Search

Background A detailed understanding of the relationship between the occipital condyle (OC) and the deeper-lying hypoglossal canal (HC) is necessary for surgeons who place screws into the OC or drill through or around the HC. Therefore, this anatomical study was performed. Methodology A total of 30 skulls (60 sides) underwent an analysis of the angle formed between the long axis of the OC and the HC, i.e., the OC/HC angle. Additionally, the lengths and widths of the OCs and foramen magnum (FM) of each skull were measured using a micrometer. Statistical analyses were performed between the left and right sides, and a Pearson's correlation coefficient was calculated between OC/HC angles and the sizes of the OCs and FM of the skulls. Results The OC/HC angle for the left and right sides ranged from 30 to 56 degrees (mean 46 degrees). The width of the OCs ranged from 9 to 18 mm (mean 13 mm). The length of the OCs was 18 to 31 mm (mean 24 mm). The mean length and width of the FM were 36 mm and 30 mm, respectively. There was no statistically significant difference between the OC/HC angle comparing left and right sides or male or female specimens. Additionally, no statistically significant differences were found between septated and non-septated HC. Pearson's correlation coefficient for left and right OC/HC angles and left and right OC lengths was r = 0.4056 and r = 0.2378, respectively. Pearson's correlation coefficient for left and right OC/HC angles and left and right OC width was r = 0.3035 and r = 0.3530, respectively. Pearson's correlation coefficient for left and right OC/HC angles and the width of the FM was r = 0.2178 and r = 0.2048, respectively. Pearson's correlation coefficient for left and right OC/HC angles and the length of the FM was r = 0.3319 and r = 0.2683, respectively. Conclusions The OC/HC angle as measured here was relatively consistent with no statistically significant differences between sides. We did not find a strong correlation between the width or length of the OC or the width or length of the FM and the OC/HC angles. Therefore, based on our study, surgeons can expect that this angle will range between 30 and 56 degrees (mean 46 degrees). Such knowledge might decrease patient morbidity following invasive procedures involving the OC., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2022, Faisal Siddiqui et al.)

The positive effects of social identification on mental health are well documented in the literature. However, most of this research has been conducted among small groups in WEIRD (Western Educated Industrialized Rich and Democratic Henrich, Heine, & Norenzayan, 2010, Behavioral and Brain Sciences , 33 , 61) settings. Understanding how social identity as a psychological source can improve resilience and welfare among frontline healthcare workers in non-WEIRD contexts can help to alleviate the negative impact of large-scale epidemics overall, especially in resource-poor settings and contribute towards improved welfare of key healthcare workers. The present research investigates whether identifying as a nurse could influence mental health and intentions to quit directly and indirectly via positive and negative emotions among a unique sample of Iranian nurses ( N  = 462) during a risky period, the COVID-19 pandemic. Multiple regression results showed that identifying as a nurse was negatively associated with negative emotions which in turn were positively related to depressive symptoms. In a similar vein, identifying as a nurse was positively associated with positive emotions which, in turn, were negatively related to intentions to quit. Results also confirmed that risk perceptions related to COVID-19 positively moderated the effect of social identification on negative emotions only. That is, identification as a nurse was associated with reduced negative emotions only when perceived risk was low. We discuss the theoretical and practical implications of the findings., Competing Interests: The authors declare no conflict of interest., (© 2022 John Wiley & Sons Ltd.)

Objective: Advances in embryo culture conditions and the development of vitrification as a revolutionary cryopreservation method have allowed for routine use of blastocyst transfer in assisted reproduction technology (ART) cycles. Several vitrification/warming media and devices have been introduced for commercial use so far. The aim of this retrospective study was to compare post-warming survival rates and clinical outcomes of human blastocysts vitrified/warmed by two different commercial methods (CryoTouch and Cryotop) during ART cycles., Methods: This retrospective study assessed a total of 50 frozen embryo transfer (FET) cycles conducted on 56 warmed blastocysts between January 2018 and December 2020. Post-warming blastocyst survival rates and clinical outcomes including clinical pregnancy and live birth rates were calculated after single blastocyst transfer cycles., Results: The results revealed no significant differences between two groups in post-warming survival rate (p-value=0.8381), clinical pregnancy rate (p-value=0.8157) and live birth rate (p-value=0.7041)., Conclusions: Post-warming survival rates and clinical outcomes were comparable with no significant difference in blastocysts vitrified/warmed by CryoTouch and Cryotop commercial methods.

Background: Non-alcoholic steatohepatitis (NASH) is the second-leading indication for liver transplantation (LT) worldwide and is projected to become the leading indication. Our study aimed to determine clinical variables that predict post-LT survival in NASH., Methods: A systematic review and meta-analysis was performed. On June 18, 2020 and April 28, 2022, Ovid MEDLINE ALL, Ovid Embase, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials were searched. No date limits were applied. Inclusion criteria specified the type of study and our study's population/comparison and outcome/timepoints. Pediatric, animal, retransplantation-only, and studies classifying cryptogenic cirrhosis patients with body mass index (BMI) <30 as NASH were excluded. Studies with duplicate cohorts and missing information were excluded from the meta-analysis. Studies were appraised using the Newcastle-Ottawa Scale. This study was preregistered in PROSPERO (CRD42020196915)., Findings: Out of 8583 studies identified, 25 studies were included in the systematic review, while 5 studies were included in the meta-analysis. Our quantitative review suggested that the following variables were predictive of post-LT NASH patient survival: recipient age, functional status, pre-LT hepatoma, model for end-stage liver disease (MELD) score, diabetes mellitus (DM), pre-LT dialysis, hepatic encephalopathy, portal vein thrombosis, hospitalization/ICU at LT, and year of LT. Predictors of graft survival included recipient age, BMI, pre-LT dialysis, and DM. Our pooled meta-analyses included five predictors of patient survival. Increased patient mortality was associated with older recipient age (HR=2·07, 95%CI: 1·71-2·50, I 2 =0, τ 2 =0, p =0·40) and pretransplant DM (HR=1·18, 95%CI: 1·08-1·28, I 2 =0, τ 2 =0, p =0·76)., Interpretation: Our systematic review and meta-analysis aimed to synthesise predictive variables of mortality in LT NASH patients. Clinically, this might help to identify modifiable risk factors that can be optimized in the post-transplant setting to improve patient outcomes and optimises decision making in the resource-limited LT setting., Funding: Toronto General and Western Hospital Foundation., Competing Interests: Dr. Bhat reports grants from Novo Nordisk, grants from Ipsen, grants from Paladin, grants from Natera, grants from Oncoustics, grants from MedoAI, grants from Lallemand, personal fees from Novartis, personal fees from Lupin, outside the submitted work. All other authors have nothing to disclose., (© 2022 The Author(s).)

Objective: The objective of this study was to evaluate the construct validity of 2 health utility instruments-the EuroQoL-5 Dimension (EQ-5D) and the Health Utilities Index-Mark 3 (HUI-3)-and to compare them with disease-specific measures in patients with head and neck cancer., Study Design: Prospective cross-sectional analysis., Setting: Princess Margaret Cancer Centre., Methods: Patients were administered the EQ-5D, HUI-3, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30) and its head and neck cancer module (EORTC QLQ-H&N35), and the University of Washington Quality of Life Questionnaire (UWQoL). Several a priori expected relations were examined. The correlative and discriminative properties of the various instruments were examined., Results: A total of 209 patients completed the 4 questionnaires. A significant ceiling effect was observed among EQ-5D responses (23% reported a maximum score of 1). The EQ-5D (rho = 0.79) and HUI-3 (rho = 0.60) had a strong correlation with the social-emotional domain of the UWQoL. The EQ-5D had a moderate correlation with the physical domain of the UWQoL (rho = 0.42), whereas the HUI-3 had a weak correlation (rho = 0.29). The EQ-5D and HUI-3 were able to distinguish among levels of health severity measured on the EORTC QLQ-C30 though not the QLQ-H&N35. Comparatively, the UWQoL was able to distinguish levels of disease severity on the EORTC QLQ-C30 and QLQ-H&N35., Conclusion: The results of this study demonstrate that disease-specific domains from head and neck quality-of-life instruments are not strongly correlated with the EQ-5D and HUI-3. Consideration should be put toward development of a disease-specific preference-based measure for health economic evaluation., Level of Evidence: 4.

