (45.7%). Complications including unexpected return to the operating room and peritonitis increased as the length of time a catheter was in place increased. Children who weighed <12.4 kg had 3.2 times greater odds of developing a leak (95% CI 1.21-8.63, p=0.02). Twelve children never used their PD catheters, 9 with acute kidney injury (AKI) who recovered from their disease more quickly than expected. No covariate was associated with nonuse. CONCLUSIONS Complications with PD catheters are common and increase the longer catheters are in place. Lower weight children are at greater risk of PD catheter leak. Decreased initial volumes of dialysate in smaller children may mitigate this risk. Nonuse may be reduced if dialysis is permitted the day of placement for children with AKI.

['Stewart|Camille L|CL|', 'Acker|Shannon N|SN|', 'Pyle|Laura L|LL|', 'Kulungowski|Ann|A|', 'Cadnapaphornchai|Melissa|M|', 'Bruny|Jennifer L|JL|', 'Karrer|Frederick|F|']

2016

34030274

Effect of ultraviolet radiation (type B) and titanium dioxide nanoparticles on the interspecific interaction between Microcystis flos-aquae and Pseudokirchneriella subcapitata.

Anthropogenic activities have led to the depletion of the ultraviolet radiation screening ozone layer, exposing aquatic biota to its harmful effects. Also, the rising applications of nanotechnology are resulting in the release and contamination of aquatic ecosystems with engineered nanometals like titanium dioxide nanoparticles (nTiO2). The rise in ultraviolet radiation interacts with nanometals, increasing their bioactivities to susceptible aquatic organisms such as algae and cyanobacteria. The effect of ultraviolet radiation B (UVB) and nTiO2 on Microcystis flos-aquae and Pseudokirchneriella subcapitata during inter-specific interaction was investigated. The specific growth rate (d-1) of M. flos-aquae exposed to nTiO2 increased significantly under monoculture conditions but was suppressed during co-culture with P. subcapitata. Contrarily, UVB stimulated the growth of the cyanobacterium regardless of the presence or absence of the green microalgae. However, there was a general decline in the growth of P. subcapitata following cultivation with M. flos-aquae and exposure to UVB and nTiO2. The chlorophyll-a and total chlorophyll content of the monocultures of M. flos-aquae exposed to nTiO2 increased while other co-culture treatments significantly decreased these parameters. The experimental treatments, UVB, nTiO2, and UVB + nTiO2 had differential effects on the pigment content of P. subcapitata. The total protein content, intracellular H2O2, peroxidase (POD), and glutathione S-transferase (GST) activity of both M. flos-aquae and P. subcapitata increased at varying degrees as a function of the treatment condition. Microcystin content was highest in co-cultures exposed to UVB. The results of this study suggest that increasing levels of nTiO2 and UVB significantly alter the growth and cellular metabolic activity of M. flos-aquae and P. subcapitata, but the cyanobacterium will probably be favored by increasing UVB levels and its interaction with nanometals like nTiO2 in aquatic ecosystems.

['Otogo|Regina Anya|RA|', 'Chia|Mathias Ahii|MA|', 'Uyovbisere|Ejiroghene Ebelechukwu|EE|', 'Iortsuun|Dora Nguemo|DN|', 'Bittencourt-Oliveira|Maria do Carmo|MDC|']

2021

31013912

A Novel Standardized Cannabis sativa L. Extract and Its Constituent Cannabidiol Inhibit Human Polymorphonuclear Leukocyte Functions.

Cannabis and cannabinoids offer significant therapeutic benefits for a wide scope of pathological conditions. Among them, the clinical issues rooted in inflammation stand out, nonetheless, the underlying mechanisms are not yet plainly understood. Circumstantial evidence points to polymorphonuclear leukocytes (PMN) as targets for the anti-inflammatory effects of cannabis. Therefore, we conducted this study to assess the effects of CM5, a novel Cannabis sativa L. extract standardized in 5% cannabidiol (CBD), on human PMN functions, including cell migration, oxidative metabolism and production of tumour necrosis factor (TNF)-α. We then sought to investigate whether such effects could be ascribed to its content in CBD. Cell migration was assessed by the Boyden chamber assay, oxidative metabolism by means of spectrofluorimetric measurement of reactive oxygen species (ROS) production, and TNF-α was measured by real time polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay (ELISA). Results show that both CM5 and CBD inhibit PMN migration, ROS and TNF-α production, indicating that CBD may be the main item responsible for the effects of CM5. CM5 is however more potent than CBD on cell migration and TNF-α production, and less effective on ROS production, suggesting that beyond CBD, other components of the cannabis plant may contribute to the biological effects of the extract. As a whole, such results support the use of cannabis standardized extract and CBD to stem inflammation; however, they also warrant in-depth investigation of the underlying cellular and molecular mechanisms to better exploit their therapeutic potential.

['Mabou Tagne|Alex|A|0000-0003-3986-8344', 'Marino|Franca|F|', 'Legnaro|Massimiliano|M|', 'Luini|Alessandra|A|', 'Pacchetti|Barbara|B|', 'Cosentino|Marco|M|0000-0002-6978-7775']

2019

31404631

Antigenic relationships between Caprine alphaherpesvirus 1 (CpHV-1) and Bovine alphaherpesvirus 1 (BoHV-1) and experimental CpHV-1 infection of kids and calves.

Caprine alphaherpesvirus 1 (CpHV-1) is a worldwide pathogen of goats and is closely related to Bovine alphaherpevirus 1 (BoHV-1). We herein studied the antigenic relationships of CpHV-1 with BoHV-1 and investigated the pathogenesis of CpHV-1 in kids and calves. Monoclonal antibody reactivity revealed that CpHV-1 and BoHV-1 share immunogenic epitopes in the major envelope glycoproteins gB, gC and gD. The antigenic relationship was further demonstrated by virus-neutralizing assays, in which CpHV-1 and BoHV-1 antisera presented varied degrees of cross-neutralization against the respective heterologous viruses. Although cross-neutralization was observed between both viruses and the heterologous antisera, BoHV-1 antisera neutralized CpHV-1 with higher efficiency than CpHV-1 antisera neutralized BoHV-1. Hence, the antigenic cross-reactivity between CpHV-1 and BoHV-1 should be considered upon serologic testing of goats and cattle in regions where the two viruses co-circulate. Intranasal (IN) inoculation of CpHV-1 (WI13-46 isolate) in seven seronegative kids resulted in efficient viral replication in the respiratory tract. Additionally, mild to moderate systemic and respiratory signs were observed, including apathy, hyperthermia, nasal discharge and respiratory distress. Dexamethasone administration to the inoculated kids between days 36 and 40 pi did not result in virus shedding in nasal secretions. However, latent infection had been established, as evidenced by the detection of CpHV-1 DNA in trigeminal ganglia and olfactory bulbs of kids euthanized at day 67 pi. Contrasting with the outcome of infection in kids, IN inoculation of CpHV-1 in calves did not result in productive infection as no virus replication or shedding were detected, and the animals did not develop clinical signs nor seroconverted. The animal experiments demonstrated that CpHV-1 was able to produce respiratory disease in kids, but did not replicate to detectable levels in calves.

['Martins|Bruno|B|', 'Ebling|Rafael C|RC|', 'Martins|Mathias|M|', 'Diel|Diego G|DG|', 'Weiblen|Rudi|R|', 'Flores|Eduardo F|EF|']

2019

25043262

Melanization reaction products of shrimp display antimicrobial properties against their major bacterial and fungal pathogens.

