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30909929

MCUR1 facilitates epithelial-mesenchymal transition and metastasis via the mitochondrial calcium dependent ROS/Nrf2/Notch pathway in hepatocellular carcinoma.

BACKGROUND Mitochondrial Ca2+ plays a critical role in tumorigenesis, including cell proliferation and metastasis. Mitochondrial calcium uniporter regulator 1 (MCUR1) has been shown to be frequently upregulated in HCC and promote cancer cell survival. However, whether MCUR1 is involved in the metastasis of HCC and its underlying mechanisms remain unknown. METHODS The effect of MCUR1 expression on epithelial-mesenchymal transition (EMT) in HCC cells was first evaluated by immunofluorescent staining and Western blot. Then, in vitro invasion and in vivo metastasis assays were used to evaluate the function of MCUR1 in HCC metastasis. The underlying mechanism has also been explored by investigating the effect of MCUR1 on ROS/Nrf2/Notch1 pathway. RESULTS MCUR1 expression was significantly higher in HCC with metastasis and associated with tumor progression. MCUR1 promoted in vitro invasion and in vivo metastasis of HCC cells by promoting EMT via Snail. Mechanistically, MCUR1-mediated mitochondrial Ca2+ signaling promoted the EMT of HCC cells by activating ROS/Nrf2/Notch1 pathway. Inhibition of ROS production, mitochondrial Ca2+ uptake, Nrf2 expression or Notch1 activity significantly suppressed MCUR1-induced EMT of HCC cells. In addition, treatment with the mitochondrial Ca2+-buffering protein parvalbumin significantly inhibited ROS/Nrf2/Notch pathway and MCUR1-induced EMT and HCC metastasis. CONCLUSIONS Our study provides evidence supporting a metastasis-promoting role for MCUR1-dependent mitochondrial Ca2+ uptake in HCC. Our findings suggest that MCUR1 may be a potential therapeutic target for HCC treatment.

['Jin|Mingpeng|M|', 'Wang|Jiaojiao|J|', 'Ji|Xiaoying|X|', 'Cao|Haiyan|H|', 'Zhu|Jianjun|J|', 'Chen|Yibing|Y|', 'Yang|Jin|J|', 'Zhao|Zheng|Z|', 'Ren|Tingting|T|http://orcid.org/0000-0002-6226-6504', 'Xing|Jinliang|J|']

2019

30479025

Phenolic Compounds and Allelopathic Potential of Fermented and Unfermented Wheat and Corn Straw Extracts.

Total phenolic (TPC) and flavonoid (TFC) content, individual phenolic compounds and antioxidant activities of methanol extracts of wheat and corn straw were determined. Germination bioassay was conducted with Abutilon theophrasti Medik., Asclepias syriaca L., and Chenopodium album L. seed. Samples were fermented by Lactobacillus plantarum and changes in TPC, TFC, antioxidant, and biological activity were investigated. TPC and TFC were significant in both samples and after fermentation their recovery was improved. All samples contain mainly quercetin, cinnamic acid, p-coumaric acid, and ferulic acid. Fermentation changed the content of phenolic and flavonoid compounds, differently in each case. All tested extracts showed high DPPH activity with IC50 being significantly lower for fermented samples. FRAP activity was also high. Crude straw extracts were overall more effective than fermented ones concerning inhibition of germination and seedlings growth, mainly without statistically significant differences between wheat and corn. Compared with mesotrione, extracts were more effective in germination and seedling growth inhibition of C. album and in seedling growth inhibition of A. theophrasti.

['Đorđević|Tijana|T|http://orcid.org/0000-0001-8798-4505', 'Sarić-Krsmanović|Marija|M|', 'Gajić Umiljendić|Jelena|J|']

2019

33538813

The microbial dimension of submarine groundwater discharge: current challenges and future directions.

Despite the relevance of submarine groundwater discharge (SGD) for ocean biogeochemistry, the microbial dimension of SGD remains poorly understood. SGD can influence marine microbial communities through supplying chemical compounds and microorganisms, and in turn, microbes at the land-ocean transition zone determine the chemistry of the groundwater reaching the ocean. However, compared with inland groundwater, little is known about microbial communities in coastal aquifers. Here, we review the state of the art of the microbial dimension of SGD, with emphasis on prokaryotes, and identify current challenges and future directions. Main challenges include improving the diversity description of groundwater microbiota, characterized by ultrasmall, inactive and novel taxa, and by high ratios of sediment-attached versus free-living cells. Studies should explore microbial dynamics and their role in chemical cycles in coastal aquifers, the bidirectional dispersal of groundwater and seawater microorganisms, and marine bacterioplankton responses to SGD. This will require not only combining sequencing methods, visualization and linking taxonomy to activity but also considering the entire groundwater-marine continuum. Interactions between traditionally independent disciplines (e.g. hydrogeology, microbial ecology) are needed to frame the study of terrestrial and aquatic microorganisms beyond the limits of their presumed habitats, and to foster our understanding of SGD processes and their influence in coastal biogeochemical cycles.

['Ruiz-González|Clara|C|0000-0003-3568-4943', 'Rodellas|Valentí|V|0000-0002-5896-9987', 'Garcia-Orellana|Jordi|J|0000-0002-0543-2641']

2021

28567342

Functional outcome of tibial fracture with acute compartment syndrome and correlation to deep posterior compartment pressure.

AIM To measure single baseline deep posterior compartment pressure in tibial fracture complicated by acute compartment syndrome (ACS) and to correlate it with functional outcome. METHODS Thirty-two tibial fractures with ACS were evaluated clinically and the deep posterior compartment pressure was measured. Urgent fasciotomy was needed in 30 patients. Definite surgical fixation was performed either primarily or once fasciotomy wound was healthy. The patients were followed up at 3 mo, 6 mo and one year. At one year, the functional outcome [lower extremity functional scale (LEFS)] and complications were assessed. RESULTS Three limbs were amputated. In remaining 29 patients, the average times for clinical and radiological union were 25.2 ± 10.9 wk (10 to 54 wk) and 23.8 ± 9.2 wk (12 to 52 wk) respectively. Nine patients had delayed union and 2 had nonunion who needed bone grafting to augment healing. Most common complaint at follow up was ankle stiffness (76%) that caused difficulty in walking, running and squatting. Of 21 patients who had paralysis at diagnosis, 13 (62%) did not recover and additional five patients developed paralysis at follow-up. On LEFS evaluation, there were 14 patients (48.3%) with severe disability, 10 patients (34.5%) with moderate disability and 5 patients (17.2%) with minimal disability. The mean pressures in patients with minimal disability, moderate disability and severe disability were 37.8, 48.4 and 58.79 mmHg respectively (P < 0.001). CONCLUSION ACS in tibial fractures causes severe functional disability in majority of patients. These patients are prone for delayed union and nonunion; however, long term disability is mainly because of severe soft tissue contracture. Intra-compartmental pressure (ICP) correlates with functional disability; patients with relatively high ICP are prone for poor functional outcome.

['Goyal|Saumitra|S|', 'Naik|Monappa A|MA|', 'Tripathy|Sujit Kumar|SK|', 'Rao|Sharath K|SK|']

2017

27648378

Effect of itraconazole on the quality of life in patients with moderate to severe seborrheic dermatitis: a randomized, placebo-controlled trial.

BACKGROUND Few studies have examined the effect of seborrheic dermatitis (SD) and/or its consequent therapy on a patient's quality of life. Itraconazole has been suggested as an effective therapy for severe SD but its impact on Quality of Life (QoL) in these patients has never been studied before. OBJECTIVE The study aimed to verify the efficacy of the itraconazole on the quality of life in patients with moderate to severe SD. METHODS A randomized, double-blind, placebo controlled trial was planned to describe the effect of SD per se on QoL and to determine the impact of oral itraconazole or placebo on QoL of SD patients. Sixty-eight patients with moderate to severe SD participated in the study to receive either itraconazole or placebo. Dermatology Life Quality Index was used to evaluate their quality of life before and after treatment. Itraconazole 200 mg/daily or placebo was prescribed for one week and then the first two days of every month for the following three months. Fifty-seven patients completed the study. RESULTS Significant improvement was observed in QoL of both itraconazole and placebo groups, but itraconazole group showed significantly higher improvement as compared to placebo (p=0.001). QoL was impaired significantly with high disease severity (p=0.002) and facial involvement (p=0.017). CONCLUSIONS Itraconazole significantly improves the QoL in patients with moderate to severe SD.

['Abbas|Zaheer|Z|', 'Ghodsi|Seyedeh Z|SZ|', 'Abedeni|Robabeh|R|']

2016

25859348

Increased risk of death in African American patients with end-stage renal disease secondary to lupus.

BACKGROUND Systemic lupus erythematosus (SLE) is a devastating systemic disease that can lead to end-stage renal disease (ESRD). Our goal was to assess the relative mortality risk associated with race in pediatric and adult populations with ESRD secondary to SLE maintained on hemodialysis (HD). METHODS We identified an inception cohort of patients who were started on HD in January 1990 from data collected by the United States Renal Data System (USRDS). Kaplan-Meier survival analyses were performed in these patients using the time at risk from 1 January 1990 through 31 December 2010, the last date of the USRDS data collection period in this dataset. Cox proportional hazard models were used to assess mortality, adjusted for age at dialysis initiation. Subjects were censored at transplantation or end of follow-up. RESULTS There were 1580 patients with ESRD secondary to SLE, 252 pediatric patients (62% African American) and 1328 adults (56% African American). African American pediatric patients with ESRD secondary to SLE had a 2-fold increased risk of death compared with African American children with other causes of ESRD [hazard ratio (HR): 2.1, 95% confidence interval (CI): 1.4-2.9, P < 0.01]. Increased risk of death was also seen in African American adults with ESRD secondary to SLE compared with both Caucasians with ESRD secondary to SLE (HR: 2.3, 95% CI: 1.2-4.2, P < 0.01) and African American adults with ESRD secondary to other diseases (HR: 1.2, 95% CI: 1.1-1.4, P < 0.01). CONCLUSION Our study suggests that there is a significant increased risk for mortality in African American children and adults with ESRD secondary to SLE. This suggests that African Americans with ESRD secondary to SLE need aggressive monitoring.

['Sule|Sangeeta|S|', 'Fivush|Barbara|B|', 'Neu|Alicia|A|', 'Furth|Susan|S|']

2014

25049980

Growth Performance, Carcass Characteristics and Meat Yield of Boer Goats Fed Diets Containing Leaves or Whole Parts of Andrographis paniculata.

The study was conducted to determine the effect of feeding diets containing Andrographis paniculata leaves (APL), whole Andrographis paniculata plant (APWP) and a control without Andrographis paniculata (AP0), on growth performance, carcass characteristics and meat yield of 24 intact Boer bucks. The results obtained indicated that inclusion of Andrographis paniculata significantly improved feed intake, weight gain, feed efficiency and live weight. The ratios of carcass to fat, lean to bone, lean to fat, and composition of meat were also improved. In addition, there were significant differences (p<0.05) between the dietary treatments in dressing percentage and chilling loss. Goats fed on AP0 (control) had significantly higher proportions of fat and bone, as well as thicker back fat than the supplemented animals (APL and APWP). Higher gut fill in animals fed Andrographis paniculata suggested slow rate of digestion, which could have improved utilization and absorption of nutrients by the animals. Goats fed Andrographis paniculata also produced higher meat yield and relatively lower fat contents (p<0.05).

['Yusuf|A L|AL|', 'Goh|Y M|YM|', 'Samsudin|A A|AA|', 'Alimon|A R|AR|', 'Sazili|A Q|AQ|']

2014

27023716

Recent advances in basic research on the trigeminal ganglion.

Peripheral tissue inflammation can alter the properties of somatic sensory pathways, causing behavioral hypersensitivity and resulting in increased responses to pain caused by noxious stimulation (hyperalgesia) and normally innocuous stimulation (allodynia). These hypersensitivities for nociception are caused by changes in the excitability of trigeminal ganglion (TG) neurons. These changes alter sensory information processing in the neurons in the medullary trigeminal nucleus of caudalis. Increasing information is becoming available regarding trigeminal neuron-neuron/neuron-satellite glial cells (SGCs) communication. The activation of intraganglionic communication plays an important role in the creation and maintenance of trigeminal pathological pain. Therefore, in this review, we focus on the recent findings for sensory functions and pharmacological modulation of TG neurons and SGCs under normal and pathological conditions, and we discuss potential therapeutic targets in glia-neuronal interactions for the prevention of trigeminal neuropathic and inflammatory pain.

['Goto|Tetsuya|T|', 'Oh|Seog Bae|SB|', 'Takeda|Mamoru|M|', 'Shinoda|Masamichi|M|', 'Sato|Tadasu|T|', 'Gunjikake|Kaori K|KK|', 'Iwata|Koichi|K|']

2016

28874126

Development and external validation of nomograms to predict the risk of skeletal metastasis at the time of diagnosis and skeletal metastasis-free survival in nasopharyngeal carcinoma.

BACKGROUND The skeletal system is the most common site of distant metastasis in nasopharyngeal carcinoma (NPC); various prognostic factors have been reported for skeletal metastasis, though most studies have focused on a single factor. We aimed to establish nomograms to effectively predict skeletal metastasis at initial diagnosis (SMAD) and skeletal metastasis-free survival (SMFS) in NPC. METHODS A total of 2685 patients with NPC who received bone scintigraphy (BS) and/or 18F-deoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and 2496 patients without skeletal metastasis were retrospectively assessed to develop individual nomograms for SMAD and SMFS. The models were validated externally using separate cohorts of 1329 and 1231 patients treated at two other institutions. RESULTS Five independent prognostic factors were included in each nomogram. The SMAD nomogram had a significantly higher c-index than the TNM staging system (training cohort, P = 0.005; validation cohort, P < 0.001). The SMFS nomogram had significantly higher c-index values in the training and validation sets than the TNM staging system (P < 0.001 and P = 0.005, respectively). Three proposed risk stratification groups were created using the nomograms, and enabled significant discrimination of SMFS for each risk group. CONCLUSION The prognostic nomograms established in this study enable accurate stratification of distinct risk groups for skeletal metastasis, which may improve counseling and facilitate individualized management of patients with NPC.

['Yang|Lin|L|http://orcid.org/0000-0002-4732-9327', 'Xia|Liangping|L|', 'Wang|Yan|Y|', 'He|Shasha|S|', 'Chen|Haiyang|H|', 'Liang|Shaobo|S|', 'Peng|Peijian|P|', 'Hong|Shaodong|S|', 'Chen|Yong|Y|']

2017

33173753

Protein losing enteropathy and pneumatosis intestinalis in a child with COVID 19 infection.

Background Severe acute respiratory syndrome corona virus 2 (SARS- CoV-2) is known as COVID 19 seems to be one of the most contagious and dangerous infection in children and adults. According to first adult studies association of gastrointestinal (GI) symptoms with COVID 19 infection was as high as 79% (1).But later study showed lower association around 18% (2).As the pandemic of COVID 19 is going on, different clinical presentation of disease especially in children are well appeared. In addition atypical presentations may confuse and mislead physician to do different diagnostic procedures and interventions. We report a 6 years and half old boy with diarrhea, abdominal pain with first diagnosis acute abdomen due to acute appendicitis. At last diagnosis of pneumatosis intestinalis due to enterocolitis was confirmed. Case presentation A 6 years and half old boy with severe abdominal pain admitted in emergency ward. He had history of fever, nine days of diarrhea and recurrent vomiting. The abdominal pain was severe with moderate tenderness in right lower quadrant. He admitted in pediatric surgery ward after surgical consultation for rolling out acute appendicitis. The results of first lab studies were shown leucopenia, lymphopenia and COVID 19 PCR was positive. During admission the cough has increased and abdominal distention has evolved. Vomiting was intractable and feeding was impossible. Pneumatosis intestinalis in ascending colon and dilatation in colon caliber were detected abdominal. Miliary like pattern in lung has reported in chest CT. Stool exam results revealed loss of protein in high amount in spite of normal pancreatic and enterocyte function. The calprotectin was high and implied high inflammation in large intestine. With all above data necrotizing enterocolitis management was started. After 14 days patients had good appetite and feeding slowly introduced. All symptoms resolved with exception of cough. Albumin and other electrolytes remained stable. The patient discharged without morbidity. Conclusion COVID 19 infection has many different and mysterious presentations. GI manifestations are among important, common presentations. The acute abdomen like presentation with different complications like pneumatosis intestinalis, protein losing enteropathy are not common but knowledge about these presentations assist physician to be aware and make decision accurately.

['Rohani|Pejman|P|', 'Karimi|Abdollah|A|', 'Tabatabaie|Sedigheh Rafiei|SR|', 'Khalili|Mitra|M|', 'Sayyari|Aliakbar|A|']

2021

34472583

Similar antibody responses against SARS-CoV-2 in HIV uninfected and infected individuals on antiretroviral therapy during the first South African infection wave.

BACKGROUND There is limited understanding of SARS-CoV-2 pathogenesis in African populations with a high burden of infectious disease comorbidities such as HIV. The kinetics, magnitude and duration of virus-specific antibodies and the underlying B cell responses in people living with HIV (PLWH) in sub-Saharan Africa have not been fully characterized. METHODS We longitudinally followed SARS-CoV-2 infected individuals in Durban, KwaZulu-Natal, South Africa and characterized SARS-CoV-2 receptor binding domain-specific IgM, IgG and IgA antibodies weekly for a month, and then at 3 months post diagnosis. 7/30 (41.7%) were PLWH, 83% (25/30) of which were on ART and with full HIV suppression. Potency of convalescent plasma neutralization was determined using a live virus neutralization assay and antibody secreting cell population frequencies were determined by flow cytometry. RESULTS Similar seroconversion rates, time to peak antibody titer, peak magnitude and durability of anti-SARS-CoV-2 IgM, IgG, IgA, were observed in HIV uninfected and PLWH with complete HIV suppression on ART. In addition, similar neutralization potency against an isolate of SARS-CoV-2, circulating at the time of sampling in the first wave of SARS-CoV-2 infections in South Africa was observed in both groups. Loss of IgA was significantly associated with age (p=0.023) and a previous diagnosis of TB (p=0.018). CONCLUSIONS Similar antibody response kinetics and neutralization potency in HIV negative and PLWH on stable ART in an African setting suggests that COVID-19 natural infections may confer comparable antibody immunity in these groups. This provides hope that COVID-19 vaccines will be effective in PLWH on stable ART.

['Snyman|Jumari|J|', 'Hwa|Shi-Hsia|SH|', 'Krause|Robert|R|', 'Muema|Daniel|D|', 'Reddy|Tarylee|T|', 'Ganga|Yashica|Y|', 'Karim|Farina|F|', 'Leslie|Alasdair|A|', 'Sigal|Alex|A|', "Ndung'u|Thumbi|T|", '|||']

2021

29599346

Bevacizumab Does Not Reduce the Lymphocele Rate in Advanced Ovarian Cancer After Complete Cytoreductive Surgery.

BACKGROUND/AIM We aimed to evaluate the impact of bevacizumab on the lymphocele rate in patients after complete cytoreductive surgery for advanced ovarian cancer. PATIENTS AND METHODS This retrospective study included patients with advanced ovarian cancer who had undergone complete cytoreductive surgery with pelvic and para-aortic lymphadenectomy at the Gustave Roussy Institute from 2005 to 2014. The introduction of bevacizumab was discussed in a multidisciplinary meeting. RESULTS During the study period, 247 patients were included; 24.6% of patients (61 patients) received adjuvant bevacizumab. The rate of symptomatic lymphocele was 34% (84 patients). In the lymphocele group, patients tended to receive adjuvant bevacizumab more often than did the control group (32% and 21%, respectively, p=0.05). In multivariate analysis, bevacizumab was not significantly associated with the risk of symptomatic lymphocele (hazard ratio(HR)=1.62, 95% confidence interval(CI)=0.87-3.01, p=0.12). CONCLUSION Adjuvant bevacizumab has no impact on the formation or duration of symptomatic lymphocele in patients after complete cytoreductive surgery for advanced ovarian cancer.

['Perrin|Morgane|M|', 'Bentivegna|Enrica|E|', 'Bonneau|Claire|C|', 'Uzan|Catherine|C|', 'Leary|Alexandra|A|', 'Pautier|Patricia|P|', 'Genestie|Catherine|C|', 'Morice|Philippe|P|', 'Gouy|Sébastien|S|']

2018

27881101

Knowledge, barriers and facilitators of exercise in dialysis patients: a qualitative study of patients, staff and nephrologists.

