BK and JC polyomaviruses and risk of urothelial bladder carcinoma: a preliminary study in the northern shores of Persian Gulf, Iran

Abstract Background: Bladder cancer is a challenging public health concern in South of Iran because of its high prevalence and the related medical expenses. Although the exact etiology of bladder cancer remains unknown, given the cell transforming ability and oncogenic potential of the members of Polyomaviridae families, this study was conducted to evaluate the magnitude of BK polyomavirus (BKPyV) and John Cunningham polyomavirus (JCPyV) among patients with bladder cancer residents in the northern shores of the Persian Gulf, South of Iran. Methods: Totally 211 patients with bladder cancer were enrolled in this study. Bladder biopsy samples of these patients and patients with interstitial cystitis as well as autoptic samples of healthy bladder were tested for detection of BKPyV and JCPyV by semi-nested PCR–RFLP followed by sequencing. Results: BKPyV and JCPyV were detected in 1.7% and 6.1% of bladder cancer samples, respectively. These samples were infected with JCPyV genotypes 2, 3 and 6 and BKPyV genotypes I and IV. BKPyV and JCPyV coinfection was detected in 2 samples. Moreover, one of the healthy bladder samples was positive for BKPyV, and one of the interstitial cystitis samples was positive for JCPyV. Although the majority of infected patients were in the age group 70–79 years, male, residents in Tangestan, stage Ta–T1, and low-grade and high-grade papillary urothelial carcinoma, the preva- lence of BKPyV and JCPyV among patients with bladder cancer was not statistically associated with age, gender, place of residency, and stage and grade of the tumor. Conclusion: Despite identifying BKPyV and JCPyV in a number of bladder cancer biopsy specimens and the high prevalence of bladder cancer among people resident in South of Iran, it is suggested that these viruses are unlikely to be effective causative factors in bladder carcinogenesis in this region. Therefore, environmental risk factors and genetic backgrounds may have a more prominent role than human polyomaviruses in the development of bladder cancer in South of Iran. Keywords: Urothelial bladder carcinoma, Human polyomavirus, BK polyomavirus, John Cunningham polyomavirus, Prevalence, Genotype, Risk factors, Ira

Prevalence of reflux nephropathy in Iranian children with solitary kidney: results of a multi-center study

Abstract Background: Given the importance of the function of the remnant kidney in children with unilateral renal agen‑ esis and the significance of timely diagnosis and treatment of reflux nephropathy to prevent further damage to the remaining kidney, we aimed to determine the prevalence of reflux nephropathy in this subgroup of pediatric patients. Methods: In general, 274 children referred to pediatric nephrologists in different parts of Iran were evaluated, of whom 199 had solitary kidney and were included in this cross‑sectional study. The reasons for referral included urinary tract infection (UTI), abnormal renal ultrasonography, being symptomatic, and incidental screening. Demographic characteristics, including age and gender were recorded. History of UTI and presence of vesicoureteral reflux (VUR) were evaluated. Results: Of the 274 children evaluated in this study with the mean age (SD) of 4.71 (4.24) years, 199 (72.6%) had solitary kidney. Among these, 118 (59.3%) were male and 81 (60.7%) were female, 21.1% had a history of UTI, and VUR was present in 23.1%. The most common cause of referral was abnormal renal ultrasonography (40.2%), followed by incidental screening (21.1%), being symptomatic (14.1%), and UTI (5.5%). In 116 children (58.3%), the right kidneys and in 83 (41.7%) the left kidneys were absent. Besides, 14.6% of the participants had consanguineous parents and 3% had a family history of solitary kidney. Upon DMSA scan, the single kidney was scarred in 13.1%, of which only 7.5% were associated with VUR. In addition, proteinuria and hematuria were observed in 6.5% and 1.5% of children, respectively. Conclusions: The prevalence of reflux nephropathy was 7.5% in children with solitary kidney with a male predomi‑ nance. Given the relatively high prevalence of reflux nephropathy in these children, screening for VUR in the remnant kidney appears to be essential in this population. Keywords: Vesicoureteral reflux, Nephropathy, Children, Solitary kidney, Renal agenesi

Silymarin Administration Attenuates Cirrhotic-induced Cardiac Abnormality in the Rats: A Possible Role of β1-adrenergic Receptors and L-type Voltage-Dependent Calcium Channels

