Tehran University of Medical Sciences

About: Tehran University of Medical Sciences is a education organization based out in Tehran, Iran. It is known for research contribution in the topics: Population & Cancer. The organization has 35661 authors who have published 57234 publications receiving 878523 citations. The organization is also known as: TUMS.

KIF1A, an Axonal Transporter of Synaptic Vesicles, Is Mutated in Hereditary Sensory and Autonomic Neuropathy Type 2

Abstract: Hereditary sensory and autonomic neuropathy type II (HSANII) is a rare autosomal-recessive disorder characterized by peripheral nerve degeneration resulting in a severe distal sensory loss. Although mutations in FAM134B and the HSN2 exon of WNK1 were associated with HSANII, the etiology of a substantial number of cases remains unexplained. In addition, the functions of WNK1/HSN2 and FAM134B and their role in the peripheral nervous system remain poorly understood. Using a yeast two-hybrid screen, we found that KIF1A, an axonal transporter of synaptic vesicles, interacts with the domain encoded by the HSN2 exon. In parallel to this screen, we performed genome-wide homozygosity mapping in a consanguineous Afghan family affected by HSANII and identified a unique region of homozygosity located on chromosome 2q37.3 and spanning the KIF1A gene locus. Sequencing of KIF1A in this family revealed a truncating mutation segregating with the disease phenotype. Subsequent sequencing of KIF1A in a series of 112 unrelated patients with features belonging to the clinical spectrum of ulcero-mutilating sensory neuropathies revealed truncating mutations in three additional families, thus indicating that mutations in KIF1A are a rare cause of HSANII. Similarly to WNK1 mutations, pathogenic mutations in KIF1A were almost exclusively restricted to an alternatively spliced exon. This study provides additional insights into the molecular pathogenesis of HSANII and highlights the potential biological relevance of alternative splicing in the peripheral sensory nervous system.

Coincidence of COVID-19 epidemic and olfactory dysfunction outbreak

Abstract: Background Recent surge of olfactory dysfunction in patients who were referred to ENT clinics and concurrent COVID-19epidemic in Iran motivated us to evaluate anosmic/hyposmic patients to find any relation between these two events. Methods This is a cross-sectional study with an online checklist on voluntary cases in all provinces of Iran between the 12th and 17th March, 2020. Cases was defined as self-reported anosmia/hyposmia in responders fewer than 4 weeks later (from start the of COVID-19 epidemic in Iran). Variables consist of clinical presentations, related past medical history, family history of recent respiratory tract infection and hospitalization. Results In this study 10069 participants aged 32.5 +/- 8.6 (7-78) years, 71.13% female and 81.68% non-smoker completed online checklist. They reported 10.55% a history of a trip out of home town and 1.1% hospitalization due to respiratory problems recently. From family members 12.17% had a history of severe respiratory disease in recent days and 48.23% had anosmia/hyposmia. Correlation between the number of olfactory disorder and reported COVID-19 patients in all 31 provinces till 16th March 2020 was highly significant (Spearman correlation coefficient=0.87, p-Value<0.001). The onset of anosmia was sudden in 76.24% and till the time of filling the questionnaire in 60.90% of patients decreased sense of smell was constant. Also 83.38 of this patients had decreased taste sensation in association with anosmia. Conclusions It seems that we have a surge in outbreak of olfactory dysfunction happened in Iran during the COVID-19 epidemic. The exact mechanism of anosmia/hyposmia in COVID-19 patients needs further investigations.

Curcumin as an anti-inflammatory agent: Implications to radiotherapy and chemotherapy.