BACKGROUND Despite growing evidence on benefits of increased physical activity in hemodialysis (HD) patients and safety of intra-dialytic exercise, it is not part of standard clinical care, resulting in a missed opportunity to improve clinical outcomes in these patients. To develop a successful exercise program for HD patients, it is critical to understand patients', staff and nephrologists' knowledge, barriers, motivators and preferences for patient exercise. METHODS In-depth interviews were conducted with a purposive sample of HD patients, staff and nephrologists from 4 dialysis units. The data collection, analysis and interpretation followed Criteria for Reporting Qualitative Research guidelines. Using grounded theory, emergent themes were identified, discussed and organized into major themes and subthemes. RESULTS We interviewed 16 in-center HD patients (mean age 60 years, 50% females, 63% blacks), 14 dialysis staff members (6 nurses, 3 technicians, 2 dietitians, 1 social worker, 2 unit administrators) and 6 nephrologists (50% females, 50% in private practice). Although majority of the participants viewed exercise as beneficial for overall health, most patients failed to recognize potential mental health benefits. Most commonly reported barriers to exercise were dialysis-related fatigue, comorbid health conditions and lack of motivation. Specifically for intra-dialytic exercise, participants expressed concern over safety and type of exercise, impact on staff workload and resistance to changing dialysis routine. One of the most important motivators identified was support from friends, family and health care providers. Specific recommendations for an intra-dialytic exercise program included building a culture of exercise in the dialysis unit, and providing an individualized engaging program that incorporates education and incentives for exercising. CONCLUSION Patients, staff and nephrologists perceive a number of barriers to exercise, some of which may be modifiable. Participants desired an individualized intra-dialytic exercise program which incorporates education and motivation, and they provided a number of recommendations that should be considered when implementing such a program.

['Jhamb|Manisha|M|', 'McNulty|Mary L|ML|', 'Ingalsbe|Gerald|G|', 'Childers|Julie W|JW|', 'Schell|Jane|J|', 'Conroy|Molly B|MB|', 'Forman|Daniel E|DE|', 'Hergenroeder|Andrea|A|', 'Dew|Mary Amanda|MA|']

2016

26955582

Reticulin immunostaining revisited.

INTRODUCTION Reticulin staining has been suggested as an inexpensive tool in the differential diagnosis of melanoma versus benign nevi. In the present study, reticulin immunostaining patterns in malignant melanomas, benign intradermal nevi, and blue nevi were observed. The concordance in evaluation of the pattern between observers was also done. MATERIALS AND METHODS A retrospective search was performed in the computer database of the Ackerman Academy of Dermatopathology for "melanoma," "melanocytic nevus," and "blue nevus". Fifty-six melanomas (30 of nodular subtype and 26 of superficial spreading subtype), 54 benign compound nevi, and 27 blue nevi were selected for the study. Patterns of reticulin staining in the dermis and the basement membrane in these melanocytic lesions were evaluated and the concordance between the two groups of authors was assessed. Statistical evaluation was performed with the Statistica(®) 10 program, Tulsa, OK. Concordance of the pattern evaluation was evaluated using Cohen's kappa coefficient. RESULTS Melanomas show a variable basement membrane pattern some of which show flat, thin and smooth pattern. Benign nevi almost never showed this flat pattern at the basement membrane zone. In the dermis, melanomas showed reticulin fibers surrounding groups of melanocytic cells while nevi predominantly had reticulin fibers around individual cells. There was greater agreement in evaluating the dermal component compared to the basement membrane pattern. CONCLUSION The dermal reticulin staining pattern may be of some value in the diagnosis of melanocytic lesions, but poor concordance in evaluation of the basement membrane zone pattern limits its usefulness.

['Torres|Kara Melissa T|KM|', 'Kazlouskaya|Viktoryia|V|', 'Parikh|Kruti|K|', 'Elston|Dirk M|DM|']

2016

29164045

Factors Related to Healthcare Service Quality in Long-term Care Hospitals in South Korea: A Mixed-methods Study.

Objectives The environment of long-term care hospitals (LTCHs) is critical to the management of the quality of their services and to patient safety, as highlighted by international studies. However, there is a lack of evidence on this topic in South Korea. This study aimed to examine the factors affecting healthcare quality in LTCHs and to explore the effectiveness of their quality management. Methods This study used a mixed methods approach with quantitative data collected in a national survey and qualitative data from semi-structured interviews with practice-based managers. The samples included 725 nationally representative LTCHs in South Korea for the quantitative analysis and 15 administrators for the in-depth interviews. Results A higher installation rate of patient-safety and hygiene-related facilities and staff with longer-tenures, especially nurses, were more likely to have better healthcare quality and education for both employees and patients. Conclusion The need for patient-safety- and hygiene-related facilities in LTCHs that serve older adults reflects their vulnerability to certain adverse events (e.g., infections). Consistent and skillful nursing care to improve the quality of LTCHs can be achieved by developing relevant educational programs for staff and patients, thereby strengthening the relationships between them.

['Sohn|Minsung|M|', 'Choi|Mankyu|M|']

2017

32975797

An in Vitro Assay to Study the Role of Opioids in Modulating Immune Cell Adhesion.

Opioids play a pivotal role in pain transmission but are also able to modulate immune cell functions. In the last decades a connection between opioids and integrins-adhesion molecules involved, among many other processes, in leukocyte recruitment at inflamed site-has been established. To study immune cell integrin-mediated adhesion, cell adhesion assay is a simple, reproducible, and valuable tool capable of unraveling concentration-dependent effects of a test candidate on integrin-mediated cell adhesion.

['Baiula|Monica|M|']

2021

33816120

Urethral squamous papilloma with multiple bladder diverticulum: A case report and literature review.

Periurethral lesions are common in post-menopausal women. The differential diagnosis includes urethral caruncle, urethral prolapse, urethral diverticulum and the notorious urethral malignancy. Non-invasive squamous lesion of the urethra is rare with limited data on clinical significance. We present a case of urethral squamous papilloma in a premenopausal woman causing significant storage and voiding symptoms.

['Sengupta|Soumish|S|', 'Basu|Supriya|S|', 'Ghosh|Kadambari|K|', 'Sengupta|Subhrajyoti|S|']

2021

27234354

Extra-cardiac manifestations of adult congenital heart disease.

Advancement in correction or palliation of congenital cardiac lesions has greatly improved the lifespan of congenital heart disease patients, resulting in a rapidly growing adult congenital heart disease (ACHD) population. As this group has increased in number and age, emerging science has highlighted the systemic nature of ACHD. Providers caring for these patients are tasked with long-term management of multiple neurologic, pulmonary, hepatic, renal, and endocrine manifestations that arise as syndromic associations with congenital heart defects or as sequelae of primary structural or hemodynamic abnormalities. In this review, we outline the current understanding and recent research into these extra-cardiac manifestations.

['Gaeta|Stephen A|SA|', 'Ward|Cary|C|', 'Krasuski|Richard A|RA|']

2016

25082714

Voiding dysfunction related to adverse childhood experiences and neuropsychiatric disorders.

OBJECTIVE Research has demonstrated the effect of adverse childhood experiences (ACEs) on later physiologic function and illness development. In the urologic literature, the relationship between bladder dysfunction and neuropsychiatric disorders is well documented. Observations in pediatric urology clinical practice suggest that a blend of these two areas of research can inform care of patients with voiding dysfunction. METHODS Retrospective review of 216 patients seen in a single pediatric urology clinic by a single provider over a 24-month period. A descriptive, correlational study design was used to assess the extent to which ACEs and neuropsychiatric disorders affected resolution of symptoms when patients were treated with a bowel and bladder retraining program. Patients were selected using diagnostic codes related to voiding dysfunction and a retrospective chart review was conducted. RESULTS A majority of patients who were seen for voiding dysfunction (60%) had at least one psychosocial factor. There is a greater prevalence of ACEs (51%) than neuropsychiatric disorders (25%). Children with either ACEs or neuropsychiatric disorders dropped out of treatment at a higher rate than those with neither. When factors were looked at separately, neuropsychiatric disorders were more likely to impede treatment progress than ACEs. CONCLUSIONS ACEs and neuropsychiatric disorders affect patients' ability to make progress with bowel and bladder retraining and to stay in treatment. Efforts specifically aimed at maintaining therapeutic relationships with patients who have ACEs are needed to fully treat this group, which typically has a high drop-out rate but high rate of resolution if they are able to stay involved in treatment.

['Logan|Bridget A|BA|', 'Correia|Katiuscia|K|', 'McCarthy|Jenna|J|', 'Slattery|Mary Jo|MJ|']

2014

23856437

Risk of transmission of Trypanosoma cruzi by wild Triatoma infestans (Hemiptera: Reduviidae) in Bolivia supported by the detection of human blood meals.

We analyzed the food sources of Bolivian wild Triatoma infestans (the main vector of Chagas disease in this country), to assess the role of these populations in the epidemiological context of Chagas disease. Ninety-eight blood meals were identified by heteroduplex assay and sequencing. Most of them were from wild mammals but surprisingly 27 were from humans. This brings to light the occurrence of human-vector contacts at risk of Trypanosoma cruzi transmission in the wild environment by highly infected insects.

['Buitrago|Nelly Lilian Rosio|NL|', 'Bosseno|Marie France|MF|', 'Waleckx|Etienne|E|', 'Brémond|Philippe|P|', 'Vidaurre|Pablo|P|', 'Zoveda|Faustine|F|', 'Brenière|Simone Frédérique|SF|']

2013

26028975

Circulating VEGF as a biomarker for diagnosis of ovarian cancer: a systematic review and a meta-analysis.

VEGF is a frequently studied angiogenic factor in ovarian cancer (OC), and is considered to have an important role in the progression of OC. However, its diagnostic value has not been widely accepted because the conclusions are inconsistent and even conflicting. Therefore, we performed a meta-analysis to evaluate the diagnostic value of VEGF in OC. A systematic literature search was conducted using the PubMed, Cochrane Library, EMBASE, Chinese National Knowledge Infrastructure, and WANFANG databases for relevant published articles (the last search update was November 18, 2014). The diagnosis sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and the summary receiver operating characteristic curves were pooled by Meta DiSc 1.4 software. A total of ten studies with 1,131 subjects were finally included in this meta-analysis. The pooled sensitivity, specificity, positive likelihood ratio, negative likelihood ratio, diagnostic odds ratio, and summary receiver operating characteristic curves were 0.67 (0.63-0.73), 0.78 (0.75-0.81), 3.08 (6.36-12.22), 0.39 (0.29-0.51), 9.10 (5.43-45.25), and 0.8175, respectively. Furthermore, to explore the sources of heterogeneity, we conducted subgroup analyses based on ethnicity and sample size. The diagnostic accuracy of VEGF was higher in an Asian population than in a Caucasian population. A similar finding was found in subgroups with the smaller sample size (<100 subjects). In conclusion, the present meta-analysis suggests that VEGF has moderate diagnostic accuracy for OC. Considering our limitations and the heterogeneity among our selected studies, larger, well-designed prospective and multicenter validation studies are needed to evaluate the diagnostic value of serum VEGF for OC.

['Liang|Bin|B|', 'He|Qun|Q|', 'Zhong|Liansheng|L|', 'Wang|Shaocheng|S|', 'Pan|Zhongcheng|Z|', 'Wang|Tianjiao|T|', 'Zhao|Yujie|Y|']

2015

25266626

Resection of individually identified high-rate high-frequency oscillations region is associated with favorable outcome in neocortical epilepsy.

OBJECTIVES High-frequency oscillations (HFOs) represent a novel electrophysiologic marker of endogenous epileptogenicity. Clinically, this propensity can be utilized to more accurately delineate the resection margin before epilepsy surgery. Currently, prospective application of HFOs is limited because of a lack of an exact quantitative measure to reliably identify HFO-generating areas necessary to include in the resection. Here, we evaluated the potential of a patient-individualized approach of identifying high-rate HFO regions to plan the neocortical resection. METHODS Fifteen patients with neocortical seizure-onset zones (SOZs) underwent intracranial electroencephalographic monitoring. To identify interictal HFOs, we applied an automated, hypersensitive HFO-detection algorithm followed by post hoc processing steps to reject false detections. The spatial relationship between HFO distribution and the SOZ was evaluated. To address high interpatient variability in HFO properties, we evaluated the high-rate HFO region, an unbiased statistical parameter, in each patient. The relationship between resection of the high-rate HFO region and postoperative outcome was examined. RESULTS Grouped data demonstrated that the rate of ripple (60-200 Hz) and fast ripple (200-500 Hz) was increased in the SOZ (both p < 0.01). Intrapatient analysis of the HFO distribution localized the SOZ in 11 patients. High-rate HFO regions were determined in all patients by an individually adjusted threshold. Resection of high-rate HFO regions was significantly associated with a seizure-free outcome (p < 0.01). The extent/ratio of SOZ or spiking region resection did not differ between seizure-free and seizure-persistent groups. SIGNIFICANCE Intrapatient analysis of high-rate HFOs provides more detailed description of HFO-generating areas and can mark the areas of clinically significant epileptogenicity--a crucial component of the neocortical epileptic network that should be removed to achieve a good outcome. Validating and adopting an unbiased quantitative HFO parameter has the potential to propel wider and prospective utilization of HFOs in the surgical treatment of neocortical epilepsy and to improve its outcome.

['Cho|Jounhong Ryan|JR|', 'Koo|Dae Lim|DL|', 'Joo|Eun Yeon|EY|', 'Seo|Dae Won|DW|', 'Hong|Seung-Chyul|SC|', 'Jiruska|Premysl|P|', 'Hong|Seung Bong|SB|']

2014

29226194

Childhood Socioeconomic Status and Stress in Late Adulthood: A Longitudinal Approach to Measuring Allostatic Load.

Objectives: This study examines how the effects of childhood socioeconomic status (SES) may carry on into late adulthood. Methods: We examine how childhood SES affects both perceived stress and allostatic load, which is a cumulative measure of the body's biologic response to chronic stress. We use the National Social Life, Health, and Aging Project, Waves 1 and 2, and suggest a novel method of incorporating a longitudinal allostatic load measure. Results: Individuals who grew up in low SES households have higher allostatic load scores in late adulthood, and this association is mediated mostly by educational attainment. Discussion: The longitudinal allostatic load measure shows similar results to the singular measures and allows us to include 2 time points into one outcome measure. Incorporating 2 separate time points into one measure is important because allostatic load is a measure of cumulative physiological dysregulation, and longitudinal data provide a more comprehensive measure.

['Graves|Katelyn Y|KY|https://orcid.org/0000-0002-1478-6142', 'Nowakowski|Alexandra C H|ACH|']

2017

33509012

Embolization of dural arteriovenous fistula during twin pregnancy - A case report and literature review.

BACKGROUND Several literature reviews have suggested that pregnancy may trigger the formation of dural arteriovenous fistulae (DAVF). However, few case reports have described DAVF discovered during pregnancy, and treatment strategies remain largely unknown.Case description: A 28-year-old primigravid woman without any medical history of note presented to our hospital for natural twin conception. She started to feel left-sided pulsatile tinnitus in 23 weeks of gestation. Magnetic resonance imaging of the head raised suspicion of left cavernous sinus DAVF with leptomeningeal venous drainage. Considering the risk of intracerebral hemorrhage due to the increased cardiac output in the third trimester of a twin pregnancy, we performed transarterial embolization for the DAVF, which was successfully achieved without complications in 28 weeks of gestation. Tinnitus resolved immediately after the procedure, and the postoperative course proved uneventful. Both fetuses were safely delivered by cesarean section on 37 1/7 weeks of gestation. CONCLUSIONS We encountered a case of cavernous sinus DAVF during a twin pregnancy. This case suggests that hemodynamic shift due to pregnancy has potential to cause higher shunt flow in an arteriovenous fistula. The timing of treatment should be determined in consideration of the hemodynamic change in the course of pregnancy. If X-ray exposures and iodine contrast media are appropriately managed, endovascular intervention is one treatment option, even during pregnancy.

['Ishigami|Daiichiro|D|https://orcid.org/0000-0003-4437-5421', 'Koizumi|Satoshi|S|https://orcid.org/0000-0001-6506-8055', 'Ishikawa|Osamu|O|https://orcid.org/0000-0003-1985-1377', 'Toshimitsu|Masatake|M|', 'Iriyama|Takayuki|T|', 'Miyawaki|Satoru|S|', 'Saito|Nobuhito|N|']

2021

32791035

Bi-allelic Loss-of-function Variants in CFAP58 Cause Flagellar Axoneme and Mitochondrial Sheath Defects and Asthenoteratozoospermia in Humans and Mice.

Multiple morphological abnormalities of the sperm flagella (MMAF) is a severe form of asthenoteratozoospermia. Although recent studies have revealed several MMAF-associated genes and demonstrated MMAF to be a genetically heterogeneous disease, at least one-third of the cases are still not well understood for their etiology. Here, we identified bi-allelic loss-of-function variants in CFAP58 by using whole-exome sequencing in five (5.6%) unrelated individuals from a cohort of 90 MMAF-affected Chinese men. Each of the men harboring bi-allelic CFAP58 variants presented typical MMAF phenotypes. Transmission electron microscopy demonstrated striking flagellar defects with axonemal and mitochondrial sheath malformations. CFAP58 is predominantly expressed in the testis and encodes a cilia- and flagella-associated protein. Immunofluorescence assays showed that CFAP58 localized at the entire flagella of control sperm and predominantly concentrated in the mid-piece. Immunoblotting and immunofluorescence assays showed that the abundances of axoneme ultrastructure markers SPAG6 and SPEF2 and a mitochondrial sheath protein, HSP60, were significantly reduced in the spermatozoa from men harboring bi-allelic CFAP58 variants. We generated Cfap58-knockout mice via CRISPR/Cas9 technology. The male mice were infertile and presented with severe flagellar defects, consistent with the sperm phenotypes in MMAF-affected men. Overall, our findings in humans and mice strongly suggest that CFAP58 plays a vital role in sperm flagellogenesis and demonstrate that bi-allelic loss-of-function variants in CFAP58 can cause axoneme and peri-axoneme malformations leading to male infertility. This study provides crucial insights for understanding and counseling of MMAF-associated asthenoteratozoospermia.

['He|Xiaojin|X|', 'Liu|Chunyu|C|', 'Yang|Xiaoyu|X|', 'Lv|Mingrong|M|', 'Ni|Xiaoqing|X|', 'Li|Qiang|Q|', 'Cheng|Huiru|H|', 'Liu|Wangjie|W|', 'Tian|Shixiong|S|', 'Wu|Huan|H|', 'Gao|Yang|Y|', 'Yang|Chenyu|C|', 'Tan|Qing|Q|', 'Cong|Jiangshan|J|', 'Tang|Dongdong|D|', 'Zhang|Jingjing|J|', 'Song|Bing|B|', 'Zhong|Yading|Y|', 'Li|Hang|H|', 'Zhi|Weiwei|W|', 'Mao|Xiaohong|X|', 'Fu|Feifei|F|', 'Ge|Lei|L|', 'Shen|Qunshan|Q|', 'Zhang|Manyu|M|', 'Saiyin|Hexige|H|', 'Jin|Li|L|', 'Xu|Yuping|Y|', 'Zhou|Ping|P|', 'Wei|Zhaolian|Z|', 'Zhang|Feng|F|', 'Cao|Yunxia|Y|']

2020

33494416

Evaluation of [64Cu]Cu-NOTA-PEG7-H-Tz for Pretargeted Imaging in LS174T Xenografts-Comparison to [111In]In-DOTA-PEG11-BisPy-Tz.

Pretargeted nuclear imaging for the diagnosis of various cancers is an emerging and fast developing field. The tetrazine ligation is currently considered the most promising reaction in this respect. Monoclonal antibodies are often the preferred choice as pretargeting vector due to their outstanding targeting properties. In this work, we evaluated the performance of [64Cu]Cu-NOTA-PEG7-H-Tz using a setup we previously used for [111In]In-DOTA-PEG11-BisPy-Tz, thereby allowing for comparison of the performance of these two promising pretargeting imaging agents. The evaluation included a comparison of the physicochemical properties of the compounds and their performance in an ex vivo blocking assay. Finally, [64Cu]Cu-NOTA-PEG7-H-Tz was evaluated in a pretargeted imaging study and compared to [111In]In-DOTA-PEG11-BisPy-Tz. Despite minor differences, this study indicated that both evaluated tetrazines are equally suited for pretargeted imaging.

['Poulie|Christian B M|CBM|', 'Jørgensen|Jesper T|JT|', 'Shalgunov|Vladimir|V|', 'Kougioumtzoglou|Georgios|G|', 'Jeppesen|Troels Elmer|TE|0000-0002-5009-4522', 'Kjaer|Andreas|A|0000-0002-2706-5547', 'Herth|Matthias M|MM|']

2021

27185330

Discovery and optimization of a novel series of highly CNS penetrant M4 PAMs based on a 5,6-dimethyl-4-(piperidin-1-yl)thieno[2,3-d]pyrimidine core.