Importance: Patient-derived xenografts (PDXs) offer the opportunity to identify patients with oral cavity squamous cell carcinoma (OSCC) who are at risk for recurrence and optimize clinical decision-making., Objective: To develop and validate a prediction score for locoregional failure (LRF) and distant metastases (DM) in OSCC that incorporates PDX engraftment in addition to known clinicopathological risk factors., Design, Setting, and Participants: In this retrospective cohort study, PDX models were generated from patients with OSCC treated with curative intent at Princess Margaret Cancer Centre (Toronto, Canada) between 2006 and 2018. The cohort included 288 patients (aged ≥18 years) with a new diagnosis of nonmetastatic (M0) OSCC whose tumor samples were available for engraftment under the skin of xenograft mice. Patients were scored as a nonengrafter if PDX formation did not occur within 6 months. Data analysis was performed between August 2006 and May 2018., Interventions: All patients received up-front curative-intent surgery followed by either observation or postoperative radiation with or without concurrent chemotherapy based on institutional guidelines., Main Outcomes and Measures: Main outcomes were LRF, DM, and overall survival (OS). Multivariable analysis (MVA) was used to identify predictors of LRF and DM. Factors retained in the final MVA were used to construct a prediction score and classify patients into risk groups., Results: Overall, 288 patients (mean [SD] age at diagnosis, 63.3 [12.3] years; 112 [39%] women and 176 [61%] men) with OSCC were analyzed. The MVA identified pT3-4, pathologic extranodal extension, and engraftment as predictors of LRF and DM. Patients whose tumors engrafted (n = 198) were more likely to develop LRF (hazard ratio [HR], 1.98; 95% CI, 1.24-3.18) and DM (HR, 2.64; 95% CI, 1.21-5.75) compared with nonengrafters. A prediction score based on the aforementioned variables identified patients at high risk and low risk for LRF (43.5% vs 26.5%), DM (38.2% vs 8.4%), and inferior OS (34% vs 66%) at 5 years. Additionally, rapid engraftment was shown to be similarly prognostic, with rapid engrafters demonstrating higher rates of relapse and poor OS., Conclusions: In this cohort study, a prediction score using OSCC PDX engraftment, in conjunction with pT3-4 and pathologic extranodal extension, was associated with improved prognostic utility of existing clinical models and predicted patients at risk for LRF, DM, and poor survival.

Background: Lean NAFLD may differ from NAFLD found in overweight or obese patients. We used the UK biobank to conduct a cross-sectional study that examined features that distinguish lean NAFLD from overweight or obese NAFLD., Methods: MRI-PDFF data were used to identify patients with NAFLD, with NAFLD defined as PDFF ≥ 5%. BMI patient cohorts were identified, with lean defined as a BMI < 25, and overweight or obese defined as a BMI ≥ 25. Variables of interest to fatty liver disease, including single nucleotide polymorphisms, were chosen from the UK biobank data portal. Logistic regression was used to generate models predictive of NAFLD in each cohort., Results: 1007 patients had NAFLD, and of these, 871 had BMI ≥ 25, and 136 BMI < 25. Factors associated with NAFLD in patients with BMI < 25 included male sex, white blood cell count, red blood cell count, triglycerides, ALT, creatinine, visceral adipose tissue, rs58542926 T, and rs738409 G. In contrast, factors associated with NAFLD in patients with BMI ≥ 25 included male sex, waist circumference, HDL cholesterol, triglycerides, serum glucose, ALT, creatinine, urate, visceral adipose tissue, rs1260326 T, rs1044498 C, rs58542926 T, and rs738409 G. For lean patients, our generated prediction score had an AUC of 0.92, sensitivity of 0.90 and specificity of 0.81. For overweight or obese patients, the prediction score had an AUC of 0.86, sensitivity of 0.87 and specificity of 0.70., Conclusions: Our analysis suggests that lean and overweight or obese NAFLD are distinct entities. We have developed a risk score incorporating both clinical and genetic factors that accurately classify lean patients with NAFLD, with the potential to serve as a tool for screening purposes., (© 2022. Asian Pacific Association for the Study of the Liver.)

To successfully navigate the environment, animals depend on their ability to continuously track their heading direction and speed. Neurons that encode angular head velocity (AHV) are fundamental to this process, yet the contribution of various motion signals to AHV coding in the cortex remains elusive. By performing chronic single-unit recordings in the retrosplenial cortex (RSP) of the mouse and tracking the activity of individual AHV cells between freely moving and head-restrained conditions, we find that vestibular inputs dominate AHV signaling. Moreover, the addition of visual inputs onto these neurons increases the gain and signal-to-noise ratio of their tuning during active exploration. Psychophysical experiments and neural decoding further reveal that vestibular-visual integration increases the perceptual accuracy of angular self-motion and the fidelity of its representation by RSP ensembles. We conclude that while cortical AHV coding requires vestibular input, where possible, it also uses vision to optimize heading estimation during navigation., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Despite the paucity of prospective evidence, stereotactic radiotherapy (SRT) is increasingly being considered in the setting of oligoprogression to delay the need to change systemic therapy., Objective: To determine the local control (LC), progression-free survival (PFS), cumulative incidence of changing systemic therapy, and overall survival (OS) after SRT to oligoprogressive metastatic renal cell carcinoma (mRCC) lesions in patients who are on tyrosine kinase inhibitor (TKI) therapy., Design, Setting, and Participants: A prospective multicenter study was performed to evaluate the use of SRT in oligoprogressive mRCC patients. Patients with mRCC who had previous stability or response after ≥3 mo of TKI therapy were eligible if they developed progression of five of fewer metastases. Thirty-seven patients with 57 oligoprogressive tumors were enrolled., Intervention: Oligoprogressive tumors were treated with SRT, and the same TKI therapy was continued afterward., Outcome Measurements and Statistical Analysis: Competing risk analyses and the Kaplan-Meir methodology were used to report the outcomes of interest., Results and Limitations: The median duration of TKI therapy prior to study entry was 18.6 mo; 1-yr LC of the irradiated tumors was 93% (95% confidence interval [CI] 71-98%). The median PFS after SRT was 9.3 mo (95% CI 7.5-15.7 mo). The cumulative incidence of changing systemic therapy was 47% (95% CI 32-68%) at 1 yr, with a median time to change in systemic therapy of 12.6 mo (95% CI 9.6-17.4 mo). One-year OS was 92% (95% CI 82-100%). There were no grade 3-5 SRT-related toxicities., Conclusions: LC of irradiated oligoprogressive mRCC tumors was high, and the need to change systemic therapy was delayed for a median of >1 yr., Patient Summary: The use of stereotactic radiotherapy in metastatic kidney cancer patients, who develop growth of a few tumors while on oral targeted therapy, can significantly delay the need to change to the next line of drug therapy., (Copyright © 2021 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Aims and Objectives: To investigate whether internal and external violence are associated with turnover intentions among nurses during demanding periods of work., Background: Workplace violence can negatively impact upon mental and physical health and turnover intentions. Research focusing on how dimensions of workplace violence, internal versus external, influence turnover intentions and the factors that mitigate these effect is lacking., Methods: An online cross-sectional survey of multi-item measures was used to collect data from 462 Iranian nurses. We employed path modelling and analysed the data using SPSS and PROCESS macro. A STROBE checklist was used to report findings., Results: Both dimensions, internal and external, of violence were positively associated with turnover intentions. Moreover, perceived invulnerability and organisational support moderates this association. When individuals perceived invulnerability and perceived organisational support are high, internal violence is no longer indirectly related to turnover intentions via job satisfaction. In a similar vein, when perceived invulnerability and perceived organisational support are low, external violence is not related to intentions to quit. When perceived invulnerability and perceived organisational support are high, however, external violence is indirectly and negatively related to intentions to quit., Conclusions: Nurses who regard themselves as invulnerable might be motivated to quit when they experience workplace violence. However, they are motivated to stay on the job when they both perceive themselves as invulnerable and the organisation as supporting., Relevance to Clinical Practice: Organisations should reconsider their policies and approach towards workplace violence especially during periods of intensive work., (© 2021 John Wiley & Sons Ltd.)

Purpose: Circulating tumor DNA (ctDNA) enables personalized treatment strategies in oncology by providing a noninvasive source of clinical biomarkers. In patients with low ctDNA abundance, tumor-naïve methods are needed to facilitate clinical implementation. Here, using locoregionally confined head and neck squamous cell carcinoma (HNSCC) as an example, we demonstrate tumor-naïve detection of ctDNA by simultaneous profiling of mutations and methylation., Experimental Design: We conducted CAncer Personalized Profiling by deep Sequencing (CAPP-seq) and cell-free Methylated DNA ImmunoPrecipitation and high-throughput sequencing (cfMeDIP-seq) for detection of ctDNA-derived somatic mutations and aberrant methylation, respectively. We analyzed 77 plasma samples from 30 patients with stage I-IVA human papillomavirus-negative HNSCC as well as plasma samples from 20 risk-matched healthy controls. In addition, we analyzed leukocytes from patients and controls., Results: CAPP-seq identified mutations in 20 of 30 patients at frequencies similar to that of The Tumor Genome Atlas (TCGA). Differential methylation analysis of cfMeDIP-seq profiles identified 941 ctDNA-derived hypermethylated regions enriched for CpG islands and HNSCC-specific methylation patterns. Both methods demonstrated an association between ctDNA abundance and shorter fragment lengths. In addition, mutation- and methylation-based ctDNA abundance was highly correlated ( r > 0.85). Patients with detectable pretreatment ctDNA by both methods demonstrated significantly worse overall survival (HR = 7.5; P = 0.025) independent of clinical stage, with lack of ctDNA clearance post-treatment strongly correlating with recurrence. We further leveraged cfMeDIP-seq profiles to validate a prognostic signature identified from TCGA samples., Conclusions: Tumor-naïve detection of ctDNA by multimodal profiling may facilitate biomarker discovery and clinical use in low ctDNA abundance applications., (©2021 The Authors; Published by the American Association for Cancer Research.)

