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31617132

Botulinum Toxin A Improves Symptoms of Gastroparesis.

BACKGROUND AND AIMS Pyloric injections of botulinum toxin A (BoNT/A) have shown benefit in open-label studies for patients with gastroparesis but not in randomized trials. We sought to examine the effectiveness of BoNT/A injections in a prospective open-label trial of patients with gastroparesis to assess specific symptom improvements over the course of 6 months. We also wanted to determine if specific biochemical measures including creatinine kinase, lactate dehydrogenase, aldolase, and C-reactive protein suggesting muscular injection could be used to predict successful response to pyloric injections of BoNT/A. METHODS Patients with gastroparesis undergoing pyloric BoNT/A injections for the treatment of symptomatic gastroparesis were enrolled. The patients completed the Gastroparesis Cardinal Symptom Index (GCSI) at the initial encounter and at 1, 3, and 6 months. Blood samples were collected before and 1 h after BoNT/A therapy. RESULTS We enrolled 34 patients for serum analysis of which 25 patients were available for symptom follow-up. Sixty-four percent of patients had an improvement in symptoms at 1 month. Patients with improved GCSI total score at 1 month had an improvement in most individual symptoms evaluated. For patients that improved at 1 month, this improvement often extended up to 6 months (p = 0.04). Serum measures studied did not correlate with clinical outcomes. CONCLUSIONS BoNT/A therapy to the pylorus provided symptomatic improvement at 1 month in 64% of patients. For those patients initially responding, the improvement can last out to 6 months. The biochemical markers did not serve to predict the outcome of injections.

['Reichenbach|Zachary Wilmer|ZW|0000-0003-4907-3502', 'Stanek|Steven|S|', 'Patel|Shyam|S|', 'Ward|Sara Jane|SJ|', 'Malik|Zubair|Z|', 'Parkman|Henry P|HP|', 'Schey|Ron|R|']

2020

28984411

Foliar application of benzovindiflupyr shows non-fungicidal effects in wheat plants.

BACKGROUND The fungicide benzovindiflupyr belongs to the class of succinate dehydrogenase inhibitors (SDHIs). Certain SDHIs have shown plant physiological effects, so-called secondary effects, that appeared to be related to the plant water status. Therefore, the effect of benzovindiflupyr on transpiration of leaves and whole wheat plants was studied under controlled conditions. Furthermore, wheat yield trials under controlled and natural drought stress in the field were conducted. RESULTS Transpiration of detached wheat leaves was reduced by benzovindiflupyr in a dose-dependent manner. Similarly, whole-plant transpiration decreased for several days following application of this fungicide. In 16 field trials under drought stress conditions that were classified as disease-free, treatment of wheat plants at the flag leaf stage or at heading with benzovindiflupyr showed a grain yield increase (+5.2%; P ≤ 0.01) that was partially attributed to an increased thousand-grain weight. CONCLUSIONS Water saving during pre-anthesis as a result of benzovindiflupyr application may be associated with better seed setting and filling under dry field conditions in wheat. The results of this research provide new insights into secondary effects of SDHIs that lead directly to yield improvements. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

['Kuznetsov|Dmitry|D|', 'Cazenave|Alexandre Brice|AB|http://orcid.org/0000-0002-9965-4762', 'Rambach|Odile|O|', 'Camblin|Philippe|P|', 'Nina|Mafalda|M|', 'Leipner|Jörg|J|http://orcid.org/0000-0002-8523-9656']

2018

28726116

A computationally efficient method for hand-eye calibration.

PURPOSE Surgical robots with cooperative control and semiautonomous features have shown increasing clinical potential, particularly for repetitive tasks under imaging and vision guidance. Effective performance of an autonomous task requires accurate hand-eye calibration so that the transformation between the robot coordinate frame and the camera coordinates is well defined. In practice, due to changes in surgical instruments, online hand-eye calibration must be performed regularly. In order to ensure seamless execution of the surgical procedure without affecting the normal surgical workflow, it is important to derive fast and efficient hand-eye calibration methods. METHODS We present a computationally efficient iterative method for hand-eye calibration. In this method, dual quaternion is introduced to represent the rigid transformation, and a two-step iterative method is proposed to recover the real and dual parts of the dual quaternion simultaneously, and thus the estimation of rotation and translation of the transformation. RESULTS The proposed method was applied to determine the rigid transformation between the stereo laparoscope and the robot manipulator. Promising experimental and simulation results have shown significant convergence speed improvement to 3 iterations from larger than 30 with regard to standard optimization method, which illustrates the effectiveness and efficiency of the proposed method.

['Zhang|Zhiqiang|Z|http://orcid.org/0000-0003-0204-3867', 'Zhang|Lin|L|', 'Yang|Guang-Zhong|GZ|']

2017

31587495

Novel and Bizarre Abnormalities of the Tooth Row in Side-Blotched Lizards (Uta) and Rock Lizards (Petrosaurus).

Multiple tooth rows along the dentary or maxilla are present in many bony and cartilaginous fishes but occur infrequently in amniotes. Although two partially overlapping rows of teeth or a few doubled tooth positions were both previously reported in extant and extinct lizards, multiple rows of teeth across the entire dental or maxillary shelf were not previously documented in any lizard taxon. Here, we report one specimen of the side-blotched lizard Uta stansburiana and two specimens of the rock lizard Petrosaurus mearnsi that have two or more marginal tooth rows that overlap for most of the dental shelf. We also describe several other phrynosomatid lizard specimens with one or two doubled tooth positions per marginal tooth-bearing skeletal element. We examined 520 total specimens of pleurodont iguanian lizards and verified that aberrant tooth row and tooth position morphologies were almost exclusively present in phrynosomatid lizards. We hypothesize that developmental irregularities in the number of odontogenic bands or in the function of zones of inhibition may have resulted in the observed tooth row abnormalities. The expression of multiple tooth rows or doubled tooth positions may be phylogenetically informative morphologies of phrynosomatid lizards. This bears further investigation from developmental, genetic, ecological, and phylogenetic perspectives. Anat Rec, 2019. © 2019 American Association for Anatomy Anat Rec, 303:2014-2025, 2020. © 2019 American Association for Anatomy.

['Scarpetta|Simon G|SG|0000-0003-0976-9337', 'Bell|Christopher J|CJ|']

2020

33796420

A Rare Case of Tibial Intraneural Ganglion Cyst Arising From the Tibiofibular Joint.

Intraneural ganglion cysts are a rare occurrence. They are most commonly found originating from the common peroneal nerve but are also frequently reported on the radial, ulnar, median, sciatic, tibial, and posterior interosseous nerves. A typical clinical presentation is posterior knee and calf pain resulting from tibial neuropathy with preferential degeneration of the popliteus muscle. Symptoms include pain, paresthesias, and decreased strength that originates in the knee and commonly extends to the plantar surface of the foot. These findings can be mistaken for lumbar neuropathies and compression of the sacral nerve roots. Differential diagnosis includes peripheral nerve sheath tumors, Baker's cysts, extraneural ganglion cysts, and atypical vascular or lymphatic malformations. In this case report, the patient was a 61-year-old male, previously in good health, who presented with progressive pain in his medial left hamstring as well as weakness in left foot plantar flexion and paresthesias in the plantar aspect of his left foot. He first noticed impairments with his ability to push off with his left foot when running. His electromyogram (EMG) was abnormal and subsequent MRI of the left leg showed a complex intraneural ganglion cyst arising from the tibiofibular joint and ascending into the tibial nerve. He underwent indirect decompression through joint resection. Unfortunately, he did not have clinical improvement on one-year follow-up. Overall, symptomatic treatment of intraneural ganglion cyst includes decompression, surgical excision, or minimally invasive decompression by percutaneous aspiration of the ganglion under ultrasound guidance.

['Mayer|Savannah L|SL|', 'Grewal|Jagmeet S|JS|', 'Gloe|Tyler|T|', 'Khasho|Catherine A|CA|', 'Harder|Steven|S|']

2021

30359185

Microbial Transplantation With Human Gut Commensals Containing CutC Is Sufficient to Transmit Enhanced Platelet Reactivity and Thrombosis Potential.

RATIONALE Gut microbes influence cardiovascular disease and thrombosis risks through the production of trimethylamine N-oxide (TMAO). Microbiota-dependent generation of trimethylamine (TMA)-the precursor to TMAO-is rate limiting in the metaorganismal TMAO pathway in most humans and is catalyzed by several distinct microbial choline TMA-lyases, including the proteins encoded by the cutC/D (choline utilization C/D) genes in multiple human commensals. OBJECTIVE Direct demonstration that the gut microbial cutC gene is sufficient to transmit enhanced platelet reactivity and thrombosis potential in a host via TMA/TMAO generation has not yet been reported. METHODS AND RESULTS Herein, we use gnotobiotic mice and a series of microbial colonization studies to show that microbial cutC-dependent TMA/TMAO production is sufficient to transmit heightened platelet reactivity and thrombosis potential in a host. Specifically, we examine in vivo thrombosis potential employing germ-free mice colonized with either high TMA-producing stable human fecal polymcrobial communities or a defined CutC-deficient background microbial community coupled with a CutC-expressing human commensal±genetic disruption of its cutC gene (ie, Clostridium sporogenes Δ cutC). CONCLUSIONS Collectively, these studies point to the microbial choline TMA-lyase pathway as a rational molecular target for the treatment of atherothrombotic heart disease.

['Skye|Sarah M|SM|', 'Zhu|Weifei|W|', 'Romano|Kymberleigh A|KA|', 'Guo|Chun-Jun|CJ|', 'Wang|Zeneng|Z|', 'Jia|Xun|X|', 'Kirsop|Jennifer|J|', 'Haag|Bridget|B|', 'Lang|Jennifer M|JM|', 'DiDonato|Joseph A|JA|', 'Tang|W H Wilson|WHW|', 'Lusis|Aldons J|AJ|', 'Rey|Federico E|FE|', 'Fischbach|Michael A|MA|', 'Hazen|Stanley L|SL|']

2018

28054281

A case of diffuse cavernous hemangioma of the appendix: laparoscopic surgery can facilitate diagnosis and treatment.

BACKGROUND A cavenous hemangioma of the appendix (CHA) is rare. The clinical pathophysiology and adequate management of a CHA have not been sufficiently explained since reports on CHA are scarce. CASE PRESENTATION A 56-year-old woman presented with chronic right lower quadrant pain. Abdominal contrast-enhanced computed tomography revealed a thickened appendix (1.5 cm in diameter) and some focal calcifications in the appendiceal wall. No acute inflammatory signs were visible around the appendix. For diagnosis and treatment, we performed a laparoscopic surgery. Intraoperative findings included purple granular lesions that were spread diffusely along the surface of the appendix. Since these lesions were spread to the terminal ileum, laparoscopic ileocecal resection was performed. Upon macroscopic inspection, purple-colored, raspberry-like lesions were found diffusely on the serosal surface of the appendix. No lesions were found on the mucosal surface. Hematoxylin and eosin staining indicated the presence of blood-filled sinus-like spaces largely in the subserosal layer. Immunohistochemistry analysis indicated that CD34-positive cells lined these spaces. Given these findings, we diagnosed the patient with a diffuse cavernous vascular malformation of the appendix. CONCLUSIONS CHA is difficult to diagnose. A laparoscopic approach may be useful for both the diagnosis and treatment of the disease.

['Takagi|Chisato|C|', 'Yamafuji|Kazuo|K|', 'Takahashi|Hidena|H|', 'Asami|Atsunori|A|', 'Takeshima|Kaoru|K|', 'Baba|Hideo|H|', 'Okamoto|Nobuhiko|N|', 'Kubochi|Kiyoshi|K|']

2017

28986775

Timeline metastatic progression: in the wake of the « seed and soil » theory.

Little is known about the natural history of cancer and its evolution to metastasis. Paget was the first to postulate the important role played by microenvironment in metastasis progression. Since, the concept of his "seed and soil" theory has been supported and confirmed. Understanding the chronology and natural course that underlie metastasis is mandatory to deepen this concept and to progress in the development of novel therapeutic strategies. A total of 413 patients who underwent treatment for brain metastasis (2013-2016) were included. The identification of previous and newly diagnosed metastasis was made during the clinical and imaging follow-up. We identified 910 metastases in our series. The 2-, 5-, and 10-year survival estimates were 80% (SD 2), 59.1% (3), and 36% (4), respectively. The median time for first metastasis, referred as metastasis-free survival (MFS) was 15.2 months (SD 1.47). MFS were determined for each metastasis location and were as follows: 7.2 months (SD 8.0) for bone, adrenal 8.4 months (SD 9.4) for adrenal, 13.2 months (SD 1.7) for brain, 14.6 months (SD 5.4) for liver, 25.7 months (SD 11.7) for pleura, 27.7 months (SD 15.9) for peritoneum, 29.8 months (SD 7.2) for spine, 30.2 months (SD 5.2) for lungs, and 54.2 months (SD 12.4) for skin (p < 0.009 log rank). We identified a metastatic timeline process for breast cancer (p < 0.0001 log rank (Mantel-Cox)) and furthermore according to breast subtype cancer (p < 0.0001). We suggest that in addition to Paget's theory, a timeline and a natural history of metastasis exist in patients with cancer. We suppose that some, but not all, primary cancers follow chronological and scheduled metastatic processes to invade organs.

['Amelot|Aymeric|A|http://orcid.org/0000-0003-3659-291X', 'Terrier|Louis-Marie|LM|', 'Mazeron|Jean-Jacques|JJ|', 'Valery|Charles-Ambroise|CA|', 'Cornu|Philippe|P|', 'Carpentier|Alexandre|A|', 'Leveque|Marc|M|']

2017

30724384

A comparative study for detecting CYP3A induction by CYP3A probe drugs and endogenous markers in cynomolgus monkeys.

CYP3A probe drugs such as midazolam and endogenous markers, and plasma 4β-hydroxycholesterol (4β-OHC) and urinary 6β-hydroxycortisol-to-cortisol ratios (6β-OHC/C) have been used as markers of CYP3A induction in cynomolgus monkeys, as with humans. However, there is limited information on their sensitivity and ability to detect CYP3A induction, as most studies were evaluated only at a high dose of the inducer, rifampicin (RIF; 20 mg/kg). In the present study, the CYP3A induction by RIF over a range doses of 0.2, 2 and 20 mg/kg (n = 4) was examined using CYP3A probe drugs (midazolam, triazolam and alprazolam) and the plasma and urinary endogenous CYP3A markers (4β-OHC and 6β-OHC/C). The sensitivity and relationship for detecting CYP3A induction was compared among the markers. Four days repeated oral administration of rifampicin to cynomolgus monkeys reduced the area under the plasma concentration-time curve of all CYP3A probe drugs in a rifampicin dose-dependent manner. Although the endogenous CYP3A markers (4β-OHC and 6β-OHC/C) were also changed for the middle (2 mg/kg) and high (20 mg/kg) doses of rifampicin, the fold-changes were relatively small, and CYP3A induction could not be detected at the lowest dose of rifampicin (0.2 mg/kg). In conclusion, CYP3A probe drugs are more sensitive for detecting CYP3A induction than endogenous CYP3A markers in cynomolgus monkeys, even for a short experimental period.

['Tahara|Harunobu|H|https://orcid.org/0000-0002-1500-208X', 'Watanabe|Miwa|M|', 'Hasegawa|Maki|M|']

2019

32383023

Deferoxamine Ameliorates Compressed Spinal Cord Injury by Promoting Neovascularization in Rats.

The therapeutic effect of deferoxamine (DFO) for spinal cord injury (SCI) has been demonstrated in previous studies; however, the exact mechanism of action is still unclear. Here, we hypothesized that DFO ameliorates spinal cord compression by promoting neovascularization. Using an SCI model of moderate compression, rats were intraperitoneally injected with 30 mg/kg or 100 mg/kg DFO for 1-2 weeks, and significant neovascularization was found in the injured spinal cord, showing overexpression of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF), and an increase in the number of new blood vessels. In addition, SCI in rats was significantly ameliorated after treatment with DFO, with less motor dysfunction, increased spared neural tissue, and improved electrophysiological conduction. By contrast, the ameliorative effect of DFO on SCI was suppressed when DFO-induced neovascularization was blocked by lenvatinib, a vascular endothelial growth factor receptor inhibitor, further suggesting that the primary pharmacological effect of DFO in SCI is the promotion of neovascularization. Therefore, we concluded that DFO effectively alleviated SCI by promoting neovascularization in the injured spinal cord. Considering that DFO is an FDA-approved free radical scavenger and iron chelator, it may represent a promising alternative strategy for SCI therapy in the future.

['Tang|Guoqing|G|', 'Chen|Yong|Y|', 'Chen|Ji|J|', 'Chen|Zhe|Z|', 'Jiang|Weimin|W|http://orcid.org/0000-0002-2362-652X']

2020

32903603

Evaluating a Two-Level vs. Three-Level Fall Risk Screening Algorithm for Predicting Falls Among Older Adults.

Background and Objectives: Falls account for the highest proportion of preventable injury among older adults. Thus, the United States' Centers for Disease Control and Prevention (CDC) developed the Stopping Elderly Accidents, Deaths, and Injuries (STEADI) algorithm to screen for fall risk. We referred to our STEADI algorithm adaptation as "Quick-STEADI" and compared the predictive abilities of the three-level (low, moderate, and high risk) and two-level (at-risk and not at-risk) Quick-STEADI algorithms. We additionally assessed the qualitative implementation of the Quick-STEADI algorithm in clinical settings. Research Design and Methods: We followed a prospective cohort (N = 200) of adults (65+ years) in the Bassett Healthcare Network (Cooperstown, NY) for 6 months in 2019. We conducted a generalized linear mixed model, adjusting for sociodemographic variables, to determine how baseline fall risk predicted subsequent daily falls. We plotted receiver operating characteristic (ROC) curves and measured the area under the curve (AUC) to determine the predictive ability of the Quick-STEADI algorithm. We identified a participant sample (N = 8) to gauge the experience of the screening process and a screener sample (N = 3) to evaluate the screening implementation. Results: For the three-level Quick-STEADI algorithm, participants at low and moderate risk for falls had a reduced likelihood of daily falls compared to those at high risk (-1.09, p = 0.04; -0.99, p = 0.04). For the two-level Quick-STEADI algorithm, participants not at risk for falls were not associated with a reduced likelihood of daily falls compared to those at risk (-0.89, p = 0.13). The discriminatory ability of the three-level and two-level Quick-STEADI algorithm demonstrated similar predictability of daily falls, based on AUC (0.653; 0.6570). Furthermore, participants and screeners found the Quick-STEADI algorithm to be efficient and viable. Discussion and Implications: The Quick-STEADI is a suitable, alternative fall risk screening algorithm. Qualitative assessments of the Quick-STEADI algorithm demonstrated feasibility in integrating a falls screening program in a clinical setting. Future research should address the validation and the implementation of the Quick-STEADI algorithm in community health settings to determine if falls screening and prevention can be streamlined in these settings. This may increase engagement in fall prevention programs and decrease overall fall risk among older adults.

['Mielenz|Thelma J|TJ|', 'Kannoth|Sneha|S|', 'Jia|Haomiao|H|', 'Pullyblank|Kristin|K|', 'Sorensen|Julie|J|', 'Estabrooks|Paul|P|', 'Stevens|Judy A|JA|', 'Strogatz|David|D|']

2020

25614624

Presenilin transmembrane domain 8 conserved AXXXAXXXG motifs are required for the activity of the γ-secretase complex.