Melanization is a rapid defense mechanism in invertebrates. The substrate specificity of phenoloxidases (POs) and the role of melanization reaction products were investigated in the black tiger shrimp, Penaeus monodon. Two PmPOs (PmproPO1 and PmproPO2) were found to display a substrate specificity towards monophenols and diphenols, and exhibit relatively weak activity against 5,6-dihydroxyindole (DHI). Systemic infection of the PmproPO1/2 co-silenced shrimp with the fungus, Fusarium solani, led to a significantly increased mortality, suggesting an important role of PmproPOs in shrimp's defense against fungal infection. Using L-DOPA, dopamine or DHI as a substrate, the melanization reaction products exhibited in vitro antimicrobial activities towards Gram-negative bacteria (Vibrio harveyi and Vibrioparahaemolyticus) and Gram-positive bacteria (Bacillus subtilis), whereas the lower effect was detected against the fungus (F. solani). SEM analysis revealed the morphological changes and damage of cell membranes of V. harveyi and F. solani after treatment with shrimp melanization reaction products. Together, these findings demonstrate the crucial functions of the proPO system and the importance of melanization reaction products in the shrimp's immune defense.

['Charoensapsri|Walaiporn|W|', 'Amparyup|Piti|P|', 'Suriyachan|Chawapat|C|', 'Tassanakajon|Anchalee|A|']

2014

33193279

Naturally Occurring tRNAs With Non-canonical Structures.

Transfer RNA (tRNA) is the central molecule in genetically encoded protein synthesis. Most tRNA species were found to be very similar in structure: the well-known cloverleaf secondary structure and L-shaped tertiary structure. Furthermore, the length of the acceptor arm, T-arm, and anticodon arm were found to be closely conserved. Later research discovered naturally occurring, active tRNAs that did not fit the established 'canonical' tRNA structure. This review discusses the non-canonical structures of some well-characterized natural tRNA species and describes how these structures relate to their role in translation. Additionally, we highlight some newly discovered tRNAs in which the structure-function relationship is not yet fully understood.

['Krahn|Natalie|N|', 'Fischer|Jonathan T|JT|', 'Söll|Dieter|D|']

2020

26781283

Rnd3/RhoE Modulates Hypoxia-Inducible Factor 1α/Vascular Endothelial Growth Factor Signaling by Stabilizing Hypoxia-Inducible Factor 1α and Regulates Responsive Cardiac Angiogenesis.

The insufficiency of compensatory angiogenesis in the heart of patients with hypertension contributes to heart failure transition. The hypoxia-inducible factor 1α-vascular endothelial growth factor (HIF1α-VEGF) signaling cascade controls responsive angiogenesis. One of the challenges in reprograming the insufficient angiogenesis is to achieve a sustainable tissue exposure to the proangiogenic factors, such as HIF1α stabilization. In this study, we identified Rnd3, a small Rho GTPase, as a proangiogenic factor participating in the regulation of the HIF1α-VEGF signaling cascade. Rnd3 physically interacted with and stabilized HIF1α, and consequently promoted VEGFA expression and endothelial cell tube formation. To demonstrate this proangiogenic role of Rnd3 in vivo, we generated Rnd3 knockout mice. Rnd3 haploinsufficient (Rnd3(+/-)) mice were viable, yet developed dilated cardiomyopathy with heart failure after transverse aortic constriction stress. The poststress Rnd3(+/-) hearts showed significantly impaired angiogenesis and decreased HIF1α and VEGFA expression. The angiogenesis defect and heart failure phenotype were partially rescued by cobalt chloride treatment, a HIF1α stabilizer, confirming a critical role of Rnd3 in stress-responsive angiogenesis. Furthermore, we generated Rnd3 transgenic mice and demonstrated that Rnd3 overexpression in heart had a cardioprotective effect through reserved cardiac function and preserved responsive angiogenesis after pressure overload. Finally, we assessed the expression levels of Rnd3 in the human heart and detected significant downregulation of Rnd3 in patients with end-stage heart failure. We concluded that Rnd3 acted as a novel proangiogenic factor involved in cardiac responsive angiogenesis through HIF1α-VEGFA signaling promotion. Rnd3 downregulation observed in patients with heart failure may explain the insufficient compensatory angiogenesis involved in the transition to heart failure.

['Yue|Xiaojing|X|', 'Lin|Xi|X|', 'Yang|Tingli|T|', 'Yang|Xiangsheng|X|', 'Yi|Xin|X|', 'Jiang|Xuejun|X|', 'Li|Xiaoyan|X|', 'Li|Tianfa|T|', 'Guo|Junli|J|', 'Dai|Yuan|Y|', 'Shi|Jianjian|J|', 'Wei|Lei|L|', 'Youker|Keith A|KA|', 'Torre-Amione|Guillermo|G|', 'Yu|Yanhong|Y|', 'Andrade|Kelsey C|KC|', 'Chang|Jiang|J|']

2016

28236290

The Area Between Exchange Curves as a Measure of Conformational Differences in Hydrogen-Deuterium Exchange Mass Spectrometry Studies.

Hydrogen-deuterium exchange mass spectrometry (HDX-MS) provides information about protein conformational mobility under native conditions. The area between exchange curves, A bec , a functional data analysis concept, was adapted to the interpretation of HDX-MS data and provides a useful measure of exchange curve dissimilarity for tests of significance. Importantly, for most globular proteins under native conditions, A bec values provide an estimate of the log ratio of exchange-competent fractions in the two states, and thus are related to differences in the free energy of microdomain unfolding. Graphical Abstract ᅟ.

['Mazur|Sharlyn J|SJ|', 'Weber|Daniel P|DP|']

2017

24124111

Increased prepulse inhibition and sensitization of the startle reflex in autistic children.

The relation between autism spectrum disorders (ASD) and schizophrenia is a subject of intense debate and research due to evidence of common neurobiological pathways in the two disorders. The objective of this study was to explore whether deficits in prepulse inhibition (PPI) of the startle reflex, as usually seen in schizophrenic patients, can be replicated in a group of children with ASD in comparison with a group of matched neuro-typically developed (NTD) controls. An additional aim was to explore possible psychophysiological subgroups within our ASD sample. In a case-control design, 35 ASD patients and 40 matched NTD controls were tested in a psychophysiological test battery. The PPI of the acoustic startle reflex was analyzed in 18 ASD subjects and 34 NTD controls. Habituation and sensitization were analyzed in 23 ASD subjects and 39 NTD controls. In trials with less intense prestimuli (76 dB), patients with ASD did not display the drop in percentage PPI normally found in healthy controls. In addition, ASD patients showed significantly increased sensitization compared with NTD controls. Combined, our results may reflect the hypersensitivity to sensory information in children with ASD. The relation to PPI deficits observed in schizophrenia is not apparent. Future research should study the developmental course of PPI deficits in ASD patients in a longitudinal design.

['Madsen|Gitte Falcher|GF|', 'Bilenberg|Niels|N|', 'Cantio|Cathriona|C|', 'Oranje|Bob|B|']

2014

25979761

Nicotinic receptor-dependent and -independent effects of galantamine, an acetylcholinesterase inhibitor, on the non-neuronal acetylcholine system in C2C12 cells.