Background: Cirrhotic cardiomyopathy is a well-recognized cardiac dysfunction in cirrhotic patients. Studies have confirmed the protective effects of silymarin in different types of cardiac injury. This study aimed to examine the effectiveness and molecular mechanism of silymarin against myocardial dysfunction and hypertrophy in a rat model of cirrhosis. Methods: The experiment was performed at Alborz University of Medical Sciences (Karaj, Iran) during 2020-2021. Thirty-two male Wistar rats were randomly divided into four groups of Sham-operated (control group for surgical procedures), Bile Duct Ligated (BDL), and two Silymarin extract (SE)-treated groups of 300 and 600 mg/Kg/day. After 28 days, serum levels of AST, ALT, GGT, and ALP, liver histopathological status, as well as cardiac mechanical function, were assessed. Cardiac β1-adrenergic receptors (β1-AR), L-type voltage-dependent calcium channels (L-VDCC), and GATA4 mRNA expression were also determined using real-time RT-PCR. Data analysis was performed using the one-way ANOVA followed by Duncan’s multiple range test. Histological data has been analyzed with Kruskal-Wallis nonparametric test. The analysis was performed at P≤0.05. Results: BDL was associated with a significant elevation in serum AST, ALT, GGT, and ALP, development of necrosis and fibrosis of the liver texture, increased Heart Weight and Heart Weight to Body Weight ratio, enhanced cardiac mechanical function as well as a significant up-regulation of ventricular β1-AR and L-VDCC. Administration of SE600, but not SE300, significantly reduced the serum levels of the enzymes and alleviated signs of liver necrosis and fibrosis. Cirrhotic-induced cardiac dysfunction was also restored by SE600, but not by the lower dose. In addition, cardiac expression of the β1-AR and L-VDCC was down-regulated toward normal values by either higher or lower doses of the SE. Conclusion: Silymarin treatment in higher dose attenuated cirrhosis-associated cardiac remodeling and reduced cardiac mechanical dysfunctions

Bone mass and microarchitecture in T2DM patients and corticosteroids therapy: the Bushehr Elderly Health program

Purpose Our study examined whether T2DM and glucocorticoids treatment affect bone quality and quantity that are measured by Bone Mineral Density (BMD) and Trabecular Bone Score (TBS). Materials & methods Participants in this study were 2294 women and men aged over 60 years who participated in stage II of the Bushehr Elderly Health (BEH) program. Patients with T2DM and those who received glucocorticoids were included. BMD was detected using the DXA method and the TBS of L1-L4 was evaluated by TBS iNsight® software. To evaluate the correlation between TBS and BMD levels with diabetes and taking corticosteroids sex-specific multivariable linear regression models were appplied. Results TBS and BMD were not significantly different in those who had received glucocorticoids versus those who did not.T2DM revealed a significant association with both BMD and TBS in men (beta = 0.12, p < 0.001 and beta = 0.063, p = 0.03, respectively). BMD values were significantly higher in diabetic women (beta = 0.073, p < 0.01). BMI had a significant association with both TBS and BMD but in an opposite direction, in women and men (BMD: beta = -0.22, -0.24, and regarding TBS: beta = 0.37, 0.25, all p-values < 0.001). Conclusion Our findings showed that T2DM had major effects on BMD in both men and women. However, T2DM only affects TBS in men. Furthermore, neither BMD nor TBS were affected by GC intake in men or women.Based on the variable importance of covariates, BMI was the most influential factor on both BMD and TBS, although in opposite directions, in both sexes

TGF-β1 receptor blockade attenuates unilateral ureteral obstruction-induced renal fibrosis in C57BL/6 mice through attenuating Smad and MAPK pathways

Renal fibrosis is characterized by accumulation of extracellular matrix components and collagen deposition. TGF-β1 acts as a master switch promoting renal fibrosis through Smad dependent and/or Smad independent pathways. Thirty-five male C57BL/6 mice were divided into five groups of seven each; sham, unilateral ureteral obstruction (UUO), UUO+galunisertib (150 and 300 mg/kg/day), galunisertib (300 mg/kg/day). The UUO markedly induced renal fibrosis and injury as indicated by renal functional loss, increased levels of collagen Iα1, fibronectin and α-SMA; it also activated both the Smad 2/3 and MAPKs pathways as indicated by increased levels of TGF-β1, p-Smad 2, p-Smad 3, p-p38, p-JNK and p-ERK. These UUO-induced changes were markedly attenuated by oral administration of galunisertib, the TGFβRI small molecule inhibitor. In conclusion, we demonstrated that TGF-β1 receptor blockade can prevent UUO-induced renal fibrosis through indirect modulation of Smad and MAPKs signaling pathways and may be useful as a therapeutic agent in treatment and/or prevention of renal fibrosis

Novel compound heterozygous variants in XYLT1 gene caused Desbuquois dysplasia type 2 in an aborted fetus: a case report

Background Desbuquois dysplasia type 2 (DBQD2) is an infrequent dysplasia with a wide range of symptoms, including facial deformities, growth retardation and short long bones. It is an autosomal recessive disorder caused by mutations in the XYLT1 gene that encodes xylosyltransferase-1. Case presentation We studied an aborted fetus from Iranian non-consanguineous parents who was therapeutically aborted at 19 weeks of gestation. Ultrasound examinations at 18 weeks of gestation revealed growth retardation in her long bones and some facial problems. Whole-exome sequencing was performed on the aborted fetus which revealed compound heterozygous XYLT1 mutations: c.742G>A; p.(Glu248Lys) and c.1537 C>A; p.(Leu513Met). Sanger sequencing and segregation analysis confirmed the compound heterozygosity of these variants in XYLT1. Conclusion The c.1537 C>A; p.(Leu513Met) variant has not been reported in any databases so far and therefore is novel. This is the third compound heterozygote report in XYLT1 and further supports the high heterogeneity of this disease

