Novel and heteroplasmic mutations in mitochondrial tRNA genes in Brugada syndrome

  Background: Brugada syndrome (BrS) is a rare cardiac arrhythmia characterized by sudden death associated with electrocardiogram patterns characterized by incomplete right bundle-branch block and ST-segment elevations in the anterior precordial leads. This syndrome predominantly is seen in younger males with structurally normal hearts. Mitochondrial variants particularly mt-tRNA mutations, are hot spots that lead to cardiological disorders. Previous studies have shown that mutations in mitochondrial tRNA genes play an important causal or modifying role in BrS. The present study aims to evaluate the involvement of mitochondrial tRNA genes in arrhythmogenic BrS. Methods: In this study, 40 Iranian patients were investigated for the presence of the mutations in 6 mitochondrial tRNA genes (tRNA Ile, Met, Gln, Asn, Ala and Trp) by PCR-SSCP analysis. Results: There were 4 mutations in tRNA genes, that for first time, were found in BrS patients and these mutations were not in controls. Three of them were heteroplasmic and located in tRNAGln (T4377A) and tRNAMet (G4407A and C4456T) which were assessed as pathogenic mutations. A homo­plasmic variant (5580T > C) in tRNATrp gene was located within the junction region between tRNATrp and tRNAAla genes. This mutation may disturb the processing of mt-tRNATrp. Conclusions: The results of this study suggest that mutations in mitochondrial tRNA genes might lead to deficiencies in translational process of critical proteins of the respiratory chain and potentially lead to BrS in Iranian subjects. (Cardiol J 2018; 25, 1: 113–119

Sleep disturbances and sexual function among men aged 45–75 years in an urban area of Iran

AbstractBackground and aimsAging in men is associated with various physical and mental symptoms, including sleep problems and sexual dysfunction. The aim of this study was to determine the status of sleep disorders and sexual dysfunction in men aged 45–75 years in Ilam, Iran.Materials and methodsIn this population-based cross-sectional study, 390 men aged 45–75 years were selected by cluster randomization in Ilam–Iran. Data were collected using 0–100 brief sexual function inventory and the sleep disorder questionnaires.ResultsTotally, 34.6% of men complained about sleep disorders: 17.4% about falling asleep, 12.8% about frequent nocturnal awakenings, 12.8% about waking up in the early hours in the morning and problem in falling asleep again, and 24.9% about fatigue and tiredness despite getting enough sleep. There was a significant relationship between all aspects of sexual function and the common problems related to sleep (p<0.001). The older, unemployed, illiterate men, those with inadequate income, those affected by chronic diseases, and/or urinary incontinence had significantly inferior sexual function compared with the others.ConclusionAccording to the high prevalence of sleep disorders in men as well as its association with sexual dysfunction, adopting health measures in this regard is necessary

Induction Effects Of Bacteroides Fragilis Derived Outer Membrane Vesicles On Toll Like Receptor 2, Toll Like Receptor 4 Genes Expression And Cytokines Concentration In Human Intestinal Epithelial Cells

Objective Gastrointestinal (GI) tract, like other mucosal surface, is colonized with a microbial population known as gut microbiota. Outer membrane vesicles (OMVs) which are produced by gram negative bacteria could be sensed by Toll like receptors (TLRs). The interaction between gut microbiota and TLRs affects homeostasis and immune responses. In this study, we evaluated TLR2, TLR4 genes expression and cytokines concentration in Caco-2 cell line treated with Bacteroides fragilis (B. fragilis) and its OMVs. Materials And Methods In this experimental study, OMVs were extracted using sequential centrifugation and their physicochemical properties were evaluated as part of quality control assessment. Caco-2 cells were treated with B. fragilis and its OMVs (180 and 350 µg/ml). Quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) was performed to assess TLR2 and TLR4 mRNA expression levels. Pro-inflammatory (IFNᵧ) and anti-inflammatory (IL- 4 and IL-10) cytokines were evaluated by ELISA. Results B. fragilis significantly decreased TLR2 and slightly increased TLR4 mRNA levels in Caco-2 cell line. The TLR2 mRNA level was slightly increased at 180 and 350 µg/ml of OMVs. Conversely, the TLR4 mRNA level was decreased at 180 µg/ml of OMVs, while it was significantly increased at 350 µg/ml of OMVs. Furthermore, B. fragilis and its OMVs significantly increased and decreased IFNᵧ concentration, respectively. Anti-inflammatory cytokines were increased by B. fragilis and its OMVs. Conclusion B. fragilis and its OMVs have pivotal role in the cross talk between gut microbiota and the host especially in the modulation of the immune system. Based on the last studies on immunomodulatory effect of B. fragilis derived OMVs on immune cells and our results, we postulate that B. fragilis derived OMVs could be possible candidates for the reduction of immune responses