This Letter describes the chemical optimization of a novel series of M4 positive allosteric modulators (PAMs) based on a 5,6-dimethyl-4-(piperidin-1-yl)thieno[2,3-d]pyrimidine core, identified from an MLPCN functional high-throughput screen. The HTS hit was potent and selective, but not CNS penetrant. Potency was maintained, while CNS penetration was improved (rat brain:plasma Kp=0.74), within the original core after several rounds of optimization; however, the thieno[2,3-d]pyrimidine core was subject to extensive oxidative metabolism. Ultimately, we identified a 6-fluoroquinazoline core replacement that afforded good M4 PAM potency, muscarinic receptor subtype selectivity and CNS penetration (rat brain:plasma Kp>10). Moreover, this campaign provided fundamentally distinct M4 PAM chemotypes, greatly expanding the available structural diversity for this exciting CNS target.

['Wood|Michael R|MR|', 'Noetzel|Meredith J|MJ|', 'Engers|Julie L|JL|', 'Bollinger|Katrina A|KA|', 'Melancon|Bruce J|BJ|', 'Tarr|James C|JC|', 'Han|Changho|C|', 'West|Mary|M|', 'Gregro|Alison R|AR|', 'Lamsal|Atin|A|', 'Chang|Sichen|S|', 'Ajmera|Sonia|S|', 'Smith|Emery|E|', 'Chase|Peter|P|', 'Hodder|Peter S|PS|', 'Bubser|Michael|M|', 'Jones|Carrie K|CK|', 'Hopkins|Corey R|CR|', 'Emmitte|Kyle A|KA|', 'Niswender|Colleen M|CM|', 'Wood|Michael W|MW|', 'Duggan|Mark E|ME|', 'Conn|P Jeffrey|PJ|', 'Bridges|Thomas M|TM|', 'Lindsley|Craig W|CW|']

2016

26500804

mBLAST: Keeping up with the sequencing explosion for (meta)genome analysis.

Recent advances in next-generation sequencing technologies require alignment algorithms and software that can keep pace with the heightened data production. Standard algorithms, especially protein similarity searches, represent significant bottlenecks in analysis pipelines. For metagenomic approaches in particular, it is now often necessary to search hundreds of millions of sequence reads against large databases. Here we describe mBLAST, an accelerated search algorithm for translated and/or protein alignments to large datasets based on the Basic Local Alignment Search Tool (BLAST) and retaining the high sensitivity of BLAST. The mBLAST algorithms achieve substantial speed up over the National Center for Biotechnology Information (NCBI) programs BLASTX, TBLASTX and BLASTP for large datasets, allowing analysis within reasonable timeframes on standard computer architectures. In this article, the impact of mBLAST is demonstrated with sequences originating from the microbiota of healthy humans from the Human Microbiome Project. mBLAST is designed as a plug-in replacement for BLAST for any study that involves short-read sequences and includes high-throughput analysis. The mBLAST software is freely available to academic users at www.multicorewareinc.com.

['Davis|Curtis|C|', 'Kota|Karthik|K|', 'Baldhandapani|Venkat|V|', 'Gong|Wei|W|', 'Abubucker|Sahar|S|', 'Becker|Eric|E|', 'Martin|John|J|', 'Wylie|Kristine M|KM|', 'Khetani|Radhika|R|', 'Hudson|Matthew E|ME|', 'Weinstock|George M|GM|', 'Mitreva|Makedonka|M|']

2015

25150451

Adaptive immune responses at mucosal surfaces of teleost fish.

This review describes the extant knowledge on the teleostean mucosal adaptive immune mechanisms, which is relevant for the development of oral or mucosal vaccines. In the last decade, a number of studies have shed light on the presence of new key components of mucosal immunity: a distinct immunoglobulin class (IgT or IgZ) and the polymeric Ig receptor (pIgR). In addition, intestinal T cells and their putative functions, antigen uptake mechanisms at mucosal surfaces and new mucosal vaccination strategies have been reported. New information on pIgR of Atlantic cod and common carp and comparison of natural and specific cell-mediated cytotoxicity in the gut of common carp and European seabass, is also included in this review. Based on the known facts about intestinal immunology and mucosal vaccination, suggestions are made for the advancement of fish vaccines.

['Rombout|Jan H W M|JH|', 'Yang|Guiwen|G|', 'Kiron|Viswanath|V|']

2014

31910806

Identifying appropriate outcomes to help evaluate the impact of the Canadian Guideline for Safe and Effective Use of Opioids for Non-Cancer Pain.

BACKGROUND The Canadian Guideline for Safe and Effective Use of Opioids for Chronic Non-Cancer Pain (COG) was developed in response to increasing rates of opioid-related hospital visits and deaths in Canada, and uncertain benefits of opioids for chronic non-cancer pain (CNCP). Following publication, we developed a list of evaluable outcomes to assess the impact of this guideline on practice and patient outcomes. METHODS A working group at the National Pain Centre at McMaster University used a modified Delphi process to construct a list of clinical and patient outcomes important in assessing the uptake and application of the COG. An advisory group then reviewed this list to determine the relevance and feasibility of each outcome, and identified potential data sources. This feedback was reviewed by the National Faculty for the Guideline, and a National Advisory Group that included the creators of the COG, resulting in the final list of 5 priority outcomes. RESULTS Five outcomes were judged clinically important and feasible to measure: 1) Effects of opioids for CNCP on quality of life, 2) Assessment of patient's risk of addiction before starting opioid therapy, 3) Monitoring patients on opioid therapy for aberrant drug-related behaviour, 4) Mortality rates associated with prescription opioid overdose and 5) Use of treatment agreements with patients before initiating opioid therapy for CNCP. Data sources for these outcomes included patient's medical charts, e-Opioid Manager, prescription monitoring programs and administrative databases. CONCLUSION Measuring the impact of best practice guidelines is infrequently done. Future research should consider capturing the five outcomes identified in this study to evaluate the impact of the COG in promoting evidence-based use of opioids for CNCP.

['Allen|Michael|M|', 'Sproule|Beth|B|', 'MacDougall|Peter|P|', 'Furlan|Andrea|A|', 'Murphy|Laura|L|', 'Borg Debono|Victoria|V|', 'Buckley|Norman|N|0000-0002-1031-6813']

2020

33146762

Interobserver reliability of Masei index validation by a multicenter collaborative group of rheumatologists.

MASEI is the main validated ultrasound score for the evaluation of enthesis. The lack of studies facing the agreement to achieve for the interpretation of the MAdrid Sonographic Enthesis Index (MASEI) among researchers from different centers in multicenter studies is of concern. The aim of this multicenter was to evaluate the interobserver reliability of MASEI. An experienced ultrasonographer-rheumatologist performed ultrasound scans of the areas included in MASEI index in three patients with Ankylosing Spondylitis and Psoriatic Arthritis. Videos were captured. The videos were then evaluated by 24 rheumatologists of the ultrasound working group of the Catalan Society of Rheumatology (EcoCAT). A face-to-face training meeting was held. Ten days after the workshop, the study participants evaluated the videos. A reliability assessment was performed. The ICC for the MASEI scores after the workshop was of 0.97 (95% CI 89-99). Reliability did not vary statistically with examiner experience. Globally, no problems of reliability by structures were seen, and all the ICCs were above 0.90 and improved slightly after the educational program. However, the correlation observed between examiners at plantar aponeursis and triceps tendon was weak. The small variability observed in the results of the index validation in our study, suggests that the MASEI index is reproducible by different observers when those are well trained and show awesome results of the enthesis when examined by ultrasound.

['Moya Alvarado|Patricia|P|http://orcid.org/0000-0001-8339-5420', 'de Agustín de Oro|Juan José|JJ|http://orcid.org/0000-0001-7702-1625', 'Aparicio Espinar|María|M|http://orcid.org/0000-0002-4666-5505', 'Armengol Pérez|Eulàlia|E|http://orcid.org/0000-0003-2798-9237', 'Busquets Pérez|Noemí|N|http://orcid.org/0000-0003-2070-4876', 'Carmona|Loreto|L|http://orcid.org/0000-0002-4401-2551', 'Casado Burgos|Enrique|E|http://orcid.org/0000-0001-8839-6430', 'Clavaguera Poch|Teresa|T|http://orcid.org/0000-0003-0394-3947', 'Cuervo Aguilera|Andrea|A|http://orcid.org/0000-0002-2730-3525', 'De Miguel Mendieta|Eugenio|E|http://orcid.org/0000-0001-5146-1964', 'Estrada Alarcón|Paula|P|http://orcid.org/0000-0002-9827-5680', 'García Casares|Elisabet|E|http://orcid.org/0000-0002-0856-923X', 'Holgado Pérez|Susana|S|http://orcid.org/0000-0003-3381-0969', 'Magallares López|Berta|B|http://orcid.org/0000-0002-4691-2342', 'Martinez Morillo|Melania|M|http://orcid.org/0000-0003-4872-0907', 'Mateo Soria|Lourdes|L|http://orcid.org/0000-0002-6394-2949', 'Moragues Pastor|Carmen|C|http://orcid.org/0000-0002-8459-7291', 'Moreno Martínez-Losa|Mireia|M|http://orcid.org/0000-0002-4365-4341', 'Ponce Fernández|Andrés|A|http://orcid.org/0000-0003-3068-5752', 'Pujol Busquets|Manel|M|http://orcid.org/0000-0003-0676-3191', 'Ramírez García|Julio|J|http://orcid.org/0000-0002-7047-8056', 'Reina Sanz|Delia|D|http://orcid.org/0000-0003-2587-2510', 'Sallés Lizarzaburu|Meritxell|M|http://orcid.org/0000-0002-3721-645X', 'Santo Panero|Pilar|P|http://orcid.org/0000-0001-5793-5569', 'Sirvent Alierta|Elena|E|', 'Valls Roc|Marta|M|http://orcid.org/0000-0002-3407-2470', 'Corominas Macías|Hèctor|H|http://orcid.org/0000-0001-7956-3866']

2020

33609666

PVCs with multiple exits and single site of origin in the outflow tract: What is the mechanism?

A 40 year old man with frequent PVCs with two different morphologies was referred for catheter ablation. Although initial mapping in the RVOT revealed fragmented potentials 20ms earlier than PVC2 onset with a good pace map score, ablation at this site was unsuccessful. Subsequent mapping in the LCC/NCC junction revealed that local ventricular activation preceded QRS onset by 30 and 28 ms for PVC1 and PVC2, respectively. Altering the pacing output at this site produced QRS morphologies similar to PVC1(low output,6mA) and PVC2(high output,15mA) with better pace map scores compared to RVOT. During high-output pacing, there was an increase in stim-QRS latency with decremental conduction. Ablation at this site was successful and suppressed both PVCs.

['Subramanian|Muthiah|M|', 'Yalagudri|Sachin|S|', 'Saggu|Daljeet Kaur|DK|', 'Vignesh Rangaswamy|Vickram|V|', 'Narasimhan|Calambur|C|']

2021

34536845

When microbial electrochemistry meets UV: The applicability to high-strength real pharmaceutical industry wastewater.

Wastewater from pharmaceutical and related industries contains many residual pharmaceutical components rich in color and high COD contents, which cannot be removed through the traditional wastewater treatment processes. Recently, microbial electrolysis ultraviolet cell (MEUC) process has shown its promising potential to remove recalcitrant organics because of its merits of wide pH range, iron-free, and without complications of iron sludge production. However, its application to the real pharmaceutical-rich industrial wastewater is still unknown. In this study, the MEUC process was validated with real ciprofloxacin-rich (6863.79 ± 2.21 µg L-1) industrial wastewater (6840 ± 110 mg L-1 of COD). The MEUC process achieved 100% removal of ciprofloxacin, 100% decolorization, and 99.1% removal of COD within 12, 60 and 30 h, respectively, when it was operated at pH-controlled at 7.8, applied voltage of 0.6 V, UV intensity of 10 mW cm-2, and cathodic aeration velocity of 0.005 mL min-1 mL-1. Moreover, fluorescence analysis showed that protein- and humic-like substances in such wastewater were effectively removed, providing further evidence of its high treatment efficiency. Furthermore, eco-toxicity testing with luminescent bacteria Vibro Feschri confirmed that the treated effluent was utterly non-toxic. The results demonstrated the broad application potential of MEUC technology for treating industrial wastewater.

['Zou|Rusen|R|', 'Tang|Kai|K|', 'Hambly|Adam C|AC|', 'Wünsch|Urban J|UJ|', 'Andersen|Henrik Rasmus|HR|', 'Angelidaki|Irini|I|', 'Zhang|Yifeng|Y|']

2022

28391382

Insufficient stability of pedicle screws in osteoporotic vertebrae: biomechanical correlation of bone mineral density and pedicle screw fixation strength.

PURPOSE Loosening of pedicle screws is one major complication of posterior spinal stabilisation, especially in the patients with osteoporosis. Augmentation of pedicle screws with cement or lengthening of the instrumentation is widely used to improve implant stability in these patients. However, it is still unclear from which value of bone mineral density (BMD) the stability of pedicle screws is insufficient and an additional stabilisation should be performed. The aim of this study was to investigate the correlation of bone mineral density and pedicle screw fatigue strength as well as to define a threshold value for BMD below which an additional stabilisation is recommended. METHODS Twenty-one human T12 vertebral bodies were collected from donors between 19 and 96 years of age and the BMD was measured using quantitative computed tomography. Each vertebral body was instrumented with one pedicle screw and mounted in a servo-hydraulic testing machine. Fatigue testing was performed by implementing a cranio-caudal sinusoidal, cyclic (0.5 Hz) load with stepwise increasing peak force. RESULTS A significant correlation between BMD and cycles to failure (r = 0.862, r 2 = 0.743, p < 0.001) as well as for the linearly related fatigue load was found. Specimens with BMD below 80 mg/cm3 only reached 45% of the cycles to failure and only 60% of the fatigue load compared to the specimens with adequate bone quality (BMD > 120 mg/cm3). CONCLUSIONS There is a close correlation between BMD and pedicle screw stability. If the BMD of the thoracolumbar spine is less than 80 mg/cm3, stability of pedicle screws might be insufficient and an additional stabilisation should be considered.

['Weiser|Lukas|L|0000-0001-9812-4658', 'Huber|Gerd|G|', 'Sellenschloh|Kay|K|', 'Viezens|Lennart|L|', 'Püschel|Klaus|K|', 'Morlock|Michael M|MM|', 'Lehmann|Wolfgang|W|']

2017

23649958

Effect of transdermal isopropyl alcohol on the international normalized ratio in five warfarin-treated patients.

Warfarin, an anticoagulant with a narrow therapeutic window, is largely metabolized by cytochrome P450 2C9. Isopropyl alcohol has been shown to inhibit the activity of this enzyme. Use of topical isopropyl alcohol as a rubefacient may place patients at risk for systemic exposure. Isopropyl alcohol's effect on the international normalized ratio (INR) has not been well characterized. We describe five patients who experienced INR elevations after topical application of isopropyl alcohol. Each patient's INR was therapeutic for at least seven visits prior to becoming supratherapeutic. All patients confirmed drug adherence and denied medication or dietary changes. Seventy percent isopropyl alcohol was used in all cases over a large body surface area of intact skin multiple times daily for several days. All patients experienced a 10% or greater increase in their INR compared to previous levels. On discontinuation of isopropyl alcohol, each patient's INR returned to and remained in therapeutic range for the next 2 months. Prediction of isopropyl alcohol's effect of the INR is confound by several factors, notably the BSA covered, concentration of alcohol in the product, contact time with the skin, and skin integrity. It is important that clinicians inquire about the use of isopropyl alcohol and educate patients about its potential risk in those receiving warfarin therapy.

['Pitcock|James J|JJ|', 'Oluyemi|Olubusola O|OO|', 'Pitcock|Margaret B|MB|']

2013

32092837

Dragon's Blood Inhibits Chronic Inflammatory and Neuropathic Pain Responses by Blocking the Synthesis and Release of Substance P in Rats.

As a traditional Chinese medicine, dragon's blood (DB) is widely used in treating various pains for thousands of years due to its potent anti-inflammatory and analgesic effects. In the present study, we observed that intragastric administration of DB at dosages of 0.14, 0.56, and 1.12 g/kg potently inhibited paw edema, hyperalgesia, cyclooxygenase-2 (COX-2) protein expression, or preprotachykinin-A mRNA expression in carrageenan-inflamed or sciatic nerve-injured (chronic constriction injury) rats, respectively. A short-term (15 s or 10 min) pre-exposure of cultured rat dorsal root ganglion (DRG) neurons to DB (0.3, 3, and 30 μg/ml) or its component cochinchinenin B (CB; 0.1, 1, and 10 μM) blocked capsaicin-evoked increases in both the intracellular calcium ion concentration and the substance P release. Moreover, a long-term (180 min) exposure of cultured rat DRG neurons to DB or CB significantly attenuated bradykinin-induced substance P release. These findings indicate that DB exerts anti-inflammatory and analgesic effects by blocking the synthesis and release of substance P through inhibition of COX-2 protein induction and intracellular calcium ion concentration. Therefore, DB may serve as a promising potent therapeutic agent for treatment of chronic pain, and its effective component CB might partly contribute to anti-inflammatory and analgesic effects.

['Li|Yu-Sang|YS|', 'Wang|Jun-Xian|JX|', 'Jia|Mei-Mei|MM|', 'Liu|Min|M|', 'Li|Xiao-Jun|XJ|', 'Tang|He-Bin|HB|']

2012

32867734

Endozoochorous dispersal by herbivores and omnivores is mediated by germination conditions.

BACKGROUND Vertebrate-mediated seed dispersal is probably the main long distance dispersal mode. Through endozoochory, large mammals act as mobile links between habitats within and among forest patches. Along with other factors, their feeding regimes do affect their contribution as dispersal vectors. We conducted a cross-species comparative experiment involving two herbivores, red deer and roe deer; and two opportunistic omnivores, wild boar and brown bear, all occurring in the forest and steppe-forest ecotone habitats of the south-eastern Caspian region. We compared their role as endozoochorous seed dispersal agents by monitoring seedling emergence in their dungs under greenhouse and natural conditions. RESULTS In total, 3078 seedlings, corresponding to 136 plant taxa sprouted from 445 paired dung sub-samples, under greenhouse and natural conditions. Only 336 seedlings, corresponding to 36 plant taxa, emerged under natural conditions, among which five taxa did not appear under greenhouse conditions. Graminoids and forbs composed 91% of the seedlings in the greenhouse whereas shrubs were more abundant under natural conditions, representing 55% of the emerged seedlings. Under greenhouse conditions, first red deer and then wild boar dispersed more species than the other two mammals, while under natural conditions brown bear was the most effective vector. We observed remarkably higher species richness and seedling abundance per dung sub-sample under buffered greenhouse conditions than we did under natural conditions. CONCLUSIONS The four sympatric mammals studied provided different seed dispersal services, both in terms of seedling abundance and species richness and may therefore be regarded as complementary. Our results highlight a positive bias when only considering germination under buffered greenhouse conditions. This must be taken into account when planning management options to benefit plant biodiversity based on the dispersal services concluded from greenhouse experiments.

['Karimi|Sorour|S|', 'Hemami|Mahmoud-Reza|MR|', 'Tarkesh Esfahani|Mostafa|M|', 'Baltzinger|Christophe|C|']

2020

33727866

Novel Experimental Drugs for Treatment of Multiple Myeloma.

Multiple myeloma (MM) is the second most frequent hematological malignancy characterized by bone marrow aberrant plasma cells proliferation leading to a genetic complex and heterogeneous disease, with a median survival ranging from two to more than 10 years. By using new drugs such as proteasome inhibitors (PIs), immunomodulatory drugs (IMiDs), monoclonal antibodies (mAbs) in different combinations and high-dose therapy followed by auto-transplantation, there has been an amazing improvement in the outcome of this disease in recent years. Despite this, MM is still considered an incurable disease, characterized by remission periods alternated with relapse/progression episodes finally leading to resistant disease. In particular, patients who become refractory to PIs, IMiDs and mAbs have a very poor outcome. Moreover, to overcome resistant residual disease, a large combination of drugs will be increasingly used in early lines of therapy; this further reduces the therapeutic options at each relapse. This natural history means that MM always needs new drugs/strategies to overcome the incoming resistance. New combinations of naked mAbs are becoming the therapy of choice for patients refractory to lenalidomide and/or PI; conjugated mAbs will be useful in triple- and more-refractory patients; CAR-T cells and bispecific mAbs have shown relevant results in very advanced stages of disease. In this review, we reported the results of these new therapies and explored their potential applications. Personalized and precision medicine seem to be the new frontier of cancer treatment. Although no single or few factors have been identified as disease drivers in MM, recurrent gene mutations were recognized and specific compounds targeting these alterations were developed and studied. Therefore, we reviewed these targeted drugs to try to understand what the best therapeutic strategy in MM is.

