Impact of Sleeve Gastrectomy on Uric Acid Levels in Patients with Obesity: A Comparative Study.

PURPOSE: This study aimed to investigate the incidence of hyperuricemia in obese individuals with or without metabolic syndrome and assess the impact of sleeve gastrectomy surgery on the amelioration of hyperuricemia and metabolic syndrome. MATERIALS AND METHODS: A prospective study was conducted on patients with obesity who were candidates for laparoscopic sleeve gastrectomy. These patients were diligently followed for 1 year after the surgical procedure. The assessment of hyperuricemia and metabolic syndrome was carried out both before and one year after the surgery. RESULTS: A total of 198 patients (30 males and 168 females) underwent sleeve gastrectomy. After 1 year, there was a notable decline in the prevalence of hyperuricemia, decreasing from 77 to 36 cases (a reduction of 46.75%) among females and from 18 to 8 cases (a reduction of 44.44%) among males. Prior to the surgery, 60.6% of patients (120 out of 198) were diagnosed with metabolic syndrome, and 36.7% of these patients exhibited improvements in their metabolic syndrome status. Among individuals with metabolic syndrome, significant enhancements were observed in various anthropometric and laboratory measurements, including reductions in hypertriglyceridemia, hyperuricemia, and hypercholesteremia. A logistic regression analysis revealed that in females, changes in creatinine, glomerular filtration rate (GFR), weight loss, body mass index (BMI), and triglyceride reduction all had a notable impact on the likelihood of recovering from hyperuricemia. CONCLUSION: These findings underscore the clinical relevance of this surgical intervention in managing obesity-related conditions.

Ideal cardiovascular health status and risk of cardiovascular disease and all-cause mortality: over a decade of follow-up in the Tehran lipid and glucose study.

Objective: To quantify the association between ideal cardiovascular health (CVH) metrics and incident cardiovascular disease (CVD) including different subtypes [coronary heart disease (CHD), stroke, and sudden death], and all-cause mortality in an Iranian population. Methods: The study population included 6,388 participants (2,726 men) aged 48.0 ± 12.4 years free of CVD at baseline. We utilized the American Heart Association's 2020 impact target criteria of ideal, intermediate, and poor CVH. The multivariate Cox proportional Hazard model, adjusted for age, sex, educational level, marital status, and family history of CVD, was applied to estimate the hazard ratio (HR) of outcomes per one additional metric of ideal CVH metrics. Furthermore, the risk was also calculated for ideal and intermediate categories considering poor category as a reference. Results: During the median follow-up of 11.26 years, 692 CVD, 589 CHD, 130 stroke, 111 sudden death, and 519 all-cause mortality events were reported. All of the individual ideal CVH metrics were independent predictors except intermediate physical activity level for CVD, BMI < 25 kg/m2, and intermediate physical activity for all-cause mortality. Each additional metrics of ideal CVH decreased the risk by 31 (0.69, 0.65-0.73) for CVD, 32 (0.68, 0.64-0.73) for CHD, 31 (0.69, 0.60-0.80) for stroke, 25 (0.75, 0.64-0.88) for sudden death, and 13% (0.87, 0.81-0.93) for all-cause mortality events. Moreover, intermediate and ideal categories of CVH metrics were associated with lower risk for different CVD outcomes, i.e., 44 (0.56, 0.48-0.65) and 76% (0.24, 0.17-0.35) for CVD; 43 (0.57, 0.47-0.67) and 75% (0.25, 0.16-0.37) for CHD, 58 (0.42, 0.29-0.61) and 86% (0.14, 0.04-0.44) for stroke; 56 (0.44, 0.29-0.66) and 55% (0.45, 0.21-0.99) for sudden death; and 25 (0.75, 0.62-0.90) and 46% (0.54, 0.37-0.80) for all-cause mortality events, respectively. We also assessed the impact of changes in ideal CVH status from phase III to phase IV (2008-2011) on CVD events among 5,666 participants. Accordingly, compared to those remaining in the poor category, all of the changes in ideal CVH categories showed a lower risk for CVD events. Conclusion: Among the Iranian population, meeting higher ideal CVH metrics is associated with a lower risk of different CVD events and mortality outcomes.

Transmission electron microscopy study of suspected primary ciliary dyskinesia patients.

