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Fluoxetine is a Selective Serotonin Reuptake Inhibitor (SSRI) that exerts its anti-depressive effect by blocking the presynaptic reuptake of the neurotransmitter serotonin, 5-hydroxytryptamine (5-HT). Although fluoxetine is usually considered safe for most patients, in the present case report, we describe a young patient with Mixed Anxiety and Depression Disorder (MADD) treated with fluoxetine 10 mg/day, who developed hypotension when the dosage was titrated up to 20 mg/day. After discontinuing the use of fluoxetine, the symptoms of hypotension improved. A temporal association and dose-dependent relationship between the hypotension and the use of fluoxetine was observed. To the best of our knowledge, this is the first case report that precisely associates regular doses of fluoxetine with the presence of hypotension. Because boosting central serotonergic function lowers blood pressure, it is suggested that a significant effect of fluoxetine on the vasomotor center may be responsible for the reduction of blood pressure. Thus, physicians should be aware of the possible risk of hypotension induced by fluoxetine and recommend patients discontinue the drug immediately if complications have occurred.

Abstract Background Knowledge of pathogenic variants in cancer‐predisposing genes is important when making breast cancer treatment decisions, but genetic testing is not universal and criteria must be met to qualify for genetic testing. The objective of this study was to evaluate the pathogenic variant yield for nine cancer predisposition genes by testing criteria, singly and in combination. Methods Women diagnosed with breast cancer between June 2013 and May 2018 were recruited from four centers in Toronto, Canada. Participants completed a demographics and family history questionnaire and clinical characteristics were collected from medical charts. Genetic testing was done for BRCA1, BRCA2, PALB2, ATM, CHEK2, BRIP1, RAD51D, RECQL, and TP53. Pathogenic variant frequencies were calculated according to five criteria (age ≤ 50, triple‐negative breast cancer, family history, bilateral breast cancer, or Jewish ethnicity). Results Of the 1006 women studied, 100 women (9.9%) were found to have a pathogenic variant in one of the nine genes tested. The highest prevalence of pathogenic variants was found in women with triple‐negative breast cancer (23%). Of the 100 pathogenic variants detected, 78 were detected in women diagnosed at age 50 or less. A total of 96% of the mutations were identified with three criteria (age of diagnosis, family history, and triple‐negative status). Conclusions Genetic testing criteria for women with breast cancer should include women with triple‐negative breast cancer, regardless of age. All women aged 50 years or below at time of breast cancer diagnosis should be offered genetic testing.

Esophageal squamous cell carcinoma (ESCC) has a very high incidence rate in northeastern Iran. Our team previously reported the BReast CAncer gene 2 (BRCA2) p.K3326* mutation as a moderately penetrant ESCC susceptibility variant in northern Iran (odds ratio (OR) = 3.64, 95% confidence interval (CI) = 1.74-7.59, P = 0.0003). Recently, it has been reported that aldehydes can induce BRCA2 haploinsufficiency in cells with a heterozygous pathogenic BRCA2 mutation and predispose them to carcinogenic effects. Based on this observation, we speculate that dysfunctional variants in Aldehyde Dehydrogenase 2 Family Member (ALDH2) may result in aldehyde-induced BRCA2 haploinsufficiency and increase cancer risk in BRCA2 mutation carriers. In support of this hypothesis, our team recently reported the breast cancer risk modifying effect of an ALDH2 common polymorphism, rs10744777, among Polish carriers of the BRCA2 p.K3326* mutation. In the current case-control study, we aimed to investigate the ESCC risk modifying effect of this ALDH2 polymorphism among BRCA2 p.K3326* mutation carriers. We assessed the interaction between the ALDH2 rs10744777 polymorphism and BRCA2 p.K3326* mutation in ESCC risk by genotyping this ALDH2 variant in the germline DNA of 746 ESCC cases and 1,373 controls from northern Iran who were previously genotyped for the BRCA2 p.K3326* mutation. Among a total of 464 individuals with TT genotype of the ALDH2 rs10744777 polymorphism, which is associated with lower ALDH2 expression, we found 9 of 164 cases versus 3 of 300 controls who carried the BRCA2 p.K3326* variant (OR = 5.66, 95% CI = 1.22-26.2, P = 0.018). This finding supports our hypothesis that the ALDH2-rs10744777 TT genotype may be a significant risk modifier of ESCC in individuals with a BRCA2 p.K3326* mutation.