['Offidani|Massimo|M|0000-0003-2749-7347', 'Corvatta|Laura|L|', 'Morè|Sonia|S|', 'Olivieri|Attilio|A|']

2021

34038885

The potential application of nanomaterials for ferroptosis-based cancer therapy.

Ferroptosis is a new type of programmed cell death, which is expected to become an important strategy of cancer treatment. Traditional strategies for inducing iron death are small molecule inducers based on biological agents. However, because of their poor water solubility, low cell targeting ability and fast metabolismin vivo, it is difficult for molecular drugs to play the long-acting role of ferroptosis induction. With the further study of ferroptosis and development of nanotechnology, nanomaterials have been proved to be more efficient drugs for inducing ferroptosis than those biological drugs. Therein, iron-based nanomaterials can directly release high concentrations of irons and increase reactive oxygen species levels in cells, which produce a better induction effect for ferroptosis. Whereas, it is challenging to differentiate nanoparticle-induced ferroptosis and traditional inducing strategies, elucidate the detailed mechanisms and further classify the synthetical methods of nanomaterials. For better guidance on the development of anticancer strategies, comprehensive summary of the latest developments of ferroptosis related nanomaterials, especially iron-based nanomaterials are in urgent need. In the paper, we summarized the main mechanisms of ferroptosis, highlighted the latest developments of nanomaterials for ferroptosis, and emphasized the advantages of iron-based nanomaterials for ferroptosis. The future prospect in this field was also discussed, paving the way for the related nanomaterials in the clinical cancer therapy.

['Li|Yingze|Y|', 'Wei|Xueyan|X|', 'Tao|Feng|F|', 'Deng|Cuijun|C|', 'Lv|Cheng|C|', 'Chen|Chang|C|', 'Cheng|Yu|Y|0000-0002-9030-2023']

2021

32825120

Anticancer Imidazoacridinone C-1311 is Effective in Androgen-Dependent and Androgen-Independent Prostate Cancer Cells.

The androgen receptor (AR) plays a critical role in prostate cancer (PCa) development and metastasis. Thus, blocking AR activity and its downstream signaling constitutes a major strategy for PCa treatment. Here, we report on the potent anti-PCa activity of a small-molecule imidazoacridinone, C-1311. In AR-positive PCa cells, C-1311 was found to inhibit the transcriptional activity of AR, uncovering a novel mechanism that may be relevant for its anticancer effect. Mechanistically, C-1311 decreased the AR binding to the prostate-specific antigen (PSA) promoter, reduced the PSA protein level, and, as shown by transcriptome sequencing, downregulated numerous AR target genes. Importantly, AR-negative PCa cells were also sensitive to C-1311, suggesting a promising efficacy in the androgen-independent PCa sub-type. Irrespective of AR status, C-1311 induced DNA damage, arrested cell cycle progression, and induced apoptosis. RNA sequencing indicated significant differences in the transcriptional response to C-1311 between the PCa cells. Gene ontology analysis showed that in AR-dependent PCa cells, C-1311 mainly affected the DNA damage response pathways. In contrast, in AR-independent PCa cells, C-1311 targeted the cellular metabolism and inhibited the genes regulating glycolysis and gluconeogenesis. Together, these results indicate that C-1311 warrants further development for the treatment of PCa.

['Niemira|Magdalena|M|0000-0002-0701-4961', 'Borowa-Mazgaj|Barbara|B|', 'Bader|Samuel B|SB|', 'Moszyńska|Adrianna|A|', 'Ratajewski|Marcin|M|0000-0001-5391-5843', 'Karaś|Kaja|K|0000-0002-1790-698X', 'Kwaśniewski|Mirosław|M|', 'Krętowski|Adam|A|0000-0002-4522-4978', 'Mazerska|Zofia|Z|', 'Hammond|Ester M|EM|', 'Skwarska|Anna|A|0000-0002-0979-026X']

2020

24022995

Do children with autism re-enact object movements rather than imitate demonstrator actions?

It has been suggested that autism-specific imitative deficits may be reduced or even spared in object-related activities. However, most previous research has not sufficiently distinguished object movement reenactment (learning about the ways in which object move) from imitation (learning about the topography of demonstrated actions). Twenty children with autism (CWA) and 20 typically developing children (TDC) were presented with puzzle boxes containing prizes. Test objects and experimental conditions were designed to isolate object- and action-related aspects of demonstrations. There were four types of video demonstrations: (a) a full demonstration by an adult; (b) a ghost demonstration with object movements alone; (c) mimed solutions demonstrated adjacent to the objects; and (d) random actions performed on the surface of the objects. There were no significant between-group differences in the degree to which CWA and TDC matched the full demonstrations, the actual demonstrations or in their times to first solution in any of the conditions. Although there was no clear imitative deficit in the CWA, regression analyses were conducted to explore in more detail whether diagnosis, verbal intelligence quotient (VIQ), nonverbal IQ NVIQ, age or motor coordination predicted performance. The results are discussed in relation to the use of extrinsic vs. intrinsic rewards and the interplay between motor coordination and the relative rigidity vs. pliability of objects.

['Custance|Deborah M|DM|', 'Mayer|Jennifer L|JL|', 'Kumar|Emmelianna|E|', 'Hill|Elisabeth|E|', 'Heaton|Pamela F|PF|']

2014

31506102

Diagnosis of giant cell arteritis by head-contrast three-dimensional computed tomography angiography: two case reports.

INTRODUCTION Temporal artery biopsy is essential for the diagnosis of giant cell arteritis. It has been shown that 18F-fluorodeoxyglucose positron emission tomography-computed tomography, magnetic resonance angiography, and ultrasonography are useful for the diagnosis of giant cell arteritis. However, there are only a few reports on the usefulness of three-dimensional computed tomography angiography in the diagnosis of giant cell arteritis. We describe two cases in which giant cell arteritis was difficult to diagnose using positron emission tomography-computed tomography and magnetic resonance angiography but was diagnosed using three-dimensional computed tomography angiography, thus showing the importance of three-dimensional computed tomography angiography in the diagnosis of giant cell arteritis. CASE PRESENTATION Case 1: An 81-year-old Japanese man. Laboratory investigations revealed normocytic anemia and raised inflammatory marker levels. Slight bleeding in the right posterior pole of his eyeball and leukoma of his left cornea were observed on fundus examination. Stenosis and stoppage of the temporal artery were detected on three-dimensional computed tomography angiography. A diagnosis of giant cell arteritis was made, and he was started on orally administered prednisolone. His headache and C-reactive protein levels improved. Four weeks after glucocorticoid steroid treatment, three-dimensional computed tomography angiography revealed improvement in stenosis and stoppage of temporal artery. Case 2: A 74-year-old Japanese woman. A dose of 20 mg of prednisolone was administered and her polymyalgia and polyarthritis improved; however, her headache and ear occlusion persisted. Although vasculitis was not detected on positron emission tomography-computed tomography, stenosis and stoppage of the temporal artery were detected on computed tomography angiography. She was diagnosed as having giant cell arteritis and started on orally administered prednisolone treatment (60 mg daily). Her headache and C-reactive protein levels improved. Four weeks after glucocorticoid treatment, three-dimensional computed tomography angiography showed improvement in stenosis and stoppage of temporal artery. CONCLUSIONS In both patients with giant cell arteritis, three-dimensional computed tomography angiography revealed improvement in stenosis and stoppage of temporal artery after glucocorticoid treatment. We conclude that computed tomography angiography along with magnetic resonance angiography, positron emission tomography-computed tomography, and ultrasonography are important for the diagnosis of giant cell arteritis.

['Kawamoto|Toshio|T|', 'Ogasawara|Michihiro|M|', 'Nakano|Souichiro|S|', 'Matsuki Muramoto|Yuko|Y|', 'Matsushita|Masakazu|M|', 'Yamanaka|Kenjiro|K|', 'Yamaji|Ken|K|', 'Tamura|Naoto|N|']

2019

32312164

Preference for O-demethylation reactions in the oxidation of 2'-, 3'-, and 4'-methoxyflavones by human cytochrome P450 enzymes.

2'-, 3'-, and 4'-Methoxyflavones (MeFs) were incubated with nine forms of recombinant human cytochrome P450 (P450 or CYP) enzymes in the presence of an NADPH-generating system and the products formed were analyzed with LC-MS/MS methods.CYP1B1.1 and 1B1.3 were highly active in demethylating 4'MeF to form 4'-hydroxyflavone (rate of 5.0 nmol/min/nmol P450) and further to 3',4'-dihydroxyflavone (rates of 2.1 and 0.66 nmol/min/nmol P450, respectively). 3'MeF was found to be oxidized by P450s to m/z 239 (M-14) products (presumably 3'-hydroxyflavone) and then to 3',4'-dihydroxyflavone. P450s also catalyzed oxidation of 2'MeF to m/z 239 (M-14) and m/z 255 (M-14, M-14 + 16) products, presumably mono- and di-hydroxylated products, respectively.At least two types of ring oxidation products having m/z 269 fragments were formed, although at slower rates than the formation of mono- and di-hydroxylated products, on incubation of these MeFs with P450s; one type was products oxidized at the C-ring, having m/z 121 fragments, and the other one was the products oxidized at the A-ring (having m/z 137 fragments).Molecular docking analysis indicated the preference of interaction of O-methoxy moiety of methoxyflavones in the active site of CYP1A2.These results suggest that 2'-, 3'-, and 4'-methoxyflavones are principally demethylated by human P450s to form mono- and di-hydroxyflavones and that direct oxidation occurs in these MeFs to form mono-hydroxylated products, oxidized at the A- or B-ring of MeF.

['Nagayoshi|Haruna|H|', 'Murayama|Norie|N|', 'Tsujino|Masaki|M|', 'Takenaka|Shigeo|S|', 'Katahira|Jun|J|', 'Kim|Vitchan|V|', 'Kim|Donghak|D|http://orcid.org/0000-0002-4421-7215', 'Komori|Masayuki|M|', 'Yamazaki|Hiroshi|H|http://orcid.org/0000-0002-1068-4261', 'Guengerich|F Peter|FP|http://orcid.org/0000-0002-7458-3048', 'Shimada|Tsutomu|T|']

2020

32453547

Room Temperature Weak-to-Strong Coupling and the Emergence of Collective Emission from Quantum Dots Coupled to Plasmonic Arrays.

Colloidal quantum dot (CQD) assemblies exhibit interesting optoelectronic properties when coupled to optical resonators ranging from Purcell-enhanced emission to the emergence of hybrid electronic and photonic polariton states in the weak and strong coupling limits, respectively. Here, experiments exploring the weak-to-strong coupling transition in CQD-plasmonic lattice hybrid devices at room temperature are presented for varying CQD concentrations. To interpret these results, generalized retarded Fano-Anderson and effective medium models are developed. Individual CQDs are found to interact locally with the lattice yielding Purcell-enhanced emission. At high CQD densities, polariton states emerge as two-peak structures in the photoluminescence, with a third polariton peak, due to collective CQD emission, appearing at still higher CQD concentrations. Our results demonstrate that CQD-lattice plasmon devices represent a highly flexible platform for the manipulation of collective spontaneous emission using lattice plasmons, which could find applications in optoelectronics, ultrafast optical switches, and quantum information science.

['Yadav|Ravindra Kumar|RK|http://orcid.org/0000-0002-3610-6398', 'Bourgeois|Marc R|MR|http://orcid.org/0000-0002-9435-9051', 'Cherqui|Charles|C|http://orcid.org/0000-0003-2818-7973', 'Juarez|Xitlali G|XG|', 'Wang|Weijia|W|', 'Odom|Teri W|TW|http://orcid.org/0000-0002-8490-292X', 'Schatz|George C|GC|http://orcid.org/0000-0001-5837-4740', 'Basu|Jaydeep Kumar|JK|http://orcid.org/0000-0002-6683-4732']

2020

34149722

Case Report: A Rare Case of Metachronous Multiple Primary Lung Cancers in a Patient With Successful Management by Switching From Anti-PD-1 Therapy to Anti-PD-L1 Therapy.

Without global standard diagnostic criteria, distinguishing multiple primary lung cancers (MPLCs) from intrapulmonary metastasis or histologic transformation has been a big challenge in clinical practice. Here, we described a rare case of metachronous adenocarcinoma and small cell lung cancer (SCLC) in a patient who developed drug resistance to pembrolizumab. Both DNA-sequencing and RNA-sequencing were performed on primary adenocarcinoma and resistant lesions. Through the comparison of primary adenocarcinoma and novel lesion mutation profiles, along with bioinformatic estimation of immune proportion by using RNA sequence data, we revealed the origin and tumor microenvironment of the two lesions. No shared mutations were detected between lung adenocarcinoma (LUAD) and SCLC from the same patient, suggesting these two lesions might be from separate primary lung cancers. Compared to LUAD, SCLC showed a relatively cold microenvironment, including negative PD-L1. The patient obtained durable clinical benefits upon treatment with atezolizumab, without experiencing immune-related adverse events. Disease progression should be monitored with prompt re-biopsy and molecular profiling to spot a potential histologic change and to shed light on therapeutic alternatives. The use of atezolizumab, either alone or in combination with other agents, may be a potential therapeutic strategy for patients with both LUAD and SCLC.

['Lin|Xinqing|X|', 'Qiu|Guihuan|G|', 'Li|Fang|F|', 'Deng|Haiyi|H|', 'Qin|Yinyin|Y|', 'Xie|Xiaohong|X|', 'Jiang|Juhong|J|', 'Song|Yong|Y|', 'Liu|Ming|M|', 'Zhou|Chengzhi|C|']

2021

24123339

Optimism, social support, and mental health outcomes in patients with advanced cancer.

OBJECTIVE Optimism and social support serve as protective factors against distress in medically ill patients. Very few studies have specifically explored the ways in which these variables interact to impact quality of life (QOL), particularly among patients with advanced cancer. The present study examined the role of optimism as a moderator of the relationship between social support and anxiety, depression, hopelessness, and QOL among patients with advanced cancer. METHODS Participants (N = 168) completed self-report assessments of psychosocial, spiritual, and physical well-being, including social support, optimism, hopelessness, depressive and anxious symptoms, and QOL. Hierarchical multiple regression analyses were conducted to determine the extent to which social support and optimism were associated with depressive and anxious symptomatology, hopelessness and QOL, and the potential role of optimism as a moderator of the relationship between social support and these variables. RESULTS Higher levels of optimism were significantly associated with fewer anxious and depressive symptoms, less hopelessness, and better QOL. Higher levels of perceived social support were also significantly associated with better QOL. Additionally, optimism moderated the relationship between social support and anxiety, such that there was a strong negative association between social support and anxiety for participants with low optimism. CONCLUSIONS This study highlights the importance of optimism and social support in the QOL of patients with advanced cancer. As such, interventions that attend to patients' expectations for positive experiences and the expansion of social support should be the focus of future clinical and research endeavors.

['Applebaum|Allison J|AJ|', 'Stein|Emma M|EM|', 'Lord-Bessen|Jennifer|J|', 'Pessin|Hayley|H|', 'Rosenfeld|Barry|B|', 'Breitbart|William|W|']

2014

29965781

RAB26-dependent autophagy protects adherens junctional integrity in acute lung injury.

Microvascular barrier dysfunction is the central pathophysiological feature of acute lung injury (ALI). RAB26 is a newly identified small GTPase involved in the regulation of endothelial cell (EC) permeability. However, the mechanism behind this protection has not been clearly elucidated. Here we found that RAB26 promoted the integrity of adherens junctions (AJs) in a macroautophagy/autophagy-dependent manner in ALI. RAB26 is frequently downregulated in mouse lungs after LPS treatment. Mice lacking Rab26 exhibited phosphorylated SRC expression and increased CDH5/VE-cadherin phosphorylation, leading to AJ destruction. rab26-null mice showed further aggravation of the effects of endotoxin insult on lung vascular permeability and water content. Depletion of RAB26 resulted in upregulation of phosphorylated SRC, enhancement of CDH5 phosphorylation, and aggravation of CDH5 internalization, thereby weakening AJ integrity and endothelial barrier function in human pulmonary microvascular endothelial cells (HPMECs). RAB26 overexpression caused active interaction between SRC and the autophagy marker LC3-II and promoted degradation of phosphorylated SRC. Furthermore, RAB26 was involved in a direct and activation-dependent manner in autophagy induction through interaction with ATG16L1 in its GTP-bound form. These findings demonstrate that RAB26 exerts a protective effect on endothelial cell (EC) permeability, which is in part dependent on autophagic targeting of active SRC, and the resultant CDH5 dephosphorylation maintains AJ stabilization. Thus, RAB26-mediated autophagic targeting of phosphorylated SRC can maintain barrier integrity when flux through the RAB26-SRC pathway is protected. These findings suggest that activation of RAB26-SRC signaling provides a new therapeutic opportunity to prevent vascular leakage in ALI. ABBREVIATIONS AJs: adherens junctions; ALI: acute lung injury; ARDS: acute respiratory distress syndrome; ATG5: autophagy related 5; ATG12: autophagy related 12; ATG 16L1: autophagy related 16 like; 1 BALF: bronchoalveolar lavage fluidCQ: chloroquine; Ctrl: control; EC: endothelial cell; GFP: green fluorescent protein; HA-tagged; RAB26WT: HA-tagged wild-type; RAB26  HA-tagged; RAB26QL: HA-tagged; RAB26Q123LHA-tagged; RAB26NI: HA-tagged; RAB26N177IHPMECs: human pulmonary microvascular endothelial cells; H&E: hematoxylin & eosin; IgG: immunoglobulin; GIF: immunofluorescence; IP: immunoprecipitationi;. p.: intraperitoneal; LPS: lipopolysaccharide; PBS: phosphate-buffered salinesi; RNA: small interfering;RNASQSTM1/p62, sequestosome; 1TBS: Tris-buffered saline; VEGF: vascular endothelial growth factor; WB: western blot; WT: wild-type.

['Dong|Weijie|W|', 'He|Binfeng|B|', 'Qian|Hang|H|', 'Liu|Qian|Q|', 'Wang|Dong|D|', 'Li|Jin|J|', 'Wei|Zhenghua|Z|', 'Wang|Zi|Z|', 'Xu|Zhi|Z|', 'Wu|Guangyu|G|', 'Qian|Guisheng|G|', 'Wang|Guansong|G|']

2018

25932003

Primary anorectal malignant melanoma treated with endoscopic mucosal resection.

Anorectal melanoma is a rare neoplasm that accounts for less than 1-4% of anorectal malignant tumors. The main therapeutic modality for anorectal melanoma is surgical treatment, with abdominoperineal resection or wide local excision being the most common approaches. A 77-year-old male with a history of cerebral infarction and hypertension presented with anal bleeding. Here, we report a case of anorectal melanoma treated by endoscopic mucosal resection with adjuvant interferon therapy rather than surgical resection. The patient has been disease-free for 5 years after endoscopic treatment.

['Park|Jong Hoon|JH|', 'Lee|Jeong Rok|JR|', 'Yoon|Hyung Seok|HS|', 'Jung|Tae Young|TY|', 'Lee|Eun Joo|EJ|', 'Lim|Jong Gu|JG|', 'Ko|Soon Young|SY|', 'Wang|Joon Ho|JH|', 'Lee|Jae Dong|JD|', 'Kim|Hye Young|HY|']

2015

34595375

Powdery mildew resistance of barley accessions from Dagestan.

Powdery mildew caused by the parasitic fungus Blumeria graminis (DC.) Golovin ex Speer f. sp. hordei Marchal is one of the most common diseases of barley. Growing resistant varieties can signif icantly minimize harmful effects of the pathogen. The specif icity in the interaction between the fungus and its host plant requires a continuous search for new donors of the resistance trait. The powdery mildew resistance of 264 barley accessions from Dagestan and genetic control of the trait in resistant forms were studied under f ield and laboratory conditions. Forty-seven barley lines carrying previously identif ied powdery mildew resistance genes were also examined. During three years, the experimental material was evaluated under severe infection pressure at the Dagestan Experiment Station of VIR (North Caucasus, Derbent). Juvenile resistance against the Northwest (St. Petersburg, Pushkin) pathogen population was evaluated in a climatic chamber. The genetic control of B. graminis resistance in the selected accessions was studied with the application of hybridological and molecular analyses. The level of genetic diversity of Dagestan barley for effective resistance to powdery mildew is very low. Only two accessions, VIR-23787 and VIR-28212, are resistant against B. graminis at both seedling and adult plant stages. The high-level resistance of breeding line VIR-28212 originating from barley landrace VIR-17554 (Ep-80 Abyssinien) from Ethiopia is controlled by the recessive gene mlo11. Accession VIR-17554 is heterogeneous for the studied trait, with the powdery mildew resistant genotypes belonging to two varieties, dupliatrum (an awnless phenotype) and nigrinudum (an awned phenotype). In accession VIR-23787, a recessive resistance gene distinct from the mlo11 allele was identif ied. This accession is supposed to be protected by a new, effective pathogen resistance gene.