We previously reported that satellite cells possess the ability to produce angiogenic factors, including fibroblast growth factor (FGF)-2 and vascular endothelial growth factor (VEGF) in vivo. However, whether C2C12 cells possess a non-neuronal cholinergic system (NNCS) or non-neuronal ACh (NNA) remains to be studied; therefore, we investigated the system using C2C12 cells and its regulatory mechanisms. C2C12 cells synthesized ACh, the level of which was comparable with that of cardiomyocytes, and the synthesis was augmented by the acetylcholinesterase inhibitor galantamine. The ChAT promoter activity was upregulated by nicotine or galantamine, partly through nicotinic receptors for both agents as well as through a non-nicotinic receptor pathway for galantamine. Further, VEGF secretion by C2C12 cells was also increased by nicotine or galantamine through nicotinic receptors as well as partly through non-nicotinic pathways in the case of galantamine. These results suggest that C2C12 cells are equipped with NNCS or NNA, which is positively regulated through nicotinic or non-nicotinic pathways, particularly in the case of galantamine. These results provide a novel concept that myogenic cells expressing NNA can be a therapeutic target for regulating angiogenic factor synthesis.

['Oikawa|Shino|S|', 'Mano|Asuka|A|', 'Iketani|Mitsue|M|', 'Kakinuma|Yoshihiko|Y|']

2015

22891082

Tropical Diabetic Hand Syndrome: report of 2 cases.

Diabetes mellitus is known to be complicated by foot lesions. However, a few cases of hand complications have been reported in some parts of the world. The case notes of two patients who presented with this condition in our hospital were retrieved and relevant information extracted. The cases of diabetic hand complications seen in our centre are here reported to draw the attention of medical practitioners to the occurrence of this potentially debilitating and occasionally fatal condition. Appropriate counselling of diabetic patients on hand care strategies and good glycemic control are important preventive measures.

['Ewezu Ngim|Ngim|N|', 'Amah|Paul|P|', 'Abang|Innocent|I|']

2012

28850330

Diabetes mellitus and hyperlipidaemia as risk factors for frequent pain in the back, neck and/or shoulders/arms among adults in Stockholm 2006 to 2010 - Results from the Stockholm Public Health Cohort.

BACKGROUND AND AIMS Frequent back, neck and/or shoulder pain (BNSP) are common conditions which pose high burden for the society. Results from previous studies suggest that diabetes and hyperlipidaemia may be associated with a higher risk of getting such conditions, but there is in general, few studies based on longitudinal designs. The aim of this study was therefore to compare the risk of developing frequent BNSP in men and women with and without diabetes and/or hyperlipidaemia. METHODS A longitudinal study based on the Stockholm Public Health Cohort was conducted based on subjects aged 45-84, who were free from pain at the mentioned sites in 2006 and followed up until 2010. The data in the current study is based on questionnaires, except socioeconomic status which was derived from Statistics Sweden. The exposure diabetes and hyperlipidaemia was self-reported and, a categorical variable was created; without any of the conditions, with hyperlipidaemia only, with diabetes only and with both conditions. The outcome frequent BNSP was defined using the following questions in the questionnaire in 2010: "During the past 6months, have you had pain in the neck or upper part of the back?", "During the past 6months, have you had pain in the lower back?", and "During the past 6months, have you had pain in the shoulders/arms?". All questions had three possible response options: no; yes, a couple of days per month or less often and; yes, a couple of days per week or more often. Those who reported weekly pain to at least one of these questions were considered to having frequent BNSP. Binomial regressions were run to calculate the crude and adjusted risk ratio (RR) in men and women separately. Additional analysis was performed in order to control for potential bias derived from individuals lost to follow-up. RESULTS A total of 10,044 subjects fulfilled the criteria to be included in the study. The mean age of the sample was 60years and evenly distributed by sex. After adjusting for age, body mass index, physical activity, high blood pressure and socioeconomic status, the RR for frequent BNSP among men with diabetes was 1.64 (95% CI: 1.23-2.18) and 1.19 (95% CI: 0.98-1.44) for hyperlipidaemia compared to men with neither diabetes nor hyperlipidaemia. Among women the corresponding RRs were 0.92 (95% CI: 0.60-1.14) and 1.23 (95% CI: 1.03-1.46). Having both diabetes and hyperlipidaemia at baseline was not associated with increased risk of frequent BNSP. Diabetes and hyperlipidaemia seems to be associated with an increased risk for frequent BNSP and the risk may differ between men and women. Behaviours and/or biological underlying mechanisms may explain the results. CONCLUSIONS This study suggests that metabolic diseases such as diabetes and hyperlipidaemia may have an impact on the pathophysiology of frequent BNSP and thus, contributes to the knowledge in musculoskeletal health. Furthermore, it confirms that men and women may differ in terms of risk factors for BNSP. IMPLICATIONS Health professionals should contemplate the results from this study when planning primary prevention strategies.

['Pico-Espinosa|Oscar Javier|OJ|', 'Skillgate|Eva|E|', 'Tettamanti|Giorgio|G|', 'Lager|Anton|A|', 'Holm|Lena W|LW|']

2017

33662897

Non-invasive survey technology for estimating the distribution of oxidant solution: A pilot injection study.

In-situ chemical oxidation (ISCO) can remove pollutants efficiently. However, the most important key to successfully conducting ISCO on site is to place the oxidant in close contact with the contaminant. Therefore, monitoring tools that provide for enhanced tracking of the injectate offer considerable benefit to guide subsequent ISCO injections. In this study, we applied the MagnetoMetric Resistivity (MMR) method to survey the distribution of an injected oxidant. A pilot test was conducted on a 10 m × 10 m site, and the sodium persulfate injection involved four pulse injections from one injection well. A magnetic field survey coupled with conventional monitoring was performed before the initial injection and after each pulse injection. The results of this study showed that groundwater samples from six observation wells and seven direct-push EC loggings did not provide sufficient data to quantify the distribution and flow behavior of the injected oxidant. However, the magnetic field survey visually showed the dynamic distribution of the injected oxidant, and the flow pathways and flow behavior were assessed accordingly. Although the flow behavior of injected solution was changeable in the aquifer, but the magnetic field survey combined with the monitoring of the well samples helped to explain the abnormal changes in the electrical conductivity of the observation wells and supports the use of the magnetic field survey technology as a method of monitoring ISCO injections.

['Tsai|Yih-Jin|YJ|', 'Wu|Ting-Nien|TN|', 'Lee|Cheng-Haw|CH|', 'Lin|Sun-Long|SL|', 'Tsai|Wen-Hsien|WH|']

2021

30027324

Dermacentor reticulatus ticks (Acari: Ixodidae) distribution in north-eastern Poland: an endemic area of tick-borne diseases.

Dermacentor reticulatus is the second most important tick species in Poland. Although the north-eastern region of Poland is considered typical for D. reticulatus and is treated as a contiguous area of Eastern populations of the meadow ticks, the occurrence of this tick species in this region to date has been recorded as separate foci. The present report supplements data on the geographical distribution of D. reticulatus in urban and natural biotopes of north-eastern Poland (Warmia and Mazury province). In 2015-2017 (during the springtime activity of ticks) adult questing D. reticulatus were found in 13 of 25 monitored localities. Six sites are located in urbanized areas, within the administrative borders of the city of Olsztyn and seven sites are in natural biotopes in the central part of Warmia and Mazury. A total of 398 adult D. reticulatus ticks, including 257 females and 141 males, were collected. A comparison of data grouped according to urban and natural type of area revealed no statistical differences between them. Taking into account the habitat type, the mean tick density was the highest in open landscapes. The identification of new foci D. reticulatus in the endemic areas of Lyme borreliosis, tick-borne encephalitis and canine babesiosis is crucial for determining the risk of diseases transmitted by ticks and taking proper preventive measures.