Background: Diplopia, or double vision, is a common ophthalmologic complaint with many underlying causes, ocular and neurological. Aripiprazole has been reported to have fewer adverse effects and better efficacy than other atypical antipsychotics. Although ocular side effects of aripiprazole are not remarkable, two cases of diplopia associated with aripiprazole have been reported in the literature. Objectives: Herein, we report the third case of diplopia, after the aripiprazole prescription in a woman with depressive disorder. Case Presentation: A 37-year-old woman was brought to our clinic with symptoms of sleep loss, displeasure, auditory hallucination, and pessimistic thoughts. After a clinical interview, the patient was diagnosed with depression with psychotic features according to the Diagnostic and Statistical Manual (DSM-V) of mental disorders. She underwent treatment with 15 mg/d aripiprazole and 20 mg/d fluoxetine. Her symptoms reduced after three months as indicated by the visual analog scale. However, the patient returned to the clinic and complained of double vision. Neither neurological nor ophthalmological problems were observed following examinations by specialists. When the dose of the drug decreased and eventually discontinued, diplopia disappeared over 24 hours. Conclusion: Since the patient had no history of diplopia and two cases of diplopia associated with aripiprazole were previously reported in the literature, we expected that the diplopia was related to the recently prescribed aripiprazole treatment. Physicians should be aware of the possible risk of diplopia-induced by aripiprazole and recommend patients discontinuing the drug immediately if complications have occurred.

Abstract Background Studies that aim at explaining phenotypes or disease susceptibility by genetic or epigenetic variants often rely on clustering methods to stratify individuals or samples. While statistical associations may point at increased risk for certain parts of the population, the ultimate goal is to make precise predictions for each individual. This necessitates tools that allow for the rapid inspection of each data point, in particular to find explanations for outliers. Results ACES is an integrative cluster- and phenotype-browser, which implements standard clustering methods, as well as multiple visualization methods in which all sample information can be displayed quickly. In addition, ACES can automatically mine a list of phenotypes for cluster enrichment, whereby the number of clusters and their boundaries are estimated by a novel method. For visual data browsing, ACES provides a 2D or 3D PCA or Heat Map view. ACES is implemented in Java, with a focus on a user-friendly, interactive, graphical interface. Conclusions ACES has been proven an invaluable tool for analyzing large, pre-filtered DNA methylation data sets and RNA-Sequencing data, due to its ease to link molecular markers to complex phenotypes. The source code is available from https://github.com/GrabherrGroup/ACES.

The Iberian ribbed newt Pleurodeles waltl has a wide spectrum of regeneration abilities. Here, Elewa et al. sequence its ~20 Gb genome and transcriptome to investigate the molecular features underlying its regenerative capacities.

Abstract Background DNA methylation is a major mechanism involved in the epigenetic state of a cell. It has been observed that the methylation status of certain CpG sites close to or within a gene can directly affect its expression, either by silencing or, in some cases, up-regulating transcription. However, a vertebrate genome contains millions of CpG sites, all of which are potential targets for methylation, and the specific effects of most sites have not been characterized to date. To study the complex interplay between methylation status, cellular programs, and the resulting phenotypes, we present PiiL, an interactive gene expression pathway browser, facilitating analyses through an integrated view of methylation and expression on multiple levels. Results PiiL allows for specific hypothesis testing by quickly assessing pathways or gene networks, where the data is projected onto pathways that can be downloaded directly from the online KEGG database. PiiL provides a comprehensive set of analysis features that allow for quick and specific pattern searches. Individual CpG sites and their impact on host gene expression, as well as the impact on other genes present in the regulatory network, can be examined. To exemplify the power of this approach, we analyzed two types of brain tumors, Glioblastoma multiform and lower grade gliomas. Conclusion At a glance, we could confirm earlier findings that the predominant methylation and expression patterns separate perfectly by mutations in the IDH genes, rather than by histology. We could also infer the IDH mutation status for samples for which the genotype was not known. By applying different filtering methods, we show that a subset of CpG sites exhibits consistent methylation patterns, and that the status of sites affect the expression of key regulator genes, as well as other genes located downstream in the same pathways. PiiL is implemented in Java with focus on a user-friendly graphical interface. The source code is available under the GPL license from https://github.com/behroozt/PiiL.git .