['Abdullaev|R A|RA|', 'Lebedeva|T V|TV|', 'Alpatieva|N V|NV|', 'Batasheva|B A|BA|', 'Anisimova|I N|IN|', 'Radchenko|E E|EE|']

2021

31963527

Synthesis of Polyhedral Borane Cluster Fused Heterocycles via Transition Metal Catalyzed B-H Activation.

Aromatic heterocycles are ubiquitous building blocks in bioactive natural products, pharmaceutical and agrochemical industries. Accordingly, the carborane-fused heterocycles would be potential candidates in drug discovery, nanomaterials, metallacarboranes, as well as photoluminescent materials. In recent years, the transition metal catalyzed B-H activation has been proved to be an effective protocol for selective functionalization of B-H bond of o-carboranes, which has been further extended for the synthesis of polyhedral borane cluster-fused heterocycles via cascade B-H functionalization/annulation process. This article summarizes the recent progress in construction of polyhedral borane cluster-fused heterocycles via B-H activation.

['Cao|Ke|K|', 'Zhang|Cai-Yan|CY|', 'Xu|Tao-Tao|TT|', 'Wu|Ji|J|', 'Wen|Xin-Yu|XY|', 'Jiang|Wen-Jun|WJ|', 'Chen|Mao|M|', 'Yang|Junxiao|J|']

2020

32754443

Proteomic Profiling of Serum Exosomes From Patients With Metastatic Gastric Cancer.

Background: Clinical management of metastatic gastric cancer (mGC) remains a major challenge due to a lack of specific biomarkers and effective therapeutic targets. Recently, accumulating evidence has suggested that exosomes play an essential role in cancer metastasis and can be an excellent reservoir of novel biomarkers and candidate therapeutic targets for cancer. Therefore, in this study, we aimed to reveal the proteomic profile of mGC-derived exosomes. Methods: Exosomes were isolated from pooled serum samples of 20 mGC patients and 40 healthy controls (HC) by ultracentrifugation. Next, quantitative proteomic analyses were applied to analyze the protein profiles of the exosomes, and bioinformatic analyses were conducted on the proteomic data. Finally, the expression of exosomal protein candidates was selectively validated in individual subjects by western blot analysis. Results: We isolated exosomes from serum samples. The size of the serum derived exosomes ranged from 30 to 150 nm in diameter. The exosomal markers CD9 and CD81 were observed in the serum exosomes. However, the exosomal negative marker calnexin, an endoplasmic reticulum protein, was not detected in exosomes. Overall, 443 exosomal proteins, including 110 differentially expressed proteins (DEPs) were identified by quantitative proteomics analyses. The bioinformatics analyses indicated that the upregulated proteins were enriched in the process of protein metabolic, whereas the downregulated proteins were largely involved in cell-cell adhesion organization. Surprisingly, 10 highly vital proteins (UBA52, PSMA1, PSMA5, PSMB6, PSMA7, PSMA4, PSMA3, PSMB1, PSMA6, and FGA) were filtered from DEPs, most of which are proteasome subunits. Moreover, the validation data confirmed that PSMA3 and PSMA6 were explicitly enriched in the serum derived exosomes from patients with mGC. Conclusion: The present study provided a comprehensive description of the serum exosome proteome of mGC patients, which could be an excellent resource for further studies of mGC.

['Ding|Xiao-Qing|XQ|', 'Wang|Zhe-Ying|ZY|', 'Xia|Di|D|', 'Wang|Rui-Xian|RX|', 'Pan|Xiao-Rong|XR|', 'Tong|Jian-Hua|JH|']

2020

24142505

Bridging the gap between functional and anatomical features of cortico-cerebellar circuits using meta-analytic connectivity modeling.

Theories positing that the cerebellum contributes to cognitive as well as motor control are driven by two sources of information: (1) studies highlighting connections between the cerebellum and both prefrontal and motor territories, (2) functional neuroimaging studies demonstrating cerebellar activations evoked during the performance of both cognitive and motor tasks. However, almost no studies to date have combined these two sources of information and investigated cortico-cerebellar connectivity during task performance. Through the use of a novel neuroimaging tool (Meta-Analytic Connectivity Modelling) we demonstrate for the first time that cortico-cerebellar connectivity patterns seen in anatomical studies and resting fMRI are also present during task performance. Consistent with human and nonhuman primate anatomical studies cerebellar lobules Crus I and II were significantly coactivated with prefrontal and parietal cortices during task performance, whilst lobules HV, HVI, HVIIb, and HVIII were significantly coactivated with the pre- and postcentral gyrus. An analysis of the behavioral domains showed that these circuits were driven by distinct tasks. Prefrontal-parietal-cerebellar circuits were more active during cognitive and emotion tasks whilst motor-cerebellar circuits were more active during action execution tasks. These results highlight the separation of prefrontal and motor cortico-cerebellar loops during task performance, and further demonstrate that activity within these circuits relates to distinct functions.

['Balsters|Joshua H|JH|', 'Laird|Angela R|AR|', 'Fox|Peter T|PT|', 'Eickhoff|Simon B|SB|']

2014

32438591

Characterizing Y-STRs in the Evaluation of Population Differentiation Using the Mean of Allele Frequency Difference between Populations.

Y-chromosomal short tandem repeats (Y-STRs) are widely used in human research for the evaluation of population substructure or population differentiation. Previous studies show that several haplotype sets can be used for the evaluation of population differentiation. However, little is known about whether each Y-STR in these sets performs well during this procedure. In this study, a total of 20,927 haplotypes of a Yfiler Plus set were collected from 41 global populations. Different configurations were observed in multidimensional scaling (MDS) plots based on pairwise genetic distances evaluated using a Yfiler set and a Yfiler Plus set, respectively. Subsequently, 23 single-copy Y-STRs were characterized in the evaluation of population differentiation using the mean of allele frequency difference (mAFD) between populations. Our results indicated that DYS392 had the largest mAFD value (0.3802) and YGATAH4 had the smallest value (0.1845). On the whole, larger pairwise genetic distances could be obtained using the set with the top fifteen markers from these 23 single-copy Y-STRs, and clear clustering or separation of populations could be observed in the MDS plot in comparison with those using the set with the minimum fifteen markers. In conclusion, the mAFD value is reliable to characterize Y-STRs for efficiency in the evaluation of population differentiation.

['Zhou|Yuxiang|Y|', 'Yao|Yining|Y|', 'Liu|Baonian|B|', 'Yang|Qinrui|Q|', 'Zhou|Zhihan|Z|', 'Shao|Chengchen|C|', 'Li|Shilin|S|', 'Tang|Qiqun|Q|', 'Xie|Jianhui|J|']

2020

28355564

SMARCAD1 Contributes to the Regulation of Naive Pluripotency by Interacting with Histone Citrullination.

Histone citrullination regulates diverse cellular processes. Here, we report that SMARCAD1 preferentially associates with H3 arginine 26 citrullination (H3R26Cit) peptides present on arrays composed of 384 histone peptides harboring distinct post-transcriptional modifications. Among ten histone modifications assayed by ChIP-seq, H3R26Cit exhibited the most extensive genomewide co-localization with SMARCAD1 binding. Increased Smarcad1 expression correlated with naive pluripotency in pre-implantation embryos. In the presence of LIF, Smarcad1 knockdown (KD) embryonic stem cells lost naive state phenotypes but remained pluripotent, as suggested by morphology, gene expression, histone modifications, alkaline phosphatase activity, energy metabolism, embryoid bodies, teratoma, and chimeras. The majority of H3R26Cit ChIP-seq peaks occupied by SMARCAD1 were associated with increased levels of H3K9me3 in Smarcad1 KD cells. Inhibition of H3Cit induced H3K9me3 at the overlapping regions of H3R26Cit peaks and SMARCAD1 peaks. These data suggest a model in which SMARCAD1 regulates naive pluripotency by interacting with H3R26Cit and suppressing heterochromatin formation.

['Xiao|Shu|S|', 'Lu|Jia|J|', 'Sridhar|Bharat|B|', 'Cao|Xiaoyi|X|', 'Yu|Pengfei|P|', 'Zhao|Tianyi|T|', 'Chen|Chieh-Chun|CC|', 'McDee|Darina|D|', 'Sloofman|Laura|L|', 'Wang|Yang|Y|', 'Rivas-Astroza|Marcelo|M|', 'Telugu|Bhanu Prakash V L|BPVL|', 'Levasseur|Dana|D|', 'Zhang|Kang|K|', 'Liang|Han|H|', 'Zhao|Jing Crystal|JC|', 'Tanaka|Tetsuya S|TS|', 'Stormo|Gary|G|', 'Zhong|Sheng|S|']

2017

27090964

Peptide reactivity associated with skin sensitization: The QSAR Toolbox and TIMES compared to the DPRA.

The molecular initiating event (MIE) of skin sensitization is the binding of a hapten to dermal proteins. This can be assessed using the in chemico direct peptide reactivity assay (DPRA) or in silico tools such as the QSAR Toolbox and TIMES SS. In this study, the suitability of these methods was analyzed by comparing their results to in vivo sensitization data of LLNA and human studies. Compared to human data, 84% of non-sensitizers and sensitizers yielded consistent results in the DPRA. In silico tools resulted in 'no alert' for 83%-100% of the non-sensitizers, but alerted only 55%-61% of the sensitizers. The inclusion of biotic and abiotic transformation simulations yielded more alerts for sensitizers, but simultaneously dropped the number of non-alerted non-sensitizers. In contrast to the DPRA, in silico tools were more consistent with results of the LLNA than human data. Interestingly, the new "DPRA profilers" (QSAR Toolbox) provided unsatisfactory results. Additionally, the results were combined in the '2 out of 3' prediction model with in vitro data derived from LuSens and h-CLAT. Using DPRA results, the model identified 90% of human sensitizers and non-sensitizers; using in silico results (including abiotic and biotic activations) instead of DPRA results led to a comparable high predictivity.

['Urbisch|D|D|', 'Honarvar|N|N|', 'Kolle|S N|SN|', 'Mehling|A|A|', 'Ramirez|T|T|', 'Teubner|W|W|', 'Landsiedel|R|R|']

2016

28781486

Frequency of Class 1 Integron and Genetic Diversity of Acinetobacter baumannii Isolated from Medical Centers in Kermanshah.

BACKGROUND AND OBJECTIVE Acinetobacter baumannii has emerged as an important pathogen in hospital and environment that can acquire transport element and antibiotic-resistant genes. The aim of this study was to determine the resistances to different antibiotics, frequency of Class 1 integron in A. baumannii and then molecular typing for A. baumannii isolated from Intensive Care Unit (ICU). MATERIALS AND METHODS A total of 100 isolates of A. baumannii were collected from patients admitted to hospitals in Kermanshah from April 2014 to September 2015. The isolates were identified using biochemical test. Antimicrobial susceptibility test for 20 antibiotics was determined by Kirby-Bauer antibiotic testing (or disc diffusion). The prevalence rate of class integrons among the isolates was determined using polymerase chain reaction and finally 80 isolates of A. baumannii obtained from the Intensive Care Unit were selected for molecular typing by pulsed-field gel electrophoresis (PFGE). RESULTS The maximum drug resistance was observed against cefotaxime, ceftriaxone, mezlocillin, imipenem, and ceftazidime and piperacillin. Twenty-nine isolates were multidrug resistant (MDR); about 21 isolates were extensively-drug resistant and none were pandrug resistance and 42 isolates (42%) contained Class 1 integrons. The results did not show a significant correlation between the presence of Class 1 integrons and incidence of MDR A. baumannii. Five clusters were obtained by PFGE. CONCLUSION This study did not show a significant correlation between the presence of Class 1 integrons and incidence of MDR A. baumannii. By PFGE analysis, the high level of similarity between some pulsotypes in A. baumannii strains showed genetic correlation between them.

['Eghbalimoghadam|Mahsa|M|', 'Farahani|Abbas|A|', 'Akbar|Farahtaj Navab|FN|', 'Mohajeri|Parviz|P|']

2017

25451254

Apolipoprotein A-I expression suppresses COX-2 expression by reducing reactive oxygen species in hepatocytes.

Abnormal lipid metabolism may contribute to the increase of reactive oxygen species (ROS) and inflammation in the pathogenesis of non-alcoholic steatohepatitis (NASH). Apolipoprotein A-I (apoA-I) accepts cellular cholesterol and phospholipids transported by ATP-binding cassette transporter A1 to generate nascent high density lipoprotein particles. Previous studies revealed that the overexpression of ABCA1 or apoA-I alleviated hepatic lipid levels by modifying lipid transport. Here, we examined the effect of apoA-I overexpression on ROS and genes involved in inflammation in both BEL-7402 hepatocytes and mice. Human apoA-I was overexpressed by transfection in BEL-7402 hepatocytes and by an adenoviral vector in C57BL/6J mice fed a methionine choline-deficient diet. The overexpression of apoA-I in both models resulted in decreased ROS and lipid peroxidation levels, as well as a reduced MAPK phosphorylation and decreased expression levels of c-Fos and COX-2. These results suggest that apoA-I overexpression can reduce steatosis by decreasing ROS levels and suppressing COX-2-induced inflammation in hepatocytes. MAPK and c-Fos are involved in this regulatory process.

['Mao|Jing|J|', 'Liu|Wei|W|', 'Wang|Yutong|Y|']

2014

24945471

Estimating the correlation between bursty spike trains and local field potentials.

To further understand rhythmic neuronal synchronization, an increasingly useful method is to determine the relationship between the spiking activity of individual neurons and the local field potentials (LFPs) of neural ensembles. Spike field coherence (SFC) is a widely used method for measuring the synchronization between spike trains and LFPs. However, due to the strong dependency of SFC on the burst index, it is not suitable for analyzing the relationship between bursty spike trains and LFPs, particularly in high frequency bands. To address this issue, we developed a method called weighted spike field correlation (WSFC), which uses the first spike in each burst multiple times to estimate the relationship. In the calculation, the number of times that the first spike is used is equal to the spike count per burst. The performance of this method was demonstrated using simulated bursty spike trains and LFPs, which comprised sinusoids with different frequencies, amplitudes, and phases. This method was also used to estimate the correlation between pyramidal cells in the hippocampus and gamma oscillations in rats performing behaviors. Analyses using simulated and real data demonstrated that the WSFC method is a promising measure for estimating the correlation between bursty spike trains and high frequency LFPs.

['Li|Zhaohui|Z|', 'Ouyang|Gaoxiang|G|', 'Yao|Li|L|', 'Li|Xiaoli|X|']

2014

31581454

Protein Expression Profiling Identifies Key Proteins and Pathways Involved in Growth Inhibitory Effects Exerted by Guggulsterone in Human Colorectal Cancer Cells.

Colorectal cancer (CRC) is a leading killer cancer worldwide and one of the most common malignancies with increasing incidences of mortality. Guggulsterone (GS) is a plant sterol used for treatment of various ailments such as obesity, hyperlipidemia, diabetes, and arthritis. In the current study, anti-cancer effects of GS in human colorectal cancer cell line HCT 116 was tested, potential targets identified using mass spectrometry-based label-free shotgun proteomics approach and key pathways validated by proteome profiler antibody arrays. Comprehensive proteomic profiling identified 14 proteins as significantly dysregulated. Proteins involved in cell proliferation/migration, tumorigenesis, cell growth, metabolism, and DNA replication were downregulated while the protein with functional role in exocytosis/tumor suppression was found to be upregulated. Our study evidenced that GS treatment altered expression of Bcl-2 mediated the mitochondrial release of cytochrome c which triggered the formation of apoptosome as well as activation of caspase-3/7 leading to death of HCT 116 cells via intrinsic apoptosis pathway. GS treatment also induced expression of p53 protein while p21 expression was unaltered with no cell cycle arrest. In addition, GS was found to inhibit NF-kB signaling in colon cancer cells by quelling the expression of its regulated gene products Bcl-2, cIAP-1, and survivin.

['Leo|Rari|R|', 'Therachiyil|Lubna|L|', 'Siveen|Sivaraman K|SK|', 'Uddin|Shahab|S|', 'Kulinski|Michal|M|', 'Buddenkotte|Joerg|J|', 'Steinhoff|Martin|M|', 'Krishnankutty|And Roopesh|AR|']

2019

25097292

Reversible bilateral sensori-neural hearing loss due to olanzapine in a male suffering from bipolar affective disorder.

An elderly male with Bipolar Affective Disorder (BPAD) developed reversible ototoxicity, manifesting as bilateral sensory-neural hearing loss (SNHL) with administration of olanzapine.

['Gupta|Sumit Kumar|SK|', 'Shwetank|Bansal|B|']

2014

32504285

microRNA-4270-5p inhibits cancer cell proliferation and metastasis in hepatocellular carcinoma by targeting SATB2.

Hepatocellular carcinoma (HCC) remains a lethal cancer type for both males and females. MicroRNAs (miRNAs) contribute to the initiation, development and metastasis of cancer. Although several miRNAs have been identified as drivers or suppressors of HCC, the molecular mechanisms of many miRNAs have not been investigated. Currently, we discovered that miR-4270-5p was a significantly downregulated miRNA in HCC. We revealed that miR-4270-5p overexpression inhibited cell proliferation and invasion of HCC cells. The data manifested that miR-4270-5p directly targeted SATB2, a key regulator of epithelial mesenchymal transition (EMT), in HCC cells and reversed the EMT process. The rescue experiments suggested that SATB2 overexpression reversed the biological function of miR-4270-5p in HCC cells. Clinical data indicated that SATB2 expression was negatively correlated with miR-4270-5p levels in HCC patients. Our findings provided potential targets for prognosis and treatment of patients with HCC.

['Wang|Yun|Y|', 'Li|Chang-Feng|CF|', 'Sun|Li-Bo|LB|', 'Li|Yong-Chao|YC|']

2020

30401755

Factors Influencing Activities of Daily Living in Subjects With COPD.

BACKGROUND Activities of daily living (ADL) are important for an independent life. As COPD progresses, the ability to complete ADL is usually reduced. Knowing the possible factors that influence the ability to perform ADL may allow better targeting of appropriate rehabilitation programs to increase the independence levels and/or to prevent further decreases in patients with COPD. Therefore, the aim of this study was to investigate ADL performance as measured by the London Chest Activity of Daily Living scale, which is a commonly used measure in patients with COPD. METHODS This cross-sectional study included 44 clinically stable subjects who were not taking antibiotics and had not made any changes in their medications for at least three weeks with a COPD diagnosis based on Global Initiative for Chronic Obstructive Lung Disease. Demographic characteristics, pulmonary function, ADL measured by the London Chest Activity of Daily Living scale, functional exercise capacity via the 6-min walk distance, disease-related symptoms measured by the COPD Assessment Test, and peripheral and respiratory muscle strength were evaluated. A multiple linear regression (stepwise) analysis was used to determine the variables that have the greatest influence on ADL (ie, the London Chest Activity of Daily Living scale score). RESULTS The London Chest Activity of Daily Living scale score had moderate correlations with the COPD Assessment Test score (r = 0.31, P = .041), maximum expiratory pressure value (r = -0.37, P = .01), 6-min walk distance (r = -0.48, P = .001), knee extensor muscle strength (r = -0.47, P = .001), handgrip strength (r = -0.44, P = .003). The 6-min walk distance, COPD Assessment Test score and maximal expiratory pressure values were significant and independent determinants of the London Chest Activity of Daily Living scale, with 40.1% of the variance in subjects with COPD. CONCLUSIONS Functional exercise capacity, disease-related symptoms, and expiratory muscle strength have the greatest influence on ADL in the subjects with COPD. The level of independence to perform ADL can be increased by improving functional exercise capacity, reducing symptoms, and increasing expiratory muscle strength in subjects with COPD.

['Ozsoy|Ismail|I|', 'Ozcan Kahraman|Buse|B|', 'Acar|Serap|S|', 'Ozalevli|Sevgi|S|', 'Akkoclu|Atila|A|', 'Savci|Sema|S|']

2019

29042735

Effectiveness of Three Different Irrigants - 17% Ethylenediaminetetraacetic Acid, Q-MIX, and Phytic Acid in Smear Layer Removal: A Comparative Scanning Electron Microscope Study.

BACKGROUND Removal of smear layer from the root canal walls is important for long-standing endodontic success. AIM The aim of this study is to evaluate and compare smear layer removing ability among 17% ethylenediaminetetraacetic acid (EDTA), Q-MIX, and phytic acid by scanning electron microscopy (SEM). MATERIALS AND METHODS This in-vitro experimental study assessed smear layer removal using three different irrigants. Thirty single-rooted freshly extracted human permanent premolars were collected, disinfected, and decoronated to a standardized root length of 13 mm. Root canals were cleaned and shaped till F2 universal rotary protaper at working length 1 mm short of the apex. They were randomly divided into three groups, and final irrigation was done accordingly. Group 1 (n = 10): with 1 ml of 17% EDTA, Group 2 (n = 10): with 1 ml of Q-MIX, Group 3 (n = 10): with 1 ml of phytic acid. Samples were then longitudinally sectioned and evaluated under SEM at coronal, middle, and apical levels. STATISTICAL ANALYSIS Two-way analysis of variance and Tukey's post hoc test were performed. The level of significance was set at 0.05. RESULTS Smear layer removing ability among irrigants and sections in descending order: 17 EDTA > Q-MIX > phytic acid; coronal > middle > apical. CONCLUSION 17% EDTA showed better and promising results followed by Q-MIX and then phytic acid.