Aims: The aims of the study were to identify predictors of locoregional failure (LRF) following surgery for pancreatic adenocarcinoma, develop a prediction risk score model of LRF and evaluate the impact of postoperative radiation therapy (PORT) on LRF., Materials and Methods: A retrospective review was conducted on patients with stages I-III pancreatic adenocarcinoma who underwent surgery at our institution (2005-2016). Univariable and then multivariable analyses were used to evaluate clinicopathological factors associated with LRF for patients who did not receive PORT. The risk score of LRF was calculated based on the sum of coefficients of the predictors of LRF. The model was applied to the entire cohort to evaluate the impact of PORT on the high- and low-risk groups for LRF., Results: In total, 467 patients were identified (median follow-up 22 months). Among patients who did not receive PORT (n = 440), predictors of LRF were pN+, involved or close ≤1 mm margin(s), moderately and poorly differentiated tumour grade and lymphovascular invasion. After adding patients who received PORT, the 2-year LRF in the high-risk group was 57% for patients who did not receive PORT (n = 242) and 32% among patients who received PORT (n = 22), with an absolute benefit to LRF of 25% (95% confidence interval 5-52%, P = 0.07). The 2-year overall survival for the high-versus the low-risk group was 36% versus 67% (P < 0.001)., Conclusion: This risk group classification could be used to identify pancreatic adenocarcinoma patients with higher risk of LRF who may benefit from PORT. However, validation and prospective evaluation are warranted., (Copyright © 2021 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Current guidelines state that infliximab is contraindicated for the treatment of immune checkpoint inhibitor-related hepatitis (ir-hepatitis) due to the risk of inducing further liver damage. As this recommendation is largely based on the use of infliximab for rheumatologic diseases, we evaluated the efficacy and hepatotoxicity of infliximab in patients with steroid-refractory immune-related adverse events (irAEs)., Methods: We retrospectively reviewed consecutive patients treated with infliximab for irAEs at Princess Margaret Cancer Centre. To assess hepatotoxicity, we compared the mean value of ALT, AST, and total bilirubin (BT) before and after infliximab treatment. We used logistic regression to assess factors associated with infliximab efficacy., Results: Between January 2010 and February 2019, 56 patients were identified. The median age of the patients was 63 (27-84) years. Colitis was the most frequent toxicity (66%), followed by pneumonitis (11%). Infliximab was used to treat ir-hepatitis in one patient. The median number of infliximab doses was 1 (1-3) and led to toxicity resolution in 43 (76%) patients. The mean ALT, AST, and BT levels before and after infliximab treatment were not statistically different. The patient treated for ir-hepatitis had a complete recovery, with no incremental liver toxicity., Conclusions: In this dose-limited setting, infliximab was effective in resolving irAEs and did not induce hepatotoxicity.

Introduction: Interruption of regulation of apoptosis can play a leading role in cancers where elevated apoptosis causes neurodegeneration, autoimmunity, AIDS, and ischemia. One famous example can be p53's downregulation, which is a tumor suppressor gene, which consequently can cause a decrease in apoptosis rate and intense tumor growth and progression and development and inactivation of 53; it can be extended to many cancers in human. Anyhow, apoptosis is a double-edge sword. There are many trials and studies are going on observation and understanding of different steps involved in apoptosis. Apoptosis has a very major role in carcinogenesis and the treatment of cancer., Aim: In this updated-cum-comprehensive review, we would like to cover what is apoptosis and cancer and also, will discuss all known methods of apoptosisdetection, their applicability in the treatment of cancer, and their advantages, disadvantages, and limitations., Material and Methods: Published articles on indexing sources such as PubMed, Scopus from 2000 to date., Result: By considering all above information including each methods pros and cons, these routine methods could be great tool with distinctive qualities in treatmentwhich can be great help from patient perspective and as well from government ad health care system point of view., Conclusion: Accurate diagnosis of cell apoptotic biopathways at different stages assists in evaluating near to exact apoptotic index, which is the perfect sign andindicator for metastasis and also prognosis, thus foreseeing treatment outcome.

Objective: The role of genetic factors in the risk of cardiovascular disease (CVD) for patients with type 1 diabetes (T1D) remains unknown. We therefore examined whether previously identified genetic factors for coronary artery disease (CAD) are associated with the risk of CVD above and beyond established demographic and clinical factors in the Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) study., Research Design and Methods: Polygenic risk scores (PRS) and individual genetic variants identified in previous studies were obtained from genome-wide genotyping performed in 1,371 DCCT/EDIC participants. Two composite CVD outcomes were considered: major adverse cardiovascular events (MACE) (CVD death or nonfatal myocardial infarction [MI] or stroke) and any CVD (MACE plus confirmed angina, silent MI, revascularization, or congestive heart failure). Cox proportional hazards models assessed the association between the genetic factors and the risk of CVD with adjustment for other factors (including age, lipids, blood pressure, and glycemia)., Results: CAD PRS was strongly associated with the subsequent risk of any CVD (42% and 38% higher risk per 1-SD increase in unadjusted and fully adjusted models, respectively; P < 0.0001) and with the risk of MACE (50% and 40% higher risk per 1-SD increase in unadjusted and fully adjusted models, respectively; P < 0.0001). Several individual single nucleotide polymorphisms were also nominally associated with the risk of any CVD and MACE., Conclusions: Genetic factors are associated with the risk of subsequent CVD in individuals with T1D above and beyond the effect of established risk factors such as age, lipids, blood pressure, and glycemia., (© 2021 by the American Diabetes Association.)

Understanding the function of the nervous system necessitates mapping the spatial distributions of its constituent cells defined by function, anatomy or gene expression. Recently, developments in tissue preparation and microscopy allow cellular populations to be imaged throughout the entire rodent brain. However, mapping these neurons manually is prone to bias and is often impractically time consuming. Here we present an open-source algorithm for fully automated 3D detection of neuronal somata in mouse whole-brain microscopy images using standard desktop computer hardware. We demonstrate the applicability and power of our approach by mapping the brain-wide locations of large populations of cells labeled with cytoplasmic fluorescent proteins expressed via retrograde trans-synaptic viral infection., Competing Interests: The authors have declared that no competing interests exist.

Objective: Individuals with diabetes have higher resting heart rate compared with those without, which may be predictive of long-term cardiovascular disease (CVD) risk. Using data from the Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) study, we evaluated whether the beneficial effect of intensive versus conventional diabetes therapy on heart rate persisted, the factors mediating the differences in heart rate between treatment groups, and the effects of heart rate on future CVD risk., Research Design and Methods: Longitudinal changes in heart rate, from annual electrocardiograms over 22 years of EDIC follow-up, were evaluated in 1,402 participants with type 1 diabetes. Linear mixed models were used to assess the effect of DCCT treatment group on mean heart rate over time, and Cox proportional hazards models were used to estimate the effect of heart rate on CVD risk during DCCT/EDIC., Results: At DCCT closeout, 52% of participants were male and mean ± SD age was 33 ± 7 years, diabetes duration 12 ± 5 years, and HbA 1c 7.4 ± 1.2% (intensive) and 9.1 ± 1.6% (conventional). Through EDIC, participants in the intensive group had significantly lower heart rate in comparison with the conventional group. While significant group differences in heart rate were fully attenuated by DCCT/EDIC mean HbA 1c , higher heart rate predicted CVD and major adverse cardiovascular events independent of other risk factors., Conclusions: After 22 years of follow-up, former intensive versus conventional therapy remained significantly associated with lower heart rate, consistent with the long-term beneficial effects of intensive therapy on CVD. DCCT treatment group effects on heart rate were explained by differences in DCCT/EDIC mean HbA 1c ., (© 2021 by the American Diabetes Association.)

This study compares knowledge, experience and understanding of genetic testing, and psychological outcomes among breast and ovarian cancer patients undergoing multi-gene panel testing via genetic counselor-mediated (GMT) or oncologist-mediated (OMT) testing models. A pragmatic, prospective survey of breast and ovarian cancer patients pursuing genetic testing between January 2017 and August 2019 was conducted at the Princess Margaret Cancer Centre in Toronto, Canada. A total of 120 (80 GMT; 40 OMT) individuals completed a survey administered one week following consent to genetic testing. Compared to OMT, the GMT cohort had higher median knowledge (8 vs. 9; p = 0.025) and experience/understanding scores (8.5 vs. 10; p < 0.001) at the time of genetic testing. Significant differences were noted in the potential psychological concerns experienced, with individuals in the GMT cohort more likely to screen positive in the hereditary predisposition domain of the Psychosocial Aspects of Hereditary Cancer tool (55% vs. 27.5%; p = 0.005), and individuals in the OMT cohort more likely to screen positive in the general emotions domain (65.0% vs. 38.8%; p = 0.007). The results of this study suggest that OMT can be implemented to streamline genetic testing; however, post-test genetic counseling should remain available to all individuals undergoing genetic testing, to ensure any psychologic concerns are addressed and that individuals have a clear understanding of relevant implications and limitations of their test results.