مقدمه: پیشرفت‌های پزشكی و بهداشتی باعث کاهش مرگ و میر و افزایش نسبی طول عمر انسان‌ها شده و جمعیت جهان و ایران به سوی کهن‌سالی رو به حرکت است. کیفیت زندگی وابسته به سلامت، به دلیل قابلیت آن در توانایی فرد در انجام وظایف روزمره‌ی زندگی، احساس سلامتی عمومی و تأثیر عوامل مختلف جسمی، روانی، اجتماعی و اقتصادی در آن از اهمیت والایی برخوردار می‌باشد. جهت مداخله در کیفیت زندگی وابسته به سلامت و اصلاح آن، نیازمند ابزار سنجش کیفیت زندگی هستیم. روش‌ها: این مطالعه‌ی ترکیبی جهت ابزارسازی در شهر اصفهان انجام شد. پس از بررسی پرسش‌نامه‌های مشابه و مصاحبه با سالمندان و کارشناسان خبره، بانک سؤالات تهیه و پرسش‌نامه‌ی اولیه ساخته شد و با ویرایش و کاهش تعداد، نهایی گردید. سپس انواع مختلف روایی آن با پرسش‌گری از 174 سالمند سالم و 56 سالمند بیمار، که به طور آسان انتخاب شدند، محاسبه گردید؛ پایایی درونی توسط ضریب آلفای کرونباخ و پایایی برونی با انجام آزمون- بازآزمون بر روی 20 سالمند با نمونه‌گیری آسان تعیین شد. برای کاهش داده‌ها از فاکتور آنالیز، روش مؤلفه‌های اصلی استفاده گردید. یافته‌ها: پرسش‌نامه‌ی سنجش کیفیت زندگی وابسته به سلامت در سالمندان دارای 4 سؤال در حیطه‌ی وضعیت سلامت جسمانی و فعالیت‌های روزانه، 7 سؤال در حیطه‌ی وضعیت سلامت روان، 2 سؤال در حیطه‌ی وضعیت سلامت اجتماعی و ارتباطات بین فردی و 2 سؤال در حیطه‌ی وضعیت اقتصادی طراحی شد. روایی محتوایی، صوری و ساختاری (همگرا و افتراقی) آن تأیید و ضریب آلفای کرونباخ برابر 3/72 درصد محاسبه شد. نتیجه‌گیری: این ابزار با توجه به خلاصه بودن، تعداد کم سؤالات، سادگی جملات و همچنین روایی و پایایی مناسب، قابل استفاده در جمعیت سالمندان بوده، می‌تواند جهت سنجش کیفیت زندگی و ریزی سلامت آن‌ها به کار گرفته شود.

Background: The most important in hospital environment relationship is the relationship between doctors and nurses. This kind of connection is the most important relationship of the doctor-patient interaction involves creating collaborative relationships and provides information to achieve a common goal of treatment. Few studies in Iran about the current level of communication between doctor and nurse was done, so assessment of barriers of communication between these two groups was essential. Methods: This descriptive-analytical study was performed at the second half of 2009 in Al-Zahra hospital in Isfahan. The target population was 80 nurses and 80 physicians. Sampling for both groups was convenient; all of them completed a researcher-made questionnaire. Content validity of questionnaire was approved by leader professors. After a pilot study with 30 questionnaires, reliability was performed by split half method. Questions were in likert span and interpreted by Mann-Whitney and chi-square tests. Finding: All 160 people participated in the project were completed the questionnaire, 50% of physicians were disagreed with the failure of the communication of nurses in prescribing drugs and in total opposition to have opposing views than nurses and more there is quite the opposite, most opposition has been communication barrier in differences religious belief almost for other physicians agree with the obstacles mentioned. Both nurses and physicians completely agree and agree with communication situations and oppose almost completely absent. Relatively both groups agree and agree completely about ways to deal with the obstacles mentioned above. There were Significant differences between the attitudes of doctors and nurses, but significant relationship does not exist between the type of attitude of doctors and their gender, also significant relationship does not exist between the attitude of nurses and their gender. The highest mean score of the answers of physicians and nurses was about the third part of the questionnaire, namely methods to deal with obstacles and the majority have consensus on this issue. Conclusion: Considering that communication skills are also having extensive background and great value in improving health systems, it seems that communication skills, both through the inclusion of the important subjects of communication skills in nursing and medical education system or by creating understanding and conducting workshops for practical communication skills in the health system can increase.

After performing de novo transcript assembly of >1 billion RNA-Sequencing reads obtained from 22 samples of different Norway spruce (Picea abies) tissues that were not surface sterilized, we found that assembled sequences captured a mix of plant, lichen, and fungal transcripts. The latter were likely expressed by endophytic and epiphytic symbionts, indicating that these organisms were present, alive, and metabolically active. Here, we show that these serendipitously sequenced transcripts need not be considered merely as contamination, as is common, but that they provide insight into the plant's phyllosphere. Notably, we could classify these transcripts as originating predominantly from Dothideomycetes and Leotiomycetes species, with functional annotation of gene families indicating active growth and metabolism, with particular regards to glucose intake and processing, as well as gene regulation.