Understanding the molecular mechanisms controlling the physiological and pathological activity of γ-secretase represents a challenging task in Alzheimer disease research. The assembly and proteolytic activity of this enzyme require the correct interaction of the 19 transmembrane domains (TMDs) present in its four subunits, including presenilin (PS1 or PS2), the γ-secretase catalytic core. GXXXG and GXXXG-like motifs are critical for TMDs interactions as well as for protein folding and assembly. The GXXXG motifs on γ-secretase subunits (e.g. APH-1) or on γ-secretase substrates (e.g. APP) are known to be involved in γ-secretase assembly and in Aβ peptide production, respectively. We identified on PS1 and PS2 TMD8 two highly conserved AXXXAXXXG motifs. The presence of a mutation causing an inherited form of Alzheimer disease (familial Alzheimer disease) in the PS1 motif suggested their involvement in the physiopathological configuration of the γ-secretase complex. In this study, we targeted the role of these motifs on TMD8 of PSs, focusing on their role in PS assembly and catalytic activity. Each motif was mutated, and the impact on complex assembly, activity, and substrate docking was monitored. Different amino acid substitutions on the same motif resulted in opposite effects on γ-secretase activity, without affecting the assembly or significantly impairing the maturation of the complex. Our data suggest that AXXXAXXXG motifs in PS TMD8 are key determinants for the conformation of the mature γ-secretase complex, participating in the switch between the physiological and pathological functional conformations of the γ-secretase.

['Marinangeli|Claudia|C|', 'Tasiaux|Bernadette|B|', 'Opsomer|Rémi|R|', 'Hage|Salim|S|', 'Sodero|Alejandro O|AO|', 'Dewachter|Ilse|I|', 'Octave|Jean Noël|JN|', 'Smith|Steven O|SO|', 'Constantinescu|Stefan N|SN|', 'Kienlen-Campard|Pascal|P|']

2015

32158203

CYP1B1, VEGFA, BCL2, and CDKN1A Affect the Development of Chronic Obstructive Pulmonary Disease.

Purpose Chronic obstructive pulmonary disease (COPD) is a progressive lung disease characterized by poor airflow. The purpose of this study was to explore the mechanisms involved in the development of COPD. Patients and Methods The mRNA expression profile GSE100281, consisting of 79 COPD and 16 healthy samples, was acquired from the Gene Expression Omnibus database. The differentially expressed genes (DEGs) between COPD samples and healthy samples were analyzed using the limma package. Functional enrichment analysis for the DEGs was carried out using the Database for Annotation, Visualization, and Integrated Discovery (DAVID) tool. Furthermore, DEG-compound pairs were predicted using the Comparative Toxicogenomics Database. The KEGG metabolite IDs corresponding to the compounds were also obtained through the MetaboAnalyst pipeline. Based on the diffusion algorithm, the metabolite network was constructed. Finally, the expression levels of key genes were determined using quantitative PCR (qPCR). Results There were 594 DEGs identified between the COPD and healthy samples, including 242 upregulated and 352 downregulated genes. A total of 696 DEG-compound pairs, such as BCL2-C00469 (ethanol) and BCL2-C00389 (quercetin) pairs, were predicted. CYP1B1, VEGFA, BCL2, and CDKN1A were included in the top 10 DEG-compound pairs. Additionally, 57 metabolites were obtained. In particular, hsa04750 (inflammatory mediator regulation of TRP channels)-C00469 (ethanol) and hsa04152 (AMPK signaling pathway)-C00389 (quercetin) pairs were found in the metabolite network. The results of qPCR showed that the expression of CYP1B1, VEGFA, BCL2, and CDKN1A was consistent with that predicted using bioinformatic analysis. Conclusion CYP1B1, VEGFA, BCL2, and CDKN1A may play important functions in the development and progression of COPD.

['Yang|Danlei|D|', 'Yan|Ying|Y|', 'Hu|Fen|F|', 'Wang|Tao|T|0000-0001-7180-8507']

2020

28586597

Identification Of Mutation Sites In Hepatitis C Virus Genotype 3a In Non-Responders To Combination Therapy With Interferon- Αlfa And Ribavirin In Residents Of Khyber Pakhtunkhwa Province Pakistan.

BACKGROUND This study was carried out to search for mutations in the gene encoding for Non- Structural Protein 5A, specifically in the interferon sensitivity determining region of hepatitis C virus (HCV) genotype 3a, isolated from serum samples of patients not responding to treatment with oral Ribavirin and Interferon alpha injections. METHODS This descriptive case series was conducted on HCV patients reporting in the attached teaching hospitals of Peshawar Medical College selected by consecutive sampling technique from 1st July to 31st December 2012. Amino acid sequencing was performed at the Centre of Applied Molecular Biology Lahore. Patients showing no clinical response after 6 months of combination therapy with Injection Interferon alpha + Ribavirin and still having positive polymerase chain reaction (Declared Non-Responders) were included in this study. RESULTS Amino acid sequencing was performed on HCV isolates from twenty non-responder and five responder patients. All these sequences were compared with Newzealand1 (NZL1) sequence from the gene bank for mutations; 0-7 mutations were observed in responders as compared to 10-27 mutations in non-responder patients (p value <0.005). CONCLUSIONS We were able to determine that there is a positive correlation between the number of mutations in NS5A ISDR and non-response to combination therapy. Synonymous mutations >10 and non-synonymous mutations >7 in this region suggest poor response to treatment.

['Muhammad|Sardar|S|', 'Rehman|Mehmud Ur|MU|', 'Ul Haq|Najibul|N|', 'Khan|Muhammad Mumtaz|MM|', 'Ahmad|Sajjad|S|']

2016

33855154

A case report of multi-ligaments injury of the ACL-MCL-PT combined with an occult fracture of the posterolateral tibial plateau.

The anterior cruciate ligament and medial collateral ligament are important static stabilizers of the knee. The patellar tendon is part of the knee extensor mechanism. The injury simultaneously involving these three structures is very rare. This paper reports a case with simultaneous ipsilateral rupture of the anterior cruciate ligament, medial collateral ligament, patellar tendon, and an occult compression fracture of the posterolateral tibial plateau. This injury pattern has not been reported in literature yet. The injury mechanism was hypothesized as a sudden anterior translation and valgus of the proximal tibia when the knee was in high flexion, followed by an eccentric quadriceps' contracture. In the followed management, ruptured medial collateral ligament and patellar tendon were sutured with augment, while the torn anterior cruciate ligament and fracture were treated conservatively. The outcome of the treatment was satisfactory, and no complication was observed. To this combined injury, a comprehensive consideration, including physical examination, multiple imaging examinations, and analysis of injury mechanism, is essential for a full diagnosis and treatment decision. Especially, computed tomography may help to identify an occult or non-displaced fracture, which would be easily misdiagnosed when nothing unusual was found in routine X-rays. In the treatment, it is suggested to perform a selective or step-by-step repair to the damaged structures, rather than an immediate total repair after injury.

['Xie|Tao|T|', 'Han|Xiao|X|', 'Zhou|Shao-Bo|SB|', 'Zhu|Liu-Long|LL|', 'He|Qi-Fang|QF|']

2021

25735891

Peptide-induced HLA-E expression in human PBMCs is dependent on peptide sequence and the HLA-E genotype.

Human Leukocyte Antigen (HLA)-E is a low-polymorphic non-classical HLA class I molecule which plays a crucial role in immune surveillance by presentation of peptides to T and natural killer (NK) cells. HLA-E polymorphism is related to HLA-E surface expression and is associated with patient outcome after stem cell transplantation. We aim to investigate the regulation of HLA-E expression level in peripheral blood mononuclear cells (PBMCs) of healthy individuals homozygous for HLA-E*01:01 or HLA-E*01:03, by using a panel of HLA-E binding peptides derived from CMV, Hsp60 and HLA class I. Basal and peptide-induced HLA-E surface expression levels were higher in PBMC from HLA-E*01:03 homozygous subjects as compared to PBMC from HLA-E*01:01 homozygous subjects. HLA-E mRNA levels were comparable between the two genotypes and remained constant after peptide stimulation. HLA-E surface expression seemed to be not only dependent on the HLA-E genotype, but also on the sequence of the peptide as evidenced by the profound difference in HLA-E upregulation with the Hsp60 and the B7 peptide. Our results showed that peptide-induced HLA-E expression is regulated at the posttranscriptional level as extracellular peptide stimulation did not influence RNA expression. This study provides new insights in the mechanism by which HLA-E expression is regulated and underlines a new role for extracellular peptides in inducing HLA-E translation, which may represent a defense mechanism against lytic viral infections and necrosis.

['Lauterbach|N|N|', 'Wieten|L|L|', 'Popeijus|H E|HE|', 'Vanderlocht|J|J|', 'van Zon|P M H|PM|', 'Voorter|C E M|CE|', 'Tilanus|M G J|MG|']

2015

24334553

In vivo antinociceptive and anticonvulsant activity of extracts of Heliotropium strigosum.

Natural healing agents are primarily focused to overcome unwanted side effects with synthetic drugs worldwide. In the proposed study, crude extracts and subsequent solvent fractions of Heliotropium strigosum were evaluated for antinociceptive and anticonvulsant activity in animal paradigms. In post acetic acid-induced writhing test, crude extract and fractions (hexane, ethyl acetate, and aqueous) demonstrated marked attenuation of nociception at test doses (50, 100, and 200 mg/kg i.p.). When challenged against thermally induced pain model, pretreatment of extracts exhibited prominent amelioration at test dose (50, 100, and 200 mg/kg i.p.). In both tests, inhibition of noxious stimulation was in a dose-dependent manner, and ethyl acetate fraction was most dominant. However, extracts did not antagonize the seizures and mortality induced by pentylenetetrazole. In conclusion, the extracts of H. strigosum illustrated significant antinociceptive effect in both centrally and peripherally acting pain models.

['Khan|Haroon|H|', 'Khan|Murad Ali|MA|', 'Hussain|Sajid|S|', 'Gaffar|Rukhsana|R|', 'Ashraf|Nadeem|N|']

2016

26957685

A comparative study on postoperative pain relief in laparoscopic cholecystectomy: Intraperitoneal bupivacaine versus combination of bupivacaine and buprenorphine.

CONTEXT To assess the analgesic efficacy of the combination of bupivacaine and buprenorphine in alleviating postoperative pain following laparoscopic cholecystectomy. AIMS Laparoscopic cholecystectomy is comparatively advantageous as it offers less pain in the postoperative period and requires a shorter hospital stay. There are only a few studies performed to evaluate the analgesic efficacy of intraperitoneal instillation of buprenorphine and bupivacaine during laparoscopic cholecystectomy. SETTINGS AND DESIGN The present research is a randomized, double-blind controlled study conducted in the Department of Anaesthesiology, Dayanand Medical College and Hospital Ludhiana, Punjab after formal ethical approval from Hospital's Ethics Committee. SUBJECTS AND METHODS This study analyzed 90 adults admitted for elective laparoscopic cholecystectomy. After the procedure, subjects were divided into three equal groups to conduct the study. Three Groups A, B, and C had intraperitoneal instillation of the 25 ml of physiological saline (0.9% normal saline), 0.25% of bupivacaine, 0.25% bupivacaine, and 0.3 mg buprenorphine, respectively. Necessary vitals were monitored and recorded. Visual analog scale (VAS) and verbal rating scale (VRS) scores were recorded and analyzed systematically. STATISTICAL ANALYSIS USED All observations were analyzed using analysis of variance and Student's t-test. RESULTS The mean pain scores were highest in Group A compared to Group B and Group C. Mean VAS and VRS scores were highest in Group C comparatively and lowest in Group A. CONCLUSION Combination of buprenorphine and bupivacaine intraperitoneally is comparatively more effective in relieving postoperative pain in comparison to intraperitoneal instillation of bupivacaine alone for postoperative pain management after laparoscopic cholecystectomy.

['Khurana|Sandeep|S|', 'Garg|Kamakshi|K|', 'Grewal|Anju|A|', 'Kaul|Tej K|TK|', 'Bose|Abhishek|A|']

2016

29562540

Amsterdam Dementia Cohort: Performing Research to Optimize Care.

The Alzheimer center of the VU University Medical Center opened in 2000 and was initiated to combine both patient care and research. Together, to date, all patients forming the Amsterdam Dementia Cohort number almost 6,000 individuals. In this cohort profile, we provide an overview of the results produced based on the Amsterdam Dementia Cohort. We describe the main results over the years in each of these research lines: 1) early diagnosis, 2) heterogeneity, and 3) vascular factors. Among the most important research efforts that have also impacted patients' lives and/or the research field, we count the development of novel, easy to use diagnostic measures such as visual rating scales for MRI and the Amsterdam IADL Questionnaire, insight in different subgroups of AD, and findings on incidence and clinical sequelae of microbleeds. Finally, we describe in the outlook how our research endeavors have improved the lives of our patients.

['van der Flier|Wiesje M|WM|', 'Scheltens|Philip|P|']

2018

32704784

Effects of different antibiotic feeding programs on morbidity and mortality and growth performance of nursery pigs housed in a wean-to-finish facility.

The objective of this study was to evaluate the effects of two antibiotic feeding programs in comparison to nonmedicated controls on the incidence of morbidity and mortality and growth performance of nursery pigs in a commercial setting. The study used 2,250 crossbred pigs in a randomized complete block design (blocking factor = start date). There were two dietary phases with three treatments in each phase: 1) nonmedicated controls vs. 2) 39 mg/kg (35 g/ton) tiamulin + 441 mg/kg (400 g/ton) chlortetracycline fed for 14 d (TIACTC) followed by 39 mg/kg (35 g/ton) tiamulin fed for 21 d (TIA) vs. 3) 28 mg/kg (25 g/ton) carbadox + 441 mg/kg (400 g/ton) oxytetracycline fed for 14 d (CAROTC) followed by 55 mg/kg (50 g/ton) carbadox fed for 21 d (CAR). Necropsy results from mortalities during the study confirmed the presence of pathogens including Pasteurella multocida and Escherichia coli, as well as Mycoplasma hyopneumoniae, Haemophilus parasuis, and Streptococcus suis. The study was carried out for a fixed time of 35 d from 6.7 ± 0.57 to 25.5 ± 2.23 kg BW. Pigs were housed in single-sex pens of 25 in a commercial wean-to-finish facility and there were 30 replicates of each treatment. All pigs were weighed as a group (i.e., pen) on days 0 (start), 14, and 35 (end) of study. Pigs had ad libitum access to feed and water throughout the study period; all feed additions to the feeder were recorded. There was no effect (P > 0.05) of antibiotic feeding program on the incidence of morbidity and mortality at any point during the study. During phase 1, TIACTC- and CAROTC-fed pigs were heavier (P < 0.05) at day 14 and had greater (P < 0.05) ADG (8.3% and 5.6% for TIACTC and CAROTC, respectively) and ADFI (4.3% and 6.5%, respectively) than controls. Pigs fed TIACTC in the first 14 d had greater (P < 0.05) G:F than the other treatments, which were similar for this measurement. In phase 2, feeding CAR resulted in greater (P < 0.05) ADG than controls, with pigs fed TIA being intermediate and different (P < 0.05) than the other treatments. Feeding antibiotics, regardless of treatment, resulted in greater (P < 0.05) ADFI than controls, but there were no differences in G:F. For the overall 35-d study period, feeding antibiotics resulted in greater (P < 0.05) ADG than controls (3.8% and 5.8%, respectively), but no difference (P > 0.05) between treatments for overall G:F. The results of this study confirm the advantage of feeding antibiotics on nursery pig growth.

['Puls|Christopher L|CL|', 'Allee|Gary L|GL|', 'Hammer|James M|JM|', 'Carr|Scott N|SN|']

2019

34415059

Involvement of TRPV4 in changes in rapidly inactivating potassium channels in the early stage of pilocarpine-induced status epilepticus in mice.

The rapidly inactivating potassium current (IA ) is important in controlling neuronal action potentials. Altered IA function and K+ channel expression have been found in epilepsy, and activation of the transient receptor potential vanilloid 4 (TRPV4) channel is involved in epilepsy pathogenesis. This study examined whether TRPV4 affects Kv4.2 and K+ channel interacting protein (KCHIP) expression and IA changes following pilocarpine-induced status epilepticus (PISE) in mice. Herein, hippocampal protein levels of Kv4.2 and KCHIP2 increased 3 h-3 d and decreased 7-30 d; that of KCHIP1 increased 3-24 h and decreased 3-30 d post-PISE. The TRPV4 antagonist HC-067047 attenuated the increased protein levels of Kv4.2 and KCHIP2 but not that of KCHIP1 post-PISE. The TRPV4 agonist GSK1016790A increased hippocampal protein levels of Kv4.2 and KCHIP2 but had no effect on KCHIP1 expression. HC-067047 attenuated the increased IA in hippocampal pyramidal neurons 24 h and 3 d post-PISE. GSK1016790A increased IA in hippocampal pyramidal neurons, shifting the voltage-dependent inactivation curve toward depolarization. The GSK1016790A-induced increase of IA was blocked by protein kinase A and calcium/calmodulin-dependent kinase II antagonists but was unaffected by protein kinase C antagonists. We conclude that TRPV4 activation may be responsible for the increases of Kv4.2 and KCHIP2 expression in hippocampi and IA in hippocampal pyramidal neurons in PISE mice, which are likely compensatory measures for hyperexcitability at the early stage of epilepsy.

['Xu|Weixing|W|', 'Wang|Yue|Y|', 'Qi|Xiuting|X|', 'Li|Kunpeng|K|', 'Zhou|Li|L|', 'Sha|Sha|S|', 'Wang|Xiaoli|X|', 'Wu|Chunfeng|C|', 'Du|Yimei|Y|', 'Chen|Lei|L|http://orcid.org/0000-0002-7382-8306']

2021

28233103

Expression times for hsp27 and hsp70 as an indicator of thermal stress during death due to fire.

The expression of heat shock proteins (hsps) increases in cases of hyperthermal cellular stress in order to protect cellular structures. Hsps can be visualized with immunohistochemical staining. We examined 48 cases of death from fire and excessive heat and a control group of 100 deaths without any perimortem thermal stress, measuring both the hsp27 and hsp70 expressions in myocardial, pulmonary, and renal tissues. The results revealed a correlation between hsp expression and survival time. Hsps are expressed rapidly within seconds or minutes after exposure to heat stress. In particular, hsp27 is expressed fast in high levels, whereas hsp70 expression is higher in the pulmonary and renal tissue of long-term survivors. In the myocardial tissue, hsp27 expression dominated in both short- and long-term survival. The expression pattern is strongly dependent on the organ structure and the survival time, which should be considered in future postmortem studies on hsps.

['Doberentz|E|E|', 'Genneper|L|L|', 'Wagner|R|R|', 'Madea|B|B|']

2017

27017053

Treatment of canine non-indolent T cell lymphoma using the VELCAP-TSC protocol: A retrospective evaluation of 70 dogs (2003-2013).

