Immunoexpression Pattern of Autophagy-Related Proteins in Human Congenital Anomalies of the Kidney and Urinary Tract.

The purpose of this study was to evaluate the spatiotemporal immunoexpression pattern of microtubule-associated protein 1 light chain 3 beta (LC3B), glucose-regulated protein 78 (GRP78), heat shock protein 70 (HSP70), and lysosomal-associated membrane protein 2A (LAMP2A) in normal human fetal kidney development (CTRL) and kidneys affected with congenital anomalies of the kidney and urinary tract (CAKUT). Human fetal kidneys (control, horseshoe, dysplastic, duplex, and hypoplastic) from the 18th to the 38th developmental week underwent epifluorescence microscopy analysis after being stained with antibodies. Immunoreactivity was quantified in various kidney structures, and expression dynamics were examined using linear and nonlinear regression modeling. The punctate expression of LC3B was observed mainly in tubules and glomerular cells, with dysplastic kidneys displaying distinct staining patterns. In the control group's glomeruli, LAMP2A showed a sporadic, punctate signal; in contrast to other phenotypes, duplex kidneys showed significantly stronger expression in convoluted tubules. GRP78 had a weaker expression in CAKUT kidneys, especially hypoplastic ones, while normal kidneys exhibited punctate staining of convoluted tubules and glomeruli. HSP70 staining varied among phenotypes, with dysplastic and hypoplastic kidneys exhibiting stronger staining compared to controls. Expression dynamics varied among observed autophagy markers and phenotypes, indicating their potential roles in normal and dysfunctional kidney development.

Unraveling the Impact of Dab1 Gene Silencing on the Expression of Autophagy Markers in Lung Development.

The purpose of this study was to evaluate the effects of Dab1 gene silencing on the immunoexpression of light chain 3 beta (Lc3b), glucose regulating protein 78 (Grp78), heat shock cognate 71 (Hsc70), mammalian target of rapamycin (mTOR) and lysosomal-associated membrane protein 2A (Lamp2a) in the lung tissue of developing yotari (Dab1-/-) and wild-type (wt) mice. The lung epithelium and mesenchyme of the embryos at gestational days E13.5 and E15.5 were examined using immunofluorescence and semi-quantitative methods. In the pulmonary mesenchyme and epithelium, Grp78 and Lc3b of moderate fluorescence reactivity was demonstrated in wt mice for both evaluated time points, while yotari mice exhibited only epithelial reactivity for the same markers. Mild punctate expression of Hsc70 was observed for both genotypes. A significant difference was present when analyzing mTOR expression, where wt mice showed strong perinuclear staining in the epithelium. According to our data, Dab1 gene silencing may result in autophagy abnormalities, which could then cause respiratory system pathologies via defective lung cell degradation by lysosome-dependent cell elimination.

Obesity and Clonal Hematopoiesis of Indeterminate Potential: Allies in Cardiovascular Diseases and Malignancies.

The clonal hematopoiesis of indeterminate potential (CHIP) is a term used to describe individuals who have detectable somatic mutations in genes commonly found in individuals with hematologic cancers but without any apparent evidence of such conditions. The mortality rate in individuals with CHIP is remarkably higher than the influence ascribed to hematologic malignancies, and it is plausible that cardiovascular diseases (CVD) could elucidate the apparent disparity. Studies have shown that the most frequently altered genes in CHIP are associated with the increased incidence of CVDs, type 2 diabetes mellitus (T2DM) and myeloid malignancies, as well as obesity. Additionally, multiple research studies have confirmed that obesity is also independently associated with these conditions, particularly the development and progression of atherosclerotic CVD. Considering the shared pathogenetic mechanisms of obesity and CHIP, our objective in this review was to investigate both preclinical and clinical evidence regarding the correlation between obesity and CHIP and the resulting implications of this interaction on the pathophysiology of CVDs and malignancies. The pro-inflammatory condition induced by obesity and CHIP enhances the probability of developing both diseases and increases the likelihood of developing CVDs, T2DM and malignancies, suggesting that a dangerous vicious loop may exist. However, it is vital to conduct additional research that will suggest targeted treatment options for obese individuals with CHIP in order to reduce harmful effects connected to these conditions.

Impact of COVID-19 Pandemic on Mental Health of Medical Students at the University of Mostar.

BACKGROUND: Previous studies have shown that medical students are more prone to depression, more tired, and more prone to emotional exhaustion, depersonalization and burnout syndrome than other students. In terms of mental health, they are a "more vulnerable" than individuals of the same age in the general population. In December 2019 in Wuhan (China) the outbreak of pneumonia caused by the new coronavirus captured worldwide attention. The implementation of strict quarantine measures kept a large number of people in self-isolation which affected all aspects of life. Objective of the study is to determine the direct impact of the COVID-19 pandemic on mental health and quality of life of medical students and the differences in the impact between genders and years of study. SUBJECT AND METHODS: This is a cross-sectional study conducted from May 25 to June 5 2020. It includes medical students who resided in the country affected by the COVID-19 pandemic. Participants completed a modified anonymous online questionnaire that assessed the Impact of Event Scale, indicators of negative mental health impacts, social and family support, and lifestyle changes due to a pandemic. RESULTS: The mean IES score in the participants showed a moderate stressful impact, with the mean IES score of females being significantly higher than that of males (29 vs. 19) with p<0.001. More than half of the participants had an IES score ≥26. With the onset of the pandemic, 71.5% of all medical students reported feeling increased stress from commitments. CONCLUSIONS: the pandemic had stressful impact on the mental health of medical students and it was significantly more stressful for women and students in the preclinical years of study. The COVID-19 pandemic had no impact on social and family support, however a positive impact on the lifestyle of medical students was found.

Association of Glomerular Filtration Rate and Carotid Intima-Media Thickness in Non-Diabetic Chronic Kidney Disease Patients over a 4-Year Follow-Up.

Patients with chronic kidney disease (CKD) have increased risk of cardiovascular events. However, the association of glomerular filtration rate (GFR) and carotid intima-media thickness (CIMT) in non-diabetic CKD patients is under-investigated. This prospective study was conducted at University Clinical Hospital Mostar over a 4-year period and enrolled a total of 100 patients with stage 2 and 4 CKD (50 patients per group). Stage 4 CKD group had significantly higher baseline CIMT values (1.13 ± 0.25 vs. 0.74 ± 0.03 mm, P < 0.001), and more atherosclerotic plaques at the study onset (13 (26%) vs. 0 (0%), P < 0.001) compared to stage 2 CKD. A statistically significant 4-year increase in GFR (coefficient of 2.51, 3.25, 2.71 and 1.50 for 1-year, 2-year, 3-year and 4-year follow-up, respectively, P < 0.05) with non-significant CIMT alterations has been observed in stage 2 CKD. Furthermore, linear mixed effects analysis revealed significant decrease in GFR (coefficient of -6.69, -5.12, -3.18 and -1.77 for 1-year, 2-year, 3-year and 4-year follow-up, respectively, P < 0.001) with increase in CIMT (coefficient of 0.20, 0.14, 0.07 and 0.03 for 1-year, 2-year, 3-year and 4-year follow-up, respectively, P < 0.001) in stage 4 CKD. GFR and CIMT showed significant negative correlation in both CKD groups during all follow-up phases (P < 0.001). Furthermore, multiple linear regression analysis revealed significant independent prediction of CIMT by baseline GFR (B = -0.85, P < 0.001), while there was no significant prediction of CIMT with other covariates. In conclusion, this study demonstrates significant association of GFR and CIMT in non-diabetic stage 2 and stage 4 CKD during the 4-year follow-up.