['Jagzap|Janhavi Balasaheb|JB|', 'Patil|Sanjay S|SS|', 'Gade|Vandana Jaykumar|VJ|', 'Chandhok|Deepika J|DJ|', 'Upagade|Madhura A|MA|', 'Thakur|Deepa A|DA|']

2017

25857778

Membrane protein expression in Lactococcus lactis.

The Gram-positive bacterium Lactococcus lactis has many properties that are ideal for the overproduction of membrane proteins in a functional form. Growth of lactococci is rapid, proceeds to high cell densities, and does not require aeration, which facilitates large-scale fermentation. The available promoter systems are strong and tightly regulated, allowing expression of toxic gene products in a controlled manner. Expressed membrane proteins are targeted exclusively to the cytoplasmic membrane, allowing the use of ionophores, ligands, and inhibitors to study activity of the membrane protein in whole cells. Constructed plasmids are stable and expression levels are highly reproducible. The relatively small genome size of the organism causes little redundancy, which facilitates complementation studies and allows for easier purification. The produced membrane proteins are often stable, as the organism has limited proteolytic capability, and they are readily solubilized from the membrane with mild detergents. Lactococci are multiple amino acid auxotrophs, allowing the incorporation of labels, such as selenomethionine. Among the few disadvantages are the low transformation frequency, AT-rich codon usage, and resistance to lysis by mechanical means, but these problems can be overcome fairly easily. We will describe in detail the protocols used to express membrane proteins in L. lactis, from cloning of the target gene to the isolation of membrane vesicles for the determination of expression levels.

['King|Martin S|MS|', 'Boes|Christoph|C|', 'Kunji|Edmund R S|ER|']

2015

29557635

Hierarchically Porous N-Doped Carbon Nanotubes/Reduced Graphene Oxide Composite for Promoting Flavin-Based Interfacial Electron Transfer in Microbial Fuel Cells.

Interfacial electron transfer between an electroactive biofilm and an electrode is a crucial step for microbial fuel cells (MFCs) and other bio-electrochemical systems. Here, a hierarchically porous nitrogen-doped carbon nanotubes (CNTs)/reduced graphene oxide (rGO) composite with polyaniline as the nitrogen source has been developed for the MFC anode. This composite possesses a nitrogen atom-doped surface for improved flavin redox reaction and a three-dimensional hierarchically porous structure for rich bacterial biofilm growth. The maximum power density achieved with the N-CNTs/rGO anode in S. putrefaciens CN32 MFCs is 1137 mW m-2, which is 8.9 times compared with that of the carbon cloth anode and also higher than those of N-CNTs (731.17 mW m-2), N-rGO (442.26 mW m-2), and the CNTs/rGO (779.9 mW m-2) composite without nitrogen doping. The greatly improved bio-electrocatalysis could be attributed to the enhanced adsorption of flavins on the N-doped surface and the high density of biofilm adhesion for fast interfacial electron transfer. This work reveals a synergistic effect from pore structure tailoring and surface chemistry designing to boost both the bio- and electrocatalysis in MFCs, which also provide insights for the bioelectrode design in other bio-electrochemical systems.

['Wu|Xiaoshuai|X|', 'Qiao|Yan|Y|http://orcid.org/0000-0001-9701-4377', 'Shi|Zhuanzhuan|Z|', 'Tang|Wei|W|', 'Li|Chang Ming|CM|http://orcid.org/0000-0002-4041-2574']

2018

26022385

Vasomotor symptoms in women and cardiovascular risk markers: Systematic review and meta-analysis.

UNLABELLED We performed a systematic review and meta-analysis of the observational or interventional studies assessing the association of vasomotor symptoms (hot flushes and night sweats) with various cardiovascular risk markers (systolic (SBP) and diastolic blood pressure (DBP), hypertension, total cholesterol, body mass index (BMI), and measures of subclinical atherosclerosis), in peri-menopausal, menopausal, or postmenopausal women. Eleven unique studies were identified with data available on 19,667 non-overlapping participants. Pooled analysis showed that women with hot flushes, compared to those without, tended to have significant higher levels of SBP (mean difference (MD): 1.95 mmHg (95%CI, 0.27 to 33.63)), and DBP (MD 1.17 mmHg (95%CI, -0.21 to 2.54)) and higher odds of having hypertension (OR: 1.18, 95%CI: 0.93 to 1.51), albeit non-significant. Similarly, women who reported night sweats compared to those who did not, had significant higher levels of SBP, (MD: 1.33 mmHg (95%CI, 0.63 to 2.03)), DBP (MD: 0.55 mmHg (95%CI, 0.19 to 0.91)), total cholesterol (MD: 0.17 mmHg (95%CI, 0.03 to 0.31)) and BMI (MD 0.64 mmHg (95%CI, 0.47 to 0.80)). Vasomotor symptoms in women were not associated with measures of subclinical atherosclerosis. Women with vasomotor symptoms may have an unfavorable cardiovascular risk profile compared to women without vasomotor complaints.

['Franco|Oscar H|OH|', 'Muka|Taulant|T|', 'Colpani|Veronica|V|', 'Kunutsor|Setor|S|', 'Chowdhury|Susmita|S|', 'Chowdhury|Rajiv|R|', 'Kavousi|Maryam|M|']

2015

30604499

The PROTAC technology in drug development.

Currently, a new technology termed PROTAC, proteolysis targeting chimera, has been developed for inducing the protein degradation by a targeting molecule. This technology takes advantage of a moiety of targeted protein and a moiety of recognizing E3 ubiquitin ligase and produces a hybrid molecule to specifically knock down a targeted protein. During the first decade, three pedigreed groups worked on the development of this technology. To date, this technology has been extended by different groups, aiming to develop new drugs against different diseases including cancers. This review summarizes the contributions of the groups for the development of PROTAC. SIGNIFICANCE OF THE STUDY: This review summarized the development of the PROTAC technology for readers and also presented the author's opinions on the application of the technology in tumor therapy.

['Zou|Yutian|Y|', 'Ma|Danhui|D|', 'Wang|Yinyin|Y|http://orcid.org/0000-0003-1285-0507']

2019

29545214

Hybrid quantitative MRI using chemical shift displacement and recovery-based simultaneous water and lipid imaging: A preliminary study.

PURPOSE To suppress olefinic signals and enable simultaneous and quantitative estimation of multiple functional parameters associated with water and lipid, we investigated a modified method using chemical shift displacement and recovery-based separation of lipid tissue (SPLIT) involving acquisitions with different inversion times (TIs), echo times (TEs), and b-values. MATERIALS AND METHODS Single-shot diffusion echo-planar imaging (SSD-EPI) with multiple b-values (0-3000 s/mm2) was performed without fat suppression to separate water and lipid images using the chemical shift displacement of lipid signals in the phase-encoding direction. An inversion pulse (TI = 292 ms) was applied to SSD-EPI to remove olefinic signals. Consecutively, SSD-EPI (b = 0 s/mm2) was performed with TI = 0 ms and TE = 31.8 ms for T1 and T2 measurements, respectively. Under these conditions, transverse water and lipid images at the maximum diameter of the right calf were obtained in six healthy subjects. T1, T2, and the apparent diffusion coefficients (ADC) were then calculated for the tibialis anterior (TA), gastrocnemius (GM), and soleus (SL) muscles, tibialis bone marrow (TB), and subcutaneous fat (SF). Perfusion-related (D*) and restricted diffusion coefficients (D) were calculated for the muscles. Lastly, the lipid fractions (LF) of the muscles were determined after T1 and T2 corrections. RESULTS The modified SPLIT method facilitated sufficient separation of water and lipid images of the calf, and the inversion pulse with TI of 292 ms effectively suppressed olefinic signals. All quantitative parameters obtained with the modified SPLIT method were found to be in general agreement with those previously reported in the literature. CONCLUSION The modified SPLIT technique enabled sufficient suppression of olefinic signals and simultaneous acquisition of quantitative parameters including diffusion, perfusion, T1 and T2 relaxation times, and LF.

['Ohno|Naoki|N|', 'Miyati|Tosiaki|T|', 'Suzuki|Shuto|S|', 'Kan|Hirohito|H|', 'Aoki|Toshitaka|T|', 'Nakamura|Yoshitaka|Y|', 'Hiramatsu|Yuki|Y|', 'Kobayashi|Satoshi|S|', 'Gabata|Toshifumi|T|']

2018

33842444

Principal Component Analysis of the Running Ground Reaction Forces With Different Speeds.

Ground reaction force (GRF) is a key metric in biomechanical research, including parameters of loading rate (LR), first impact peak, second impact peak, and transient between first and second impact peaks in heel strike runners. The GRFs vary over time during stance. This study was aimed to investigate the variances of GRFs in rearfoot striking runners across incremental speeds. Thirty female and male runners joined the running tests on the instrumented treadmill with speeds of 2.7, 3.0, 3.3, and 3.7 m/s. The discrete parameters of vertical average loading rate in the current study are consistent with the literature findings. The principal component analysis was modeled to investigate the main variances (95%) in the GRFs over stance. The females varied in the magnitude of braking and propulsive forces (PC1, 84.93%), whereas the male runners varied in the timing of propulsion (PC1, 53.38%). The female runners dominantly varied in the transient between the first and second peaks of vertical GRF (PC1, 36.52%) and LR (PC2, 33.76%), whereas the males variated in the LR and second peak of vertical GRF (PC1, 78.69%). Knowledge reported in the current study suggested the difference of the magnitude and patterns of GRF between male and female runners across different speeds. These findings may have implications for the prevention of sex-specific running-related injuries and could be integrated with wearable signals for the in-field prediction and estimation of impact loadings and GRFs.

['Yu|Lin|L|', 'Mei|Qichang|Q|', 'Xiang|Liangliang|L|', 'Liu|Wei|W|', 'Mohamad|Nur Ikhwan|NI|', 'István|Bíró|B|', 'Fernandez|Justin|J|', 'Gu|Yaodong|Y|']

2021

30455048

Influence of Frailty on Cognitive Decline: A Population-Based Cohort Study in Rural Ecuador.

OBJECTIVE To assess the influence of frailty on cognitive decline. DESIGN Population-based prospective cohort study. SETTINGS/PARTICIPANTS Community-dwelling older adults living in a rural Ecuadorian village, fulfilling the following criteria: age ≥60 years at baseline Montreal Cognitive Assessment (MoCA) and frailty assessment, a baseline brain magnetic resonance imaging, and a follow-up MoCA performed at least 12 months after the baseline. MEASURES Frailty was evaluated by the Edmonton Frailty Scale (EFS) and cognitive performance by MoCA. The relationship between baseline EFS and MoCA decline was assessed by longitudinal linear and fractional polynomial models, adjusted for relevant confounders. The score of the cognitive component of the EFS was subtracted, and an alternative fractional polynomial model was fitted to settle the impact of such cognitive question on the model. RESULTS A total of 252 individuals, contributing 923.7 person-years of follow-up (mean: 3.7 ± 0.7 years) were included. The mean EFS score was 4.7 ± 2.5 points. The mean baseline MoCA score was 19.5 ± 4.5 points, and that of the follow-up MoCA was 18.1 ± 4.9 points (P = .001). Overall, 154 (61%) individuals had lower MoCA scores in the follow-up. The best fitted longitudinal linear model showed association between baseline EFS score and MoCA decline (P = .027). There was a continuous increase in MoCA decline in persons with an EFS ≥7 points (nonlinear relationship). Fractional polynomials explained the effect of the EFS on MoCA decline. For the complete EFS score, the β coefficient was 2.43 (95% confidence interval 1.22-3.63). For the effect of the EFS (without its cognitive component) on MoCA decline, the relationship was still significant (β 4.86; 95% confidence interval 2.6-7.13). CONCLUSIONS/IMPLICATIONS Over a 3.7-year period, 61% of older adults living in Atahualpa experienced cognitive decline. Such decline was significantly associated with frailty status at baseline. Region-specific risk factors influencing this relationship should be further studied to reduce its burden in rural settings.

['Del Brutto|Oscar H|OH|', 'Mera|Robertino M|RM|', 'Zambrano|Mauricio|M|', 'Sedler|Mark J|MJ|']

2019

33857909

Oviduct fluid during IVF moderately modulates polyspermy in in vitro-produced goat embryos during the non-breeding season.

The present study determined i) the presence of proteins (oviduct-specific glycoprotein, OVGP1; heat shock protein-70A, HSPA1A; heat shock protein-A8, HSPA8; annexin A1, ANXA1; annexin A5, ANXA5; and myosin-9, MYH9) known to be involved in early reproduction in the oviduct fluid (OF) of anestrous goats; and ii) the functional effect of during IVF on polyspermy modulation and embryonic development. In vitro-matured oocytes were co-cultured with spermatozoa (1.0, 2.0, or 4.0 x 106 cells/mL) for 18 h in SOF medium supplemented with 5 μg/mL of heparin, 4 μg/mL gentamicin, and 10% estrus sheep serum (CTRL1, CTRL2, and CTRL4 groups) or the same medium plus 10% OF (OF1, OF2, and OF4 groups) obtained from anestrus goats. The analysis of OF by western blotting confirmed the presence of the six proteins tested for. The increase in sperm concentration had no effect (P > 0.05) on the penetration rate in any group; however, monospermy rate decreased as sperm concentration was increased in both OF and CTRL. Regardless of the concentration used, when data were pooled, OF supplementation improved (P < 0.05) monospermy and tended (P = 0.057) to enhance IVF efficiency. Additionally, IVF efficiency was higher (P < 0.05) in OF1 than in OF4 [60 ± 13 vs 37 ± 5%). The development capacity was not affected (P > 0.05) by the sperm concentration and OF treatment, and the average values were cleavage (72 ± 2.6%), blastocyst (37 ± 3.0%), blastocyst in relation to the cleaved (51 ± 4.8%), hatched (62 ± 1.2%), and number of cells per blastocyst (174 ± 1.8%). In conclusion, the six proteins analyzed are present in the OF of anestrous goats, and the supplementation of this OF during IVF may modulate the polyspermy incidence and enhance IVF efficiency, especially when 1x106 sperm per mL is used.

['Bragança|G M|GM|', 'Alcântara-Neto|A S|AS|', 'Batista|R I T P|RITP|', 'Brandão|F Z|FZ|', 'Freitas|V J F|VJF|', 'Mermillod|P|P|', 'Souza-Fabjan|J M G|JMG|']

2021

27251784

A qualitative study of patient experiences of Type 2 Diabetes care delivered comparatively by General Practice Nurses and Medical Practitioners.

AIMS AND OBJECTIVES To explore patient experiences of type 2 diabetes mellitus care delivered by general practice nurses in collaboration with the general practitioner. BACKGROUND Australian general practice nurses are expanding their role in multidisciplinary type 2 diabetes care with limited research on patient perceptions of care provision within this collaborative model. DESIGN Qualitative interpretive. METHODS Purposeful sampling was used to invite the patients (n = 10). Data were collected from semi-structured face-to-face interviews. Braun and Clarke's () inductive coding thematic analysis process was used to interpret the data. RESULTS All participants experienced their General Practice Nurse consultation as a clinical assessment for their General Practitioner. While they appreciated the extra time with the General Practice Nurse, they were unsure of the purpose of the consultation beyond clinical assessment. They described the ongoing challenge of living with T2DM and identified a need for additional information and advice. CONCLUSION The results suggest that the model of general practice nurse type 2 diabetes care has an important role to play in the delivery of effective ongoing care of patients. However, this role requires further development to ensure that it is understood by the patients as a role that not only conducts clinical assessments but also provides relevant education and self-management support as part of a collaborative approach to care delivery with General Practitioners. RELEVANCE TO PRACTICE The findings are relevant to primary health care clinicians providing diabetes care to inform more relevant supportive care by general practice nurses.

['Boyle|Eileen|E|', 'Saunders|Rosemary|R|', 'Drury|Vicki|V|']

2016

31306916

Teaching a novel word: Parenting styles and toddlers' word learning.

We examined the styles that parents adopted while teaching a novel word to their toddlers and whether those styles related to children's word learning and engagement during the task. Participants were 36 parents and their toddlers (Mage = 20 months). Parents were videotaped while teaching their children a name for a novel object. Parental utterances were transcribed verbatim and coded for cognitive and autonomy support. Children's utterances were coded for elicited and spontaneous contributions. Children's ability to recognize and process the novel word was assessed using the Looking-While-Listening task. Two parental cognitive support styles were identified via cluster analysis: "Cognitive Scaffolders," who combined a diversity of teaching moves, and "Labelers," who focused on labeling the novel object for the children. Similarly, two parental autonomy support styles were identified: "Followers," who focused on following the children's lead and providing positive feedback, and "Non-followers," who used diverse communicative ways to engage the children. Compared with parents who were Labelers, parents who were Cognitive Scaffolders were not more or less likely to be Followers. Children of Cognitive Scaffolders were better at recognizing the novel word, and children of Followers were more engaged (provided more elicited and spontaneous contributions) in the word-teaching task. Children's ability to recognize the novel word was not related to their engagement. Findings highlight the unique contributions of parental cognitive and autonomy support to children's word learning and engagement.

['Wei|Ran|R|', 'Ronfard|Samuel|S|', 'Leyva|Diana|D|', 'Rowe|Meredith L|ML|']

2019

31235568

Decoding team and individual impact in science and invention.

Scientists and inventors increasingly work in teams, raising fundamental questions about the nature of team production and making individual assessment increasingly difficult. Here we present a method for describing individual and team citation impact that both is computationally feasible and can be applied in standard, wide-scale databases. We track individuals across collaboration networks to define an individual citation index and examine outcomes when each individual works alone or in teams. Studying 24 million research articles and 3.9 million US patents, we find a substantial impact advantage of teamwork over solo work. However, this advantage declines as differences between the team members' individual citation indices grow. Team impact is predicted more by the lower-citation rather than the higher-citation team members, typically centering near the harmonic average of the individual citation indices. Consistent with this finding, teams tend to assemble among individuals with similar citation impact in all fields of science and patenting. In assessing individuals, our index, which accounts for each coauthor, is shown to have substantial advantages over existing measures. First, it more accurately predicts out-of-sample paper and patent outcomes. Second, it more accurately characterizes which scholars are elected to the National Academy of Sciences. Overall, the methodology uncovers universal regularities that inform team organization while also providing a tool for individual evaluation in the team production era.

['Ahmadpoor|Mohammad|M|', 'Jones|Benjamin F|BF|0000-0001-9697-9388']

2019

30891086

Micronutrient supplementation in pregnancy: Who, what and how much?

Pregnancy represents a period of major physiological and metabolic change, aiming to ensure proper fetal growth and development, as well as maternal preservation. This review focuses on maternal nutrition, and particularly on micronutrient deficiencies and supplementation during pregnancy. Nutrient deficiencies and consequences in pregnant women are presented, with an overview of current recommendations for dietary supplementation in pregnancy, even considering the risk of micronutrient overload. Appropriate universal supplementation and prophylaxis/treatment of nutritional needs currently appear to be the most cost-effective goal in low-income countries, thus ensuring adequate intake of key elements including folate, iron, calcium, vitamin D and A. In high-income countries, a proper nutritional assessment and counselling should be mandatory in obstetric care in order to normalize pregestational body mass index, choose a healthy dietary pattern and evaluate the risk of deficiencies.

['Parisi|F|F|', 'di Bartolo|I|I|', 'Savasi|V M|VM|', 'Cetin|I|I|']

2019

21747664

Importance of early electrocardiographic recognition and timely management of hyperkalemia in geriatric patients.

Hyperkalemia is a potentially life-threatening electrolyte imbalance that can be difficult to diagnose due to the paucity of specific signs and symptoms. Because hyperkalemia can lead to sudden death from cardiac arrhythmias and asystole, any patient whose history, physical examination or laboratory studies raise clinical suspicion of hyperkalemia requires an immediate 12-lead electrocardiogram to ascertain whether electrocardiographic manifestations of electrolyte imbalance are present. The current report describes a case involving an elderly man who developed hyperkalemia secondary to acute-on-chronic kidney injury. Factors affecting the vulnerability of geriatric patients to hyperkalemia, the electrocardiographic manifestations of elevated serum potassium levels, and the importance of timely recognition and management are discussed. Understanding the factors that contribute to hyperkalemia, timely recognition of electrocardiogram changes and timely initiation of appropriate therapy are all critical in the approach to hyperkalemia in the geriatric patient.