PrACTiC: A Predictive Algorithm for Chemoradiotherapy-Induced Cytopenia in Glioblastoma Patients

Background. Chemotherapy-induced cytopenia is the most frequent side effect of chemoradiotherapy in glioblastoma patients which may lead to reduced delivery of treatment. *is study aims to develop a predictive model that is able to forecast the cytopenia induced by temozolomide (TMZ) during concomitant chemoradiotherapy. Methods. Medical records of 128 patients with newly diagnosed glioblastoma were evaluated to extract the baseline complete blood test before and during the six weeks of chemoradiotherapy to create a dataset for the development of ML models. Using the constructed dataset, different ML algorithms were trained and tested. Results. Our proposed algorithm achieved accuracies of 85.6%, 88.7%, and 89.3% in predicting thrombocytopenia, lymphopenia, and neutropenia, respectively. Conclusions. *e algorithm designed and developed in this study, called PrACTiC, showed promising results in the accurate prediction of thrombocytopenia, neutropenia, and lymphopenia induced by TMZ in glioblastoma patients. PrACTiC can provide valuable insight for physicians and help them to make the necessary treatment modifications and prevent the toxicitie

Obesity Accelerates Leukocyte Telomere Length Shortening in Apparently Healthy Adults: A Meta-Analysis

Background: Shorter telomere length is associated with numerous comorbidities. Several studies have investigated the role of obesity in telomere shortening. In the current systematic review and meta-analysis, we summarized the results of studies that evaluated the association between obesity and telomere length. Methods: A systematic search from Scopus, PubMed, Embase, and ProQuest electronic databases up to 19 March 2021 without language restriction was performed and after data extraction and screening, 19 manuscripts were eligible to be included in the final meta-synthesis. Results: The highest category of telomere length was associated with an approximate 0.75 kg/m2 reduction in body mass index (BMI; WMD = −0.75 kg/m2; CI = −1.19, −0.31; p < 0.001; I2 = 99.4%). Moreover, overweight/obese individuals had 0.036 kbp shorter telomere length compared with non-overweight/obese adults (WMD = −0.036; CI = −0.05, −0.02; p = 0.030; I2 = 100%). According to the results of subgroupings, continent, age, and sample size could be possible sources of heterogeneity. Conclusion: From the results, it was clear that obesity was associated with shorter telomere length. Because of the observational design of included studies, the causality inference of results should be done with caution; thus, further longitudinal studies are warranted for better inference of causal association

The economic burden of osteoporosis in Iran in 2020

Osteoporosis, the most common metabolic bone disease, leads to increased susceptibility to fractures. In 2020, about 150,000 osteoporotic fractures occurred in Iran. Osteoporosis and related fractures cost the community US$393 million. Introduction The present study aimed at estimating the economic burden of osteoporosis in Iran in 2020. Methods We estimated the annual economic burden of osteoporosis in the above 50 years old population using a prevalence-based approach and from a societal perspective. The incidence of osteoporosis and related fractures were estimated based on meta-analysis reports in Iran and international comparisons. The direct medical and non-medical costs as well as the monetary value of quality-adjusted life-years (QALYs) lost because of fractures were estimated. Cost data were extracted from patient records, medical services prices, and previous literature. Results A total of 154,530 osteoporotic fractures were estimated in Iran in 2020. The shares of the hip, vertebral, forearm, and other fractures were 14$ 393.24 million (US$ 2165 million purchasing power parity 2020). Direct medical and non-medical cost (47.44%), QALY loss (29.65%), and long-term care for prior hip fracture costs (9.4%) were the main component of the economic burden of osteoporosis. Conclusion The economic burdens of osteoporosis are significant in Iran. Interventions to prevent osteoporosis and especially associated fractures, such as screening and prophylaxis, can reduce the cost of the disease and improve patients’ quality of life. Further studies are needed to identify cost-effective and feasible interventions in Iran

Health impacts quantification attributed to ambient particulate matter in the nearest Iranian city to the main dust source

Urban air contamination is one of the ten most dangerous parameters for human health, which causes cardiovascular disease, respiratory, metabolic diseases, and decreased lung function. Air Q is a reliable software for studying the impacts of atmospheric contaminants on human health, and today, it is widely used in the environment. The purpose of this research was to quantify the mortality and morbidity rates that corresponded to ambient particulate matter (PM) in Rigan City. To perform this, the Air Q software was used. The findings reflected that the yearly mean values of PM10 and PM2.5 are 264.83 and 50.45 μg/m3. The findings indicated that the PM10 and PM2.5 content in Rigan was above standard levels described by WHO. The total number of deaths, cardiovascular deaths, and respiratory deaths due to PM in Rigan were estimated as 70.3, 45.8, and 10.7 persons, respectively. Hospital admissions for cardiovascular and respiratory diseases correlated to PM10 were estimated at 154.2 and 59 persons, respectively. Acute myocardial infarction associated with PM2.5 was 2.7 persons. Overall, the data in this study may be helpful to national and regional policymakers who are responsible for managing and preventing atmospheric contamination and assessing the costs of health risks