The immunophenotype of canine non-indolent lymphoma has prognostic value; dogs with T cell lymphoma have a poorer response rate and shorter survival times than dogs with B cell lymphoma. This study sought to retrospectively evaluate prognostic factors for complete remission (CR), progression free survival (PFS) and overall survival time (OST) in 70 dogs with T cell lymphoma treated with an alkylator-rich, combination protocol. The overall remission was 72.9%; 45 dogs (64.3%) achieved CR and six (8.6%) achieved partial remission. Dogs that were neutropenic at diagnosis were significantly more likely to achieve CR. The median overall PFS was 175 days; 1, 2 and 3 year PFS were 26.8%, 15.8%, and 12.6%, retrospectively, after commencing chemotherapy. Median PFS was significantly longer for dogs that achieved CR. Median OST was 237 days. The 1, 2 and 3 year survival rates were 31%, 20.2% and 11.5%, retrospectively, after commencing chemotherapy. The median OST was significantly longer for dogs that achieved CR and significantly shorter for Boxers and those in substage b at diagnosis. More than 30% of dogs treated with this protocol survived >1 year, suggesting that favourable outcomes and longer survival are possible for a proportion of dogs with T cell lymphoma.

['Goodman|Ingrid H|IH|', 'Moore|Antony S|AS|', 'Frimberger|Angela E|AE|']

2016

24170309

Integrating gerontological content across advanced practice registered nurse programs.

PURPOSE Faculty members across the country are faced with integrating gerontological content and competencies across advanced practice registered nurse (APRN) programs that focus on the adult-gerontology population. The purpose of this initiative was to effectively and efficiently integrate gerontological content into the adult management courses for several APRN programs in acute and primary care at one university's college of nursing. DATA SOURCES Current literature, resources for integrating adult-gerontology content, course evaluations, and end of program surveys were used in this project. CONCLUSION This curricular update effectively utilized resources and engaged faculty across programs to infuse gerontological content into the adult management courses. Students from multiple programs sharing these courses benefited from gerontological lecturers, content, and learning activities. The content gaps were integrated into existing courses rather than developing a new course. Current outcome data reflect this was an effective curricular change. IMPLICATIONS FOR PRACTICE In conjunction with meeting national requirements for integrating adult-gerontology content into APRN curriculum, APRNs prepared with enhanced gerontological knowledge and skills build a workforce that is competent to improve care for older adults across the continuum of care.

['Murphy|Marcia Pencak|MP|', 'Miller|Joanne M|JM|', 'Siomos|Martha Zervopoulos|MZ|', 'Braun|Lynne|L|', 'Hinch|Barbara|B|', 'Swartwout|Kathryn|K|']

2014

33709636

A novel machine learning approach (svmSomatic) to distinguish somatic and germline mutations using next-generation sequencing data.

Somatic mutations are a large category of genetic variations, which play an essential role in tumorigenesis. Detection of somatic single nucleotide variants (SNVs) could facilitate downstream analysis of tumorigenesis. Many computational methods have been developed to detect SNVs, but most require normal matched samples to differentiate somatic SNVs from the normal state, which can be difficult to obtain. Therefore, developing new approaches for detecting somatic SNVs without matched samples are crucial. In this work, we detected somatic mutations from individual tumor samples based on a novel machine learning approach, svmSomatic, using next-generation sequencing (NGS) data. In addition, as somatic SNV detection can be impacted by multiple mutations, with germline mutations and co-occurrence of copy number variations (CNVs) common in organisms, we used the novel approach to distinguish somatic and germline mutations based on the NGS data from individual tumor samples. In summary, svmSomatic: (1) considers the influence of CNV co-occurrence in detecting somatic mutations; and (2) trains a support vector machine algorithm to distinguish between somatic and germline mutations, without requiring normal matched samples. We further tested and compared svmSomatic with other common methods. Results showed that svmSomatic performance, as measured by F1-score, was significantly better than that of others using both simulation and real NGS data.

['Mao|Yu-Fang|YF|', 'Yuan|Xi-Guo|XG|', 'Cun|Yu-Peng|YP|']

2021

24972616

The life of John Cedric Goligher (1912-1998) revisited.

John Cedric Goligher was one of the great figures in British surgery. Although he practised general surgery as well, the medical community around the world elected him the pre-eminent colon and rectal surgeon of his time. Technically he was considered a master surgeon with enormous personal experience that was expressed in many papers and books written throughout his life. As the Chairman of the University Department of Surgery at the General Infirmary at Leeds, he developed many prospective controlled studies that granted him a national and international reputation. This paper aims to render him posthumous credit by remembering his career, literature contributions and the importance of his legacy to the surgical community.

['Campos|Fábio Guilherme|FG|', 'Nahas|Sérgio Carlos|SC|', 'Cecconello|Ivan|I|']

2016

24530351

Assaying benzene, a parquet varnish, and a synthetic thinner with respect to induction of in vivo chromosome loss in wing primordial cells of Drosophila.

An assay detecting the in vivo loss of mwh(+)Y, a genetically engineered Y chromosome, in cells of the Drosophila wing primordia was published recently. Loss of the mwh(+)Y chromosome in any of the wing-disk cells - in a multiple wing hairs homozygous background - leads to the formation of an mwh mosaic spot (clone) in the emerging wing. The frequency and the size of the mwh clones allow detection and quantitative evaluation of environmental and/or genetic agents inducing chromosome loss. Using this novel technique, we analyzed the potential of vapors of benzene, a parquet varnish, and a synthetic thinner to induce chromosome loss. Exposure to 0.047μg/ml benzene vapor for one day or to 0.175μg/ml for four hours resulted in a significantly elevated mwh clone-frequency confirming the ability of benzene to induce chromosome loss. A one-day exposure to vapors of a parquet varnish or a 6-h exposure to vapors of a synthetic thinner slightly, yet significantly elevated the frequency of chromosome loss. Results of the present paper show the potential of vapors of the analyzed parquet varnish and synthetic thinner to induce chromosome loss, and illustrate the usefulness of the new technique.

['Soós|István|I|', 'Szabad|János|J|']

2014

29163510

The Equivocal Role of Th17 Cells and Neutrophils on Immunopathogenesis of Leishmaniasis.

Advances in the understanding of leishmaniasis progression indicate that cellular interactions more complex than the Th1/Th2 paradigm define the course of infection. Th17 cells are a crucial modulator of adaptive immunity against Leishmania parasites acting mainly on neutrophil recruitment and playing a dual role at the site of infection. This review describes the roles of both these cell types in linking innate defense responses to the establishment of specific immunity. We focus on the Th17-neutrophil interaction as a crucial component of anti-Leishmania immunity, and the clinical evolution of cutaneous or visceral leishmaniasis. To date, information obtained through experimental models and patient evaluations suggests that the influence of the presence of interleukin (IL)-17 (the main cytokine produced by Th17 cells) and neutrophils during Leishmania infections is strictly dependent on the tissue (skin or liver/spleen) and parasite species. Also, the time at which neutrophils are recruited, and the persistence of IL-17 in the infection microenvironment, may also be significant. A clearer understanding of these interactions will enable better measurement of the influence of IL-17 and its regulators, and contribute to the identification of disease/resistance biomarkers.

['Gonçalves-de-Albuquerque|Suênia da C|SDC|', 'Pessoa-E-Silva|Rômulo|R|', 'Trajano-Silva|Lays A M|LAM|', 'de Goes|Tayná Correia|TC|', 'de Morais|Rayana C S|RCS|', 'da C Oliveira|Cíntia N|CN|', 'de Lorena|Virgínia M B|VMB|', 'de Paiva-Cavalcanti|Milena|M|']

2017

30609596

Ratiometric fluorescent probe based on ESIPT for the highly selective detection of cysteine in living cells.

A new simple and facile fluorescent ratiometric probe (probe 1) has been designed for the detection of cysteine (Cys). Probe 1 as the fluorophore contains a typical excited-state intramolecular proton transfer (ESIPT) dye. In probe 1 to restore the ESIPT process, the group of acrylate which acts as the recognition unit can block the ESIPT process and can be selectively achieved by Cys, which makes the probe as the ratiometric fluorescent detection for Cys in aqueous solution. This probe shows highly selectivity towards Cys over other biothiols including glutathione (GSH) and homocysteine (Hcy) because of specific cyclization between Cys and acrylate group, and having a detection limit of 42.3 nM. In addition, the experiment of cell imaging shows that probe 1 possesses low cytotoxicity and excellent cell permeability towards the living cells, and has been successfully applied to the ratiometric imaging not only for the endogenous but also for the exogenous cysteine in the living cells effectively.

['Li|Xinran|X|', 'Ma|Hong|H|', 'Qian|Jing|J|', 'Cao|Ting|T|', 'Teng|Zhidong|Z|', 'Iqbal|Kanwal|K|', 'Qin|Wenwu|W|', 'Guo|Huichen|H|']

2019

23819848

Enterocutaneous fistulae in familial adenomatous polyposis patients with abdominal desmoid disease.

AIM Enterocutaneous fistula is a severe complication of intra-abdominal desmoid disease. It is hard to repair because of the presence of the desmoid itself, the possibility of distal obstruction and the complexity of multiple laparotomies. Here we report the outcome of a series of patients presenting with abdominal desmoid disease and associated enterocutaneous fistula. METHOD This is a retrospective, descriptive study of patients presenting to a hereditary colorectal cancer registry with familial adenomatous polyposis-related intra-abdominal desmoid disease and associated enterocutaneous fistulae. Patients were identified through the registry database and aspects of their treatment and outcome were abstracted. RESULTS Sixteen patients (11 women, five men) were treated. The mean age at index surgery was 25.2 years and mean time to first fistula was 115.6 (± 92.7 standard deviation) months from index surgery. Index surgery included restorative proctocolectomy with ileal pouch (n = 9), colectomy with ileorectal anastomosis (n = 4) and proctocolectomy with end ileostomy (n = 1). One patient had only a small bowel bypass and another did not have any index surgery. Ten patients underwent laparotomy for the enterocutaneous fistula; eight had a repair ± resection, one had a diversion and one a bypass. All eight patients who had a repair healed, and the bypassed fistula was successfully palliated. Three fistulae recurred and two were successfully repaired at a second procedure. One patient was explored but nothing could be done for the fistula. Two surgery patients died of causes unrelated to the fistula. Six patients received medical treatment, four of whom died. CONCLUSION Selected desmoid-related enterocutaneous fistulae can be repaired successfully.

['Xhaja|X|X|', 'Church|J|J|']

2013

32432978

College-attending young men's sexual and reproductive health knowledge, attitudes and practices.

Objective: Male involvement in contraceptive practice remains low. Family planning and pediatric health associations have recommended an emphasis on long-acting reversible contraceptives (LARC) in clinical counseling with adolescents and young adults, raising concerns about the resulting adverse impact on sexually transmitted infection (STI) rates. Participants: College-attending men responded to an internet based questionnaire (n=31) and a phone-based qualitative interview (n=25). Methods: Our survey solicited attitudes toward and knowledge of contraceptive methods and assessed communication practices with sexual partners regarding use of contraception and disease prevention. Results: Knowledge about female methods of contraception was low, with a comparatively high level of knowledge about Plan B. Parents and health care providers were cited as the most helpful sources of information. Conversations about protection with sexual partners were reported by most men, due mainly to fear of unplanned pregnancy, not STI. Conclusion: Addressing couple communication and dual protection among college-attending men needs greater emphasis.

['Gollub|Erica L|EL|', 'Beauvais|Shirley|S|', 'Roye|Carol|C|']

2020

34258488

Patient-Reported Complications, Symptoms, and Experiences of Living With X-Linked Hypophosphatemia Across the Life-Course.

Context X-linked hypophosphatemia (XLH) is a rare, genetic phosphate-wasting disease resulting in bone, muscular, and dental problems, beginning in childhood and increasing in adulthood. Objective This qualitative analysis aimed to explore patient-reported symptoms, complications, and experiences of XLH over the life-course, using data from a large multinational online survey. Methods Responses to 2 open-ended questions from 209 adults and 86 children/adolescents (proxy report) with self-reported XLH were analyzed in 8 age groups. Two researchers independently coded and analyzed the responses, using thematic analysis, with differences settled among a multidisciplinary group. Six themes were identified, with age subgroup analysis conducted on the 3 most common, according to coding frequency. Results Within theme 1, "Clinical Signs and Symptoms of XLH," "Pain" was a dominant subtheme across the life-course, but "Skeletal Pathology" dominated the responses of children/adolescents. Within theme 2, "Impacts of Clinical Signs and Symptoms," interference with "Physical Exertion" and "Emotional Wellbeing" (comprising depression/anxiety in adults and lack of self-esteem in children/adolescents) was reported across all ages. For theme 3, "Negative Treatment Experiences," "Medication" was problematic for children, with adults reporting lack of "Access to Appropriate Treatment." Three further themes were identified: "Resilience," "Positive Treatment Experiences," and "Information Needs." Conclusion The multiple burdens imposed on people with XLH throughout their lifetime encompassed the physical, emotional, and social, although the most challenging symptoms or complications differed between ages. Burden was further exacerbated by adults' lack of access to appropriate treatment, illustrating the need for age-appropriate multidisciplinary care.

['Cheung|Moira|M|https://orcid.org/0000-0003-0742-7595', 'Rylands|Angela J|AJ|https://orcid.org/0000-0002-7790-4724', 'Williams|Angela|A|', 'Bailey|Karen|K|https://orcid.org/0000-0003-1985-4826', 'Bubbear|Judith|J|']

2021

32712956

The temporal association between incident late-life depression and incident dementia.

OBJECTIVE There is an established association between depression and subsequent dementia. The present study examined temporal associations between incident late-life depression and subsequent dementia, also considering age and sex. METHODS We used longitudinal health claims data from the largest German health insurance provider ('Allgemeine Ortskrankenkasse') considering up to 9 follow-up years in piecewise exponential models. ICD-10 codes were used to define incident depression and dementia in individuals ≥65 years (n = 97 110). RESULTS Incident depression was associated with a higher risk of subsequent dementia (incidence rate ratios (IRR) adjusted for age and sex: IRR = 1.58, 95% CI = 1.51-1.64). The strongest association was found for the shortest interval of 1 quarter (IRR = 2.04, 95% CI = 1.88-2.21), with significant associations up to an interval of roughly 3 years. The association was more pronounced and lasted for more quarters in the younger portion of this study group (ages from 65-74: IRR = 2.00, 95% CI = 1.83-2.18; 75-84: IRR = 1.64, 95% CI = 1.55-1.73; ≥85: IRR = 1.19, 95% CI = 1.08-1.31). It was stronger among men than women (men: IRR = 1.98, 95% CI = 1.84-2.14; women: IRR = 1.44, 95% CI = 1.37-1.51) with no sex-specific temporal association. CONCLUSION This large claims data study confirmed that incident late-life depression is associated with a higher risk of dementia within the 3 years following diagnosis. Hence, incident late-life depression should prompt further cognitive examinations and referrals to specialists. This might apply especially to younger seniors and men.

['Heser|K|K|0000-0002-9738-2572', 'Fink|A|A|0000-0003-2106-2940', 'Reinke|C|C|0000-0003-3228-1794', 'Wagner|M|M|0000-0003-2589-6440', 'Doblhammer|G|G|0000-0001-7746-0652']

2020

28545974

Development of 5-hydroxypyrazole derivatives as reversible inhibitors of lysine specific demethylase 1.

A series of reversible inhibitors of lysine specific demethylase 1 (LSD1) with a 5-hydroxypyrazole scaffold have been developed from compound 7, which was identified from the patent literature. Surface plasmon resonance (SPR) and biochemical analysis showed it to be a reversible LSD1 inhibitor with an IC50 value of 0.23µM. Optimisation of this compound by rational design afforded compounds with Kd values of <10nM. In human THP-1 cells, these compounds were found to upregulate the expression of the surrogate cellular biomarker CD86. Compound 11p was found to have moderate oral bioavailability in mice suggesting its potential for use as an in vivo tool compound.

['Mould|Daniel P|DP|', 'Bremberg|Ulf|U|', 'Jordan|Allan M|AM|', 'Geitmann|Matthis|M|', 'Maiques-Diaz|Alba|A|', 'McGonagle|Alison E|AE|', 'Small|Helen F|HF|', 'Somervaille|Tim C P|TCP|', 'Ogilvie|Donald|D|']

2017

28684295

On the origin of mitosing cells: A historical appraisal of Lynn Margulis endosymbiotic theory.

Although for a long-time symbiosis was considered to be quite rare and with no role in evolutionary processes, Lynn Margulis demonstrated that endosymbiotic events played a key role in the origin and evolution of eukaryotic cells. Starting with her seminal assay in the Journal of Theoretical Biology in 1967 (authored as Lynn Sagan), her lifelong work on eukaryogenesis and the role of symbiosis in evolution stands as a valid and authoritative contribution to science. As was quick to acknowledge, she was not the first to discuss the significance of symbiosis to explain the origin of mitochondria and chloroplasts, but no one else had done it to her extent and depth, nor had anyone provided a variety of testable hypotheses. While it is true that some of her proposals were incomplete or mistaken, morphological, biochemical and geochemical evidence together with phylogenomic analyses of mitochondria, chloroplasts and eukaryotic nuclear genomes have demonstrated the validity of her evolutionary scheme, as well that of her specific predictions on the chimeric nature of genomes and the mosaicism of metabolic pathways in eukaryotic cells.

['Lazcano|Antonio|A|', 'Peretó|Juli|J|']

2017

31110743

Diffuse alveolar hemorrhage caused by IgA deposition associated with multiple myeloma.

We report a man with diffuse alveolar hemorrhage caused by multiple myeloma who was diagnosed with the aid of bronchoalveolar lavage and transbronchial lung biopsy. Multiple myeloma should be considered as an important differential diagnosis in patients with diffuse alveolar hemorrhage, and bronchoscopy may help to differentiate the cause.

['Furube|Atsuki|A|https://orcid.org/0000-0002-4342-5098', 'Kagiyama|Naho|N|', 'Ishiguro|Takashi|T|https://orcid.org/0000-0001-6004-1769', 'Takaku|Yotaro|Y|', 'Kurashima|Kazuyoshi|K|', 'Shimizu|Yoshihiko|Y|', 'Takayanagi|Noboru|N|']

2019

28895157

Laryngeal exposure and margin status in glottic cancer treated by transoral laser microsurgery.

OBJECTIVE Laryngeal exposure is one of the most limiting factors in transoral laser microsurgery (TLM) for glottic cancer. We evaluated the correlation between the degree of laryngeal exposure, as assessed by an easy previously described scoring tool (Laryngoscore), and histopathologic surgical margin status after TLM. STUDY DESIGN Prospective evaluation of 147 patients affected by Tis-T2 glottic cancer treated by TLM with curative intent between January 2012 and April 2016. METHODS All patients were preoperatively assessed and classified as having good (group A including Laryngoscore class 0-I) or suboptimal laryngeal exposure (group B including class II-III). Margins were classified as negative (more than 1 mm margin between healthy tissue and tumor) or positive (one/multiple superficial or deep margins involved by invasive or in situ carcinoma). Patients with multiple superficial or deep margin positivity were scheduled for TLM re-excision, open partial laryngectomy, or postoperative radiotherapy. RESULTS Twenty-one type I, 54 type II, 19 type III, 7 type IV, 41 type V, and 5 type VI cordectomies (according to the European Laryngological Society classification) were performed with an en-bloc or multi-bloc technique according to the size, site, and exposure of the lesion. Group A included 109 (74%) and group B included 38 (26%) patients. Positive surgical margins were overall observed in 39 (26.5%) cases: 21 (19.2%) in group A versus 18 (47.4%) in group B (P = 0.001). CONCLUSION Laryngeal exposure is one of the most important factors influencing TLM resection of glottic cancer within safe surgical margins. The importance of its adequate preoperative assessment cannot be overemphasized. LEVEL OF EVIDENCE 2b. Laryngoscope, 128:1146-1151, 2018.