Today, the direct-acting antiviral agents (DAAs) such as sofosbuvir (SOF) and ledipasvir (LED) are widely used to treat the hepatitis virus infection. The aim of this study was to develop a rapid, simple and valid method for simultaneous determination of SOF and LED in human plasma for bioavailability and pharmacokinetic studies. Chromatographic analysis was performed on the C 18 column (Blue Orchid, 1.8 μm, 50 × 2 mm) using 0.1 % formic acid in water (pH 2.6) and acetonitrile (60:40; v/v) as mobile phase at a flow rate of 0.5 mL/min. The UV detector was set at 328 nm and 260 nm for analysis of SOF and LED, respectively. To 400 μL of plasma, 100 μL of clonazepam as the internal standard (I.S, 7 μg/mL) was added and the mixture subjected to liquid-liquid extraction using 1000 μL diethyl ether. The calibration curves were linear with coefficients of variation less than 8% for all analyses. The limit of quantification (LOQ) was 20 and 5 ng/mL for SOF and LED, respectively. The results of inter-day and intra-day precision showed good reproducibility and the total analysis time was 1.2 min. This method successfully applied for determination SOF and LED in four healthy volunteers., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020. Published by Elsevier B.V.)

Background: We aimed to compare unstimulated saliva flow using 3-minute modified Schirmer test (MST) following bilateral vs unilateral radiotherapy (RT) in oropharyngeal carcinoma (OPC)., Methods: We reviewed OPC patients treated with definitive intensity-modulated radiation therapy (IMRT) between 2011 and 2017. MST was measured at baseline, 1-/6-/12-/24-month post-RT. MST values were compared between bilateral-RT vs unilateral-RT groups. Multivariable logistic regression analysis (MVA) identified predictors of hyposalivation (MST < 25 mm)., Results: Total 498 bilateral-RT and 36 unilateral-RT patients were eligible. The MST values at 1-/6-/12-/24-month post-RT were all significantly reduced from baseline for the entire cohort. Baseline unilateral-RT and bilateral-RT MST values (in mm) were similar (P = .2), but much higher for unilateral-RT 1-month (mean: 19.1 vs 13.0, P = .03), 6-month (20.5 vs 9.3, P < .001), 12-month (20.1 vs 11.9, P < .01), and 24-month post-RT (22.2 vs 13.9, P = .04). MVA confirmed that unilateral RT reduced the likelihood of hyposalivation vs bilateral RT (OR 2.36, P = .006)., Conclusion: Unilateral RT reduces unstimulated salivary flow in OPC patients., (© 2020 Wiley Periodicals LLC.)

Enterobacteriaceae spp., owing to their high durability and antibiotic-resistant mechanisms, are described as an eminent part of health treatments in hospital-acquired infections. This study aimed to estimate the prevalence of clinical isolated Enterobacteriaceae spp., and their multidrug-resistant rate in the north of Iran. In this cross-sectional study, over two years (2017-2019), clinical isolates were collected and Enterobacteriaceae spp. were identified using the standard media culture and Analytical Profile Index (API 20E) kit from two centers in the north of Iran. Isolates were confirmed by targeting the rpoB gene. Moreover, the susceptibility patterns of isolates were assessed using disc diffusion methods according to the Clinical Laboratory Standard Institute (CLSI) guidelines. Out of 2645 clinical specimens, 297 (11.2%) were confirmed as Enterobacteriaceae spp. containing Eshershia. coli 93 (31%), Citrobacter freundii 65 (21.9%), Klebsiella pneumoniae 48 (16.2%), Enterobacter spp. 43 (14.5%), and Proteus spp. 23 (7.7%). As much as 8.7% of other spp. Ampicillin (81.1%) and cephalexin (80.9%) have been shown to have the greatest resistant, and nalidixic acid (65%) and amikacin (59.2%) were the most sensitive drugs. Multidrug-resistance (MDR) strains are more isolated in the Burn and Burn intensive care unit (BICU) than other wards. The MDR frequency in Bouali and Zareh hospitals were 65 (49.61%) and 130 (78.31%), respectively. Considering the high isolation rates of MDR Enterobacteriaceae spp., preventive measures need to be taken to remove the mentioned bacteria from hospital wards.

Background: Diabetes mellitus (DM) is a well-known clinical entity with various late complications. There is a surge of research aiming to use the medical herb in the management of DM., Objective: This study aimed to investigate whether the alleviation of DM by an isolated compound from Rosa canina is mediated by DNA methylation in STZ-diabetic rats., Methods: Sixty adult Wistar male rats were classified into control, diabetic and treatment groups. Rats were treated with STZ (40 mg/kg), metformin (500 mg/kg), and oligosaccharide fraction (OF; 10, 20 and 30 mg/kg) isolated from Rosa canina. DNA was extracted from the blood and pancreas to determine DNA methylation using the Global DNA Methylation kit. The expressions of DNA methyltransferases (Dnmts), PDX1, Ins1, GCK and PTP1B2 were determined by using qRT-PCR., Results: The significant blood glucose-lowering potential of OF was associated with a reduced level of global DNA methylation (p < 0.05). The expression levels of Dnmts 1 and 3α increased in the pancreas and blood from diabetic rats compared to control group which declined by OF treatment (p < 0.05). Paradoxically, the expression of Dnmt 3β augmented in the pancreas and blood of OF group compared to diabetic ones (p < 0.05). Besides, the expressions of Pdx1, PTP1B2, Ins1 and GCK increased in OF-treated rats compared to diabetic groups., Conclusion: Results revealed that DNA methylation plays a causal role in the effectiveness of the isolated OF. Furthermore, the possible regenerative potential of oligosaccharide in diabetic rats may have contributed to the modulation of DNA methylation.

Objective: MicroRNAs act locally and systemically to impact osteoarthritis (OA) pathophysiology, but comprehensive profiling of the circulating miRNome in early vs late stages of OA has yet to be conducted. Sequencing has emerged as the preferred method for microRNA profiling since it offers high sensitivity and specificity. Our objective was to sequence the miRNome in plasma from 91 patients with early [Kellgren-Lawrence (KL) grade 0 or 1 (n = 41)] or late [KL grade 3 or 4 (n = 50)] symptomatic radiographic knee OA to identify unique microRNA signatures in each disease state., Design: MicroRNA libraries were prepared using the QIAseq miRNA Library Kit and sequenced on the Illumina NextSeq 550. Counts were produced for microRNAs captured in miRBase and for novel microRNAs. Statistical, bioinformatics, and computational biology approaches were used to refine and interpret the final list of microRNAs., Results: From 215 differentially expressed microRNAs (FDR < 0.01), 97 microRNAs showed an increase or decrease in expression in ≥85% of samples in the early OA group as compared to the median expression in the late OA group. Increasing this threshold to ≥95%, seven microRNAs were identified: hsa-miR-335-3p, hsa-miR-199a-5p, hsa-miR-671-3p, hsa-miR-1260b, hsa-miR-191-3p, hsa-miR-335-5p, and hsa-miR-543. Four novel microRNAs were present in ≥50% of early OA samples and had 27 predicted gene targets in common with the prioritized set of predicted gene targets from the 97 microRNAs, suggesting common underlying mechanisms., Conclusion: Sequencing of well-characterized patient cohorts produced unbiased profiling of the circulating miRNome and identified a unique panel of 11 microRNAs in early radiographic knee OA., (Copyright © 2020 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: Sexual health problems have been identified as an unmet need in head and neck cancer (HNC) survivors. In particular, little is known about such outcomes in survivors of nasopharyngeal cancer (NPC)., Materials and Methods: A cross-sectional study of NPC survivors with ≥4y follow-up was undertaken. Sexual satisfaction was assessed using the optional "I am satisfied with my sex life" item of the FACT-H&N. Other patient-reported outcomes measures were also captured including fatigue (FACIT-F), HNC symptom burden (MDASI-HN), emotional distress (HADS) and frontal function (FrSBE). Univariate and multivariate analyses were performed to determine factors influencing sexual satisfaction., Results: The sexual satisfaction item was answered by 85/103 (83%) enrollees. Female (p < 0.001) and non-partnered (p = 0.0045) patients were more likely to abstain from answering. The distribution of responses were: "very much" (26%), "quite a bit" (21%), "somewhat" (20%), "a little bit" (13%) and "not at all" (20%). Sexual satisfaction was associated with multiple patient-reported measures on univariate analysis, including quality of life, fatigue, a priori selected HNC symptoms (pain, taste), emotional distress, frontal lobe function, body image and relationship strength. On multivariate analysis, only relationship strength and emotional distress remained significant. Sociodemographic factors (age, sex, marital status) and other selected orofacial toxicities were not significant., Conclusions: Nearly half (47%) of our sample reported being in the higher satisfaction range. While reassuring in the context of comparative population level data, a number of factors including toxicity, psychological and social factors were associated with sexual satisfaction responses. Prospective evaluation of this unmet need is required., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Chromium (Cr) is an essential trace element which found naturally in a daily diet and available in the form of supplementary tablets to boost disorders like diabetes mellitus (DM) and functions like lipid metabolism and beneficial on depression too. Diabetes is one of the most prevalent endocrine diseases or in other words, the most severe metabolic syndrome (MS), which associated with high production of free-radicals which is out of bodies detoxifying machine capacity or high oxidative stress (HOS), vasculitis and elevated lipid profile. many research papers and clinical trials published about the significance of chromium on biological activities, pre and post clinical. For this review research articles, clinical trials, from 1 st Jan'10 to 31 st Dec'18 and refer literature for the biochemical, pharmacological and biological activity of Chromium. Primarily articles gathered from the above search engines. Then precisely according to our aim and goal and regarding designed objectives dismisses similar articles and finally came to 84 articles for the above said period. This review trying to cover the entire picture from what chromium is to the recent updates on their greater role in increasing insulin sensitivity of cells and enhancing lipid metabolism and even recent findings suggest its positive effects including prevention and ameliorating properties on depression. The biological activities, pharmacological features, clinical implications including efficacy and role of chromium compounds on the glycaemic index will be discussed. The outcome of this review is to bring the pros and cons of chromium supplementation along with is safety and toxicity concern beside molecular pathways, biochemistry and clinical trials, all in one comprehensive review., Competing Interests: Conflict of interestThe authors declare that there is no conflict of interest regarding the publication of this article., (© Springer Nature Switzerland AG 2020.)