Clinical Reasoning in Dentistry

Background: Clinical reasoning is the core competency of healthcare. It involves cognition and interaction with the environment to understand clinical situations, make diagnostic and therapeutic decisions, and address clinical problems. Defining competency in clinical reasoning is a difficult objective for dental educators because of our limited understanding of this phenomenon which compromises the validity of any curricular model and assessment method that have been used to date. Objectives: To describe the process and strategies of clinical reasoning used by dental clinicians across different levels of expertise to develop a conceptual framework for curricular design and assessment of competency. Methods: Using “think-aloud” method, I interviewed 18 dental students about biopsychosocial issues influencing oral health identified in 6 vignettes; and 8 orthodontic residents plus 11 orthodontists about problems of craniofacial growth and malocclusion presented in 2 vignettes. The interview transcripts were analyzed to explore the process and strategies of clinical reasoning used by the participants. Results: The reasoning process in both groups included: 1) a ritualistic approach to collect information for a treatment plan; 2) forward and backward reasoning to make and test hypotheses from clinical information; 3) pattern recognition and an integrated script of knowledge and experience triggered by related attributes of the script leading to a clinical diagnosis and plan; and 4) decision trees to evaluate treatment options and maximize the probability and utility of outcomes. Seven reasoning strategies (scientific, conditional, collaborative, narrative, ethical, pragmatic and “part-whole”) were used by both groups. However, experienced clinicians were more confident in their appraisal of uncertain situations and dilemmas as they integrated several reasoning strategies in the process; used refined scripts of knowledge and experience in familiar situations; and were able to reflect on the impact on their reasoning of the larger social, cultural and political context. Conclusions: Clinical reasoning in dentistry is a contextual and interactive phenomenon that requires integration of specific reasoning strategies to address the biopsychosocial factors influencing oral health. Expertise in clinical reasoning develops through continuous framing and solving problems to refine networks of knowledge and experience and develop adaptive strategies to address the contextual determinants of oral health.Dentistry, Faculty ofGraduat

Clinical Reasoning in Dentistry: A Conceptual Framework for Dental Education

Objectives. To describe the process and strategies of clinical reasoning used by dental clinicians across different levels of expertise to develop a conceptual framework for curricular design and assessment of competency. Methods. Using “think-aloud” method, we interviewed 18 dental students about biopsychosocial issues influencing oral health identified in 6 vignettes; and 8 orthodontic residents plus 11 orthodontists about problems of craniofacial growth and malocclusion presented in 2 vignettes. The interview transcripts were analyzed to explore the process and strategies of clinical reasoning used. Results. The reasoning process in both groups included: 1) a ritualistic approach to collect information for a treatment plan; 2) forward and backward reasoning to make and test hypotheses from clinical information; 3) pattern recognition and an integrated script of knowledge and experience triggered by related attributes of the script leading to a clinical diagnosis and plan; and 4) decision trees to evaluate treatment options and maximize the probability and utility of outcomes. Seven reasoning strategies (scientific, conditional, collaborative, narrative, ethical, pragmatic and “part-whole”) were used by both groups. However, experienced clinicians were more confident in their appraisal of uncertain situations and dilemmas as they integrated several reasoning strategies in the process; used refined scripts of knowledge and experience in familiar situations; and were able to reflect on the impact on their reasoning of the larger social, cultural and political context. Conclusions. Clinical reasoning in dentistry is a contextual and interactive phenomenon that requires integration of specific reasoning strategies to address the biopsychosocial factors influencing oral health. Grants. This study was supported by the Institute for the Scholarship of Teaching and Learning at University of British Columbia, Vancouver, Canada

Assessment of a new algorithm in the management of acute respiratory tract infections in children

Objectives: To assess the practicability of a new algorithm in decreasing the rate of incorrect diagnoses and inappropriate antibiotic usage in pediatric Acute Respiratory Tract Infection (ARTI). Materials and Methods: Children between 1 month to15 years brought to outpatient clinics of a children′s hospital with acute respiratory symptoms were managed according to the steps recommended in the algorithm. Results: Upper Respiratory Tract Infection, Lower Respiratory Tract Infection, and undifferentiated ARTI accounted for 82%, 14.5%, and 3.5% of 1 209 cases, respectively. Antibiotics were prescribed in 33%; for: Common cold, 4.1%; Sinusitis, 85.7%; Otitis media, 96.9%; Pharyngotonsillitis, 63.3%; Croup, 6.5%; Bronchitis, 15.6%; Pertussis-like syndrome, 82.1%; Bronchiolitis, 4.1%; and Pneumonia, 50%. Conclusion: Implementation of the ARTIs algorithm is practicable and can help to reduce diagnostic errors and rate of antibiotic prescription in children with ARTIs