['Piazza|Cesare|C|0000-0002-2391-9357', 'Paderno|Alberto|A|', 'Grazioli|Paola|P|', 'Del Bon|Francesca|F|', 'Montalto|Nausica|N|', 'Perotti|Pietro|P|', 'Morello|Riccardo|R|', 'Filauro|Marta|M|', 'Nicolai|Piero|P|', 'Peretti|Giorgio|G|']

2018

26594215

The Ins and Outs of B Cells in Multiple Sclerosis.

B cells play a central role in multiple sclerosis (MS) pathology. B and plasma cells may contribute to disease activity through multiple mechanisms: antigen presentation, cytokine secretion, or antibody production. Molecular analyses of B cell populations in MS patients have revealed significant overlaps between peripheral lymphoid and clonally expanded central nervous system (CNS) B cell populations, indicating that B cell trafficking may play a critical role in driving MS exacerbations. In this review, we will assess our current knowledge of the mechanisms and pathways governing B cell migration into the CNS and examine evidence for and against a compartmentalized B cell response driving progressive MS pathology.

['Blauth|Kevin|K|', 'Owens|Gregory P|GP|', 'Bennett|Jeffrey L|JL|']

2015

27110803

Mitigating Stress and Supporting Health in Deprived Urban Communities: The Importance of Green Space and the Social Environment.

Environment-health research has shown significant relationships between the quantity of green space in deprived urban neighbourhoods and people's stress levels. The focus of this paper is the nature of access to green space (i.e., its quantity or use) necessary before any health benefit is found. It draws on a cross-sectional survey of 406 adults in four communities of high urban deprivation in Scotland, United Kingdom. Self-reported measures of stress and general health were primary outcomes; physical activity and social wellbeing were also measured. A comprehensive, objective measure of green space quantity around each participant's home was also used, alongside self-report measures of use of local green space. Correlated Component Regression identified the optimal predictors for primary outcome variables in the different communities surveyed. Social isolation and place belonging were the strongest predictors of stress in three out of four communities sampled, and of poor general health in the fourth, least healthy, community. The amount of green space in the neighbourhood, and in particular access to a garden or allotment, were significant predictors of stress. Physical activity, frequency of visits to green space in winter months, and views from the home were predictors of general health. The findings have implications for public health and for planning of green infrastructure, gardens and public open space in urban environments.

['Ward Thompson|Catharine|C|', 'Aspinall|Peter|P|', 'Roe|Jenny|J|', 'Robertson|Lynette|L|', 'Miller|David|D|']

2016

26811726

Evaluation of Immunogenicity of Cocktail DNA Vaccine Containing Plasmids Encoding Complete GRA5, SAG1, and ROP2 Antigens of Toxoplasma gondii in BALB/C Mice.

BACKGROUND Severe and fatal complications of toxoplasmosis urge development of effective vaccines against the disease. The current study was performed to evaluate cocktail DNA vaccine containing plasmids encoding GRA5, SAG1, and ROP2 genes of Toxoplasma gondii in BALB/c mice in Tarbiat Modares University in 2012. METHODS The plasmids containing complete GRA5, SAG1, and ROP2 genes were mass extracted and then the recombinant plasmids were administered via intramuscular injections according to immunized mice three times with three-week intervals. Then splenocytes were cultured, and proliferation as well as cytokine assays were carried out. The other mice in each group were inoculated by the parasite and mortality of the mice was evaluated on a daily basis. RESULTS The results of cytokine assay for INF-γ were higher in the mice that received the cocktail DNA containing recombinant plasmids. Evaluation of proliferation of splenocytes using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay indicated induction of cellular response. Measurement of total IgG and the isotypes of IgG1 and IgG2a showed that the cocktail DNA stimulated IgG and IgG2a production in comparison with the control groups (P<0.05). Furthermore, the survival rate of mice in the groups that received the cocktail DNA was significantly higher than that in the control groups (P<0.05). CONCLUSION Administration of the cocktail DNA vaccine led to production of higher levels of IFN-γ, confirmed by secretion of IgG2a, and the immune response was shifted toward Th1. Thus, the cocktail DNA containing the recombinant plasmids can be an appropriate candidate for immunization against toxoplasmosis.

['Naserifar|Razi|R|', 'Ghaffarifar|Fatemeh|F|', 'Dalimi|Abdolhosein|A|', 'Sharifi|Zohreh|Z|', 'Solhjoo|Kavous|K|', 'Hosseinian Khosroshahi|Kami|K|']

2015

26157409

Eighteen-month-olds' memory interference and distraction in a modified A-not-B task is not associated with their anticipatory looking in a false-belief task.

Infants' performance in non-verbal false-belief tasks is often interpreted as if they have understood false beliefs. This view has been questioned by a recent account that explains infants' performance in non-verbal false-belief tasks as the result of susceptibility to memory interference and distraction. We tested this alternative account by investigating the relationship between infants' false-belief understanding, susceptibility to memory interference and distraction, and general cognitive development in 18-month-old infants (N = 22). False-belief understanding was tested in an anticipatory looking paradigm of a standard false-belief task. Susceptibility to memory interference and distraction was tested in a modified A-not-B task. Cognitive development was measured via the Mental Scale of the Bayley Scales of Infant Development. We did not find any relationship between infants' performance in the false-belief task and the A-not-B task, even after controlling for cognitive development. This study shows that there is no ubiquitous relation between susceptibility to memory interference and distraction and performance in a false-belief task in infancy.

['Zmyj|Norbert|N|', 'Prinz|Wolfgang|W|', 'Daum|Moritz M|MM|']

2015

33384213

Mind Meets Machine: Towards a Cognitive Science of Human-Machine Interactions.

As robots advance from the pages and screens of science fiction into our homes, hospitals, and schools, they are poised to take on increasingly social roles. Consequently, the need to understand the mechanisms supporting human-machine interactions is becoming increasingly pressing. We introduce a framework for studying the cognitive and brain mechanisms that support human-machine interactions, leveraging advances made in cognitive neuroscience to link different levels of description with relevant theory and methods. We highlight unique features that make this endeavour particularly challenging (and rewarding) for brain and behavioural scientists. Overall, the framework offers a way to study the cognitive science of human-machine interactions that respects the diversity of social machines, individuals' expectations and experiences, and the structure and function of multiple cognitive and brain systems.

['Cross|Emily S|ES|', 'Ramsey|Richard|R|']

2021

25852262

Helicobacter pylori eradication in gastric diffuse large B cell lymphoma.

Diffuse large B cell lymphoma (DLBCL) of the stomach is a heterogenous disease. There are tumors without histological evidence of mucosa-associated lymphoid tissue (MALT) lymphoma, which are classified as pure or de novo DLBCL and those with evidence of MALT, which are classified as DLBCL (MALT). The association between Helicobacter pylori (H. pylori) and gastric MALT lymphoma and remission with H. pylori eradication was shown in the 1990s. In recent years, scientists from Taiwan and others have shown that high-grade gastric lymphomas may be dependent on H. pylori and eradication of this microorganism is effective in these cases. This entity is biologically distinct from H. pylori (-) cases and has a better clinical outcome. There are sufficient data about the complete remission in some of these cases with brief treatment with antibiotics. With this strategy, it is possible to save some of these cases from the harmful effects of standard chemotherapy. It is time to treat these cases with H. pylori eradication. However, strict histopathological follow-up is crucial and histopathological response must be evaluated according to the scoring system proposed by Groupe d'Etude des Lymphomes de l'Adulte. If there is no sufficient response, chemotherapy must be given immediately. These results suggest that H. pylori dependency and high-grade transformation in gastric MALT lymphomas are distinct events.

['Paydas|Semra|S|']

2015

32107617

Management of laryngeal candidiasis: an evidence-based approach for the otolaryngologist.

PURPOSE The authors aim to review available reports regarding laryngeal candidiasis and describe the existing evidence on the demographics, clinical manifestations, diagnosis, therapeutic options, and outcomes of this infection. METHODS A review of articles on laryngeal candidiasis was conducted using PubMed® database from its inception through July 2019. RESULTS Patients were mainly females presenting with complaints of dysphonia and associated gastroesophageal reflux history or inhaled corticosteroids use; although local predisposing factors were common, most patients were immunocompetent. The main anatomical affected subsite was the glottis with the presence of leukoplastic lesions. The diagnostic approach remains controversial, since some authors recommend prompt lesion biopsy and others rely on empirical antifungal treatment that showed effective results regarding symptoms and lesions resolution. CONCLUSION Laryngeal Candida infection is thought to be a rare condition, with limited available literature. The correct diagnosis is difficult for the otolaryngologist and a high level of suspicion is required. The authors emphasize the need to include this condition into the differential diagnosis in patients with predisposing factors presenting with suspected lesions. In addition, the conservative diagnostic approach with antifungal treatment seems to provide effective outcomes, although comparative clinical studies between diagnostic options are lacking.

['Valente|Pedro|P|http://orcid.org/0000-0001-9080-1124', 'Ferreira|Joana|J|', 'Pinto|Isabel|I|', 'Medeiros|Nuno|N|', 'Oliveira|Pedro|P|', 'Castro|Eugénia|E|', 'Condé|Artur|A|']

2020

32235292

Hybridized-GNSS Approaches to Train Positioning: Challenges and Open Issues on Uncertainty.

In recent years, the development of advanced systems and applications has propelled the adoption of autonomous railway traffic and train positioning, with several ongoing initiatives and experimental testbeds aimed at proving the suitability and reliability of the Global Navigation Satellite System signals and services, in this specific application domain. To satisfy the strict safety and accuracy requirements aimed at assuring the position solution's integrity, availability, accuracy and reliability, recent proposals suggest the hybridization of the Global Navigation Satellite System with other technologies. The integration with localization techniques that are expected to be available with the upcoming fifth generation mobile communication networks is among the most promising approaches. In this work, different approaches to the design of hybrid positioning solutions for the railway sector are examined, under the perspective of the uncertainty evaluation of the attained results and performance. In fact, the way the uncertainty associated to the positioning measurements performed by different studies is reported is often not consistent with the Guide to the Expression of Uncertainty in Measurement, and this makes it very difficult to fairly compare the different approaches in order to identify the best emerging solution. Under this perspective, the review provided by this work highlights a number of open issues that should drive future research activities in this field.

['Spinsante|Susanna|S|', 'Stallo|Cosimo|C|']

2020

33971594

Controlling factors of seasonal and spatial variation of riverine CO2 partial pressure and its implication for riverine carbon flux.

Global carbon cycle is closely related to the earth's energy budget, because CO2 plays an active role in the global climate change. The higher CO2 partial pressure (pCO2) in inland water in comparison with atmosphere, causing a CO2 evasion from water to the air. However, the relationship between CO2 evasion, riverine carbon export, and hydrochemistry in watershed has remained largely unknown. This study collected 84 river water samples in Jiulongjiang River, to further address this subject on a small watershed scale. Water temperature fluctuation, riverine photosynthesis, and acidic matter input could not account for the seasonal variation of pCO2 in Jiulongjiang River. The spatial shifts of pCO2 were derived from the mixing process between headwater and soil influx. The soil influx with high pCO2 compensated the CO2 lost from evasion and caused pCO2 in Jiulongjiang River higher than the atmospheric level. The seasonal variation of pCO2 was caused by the precipitation difference between the wet season and dry season. The addition of rainwater significantly decreased the riverine pCO2 and HCO3- concentration in the wet season. The CO2 evasion rate in Jiulongjiang River was clearly higher than that in most worldwide large rivers. The annual CO2 evasion flux in Jiulongjiang River Basin was estimated about 2.48 × 105 T C/year, which was higher than the riverine total carbon export. The CO2 evasion rate exhibited significantly positive relationship with water surface area, indicating that the global CO2 evasion flux may be roughly estimated based on the observed regression relationship. Overall, our study indicated that it still requires collaborative effects to investigate the carbon dynamics in river water, more estimations of CO2 outgassing flux from river water under different hydrologic and geologic conditions are necessary.

['Liu|Jinke|J|', 'Han|Guilin|G|']

2021

29974796

Subchondral drilling for chondral flaps reduces the risk of total hip arthroplasty in femoroacetabular impingement surgery at minimum five years follow-up.

INTRODUCTION: The best treatment of acetabular chondral flaps during surgery for femoroacetabular impingement (FAI) is unknown. We asked if subchondral drilling improves clinical and radiographic outcome and if there are factors predicting failure. METHODS: We treated 79 patients with symptomatic FAI and acetabular chondral flaps with surgical hip dislocation between January 2000 and December 2007. Exclusion of all patients with previous hip pathology or trauma resulted in 62 patients (80 hips). The chondral flap was slightly debrided in 43 patients/51 hips (control group). In 28 patients/29 hips (study group), additional osseous drilling was performed. 4 patients (5 hips, 6%) were lost to follow-up. Mean follow-up was 9 years (5-13 years). The groups did not differ in demographic data, radiographic parameters or follow-up. Clinical outcome was assessed with the Merle d'Aubigné score, modified Harris Hip Score and University of California Los Angeles activity score and progression of osteoarthritis with the Tönnis grade. RESULTS: No patient underwent conversion to total hip arthroplasty (THA) in the drilling group compared to 7 patients (8 hips, 16%) in the control group ( p = 0.005); in the remaining hips, clinical scores and progression of Tönnis grade did not differ. Increased acetabular coverage, age and body mass index were univariate predictive factors for conversion to THA. No drilling was as an independent predictive factor for conversion to THA (hazard ratio 58.07, p = 0.009). CONCLUSION: Subchondral drilling under acetabular chondral flaps during surgical treatment of FAI is an effective procedure to reduce the rate of conversion to THA.

['Haefeli|Pascal C|PC|', 'Tannast|Moritz|M|', 'Beck|Martin|M|', 'Siebenrock|Klaus A|KA|', 'Büchler|Lorenz|L|']

2019

33805138

Potency Testing of Venoms and Antivenoms in Embryonated Eggs: An Ethical Alternative to Animal Testing.

Venoms are complex mixtures of biologically active molecules that impact multiple physiological systems. Manufacture of antivenoms (AVs) therefore requires potency testing using in vivo models to ensure AV efficacy. As part of ongoing research to replace small animals as the standard model for AV potency testing, we developed an alternate in vivo method using the embryonated egg model (EEM). In this model, the survival of chicken embryos envenomated in ovo is determined prior to 50% gestation, when they are recognized as animals by animal welfare legislation. Embryos were found to be susceptible to a range of snake, spider, and marine venoms. This included funnel-web spider venom for which the only other vertebrate, non-primate animal model is newborn mice. Neutralization of venom with standard AV allowed correlation of AV potency results from the EEM to results from animal assays. Our findings indicate that the EEM provides an alternative, insensate in vivo model for the assessment of AV potency. The EEM may enable reduction or replacement of the use of small animals, as longer-term research that enables the elimination of animal use in potency testing continues.

['Verity|Erin E|EE|', 'Stewart|Kathy|K|', 'Vandenberg|Kirsten|K|', 'Ong|Chi|C|', 'Rockman|Steven|S|']

2021

28683450

Acute Kidney Injury and Hemolytic Anemia Secondary to Mycoplasma pneumoniae Infection.

Glomerulonephritis as well as kidney injury secondary to fulminant intravascular hemolysis are rare extrapulmonary manifestations of Mycoplasma pneumoniae infection. We describe a 50-year-old female diagnosed with M. pneumoniae infection-associated hemolytic anemia, characterized by negative cold agglutinin tests but with laboratory evidence of complement alternative pathway activation. The patient presented both with anemia and severe kidney failure and she was treated with steroids and red blood cell transfusions along with plasmapheresis. She also received a short course of antibiotics. Renal biopsy showed combined features of resolving postinfectious glomerulonephritis and hemolysis-associated extensive acute tubular injury characterized by renal hemosiderosis and intratubular hemoglobin casts. Electron microscopy revealed features of glomerular microangiopathic injury. The treatment led to complete disease remission and a favorable renal outcome at the first year follow-up.

['Carrara|Camillo|C|', 'Abbate|Mauro|M|', 'Sabadini|Ettore|E|', 'Remuzzi|Giuseppe|G|']

2017

30587043

A daily diary study of internalised weight bias and its psychological, eating and exercise correlates.

OBJECTIVE The current investigation extends ecological momentary assessment (EMA) and daily diary weight stigma research in internalised weight bias (IWB). This investigation used daily diaries to examine the relationship between IWB, mood, coping, body appreciation, exercise behaviours and eating behaviours. DESIGN The study sample consisted of individuals who were overweight or obese (85% female) with MBMI = 36.0, SDBMI = 6.2. Participants completed a daily diary each evening and wore a Fitbit for 30 days. MAIN OUTCOME MEASURES Participants reported on IWB, mood, coping, body appreciation, exercise behaviours and eating behaviours. RESULTS Both within- and between-subjects IWB were significantly related to positive affect, negative affect, several coping responses, body appreciation, eating behaviours and the urge to avoid exercise. Exploratory analyses indicated that positive and negative affect mediated many of the associations between IWB and coping responses, body appreciation, and eating and exercise behaviours. CONCLUSION This investigation provides evidence that IWB experiences have daily impacts on psychological well-being, body appreciation, coping, eating and exercise behaviours. Also, this study raises awareness about IWB and its potential impact on psychological well-being and health behaviours.

['Carels|Robert A|RA|', 'Hlavka|Reid|R|', 'Selensky|Jennifer C|JC|', 'Solar|Chelsey|C|', 'Rossi|James|J|', 'Caroline Miller|J|J|']

2019

29080001

The relevance of the Hippocratic Oath to the ethical and moral values of contemporary medicine. Part I: The Hippocratic Oath from antiquity to modern times.

The present paper discusses the relevance and significance of the Hippocratic Oath to contemporary medical ethical and moral values. It attempts to answer the questions about some controversial issues related to the Oath. The text is divided in two parts. Part I discusses the general attributes and ethical values of the Oath, while Part II presents a detailed analysis of each passage of the Oath with regard to perennial ethical principles and moral values. Part I starts with the contribution of Hippocrates and his School of Cos to medicine. It continues by examining the moral dilemmas concerning physicians and patients in the Classical Times and in the Modern World. It also investigates how the Hippocratic Oath stands nowadays, with regard to the remarkable and often revolutionary advancements in medical practice and the significant evolution in medical ethics. Further, it presents the debate and the criticism about the relevance of the general attributes and ethical values of the Oath to those of modern societies. Finally, it discusses the endurance of the ethical values of the Hippocratic Oath over the centuries until today with respect to the physicians' commitment to the practice of patient-oriented medicine. Part I concludes with the Oath's historic input in the Judgment delivered at the close of the Nuremberg "Doctors' Trial"; this Judgement has become legally binding for the discipline in the Western World and was the basis of the Nuremberg Code. The ethical code of the Oath turned out to be a fundamental part of western law not only on medical ethics but also on patients' rights regarding research.