Diabetes mellitus is the most common metabolic disorder characterized by chronic hyperglycemia. There has been a surge of research studies aiming to use natural products in the management of diabetes. The objective of this study was to isolate and characterize the structure and anti-diabetic mechanisms of the main ingredient from Rosa canina. The oligosaccharide was isolated from Rosa canina fruits and characterized by a combination of FTIR, NMR and Mass spectrometry. Wistar rats were divided into negative control, diabetic (type 2), isolated oligosaccharide (IO)-treated diabetic and positive diabetic controls. Oral glucose tolerance, gluconeogenesis and α-glucosidase inhibitory tests as well as immunohistochemistry and quantitative real time-PCR were performed to elucidate the molecular anti-diabetic mechanisms of IO. Structural analyses confirmed the oligosaccharide structure of isolated fraction. Gluconeogenesis and α-glucosidase activity were inhibited by IO in diabetic rats. The oral glucose tolerance test was improved significantly in the group treated with the IO (P < 0.05). Pancreatic β-cells and tissue pathological examination showed a significant improvement after the treatment period. In addition, the expression of Ngn3, Nkx6.1 and insulin increased in oligosaccharide-treated compared to untreated diabetic rats. Owing to the verified anti-diabetic effects and regenerative potential, isolated oligosaccharide could be considered as the promising drug in the management of diabetes., Competing Interests: Declaration of competing interest We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome., (Copyright © 2020. Published by Elsevier Ltd.)

Background and Purpose: Because of the high prevalence, diabetes is considered a global health threat. Hence, the need for effective, cheap, and comfortable therapies are highly felt. In previous study, a novel oligosaccharide with strong anti-diabetic activity in the crude extract of Rosa canina fruits, from the rosacea family, was identified. The present study was designed to ensure its efficacy using in vivo and in vitro studies., Experimental Approach: Crude extract and its purified oligosaccharide were prepared from corresponding herb. Adult male Wistar rats were randomly divided into four groups of 10 each, as follows: group 1, healthy control rats given only sterile normal saline; group 2, diabetic control rats received sterile normal saline; group 3, diabetic rats treated with crude extract of Rosa canina (40% w/v) by oral gavage for 8 weeks; group 4, diabetic rats treated with purified oligosaccharide of Rosa canina (2 mg/kg) by oral gavage for 8 weeks. After treatment, body weight, fasting blood glucose, serum insulin levels and islet beta-cell repair and proliferation were investigated. The possible cytoprotective action of oligosaccharide was evaluated in vitro . The effect of oligosaccharide on apoptosis and insulin secretion in cell culture media were examined. Real-time PCR was used to determine the expression level of some glucose metabolism-related regulator genes., Findings / Results: In the animal model of diabetes, the insulin levels were increased significantly due to the regeneration of beta-cells in the islands of langerhans by the purified oligosaccharide. In vitro cell apoptosis examination showed that high concentration of oligosaccharide increased cell death, while at low concentration protected cells from streptozotocin-induced apoptosis. Molecular study showed that the expression of Ins1 and Pdx1 insulin production genes were increased, leading to increased expression of insulin-dependent genes such as Gck and Ptp1b . On the other hand, the expression of the Slc2a2 gene, which is related to the glucose transporter 2, was significantly reduced due to insulin concentrations., Conclusion and Implications: The purified oligosaccharide from Rosa canina was a reliable anti-diabetic agent, which acted by increasing insulin production in beta-cells of the islands of Langerhans., Competing Interests: The authors declare no conflict of interest for this study., (Copyright: © 2020 Research in Pharmaceutical Sciences.)

Diabetes, a disease with abnormal production or use of insulin, is a growing concern that affects many individuals globally. Although many attempts have been made, there is no satisfactory treatment for diabetes. Recently, scientists have been exploring a promising treatment of diabetes involving herbal medicine. In this line, we show that Momordica charantia, a tendril-bearing vine belonging to the Cucurbitaceae family, permanently normalizes blood glucose levels comparable to healthy rats. Most importantly, M. charantia increases the expression of Insulin and Pdx1 genes while lowers the expression Glut2. Moreover, the number and size of the pancreatic islets have remarkably increased in treated animals. Liver ALT, AST, and ALP enzyme activities fell into normal range in treated animals suggesting the protective effect of M. charantia. These data indicate that M. Charantia improves the pancreas function by activating pancreatic beta cells and protecting liver tissue. PRACTICAL APPLICATIONS: Owing to the effectiveness of Momordica Charantia extracts in management of diabetes in STZ-induced diabetic rats, we have intention to evaluate the powder of Charantia to discover novel drug for treating diabetes. It is expected that the results could be translated in clinical trials., (© 2019 Wiley Periodicals, Inc.)

Background: Modern technology has reduced physical workload and imposed high mental workload on the control room operators in industrial settings. The present study was conducted among control room operators to assess their mental workload, investigate their workability, examine the relationship between mental workload and workability, and determine the factors associated with workability., Methods: This cross-sectional study was carried out among 213 control room operators in six Iranian process industries. Task Load Index (NASA-TLX) was used to assess the mental workload, and Work Ability Index (WAI) was used to determine workability. The relationships between demographic characteristics and dimensions of mental workload and workability were examined by univariate tests. Logistic regression analysis was also used to determine the factors associated with the operators' workability., Results: The results showed a high mental workload in the study population (82.38±8.8). Yet, the operators showed a good and excellent level of workability (56.4%). Pearson's correlation coefficient revealed a significant inverse linear relationship between the mean score of mental workload and workability (r=-0.581). Besides, regression modeling demonstrated that mental demand (OR=0.90), temporal demand (OR=0.90), effort (OR=0.91), frustration (OR=0.92), from NASA-TLX subscales were significantly associated with workability. Moreover, mental and temporal demands were important factors associated with reduced workability., Conclusion: Monitoring tasks imposes high mental workload on the control room operators, which may result in adverse effects on their workability as well as on the safety of the system.

Lead chalcogenide quaternary systems have been shown to provide high thermoelectric (TE) efficiency superior to those of binary and ternary lead chalcogenides, arising from both altered electronic band structures and a reduction in lattice thermal conductivity. Here, we have synthesized single-phase samples of the quaternary compound (PbTe) 0.55 (PbS) 0.1 (PbSe) 0.35 doped with Na and characterized their TE properties. We show that the dopant solubility is limited to 1 at. %. A very low lattice thermal conductivity of ∼0.6 W m -1 K -1 at 850 K is achieved at all dopant concentrations because of phonon scattering from point defects associated with solute atoms with high contrast atomic mass. As a result, a high TE figure of merit of approximately 1.5 is achieved at 823 K in heavily doped samples. Moreover, the figure of merit is greater than 1 over a wide temperature range above 675 K., Competing Interests: The authors declare no competing financial interest.