['Kubiak|Katarzyna|K|http://orcid.org/0000-0001-6400-8958', 'Sielawa|Hanna|H|', 'Dziekońska-Rynko|Janina|J|', 'Kubiak|Dariusz|D|', 'Rydzewska|Martyna|M|', 'Dzika|Ewa|E|']

2018

29204481

Corrosion and adverse tissue reaction after modular unipolar hip hemiarthroplasty.

Modern unipolar hip hemiarthroplasty, commonly used for displaced femoral neck fracture, is now modular, with both a variable length cobalt-chromium adapter-sleeve and large femoral head. Patients with these modular components may develop symptomatic trunnion corrosion, with elevated serum metal levels. We report the case of an 82-year-old woman, 5.5 years after a modular unipolar hip hemiarthroplasty, who presented with a 4-month history of hip pain and limp. Evaluation showed elevated serum cobalt and chromium levels and an acetabular cyst. At revision, fluid, tissue, and gross inspection were consistent with trunnion corrosion. The hip was revised with a ceramic head and dual mobility acetabular component, with a good result at 1 year. The designs of commercially available, modern unipolar hip hemiarthroplasty prostheses are reviewed.

['Moore|Brian F|BF|', 'Lachiewicz|Paul F|PF|']

2017

32319639

HBV DNA integrates into upregulated ZBTB20 in patients with hepatocellular carcinoma.

Hepatitis B virus (HBV) affects the malignant phenotype of hepatocellular carcinoma (HCC). The aim of the present study was to investigate the integration sites of HBV DNA and the expression of the zinc finger protein, zinc finger and BTB domain containing 20 (ZBTB20) in patients with hepatocellular carcinoma. Integration of the HBV gene was detected using a high‑throughput sequencing technique based on the HBV‑Alu‑PCR method. The expression of ZBTB20 was detected by western blotting. HBVX integration sites were detected in ~70% of the HCC tissue samples. HBV‑integrated subgene X detection suggested that 67% of the integrated specimens were inserted into the host X gene in a forward direction, 57% in a reverse direction, 24% in both forward and reverse directions, and 38% had two HBV integration sites. A total of 3,320 HBV integration sites were identified, including 1,397 in HCC tissues, 1,205 in paracancerous tissues and 718 in normal liver tissues. HBV integration fragments displayed enrichment in the 200‑800 bp region. Additionally, the results suggested that HBV was highly integrated into transmembrane phosphatase with tensin homology, long intergenic non‑protein coding RNA (LINC)00618, LOC101929241, ACTR3 pseudogene 5, LINC00999, LOC101928775, deleted in oesophageal cancer 1, LINC00824, EBF transcription factor 2 and ZBTB20 in tumour tissues. Furthermore, the expression of ZBTB20 was upregulated in HCC tissues compared with normal control liver tissues, and was associated with HBV integration frequency. The present study suggested that HBV DNA integrated into upregulated ZBTB20 in patients with hepatocellular carcinoma, which might promote the occurrence and development of HCC. Furthermore, the results of the present study may provide a theoretical basis for the diagnosis and treatment of HCC.

['He|Zebao|Z|', 'Zhu|Jiansheng|J|', 'Mo|Jinggang|J|', 'Zhao|Haihong|H|', 'Chen|Qiuyue|Q|']

2020

29619405

Effects of the modern food environment on striatal function, cognition and regulation of ingestive behavior.

Emerging evidence from human and animal studies suggest that consumption of palatable foods rich in fat and/or carbohydrates may produce deleterious influences on brain function independently of body weight or metabolic disease. Here we consider two mechanisms by which diet can impact striatal circuits to amplify food cue reactivity and impair inhibitory control. First, we review findings demonstrating that the energetic properties of foods regulate nucleus accumbens food cue reactivity, a demonstrated predictor of weight gain susceptibility, which is then sensitized by chronic consumption of an energy dense diet. Second, we consider evidence for diet-induced adaptations in dorsal striatal dopamine signaling that is associated with impaired inhibitory control and negative outcome learning.

['Burke|Mary V|MV|', 'Small|Dana M|DM|']

2016

26681671

Highly Efficient Storage of Pulse Energy Produced by Triboelectric Nanogenerator in Li3V2(PO4)3/C Cathode Li-Ion Batteries.

Triboelectric nanogenerator (TENG) has been considered as a new type of energy harvesting technology, which employs the coupling effects of triboelectrification and electrostatic induction. One key factor having limited its application is the energy storage. In this work, a high performance Li3V2(PO4)3/C material synthesized by low-cost hydrothermal method followed with subsequent annealing treatment was studied to efficiently store the power generated by a radial-arrayed rotary TENG. Not only does the Li3V2(PO4)3/C exhibit a discharge capacity of 128 mAh g(-1) at 1 C with excellent cyclic stability (capacity retention is 90% after 1000 cycles at a rate of 5 C) in Li-ion battery, but also shows outstanding energy conversion efficiency (83.4%) compared with the most popular cathodic materials: LiFePO4 (74.4%), LiCoO2 (66.1%), and LiMn2O4 (73.6%) when it was charged by high frequency and large current electricity directly from by TENG.

['Nan|Xihui|X|', 'Zhang|Changkun|C|', 'Liu|Chaofeng|C|', 'Liu|Mengmeng|M|', 'Wang|Zhong Lin|ZL|', 'Cao|Guozhong|G|']

2016

33621764

Efficacy of topical isoconazole nitrate in the treatment of otomycosis.

PURPOSE Various agents with various antifungal properties are widely used for otomycosis eradication. However, there is still no consensus on the most effective agent. Therefore, the present study aims to investigate the efficacy of topical 1% isoconazole nitrate cream in the treatment of otomycosis. METHODS This prospective study included 43 patients who were applied to our outpatient clinic with complaints of ear pain, itching, aural fullness, and hypoacusis, and were diagnosed with unilateral otomycosis. After aspiration and cleaning, the external ear canal was filled with 1% isoconazole nitrate cream using an iv cannula and insulin syringe. Control examinations were performed on the 5th, 10th, 15th, and 20th days. In the follow-up examinations, patients were asked about how many days after the cream administration the pain and itching completely relief and the answers were recorded. RESULTS In the first control examination of 23 (92%) of 25 patients with pain, it was observed that the pain and otoendoscopic examination findings completely recovered. In the second control, it was found that both pain and otoendoscopic examination findings completely recovered in the remaining 2 patients (25 patients, 100%). 35 patients complained of itching and it was observed that itching and otoendoscopic examination findings completely recovered in 26 patients (75%) in the first control, 5 more patients (31 patients, 88.6%) in the second control, and 2 more patients (33 patients, 94.3%) in the third control examination. CONCLUSION Isoconazole nitrate cream appears to be an effective and easily applicable agent for the treatment of otomycosis.

['Gülüstan|Filiz|F|', 'Abakay|Mehmet Akif|MA|', 'Demir|Emine|E|']

2021

27867912

Central Neurocytoma: A Review of Clinical Management and Histopathologic Features.

Central neurocytoma (CN) is a rare, benign brain tumor often located in the lateral ventricles. CN may cause obstructive hydrocephalus and manifest as signs of increased intracranial pressure. The goal of treatment for CN is a gross total resection (GTR), which often yields excellent prognosis with a very high rate of tumor control and survival. Adjuvant radiosurgery and radiotherapy may be considered to improve tumor control when GTR cannot be achieved. Chemotherapy is also not considered a primary treatment, but has been used as a salvage therapy. The radiological features of CN are indistinguishable from those of other brain tumors; therefore, many histological markers, such as synaptophysin, can be very useful for diagnosing CNs. Furthermore, the MIB-1 Labeling Index seems to be correlated with the prognosis of CN. We also discuss oncogenes associated with these elusive tumors. Further studies may improve our ability to accurately diagnose CNs and to design the optimal treatment regimens for patients with CNs.