['Askitopoulou|Helen|H|http://orcid.org/0000-0001-7357-8290', 'Vgontzas|Antoniοs N|AN|']

2018

29168268

Lifetime marijuana use and subclinical atherosclerosis: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

BACKGROUND AND AIMS Unlike tobacco, the effect of marijuana smoke on subclinical atherosclerosis, a surrogate measure for cardiovascular disease, is not known. This study aimed to determine the association between lifetime exposure to marijuana and measures of subclinical atherosclerosis in mid-life. DESIGN, SETTING AND PARTICIPANTS We used data from the US-based Coronary Artery Risk Development in Young Adults (CARDIA) study, a cohort of black and white men and women aged 18-30 years at baseline in 1985-86, with up to seven follow-up examinations over 25 years. A total of 3498 participants in the CARDIA study were included in this study. MEASUREMENTS Cumulative years of exposure to marijuana (expressed in 'marijuana-years', with 1 marijuana-year equivalent to 365 days of use) using repeated assessments every 2-5 years for 25 years. Abdominal artery calcium (AAC) and coronary artery calcium (CAC) scores were measured by computed tomography at year 25 examination. RESULTS Among 3117 participants with AAC and CAC measurements, 2627 (84%) reported past marijuana use and 1536 (49%) past daily tobacco smoking. Compared with tobacco smokers, 46% of whom reported 10 or more pack-years of use, only 12% of marijuana users reported 5 or more marijuana-years of use and only 6% reported having used marijuana daily. We found a significant interaction between never and ever tobacco users on the association between cumulative marijuana use and AAC (P = 0.05). Among those who never smoked tobacco, cumulative marijuana-years were not associated with AAC or CAC in models adjusted for demographics, cardiovascular risk factors, licit and illicit drug exposure and depression symptoms. However, among ever tobacco smokers, marijuana exposure was associated with AAC and CAC. At 5 marijuana-years of exposure, using AAC = 0 and CAC = 0 as a reference group, the odds ratio (OR) was 1.97 [95% confidence interval (CI) = 1.21-3.21, P = 0.007] for AAC > 0/CAC = 0 and 1.83 (95% CI = 1.02-3.31, P = 0.04) for CAC > 0), regardless of AAC. Tobacco smoking was associated strongly with both AAC and CAC. CONCLUSION Marijuana use appears to be associated with subclinical atherosclerosis, but only among ever tobacco users.

['Auer|Reto|R|0000-0003-4222-4849', 'Sidney|Stephen|S|', 'Goff|David|D|', 'Vittinghoff|Eric|E|', 'Pletcher|Mark J|MJ|', 'Allen|Norrina B|NB|', 'Reis|Jared P|JP|', 'Lewis|Cora E|CE|', 'Carr|Jeffrey|J|', 'Rana|Jamal S|JS|']

2018

24948843

CALIBRATING NON-CONVEX PENALIZED REGRESSION IN ULTRA-HIGH DIMENSION.

We investigate high-dimensional non-convex penalized regression, where the number of covariates may grow at an exponential rate. Although recent asymptotic theory established that there exists a local minimum possessing the oracle property under general conditions, it is still largely an open problem how to identify the oracle estimator among potentially multiple local minima. There are two main obstacles: (1) due to the presence of multiple minima, the solution path is nonunique and is not guaranteed to contain the oracle estimator; (2) even if a solution path is known to contain the oracle estimator, the optimal tuning parameter depends on many unknown factors and is hard to estimate. To address these two challenging issues, we first prove that an easy-to-calculate calibrated CCCP algorithm produces a consistent solution path which contains the oracle estimator with probability approaching one. Furthermore, we propose a high-dimensional BIC criterion and show that it can be applied to the solution path to select the optimal tuning parameter which asymptotically identifies the oracle estimator. The theory for a general class of non-convex penalties in the ultra-high dimensional setup is established when the random errors follow the sub-Gaussian distribution. Monte Carlo studies confirm that the calibrated CCCP algorithm combined with the proposed high-dimensional BIC has desirable performance in identifying the underlying sparsity pattern for high-dimensional data analysis.

['Wang|Lan|L|', 'Kim|Yongdai|Y|', 'Li|Runze|R|']

2013

32455798

Hydrostatic Pressure Regulates Oxidative Stress through microRNA in Human Osteoarthritic Chondrocytes.

Hydrostatic pressure (HP) modulates chondrocytes metabolism, however, its ability to regulate oxidative stress and microRNAs (miRNA) has not been clarified. The aim of this study was to investigate the role of miR-34a, miR-146a, and miR-181a as possible mediators of HP effects on oxidative stress in human osteoarthritis (OA) chondrocytes. Chondrocytes were exposed to cyclic low HP (1-5 MPa) and continuous static HP (10 MPa) for 3 hrs. Metalloproteinases (MMPs), disintegrin and metalloproteinase with thrombospondin motif (ADAMTS)-5, type II collagen (Col2a1), miR-34a, miR-146a, miR-181a, antioxidant enzymes, and B-cell lymphoma 2 (BCL2) were evaluated by quantitative real-time polymerase chain reaction qRT-PCR, apoptosis and reactive oxygen species ROS production by cytometry, and β-catenin by immunofluorescence. The relationship among HP, the studied miRNA, and oxidative stress was assessed by transfection with miRNA specific inhibitors. Low cyclical HP significantly reduced apoptosis, the gene expression of MMP-13, ADAMTS5, miRNA, the production of superoxide anion, and mRNA levels of antioxidant enzymes. Conversely, an increased Col2a1 and BCL2 genes was observed. β-catenin protein expression was reduced in cells exposed to HP 1-5 MPa. Opposite results were obtained following continuous static HP application. Finally, miRNA silencing enhanced low HP and suppressed continuous HP-induced effects. Our data suggest miRNA as one of the mechanisms by which HP regulates chondrocyte metabolism and oxidative stress, via Wnt/β-catenin pathway.

['Cheleschi|Sara|S|', 'Barbarino|Marcella|M|', 'Gallo|Ines|I|', 'Tenti|Sara|S|', 'Bottaro|Maria|M|', 'Frati|Elena|E|', 'Giannotti|Stefano|S|', 'Fioravanti|Antonella|A|']

2020

33496010

Predictors and priority of caring behaviours in intensive care units.

BACKGROUND There is an increasing number of studies addressing nurses' perception of caring behaviours; however, on the issue of quality of care, it is important to understand why nurses focus more on certain elements of caring than others, and this needs to investigate influencing factors on, priorities, and predictors of caring behaviours. AIMS The main goal of this study was to determine the predictors and priorities of nurses' caring behaviours in intensive care units to improve the quality of care and patient outcomes. METHODS This is a cross-sectional survey of nurses working in adult and pediatric ICUs in Iran. The participants were 470 ICU nurses from eight hospitals in Iran. Data were collected over 6 months in 2018 using the Persian version of "Caring Assessment Report Evaluation Q-Care"; "Determinants of Nurse Caring Behaviors"; and a demographic data form. RESULTS By broad descriptive and analytical analysis, thirteen items were recognized as predictors of caring behaviours. The most important individual predictors reported as "interest in the nursing profession," "moral obligation," and "job experience," respectively. The most important perceived nursing behaviours were, respectively, subscales of "accessible," "monitors/follow-through" and "explains/facilitates." CONCLUSION The results provide insight into new and context-specific predictors of nurses' caring behaviours. These findings suggest that nursing managers, besides selecting skilful staff for ICUs, may consider employing those of higher "interest in the nursing profession"; "moral obligation"; and "job experience." They, also, need to be aware that organizational culture, climate, and values have a great impact on the caring behaviours of nurses. This could help them to handle the complex issue of improving the quality of care more efficiently.

['Salimi|Saleh|S|https://orcid.org/0000-0002-7969-0619', 'Tarbiat|Shadi|S|']

2021

31106826

Current approaches to measure nitric oxide in plants.

Nitric oxide (NO) is now established as an important signalling molecule in plants where it influences growth, development, and responses to stress. Despite extensive research, the most appropriate methods to measure and localize these signalling radicals are debated and still need investigation. Many confounding factors such as the presence of other reactive intermediates, scavenging enzymes, and compartmentation influence how accurately each can be measured. Further, these signalling radicals have short half-lives ranging from seconds to minutes based on the cellular redox condition. Hence, it is necessary to use sensitive and specific methods in order to understand the contribution of each signalling molecule to various biological processes. In this review, we summarize the current knowledge on NO measurement in plant samples, via various methods. We also discuss advantages, limitations, and wider applications of each method.

['Vishwakarma|Abhaypratap|A|', 'Wany|Aakanksha|A|', 'Pandey|Sonika|S|', 'Bulle|Mallesham|M|', 'Kumari|Aprajita|A|', 'Kishorekumar|Reddy|R|', 'Igamberdiev|Abir U|AU|', 'Mur|Luis A J|LAJ|', 'Gupta|Kapuganti Jagadis|KJ|']

2019

32046057

WEDM of Copper for the Fabrication of Large Surface-Area Micro-Channels A Prerequisite for the High Heat-Transfer Rate.

To get the maximum heat transfer in real applications, the surface area of the micro-features (micro-channels) needs to be large as possible. It can be achieved by producing a maximum number of micro-channels per unit area. Since each successive pair of the micro-channels contain an inter-channels fin, therefore the inter-channels fin thickness (IFT) plays a pivotal role in determining the number of micro-channels to be produced in the given area. During machining, the fabrication of deep micro-channels is a challenge. Wire-cut electrical discharge machining (EDM) could be a viable alternative to fabricate deep micro-channels with thin inter-channels fins (higher aspect ratio) resulting in larger surface area. In this research, minimum IFT and the corresponding machining conditions have been sought for producing micro-channels in copper. The other attributes associated with the micro-channels have also been deeply investigated including the inter-channels fin height (IFH), inter-channels fin radius (IFR) and the micro-channels width (MCW). The results reveal that the inter-channels fin is the most critical feature to control during the wire electrical discharge machining (WEDM) of copper. Four types of fin shapes have been experienced, including the fins: broken at the top end, deflected at the top end, curled bend at the top, and straight with no/negligible deflection.

['Ahmed|Naveed|N|', 'Pervez Mughal|Mohammad|M|', 'Shoaib|Waqar|W|', 'Farhan Raza|Syed|S|', 'M Alahmari|Abdulrhman|A|']

2020

27637594

A cross-sectional study of swine influenza in intensive and extensive farms in the northeastern region of the state of São Paulo, Brazil.

Swine influenza (SI) is a seasonal infectious disease highly important to the world pig industry. Loss of daily weight gain, increased costs for the prevention and treatment of secondary infections are the main economic losses associated with the presence of this disease. However, some epidemiological features of SI remain quite unclear. This study focused on assessing the prevalence of swine influenza virus (SIV) infection in intensive and extensive pig herds and associating risk factors. A set of 601 blood samples of five intensive farrow-to-finish farms and 361 blood samples from 56 extensive farms were analyzed using an indirect ELISA kit CIVTEST SUIS INFLUENZA®, Hipra (Amer, Spain), in order to detect anti-SIV antibodies. In total, 24.13 % of samples from intensive herds were positive, while no positive samples were detected in extensive rearing herds. Sow and weaning piglets had the highest prevalence values. In the intensive rearing system, occurrence of reproductive disorders and exposure to recently introduced animals were positively associated with the disease occurrence in swine herds. The findings highlight the importance of sows in the epidemiology of the disease and bring information about risk factors involved in the occurrence of swine influenza in intensive herds.

['Almeida|Henrique Meiroz de Souza|HM|', 'Storino|Gabriel Yuri|GY|', 'Pereira|Daniele Araújo|DA|', 'Gatto|Igor Renan Honorato|IR|', 'Mathias|Luis Antonio|LA|', 'Montassier|Hélio José|HJ|', 'de Oliveira|Luís Guilherme|LG|']

2017

33129689

Expanding the clinical and metabolic phenotype of DPM2 deficient congenital disorders of glycosylation.

Pathogenic alterations in the DPM2 gene have been previously described in patients with hypotonia, progressive muscle weakness, absent psychomotor development, intractable seizures, and early death. We identified biallelic DPM2 variants in a 23-year-old male with truncal hypotonia, hypertonicity, congenital heart defects, intellectual disability, and generalized muscle wasting. His clinical presentation was much less severe than that of the three previously described patients. This is the second report on this ultra-rare disorder. Here we review the characteristics of previously reported individuals with a defect in the DPM complex while expanding the clinical phenotype of DPM2-Congenital Disorders of Glycosylation. In addition, we offer further insights into the pathomechanism of DPM2-CDG disorder by introducing glycomics and lipidomics analysis.

['Radenkovic|Silvia|S|', 'Fitzpatrick-Schmidt|Taylor|T|', 'Byeon|Seul Kee|SK|', 'Madugundu|Anil K|AK|', 'Saraswat|Mayank|M|', 'Lichty|Angie|A|', 'Wong|Sunnie Y W|SYW|', 'McGee|Stephen|S|', 'Kubiak|Katharine|K|', 'Ligezka|Anna|A|', 'Ranatunga|Wasantha|W|', 'Zhang|Yuebo|Y|', 'Wood|Tim|T|', 'Friez|Michael J|MJ|', 'Clarkson|Katie|K|', 'Pandey|Akhilesh|A|', 'Jones|Julie R|JR|', 'Morava|Eva|E|']

2021

33034105

Binding of direct oral anticoagulants to the FA1 site of human serum albumin.

The anticoagulant therapy is widely used to prevent and treat thromboembolic events. Until the last decade, vitamin K antagonists were the only available oral anticoagulants; recently, direct oral anticoagulants (DOACs) have been developed. Since 55% to 95% of DOACs are bound to plasma proteins, the in silico docking and ligand-binding properties of drugs apixaban, betrixaban, dabigatran, edoxaban, and rivaroxaban and of the prodrug dabigatran etexilate to human serum albumin (HSA), the most abundant plasma protein, have been investigated. DOACs bind to the fatty acid (FA) site 1 (FA1) of ligand-free HSA, whereas they bind to the FA8 and FA9 sites of heme-Fe(III)- and myristic acid-bound HSA. DOACs binding to the FA1 site of ligand-free HSA has been validated by competitive inhibition of heme-Fe(III) recognition. Values of the dissociation equilibrium constant for DOACs binding to the FA1 site (ie, calc KDOAC ) derived from in silico docking simulations (ranging between 1.2 × 10-8 M and 1.4 × 10-6 M) agree with those determined experimentally from competitive inhibition of heme-Fe(III) binding (ie, exp KDOAC ; ranging between 2.5 × 10-7 M and 2.2 × 10-6 M). In addition, this study highlights the inequivalence of rivaroxaban binding to mammalian serum albumin. Given the HSA concentration in vivo (~7.5 × 10-4 M), values of KDOAC here determined indicate that the formation of the HSA:DOACs complexes in the absence and presence of FAs and heme-Fe(III) may occur in vivo. Therefore, HSA appears to be an important determinant for DOACs transport.

['De Simone|Giovanna|G|0000-0002-9358-9891', 'Pasquadibisceglie|Andrea|A|0000-0002-1630-6982', 'di Masi|Alessandra|A|0000-0002-1122-8663', 'Buzzelli|Valeria|V|', 'Trezza|Viviana|V|0000-0002-3922-6045', 'Macari|Gabriele|G|0000-0001-7519-4418', 'Polticelli|Fabio|F|0000-0002-7657-2019', 'Ascenzi|Paolo|P|0000-0002-6449-2150']

2021

31889494

Transforming Non-Selective Angiotensin-Converting Enzyme Inhibitors in C- and N-domain Selective Inhibitors by Using Computational Tools.

The two-domain dipeptidylcarboxypeptidase Angiotensin-I-converting enzyme (EC 3.4.15.1; ACE) plays an important physiological role in blood pressure regulation via the reninangiotensin and kallikrein-kinin systems by converting angiotensin I to the potent vasoconstrictor angiotensin II, and by cleaving a number of other substrates including the vasodilator bradykinin and the anti-inflammatory peptide N-acetyl-SDKP. Therefore, the design of ACE inhibitors is within the priorities of modern medical sciences for treating hypertension, heart failures, myocardial infarction, and other related diseases. Despite the success of ACE inhibitors for the treatment of hypertension and congestive heart failure, they have some adverse effects, which could be attenuated by selective domain inhibition. Crystal structures of both ACE domains (nACE and cACE) reported over the last decades could facilitate the rational drug design of selective inhibitors. In this review, we refer to the history of the discovery of ACE inhibitors, which has been strongly related to the development of molecular modeling methods. We stated that the design of novel selective ACE inhibitors is a challenge for current researchers which requires a thorough understanding of the structure of both ACE domains and the help of molecular modeling methodologies. Finally, we performed a theoretical design of potential selective derivatives of trandolaprilat, a drug approved to treat critical conditions of hypertension, to illustrate how to use molecular modeling methods such as de novo design, docking, Molecular Dynamics (MD) simulations, and free energy calculations for creating novel potential drugs with specific interactions inside nACE and cACE binding sites.

['Alfaro|Sergio|S|', 'Navarro-Retamal|Carlos|C|', 'Caballero|Julio|J|']

2020

24711743

The Control of Hyperglycemia by Estriol and Progesterone in Alloxan induced Type I Diabetes Mellitus Mice Model through Hepatic Insulin Synthesis.

As much as 20% of the women in menopause are reported to develop type I diabetes mellitus. The cessation of the ovarian syntheses of the female sex hormones is known to cause menopause in women, and the roles of estriol (one of the most abundant estrogens) and progesterone were investigated for hepatic insulin synthesis through estriol and progesterone induced synthesis of nitric oxide in the liver cells. Type 1 Diabetic mellitus mice were prepared by alloxan treatment, Nitric oxide was determined by methemoglobin method. Insulin was determined by enzyme linked immunosorbant assay. Injection of either 3.5 µM estriol or 3.5 nM progesterone to the diabetic mice which cannot synthesize pancreatic insulin, reduced the blood glucose level from 600 mg/dl to 120 mg/dl and 500 ± 25 mg/dl to 120 ± 6 mg/dl in 6 and 10 h respectively with simultaneous increase of the plasma insulin from 0 µunits/ml to 40 µunits/ml and 0 µunits/ml to 9.5 µunits/ml in the case of estriol and progesterone respectively with stimulated NO synthesis. The inhibition of the steroids induced NO synthesis by using NAME (NG-methyl-l-arginine acetate ester) in the reaction mixture resulted in the inhibition of hepatic insulin synthesis. Use of pure NO solution in 0.9% NaCl instead of either estriol or progesterone in the reaction mixture was found to stimulate the hepatic insulin synthesis. Both estriol and progesterone might be involved in the prevention of type 1 diabetes mellitus through the hepatic insulin synthesis even when the pancreatic insulin synthesis was impaired.

['Bhattacharya|Suman|S|', 'Bank|Sarbashri|S|', 'Maiti|Smarajit|S|', 'K Sinha|Asru|A|']

2014

28474130

Blood vessel segmentation in color fundus images based on regional and Hessian features.

PURPOSE To propose a new algorithm of blood vessel segmentation based on regional and Hessian features for image analysis in retinal abnormality diagnosis. METHODS Firstly, color fundus images from the publicly available database DRIVE were converted from RGB to grayscale. To enhance the contrast of the dark objects (blood vessels) against the background, the dot product of the grayscale image with itself was generated. To rectify the variation in contrast, we used a 5 × 5 window filter on each pixel. Based on 5 regional features, 1 intensity feature and 2 Hessian features per scale using 9 scales, we extracted a total of 24 features. A linear minimum squared error (LMSE) classifier was trained to classify each pixel into a vessel or non-vessel pixel. RESULTS The DRIVE dataset provided 20 training and 20 test color fundus images. The proposed algorithm achieves a sensitivity of 72.05% with 94.79% accuracy. CONCLUSIONS Our proposed algorithm achieved higher accuracy (0.9206) at the peripapillary region, where the ocular manifestations in the microvasculature due to glaucoma, central retinal vein occlusion, etc. are most obvious. This supports the proposed algorithm as a strong candidate for automated vessel segmentation.