Background: Methamphetamine is a neuro-stimulant with neurodegenerative effects, and ambiguous mechanism of action. Metformin is an antidiabetic agent with neuroprotective properties but not fully understood mechanisms. The present study investigated the molecular basis of metformin neuroprotection against methamphetamine-induced neurodegeneration., Brief Method: Sixty adult male rats were randomly divided into six groups: group 1 (received normal saline), group 2 (received 10 mg/kg of methamphetamine) and groups 3, 4, 5 and 6 [received methamphetamine (10 mg/kg) plus metformin (50, 75, 100 and 150 mg/kg) respectively]. Elevated Plus Maze (EPM), Open Field Test (OFT), Forced Swim Test (FST), Tail Suspension Test (TST) and Morris Water Maze (MWM) were used to assess the level of anxiety, depression and cognition in experimental animals. Also animals' hippocampus were isolated and oxidative stress and inflammatory parameters and expression of total and phosphorylated forms of cAMP response element binding (CREB), brain-derived neurotrophic factor (BDNF), protein kinase B (Akt) and glycogen synthase kinase 3 (GSK3) proteins were evaluated by ELISA method., Results: According to the data obtained, methamphetamine caused significant depression, anxiety, motor activity disturbances and cognition impairment in experimental animals. Metformin, in all used doses, decreased methamphetamine induced behavioral disturbances. Also chronic administration of methamphetamine could increase malondialdehyde (MDA), tumor necrosis factor-Alpha (TNF-α) and interleukine-1 beta (IL-1β) in rats, while caused reduction of superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities. Metformin, especially in high doses, could prevent these malicious effects of methamphetamine. Also Metformin could activate CREB (both forms), BDNF and Akt (both forms) proteins' expression and inhibited GSK3 (both forms) protein expression in methamphetamine treated rats., Significance: According to obtained data, metformin could protect the brain against methamphetamine-induced neurodegeneration probably by mediation of CREB/BDNF or Akt/GSK3 signaling pathways. These data suggested that CREB/BDNF or Akt/GSK3 signaling pathways may have a critical role in methamphetamine induced neurotoxicity and/or neuroprotective effects of metformin., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Duloxetine is used for treating depression and anxiety. The current study evaluated the effects of duloxetine against methamphetamine withdrawal-induced anxiety, depression, and motor disturbances and methamphetamine use-induced cognitive impairments., Materials and Methods: Ninety-six adult male rats were used for two independent experiments. Each experiment consisted of Groups 1 and 2 which received normal saline (0.2 ml/rat) and methamphetamine (10 mg/kg) respectively, Groups 3, 4, and 5 received both methamphetamine and duloxetine at doses of 5, 10, and 15 mg/kg, respectively. Groups 6, 7, and 8 received 5, 10, and 15 mg/kg of duloxetine, respectively. All administrations were performed for 21 days. In experiment 1, elevated plus maze (EPM), open-field test (OFT), forced swim test (FST), and tail suspension test (TST) were used to examine anxiety and depression in animals during withdrawal period. In experiment 2, Morris water maze (MWM) test was used to assess the effect of methamphetamine use followed by duloxetine treatment, on learning and memory. In the experiments, the expression of cyclic AMP response element binding (CREB) and brain-derived neurotrophic factor (BDNF) proteins were evaluated using enzyme-linked immunosorbent assay., Results: In the first experiment, duloxetine at all doses attenuated methamphetamine withdrawal induced-depression, anxiety, and motor disturbances in FST, OFT, EPM, and TST. In the second experiment, duloxetine at all doses attenuated methamphetamine use-induced cognitive impairment in MWM. In both experiments, duloxetine activated cAMP, CREB, and BDNF proteins' expression in methamphetamine-treated rats., Conclusions: Duloxetine can protect the brain against methamphetamine withdrawal-induced mood and motor disturbances and can also inhibit methamphetamine-induced cognitive impairment, possibly via cAMP/CREB/BDNF signaling pathway., Competing Interests: There are no conflicts of interest.

Objective: Over the last years, vitrification has been widely used for oocyte cryopreservation, in animals and humans; however, it frequently causes minor and major epigenetic modifications. The effect of oocyte vitrification on levels of acetylation of histone H4 at lysine 12 (AcH4K12), and histone acetyltransferase (Hat) expression, was previously assessed; however, little is known about the inhibition of Hat expression during oocyte vitrification. This study evaluated the effect of anacardic acid (AA) as a Hat inhibitor on vitrified mouse oocytes., Materials and Methods: In this experimental study, 248 mouse oocytes at metaphase II (MII) stage were divided in three experimental groups namely, fresh control oocytes (which were not affected by vitrification), frozen/thawed oocytes (vitrified) and frozen/thawed oocytes pre-treated with AA (treatment). Out of 248 oocytes, 173 oocytes were selected and from them, 84 oocytes were vitrified without AA (vitrified group) and 89 oocytes were pretreated with AA, and then vitrified (treatment group). Fresh MII mouse oocytes were used as control group. Hat expression and AcH4K12 levels were assessed by using real-time quantitative polymerase chain reaction (PCR) and immunofluoresce staining, respectively. In addition, survival rate was determined in vitrified and treatment oocytes., Results: Hat expression and AcH4K12 modification significantly increased [4.17 ± 1.27 (P≤0.001) and 97.57 ± 6.30 (P<0.001), respectively] in oocytes that were vitrified, compared to the fresh oocytes. After treatment with AA, the Hat mRNA expression and subsequently H4K12 acetylation levels were significantly reduced [0.12 ± 0.03 (P≤0.001) and 89.79 ± 3.20 (P≤0.05), respectively] in comparison to the vitrified group. However, the survival rate was not significantly different between the vitrified (90.47%) and treatment (91.01%) groups (P>0.05)., Conclusion: The present study suggests that AA reduces vitrification risks caused by epigenetic modifications, but does not affect the quality of vitrification. In fact, AA as a Hat inhibitor was effective in reducing the acetylation levels of H4K12., Competing Interests: There is no conflict of interest in this study., (Copyright© by Royan Institute. All rights reserved.)

Background: Forced exercise can act as non-pharmacologic neuroprotective agent. In current study, we tried the involved molecular mechanisms of protective effects of forced exercise against methamphetamine induced neurodegeneration., Materials and Methods: Forty adult male rats were divided to Group 1 and 2 which received normal saline and methamphetamine (10 mg/kg) respectively for 30 days. Groups 3, 4 and 5 were treated with methamphetamine for first 15 days and then were treated by forced exercise, bupropion (20 mg/kg/day) or combination of them for the following 15 days. Between 26 th and 30 th days, Morris Water Maze (MWM) was used to evaluate the cognition. On day 31, hippocampus was isolated from each rat and oxidative, antioxidant and inflammatory factors also the level of total and phosphorylated forms of cAMP response element-binding protein (CREB) and brain derived neurotrophic factor (BDNF) proteins were also evaluated., Results: Chronic abuse of methamphetamine could decreases cognition and increase malondialdehyde (MDA), Tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1β), while caused decreases in superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GR) activities all these changes was significant ( P < 0.001) in compared to control group while treatment with bupropion, forced exercise and bupropion in combination with forced exercise could prevent all these malicious effects of methamphetamine ( P < 0.001). Bupropion, forced exercise and bupropion in combination with forced exercise could activate CREB (both forms) and activates BDNF proteins' expression with P < 0.001 in methamphetamine treated rats., Conclusions: P-CREB/BDNF signaling pathways might have critical role in forced exercise protective effects against methamphetamine induced neurodegeneration., Competing Interests: There are no conflicts of interest.

Objective: Craniometry is a subset of anthropometry, which measures the anatomical sizes of the head and face (craniofacial indicators). These dimensions are used in designing devices applied in the facial area, including respirators. This study was conducted to measure craniofacial dimensions of Iranian male workers required for face protective equipment design., Methods: In this study, facial anthropometric dimensions of 50 randomly selected Iranian male workers were measured by photographic method and Digimizer version 4.1.1.0. Ten facial dimensions were extracted from photographs and measured by Digimizer version 4.1.1.0. Mean, standard deviation and 5th, 50th and 95th percentiles for each dimension were determined and the relevant data bank was established., Results: The anthropometric data bank for the 10 dimensions required for respirator design was provided for the target group with photo-anthropometric methods. The results showed that Iranian face dimensions were different from those of other nations and ethnicities., Conclusions: In this pilot study, anthropometric dimensions required for half-mask respirator design for Iranian male workers were measured by Digimizer version 4.1.1.0. The obtained anthropometric tables could be useful for the design of personal face protective equipment.

Objectives: We evaluated the effect of melatonin, as a potent antioxidant agent, on glutathione (GSH) and reactive oxygen species (ROS) levels, as well as histone H3 lysine 9 (H3K9), and H4 lysine 12 (H4K12) acetylation when added to oocytes culture medium., Materials and Methods: In this experimental study, two in vitro and in vivo groups were used. In the in vitro group, cumulus oocyte complexes (COCs) from the ovaries of B6D2F1 mice were cultured in maturation medium containing two doses of melatonin (10 -9 and 10 -6 M) and without melatonin [control group treated with dimethyl sulfoxide (DMSO)] for 22-24 hour. The cumulus expansion and nuclear status were monitored by an inverted microscope. Next, COCs were isolated from the oviducts of superovulated mice and studied as the in vivo group. In in vitro and in vivo matured oocytes, GSH and ROS levels were assessed by monochlorobimane (MCB) and 2-7-dichlorodihydrofluorescein diacetate (H2DCFDA) staining, respectively. Changes in histone acetylation were examined by immunofluorescent staining with specific antibodies against acetylated H3K9 and H4K12., Results: The H4K12 acetylation and ROS levels were significantly higher in the oocytes matured in the in vitro group compared to the in vivo group (P<0.05). Furthermore, glutathione levels in the in vitro group were considerably lower than that of the in vivo group (P<0.05). Melatonin at the concentration of 10 -6 M had the most substantial effect on nuclear maturation and histone acetylation as well as glutathione and ROS levels in the in vitro group (P<0.05)., Conclusions: Exogenous melatonin improves the competence of mouse oocytes during in vitro maturation (IVM)., Competing Interests: There is no conflict of interest in this study., (Copyright© by Royan Institute. All rights reserved.)