The domestic dog, Canis familiaris, is a well-established model system for mapping trait and disease loci. While the original draft sequence was of good quality, gaps were abundant particularly in promoter regions of the genome, negatively impacting the annotation and study of candidate genes. Here, we present an improved genome build, canFam3.1, which includes 85 MB of novel sequence and now covers 99.8% of the euchromatic portion of the genome. We also present multiple RNA-Sequencing data sets from 10 different canine tissues to catalog ∼175,000 expressed loci. While about 90% of the coding genes previously annotated by EnsEMBL have measurable expression in at least one sample, the number of transcript isoforms detected by our data expands the EnsEMBL annotations by a factor of four. Syntenic comparison with the human genome revealed an additional ∼3,000 loci that are characterized as protein coding in human and were also expressed in the dog, suggesting that those were previously not annotated in the EnsEMBL canine gene set. In addition to ∼20,700 high-confidence protein coding loci, we found ∼4,600 antisense transcripts overlapping exons of protein coding genes, ∼7,200 intergenic multi-exon transcripts without coding potential, likely candidates for long intergenic non-coding RNAs (lincRNAs) and ∼11,000 transcripts were reported by two different library construction methods but did not fit any of the above categories. Of the lincRNAs, about 6,000 have no annotated orthologs in human or mouse. Functional analysis of two novel transcripts with shRNA in a mouse kidney cell line altered cell morphology and motility. All in all, we provide a much-improved annotation of the canine genome and suggest regulatory functions for several of the novel non-coding transcripts.

Background: Children account for 30-70% of all patients seen in outpatient clinics. Studies have shown integrated methods to improve quality of outpatient care in children. The present study aimed to compare quality of care between routine and integrated methods in pediatric outpatient setting. Methods: This double-blinded prospective study was carried out in two pediatric clinics of Amin Hospital (Isfahan, Iran). Non-probability convenience sampling was used to select 100 children. Performance of medical interns in visiting these children was assessed by an observer through a checklist. Then, students in clinic A were trained in Integrated Management of Childhood Illness (IMCI) algorithms. The performance of the two groups in visiting 100 children was reevaluated at the end of the period again. The mean of their scores and frequency of each item of the checklist was calculated and compared between the two groups. Findings: The mean scores of performance of the two groups had no significant difference. Only the frequency of few items of the checklist was significantly different between the two groups. Conclusion: We found no significant difference between the two groups. It may be due to short training period, interest in textbooks, lack of knowledge about efficacy of IMCI algorithms in the future work, and not having adequate time for practicing. Another reason may be low power of our study. Keywords: Integrated management of childhood illness, Quality of health care, Preschool children

Background: In recent years, it is well-known that vitamin D deficiency has many complications, especially in elderly people and especially in Iran due to existence of multiple risk factors. So, awareness of vitamin D average and identify risk factors can be helpful to find ways to improve life in elderly. Methods: This cross-sectional study was conducted in Isfahan, Iran, during 2011. Our cases were 180 women with the age of more than 60 years referred to 2 laboratories in Isfahan. The 25(OH)D serum level were measured by ELISA method and then, final statistical evaluations were analyzed. Findings: The mean vitamin D concentration was 141.55 ± 70.13 nm/l and the minimum and maximum serum levels of vitamin D were 36.9 and 365.8 nm/l, respectively. The ANOVA test showed that the mean vitamin D level had a significant difference according to age group (P = 0.043) and body mass index (BMI) (P = 0.023). The mean vitamin D level was significantly higher in women using vitamin D supplements (P = 0.003). Conclusion: According to this study, due to prevalence of vitamin D deficiency in Iran, it is necessary to identify its risk factors and prevent it in elderly people. Keywords: Vitamin D, Deficiency, 25(OH)D, Elderly, Complications

Background: One of the major causes of mortality in patients with kidney failure requiring dialysis is cardiovascular diseases. Metabolic syndrome refers to a collection of metabolic disorders that causes systemic inflammation and therefore plays an important role in increasing the incidence of cardiovascular disorders and the associated mortality and morbidity. Given the increasing prevalence of metabolic syndrome in the general population, this study was designed to investigate the prevalence of metabolic syndrome in patients on peritoneal dialysis and hemodialysis. Methods: A cross-sectional study on 170 patients on dialysis was performed in Alzahra Hospital, Isfahan, Iran. Blood samples were obtained to examine glucose, lipid profile, hemoglobin, albumin, parathyroid hormone (PTH), calcium, phosphorus, and white blood cell count (WBC). Blood pressure, weight, height, and waist circumference were also measured by standard methods. The information of patients was recorded in a questionnaire. Findings: Metabolic syndrome was observed in 67% of the studied population. The prevalence of metabolic syndrome was higher in females than males (77% vs. 57%). The syndrome was also more prevalent among peritoneal dialysis patients than individuals on hemodialysis (73% vs. 47%). The highest prevalence in hemodialysis patients was seen in patients who were dialyzed through a temporary catheter. The average weight, body mass index, albumin levels, and WBC were significantly higher in patients with metabolic syndrome. However, the differences in hemoglobin, PTH, calcium, and phosphorus values were not statistically significant between patients with and without metabolic syndrome. Conclusion: The prevalence of metabolic syndrome is high in dialysis, especially in peritoneal dialysis, patients. In addition, women are more at risk than men. Therefore, in order to prevent cardiovascular mortality and morbidity, these patients need to be regularly examined to diagnose and treat the risk factors of metabolic syndrome as soon as possible.