Primary ciliary dyskinesia (PCD) is a rare autosomal recessive condition often presenting with chronic respiratory infections in early life. Transmission electron microscopy (TEM) is used to detect ciliary ultrastructural defects. In this study, we aimed to assess ciliary ultrastructural defects using quantitative methods on TEM to identify its diagnostic role in confirming PCD. Nasal samples of 67 patients, including 37 females and 30 males (20.3 ± 10.7 years old), with suspected PCD symptoms were examined by TEM. The most common presentations were bronchiectasis: 26 (38.8%), chronic sinusitis: 23 (34.3%), and recurrent lower respiratory infections: 21 (31.3%). Secondary ciliary dyskinesia, including compound cilia (41.4%) and extra-tubules (44.3%), were the most prevalent TEM finding. Twelve patients (17.9%) had hallmark diagnostic criteria for PCD (class 1) consisting of 11 (16.4%) outer and inner dynein arm (ODA and IDA) defects and only one concurrent IDA defect and microtubular disorganization. Also, 11 patients (16.4%) had probable criteria for PCD (class 2), 26 (38.8%) had other defects, and 18 (26.9%) had normal ciliary ultrastructure. Among our suspected PCD patients, the most common ultrastructural ciliary defects were extra-tubules and compound cilia. However, the most prevalent hallmark diagnostic defect confirming PCD was simultaneous defects of IDA and ODA.

Combined molecular, structural and memory data unravel the destructive effect of tramadol on hippocampus.

Tramadol is a synthetic analogue of codeine and stimulates neurodegeneration in several parts of the brain that leads to various behavioral impairments. Despite the leading role of hippocampus in learning and memory as well as decreased function of them under influence of tramadol, there are few studies analyzing the effect of tramadol administration on gene expression profiling and structural consequences in hippocampus region. Thus, we sought to determine the effect of tramadol on both PC12 cell line and hippocampal tissue, from gene expression changes to structural alterations. In this respect, we investigated genome-wide mRNA expression using high throughput RNA-seq technology and confirmatory quantitative real-time PCR, accompanied by stereological analysis of hippocampus and behavioral assessment following tramadol exposure. At the cellular level, PC12 cells were exposed to 600 µM tramadol for 48 hrs, followed by the assessments of ROS amount and gene expression levels of neurotoxicity associated with neurodegenerative pathways such as apoptosis and autophagy. Moreover, the structural and functional alteration of the hippocampus under chronic exposure to tramadol was also evaluated. In this regard, rats were treated with tramadol at doses of 50 mg/kg for three consecutive weeks. In vitro data revealed that tramadol provoked ROS production and caused the increase in the expression of autophagic and apoptotic genes in PC12 cells. Furthermore, in-vivo results demonstrated that tramadol not only did induce hippocampal atrophy, but it also triggered microgliosis and microglial activation, causing upregulation of apoptotic and inflammatory markers as well as over-activation of neurodegeneration. Tramadol also interrupted spatial learning and memory function along with long-term potentiation (LTP). Taken all together, our data disclosed the neurotoxic effects of tramadol on both in vitro and in-vivo. Moreover, we proposed a potential correlation between disrupted biochemical cascades and memory deficit under tramadol administration.

Design, Synthesis, and In Vitro and In Vivo Evaluation of Novel Fluconazole-Based Compounds with Promising Antifungal Activities.

Demand has arisen for developing new azole antifungal agents with the growth of the resistant rate of infective fungal species to current azole antifungals in recent years. Accordingly, the present study reports the synthesis of novel fluconazole (FLC) analogues bearing urea functionality that led to discovering new azole agents with promising antifungal activities. In particular, compounds 8b and 8c displayed broad-spectrum activity and superior in vitro antifungal capabilities compared to the standard drug FLC against sensitive and resistant Candida albicans (C. albicans). The highly active compounds 8b and 8c had potent antibiofilm properties against FLC-resistant C. albicans species. Additionally, these compounds exhibited very low toxicity for three mammalian cell lines and human red blood cells. Time-kill studies revealed that our synthesized compounds displayed a fungicidal mechanism toward fungal growth. Furthermore, a density functional theory (DFT) calculation, additional docking, and independent gradient model (IGM) studies were performed to analyze their structure-activity relationship (SAR) and to assess the molecular interactions in the related target protein. Finally, in vivo results represented a significant reduction in the tissue fungal burden and improvements in the survival rate in a mice model of systemic candidiasis along with in vitro and in silico studies, demonstrating the therapeutic efficiency of compounds 8b and 8c as novel leads for candidiasis drug discovery.

Sudden cardiac death among Iranian population: a two decades follow-up of Tehran lipid and glucose study.