['Lee|Seung J|SJ|', 'Bui|Timothy T|TT|', 'Chen|Cheng Hao Jacky|CH|', 'Lagman|Carlito|C|', 'Chung|Lawrance K|LK|', 'Sidhu|Sabrin|S|', 'Seo|David J|DJ|', 'Yong|William H|WH|', 'Siegal|Todd L|TL|', 'Kim|Minsu|M|', 'Yang|Isaac|I|']

2016

27679575

Vam3, a Compound Derived from Vitis amurensis Rupr., Attenuated Colitis-Related Tumorigenesis by Inhibiting NF-κB Signaling Pathway.

BACKGROUND Chronic inflammation is one of the important mediators of colitis-related colon cancer (CRC). Abundant mast cells (MCs) were observed in the tumor microenvironment and mediators released upon MC activation play an important role in the process of chronic inflammation. Previously, we found that activation of intestine mucosal MCs recruited and modulated the inflammatory CD11b(+)Gr1(+) cells to promote the CRC development. In the current study we investigated the effects of Vam3, a resveratrol dimer with potent anti-inflammatory effects, on CRC development. METHODS RBL-2H3 cells, a basophilic leukemia cell line, were pretreated with 2.5 or 5 µM Vam3 and then stimulated with dinitrophenol-conjugated bovine serum albumin (DNP-BSA) plus lipopolysaccharide (LPS). The MC degranulation was determined by measuring β-hexosaminidase release. Generation of TNF-α and IL-6 in RBL-2H3 cells or in peritoneal macrophages was determined by ELISA and real-time qPCR. NF-κB p65 and phospho-NF-κB p65 expression was determined by Western blotting. NF-κB activity in RAW264.7 cells was determined by luciferase reporter assay. CRC was induced in C57BL/6 mice by intraperitoneal injection of azoxymethane (AOM), followed by oral exposure to dextran sodium sulfate (DSS). Vam3 at 50 mg/kg, or disodium cromoglycate (DSCG, MC stabilizer) at 100 mg/kg, or vehicle were administrated to the mice 4 weeks after DSS withdrawal. Levels of TNF-α, IL-6, and mouse MC protease-1 were determined by ELISA. Infiltration of CD11b(+)Gr1(+) cells was determined by flow cytometry analysis. One-way ANOVA was used to compare difference between groups. RESULTS Pretreatment with Vam3 significantly inhibited RBL-2H3 cell degranulation and inflammatory cytokine production from RBL-2H3 cells and from peritoneal macrophages. After Vam3 treatment, NF-κB activity in RAW264.7 cells, and expressions of phospho-NF-κB p65 in RBL-2H3 cells and in peritoneal macrophages were significantly down-regulated. In the AOM plus DSS-induced CRC murine model, the Vam3 and DSCG-treated mice had less tumor numbers than those treated with vehicle. Expression of phospho-NF-κB p65, production of inflammatory cytokines, and infiltration of MCs and CD11b(+)Gr1(+) cells were attenuated in the Vam3-treated mice. CONCLUSION Vam3 treatment could attenuate the CRC development. This effect may be due to its inhibition on NF-κB signaling pathway in MCs and macrophages of the inflamed intestines.

['Xuan|Lingling|L|', 'Jiang|Rentao|R|', 'Wu|Zhiyuan|Z|', 'Yi|Honggan|H|', 'Yao|Chunsuo|C|', 'Hou|Qi|Q|', 'Qu|Chunfeng|C|']

2016

33403412

The Combined Use of Spreader Flap and Asymmetric Spreader Graft in Crooked Nose.

OBJECTIVE The crooked nose is still a challenging deformity for rhinoplasty surgeons although a significant number of correction methods have previously been described. The aim of this study is to present a new technique that the authors have used to correct the crooked nose in selected patients. MATERIALS AND METHODS This retrospective study was carried out on 53 patients who underwent open technique rhinoplasty due to crooked nose. Pictures were taken from five different angles using digital cameras and recorded pre- and postoperatively. Patients who have a minimum follow-up period of 12 months are included in the study. RESULTS Fifty-three patients who have I-shaped and C-shaped crooked nose were enrolled in this study. The mean ages were 27.4 years. The mean follow-up period of the patients was 19.1 months. Patients who have I-shaped and C-shaped crooked nose deviation angle values were calculated preoperatively as 7.1 ± 2.1 and 163.4 ± 3.6, respectively. Postoperatively, deviation angle values were 0.75 ± 0.83 and 177.9 ± 3.1. Postoperative deviation angles were significantly lower than preoperative angles on patients who have I-shaped crooked noses (p < 0.001). On patients who have C-shaped crooked nose, postoperative deviation angles were significantly higher than preoperative angles (p < 0.001). CONCLUSIONS This unique study shows that the combined use of one-sided spreader flap and asymmetric spreader grafts is a very good choice for satisfactory long-term outcome and durable correction of crooked nose deformity. LEVEL OF EVIDENCE IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266 .

['Gökler|Ozan|O|http://orcid.org/0000-0003-1621-3687', 'Koçak|İlker|İ|']

2021

32739545

The Masquelet technique combined with the muscle flap for use in emergency management of acute Gustilo type III trauma of the lower limb with segmental bone loss:Case series.

BACKGROUND Gustilo-Anderson type III traumas have been described as high-energy injuries with severe bone defects and extensive soft tissue damage, which remain a challenging entity, due to an inherent risk of infection, nonunion and even amputation. The emergency management of such severe trauma presents additional difficulties. Our study attempts to retrospectively evaluate the Masquelet technique combined with the muscle flap for the management of Gustilo type III trauma of the lower limb with segmental bone loss in emergencies and assess key points of success in this technique. MATERIAL AND METHODS From June 2014 to December 2017, 17 patients of Gustilo type IIIA/B/C trauma of lower limb with segmental bone loss, were recruited for our studies. All the cases experienced thorough debridement, stabilization of fracture and antibiotic-impregnated cement spacer insertion. When necessary, muscle flap surgeries were performed immediately. After wound healing, cement spacers were removed, and cancellous bone was filled to repair bone defects. Procedures were performed by two experienced orthopedic surgeons. RESULTS Among the patients studied, retrograde translocations of the medial head of the gastrocnemius were performed in 5 cases, medial hemimuscular flaps of soleus in 3 cases, and medial head of the gastrocnemius combined with medial hemimuscular flaps of soleus in 4 cases. One patient developed a necrotic soleus flap and was treated with the cross-leg flap. Using a mean 28.2 months of follow-up, results were analyzed radiologically and clinically. Failures (include infection and nonunion) were not noted. And all the patients returned to full weight bearing without pain. According to the Paley fracture healing score, 15 patients showed excellent results and 2 patients displayed good results regarding bone outcomes. When considering functional outcomes, 14 patients exhibited excellent results and 3 patients displayed good results. CONCLUSIONS The muscle flap is synergistic with the Masquelet technique in the emergency management of severe complex fractures. The combination of both techniques in emergency surgery demonstrates an alternative option for the treatment of acute Gustilo type III trauma of the lower limb with segmental bone loss, which can effectively prevent bone infection and amputation. We also demonstrate that firm fixation is key to the Masquelet technique.