['McIntyre|William F|WF|', 'Femenía|Francisco|F|', 'Arce|Mauricio|M|', 'Pérez-Riera|Andrés Ricardo|AR|', 'Baranchuk|Adrian|A|']

2011

32388840

The capacity of goat epidermal adult stem cells to reconstruct the damaged ocular surface of total LSCD and activate corneal genetic programs.

Epidermal adult stem cells (EpiASCs) have the potential for unlimited proliferation and differentiation, however, the ability of these stem cells to activate corneal genetic programs in response to corneal stroma stimulation needs to be further validated. Herein, a feasible strategy was developed to reconstruct the damaged corneal surface in a goat model with total limbal stem cell deficiency (LSCD) by transplanting EpiASCs, which had been explanted and cultured from the skin of an adult ram goat and were then purified by selecting single cell-derived clones and cultivating them on a denuded human amniotic membrane (HAM). These artificial tissues were then successfully transplanted into ewe goats with total LSCD. Binding of EpiASCs to the base membrane of an EpiASCs-HAM-Sheet (EHS) indicated their proliferating status. After transplantation, the EpiASCs could survive in the host tissue and they reconstructed the damaged ocular surface of total LSCD. The crystal reconstructed corneal epithelium expressed CK3 and Pax-6 similar to normal corneal epithelium and expressed the Sry gene after transplantation. These results demonstrated that EpiASCs could be induced to differentiate into corneal epithelial cell types in a corneal microenvironment and had the ability to activate corneal genetic programs. This work offer a foundation for promoting tissue-engineered cornea into clinical application.

['Zhang|Pei|P|', 'Ma|Xi-Ya|XY|', 'Huang|Dian-Tong|DT|', 'Yang|Xue-Yi|XY|']

2020

26311811

Dietary Whey and Casein Differentially Affect Energy Balance, Gut Hormones, Glucose Metabolism, and Taste Preference in Diet-Induced Obese Rats.

BACKGROUND Dietary whey and casein proteins decrease food intake and body weight and improve glycemic control; however, little is known about the underlying mechanisms. OBJECTIVE We determined the effects of dietary whey, casein, and a combination of the 2 on energy balance, hormones, glucose metabolism, and taste preference in rats. METHODS In Expt. 1, Obesity Prone CD (OP-CD) rats were fed a high-fat control diet (33% fat energy) for 8 wk, and then randomly assigned to 4 isocaloric dietary treatments (n = 12/group): the control treatment (CO; 14% protein energy from egg white), the whey treatment (WH; 26% whey + 14% egg white), the casein treatment (CA; 26% casein + 14% egg white), or the whey plus casein treatment (WHCA; 13% whey + 13% casein + 14% egg white) for 28 d. Measurements included food intake, energy expenditure, body composition, metabolic hormones, glucose tolerance and key tissue markers of glucose and energy metabolism. In Expt. 2, naïve OP-CD rats were randomly assigned to 3 groups (n = 8/group). During an 8 d conditioning period, each group received on alternate days either the CO or WH, CO or CA, or CO or WHCA. Subsequently, preferences for the test diets were assessed on 2 consecutive days with food intake measurements at regular intervals. RESULTS In Expt. 1, food intake was decreased by 17-37% for the first 14 d in the WH and CA rats, and by 18-34% only for the first 4 d in the WHCA compared with the CO rats. Fat mass decreased by 21-28% for the WH rats and 17-33% for the CA rats from day 14 onward, but by 30% only on day 28 in WHCA rats, relative to CO rats. Thus, food intake, body weight, and fat mass decreased more rapidly in WH and CA rats than in WHCA rats. Energy expenditure in WH rats decreased for the first 4 d compared with CA and WHCA rats, and for the first 7 d compared with the CO rats. Circulating leptin, glucose-dependent insulinotropic polypeptide, interleukin 6, and glucose concentrations were lower in WH, CA, and WHCA rats than in CO rats. Plasma glucagon-like peptide 1 concentrations were greater in WH than in CA or WHCA rats. The improvements in glucose tolerance were greater in WH than in WHCA rats. The plasma membrane glucose transporter 4 (GLUT4)-to-total GLUT4 ratio in skeletal muscle was greater in CA and WHCA rats than in CO rats; other markers of glucose and energy metabolism in the adipose and cardiac tissues did not differ. In Expt. 2, during 4 conditioning trials, daily food intake was decreased in WH, CA, and WHCA rats by 26-37%, 30-43%, and 23-33%, respectively, compared with CO rats. Preferences for WH and CA rats were 45% and 31% lower, respectively, than those for CO rats, but that for WHCA rats did not differ. CONCLUSION Together, these data demonstrate that in obese rats, whey, casein, and their combination improve energy balance through differential effects on food intake, taste preference, energy expenditure, glucose tolerance, and gut hormone secretion.

['Pezeshki|Adel|A|', 'Fahim|Andrew|A|', 'Chelikani|Prasanth K|PK|http://orcid.org/0000-0002-7300-2918']

2015

31569048

A Nanoparticle-Based Affinity Sensor that Identifies and Selects Highly Cytokine-Secreting Cells.

We developed a universal method termed OnCELISA to detect cytokine secretion from individual cells by applying a capture technology on the cell membrane. OnCELISA uses fluorescent magnetic nanoparticles as assay reporters that enable detection on a single-cell level in microscopy and flow cytometry and fluorimetry in cell ensembles. This system is flexible and can be modified to detect different cytokines from a broad range of cytokine-secreting cells. Using OnCELISA we have been able to select and sort highly cytokine-secreting cells and identify cytokine-secreting expression profiles of different cell populations in vitro and ex vivo. We show that this system can be used for ultrasensitive monitoring of cytokines in the complex biological environment of atherosclerosis that contains multiple cell types. The ability to identify and select cell populations based on their cytokine expression characteristics is valuable in a host of applications that require the monitoring of disease progression.

['Liu|Guozhen|G|', 'Bursill|Christina|C|', 'Cartland|Siân P|SP|', 'Anwer|Ayad G|AG|', 'Parker|Lindsay M|LM|', 'Zhang|Kaixin|K|', 'Feng|Shilun|S|', 'He|Meng|M|', 'Inglis|David W|DW|', 'Kavurma|Mary M|MM|', 'Hutchinson|Mark R|MR|', 'Goldys|Ewa M|EM|']

2019

24718416

Astringency is a trigeminal sensation that involves the activation of G protein-coupled signaling by phenolic compounds.

Astringency is an everyday sensory experience best described as a dry mouthfeel typically elicited by phenol-rich alimentary products like tea and wine. The neural correlates and cellular mechanisms of astringency perception are still not well understood. We explored taste and astringency perception in human subjects to study the contribution of the taste as well as of the trigeminal sensory system to astringency perception. Subjects with either a lesion or lidocaine anesthesia of the Chorda tympani taste nerve showed no impairment of astringency perception. Only anesthesia of both the lingual taste and trigeminal innervation by inferior alveolar nerve block led to a loss of astringency perception. In an in vitro model of trigeminal ganglion neurons of mice, we studied the cellular mechanisms of astringency perception. Primary mouse trigeminal ganglion neurons showed robust responses to 8 out of 19 monomeric phenolic astringent compounds and 8 polymeric red wine polyphenols in Ca(2+) imaging experiments. The activating substances shared one or several galloyl moieties, whereas substances lacking the moiety did not or only weakly stimulate responses. The responses depended on Ca(2+) influx and voltage-gated Ca(2+) channels, but not on transient receptor potential channels. Responses to the phenolic compound epigallocatechin gallate as well as to a polymeric red wine polyphenol were inhibited by the Gαs inactivator suramin, the adenylate cyclase inhibitor SQ, and the cyclic nucleotide-gated channel inhibitor l-cis-diltiazem and displayed sensitivity to blockers of Ca(2+)-activated Cl(-) channels.

['Schöbel|Nicole|N|', 'Radtke|Debbie|D|', 'Kyereme|Jessica|J|', 'Wollmann|Nadine|N|', 'Cichy|Annika|A|', 'Obst|Katja|K|', 'Kallweit|Kerstin|K|', 'Kletke|Olaf|O|', 'Minovi|Amir|A|', 'Dazert|Stefan|S|', 'Wetzel|Christian H|CH|', 'Vogt-Eisele|Angela|A|', 'Gisselmann|Günter|G|', 'Ley|Jakob P|JP|', 'Bartoshuk|Linda M|LM|', 'Spehr|Jennifer|J|', 'Hofmann|Thomas|T|', 'Hatt|Hanns|H|']

2014

27536147

Survival benefit and safety of the combinations of FOLFOXIRI ± bevacizumab versus the combinations of FOLFIRI ± bevacizumab as first-line treatment for unresectable metastatic colorectal cancer: a meta-analysis.

BACKGROUND The survival of patients with metastatic colorectal cancer (mCRC) could be improved with exposure to three active drugs, irinotecan, fluorouracil/leucovorin, and oxaliplatin, irrespective of their sequence. However, only 50%-80% of patients can be exposed to all the three drugs in a sequential strategy with two-drug combinations. We carried out this systematic assessment to compare the survival benefit and safety of FOLFOXIRI (irinotecan, fluorouracil/leucovorin, and oxaliplatin) ± bevacizumab (with or without bevacizumab) versus FOLFIRI (irinotecan and fluorouracil/leucovorin) ± bevacizumab (with or without bevacizumab) as first-line treatment for unresectable mCRC. METHODS PubMed and EMBASE were searched for original articles written in English and published before December 2015. A total of 1,035 patients from three randomized controlled trials were included. RESULTS Our results demonstrated that overall survival (hazard ratio [HR], 0.84; 95% confidence interval [CI], 0.73-0.97), progression-free survival (HR, 0.69; 95% CI, 0.59-0.81), and overall response rate (odds ratio, 1.96; 95% CI, 1.28-2.98) were significantly improved in the FOLFOXIRI ± bevacizumab arm compared to the FOLFIRI ± bevacizumab arm. Significantly higher incidences of neutropenia, anemia, diarrhea, stomatitis, and neuropathy were observed in the FOLFOXIRI ± bevacizumab arm. CONCLUSION Current evidence shows that the combination of FOLFOXIRI ± bevacizumab significantly improves the overall survival, progression-free survival, and overall response rate of patients with mCRC, with an increased but manageable toxicity, compared with the combinations of FOLFIRI ± bevacizumab. The combination of FOLFOXIRI ± bevacizumab should be considered as a treatment option for these patients under the premise of reasonable selection of target population.

['Xu|Wei|W|', 'Kuang|Meng|M|', 'Gong|Yang|Y|', 'Cao|Chunxiang|C|', 'Chen|Jinfei|J|', 'Tang|Cuiju|C|']

2016

31309704

Haploidentical stem cell transplantation with posttransplant cyclophosphamide for refractory systemic juvenile xanthogranuloma.

Juvenile xanthogranuloma (JXG) is a generally benign, self-limited histiocytic disorder, which belongs to non-Langerhans cell histiocytoses (non-LCH). However, systemic JXG can be fatal in rare cases. We present the case of an 11-year-old female with systemic JXG, who experienced repeated vertebral compression fractures and did not fully respond to systemic chemotherapy. Based on its reported efficacy in LCH, the patient underwent human leukocyte antigen-haploidentical hematopoietic stem cell transplantation (HSCT) with posttransplant cyclophosphamide. The patient did not suffer major complications and has not experienced relapse for 13 months since HSCT. HSCT may be a potential treatment option for patients with refractory non-LCH.

['Ito|Jumpei|J|0000-0002-8196-8501', 'Shima|Haruko|H|0000-0003-3432-8832', 'Inoue|Kyohei|K|', 'Yamazaki|Fumito|F|', 'Shimada|Hiroyuki|H|']

2019

28709100

Domestic well locations and populations served in the contiguous U.S.: 1990.

We estimate the location and population served by domestic wells in the contiguous United States in two ways: (1) the "Block Group Method" or BGM, uses data from the 1990 census, and (2) the "Road-Enhanced Method" or REM, refines the locations by using a buffer expansion and shrinkage technique along roadways to define areas where domestic wells exist. The fundamental assumption is that houses (and therefore domestic wells) are located near a named road. The results are presented as two nationally-consistent domestic-well population datasets. While both methods can be considered valid, the REM map is more precise in locating domestic wells; the REM map has a smaller amount of spatial bias (Type 1 and Type 2 errors nearly equal vs biased in Type 1), total error (10.9% vs 23.7%), and distance error (2.0km vs 2.7km), when comparing the REM and BGM maps to a calibration map in California. However, the BGM map is more inclusive of all potential locations for domestic wells. Independent domestic well datasets from the USGS, and the States of MN, NV, and TX show that the BGM captures about 5 to 10% more wells than the REM. One key difference between the BGM and the REM is the mapping of low density areas. The REM reduces areas mapped as low density by 57%, concentrating populations into denser regions. Therefore, if one is trying to capture all of the potential areas of domestic-well usage, then the BGM map may be more applicable. If location is more imperative, then the REM map is better at identifying areas of the landscape with the highest probability of finding a domestic well. Depending on the purpose of a study, a combination of both maps can be used.

['Johnson|Tyler D|TD|', 'Belitz|Kenneth|K|']

2017

31287240

Synergistic effects of depression and obesity on type 2 diabetes incidence in Chinese adults.

BACKGROUND Cross-sectional studies have supported the association among depression, obesity, and type 2 diabetes, but the causality remains controversial in Chinese adults. In this longitudinal study, we evaluated the synergistic effect of depression and obesity on the risk of type 2 diabetes. METHODS This study included 2809 participants randomly selected from the Qingdao Diabetes Prevention Program, and their type 2 diabetes incidence was determined over a follow-up period of 3 years. The WHO 2006 criteria and the Zung Self-Rating Depression Scale score were employed to identify type 2 diabetes and depression at baseline, respectively. Multivariable-adjusted logistic regression was used to evaluate the synergistic effects of depression and obesity indicators on type 2 diabetes, with adjustment for age, sex, family history of diabetes, and other potential risk factors. RESULTS During 3-year follow-up, 316 new incident cases were identified. The relative risk and 95% confidence interval of depression for diabetes incidence was 1.52 (1.05-2.21), after controlling for potential confounders. Sensitivity analysis showed that depression was significantly associated with diabetes incidence in women, younger people, and obese people (1.82 [1.14-2.92], 1.94 [1.25-3.02], and 4.29 [1.44-12.78], respectively]. The synergistic effects of positive depression and body mass index ≥30 kg/m2 on type 2 diabetes incidence were observed, with a synergy index of 5.49 (1.75-17.19). CONCLUSIONS Depression was associated with a 52% increased risk of type 2 diabetes incidence and exerts synergistic effects with obesity on diabetes incidence in Chinese adults. Early identification and intervention for depression and obesity can reduce the risk of diabetes.

['Ning|Feng|F|https://orcid.org/0000-0003-0168-1613', 'Zhang|Dong|D|', 'Xue|Bai|B|', 'Zhang|Lei|L|', 'Zhang|Jintai|J|', 'Zhu|Zhigang|Z|', 'Zhang|Dongfeng|D|', 'Gao|Ruqin|R|', 'Pang|Zengchang|Z|', 'Qiao|Qing|Q|', '|||']

2020

33905821

Exosomal miR-208b related with oxaliplatin resistance promotes Treg expansion in colorectal cancer.

Oxaliplatin resistance is a challenge in the treatment of colorectal cancer (CRC) patients. Regulatory T cells (Tregs) are well known for their immunosuppressive roles, and targeting Tregs is an effective way to improve chemosensitivity. Exosome-delivered microRNA (miRNA) might be used as a potential biomarker for predicting chemosensitivity. However, the relationship between Tregs and exosomal miRNAs remains largely unknown. TaqMan low-density array was performed to screen the differentially expressed serum miRNAs from pooled serum of patients who had FOLFOX treatment. Differential expression was validated using qRT-PCR in individual samples. Exosomes were isolated by sequential differential centrifugation, and they were verified by transmission electron microscopy. The RNA and protein levels were determined by quantitative real-time PCR and western blotting. A mouse xenograft model was adopted to evaluate the correlation between exosome-derived miR-208b and Tregs in vivo. We demonstrated that circulating miR-208b is a non-invasive marker for predicting FOLFOX sensitivity in CRC. miR-208b in colon cancer was secreted by tumor cells in the pattern of exosomes, and oxaliplatin-resistant cells showed the most obvious phenomenon of miR-208b increase. Colon cancer cell-secreted miR-208b was sufficiently delivered into recipient T cells to promote Treg expansion by targeting programmed cell death factor 4 (PDCD4). Furthermore, in vivo studies indicated that Treg expansion mediated by cancer cell-secreted miR-208b resulted in tumor growth and oxaliplatin resistance. Our results demonstrate that tumor-secreted miR-208b promotes Treg expansion by targeting PDCD4, and it may be related to a decrease of oxaliplatin-based chemosensitivity in CRC. These findings highlight a potential role of exosomal miR-208b as a predictive biomarker for oxaliplatin-based therapy response, and they provide a novel target for immunotherapy.

['Ning|Tao|T|', 'Li|Jialu|J|', 'He|Yi|Y|', 'Zhang|Haiyang|H|', 'Wang|Xinyi|X|', 'Deng|Ting|T|', 'Liu|Rui|R|', 'Li|Hongli|H|', 'Bai|Ming|M|', 'Fan|Qian|Q|', 'Zhu|Kegan|K|', 'Ying|Guoguang|G|', 'Ba|Yi|Y|']

2021

29550312

FDG PET/CT for Early Detection and Localization of Left Ventricular Assist Device Infection: Impact on Patient Management and Outcome.

OBJECTIVES The feasibility of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) for the diagnosis of left ventricular assist device (LVAD) infection has been demonstrated. Beyond the diagnoses of LVAD infection, the authors hypothesized that the pattern and site of the infection along its various components may significantly impact clinical management and patient outcome. BACKGROUND In patients with end-stage heart failure, the clinical use of LVAD for destination therapy is on the rise, accompanied by a higher prevalence of infections and serious complications. METHODS FDG PET/CT was performed in 35 heart failure patients with LVAD, 24 with and 11 without clinical suspicion of infection. Microbiology and/or clinical follow-up were used as the final diagnosis standard. Survival rates were compared in patients with and without FDG evidence of infection, and in relation to peripheral (exit wound site or driveline) versus central (cannula or pump) device infection. RESULTS Of 35 patients, 28 (80%) showed metabolic evidence of LVAD infection: 5 limited to the periphery and 23 with extension to the central components of the device. The remaining 7 patients showed no metabolic evidence of infection, which was confirmed by microbiology and clinical follow-up. When CT images were interpreted independently from the FDG PET and clinical information, only 4 of 35 (11%) suggested the possibility of infection. Fourteen of 28 (50%) infected patients died during a mean of 23 months of follow-up after the diagnosis by FDG PET/CT: 12 (86%) with central infection and only 2 with peripheral infection. By contrast, none of the 7 (0%) noninfected patients died (p = 0.03). CONCLUSIONS FDG PET/CT is a useful technique for identifying LVAD infection and determining the site and pattern of the infection. The latter has clinical management and patient outcome implications.

['Kim|Jongho|J|', 'Feller|Erika D|ED|', 'Chen|Wengen|W|', 'Liang|Yuanyuan|Y|', 'Dilsizian|Vasken|V|']

2019

33152986

Dichotic listening is associated with phonological awareness in Australian aboriginal children with otitis media: A remote community-based study.

OBJECTIVE Recent literature has highlighted a link between hearing loss as a result of otitis media in the early years of life and impacted binaural processing skills in later childhood. Such findings are of particular relevance to Indigenous Australian children, who tend to experience otitis media earlier in life and for longer periods than their non-Indigenous counterparts. There is also growing interest in the effects of reduced auditory processing ability on a child's early learning of language and, specifically, on phonological awareness that contributes to word reading skills. The aim of the present study was to determine the association between hearing thresholds, dichotic listening skills and phonological awareness in children with pervasive otitis media (OM) from remote Indigenous communities of Australia who generally do not speak English as a first language. METHODS Participants included one hundred and one children between the ages of 4.8-7.9 years (mean 6.1 years) from three separate remote Northern Territory communities. Evaluations included otoscopy, air conduction PTA, and tympanometry. All children were also assessed on the Dichotic Digits difference test (DDdT) and the Foundations of Early Literacy Assessment (FELA), assessing children's dichotic listening and phonological awareness respectively. RESULTS The results showed that 56% of the children had middle ear dysfunctions (type B and type C on tympanometry results) in at least one ear on the day. Partial correlation showed a significant correlation, between dichotic scores and FELA with age as covariate (r = 0.45, p < 0.001). One way ANOVA showed females exhibited a significantly higher performance compared to males on FELA [F (1, 99) = 5.47, p = 0.021]. The overall regression model was found to be significant in predicting total FELA scores [F (7, 77) = 7.56, p < 0.0005]. Age and gender as well as dichotic listening scores explain 40.7% of the variance. CONCLUSIONS The results reinforce the importance of managing the ear health of Indigenous children, clarifying the impact this has on listening and phonological awareness. These findings highlight the importance of evaluating children's listening abilities, and how poor listening can impact phonological awareness. The findings have important implications for ensuring optimal listening and learning conditions in schools in remote NT communities.