Background: Patients with type 1 diabetes are more at risk of coronary artery disease than the general population. Although evidence points to a genetic risk there have been no study investigating genetic risk factors of coronary artery disease specific to individuals with type 1 diabetes. To identify low frequency and common genetic variations associated with coronary artery disease in populations of individuals with type 1 diabetes., Methods: A two-stage genome wide association study was conducted. The discovery phase involved the meta-analysis of three genome-wide association cohorts totaling 434 patients with type 1 diabetes and coronary artery disease (cases) and 3123 T1D individuals with no evidence of coronary artery disease (controls). Replication of the top association signals (p < 10 -5 ) was performed in five additional independent cohorts totaling 585 cases and 2612 controls., Results: One locus (rs115829748, located upstream of the MAP1B gene) reached the statistical threshold of 5 × 10 -8 for genome-wide significance but did not replicate. Nevertheless, three single nucleotide polymorphisms provided suggestive evidence for association with coronary artery disease in the combined studies: CDK18 rs138760780 (OR = 2.60 95% confidence interval [1.75-3.85], p = 2.02 × 10 -6 ), FAM189A2 rs12344245 (OR = 1.85 [1.41-2.43], p = 8.52 × 10 -6 ) and PKD1 rs116092985 (OR = 1.53 [1.27-1.85], p = 1.01 × 10 -5 ). In addition, our analyses suggested that genetic variations at the ANKS1A, COL4A2 and APOE loci previously found associated with coronary artery disease in the general population could have stronger effects in patients with type 1 diabetes., Conclusions: This study suggests three novel candidate genes for coronary artery disease in the subgroup of patients affected with type 1 diabetes. The detected associations deserve to be definitively validated in additional epidemiological studies.

Objective: The concept of coping with disease appears frequently in the literature; however, there is no precise definition of coping. The aim of this study is to clarify coping concept, and to identify its attributes, antecedents, and consequences in patients with multiple sclerosis., Methods: Rodgers' evolutionary method of concept analysis was used to clarify the concept of coping. A literature review was conducted with key terms 'multiple sclerosis', 'coping', 'adjustment', and 'deal with'. After searching databases, 1370 papers were found for the period 1995-2017. Finally, 55 articles and texts were selected for analysis. Data analysis was carried out using thematic analysis. An independent researcher checked the process to ensure credibility and reduce personal bias., Results: Coping with multiple sclerosis is a multidimensional concept with three main attributes: maintenance of emotional balance, acceptance of the disease, and self-regulation. Social support, awareness toward the disease, attitude toward the disease, and religious-spiritual beliefs were found as antecedents. Health promotion, adherence to treatment regimen, independence in personal life and social relationships, and improvement of family relationships were found as consequences of these attributes., Conclusion: These findings not only add to the body of knowledge in health science, but also serve as an important motivation for further theory development and research in this context. Nurses and health professions can also benefit from a deeper understanding of coping concept in providing and planning healthcare for these patients.

To interpret visual-motion events, the underlying computation must involve internal reference to the motion status of the observer's head. We show here that layer 6 (L6) principal neurons in mouse primary visual cortex (V1) receive a diffuse, vestibular-mediated synaptic input that signals the angular velocity of horizontal rotation. Behavioral and theoretical experiments indicate that these inputs, distributed over a network of 100 L6 neurons, provide both a reliable estimate and, therefore, physiological separation of head-velocity signals. During head rotation in the presence of visual stimuli, L6 neurons exhibit postsynaptic responses that approximate the arithmetic sum of the vestibular and visual-motion response. Functional input mapping reveals that these internal motion signals arrive into L6 via a direct projection from the retrosplenial cortex. We therefore propose that visual-motion processing in V1 L6 is multisensory and contextually dependent on the motion status of the animal's head., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Unsafe behaviors are main causes of accidents mostly influenced by personal characteristics, social environment and also individual biorhythm cycles. This study was carried out to find out whether personality traits and biorhythm could affect the incidence of unsafe behaviors among city bus drivers., Methods: This cross-sectional study was conducted on 224 bus drivers in Shiraz, Iran, 2014. The data were collected using NEO personality traits questionnaire. Also, a self-constructed checklist was used to investigate the drivers' unsafe behaviors. Information on drivers' biorhythm was analyzed by Natural Biorhythm software version 3.2. The relationship between demographic characteristics, personality traits and biorhythm were examined by T-Test, One-way ANOVA, correlation coefficient and Chi square tests. Multiple linear regression analysis was used to investigate the factors influencing the incidence of unsafe behaviors., Results: 28.6% of participants have experienced critical days in their biorhythm cycles. Also the mean percentage of unsafe behavior was 54.08 ± 11.91 among the subjects of the study.Significantly negative correlations were observed between each personality factor and the percentage of unsafe behaviors. Also, there was a significant relationship between percentage of derivers' unsafe behaviors and the general cycle of biorhythm (having at least one critical day in each of the cycles)., Conclusions: Taking the measures including selection of low-risk traffic routes in the critical days and considering the personality traits at the time of employment could be effective in reducing the unsafe behaviors and accidents.

Background: Touch screen computers require significant arm and hand movements. This can result to body discomfort and biomechanical load in users., Objectives: This study was carried out to examine posture and users' discomfort while using touch screen device as compared with mouse-keyboard and touch pad-keyboard., Methods: Twenty three (23) students participated in this experimental study. The subjects completed pre-defined tasks in three 15 min trials by means of touch screen, touch pad-keyboard and mouse-keyboard as input devices. Postural angles were measured by Qualisys motion capture system. Body discomfort was assessed by a 10-cm visual analog scale. Rating scale was employed to assess the perception of subjects on the posture of body parts while utilizing the three devices., Results: There was no significant difference in head inclination when using the three types of devices. Nevertheless, the mean of neck (p = 0.005) and trunk (p < 0.0001) inclinations as well as arm angle (p < 0.0001) while using touch screen, differed significantly from the two other devices and were more deviated from neutral posture. The type of input device was found to have significant effect on the right shoulder (p = 0.017), right elbow (p = 0.031), right wrist/hand (p = 0.004) and whole body discomfort (p = 0.026). Touch screen caused more discomfort in the mentioned regions when compared to the other two devices. Friedman test showed that differences of mean ratings for perceived shoulder and elbow postures in the 3 trials were significant (p = 0.005 and p = 0.011, respectively). Touch screen was the most unfavorable input device based on the subjects' judgment., Conclusion: Touch screen caused more deviated postural angles, increased body discomfort and unfavorable postures.

Background: The present study was carried out to assess the relationship between sickness absence and occupational stress, sleep quality, and amplitude and stability of circadian rhythm as well as to determine contributing factors of sickness absence., Methods: This cross sectional study was conducted on 400 randomly selected employees of an Iranian gas company. The data were collected using Pittsburgh sleep quality index, Karolinska sleepiness scale, circadian type inventory, and Osipow occupational stress questionnaires., Results: The mean age and job tenure of the participants were 33.18 ± 5.64 years and 6.06 ± 4.99 years, respectively. Also, the participants had been absent from work on average 2.16 days a year. According to the results, 209 participants had no absences, 129 participants had short-term absences, and 62 participants had long-term absences. The results showed a significant relationship between short-term absenteeism and amplitude of circadian rhythm [odds ratio (OR) = 6.13], sleep quality (OR = 14.46), sleepiness (OR = 2.08), role boundary (OR = 6.45), and responsibility (OR = 5.23). Long-term absenteeism was also significantly associated with amplitude of circadian rhythm (OR = 2.42), sleep quality (OR = 21.56), sleepiness (OR = 6.44), role overload (OR = 4.84), role boundary (OR = 4.27), and responsibility (OR = 3.72)., Conclusion: The results revealed that poor sleep quality, amplitude of circadian rhythm, and occupational stress were the contributing factors for sickness absence in the study population.

Background: Job stress and job satisfaction are important factors affecting workforce productivity. This study was carried out to investigate the job stress, job satisfaction, and workforce productivity levels, to examine the effects of job stress and job satisfaction on workforce productivity, and to identify factors associated with productivity decrement among employees of an Iranian petrochemical industry., Methods: In this study, 125 randomly selected employees of an Iranian petrochemical company participated. The data were collected using the demographic questionnaire, Osipow occupational stress questionnaire to investigate the level of job stress, Job Descriptive Index to examine job satisfaction, and Hersey and Goldsmith questionnaire to investigate productivity in the study population., Results: The levels of employees' perceived job stress and job satisfaction were moderate-high and moderate, respectively. Also, their productivity was evaluated as moderate. Although the relationship between job stress and productivity indices was not statistically significant, the positive correlation between job satisfaction and productivity indices was statistically significant. The regression modeling demonstrated that productivity was significantly associated with shift schedule, the second and the third dimensions of job stress (role insufficiency and role ambiguity), and the second dimension of job satisfaction (supervision)., Conclusion: Corrective measures are necessary to improve the shift work system. "Role insufficiency" and "role ambiguity" should be improved and supervisor support must be increased to reduce job stress and increase job satisfaction and productivity.