['Deng|Linglong|L|', 'Yu|Aixi|A|', 'Qi|Baiwen|B|', 'Lei|Jun|J|', 'De Souza|Cristabelle|C|', 'Zhu|Shaobo|S|', 'Yu|Li|L|']

2020

34007171

Etanercept Protected Against Cigarette Smoke Extract-Induced Inflammation and Apoptosis of Human Pulmonary Artery Endothelial Cells via Regulating TNFR1.

Purpose Etanercept (ETN), a tumor necrosis factor-α (TNF-α) inhibitor, has been applied in the treatment of many diseases. However, whether it has effects on chronic obstructive pulmonary disease (COPD) and its interaction with tumor necrosis factor receptor 1 (TNFR1) remained unknown. Methods Histopathological analysis of lung tissues from non-smokers and smokers with or without COPD was conducted using hematoxylin-eosin (H&E) staining, Van Gieson (VG) staining, and terminal transferase-mediated biotin dUTP nick end labeling (TUNEL). TNF-α content was measured using Immunohistochemistry. Correlation analysis among apoptosis rate, smoke index, the FEV1/FVC ratio, and TNF-α-positive cells was performed. After ETN treatment and transfection of overexpressed or silenced TNFR1, levels of inflammatory cytokines, apoptosis and related genes expressions in cigarette smoke extract (CSE)-treated human pulmonary artery endothelial cells (HPAECs) were detected using enzyme-linked immunosorbent assay (ELISA), Hoechst 33342 staining, flow cytometry, quantitative real-time PCR (qRT-PCR) and Western blot. Results Pulmonary arterial remodeling and increased apoptotic and TNF-α+ HPAECs were found in lung tissue of smokers with or without COPD, with higher degrees in smokers with COPD. The numbers of apoptotic and TNF-α+ HPAECs were positively correlated with smoke index, while the FEV1/FVC ratio was negatively correlated with apoptotic HPAECs. In HPAECs, ETN downregulated the expressions of proteins related to CSE-induced apoptosis and the TNF receptor family, decreased CSE-induced cell apoptosis and inflammatory cytokine levels, and inhibited TNFR1 expression and p65 phosphorylation. Overexpressed TNFR1 reversed the effects of ETN on CSE-treated HPAECs, whereas silencing TNFR1 did the opposite. Conclusion ETN protected HPAECs against CSE-induced inflammation and apoptosis via downregulating TNFR1, thus providing a potential therapy for smoking-induced COPD.

['Xue|Hong|H|', 'Xie|Baosong|B|', 'Xu|Nengluan|N|', 'Li|Hongru|H|', 'Chen|Qianshun|Q|', 'Xie|Weiping|W|', 'Wang|Hong|H|']

2021

24668556

Molecular diagnosis in clinical parasitology: when and why?

Microscopic detection and morphological identification of parasites from clinical specimens are the gold standards for the laboratory diagnosis of parasitic infections. The limitations of such diagnostic assays include insufficient sensitivity and operator dependence. Immunoassays for parasitic antigens are not available for most parasitic infections and have not significantly improved the sensitivity of laboratory detection. Advances in molecular detection by nucleic acid amplification may improve the detection in asymptomatic infections with low parasitic burden. Rapidly accumulating genomic data on parasites allow the design of polymerase chain reaction (PCR) primers directed towards multi-copy gene targets, such as the ribosomal and mitochondrial genes, which further improve the sensitivity. Parasitic cell or its free circulating parasitic DNA can be shed from parasites into blood and excreta which may allow its detection without the whole parasite being present within the portion of clinical sample used for DNA extraction. Multiplex nucleic acid amplification technology allows the simultaneous detection of many parasitic species within a single clinical specimen. In addition to improved sensitivity, nucleic acid amplification with sequencing can help to differentiate different parasitic species at different stages with similar morphology, detect and speciate parasites from fixed histopathological sections and identify anti-parasitic drug resistance. The use of consensus primer and PCR sequencing may even help to identify novel parasitic species. The key limitation of molecular detection is the technological expertise and expense which are usually lacking in the field setting at highly endemic areas. However, such tests can be useful for screening important parasitic infections in asymptomatic patients, donors or recipients coming from endemic areas in the settings of transfusion service or tertiary institutions with transplantation service. Such tests can also be used for monitoring these recipients or highly immunosuppressed patients, so that early preemptive treatment can be given for reactivated parasitic infections while the parasitic burden is still low.

['Wong|Samson S Y|SS|', 'Fung|Kitty S C|KS|', 'Chau|Sandy|S|', 'Poon|Rosana W S|RW|', 'Wong|Sally C Y|SC|', 'Yuen|Kwok-Yung|KY|']

2014

34119520

DNA polymerase λ promotes error-free replication through Watson-Crick impairing N1-methyl-deoxyadenosine adduct in conjunction with DNA polymerase ζ.

In a previous study, we showed that replication through the N1-methyl-deoxyadenosine (1-MeA) adduct in human cells is mediated via three different Polι/Polθ, Polη, and Polζ-dependent pathways. Based on biochemical studies with these Pols, in the Polι/Polθ pathway, we inferred a role for Polι in the insertion of a nucleotide (nt) opposite 1-MeA and of Polθ in extension of synthesis from the inserted nt; in the Polη pathway, we inferred that this Pol alone would replicate through 1-MeA; in the Polζ pathway, however, the Pol required for inserting an nt opposite 1-MeA had remained unidentified. In this study, we provide biochemical and genetic evidence for a role for Polλ in inserting the correct nt T opposite 1-MeA, from which Polζ would extend synthesis. The high proficiency of purified Polλ for inserting a T opposite 1-MeA implicates a role for Polλ-which normally uses W-C base pairing for DNA synthesis-in accommodating 1-MeA in a syn confirmation and forming a Hoogsteen base pair with T. The potential of Polλ to replicate through DNA lesions by Hoogsteen base pairing adds another novel aspect to Polλ's role in translesion synthesis in addition to its role as a scaffolding component of Polζ. We discuss how the action mechanisms of Polλ and Polζ could be restrained to inserting a T opposite 1-MeA and extending synthesis thereafter, respectively.

['Yoon|Jung-Hoon|JH|', 'Basu|Debashree|D|', 'Choudhury|Jayati Roy|JR|', 'Prakash|Satya|S|', 'Prakash|Louise|L|']

2021

24566615

Immunosuppressive agent leflunomide: a SWNTs-immobilized dihydroortate dehydrogenase inhibitory effect and computational study of its adsorption properties on zigzag single walled (6,0) carbon and boron nitride nanotubes as controlled drug delivery devices.

Leflunomide [HWA 486 or RS-34821, 5-methyl-N-(4trifluoromethylphenyl)-4-isoxazole carboximide] is an immunosuppressive agent effective in the treatment of rheumatoid arthritis. Dihydroortate dehydrogenase (DHODH, EC 1.3.3.1) immobilization on the nanotubes was carried out and biochemical characterization of free and immobilized enzyme was determined. In comparison with free enzyme, the immobilized DHODH showed improved stability and reusability for investigation of inhibition pattern of drugs such as leflunomide. The experimental data showed that, DHODH was inhibited by the active metabolite of leflunomide (RS-61980) with a Ki and KI of 0.82 and 0.06 mM, respectively. Results exhibited mixed-type inhibition kinetics towards dihydroorotate as a substrate in the free and immobilized enzyme. Furthermore, the behavior of anticancer drug leflunomide adsorbed on the external surface of zigzag single walled (6,0) carbon and boron nitride nanotubes (SWCNT and SWBNNT) was studied by means of DFT calculations at the B3LYP/6-31G(*) level of theory. The larger adsorption energies and charges transfer showed that the adsorption of leflunomide onto SWBNNT is more stable than that the adsorption of leflunomide onto SWCNT. Frontier molecular orbitals (HOMO and LUMO) suggest that adsorption of leflunomide onto SWBNNT behave as charge transfer compounds with leflunomide as an electron donor and SWBNNT as an electron acceptor. Thus, nanotubes (NTs) have been proposed and actively explored as multipurpose innovative carriers for drug delivery and diagnostic application. The AIM theory has been also applied to analyze the properties of the bond critical points: their electron densities and their laplacians. Also, the natural bond orbital (NBO) calculations were performed to derive natural atomic orbital occupancies, and partial charges of the interacting atoms in the equilibrium tube-molecule distance.