['Sharma|Mridula|M|', 'Darke|Amelia|A|', 'Wigglesworth|Gillian|G|', 'Demuth|Katherine|K|']

2020

24444550

Utility of real-time three-dimensional echocardiography for Duchenne muscular dystrophy with echocardiographic limitations.

Duchenne muscular dystrophy (DMD) is strongly associated with a unique form of dilated cardiomyopathy. Cardiac complications are the leading cause of death in DMD; thus, longitudinal assessments and early intervention for cardiac dysfunction are necessary to improve prognosis. Two-dimensional echocardiography, which is routinely used for cardiac assessment, has some limitations for quantitative analyses in DMD patients with thoracic deformities and regional wall motion abnormalities in the left ventricle. Recently, real-time three-dimensional echocardiography has emerged as a feasible tool for cardiac assessment in various cardiac diseases. The aim of this study was to examine the utility of this technology in DMD. We evaluated left ventricular ejection fraction (LVEF), a major parameter of left ventricular function, in 17 male DMD patients. LVEF values measured by real-time three-dimensional echocardiography were compared with those determined by two established nuclear cardiology methods: "the first-pass method of radionuclide angiocardiography" and "quantitative electrocardiogram-gated single-photon emission computed tomography". A good correlation was observed for LVEF values, particularly between real-time three-dimensional echocardiography and "the first-pass method of radionuclide angiocardiography" (r=0.90, p<0.05). Thus, real-time three-dimensional echocardiography can provide an accurate measurement of LVEF in DMD patients with echocardiographic limitations.

['Tsuburaya|Rie S|RS|', 'Uchizumi|Hiroshi|H|', 'Ueda|Michio|M|', 'Demura|Yutaka|Y|', 'Mukaida|Souichi|S|', 'Sudou|Shinji|S|', 'Irahara|Kaori|K|', 'Sakai|Naoko|N|', 'Shiraishi|Kazuhiro|K|']

2014

31612333

Changing Childbearing Norms During an Era of ART Expansion in Malawi, 2009 to 2015.

Community norms shape the childbearing goals and behaviors of persons living with HIV/AIDS (PLWHA) but little is known about how norms around HIV-positive childbearing have changed with expanded access to antiretroviral treatment (ART). We analyze data collected in 2009 and 2015 by the Tsogolo la Thanzi (TLT) project-a longitudinal, population-based study of young adults in southern Malawi. Respondents were asked about the acceptability of childbearing using vignettes that varied a hypothetical couple's HIV status and number of children. We assess mean differences in support for childbearing over time and by respondent gender and serostatus. The acceptability of childbearing for PLWHA increased dramatically over the 6-year period; however, support levels varied based on a couple's current number of children and whether they were seropositive concordant or discordant. Differences in attitudes by gender and HIV status diminished over time, pointing to a population-level convergence in norms about acceptable childbearing.

['Garver|Sarah|S|http://orcid.org/0000-0001-9850-4685', 'Trinitapoli|Jenny|J|', 'Yeatman|Sara|S|']

2020

28342027

A comparative evaluation of Ac225 vs Bi213 as therapeutic radioisotopes for targeted alpha therapy for cancer.

The Ac225:Bi213 generator is the mainstay for preclinical and clinical studies of targeted alpha therapy for cancer. Both Ac225 (four alpha decays) and Bi213 (one alpha decay) are being used to label targeting vectors to form the alpha immunoconjugate for cancer therapy. This paper considers the radiobiological and economic aspects of Ac225 vs Bi213 as the preferred radioisotope for preclinical and clinical TAT. The in vitro and in vivo evidence and the role of DNA repair processes is examined. The maximum tolerance dose and therapeutic gain are endpoints for comparison. Ac225 has the higher therapeutic gain, when normalised to equal alpha production. However, the slow repair of double strand breaks reduces this advantage. Comparisons are made for the specific energy deposition in targeted and non-targeted cells, for endothelial cells by direct or indirect targeting, the need for sparing agents to save critical organs and cost considerations for preclinical and clinical trials and clinical use. Overall, Ac225 is found to have the better or equal performance to Bi213 at a much lower cost.

['Allen|Barry J|BJ|']

2017

30772279

General and abdominal adiposity and the risk of Parkinson's disease: A prospective cohort study.

INTRODUCTION Due to demographic change, an increase in the frequency of Parkinson's disease (PD) patients is expected in the future and, thus, the identification of modifiable risk factors is urgently needed. We aimed to examine the associations of body mass index (BMI) and waist circumference (WC) with incident PD. METHODS In 13 of the 23 centers of the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a total of 734 incident cases of PD were identified between 1992 and 2012 with a mean follow-up of 12 years. Cox proportional hazards regression was used to calculate hazard ratios (HR) with 95% confidence intervals (CI). We modelled anthropometric variables as continuous and categorical exposures and performed subgroup analyses by potential effect modifiers including sex and smoking. RESULTS We found no association between BMI, WC and incident PD, neither among men nor among women. Among never and former smokers, BMI and waist circumference were also not associated with PD risk. For male smokers, however, we observed a statistically significant inverse association between BMI and PD risk (HR 0.51, 95%CI: 0.30, 0.84) and the opposite for women, i.e. a significant direct association of BMI (HR 1.79, 95%CI: 1.04, 3.08) and waist circumference (HR 1.64, 95%CI: 1.03, 2.61) with risk of PD. CONCLUSION Our data revealed no association between excess weight and PD risk but a possible interaction between anthropometry, sex and smoking.

['Riso|Lukas|L|', 'Kaaks|Rudolf|R|', 'Kühn|Tilman|T|', 'Sookthai|Disorn|D|', 'Forsgren|Lars|L|', 'Trupp|Miles|M|', 'Trichopoulou|Antonia|A|', 'La Vecchia|Carlo|C|', 'Karakatsani|Anna|A|', 'Gavrila|Diana|D|', 'Ferrari|Pietro|P|', 'Freisling|Heinz|H|', 'Petersson|Jesper|J|', 'Lewan|Susanne|S|', 'Vermeulen|Roel Ch|RC|', 'Panico|Salvatore|S|', 'Masala|Giovanna|G|', 'Ardanaz|Eva|E|', 'Krogh|Vittorio|V|', 'Perneczky|Robert|R|', 'Middleton|Lefkos T|LT|', 'Mokoroa|Olatz|O|', 'Sacerdote|Carlotta|C|', 'Sieri|Sabrina|S|', 'Hayat|Shabina A|SA|', 'Brayne|Carol|C|', 'Riboli|Elio|E|', 'Vineis|Paolo|P|', 'Gallo|Valentina|V|', 'Katzke|Verena A|VA|']

2019

28442919

Gastric cancer, nutritional status, and outcome.

BACKGROUND We aim to investigate the prognostic value of several nutrition-based indices, including the prognostic nutritional index (PNI), performance status, body mass index, serum albumin, and preoperative body weight loss in patients with gastric cancer (GC). MATERIALS AND METHODS We retrospectively analyzed the records of 1,330 consecutive patients with GC undergoing curative surgery between October 2000 and September 2012. The relationship between nutrition-based indices and overall survival (OS) was examined using Kaplan-Meier analysis and Cox regression model. RESULTS Following multivariate analysis, the PNI and preoperative body weight loss were the only nutritional-based indices independently associated with OS (hazard ratio [HR]: 1.356, 95% confidence interval [CI]: 1.051-1.748, P=0.019; HR: 1.152, 95% CI: 1.014-1.310, P=0.030, retrospectively). In stage-stratified analysis, multivariate analysis revealed that preoperative body weight loss was identified as an independent prognostic factor only in patients with stage III GC (HR: 1.223, 95% CI: 1.065-1.405, P=0.004), while the prognostic significance of PNI was not significant (all P>0.05). In patients with stage III GC, preoperative body weight loss stratified 5-year OS from 41.1% to 26.5%. When stratified by adjuvant chemotherapy, the prognostic significance of preoperative body weight loss was maintained in patients treated with surgery plus adjuvant chemotherapy and in patients treated with surgery alone (P<0.001; P=0.003). CONCLUSION Preoperative body weight loss is an independent prognostic factor for OS in patients with GC, especially in stage III disease. Preoperative body weight loss appears to be a superior predictor of outcome compared with other established nutrition-based indices.

['Liu|Xuechao|X|', 'Qiu|Haibo|H|', 'Kong|Pengfei|P|', 'Zhou|Zhiwei|Z|', 'Sun|Xiaowei|X|']

2017

29346008

Follow-Up Care Provider Preferences of Adolescent and Young Adult Cancer Survivors.

PURPOSE To explore the experiences and perspectives of adolescent and young adult (AYA) cancer survivors regarding patient-provider relationships and their preferences surrounding type of healthcare provider for follow-up care. METHODS We recruited AYA cancer survivors who were diagnosed between the ages of 15 and 39 using the Utah Cancer Registry. Twenty-eight survivors participated in six focus groups held between March and May of 2015 in Salt Lake City and St. George, Utah. This analysis focuses on how survivors' preferences about type of healthcare provider may influence their transition into, and utilization of, follow-up care. RESULTS On average, survivors were 6.3 (standard deviation = 1.7) years from their cancer diagnosis. A majority of survivors expressed a desire not to transition to a new provider and preferred continuing to see their oncologist for follow-up care. For these survivors, this was due to already having a close relationship with their oncologist and because they trusted their provider's knowledge about cancer and how to handle late effects. However, survivors placed emphasis on being comfortable with their healthcare provider, regardless of provider type. CONCLUSIONS Our findings demonstrate the importance of formalizing provider transitions and roles after cancer therapy to improve patient comfort with new providers. By understanding the complexities of the transition from active cancer treatment to follow-up care for AYA survivors, these findings can inform programs undertaking post-care educational activities to ensure a seamless transition into survivorship care. Survivorship care plans can facilitate these transitions and improve patient confidence in follow-up care.

['Ramsay|Joemy M|JM|', 'Mann|Karely|K|', 'Kaul|Sapna|S|', 'Zamora|Eduardo R|ER|', 'Smits-Seemann|Rochelle R|RR|', 'Kirchhoff|Anne C|AC|']

2018

23746052

Evaluating the predictivity of virtual screening for ABL kinase inhibitors to hinder drug resistance.

Virtual screening methods are now widely used in early stages of drug discovery, aiming to rank potential inhibitors. However, any practical ligand set (of active or inactive compounds) chosen for deriving new virtual screening approaches cannot fully represent all relevant chemical space for potential new compounds. In this study, we have taken a retrospective approach to evaluate virtual screening methods for the leukemia target kinase ABL1 and its drug-resistant mutant ABL1-T315I. 'Dual active' inhibitors against both targets were grouped together with inactive ligands chosen from different decoy sets and tested with virtual screening approaches with and without explicit use of target structures (docking). We show how various scoring functions and choice of inactive ligand sets influence overall and early enrichment of the libraries. Although ligand-based methods, for example principal component analyses of chemical properties, can distinguish some decoy sets from active compounds, the addition of target structural information via docking improves enrichment, and explicit consideration of multiple target conformations (i.e. types I and II) achieves best enrichment of active versus inactive ligands, even without assuming knowledge of the binding mode. We believe that this study can be extended to other therapeutically important kinases in prospective virtual screening studies.

['Gani|Osman A B S M|OA|', 'Narayanan|Dilip|D|', 'Engh|Richard A|RA|']

2013

26278455

Exploding Nitromethane in Silico, in Real Time.

Nitromethane (NM) is widely applied in chemical technology as a solvent for extraction, cleaning, and chemical synthesis. NM was considered safe for a long time, until a railroad tanker car exploded in 1958. We investigate the detonation kinetics and explosion reaction mechanisms in a variety of systems consisting of NM, molecular oxygen, and water vapor. Reactive molecular dynamics allows us to simulate reactions in time-domain, as they occur in real life. High polarity of the NM molecule is shown to play a key role, driving the first exothermic step of the reaction. Rapid temperature and pressure growth stimulate the subsequent reaction steps. Oxygen is important for faster oxidation, whereas its optimal concentration is in agreement with the proposed reaction mechanism. Addition of water (50 mol %) inhibits detonation; however, water does not prevent detonation entirely. The reported results provide important insights for improving applications of NM and preserving the safety of industrial processes.

['Fileti|Eudes Eterno|EE|', 'Chaban|Vitaly V|VV|', 'Prezhdo|Oleg V|OV|']

2014

29375796

Interspecies introgressive hybridization in spiny frogs Quasipaa (Family Dicroglossidae) revealed by analyses on multiple mitochondrial and nuclear genes.

Introgression may lead to discordant patterns of variation among loci and traits. For example, previous phylogeographic studies on the genus Quasipaa detected signs of genetic introgression from genetically and morphologically divergent Quasipaa shini or Quasipaa spinosa. In this study, we used mitochondrial and nuclear DNA sequence data to verify the widespread introgressive hybridization in the closely related species of the genus Quasipaa, evaluate the level of genetic diversity, and reveal the formation mechanism of introgressive hybridization. In Longsheng, Guangxi Province, signs of asymmetrical nuclear introgression were detected between Quasipaa boulengeri and Q. shini. Unidirectional mitochondrial introgression was revealed from Q. spinosa to Q. shini. By contrast, bidirectional mitochondrial gene introgression was detected between Q. spinosa and Q. shini in Lushan, Jiangxi Province. Our study also detected ancient hybridizations between a female Q. spinosa and a male Q. jiulongensis in Zhejiang Province. Analyses on mitochondrial and nuclear genes verified three candidate cryptic species in Q. spinosa, and a cryptic species may also exist in Q. boulengeri. However, no evidence of introgressive hybridization was found between Q. spinosa and Q. boulengeri. Quasipaa exilispinosa from all the sampling localities appeared to be deeply divergent from other communities. Our results suggest widespread introgressive hybridization in closely related species of Quasipaa and provide a fundamental basis for illumination of the forming mechanism of introgressive hybridization, classification of species, and biodiversity assessment in Quasipaa.

['Zhang|Qi-Peng|QP|0000-0003-1522-0914', 'Hu|Wen-Fang|WF|', 'Zhou|Ting-Ting|TT|', 'Kong|Shen-Shen|SS|', 'Liu|Zhi-Fang|ZF|', 'Zheng|Rong-Quan|RQ|']

2018

32684452

Between-cow variation in the components of feed efficiency.

A meta-analysis based on an individual-cow data set was conducted to investigate between-cow variations in the components and measurements of feed efficiency (FE) and to explore the associations among these components. Data were taken from 31 chamber studies, consisting of a total of 841 cow/period observations. The experimental diets were based on grass or corn silages, fresh grass, or a mixture of fresh grass and straw, with cereal grains or by-products as energy supplements, and soybean or canola meal as protein supplements. The average forage-to-concentrate ratio across all diets on a dry matter basis was 56:44. Variance component and repeatability estimates of FE measurements and components were determined using diet, period, and cow within experiment as random effects in mixed procedures of SAS (SAS Institute Inc., Cary, NC). The between-cow coefficient of variation (CV) in gross energy intake (GE; CV = 0.10) and milk energy (El) output as a proportion of GE (El/GE; CV = 0.084) were the largest among all component traits. Similarly, the highest repeatability estimates (≥0.50) were observed for these 2 components. However, the between-cow CV in digestibility (DE/GE), metabolizability [metabolizable energy (ME)/GE], methane yield (CH4E/GE), proportional urinary energy output (UE/GE), and heat production (HP/GE), as well as the efficiency of ME use for lactation (kl), were rather small. The least repeatable component of FE was UE/GE. For FE measurements, the between-cow CV in residual energy-corrected milk (RECM) was larger than for residual feed intake (RFI), suggesting a greater possibility for genetic gain in RECM than in RFI. A high DE/GE was associated with increased CH4E/GE (r = 0.24), HP/GE (r = 0.12), ME/GE (r = 0. 91), energy balance as a proportion of GE (EB/GE; r = 0.35), and kl (r = 0.10). However, no correlation between DE/GE and GE intake or UE/GE was observed. Increased proportional milk energy adjusted to zero energy balance (El(0)/GE) was associated with increases in DE/GE, ME/GE, EB/GE, and kl but decreases in UE/GE, CH4E/GE, and HP/GE, with no effect on GE intake. In conclusion, several mechanisms are involved in the observed differences in FE among dairy cows, and reducing CH4E yield (CH4E/GE) may inadvertently result in reduced GE digestibility. However, the selection of dairy cows with improved energy utilization efficiencies offers an effective approach to lower enteric CH4 emissions.

['Guinguina|A|A|', 'Yan|T|T|', 'Lund|P|P|', 'Bayat|A R|AR|', 'Hellwing|A L F|ALF|', 'Huhtanen|P|P|']

2020

32823395

Human immunodeficiency virus and intraocular inflammation in the era of highly active anti retroviral therapy - An update.

Intraocular inflammation in patients with human immunodeficiency virus (HIV) infection is commonly due to infectious uveitis. Ocular lesions due to opportunistic infections (OI) are the most common and have been described extensively in the pre highly active antiretroviral therapy (HAART) era. Many eye lesions were classified as acquired immunodeficiency syndrome (AIDS) defining illnesses. HAART-associated improvement in immunity of the individual has changed the pattern of incidence of these hitherto reported known lesions leading to a marked reduction in the occurrence of ocular OI. Newer ocular lesions and newer ocular manifestations of known agents have been noted. Immune recovery uveitis (IRU), the new menace, which occurs as part of immune recovery inflammatory syndrome (IRIS) in the eye, can present with significant ocular inflammation and can pose a diagnostic and therapeutic challenge. Balancing the treatment of inflammation with the risk of reactivation of OI is a task by itself. Ocular involvement in the HAART era can be due to the adverse effects of some systemic drugs used in the management of HIV/AIDS. Drug-associated retinal toxicity and other ocular side effects are being increasingly reported. In this review, we discuss the ocular manifestations in HIV patients and its varied presentations following the introduction of HAART, drug-associated lesions, and the current treatment guidelines.

['Sudharshan|Sridharan|S|', 'Nair|Nivedita|N|', 'Curi|Andre|A|', 'Banker|Alay|A|', 'Kempen|John H|JH|']

2020

26558047

Improving the compliance of the recurrent stone-former.

OBJECTIVE To provide an overview of aspects of compliance by the recurrent stone-former, and to give recommendations for its improvement. About half of all stone-formers have one recurrence during their lifetime. To avoid recurrent stone formation it is necessary to use metaphylaxis, based on individual risks. However, all general and specific efforts are meaningless if patients are not willing or are incapable of following the proposed therapy in the long-term. METHODS PubMed was searched for articles on urolithiasis, metaphylaxis, compliance and adherence, and relevant papers were reviewed. RESULTS Compliance is a multidimensional phenomenon which is determined by the interaction of different factors, i.e. social and economic, therapy-related, patient-related, condition-related, and healthcare team and system-related factors. Subsequently there are several different interventional possibilities at the urologist's disposal to effect better compliance by the patient. CONCLUSIONS The treatment and metaphylaxis of the recurrent stone-former present a particularly pertinent challenge. Patient compliance has an immense influence on the success of the treatment with respect to metaphylaxis, which is the decisive factor for preventing stone recurrence.

['Fritsche|Hans-Martin|HM|', 'Dötzer|Kristina|K|']

2012

34637051

Clinical Translation of Neutrophil Imaging and Its Role in Cancer.

Neutrophils are the first line of defense against pathogens and abnormal cells. They regulate many biological processes such as infections and inflammation. Increasing evidence demonstrated a role for neutrophils in cancer, where different subpopulations have been found to possess both pro- or anti-tumorigenic functions in the tumor microenvironment. In this review, we discuss the phenotypic and functional diversity of neutrophils in cancer, their prognostic significance, and therapeutic relevance in human and preclinical models. Molecular imaging methods are increasingly used to probe neutrophil biology in vivo, as well as the cellular changes that occur during tumor progression and over the course of treatment. This review will discuss the role of neutrophil imaging in oncology and the lessons that can be drawn from imaging in infectious diseases and inflammatory disorders. The major factors to be considered when developing imaging techniques and biomarkers for neutrophils in cancer are reviewed. Finally, the potential clinical applications and the limitations of each method are discussed, as well as the challenges for future clinical translation.

['Lau|Doreen|D|', 'Lechermann|Laura M|LM|', 'Gallagher|Ferdia A|FA|']

2021