Background: The Nordic Safety Climate Questionnaire-50 (NOSACQ-50) was developed by a team of Nordic occupational safety researchers based on safety climate and psychological theories. The aim of this study was to develop and validate the Persian version of NOSACQ-50 and assess the score of safety climate on a group of workers in a steel company in Iran., Methods: The Persian version of NOSACQ-50 was distributed among 661 employees of a steel company in Qazvin Province (Iran). Exploratory factor analysis (EFA) and confirmatory factor analysis were used to determine the dimensions of the questionnaire. The reliability of the questionnaire was assessed using Cronbach α coefficient. Pearson correlation test was applied to investigate the correlation between different dimensions., Results: The results of EFA showed that the Persian version of NOSACQ-50 consisted of six dimensions. The Cronbach α coefficient of the questionnaire was 0.94. The mean score of safety climate in all dimensions was 2.89 (standard deviation 0.60)., Conclusion: The Persian version of NOSACQ-50 had a satisfactory validity for measuring safety climate in the studied Iranian population.

Objective: Assessment of the contribution of non-medical factors to mode of delivery and birth preference in Iranian pregnant women in southwestern Iran., Study Design: This cohort study used data from a structured questionnaire completed in early pregnancy and information about the subsequent delivery obtained through personal contact. Women were recruited by random sampling from antenatal clinics when scheduling visits over the course of 5 weeks from December 2012 to February 2013 and were followed-up 1 month after birth. Of the 2199 women recruited, 99.63% were eligible for the study., Results: Of the 748 women who expressed a desire to deliver their babies by cesarean section (CS) in early pregnancy, 87% had an elective cesarean section. The logistic regression analyses showed that normative beliefs (odds ratio [OR] 1.792, 95% confidence interval (1) 1.073-2.993), control beliefs (OR: 0.272, 95% CI: 0.162-0.459), and evaluation of outcomes (OR: 0.431, 95% CI: 0.268-0.692) favored the preference for cesarean section. The desire for delivery by elective cesarean section was associated with normative beliefs (OR: 1.138; 95% CI: 1.001-1.294), control beliefs (OR: 0.804; 95% CI: 0.698-0.927), and expectations about maternity care (OR: 0.772; 95% CI: 0.683-0.873), medical influences (OR: 1.150; 95% CI: 1.023-1.291), evaluation of outcome (OR: 0.789; 95% CI: 0.696-0.894), age, preference for cesarean section (OR: 5.445; 95% CI: 3.928-7.546), spouse educational level, and number of live births., Conclusions: A woman's preference for delivery by cesarean section influenced their subsequent mode of delivery. Asking women in early pregnancy about their preferred mode of delivery provides the opportunity to extend their supports which might reduce the rate of elective cesarean section. This decision is affected by age, spouse educational level, number of live births, and preconceived maternal attitudes about delivery.

Study Design: Case report and relevant literature review., Objective: To discuss the management of severe flexion-distraction injury of the subaxial cervical spine in a multisystem trauma patient., Summary of Background Data: Traumatic cervical spine injury from flexion-distraction injury can cause significant instability requiring extensive instrumentation complicated by vascular and soft tissue injuries., Methods: The medical record of a patient who suffered traumatic flexion-distraction injury was reviewed for relevant clinical and radiology data. A literature review on the management of traumatic cervical injuries was performed using the PubMed database., Results: We report a case of 21-year-old woman who suffered a C5-C6 flexion-distraction injury. After she underwent anterior cervical discectomy and fusion (ACDF), her care was transferred to the senior author (S.K.) due to the severity of the distraction. The patient returned to the OR the next day and underwent removal of implants at C5 and corpectomy with anterior and posterior instrumentation., Conclusion: There are many ways to manage a flexion-distraction injury of the cervical spine. In a polytrauma patient, the surgical strategy can become complex. We present a surgical option with an acceptable outcome.

Background: Vision impairment in children is one of the most severe disabilities that cause stress in parents. Therefore, it seems necessary to establish and conduct interventions for controlling parenting stress and preventing its negative consequences. This study aimed to investigate the effect of life skills training (LST) program on parenting stress of mothers with blind children aged 7 to 12 years., Methods: This study was a non-blinded randomized controlled trial. 52 mothers with blind children studying at Shoorideh Shirazi educational complex, Shiraz, Iran in 2013 were enrolled, using census sampling method. Balanced block randomization method was used to allocate the participants to groups. The intervention group participated in an LST program consisting of 5 two-hour sessions per week for 5 consecutive weeks but the control group didn't. Data were collected using a demographic questionnaire and Parenting Stress Index; they were completed three times by the participants of both groups before, immediately after, and one month after the intervention. Collected data were analyzed using Chi-square, independent t-test and repeated measures analysis of variances (ANOVA)., Results: The LST program could decrease parenting stress in the intervention group mothers (P<0/001). This statistically significant reduction in the mean scores of parenting stress was observed in both children and parents., Conclusion: LST program could reduce parenting stress in mothers with blind children. Therefore, it can be used as an efficient, cost-effective and simple technique for managing parenting stress in such parents., Trial Registration Number: IRCT201405147531N6.

The individual's perception of health, when health is understood to include many dimensions of life, is considered the basis for any improvement in health status. Therefore, the present study aimed to assess the reliability and validity of the Persian version of the Perceived Wellness Scale (PWS) by applying it to employees of the Shiraz University of Medical Sciences. This cross-sectional study was conducted with 180 staff members of the university selected by convenience sampling. The study instrument was a Persian version of the PWS prepared through a translation and back-translation process. The reliability and validity of the instrument were assessed by using confirmatory factor analysis (CFA) and Cronbach's alpha coefficient. A total of 180 employees participated in the study. The mean age of the participants was 32.29 years (SD = 7.39) and 78.1% of the participants were women. The results showed that the Persian version of the PWS is acceptable. Cronbach's alpha coefficient was 0.87 for the whole scale, ranging from 0.68 to 0.85 on different dimensions of the scale. The results of split-half reliability and CFA indicated that the reliability and validity of the PWS are acceptable. The PWS is therefore an effective tool for evaluating the different dimensions of perceived wellness in the Iranian population.

Background: Gradual weight reduction has been shown to be associated with improvements in liver enzymes. However, some evidence demonstrated that liver enzymes may transiently increase immediately after a diet-induced weight loss., Objectives: This study was designed to assess the effects of a hypocaloric, almond-enriched diet (AED) compared with a hypocaloric nut-free diet (NFD) on liver function tests in the context of a three-month weight reduction program in overweight/obese women., Patients and Methods: This randomized controlled clinical trial was registered at Iranian Registry of Clinical Trials with ID number of IRCT2013062313751N1. Overweight and obese Iranian women [n = 108; age = 42.7 y, body mass index = 29.6 kg/m(2)] were randomly assigned to consume an AED or NFD. The carefully planned hypocaloric diets were identical for both groups except for the AED group who consumed 50 grams of almonds daily for three months. Anthropometric measurements and laboratory measurements including alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and γ-glutamyltransferase (GGT) were assessed before and immediately after the intervention., Results: Of 108 participants, 50 women in AED group and 50 women in NFD group completed the protocol of the study (response rate: 92.6 %). The AED led to a median weight loss of 3.79 kg (interquartile range: 4.4 kg). Significant decreases within AED and NFD were observed in ALT (-16.6 ± 16.3 and -11.7 ± 16.8, P < 0.001, respectively). Similar significant decreases were observed in AST (-13.6 ± 15.7 and -7.7 ± 16.1; P < 0.001, respectively). The decrease in GGT was also significant in both groups (-11.4 ± 21.6 and -6.2 ± 19.8; P < 0.001 respectively). ALT, AST and GGT decreased significantly in the AED group compared to the NFD group (P < 0.001)., Conclusions: AED improved liver enzymes in obese women. However, mild, transient increases in ALT and AST values can be observed immediately after an NFD in women.

Background: A permit to work (PTW) is a formal written system to control certain types of work which are identified as potentially hazardous. However, human error in PTW processes can lead to an accident., Methods: This cross-sectional, descriptive study was conducted to estimate the probability of human errors in PTW processes in a chemical plant in Iran. In the first stage, through interviewing the personnel and studying the procedure in the plant, the PTW process was analyzed using the hierarchical task analysis technique. In doing so, PTW was considered as a goal and detailed tasks to achieve the goal were analyzed. In the next step, the standardized plant analysis risk-human (SPAR-H) reliability analysis method was applied for estimation of human error probability., Results: The mean probability of human error in the PTW system was estimated to be 0.11. The highest probability of human error in the PTW process was related to flammable gas testing (50.7%)., Conclusion: The SPAR-H method applied in this study could analyze and quantify the potential human errors and extract the required measures for reducing the error probabilities in PTW system. Some suggestions to reduce the likelihood of errors, especially in the field of modifying the performance shaping factors and dependencies among tasks are provided.