['Raissi|Heidar|H|', 'Mollania|Fariba|F|']

2014

29803333

First five generations Chinese family of tuberous scleroses complex due to a new mutation of the TSC1 gene.

Tuberous scleroses complex (TSC) is a rare neurocutaneous syndrome and has autosomal dominant inheritance. However, larger family with TSC is very rare. Here, we report the first five generations family with TSC from China, and localize the pathogenic gene. A boy with TSC and epilepsy underwent preoperative evaluation and epileptic surgery. His TSC family history was gotten, and the clinical data of a Chinese family with TSC were collected in 2016. Complete exons sequencing was performed in the proband and his parents, and whole exons sequence of TSC was performed in the other family members. The family showed autosomal dominant inheritance, and it was the largest reported family with TSC. In this pedigree, there were 14 patients in 5 generations, but only 1 case with epilepsy in them. All of examined patients had TSC 1 gene exon 15 c.1846delG p.A616Pfs*13 mutation. In conclusion, TSC patients with TSC 1 deletion presented mild neurological symptom and rendered larger family.

['Cui|Jianfei|J|', 'Yu|Xiaoman|X|', 'Liang|Shuli|S|', 'Zhang|Shaohui|S|', 'Hu|Xiaohong|X|']

2018

32147146

An Update on Existing and Emerging Data for Meropenem-Vaborbactam.

PURPOSE The search for new agents to treat multidrug-resistant gram-negative bacterial infections has been ongoing. Specifically, carbapenem-resistant Enterobacteriaceae (CRE) infections often exhibit multiple resistance mechanisms, including alterations in drug structure, bacterial efflux pumps, and drug permeability. Vaborbactam, a cyclic boronic acid pharmacophore, has the highest potency in vitro with meropenem as an inhibitor of class A carbapenemases, including Klebsiella pneumoniae carbapenemase (KPC). This combination product was approved by the US Food and Drug Administration for complicated urinary tract infections (cUTIs) in August 2017, and recent Phase III trial data have expanded the literature available. This article aimed to describe the literature regarding spectrum of activity, dosing and administration, including pharmacokinetic and pharmacodynamics properties, safety profile, and efficacy end points. METHODS The terms meropenem, vaborbactam, RPX7009, and meropenem-vaborbactam were used to search for literature via PubMed, ClinicalTrials.gov, and published abstracts from 2013 to July 2019. Abstracts from IDWeek 2019 were also searched via these terms. Results were limited to availability in English. FINDINGS Meropenem-vaborbactam covers a spectrum of gram-negative bacterial pathogens, including K pneumoniae, Escherichia coli, and Enterobacter cloacae complex. Although the addition of vaborbactam to meropenem results in MIC lowering for KPC-positive Enterobacteriaceae, in vitro data reveal limited activity against resistant strains of Acinetobacter species and Pseudomonas aeruginosa. Data from 2 Phase III studies compare the drug with available therapies for the following indications: cUTIs, acute pyelonephritis, hospital-acquired and ventilator-acquired bacterial pneumonia, bacteremia, and complicated intra-abdominal infections. Outcomes include an improvement in clinical success when compared with piperacillin-tazobactam (98.4% vs 94%; 95% CI, 0.7%-9.1%; P < 0.001 for noninferiority) for overall treatment of cUTIs and acute pyelonephritis and clinical cure (64.3% vs 33.3%; P = 0.04) when compared with best available therapy for CRE infections in various sites of infection. Adverse events have been described as mild to moderate, with few events requiring discontinuation of the drug therapy. IMPLICATIONS Currently, meropenem-vaborbactam is approved for treatment of cUTIs and acute pyelonephritis; however, off-label use, in particular for CRE infections, appears beneficial. Clinical trials to date have found an improvement in clinical cure and potentially an improved tolerability compared with standard therapies. Most of the evidence for meropenem-vaborbactam activity and the role in therapy focuses on KPC-producing organisms; however, because in vitro activity has been found with some non-KPC-producing CRE, its role may be further described from upcoming in vivo cases and postmarketing research.

['Shoulders|Bethany R|BR|', 'Casapao|Anthony M|AM|', 'Venugopalan|Veena|V|']

2020

33936093

SAMD9 Is Relating With M2 Macrophage and Remarkable Malignancy Characters in Low-Grade Glioma.

Immunoreactions regulated by TAMs (Tumor-associated macrophages) play a pivotal role in tumorigenesis and metastasis. In recent decades, treatments based on immune regulation have achieved revolutionary breakthroughs in cancer targeted therapies. The phenotypes of TAMs in gliomas are more heterogeneous and inherently complex than can be simply defined by classification into the M1 and M2 polarized states. The detailed mechanisms surrounding infiltrating macrophage phenotype and glioma characteristics remain undefined. SAMD9 (Sterile Alpha Motif Domain-Containing Protein 9) was found to be highly expressed in glioma and closely related to histological and genetic features in CGGA and TCGA databases. Simultaneously, we present evidence to show that there was a positive association between SAMD9 and malignancy characters in LGG. Univariable and Multivariate proportional hazard Cox analysis showed that SAMD9 was an independent prognostic factor for LGG. Surprisingly, Gene Ontology (GO) analysis showed SAMD9 expression level was remarkably well correlated with immunological responses and the Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis supported the connection with immune responses and tumorigenesis. Immune infiltration analysis demonstrated that high SAMD9 expression resulted in an accumulation of macrophages by CIBERSORT and TIMER databases, especially positively related to macrophage total marker gene AIF1 and Macrophage M2 marker gene CD163. IHC staining further indicated a high correlation of SAMD9 with those specific macrophage markers in the immune response. Human THP-1 cells were induced into M2 macrophages, which were then co-cultured with LN229 cells. Silencing of SAMD9 by shRNA in LN229 cells attenuated the infiltration abilities of M2 macrophage. SAMD9 explored immune response via relating of M2 macrophage in vitro. Our results revealed SAMD9 acted as the malignancy characters in LGG, enrichment with M2 macrophage.

['Ma|Wenping|W|', 'Zhang|Kenan|K|', 'Bao|Zhaoshi|Z|', 'Jiang|Tao|T|', 'Zhang|Ying|Y|']

2021

33366351

The complete mitochondrial genome of the hybrid of Jersey cattle (Bos taurus; ♂) × Gannan yak (Bos grunniens; ♀).

In this study, we reconstructed the complete mitochondrial genome of the hybrid of Jersey cattle (Bos taurus; ♂) × Gannan yak (Bos grunniens; ♀) from Illumina sequencing reads. The mitochondrial genome is 16,322 bp in length with an A + T-biased nucleotide composition, and encodes 13 protein-coding genes, 22 tRNAs, and 2 rRNAs along with a noncoding control region. In addition, its gene order is identical to those of previously published mitochondrial genomes of the genera Bison and Bos. Phylogenetic analysis indicates that this hybrid is most closely related to Gannan yak and Jinchuan yak.