['Shah|Syed Ayaz Ali|SAA|', 'Tang|Tong Boon|TB|', 'Faye|Ibrahima|I|', 'Laude|Augustinus|A|']

2017

28678476

Core-Shell Molecularly Imprinted Polymer Nanoparticles as Synthetic Antibodies in a Sandwich Fluoroimmunoassay for Trypsin Determination in Human Serum.

We describe the application of a fluorescently labeled water-soluble core-shell molecularly imprinted polymer (MIP) for fluorescence immunoassay (FIA) to detect trypsin. p-Aminobenzamidine (PAB), a competitive inhibitor of trypsin, was immobilized in the wells of a microtiter plate enabling the capture of trypsin in an oriented position, thus maintaining its native conformation. Fluorescent MIP nanoparticles, which bound selectively to trypsin, were used for quantification. The MIP was prepared by a multistep solid-phase synthesis approach on glass beads functionalized with PAB, orientating all trypsin molecules in the same way. The core-MIP was first synthesized, using a thermoresponsive polymer based on N-isopropylacrylamide, so as to enable its facile liberation from the immobilized template by a simple temperature change. The shell, mainly composed of allylamine to introduce primary amino groups for postconjugation of fluorescein isothiocyanate (FITC), was grafted in situ on the core-MIP, whose binding cavities were still bound and protected by the immobilized trypsin. The resulting core-shell MIP was endowed with a homogeneous population of high-affinity binding sites, all having the same orientation. The MIP has no or little cross-reactivity with other serine proteases and unrelated proteins. Our MIP-based FIA system was successfully applied to detect low trypsin concentrations spiked into nondiluted human serum with a low limit of quantification of 50 pM, which indicates the significant potential of this assay for analytical and biomedical diagnosis applications.

['Xu|Jingjing|J|', 'Haupt|Karsten|K|', 'Tse Sum Bui|Bernadette|B|http://orcid.org/0000-0002-4170-2303']

2017

30121784

Thioredoxin overexpression in both the cytosol and mitochondria accelerates age-related disease and shortens lifespan in male C57BL/6 mice.

To investigate the role of increased levels of thioredoxin (Trx) in both the cytosol (Trx1) and mitochondria (Trx2) on aging, we have conducted a study to examine survival and age-related diseases using male mice overexpressing Trx1 and Trx2 (TXNTg × TXN2Tg). Our study demonstrated that the upregulation of Trx in both the cytosol and mitochondria in male TXNTg × TXN2Tg C57BL/6 mice resulted in a significantly shorter lifespan compared to wild-type (WT) mice. Cross-sectional pathology data showed a slightly higher incidence of neoplastic diseases in TXNTg × TXN2Tg mice than WT mice. The incidence of lymphoma, a major neoplastic disease in C57BL/6 mice, was slightly higher in TXNTg × TXN2Tg mice than in WT mice, and more importantly, the severity of lymphoma was significantly higher in TXNTg × TXN2Tg mice compared to WT mice. Furthermore, the total number of histopathological changes in the whole body (disease burden) was significantly higher in TXNTg × TXN2Tg mice compared to WT mice. Therefore, our study suggests that overexpression of Trx in both the cytosol and mitochondria resulted in deleterious effects on aging and accelerated the development of age-related diseases, especially cancer, in male C57BL/6 mice.

['Cunningham|Geneva M|GM|', 'Flores|Lisa C|LC|', 'Roman|Madeline G|MG|', 'Cheng|Christie|C|', 'Dube|Sara|S|', 'Allen|Colton|C|', 'Valentine|Joseph M|JM|', 'Hubbard|Gene B|GB|', 'Bai|Yidong|Y|', 'Saunders|Thomas L|TL|', 'Ikeno|Yuji|Y|0000-0002-9234-8738']

2018

30861479

Polytetrafluoroethylene-assisted N/F co-doped hierarchically porous carbon as a high performance electrode for supercapacitors.

In this study, we propose a novel template and chemical activation method to fabricate the nitrogen and fluorine co-doped hierarchically porous carbon with polytetrafluoroethylene-polyaniline as the precursor and KOH as the activation reagent. The key to this strategy is the utilization of polytetrafluoroethylene as an additive during the process, which not only serves as a fluorine source but also acts as a template to increase the specific surface area. Moreover, polytetrafluoroethylene disappears after carbonization without requiring a complicated template-removal process. The as-prepared materials possess a favorable hierarchical porous structure that is conductive to the transportation and diffusion of ions. They also acquire effective nitrogen and fluorine co-doping to further improve the electrochemical performance. The optimized carbon material displays a high specific capacitance (291 F g-1 at 0.5 A g-1) and maintains 180 F g-1 even at 100 A g-1 in 6 M KOH. Moreover, it presents an excellent cycling performance with 95.5% capacitance retention after 10,000 cycles. The fabricated symmetric supercapacitor delivers high energy densities of 12.91 Wh kg-1. These results represent a new performance record for nitrogen and fluorine co-doped porous carbon-based supercapacitors, rendering the polytetrafluoroethylene particles to be a promising template for producing porous carbon materials.

['Zhou|Jiangqi|J|', 'Xu|Lingrui|L|', 'Li|Lijie|L|', 'Li|Xin|X|']

2019

22500249

Effects of Tamsulosin on Urinary Bladder Function and Neuronal Activity in the Voiding Centers of Rats with Cyclophosphamide-induced Overactive Bladder.

PURPOSE The overactive bladder (OAB) syndrome is characterized by urgency usually with frequency and nocturia. Tamsulosin, α(1)-adrenergic receptor antagonist, is widely used to reduce symptoms of urinary obstruction and prostatic hyperplasia. Tamsulosin can across the blood-brain barrier. We investigated the effects of tamsulosin on the symptoms of OAB in relation to neuronal activity using rats. METHODS Adult female Sprague-Dawley rats, weighing 250±10 g (9 weeks old), were used in this study. The animals were divided into five groups (n=8 in each group): control group, OAB-induced group, OAB-induced and 0.01 mg/kg tamsulosin-treated group, OAB-induced and 0.1 mg/kg tamsulosin-treated group, and OAB-induced and 1 mg/kg tamsulosin-treated group. OAB was induced by intraperitoneal injection of cyclophosphamide (75 mg/kg) every third day for 10 days. The rats in the tamsulosin-treated groups orally received tamsulosin once a day for 14 consecutive days at the respective dose of the groups, starting 1 day after the induction of OAB. Cystometry for bladder pressure determination, immunohistochemistry for c-Fos, nicotinamide adenine dinucleotide phosphate-diaphorase histochemistry for nitric oxide synthase (NOS) in the neuronal voiding centers and western blot for inducible NOS in the bladder were conducted. RESULTS Cyclophosphamide injection enhanced contraction pressure and time, representing the induction of OAB. Contraction pressure and time were significantly suppressed by tamsulosin treatment. c-Fos and NOS expressions in the neuronal voiding centers were enhanced by induction of OAB. OAB-induced c-Fos and NOS expressions were suppressed by tamsulosin treatment. CONCLUSIONS Tamsulosin exerts inhibitory effect on neuronal activation in the neuronal voiding centers of OAB. The present results suggest the possibility that tamsulosin is effective therapeutic modality for ameliorating the symptoms of OAB.

['Kim|Sung-Eun|SE|', 'Shin|Mal-Soon|MS|', 'Kim|Chang-Ju|CJ|', 'Park|Ji-Hyeon|JH|', 'Chung|Kyung-Jin|KJ|', 'Jung|Han|H|', 'Kim|Khae-Hawn|KH|', 'Lee|Jung-Hwan|JH|', 'Ko|Il-Gyu|IG|']

2012

21892339

Estradiol valerate and dienogest: a new approach to oral contraception.

Most combination oral contraceptives contain ethinyl estradiol and a progestin. A new and novel oral contraceptive formulation combines estradiol valerate (E2V) with dienogest (DNG) in a four-phase dosing regimen. 17β-estradiol is a naturally-occurring estrogen, and a contraceptive pill containing such an estrogen offers potential benefits with regard to metabolic side effects and adverse events. Dienogest is derived from 19-nortestosterone and exerts profound progestational effects on the endometrium, but it differs from other progestins in its class by its antiandrogenic activity. Estradiol valerate plus dienogest (E2V/DNG) is now available in a four-phasic regimen that integrates an estrogen stepdown and progestin stepup dosing approach along with a short two-day hormone-free interval. This regimen offers safe, reliable contraception and has been shown to be an effective treatment for heavy menstrual bleeding. Metabolic effects and adverse events appear similar to those reported with oral contraceptives containing ethinyl estradiol.

['Kiley|Jessica W|JW|', 'Shulman|Lee P|LP|']

2011

24975698

A prospective study of one-carbon metabolism biomarkers and cancer of the head and neck and esophagus.

Experimental and epidemiological data suggest that factors of one-carbon metabolism are important in the pathogenesis of several cancers, but prospective data on head and neck cancer (HNC) and esophagus cancer are limited. The European Prospective Investigation into Cancer and Nutrition (EPIC) study recruited 385,747 participants from 10 countries who donated a blood sample. The current study included 516 cancer cases of the head and neck and esophagus and 516 individually matched controls. Plasma levels of vitamins B2, B6, B9 (folate), B12, and methionine and homocysteine were measured in pre-diagnostic plasma samples and analyzed in relation to HNC and esophagus cancer risk, as well as post-diagnosis all-cause mortality. After controlling for risk factors, study participants with higher levels of homocysteine had elevated risk of HNC, the odds ratio (OR) in conditional analysis when comparing the top and bottom quartiles of homocysteine [ORQ4 vs. Q1 ] being 2.13 (95% confidence interval [95% CI] 1.13-4.00, p for trend 0.009). A slight decrease in HNC risk was also seen among subjects with higher levels of folate (ORQ4 vs. Q1 0.63, 95% CI 0.35-1.16, p for trend 0.02). Subgroup analyses by anatomical sub-site indicated particularly strong associations with circulating homocysteine for oral cavity and gum cancer (p for trend 8×10(-4)), as well as for oropharynx cancer (p for trend 0.008). Plasma concentrations of the other investigated biomarkers did not display any clear association with risk or survival. In conclusion, study participants with elevated circulating levels of homocysteine had increased risk of developing squamous cell carcinoma of the head and neck.

['Fanidi|Anouar|A|', 'Relton|Caroline|C|', 'Ueland|Per Magne|PM|', 'Midttun|Øivind|Ø|', 'Vollset|Stein Emil|SE|', 'Travis|Ruth C|RC|', 'Trichopoulou|Antonia|A|', 'Lagiou|Pagona|P|', 'Trichopoulos|Dimitrios|D|', 'Bueno-de-Mesquita|H Bas|HB|', 'Ros|Martine|M|', 'Boeing|Heiner|H|', 'Tumino|Rosario|R|', 'Panico|Salvatore|S|', 'Palli|Domenico|D|', 'Sieri|Sabina|S|', 'Vineis|Paolo|P|', 'Sánchez|María-José|MJ|', 'Huerta|José María|JM|', 'Barricarte Gurrea|Aurelio|A|', 'Luján-Barroso|Leila|L|', 'Quirós|J Ramón|JR|', 'Tjønneland|Anne|A|', 'Halkjær|Jytte|J|', 'Boutron-Ruault|Marie-Christine|MC|', 'Clavel-Chapelon|Françoise|F|', 'Cadeau|Claire|C|', 'Weiderpass|Elisabete|E|', 'Johansson|Mikael|M|', 'Riboli|Elio|E|', 'Brennan|Paul|P|', 'Johansson|Mattias|M|']

2015

34287131

Replication in Human Intestinal Enteroids of Infectious Norovirus from Vomit Samples.

A typical clinical symptom of human norovirus infection is projectile vomiting. Although norovirus RNA and viral particles have been detected in vomitus, infectivity has not yet been reported. We detected replication-competent norovirus in 25% of vomit samples with a 13-fold to 714-fold increase in genomic equivalents, confirming infectious norovirus.

['Hagbom|Marie|M|', 'Lin|Jenny|J|', 'Falkeborn|Tina|T|', 'Serrander|Lena|L|', 'Albert|Jan|J|', 'Nordgren|Johan|J|', 'Sharma|Sumit|S|']

2021

34796193

Translatomics Probes Into the Role of Lycopene on Improving Hepatic Steatosis Induced by High-Fat Diet.

Liver is an important organ for fat metabolism. Excessive intake of a high-fat/energy diet is a major cause of hepatic steatosis and its complications such as non-alcoholic fatty liver disease and non-alcoholic steatohepatitis. Supplementation with lycopene, a natural compound, is effective in lowering triglyceride levels in the liver, although the underlying mechanism at the translational level is unclear. In this study, mice were fed a high-fat diet (HFD) to induce hepatic steatosis and treated with or without lycopene. Translation omics and transcriptome sequencing were performed on the liver to explore the regulatory mechanism of lycopene in liver steatosis induced by HFD, and identify differentially expressed genes (DEGs). We identified 1,358 DEGs at the translational level. Through transcriptomics and translatomics joint analysis, we narrowed the range of functional genes to 112 DEGs and found that lycopene may affect lipid metabolism by regulating the expression of LPIN1 at the transcriptional and translational levels. This study provides a powerful tool for translatome and transcriptome integration and a new strategy for the screening of candidate genes.

['Huang|Tengda|T|', 'Yu|Jingsu|J|', 'Ma|Zeqiang|Z|', 'Fu|Qinghua|Q|', 'Liu|Siqi|S|', 'Luo|Zupeng|Z|', 'Liu|Kang|K|', 'Yu|Lin|L|', 'Miao|Weiwei|W|', 'Yu|Dongling|D|', 'Song|Ziyi|Z|', 'Li|Yixing|Y|', 'Zhou|Lei|L|', 'Xu|Gaoxiao|G|']

2021

27066733

Families and Disability Onset: Are Spousal Resources Less Important for Individuals at High Risk of Dementia?

OBJECTIVE To determine whether social contacts and spousal characteristics predict incident instrumental or basic activities of daily living (I/ADL) limitations and whether effects differ for individuals with high risk of dementia. DESIGN Cohort study. SETTING Biennial interviews of Health and Retirement Study participants over up to 12 years. PARTICIPANTS 4,125 participants aged 65 years and older without baseline I/ADL limitations. MEASUREMENTS Participants' family characteristics (living arrangements, proximity to children, contacts with friends, marital status, and spouse's depression, employment, and education) and dementia probability (high versus low risk of dementia based on direct and proxy cognitive assessments) were characterized at baseline. Family characteristics and their interactions with dementia probability were used to predict incident I/ADL limitations in pooled logistic regressions. RESULTS ADL limitation incidence was higher among the unmarried (odds ratio [OR] versus married: 1.14; 95% CI: 1.01-1.30); those married to a depressed spouse (OR versus nondepressed spouse: 1.56, 95% CI: 1.21-2.00); or whose spouse had less than high school education (OR versus spouse with high school or more: 1.29, 95% CI: 1.06-1.57). Living with someone other than a spouse compared with living with a spouse predicted higher risk of both incident ADL (OR: 1.35; 95% CI: 1.11-1.65), and IADL (OR: 1.30; 95% CI: 1.06-1.61) limitations. Effects were similar for respondents with high and low dementia probability. CONCLUSIONS Regardless of dementia risk, older adults may receive important marriage benefits, which help delay disability. The salience of spouse's education and depression status implicate modifiable mechanisms, such as information and instrumental support, which may be amenable to interventions.

['Rist|Pamela M|PM|', 'Liu|Sze Y|SY|', 'Glymour|M Maria|MM|']

2016

25870389

Social immunity and the evolution of group living in insects.

The evolution of group living requires that individuals limit the inherent risks of parasite infection. To this end, group living insects have developed a unique capability of mounting collective anti-parasite defences, such as allogrooming and corpse removal from the nest. Over the last 20 years, this phenomenon (called social immunity) was mostly studied in eusocial insects, with results emphasizing its importance in derived social systems. However, the role of social immunity in the early evolution of group living remains unclear. Here, I investigate this topic by first presenting the definitions of social immunity and discussing their applications across social systems. I then provide an up-to-date appraisal of the collective and individual mechanisms of social immunity described in eusocial insects and show that they have counterparts in non-eusocial species and even solitary species. Finally, I review evidence demonstrating that the increased risks of parasite infection in group living species may both decrease and increase the level of personal immunity, and discuss how the expression of social immunity could drive these opposite effects. By highlighting similarities and differences of social immunity across social systems, this review emphasizes the potential importance of this phenomenon in the early evolution of the multiple forms of group living in insects.

['Meunier|Joël|J|']

2015

26261878

Warmer winters modulate life history and energy storage but do not affect sensitivity to a widespread pesticide in an aquatic insect.

Despite the increased attention for the effects of pesticides under global warming no studies tested how winter warming affects subsequent sensitivity to pesticides. Winter warming is expected to cause delayed negative effects when it increases metabolic rates and thereby depletes energy reserves. Using a common-garden experiment, we investigated the combined effect of a 4 °C increase in winter temperature and subsequent exposure to chlorpyrifos in the aquatic larvae of replicated low- and high-latitude European populations of the damselfly Ischnura elegans. The warmer winter (8 °C) resulted in a higher winter survival and higher growth rates compared to the cold winter (4 °C) commonly experienced by European high-latitude populations. Low-latitude populations were better at coping with the warmer winter, indicating thermal adaptation to the local winter temperatures. Subsequent chlorpyrifos exposure at 20 °C induced strong negative effects on survival, growth rate, lipid content and acetylcholinesterase activity while phenoloxidase activity increased. These pesticide effects were not affected by winter warming. Our results suggest that for species where winter warming has positive effects on life history, no delayed effects on the sensitivity to subsequent pesticide exposure should be expected.

['Arambourou|Hélène|H|', 'Stoks|Robby|R|']

2015

30062658

(-)-4-O-(4-O-β-D-glucopyranosylcaffeoyl) Quinic Acid Inhibits the Function of Myeloid-Derived Suppressor Cells to Enhance the Efficacy of Anti-PD1 against Colon Cancer.

PURPOSE Immunotherapy in the clinic has demonstrated its potential to control cancer through disinhibiting the immune system, especially for immune checkpoint inhibitors such as anti-programmed cell death protein 1/anti-programmed death-ligand 1 (anti-PD1/anti-PD-L1). However, although these new immunotherapies have resulted in durable clinical responses in various cancers, multiple mechanisms of immune resistance and suppression exist in tumors. One significant barrier to efficacy of anti-PD1 against colon cancer may be the recruitment of myeloid-derived suppressor cells (MDSCs) into the tumor microenvironment. Here we demonstrated functional inhibition of G-MDSC with (-)-4-O-(4-O-β-D-glucopyranosylcaffeoyl) quinic acid (QA), an inhibitor of PI3Kδ/γ, reshaped the tumor immune microenvironment and promoted cytotoxic T cell-mediated tumor regression, resultantly enhancing responses to anti-PD1 treatment in colon tumor model. METHODS A syngeneic colon tumor mouse model was used to study the effects of QA on tumor immune microenvironment and its potential synergistic effects with anti-PD1 blockade. RESULTS QA treatment inhibited G-MDSC function in the tumor tissue. Additionally, combination treatment induced CD8+ T lymphocyte-dependent tumor growth delay and prolonged survival time in colon cancer. CONCLUSIONS Our results offered opportunities for new combination strategies using a selective small molecule PI3Kδ/γ inhibitor, to suppress MDSCs to enhance responses to immune checkpoint blockade in colon cancer.