Abstract: Cancer is the second cause of death worldwide. Chemotherapy and radiotherapy are the most common modalities for the treatment of cancer. Experimental studies have shown that inflammation plays a central role in tumor resistance and the incidence of several side effects following both chemotherapy and radiotherapy. Inflammation resulting from radiotherapy and chemotherapy is responsible for adverse events such as dermatitis, mucositis, pneumonitis, fibrosis, and bone marrow toxicity. Chronic inflammation may also lead to the development of second cancer during years after treatment. A number of anti-inflammatory drugs such as nonsteroidal anti-inflammatory agents have been proposed to alleviate chronic inflammatory reactions after radiotherapy or chemotherapy. Curcumin is a well-documented herbal anti-inflammatory agents. Studies have proposed that curcumin can help management of inflammation during and after radiotherapy and chemotherapy. Curcumin targets various inflammatory mediators such as cyclooxygenase-2, inducible nitric oxide synthase, and nuclear factor κB (NF-κB), thereby attenuating the release of proinflammatory and profibrotic cytokines, and suppressing chronic production of free radicals, which culminates in the amelioration of tissue toxicity. Through modulation of NF-κB and its downstream signaling cascade, curcumin can also reduce angiogenesis, tumor growth, and metastasis. Low toxicity of curcumin is linked to its cytoprotective effects in normal tissues. This protective action along with the capacity of this phytochemical to sensitize tumor cells to radiotherapy and chemotherapy makes it a potential candidate for use as an adjuvant in cancer therapy. There is also evidence from clinical trials suggesting the potential utility of curcumin for acute inflammatory reactions during radiotherapy such as dermatitis and mucositis.

Clinical Predictors for Germline Mutations in Head and Neck Paraganglioma Patients: Cost Reduction Strategy in Genetic Diagnostic Process as Fall-Out

Abstract: Multiple genes and their variants that lend susceptibility to many diseases will play a major role in clinical routine. Genetics-based cost reduction strategies in diagnostic processes are important in the setting of multiple susceptibility genes for a single disease. Head and neck paraganglioma (HNP) is caused by germline mutations of at least three succinate dehydrogenase subunit genes ( SDHx ). Mutation analysis for all 3 costs ∼US$2,700 per patient. Genetic classification is essential for downstream management of the patient and preemptive management of family members. Utilizing HNP as a model, we wanted to determine predictors to prioritize the most heritable clinical presentations and which gene to begin testing in HNP presentations, to reduce costs of genetic screening. Patients were tested for SDHB, SDHC , and SDHD intragenic mutations and large deletions. Clinical parameters were analyzed as potential predictors for finding germline mutations. Cost reduction was calculated between prioritized gene testing compared with that for all genes. Of 598 patients, 30.6% had SDHx germline mutations: 34.4% in SDHB , 14.2% SDHC , and 51.4% SDHD . Predictors for an SDHx mutation are family history [odds ratio (OR), 37.9], previous pheochromocytoma (OR, 10.9), multiple HNP (OR, 10.6), age ≤40 years (OR, 4.0), and male gender (OR, 3.5). By screening only preselected cases and a stepwise approach, 60% cost reduction can be achieved, with 91.8% sensitivity and 94.5% negative predictive value. Our data give evidence that clinical parameters can predict for mutation and help prioritize gene testing to reduce costs in HNP. Such strategy is cost-saving in the practice of genetics-based personalized health care. [Cancer Res 2009;69(8):3650–6]

A 12-week double-blind randomized clinical trial of vitamin D 3 supplementation on body fat mass in healthy overweight and obese women

Abstract: Vitamin D concentrations are linked to body composition indices, particularly body fat mass. Relationships between hypovitaminosis D and obesity, described by both BMI and waist circumference, have been mentioned. We have investigated the effect of a 12-week vitamin D3 supplementation on anthropometric indices in healthy overweight and obese women. In a double-blind, randomized, placebo-controlled, parallel-group trial, seventy-seven participants (age 38±8.1 years, BMI 29.8±4.1 kg/m2) were randomly allocated into two groups: vitamin D (25 μg per day as cholecalciferol) and placebo (25 μg per day as lactose) for 12 weeks. Body weight, height, waist, hip, fat mass, 25(OH) D, iPTH, and dietary intakes were measured before and after the intervention. Serum 25(OH)D significantly increased in the vitamin D group compared to the placebo group (38.2±32.7 nmol/L vs. 4.6±14.8 nmol/L; P<0.001) and serum iPTH concentrations were decreased by vitamin D3 supplementation (-0.26±0.57 pmol/L vs. 0.27±0.56 pmol/L; P<0.001). Supplementation with vitamin D3 caused a statistically significant decrease in body fat mass in the vitamin D group compared to the placebo group (-2.7±2.1 kg vs. -0.47±2.1 kg; P<0.001). However, body weight and waist circumference did not change significantly in both groups. A significant reverse correlation between changes in serum 25(OH) D concentrations and body fat mass was observed (r = -0.319, P = 0.005). Among healthy overweight and obese women, increasing 25(OH) D concentrations by vitamin D3 supplementation led to body fat mass reduction. This trial is registered at clinicaltrials.gov as NCT01344161.