['Guo|Xian|X|', 'Bao|Pengjia|P|', 'Wu|Xiaoyun|X|', 'Yang|Zhen|Z|', 'Shi|Shengguang|S|', 'Xiong|Lin|L|', 'Pei|Jie|J|', 'Yan|Ping|P|']

2019

30039331

Comprehensive optimization of precursor-directed production of BC194 by Streptomyces rochei MB037 derived from the marine sponge Dysidea arenaria.

BC194, a derivative of borrelidin (BN) that features a lower cytotoxicity than that of BN due to an altered starter unit, trans-1,2-cyclobutanedicarboxylic acid (trans-1,2-CBDA), is a potent inhibitor of angiogenesis. However, BC194 production has only been reported to occur via mutasynthesis, which requires tedious, multistep genetic manipulation. In this study, we surveyed several factors contributing to the precursor-directed biosynthesis of BC194 and provided an alternative method for the production of BC194 that is directly applicable to other BN-producing strains. First, the precursor-directed biosynthesis of BC194 by a BN-producing strain, Streptomyces rochei MB037 derived from sponge Dysidea arenaria, was carried out in modified Radix astragali (RA) medium with 5 mM trans-1,2-CBDA. Next, possible inhibitors of BN starter unit trans-1,2-cyclopentanedicarboxylic acid (trans-1,2-CPDA) biosynthesis were investigated. It was found that potassium ferricyanide was a possible inhibitor of 3,4-dihydroxyphenylacetate 2,3-dioxygenase (DHPAO) and capable of suppressing the yield of BN and increasing the BC194 yield by 112.5% (from 5.2 ± 0.76 to 11.9 ± 0.59 mg/L). BC194 yield was further enhanced in the presence of 50 mM trans-1,2-CBDA, reaching 20.2 ± 0.62 mg/L. Furthermore, 3% macroporous adsorbent DA-201 resin was added to the fermentation broth, enabling a further 36.6% increase in BC194 production and reaching 27.59 ± 1.15 mg/L. Moreover, an efficient separation of BC194 with approximately 95% purity was developed by employing high-speed counter-current chromatography (HSCCC), achieving an improved recovery (approximately 93%).

['Li|Yingxin|Y|', 'Zhang|Fengli|F|', 'Banakar|Shivakumar|S|', 'Li|Zhiyong|Z|']

2018

30306032

Loop Electrosurgical Excision Procedure versus Cryotherapy in the Treatment of Cervical Intraepithelial Neoplasia: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

Aim Invasive cervical cancer is proceeded by a phase of preinvasive disease that is slow to progress and can be detected, treated, and collectively referred to as cervical intraepithelial neoplasia (CIN). Several excisional and ablative treatments for CIN have been studied, with loop electrosurgical excision procedure (LEEP) and cryotherapy being the two most commonly utilized. The objective of this systematic review and meta-analysis of randomized controlled trials (RCTs) was to compare the compare harms and benefits of LEEP versus cryotherapy in women with CIN. Methods Electronic databases were searched from their inception until May 2018. We included all RCTs comparing cryotherapy versus LEEP in women with CIN. We included trials evaluating both HIV-seropositive and HIV-seronegative women. The primary outcome was the persistence of the disease at 6-month follow-up. Meta-analysis was performed using the random-effects model to produce summary treatment effects in terms of relative risk (RR) with 95% confidence interval (CI). Results Four trials, including 1035 women with CIN, were identified as relevant and included in the meta-analysis. Women who received LEEP for CIN had a significantly lower persistence at 6-month follow-up biopsy (RR: 0.87, 95% CI: 0.76-0.99) and significantly lower recurrence at 12-month follow-up biopsy (RR: 0.91, 95% CI: 0.84-0.99) compared to those who received cryotherapy. No between-group differences were found in the complications rate, but the analyses were not powered for these outcomes. Conclusions In women with CIN, treatment with LEEP was associated with a significantly lower risk of persistence disease at 6 months and recurrence disease at 12 months compared to treatment with cryotherapy.

["D'Alessandro|Pietro|P|", 'Arduino|Bruno|B|', 'Borgo|Maria|M|', 'Saccone|Gabriele|G|', 'Venturella|Roberta|R|', 'Di Cello|Annalisa|A|', 'Zullo|Fulvio|F|']

2018

34172434

A systematic review about the role of preoperative 18F-FDG PET/CT for prognosis and risk stratification in patients with endometrial cancer.

OBJECTIVE To analyse the available literature on the prognostic value of preoperative 18F-FDG PET/CT metabolic parameters and their usefulness in risk stratification in patients with endometrial cancer (EC). MATERIAL AND METHODS Pubmed searches used "(endometr* OR uter*) AND (PET OR FDG)" as keywords from January-2000 to June-2020. References in included articles were checked for possible publications not included in the first search. Studies evaluating the prognostic value of preoperative 18F-FDG PET/CT and its role for risk stratification in patients with EC were included. Non-original articles (reviews, editorials, letters, legal cases, interviews, case reports, etc.) were not included. RESULTS Twenty-six studies (1918 patients) were selected according to the inclusion criteria in this review. Thirteen studies (939 patients) related to the prognostic role of preoperative 18F-FDG PET/CT and 14 studies (1036 patients) related to its role in risk stratification were included. Parameters such as SUVmax, metabolic tumour volume (MTV) and total lesion glycolysis (TLG) of the primary tumour were analysed. CONCLUSIONS Preoperative SUVmax is useful for non-invasive diagnosis and for deciding the appropriate therapeutic strategy, as it could be used as an independent prognostic marker for recurrence and survival in EC. In addition, both preoperative VTM and GTL could be independent prognostic factors for predicting recurrence and survival, but there is still insufficient scientific evidence. The usefulness of SUVmax for risk stratification is limited (there is insufficient literature that 18F-FDG PET/CT can replace surgical staging), although VTM and GTL are more accurate and have a valuable role in risk stratification of EC. However, larger multicentre studies with adequate follow-up time are needed to confirm these findings.

['Noriega-Álvarez|Edel|E|', 'García Vicente|Ana M|AM|', 'Jiménez Londoño|Germán A|GA|', 'Martínez Bravo|Wilson R|WR|', 'González García|Beatriz|B|', 'Soriano Castrejón|Ángel M|ÁM|']

2021

34321946

Neuro-Ophthalmological Manifestations in Children with Down Syndrome: Current Perspectives.

Down syndrome, caused by an extra copy of all or part of chromosome 21, is the most prevalent intellectual disability of genetic origin. Among numerous comorbidities which are part of the phenotype of individuals with Down syndrome, ocular problems appear to be highly prevalent. Neuro-ophthalmological manifestations, such as ocular alignment and motility disturbances, amblyopia, hypoaccommodation or optic nerve abnormalities, and other organic ocular anomalies frequently reported in Down syndrome, may lead to an overall decrease in visual acuity. Although numerous studies have reported ocular anomalies related to Down syndrome, it remains challenging to determine the impact of each anomaly upon the decreased visual acuity, as most such individuals have more than one ocular problem. Even in children with Down syndrome and no apparent ocular defect, visual acuity has been found to be reduced compared with typically developing children. Pediatric ophthalmological examination is a critical component of a multidisciplinary approach to prevent and treat ocular complications and improve the visual outcome in children with Down syndrome. This narrative review aims to provide a better understanding of the neuro-ophthalmological manifestations and discuss the current ophthalmological management in children with Down syndrome.

['Postolache|Lavinia|L|0000-0001-5846-0673', 'Monier|Anne|A|', 'Lhoir|Sophie|S|']

2021