['Lin|HongYue|H|', 'Wu|YuZhu|Y|', 'Chen|JinPing|J|', 'Huang|ShuRong|S|', 'Wang|YangQiang|Y|']

2018

31268381

Effect of uvulopalatopharyngoplasty (UPPP) on atherosclerosis and cardiac functioning in obstructive sleep apnea patients.

Background: Obstructive sleep apnea (OSA) is associated with several cardiovascular comorbidities including hypertension, arteriosclerosis, and heart failure. Uvulopalatopharyngoplasty (UPPP) is a frequently performed surgical treatment for OSA. Aims/Objectives: To analyze if UPPP can improve cardiac parameters associated with atherosclerosis and reduce the cardiac burden in OSA patients. Material and methods: A prospective cohort study was performed at a single tertiary care center where OSA patients undergoing UPPP were evaluated. Preoperative and 6-month postoperative cardiac parameters namely carotid artery intima-media thickness (CIMT), arterial stiffness parameters, echocardiography, and polysomnography (PSG) results were compared. Results: Fifty three patients were included in the study. The success and response rate of UPPP was 60.4%. Following the surgery, significant reduction in arterial stiffness index (β) (12.4 ± 4.1 vs. 11.2 ± 4.0, p = .01), and elasticity modulus (Ep) (172.8 ± 68.3 vs. 156.6 ± 55.3, p = .05) was noticed. Additionally, echocardiographic parameters namely velocity across aortic valve (121.9 ± 22.9 vs. 109.4 ± 17.7, p = .01) and velocity across pulmonary valve (107.4 ± 16.4 vs. 94.2 ± 16.9, p < .01) significantly decreased following UPPP. Conclusions and significance: UPPP significantly improves parameters related to carotid atherosclerosis and has the potential to reduce cardiac burden in OSA patients.

['Zhan|Xiaojun|X|', 'Li|Li|L|', 'Wu|Chan|C|', 'Chitguppi|Chandala|C|', 'Huntley|Colin|C|', 'Fang|Fang|F|', 'Wei|Yongxiang|Y|']

2019

31193758

Hydrocarbon reservoir characterization and discrimination using well-logs over "AIB-EX" Oil Field, Niger Delta.

A computerized advanced statistical analysis which involves the characterization of reservoir elements involving mapping of lithofacies and pore fluids through crossplots of basic seismic variables in both bi-variate and tri-variate domains and functional transformations including rotation of axes have been used as discriminant tools over "AIB-EX" Oil Field, Niger Delta. The methodology encompasses reconstruction of geologic lithofacies information from geophysical logs. Reservoir characterization, rock physics analysis and log inversion were carried out using IHS Kingdom Advanced and Origin software. Three reservoir zones namely A, B, and C were analyzed. The obtained results characterized the reservoir elements as: shale, sandy-shale, shaly-sand and sand (with respective GR counts and P-wave velocity of 105-125 API and 2400-3600 m/s, 75-105 API and 2100-5000 m/s, 45-75 API and 2200-4750 m/s, and 10-45 API and 2000-4600 m/s) which represents seismic scale sedimentary units called lithofacies. Also, the results of both the bi-variate crossplots (GR and P-wave velocity) and tri-variate crossplots (GR, P-wave velocity, and resistivity) have not only differentiated the different lithology but have discriminated the saturating fluid (water or hydrocarbon). The pore fluids were further characterized as either brine or oil based on powerful discriminant tools such as plots of acoustic impedance versus porosity and elastic impedance versus porosity. Conclusively, the result of the research confirmed that hydrocarbon reservoirs can be discriminated with varying degree of effectiveness in various domains using the adopted approach. The obtained result, which can also be used to calibrate seismic inversion, yielded a reliable seismic lithofacies map in the presence of high resolution 3-D seismic data.

['Olorunniwo|Ibukun|I|', 'Olotu|Sunday J|SJ|', 'Alao|Olatunbosun A|OA|', 'Adepelumi|Adekunle A|AA|']

2019

31836166

Serum concentration of homocysteine in spontaneous feline chronic kidney disease.

Serum homocysteine (Hcy) increases in people and dogs with chronic kidney disease (CKD). Hyperhomocysteinemia (HHcy) has also been associated with CKD-related hypertension and proteinuria. The aims of this study were to: (1) validate an enzymatic method for quantification of Hcy in feline serum; (2) evaluate whether HHcy was associated with the presence and severity of CKD, proteinuria or hypertension; and (3) determine whether HHcy could predict disease progression. The intra- and inter-assay coefficients of variation (CVs) and the recovery rates of linearity under dilution and spiking recovery tests of the enzymatic method were 3.1-6.7%, 11.6-12.5%, 96.9±5.4% and 96.9±5.4%, respectively. Healthy cats at risk of CKD (n=17) and cats with CKD (n=19) were sampled over a 6-month period (63 samples in total). Cats with CKD had significantly higher Hcy concentrations (P=0.005) than cats at risk. The concentration of Hcy was higher (P=0.002) in moderate-severe CKD than in mild CKD and correlated moderately with serum creatinine (P<0.0001; r=0.51). The concentration of Hcy increased with the magnitude of proteinuria and correlated weakly with urinary protein to creatinine ratio (P=0.045; r=0.26). HHcy was not associated with hypertension. At the time of enrollment, Hcy concentration was significantly higher (P=0.046) in cats that developed CKD compared to cats that remained stable. The enzymatic method for Hcy measurement in feline serum was precise and accurate. HHcy was relatively common in cats with advanced CKD and seemed to predict disease progression, but further studies are warranted.

['Giraldi|M|M|', 'Paltrinieri|S|S|', 'Curcio|C|C|', 'Scarpa|P|P|']

2019

34156820

Employing Cathodoluminescence for Nanothermometry and Thermal Transport Measurements in Semiconductor Nanowires.

Thermal properties have an outsized impact on efficiency and sensitivity of devices with nanoscale structures, such as in integrated electronic circuits. A number of thermal conductivity measurements for semiconductor nanostructures exist, but are hindered by the diffraction limit of light, the need for transducer layers, the slow scan rate of probes, ultrathin sample requirements, or extensive fabrication. Here, we overcome these limitations by extracting nanoscale temperature maps from measurements of bandgap cathodoluminescence in GaN nanowires of <300 nm diameter with spatial resolution limited by the electron cascade. We use this thermometry method in three ways to determine the thermal conductivities of the nanowires in the range of 19-68 W/m·K, well below that of bulk GaN. The electron beam acts simultaneously as a temperature probe and as a controlled delta-function-like heat source to measure thermal conductivities using steady-state methods, and we introduce a frequency-domain method using pulsed electron beam excitation. The different thermal conductivity measurements we explore agree within error in uniformly doped wires. We show feasible methods for rapid, in situ, high-resolution thermal property measurements of integrated circuits and semiconductor nanodevices and enable electron-beam-based nanoscale phonon transport studies.

['Mauser|Kelly W|KW|https://orcid.org/0000-0001-9903-8559', 'Solà-Garcia|Magdalena|M|https://orcid.org/0000-0002-2614-1050', 'Liebtrau|Matthias|M|https://orcid.org/0000-0002-2374-696X', 'Damilano|Benjamin|B|', 'Coulon|Pierre-Marie|PM|', 'Vézian|Stéphane|S|', 'Shields|Philip A|PA|https://orcid.org/0000-0003-0517-132X', 'Meuret|Sophie|S|https://orcid.org/0000-0001-8511-9972', 'Polman|Albert|A|https://orcid.org/0000-0002-0685-3886']

2021

28638345

Heterogeneity and Developmental Connections between Cell Types Inhabiting Teeth.

Every tissue is composed of multiple cell types that are developmentally, evolutionary and functionally integrated into the unit we call an organ. Teeth, our organs for biting and mastication, are complex and made of many different cell types connected or disconnected in terms of their ontogeny. In general, epithelial and mesenchymal compartments represent the major framework of tooth formation. Thus, they give rise to the two most important matrix-producing populations: ameloblasts generating enamel and odontoblasts producing dentin. However, the real picture is far from this quite simplified view. Diverse pulp cells, the immune system, the vascular system, the innervation and cells organizing the dental follicle all interact, and jointly participate in transforming lifeless matrix into a functional organ that can sense and protect itself. Here we outline the heterogeneity of cell types that inhabit the tooth, and also provide a life history of the major populations. The mouse model system has been indispensable not only for the studies of cell lineages and heterogeneity, but also for the investigation of dental stem cells and tooth patterning during development. Finally, we briefly discuss the evolutionary aspects of cell type diversity and dental tissue integration.

['Krivanek|Jan|J|', 'Adameyko|Igor|I|', 'Fried|Kaj|K|']

2017

28180961

Dermal phospho-alpha-synuclein deposits confirm REM sleep behaviour disorder as prodromal Parkinson's disease.

Phosphorylated alpha-synuclein (p-alpha-syn) deposits, one of the neuropathological hallmarks of Parkinson's disease (PD), have recently been detected in dermal nerve fibres in PD patients with good specificity and sensitivity. Here, we studied whether p-alpha-syn may serve as a biomarker in patients with a high risk of developing PD, such as those with REM sleep behaviour disorder (RBD). We compared the presence and distribution of p-alpha-syn deposits in dermal nerve fibres in 18 patients with RBD, 25 patients with early PD and 20 normal controls. Skin biopsy was taken at C7, Th10, and the upper and lower leg. Presynaptic dopamine transporter imaging using FP-CIT-SPECT was performed in all patients with RBD and in 11 patients with PD. All RBD patients underwent olfactory function testing. The likelihood ratio (LR) for prodromal PD was calculated for each patient based on published research criteria. Skin serial sections were assessed by double-immunofluorescence labelling with antibodies to pSer129-alpha-syn under blinded conditions. P-alpha-syn was visualized in 10/18 patients with RBD (sensitivity of 55.6%) and in 20/25 early PD patients (sensitivity of 80%) but in none of the controls (specificity of 100%). The percentage of dermal structures innervated by p-alpha-syn-positive fibres was negatively correlated with dopamine transporter binding in the FP-CIT-SPECT (ρ = -0.377, p = 0.048), with olfactory function (ρ = -0.668, p = 0.002), and positively correlated with the total LR for RBD to present prodromal PD (ρ = 0.531, p = 0.023). Dermal p-alpha-syn can be considered a peripheral histopathological marker of synucleinopathy and can be detected in a subgroup of RBD patients presumably representing prodromal PD. Dermal p-alpha-syn is detectable in RBD patients without PD motor symptoms, thereby stratifying a patient group that is of great interest for clinical trials testing disease-modifying drugs.

['Doppler|Kathrin|K|', 'Jentschke|Hanna-Maria|HM|', 'Schulmeyer|Lena|L|', 'Vadasz|David|D|', 'Janzen|Annette|A|', 'Luster|Markus|M|', 'Höffken|Helmut|H|', 'Mayer|Geert|G|', 'Brumberg|Joachim|J|', 'Booij|Jan|J|', 'Musacchio|Thomas|T|', 'Klebe|Stephan|S|', 'Sittig-Wiegand|Elisabeth|E|', 'Volkmann|Jens|J|', 'Sommer|Claudia|C|', 'Oertel|Wolfgang H|WH|']

2017

25332442

Use of diffusion tensor imaging in assessing superficial myometrial invasion by endometrial carcinoma: a preliminary study.

BACKGROUND Magnetic resonance imaging (MRI) remains the standard modality for local staging of gynecological malignancies, but it has several limitations, especially when differentiating a cancer limited to the endometrium from a cancer invading the superficial myometrium. PURPOSE To explore 1.5 T diffusion tensor imaging (DTI) in assessing superficial myometrial infiltration by endometrial carcinoma. MATERIAL AND METHODS We analyzed the sensitivity of apparent diffusion coefficient (ADC) versus fractional anisotropy (FA) in diagnosing superficial myometrial infiltration compared to DCE-MRI and T2-weighted imaging (T2WI) in 35 patients with endometrial cancer. For each patient, T2WI-DWI fusion images were generated, and five regions of interest (ROIs) were placed on corresponding DTI images. ADC and FA were calculated, and fiber tractography (FT) images for each level were obtained. ADC and FA values for the five ROIs were compared. RESULTS In distinguishing cancerous versus non-cancerous areas within superficial myometrium, median ADC values were significantly lower (1.16 vs. 1.48, respectively; P < 0.001) and median FA values were significantly higher (0.41 vs. 0.27; P < 0.001, respectively). ADC's versus FA's sensitivity, specificity, PPV, NPV, and accuracy for diagnosing superficial myometrial invasion were 74.3%, 88.6%, 86.7%, 77.5%, 81.4% versus 88.6%, 97.1%, 96.9%, 89.5%, 92.9%, respectively. T2WI and DCE-MR showed a sensitivity of 80.0% and 77.1%, respectively, in diagnosing myometrial invasion. CONCLUSION Both ADC and FA were able to distinguish between cancerous verss non-cancerous areas within superficial myometrium (although FA was more sensitive based on AUC values). In addition, FA was superior to ADC, and more sensitive than T2WI and DCE-MR, in evaluating myometrial invasion. FT images provided visual confirmation of irregular arrangement and direction of the fibers due to proliferation of stromal cells caused by superficial myometrial invasion.

['Zhang|Longmin|L|', 'Liu|Ailian|A|', 'Zhang|Ting|T|', 'Song|Qingwei|Q|', 'Wei|Qiang|Q|', 'Wang|Heqing|H|']

2015

23632016

Unusual cytochrome p450 enzymes and reactions.

Cytochrome P450 enzymes primarily catalyze mixed-function oxidation reactions, plus some reductions and rearrangements of oxygenated species, e.g. prostaglandins. Most of these reactions can be rationalized in a paradigm involving Compound I, a high-valent iron-oxygen complex (FeO(3+)), to explain seemingly unusual reactions, including ring couplings, ring expansion and contraction, and fusion of substrates. Most P450s interact with flavoenzymes or iron-sulfur proteins to receive electrons from NAD(P)H. In some cases, P450s are fused to protein partners. Other P450s catalyze non-redox isomerization reactions. A number of permutations on the P450 theme reveal the diversity of cytochrome P450 form and function.

['Guengerich|F Peter|FP|', 'Munro|Andrew W|AW|']

2013

26385797

Impact Factors and Risk Analysis of Tropical Cyclones on a Highway Network.

Coastal areas typically have high social and economic development and are likely to suffer huge losses due to tropical cyclones. These cyclones have a great impact on the transportation network, but there have been a limited number of studies about tropical-cyclone-induced transportation network functional damages, especially in Asia. This study develops an innovative measurement and analytical tool for highway network functional damage and risk in the context of a tropical cyclone, with which we explored the critical spatial characteristics of tropical cyclones with regard to functional damage to a highway network by developing linear regression models to quantify their relationship. Furthermore, we assessed the network's functional risk and calculated the return periods under different damage levels. In our analyses, we consider the real-world highway network of Hainan province, China. Our results illustrate that the most important spatial characteristics were location (in particular, the midlands), travel distance, landfalling status, and origin coordinates. However, the trajectory direction did not obviously affect the results. Our analyses indicate that the highway network of Hainan province may suffer from a 90% functional damage scenario every 4.28 years. These results have critical policy implications for the transport sector in reference to emergency planning and disaster reduction.

['Yang|Saini|S|', 'Hu|Fuyu|F|', 'Jaeger|Carlo|C|']

2016

26951862

New advances in the diagnosis of canine and feline liver and pancreatic disease.

The diagnosis of liver and pancreatic disorders in dogs and cats present their own set of challenges. However, as new diagnostic tests are developed and the optimal ways in which to use existing tests are determined, the ability of the veterinary profession to make these diagnoses continues to improve. Histopathological assessment is considered to be the reference standard for the diagnosis of many hepatic and pancreatic diseases, but it has some inherent limitations. New classes of diagnostic tests for liver disease that are currently being studied include direct and indirect serum markers of hepatic fibrosis, such as hyaluronic acid; novel markers of hepatocellular injury, such as circulating microRNAs; and quantitative tests of hepatic microsomal function. Assays for pancreas-specific lipase have greatly improved the ability of practitioners to diagnose pancreatitis in dogs and cats. However, further research is needed to fully understand the characteristics of these assays, especially in patients with concurrent non-pancreatic disease. The more common use and refinement of CT and MRI to assess the hepatobiliary system and pancreas of dogs and cats also have huge potential to improve diagnostic capabilities.

['Lidbury|Jonathan A|JA|', 'Suchodolski|Jan S|JS|']

2016

33811676

Systematic Review of Cultural Aspects of Stigma and Mental Illness among Racial and Ethnic Minority Groups in the United States: Implications for Interventions.

Stigma is integral to understanding mental health disparities among racial and ethnic minority groups in the United States. We conducted a systematic review to identify empirical studies on cultural aspects of mental illness stigma (public, structural, affiliative, self) among three racial and ethnic minority groups (Asian Americans, Black Americans, Latinx Americans) from 1990 to 2019, yielding 97 articles. In comparison studies (N = 25), racial and ethnic minority groups often expressed greater public and/or self-stigma than White American groups. In within-group studies (N = 65; Asian American, n = 21; Black American, n = 18; Latinx American; n = 26), which were primarily qualitative (73%), four major cultural themes emerged: 1) service barriers including access and quality (structural stigma); 2) family experiences including concealment for family's sake, fear of being a burden, and stigma extending to family (affiliative stigma); 3) lack of knowledge about mental illness and specific cultural beliefs (public stigma); and 4) negative emotional responses and coping (self-stigma). These findings confirmed stigma has both similar and unique cultural aspects across groups. Despite this, few studies tested stigma reduction interventions (N = 7). These cultural insights can inform contextual change at the health systems and community levels to reduce stigma, and empowerment at the interpersonal and individual levels to resist stigma.

['Misra|Supriya|S|', 'Jackson|Valerie W|VW|', 'Chong|Jeanette|J|', 'Choe|Karen|K|', 'Tay|Charisse|C|', 'Wong|Jazmine|J|', 'Yang|Lawrence H|LH|']

2021

31759051

MicroRNA-998-3p contributes to Cry1Ac-resistance by targeting ABCC2 in lepidopteran insects.

Cry protein toxins produced by Bacillus thuringiensis (Bt) are now widely used in sprays and transgenic crops to control insect pests. Most recently, ATP-binding cassette transporter proteins (ABC transporter), including ABCC2, ABCC3, ABCG1, ABCA2 and ABCB1, were reported as putative receptors for different Cry toxins. However, little is known about the regulatory mechanism involved in the expression of these ABC transporter genes. In the present study, a conserved target site of miR-998-3p was identified from the coding sequence (CDS) of ABCC2 in diverse lepidopteran insects. Luciferase reporter assays demonstrated that miR-998-3p could bind to the CDS of ABCC2 and down-regulate its expression through a conserved site and several non-conserved sites in three representative lepidopteran pests, including Helicoverpa armigera, Spodoptera exigua and Plutella xylostella. Injection of miR-998-3p agomir significantly reduced the abundance of ABCC2, accompanied by increased tolerance to Cry1Ac toxin in H. armigera, S. exigua and P. xylostella (Cry-S) larvae, while injection of miR-998-3p antagomir increased the abundance of ABCC2 dramatically, and thereby reduced the Cry1Ac resistance in a Cry1Ac resistant population of P. xylostella (GX-R). These results give a better understanding of the mechanisms of post-transcriptional regulation of ABCC2, and will be helpful for further studies on the role of miRNAs in the regulation of Cry1Ac resistance in lepidopteran pests.