Sudden cardiac death (SCD) is described as death within one hour, if observed, from the onset of symptoms, and within 24 h of being alive and well if not observe. Study population includes 3705 men and 4446 women, aged ≥ 30 years. Multivariable Cox proportional hazard models were used to determine the risk factors associated with SCD. After a median follow-up of 17.9 years, 244 SCD (165 in males) occurred. The age-standardized incidence rate (95% confidence intervals (CI)) of SCD was 2.3 (2.1-2.7) per 1000 person-year. Current smoking [Hazard ratio (HR): 2.43, 95% CI: 1.73-3.42], high waist circumference [1.49: 1.04-2.12], hypertension [1.39: 1.05-1.84], type 2 diabetes mellitus [2.78: 2.09-3.69], pulse rate ≥ 90 beats per/minute [1.72: 1.22-2.42] and prevalent cardiovascular disease [1.75: 1.26-2.45] were significant risk factors. The corresponding population attributed fractions (PAF) were 14.30, 16.58, 14.03, 19.60, 7.62, and 8.30, respectively. Being overweight [0.58: 0.40-0.83] and obese [0.61: 0.38-0.98] decreased the risk of SCD. After excluding known diabetes cases from our data analysis, the newly diagnosed diabetes still showed an HR of 2.0 (1.32-3.00) with a PAF of 7.15% in the full adjustment model. To deal with sudden death as a catastrophic outcome, multi-component strategies by policy health makers are suggested.

A Review on Molecular Mechanisms of Antifungal Resistance in Candida glabrata: Update and Recent Advances.

Candida glabrata is the second frequent etiologic agent of mucosal and invasive candidiasis. Based on the recent developments in molecular methods, C. glabrata has been introduced as a complex composed of C. glabrata, Candida nivariensis, and Candida bracarensis. The four main classes of antifungal drugs effective against C. glabrata are pyrimidine analogs (flucytosine), azoles, echinocandins, and polyenes. Although the use of antifungal drugs is related to the predictable development of drug resistance, it is not clear why C. glabrata is able to rapidly resist against multiple antifungals in clinics. The enhanced incidence and antifungal resistance of C. glabrata and the high mortality and morbidity need more investigation regarding the resistance mechanisms and virulence associated with C. glabrata; additional progress concerning the drug resistance of C. glabrata has to be further prevented. The present review highlights the mechanism of resistance to antifungal drugs in C. glabrata.

Comparison of Antifungal Properties of Gold, Silver, and Selenium Nanoparticles Against Amphotericin B-Resistant Candida glabrata Clinical Isolates.

BACKGROUND: The present study aimed to investigate the antifungal activity of Nanoparticles (NPs) against amphotericin B-resistant Candida glabrata (C. glabrata) strains. METHODS: Twelve resistant (C. glabrata) strains were isolated from archived clinical isolates. Antifungal activity was conducted according to Clinical and Laboratory Standards Institute's (CLSI) guidelines, document M27-A3/S4. The Scanning Electron Microscope (SEM) was used to observe the morphological changes of strains exposed to each nanoparticle. RESULTS: Minimum Inhibitory Concentration (MIC) of nanoparticles of all strains was in the concentration range of 0.125 to 0.5 µg/Ml. The synthesized Ag-NPs showed superior antifungal activity against (C. glabrata) compared to Se-NPs and Au-NPs. The scanning electron microscope images revealed the difference in the fungal morphology between the untreated and treated fungi with nanoparticles. CONCLUSION: The Ag-NPs, followed by Se-NPs synthesized, revealed significant anti-fungal activity against resistance regardless of their antifungal-resistant mechanisms.

Sex-specific incidence rates and risk factors for fracture: A 16-year follow-up from the Tehran lipid and glucose study.

OBJECTIVE: To examine the population-based incidence of any-fracture and its potential risk factors in a sex-split cohort of the Iranian population. MATERIALS AND METHODS: A total of 3477 men and 4085 women with a mean (SD) age of 47.92(13.1) and 45.88(11.47) years, respectively were entered into the study. The age-standardized incidence rates per 100,000 person-years were reported for the whole population and each sex separately. Cox proportional hazard models were used to estimate hazard ratios (HR) for potential risk factors. Only fractures requiring inpatients' care were considered as the outcome. We also defined major osteoporotic fractures (MOF) as the composite of the fractures that occurred in the vertebral, wrist, hip and pelvic sites among population aged ≥50 years. RESULTS: During the median (IQR) follow-up of 15.9 years, 4.34%men and 3.75% women experienced at least one incident any-fracture. The annual age-standardized incidence rates (95% CI) among men and women were 330.9 (279.6-388.9) and 319.4(268.1-377.3) per 100,000 person-years, respectively; the corresponding values for incidence of MOF was 202.2(142.3-278.6) in men and 342.1(260.4-441.0) per 100,000 person-years for women. In the multivariable model, among the whole population, age groups ≥50 years, central obesity [HR: 95% CI 1.77(1.32-2.39)], current smoking [1.59(1.15-2.20)] and using steroid medications [2.20(1.04-4.67)] significantly increased the risk of incident fracture (all P < 0.05); however the impact of the first two risk factors were more prominent among women (P for interaction ≤0.01). Moreover, being obese was associated with a lower risk of incident first fracture in the total population [HR: 95% CI: 0.61(0.40-0.92)]. Being men [HR: 95% CI: 0.54(0.30-0.99)] and prediabetes status [HR: 95% CI: 0.53(0.30-0.95)] were also associated with lower risk for MOF. CONCLUSION: This is the first report of long-term incidence rate of any-fracture and MOF conducted in the metropolitan city of Tehran. Among modifiable risk factors of fracture, in the whole population smoking habit and using steroid medications and particularly for women central obesity should be considered as main risk factors for preventive strategies. Prediabetes status was associated with lower risk of MOF.