['Zhu|Bin|B|', 'Sun|Xi|X|', 'Nie|Ximan|X|', 'Liang|Pei|P|', 'Gao|Xiwu|X|']

2020

26680287

The specter of discrimination: Fear of interpersonal racial discrimination among adolescents in Chicago.

This analysis examines fear of interpersonal racial discrimination among Black, Hispanic, and White adolescents. The extent and correlates of these concerns are examined using survey data from the Project for Human Development in Chicago Neighborhoods. Borrowing from the fear-of-crime literature, the contact hypothesis, and group threat theory, several hypotheses are developed linking discrimination fear to direct personal experience with discrimination, indirect or vicarious experience, and environmental signals of discrimination. Results show that about half of Blacks and Hispanics have feared discrimination in the past year. Multivariate results indicate that fear is most likely if one has experienced victimization first-hand and when one's parent is affected by discrimination. Further, a larger presence neighborhood outgroups produces greater fear. Overall, discrimination fear constitutes an additional obstacle for minority adolescents as they transition to adulthood. The phenomenon warrants increased scholarly attention and represents a fruitful avenue for future research.

['Herda|Daniel|D|']

2016

25712626

Idelalisib- a PI3Kδ targeting agent for B-cell malignancies.

Idelalisib, the first in-class phosphotidlyinositol 3-kinase delta (PI3Kδ) inhibitor, was approved by the US Food and Drug Administration in July 2014. It simultaneously received breakthrough therapy designation in combination with rituximab for the treatment of relapsed chronic lymphocytic leukemia (CLL) as well as accelerated approval as monotherapy for the treatment of relapsed follicular lymphoma and relapsed small lymphocytic lymphoma. In a pivotal phase III study of 220 patients with relapsed CLL, the overall response rate of patients who received rituximab plus idelalisib was 81%. The median progression-free survival (PFS) was 5 months with rituximab plus placebo group, but was not reached in the idelalisib arm. At 24 weeks, the PFS in patients receiving idelalisib was 93%. In a phase II trial of 125 patients with relapsed or refractory indolent non-Hodgkin lymphoma who received idelalisib 150 mg twice daily, the response rate was 57%. Complete response was seen in 6% of patients. The median duration of response was 12.5 months, and median PFS was 11 months. Idelalisib is a promising new therapy for relapsed indolent B-cell malignancies.

['Hewett|Yvonne G|YG|', 'Uprety|Dipesh|D|', 'Shah|Binay K|BK|']

2016

32425966

Arp2/3 Complex Is Required for Auxin-Driven Cell Expansion Through Regulation of Auxin Transporter Homeostasis.

The Arp2/3 complex is an actin nucleator shown to be required throughout plant morphogenesis, contributing to processes such as cell expansion, tissue differentiation or cell wall assembly. A recent publication demonstrated that plants lacking functional Arp2/3 complex also present defects in auxin distribution and transport. This work shows that Arp2/3 complex subunits are predominantly expressed in the provasculature, although other plant tissues also show promoter activity (e.g., cotyledons, apical meristems, or root tip). Moreover, auxin can trigger subunit expression, indicating a role of this phytohormone in mediating the complex activity. Further investigation of the functional interaction between Arp2/3 complex and auxin signaling also reveals their cooperation in determining pavement cell shape, presumably through the role of Arp2/3 complex in the correct auxin carrier trafficking. Young seedlings of arpc5 mutants show increased auxin-triggered proteasomal degradation of DII-VENUS and altered PIN3 distribution, with higher levels of the protein in the vacuole. Closer observation of vacuolar morphology revealed the presence of a more fragmented vacuolar compartment when Arp2/3 function is abolished, hinting a generalized role of Arp2/3 complex in endomembrane function and protein trafficking.

['García-González|Judith|J|', 'Kebrlová|Štépánka|Š|', 'Semerák|Matěj|M|', 'Lacek|Jozef|J|', 'Kotannal Baby|Innu|I|', 'Petrášek|Jan|J|', 'Schwarzerová|Kateřina|K|']

2020

27064692

Service innovation through social robot engagement to improve dementia care quality.

Assistive technologies, such as robots, have proven to be useful in a social context and to improve the quality of life for people with dementia (PwD). This study aims to show how the engagement between two social robots and PwD in Australian residential care facilities can improve care quality. An observational method is adopted in the research methodology to discover behavioural patterns during interactions between the robots and PwD. This observational study has undertaken to explore the improvement arising from: (1) approaching social baby-face robots (AR), (2) experiencing pleasure engaging with the robots (P), (3) interacting with the robots (IR), and (4) interacting with others (IO). The findings show that social robots can improve diversion therapy service value to PwD through sensory enrichment, positive social engagement, and entertainment. More than 11,635 behavioral reactions, such as facial expressions and gestures, from 139 PwD over 5 years were coded, in order to identify the engagement effectiveness between PwD and two social robots named Sophie and Jack. The results suggest that these innovative social robots can improve the quality of care for people suffering from dementia.

['Chu|Mei-Tai|MT|', 'Khosla|Rajiv|R|', 'Khaksar|Seyed Mohammad Sadegh|SM|', 'Nguyen|Khanh|K|']

2017

23729915

Care robots for the supermarket shelf: a product gap in assistive technologies.

The literature on the development of assistive robots is dominated by technological papers with little consideration of how such devices might be commercialised for a mass market at a price that is affordable for older people and their families as well as public services and care insurers. This article argues that the focus of technical development in this field is too ambitious, neglecting the potential market for an affordable device that is aleady in the realm of the 'adjacent possible' given current technology capabilities. It also questions on both ethical and marketing grounds the current effort to develop assistive robots with pet-like or human-like features. The marketing literature on 'really new products' has so far not appeared to inform the development of assistive robots but has some important lessons. These include using analogies with existing products and giving particular attention to the role of early adopters. Relevant analogies for care robots are not animals or humans but useful domestic appliances and personal technologies with attractive designs, engaging functionality and intuitive usability. This points to a strategy for enabling mass adoption - which has so far eluded even conventional telecare - of emphasising how such an appliance is part of older people's contemporary lifestyles rather than a sign of age-related decline and loss of independence.

['Blackman|Tim|T|']

2013

33507725

Flexible Artificial Sensory Systems Based on Neuromorphic Devices.

Emerging flexible artificial sensory systems using neuromorphic electronics have been considered as a promising solution for processing massive data with low power consumption. The construction of artificial sensory systems with synaptic devices and sensing elements to mimic complicated sensing and processing in biological systems is a prerequisite for the realization. To realize high-efficiency neuromorphic sensory systems, the development of artificial flexible synapses with low power consumption and high-density integration is essential. Furthermore, the realization of efficient coupling between the sensing element and the synaptic device is crucial. This Review presents recent progress in the area of neuromorphic electronics for flexible artificial sensory systems. We focus on both the recent advances of artificial synapses, including device structures, mechanisms, and functions, and the design of intelligent, flexible perception systems based on synaptic devices. Additionally, key challenges and opportunities related to flexible artificial perception systems are examined, and potential solutions and suggestions are provided.

['Sun|Fuqin|F|', 'Lu|Qifeng|Q|', 'Feng|Simin|S|', 'Zhang|Ting|T|0000-0001-5008-2081']

2021

25206506

Electric stimulation and decimeter wave therapy improve the recovery of injured sciatic nerves.

Drug treatment, electric stimulation and decimeter wave therapy have been shown to promote the repair and regeneration of the peripheral nerves at the injured site. This study prepared a Mackinnon's model of rat sciatic nerve compression. Electric stimulation was given immediately after neurolysis, and decimeter wave radiation was performed at 1 and 12 weeks post-operation. Histological observation revealed that intraoperative electric stimulation and decimeter wave therapy could improve the local blood circulation of repaired sites, alleviate hypoxia of compressed nerves, and lessen adhesion of compressed nerves, thereby decreasing the formation of new entrapments and enhancing compressed nerve regeneration through an improved microenvironment for regeneration. Immunohistochemical staining results revealed that intraoperative electric stimulation and decimeter wave could promote the expression of S-100 protein. Motor nerve conduction velocity and amplitude, the number and diameter of myelinated nerve fibers, and sciatic functional index were significantly increased in the treated rats. These results verified that intraoperative electric stimulation and decimeter wave therapy contributed to the regeneration and the recovery of the functions in the compressed nerves.

['Zhao|Feng|F|', 'He|Wei|W|', 'Zhang|Yingze|Y|', 'Tian|Dehu|D|', 'Zhao|Hongfang|H|', 'Yu|Kunlun|K|', 'Bai|Jiangbo|J|']

2013

29451852

Delta Opioids: Neuroprotective Roles in Preclinical Studies.

Since ancient times, opioids have been used clinically and abused recreationally. In the early stages (about 1,000 AD) of opium history, an Arab physician, Avicenna, administered opioids to control diarrhea and eye diseases. 1 Opioids have very strong pain relieving properties and they also regulate numerous cellular responses. Opioid receptors are expressed throughout the body, including the nervous system, heart, lungs, liver, gastrointestinal tract, and retina. 2-6 Delta opioid receptors (DORs) are a very attractive target from the perspective of both receptor function and their therapeutic potential. Due to a rapid progress in mouse mutagenesis and development of small molecules as DOR agonist, novel functions and roles of DORs have emerged in recent years. This review article focuses on the recent advances in the neuroprotective roles of DOR agonists in general and retina neuroprotection in particular. Rather than being exhaustive, this review highlights the selected studies of DOR function in neuroprotection. We also highlight our preclinical studies using rodent models to demonstrate the potentials of DOR agonists for retinal neuroprotection. Based on existing literature and our recently published data on the eye, DOR agonists possess therapeutic abilities that protect the retina and optic nerve injury against glaucoma and perhaps other retinopathies as well. This review also highlights the signaling events associated with DOR for neuroprotection in the eye. There is a need for translational research on DORs to recognize their potential for clinical application such as in glaucoma.

['Husain|Shahid|S|']

2018

32437881

Pediatrician Attitudes Toward and Experiences With Telehealth Use: Results From a National Survey.

BACKGROUND The American Academy of Pediatrics 2015 policy statement on telehealth proposed that telehealth could increase access to high-quality pediatric care and that pediatricians should work to reduce barriers to telehealth for their patients. However, little is known about pediatricians' experiences with and attitudes toward telehealth. METHODS Data from a nationally representative survey of American Academy of Pediatrics postresidency US member pediatricians in 2016, restricted to respondents providing direct patient care (n = 744; response rate = 48.7%). Survey collected information on experience with telehealth in the previous 12 months, perceived barriers to telehealth incorporation, and conditions under which nonusers would consider using telehealth. In addition to descriptive statistics, we used multivariable logistic regression to examine characteristics associated with any telehealth experience in the past 12 months. RESULTS Fifteen percent of pediatricians reported any telehealth use in the 12 months prior to the survey. The most commonly reported barriers to telehealth adoption were insufficient payment and billing issues. Multivariable regression models indicated that pediatricians in rural areas, the West, and subspecialists were most likely to report telehealth use, and identifying barriers was negatively associated with telehealth use. Among nonusers, over half indicated they would consider adopting telehealth if they were paid for the visits. CONCLUSION Telehealth is considered an important health care delivery mechanism, but only 15% of pediatricians in 2016 reported having used telehealth. Reducing barriers will be instrumental in promoting future telehealth adoption. Many barriers have been reduced during the response to COVID-19, and the impact of these policy changes will need further study.

['Sisk|Blake|B|', 'Alexander|Joshua|J|', 'Bodnar|Chelsea|C|', 'Curfman|Alison|A|', 'Garber|Kelli|K|', 'McSwain|S David|SD|', 'Perrin|James M|JM|']

2020

26188533

Prevalence and correlates of mitral annular calcification in adults with chronic kidney disease: Results from CRIC study.

BACKGROUND Risk factors for mitral annular calcification (MAC) and cardiovascular disease (CVD) demonstrate significant overlap in the general population. The aim of this paper is to determine whether there are independent relationships between MAC and demographics, traditional and novel CVD risk factors using cardiac CT in the Chronic Renal Insufficiency Cohort (CRIC) in a cross-sectional study. METHODS A sample of 2070 subjects underwent coronary calcium scanning during the CRIC study. Data were obtained for each participant at time of scan. SUBJECTS were dichotomized into the presence and absence of MAC. Differences in baseline demographic and transitional risk factor data were evaluated across groups. Covariates used in multivariable adjustment were age, gender, BMI, HDL, LDL, lipid lowering medications, smoking status, family history of heart attack, hypertension, diabetes mellitus, phosphate, PTH, albuminuria, and calcium. RESULTS Our study consisted of 2070 subjects, of which 331 had MAC (prevalence of 16.0%). The mean MAC score was 511.98 (SD 1368.76). Age and white race remained independently associated with presence of MAC. Decreased GFR was also a risk factor. African American and Hispanic race, as well as former smoking status were protective against MAC. In multivariable adjusted analyses, the remaining covariates were not significantly associated with MAC. Among renal covariates, elevated phosphate was significant. CONCLUSION In the CRIC population, presence of MAC was independently associated with age, Caucasian race, decreased GFR, and elevated phosphate. These results are suggested by mechanisms of dysregulation of inflammation, hormones, and electrolytes in subjects with renal disease.

['Abd Alamir|Moshrik|M|', 'Radulescu|Vlad|V|', 'Goyfman|Michael|M|', 'Mohler|Emile R|ER|', 'Gao|Yan Lin|YL|', 'Budoff|Matthew J|MJ|', '|||']

2015

31153706

Impact of the pattern of interstitial lung disease on mortality in rheumatoid arthritis: A systematic literature review and meta-analysis.

OBJECTIVE An important extra-articular manifestation of rheumatoid arthritis (RA) is interstitial lung disease (ILD). The relationship between the usual interstitial pneumonia (UIP) pattern and mortality in patients with RA is unclear. The purpose of this study was to complete a systematic literature review and meta-analysis on the association between RA-ILD pattern and mortality risk. METHODS We performed a systematic literature review through December 12, 2018. Study characteristics, unadjusted and adjusted relative risks (RR) of mortality for ILD pattern were extracted from the identified studies and quality assessments were performed. RR for mortality (RA-UIP vs. other RA-ILD) was pooled using inverse variance weighting and random effects models. RESULTS Ten retrospective cohort studies met our eligibility criteria. A total of 1256 RA-ILD patients were included with 484 total deaths. Meta-analysis yielded a pooled RR of 1.66 (95% confidence interval1.07 to 2.56) for death among those with UIP RA-ILD compared with other patterns. In sub-group analysis when pooling studies comparing UIP to NSIP pattern of RA-ILD, the RR was 2.39 (95% CI 0.86-6.68). CONCLUSION Through a systematic literature review and meta-analysis, we found UIP pattern to be associated with a higher mortality risk in RA-ILD compared to other patterns of RA-ILD although more recent studies emphasize the importance of pulmonary physiology and the extent of lung involvement as significant predictors of mortality rather than the pattern of RA-ILD. Recognizing the small number of studies satisfying eligibility and inconsistent accounting for confounders, further study of mortality risk in RA-ILD is needed with standardized assessment of various RA, ILD, and patient-related factors.

['Singh|Namrata|N|', 'Varghese|Jimmy|J|', 'England|Bryant R|BR|', 'Solomon|Joshua J|JJ|', 'Michaud|Kaleb|K|', 'Mikuls|Ted R|TR|', 'Healy|Heather S|HS|', 'Kimpston|Emily M|EM|', 'Schweizer|Marin L|ML|']

2019

26208767

Skin Care.

Aging skin is among the most common patient concerns in a facial plastic surgery practice. Ultraviolet (UV)-induced damage expedites the pace of intrinsic aging, resulting in many of the visible signs of aging, such as rough skin texture, pigmentation irregularities, fine and deep wrinkling, and inelasticity. Primary prevention of UV and environmental damage with proper skin care and the use of sunscreen are critical. There is great interest in topically applied products to reverse or delay the visible signs of photoaging. We discuss the most common topically applied agents for photoaging, reviewing their mechanisms and supporting evidence.

['Clark|Amelia|A|', 'Hessler|Jill L|JL|']

2015

33754027

Vertebral-specific activation of the CX3CL1/ICAM-1 signaling network mediates non-small-cell lung cancer spinal metastasis by engaging tumor cell-vertebral bone marrow endothelial cell interactions.

Rationale: The spine is one of the most common metastatic sites of non-small cell lung cancer (NSCLC), and NSCLC spinal metastasis results in serious consequences. Metastatic extravasation of disseminated cancer cells including increased invasiveness, adhesion and transendothelial migration is crucial for tumor metastasis. This study aimed to investigate the mechanisms underlying NSCLC spinal metastasis based on the C-X3-C motif chemokine ligand 1- (CX3CL1) and intercellular adhesion molecule-1- (ICAM-1) mediated signaling network. Methods: Immunohistochemistry, western blotting, and reverse transcription-quantitative PCR were conducted to detect the distribution of CX3CL1/ICAM-1 in different organs. Transwell, adhesion, and transendothelial migration assays were performed to evaluate the regulatory effects of CX3CL1/ICAM-1 on NSCLC cell invasion, adhesion, and transendothelial migration in vitro. A spontaneous spinal metastasis mouse model was established via injection of NSCLC cells into the left cardiac ventricle of NOD/SCID mice. The effects of CX3CL1/ICAM-1 on NSCLC spinal metastasis in vivo were validated using bioluminescent, micro-computerized tomography, immunohistochemistry and histological analyses. Results: CX3CL1 expression was specifically higher in vertebral bone compared with limb bones and lung tissue, and was associated with NSCLC spinal metastasis. Mechanically, vertebral bone marrow endothelial cells (VBMECs) enhanced NSCLC cell invasion via CX3CL1 signaling-mediated activation of the PI3K/AKT pathway. Furthermore, we found that VBMECs effectively induced ICAM-1-dependent NSCLC cell adhesion in coordination with platelets through the CX3CL1/ICAM-1/LFA-1 pathway. Meanwhile, CX3CL1 enhanced NSCLC cell transendothelial migration by increasing permeability of VBMECs via ICAM-1-dependent activation of the Src/GEF-H1 pathway. Interestingly, NSCLC cells were indicated to promote CX3CL1 secretion of VBMECs through MAPK14/ADMA17-dependent CX3CL1 release and NF-κB-dependent CX3CL1 synthesis. Based on these findings, we revealed a novel feedback cycle between circulating NSCLC cells and VBMECs mediated by CX3CL1/ICAM-1 signaling. Further disengagement of the CX3CL1/ICAM-1-mediated feedback cycle in vivo significantly restricted metastasis and prolonged mouse survival. Conclusions: Our results indicated a unique feedback cycle between circulating NSCLC cells and VBMECs mediated by CX3CL1/ICAM-1 signaling, which is necessary for NSCLC spinal metastasis. This work provides a new perspective for underlying the mechanisms of NSCLC spinal metastasis and indicates potential novel targets for the prevention of NSCLC spinal metastasis.

['Wang|Ketao|K|', 'Jiang|Libo|L|', 'Hu|Annan|A|', 'Sun|Chi|C|', 'Zhou|Lei|L|', 'Huang|Yiwei|Y|', 'Chen|Qing|Q|', 'Dong|Jian|J|', 'Zhou|Xiaogang|X|', 'Zhang|Feng|F|']

2021