Number of parity/live birth(s) and cardiovascular disease among Iranian women and men: results of over 15 years of follow-up.

BACKGROUND: Most previous studies conducted in non-Middle Eastern populations have suggested that an increase in the number of parity/live birth(s) leads to cardiovascular disease (CVD) development, although their findings were inconclusive on this issue for both sexes. Biologic and socioeconomic pathways were suggested to explain this association. We studied this issue among urban Iranian men and women. METHODS: In this population-based cohort study, which included 3929 women and 2571 men aged ≥30 years, data for the number of parity/live birth(s) were obtained by a standard questionnaire. Participants were then annually followed for CVD events. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the number of parity/live birth(s) and other traditional CVD risk factors. RESULTS: During more than 15 years of follow-up, 456 and 524 CVD events have occurred among women and men, respectively. Among women, a J-shaped association was found between the number of live births and incident CVD with the lowest risk for women with two live births. Among women in multivariable analyses, each unit increase in parity had a HR of 1.05 (CI: 1.01-1.10), and having ≥4 parity was associated with a HR of 1.86 (0.97-3.56, p-value = 0.061). Among men, in comparison with participants who had 1 child, multivariable HRs of having 2, 3, and ≥ 4 children were 1.97 (1.24-3.12), 2.08 (1.31-3.31), and 2.08 (1.30-3.34), respectively. CONCLUSION: To the best of our knowledge, the current study is the first report on this issue in the Middle East and North Africa region, a region with a high burden of CVD. It can now be suggested that the number of parity/live birth(s) is linked to CVD among the Iranian population, with this issue being more prominent among men. Further research is needed to support our results and clarify the pathways between the number of parity/live birth(s) and CVD development among Iranian populations by considering potential risk factors, especially psycho-socio-economic risk factors.

Chronic administration of methylphenidate did not affect memory and GDNF levels but increase astrogliosis in adult male rat's hippocampus.

BACKGROUND: ADHD is the most common developmental disorder affecting approximately three to seven percent of school-aged children and 2.5 percent of adults worldwide. The drug of choice for the pharmacotherapy of ADHD is Methylphenidate (MPH). However, there is growing concerns about side effects resulting from its potential interference with brain anatomical and behavioral development. AIM: This article focuses on the adverse effects of MPH on the rat's hippocampus. METHODS: The animals received an oral dose of 5 mg/kg MPH or normal saline, as the vehicle, on a daily basis for 30 days. Y-maze test, passive avoidance, Barnes maze and field potential recording were conducted. Western blot for detecting the neurotrophic factor of GDNF and immunohistochemistry of astrogliosis were performed. RESULTS: Our results revealed that MPH treatment suppressed the willingness of rats to explore new environments. Also, it had no effect on improving long-term potentiation, long-term memory and spatial memory in the MPH group as opposed to the control group. There was also a significant increase of astrogliosis in the treated rats' hippocampi. On the other hand, there was not a significant relationship between MPH administration and the decrement of the GDNF level. CONCLUSION: We encourage the need to conduct more research on the adverse effects of MPH on the brain.

Tramadol: a Potential Neurotoxic Agent Affecting Prefrontal Cortices in Adult Male Rats and PC-12 Cell Line.

Tramadol is a synthetic analogue of codeine that is often prescribed for the treatment of mild to moderate pains. It has a number of side effects including emotional instability and anxiety. In this study, we focus on the structural and functional changes of prefrontal cortex under chronic exposure to tramadol. At the cellular level, the amounts of ROS and annexin V in PC12 cells were evidently increased upon exposure to tramadol (at a concentration of 600 µM for 48 h). To this end, the rats were daily treated with tramadol at doses of 50 mg/kg for 3 weeks. Our findings reveal that tramadol provokes atrophy and apoptosis by the induction of apoptotic markers such as Caspase 3 and 8, pro-inflammatory markers, and downregulation of GDNF. Moreover, it triggers microgliosis and astrogliosis along with neuronal death in the prefrontal cortex. Behavioral disturbance and cognitive impairment are other side effects of tramadol. Overall, our results indicate tramadol-induced neurodegeneration in the prefrontal cortex mainly through activation of neuroinflammatory response.