Vaccine-Induced Protection from Homologous Tier 2 SHIV Challenge in Nonhuman Primates Depends on Serum-Neutralizing Antibody Titers

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Age-dependent changes of gene expression in the Drosophila head

Previous gene expression profiling studies in Drosophila have provided clues for understanding the aging process at the gene expression level. For a detailed understanding, studies of specific regions of the body are necessary. We therefore employed microarray analysis to examine gene expression changes in the Drosophila head during aging. Six hundred and eighty-four of the 5405 genes present in the microarray showed significant age-dependent changes as determined by significance analysis of microarray (SAM) (q < 0.05). The biological significance of the changes was analyzed using the gene annotations provided by the Gene Ontology Consortium. Major changes involved genes affecting energy metabolism (proton transport, energy pathways, oxidative phosphorylation) and neuronal function, especially responses to light. Genes involved in protein catabolism and several other metabolic processes also showed age-dependent changes. Most of the changes were reductions in gene expression and occurred before day 13 of adult life. After day 13, the age-dependent gene expression changes were relatively smaller than earlier life. Interestingly, the two biological processes of major gene expression changes are related to the two known environmental changes that increase life span in Drosophila: caloric restriction and light reduction. Our findings suggest that light signaling and energy metabolism may be important biological processes affected by aging and be interesting targets for the further investigation related to the longevity in Drosophila.     

In Vivo Evaluation of Dendropanax morbifera Leaf Extract for Anti-Obesity and Cholesterol-Lowering Activity in Mice

Metabolic syndrome is a worldwide health problem, and obesity is closely related to type 2 diabetes, cardiovascular disease, hypertension, and cancer. According to WHO in 2018, the prevalence of obesity in 2016 tripled compared to 1975. D. morbifera reduces bad cholesterol and triglycerides levels in the blood and provides various antioxidant nutrients and germicidal sub-stances, as well as selenium, which helps to remove active oxygen. Moreover, D. morbifera is useful for treating cardiovascular diseases, hypertension, hyperlipidemia, and diabetes. Therefore, we study in vivo efficacy of D. morbifera to investigate the prevention effect of obesity and cholesterol. The weight and body fat were effectively reduced by D. morbifera water (DLW) extract administration to high-fat diet-fed C57BL/6 mice compared to those of control mice. The group treated with DLW 500 mg∙kg⁻¹∙d⁻¹ had significantly lower body weights compared to the control group. In addition, High-density lipoprotein (HDL) cholesterol increased in the group treated with DLW 500 mg∙kg⁻¹∙d⁻¹. The effect of DLW on the serum lipid profile could be helpful to prevent obesity. DLW suppresses lipid formation in adipocytes and decreases body fat. In conclusion, DLW can be applied to develop anti-obesity functional foods and other products to reduce body fat.     

Waning Antibody Responses in Asymptomatic and Symptomatic SARS-CoV-2 Infection

We investigated the kinetics of severe acute respiratory syndrome coronavirus 2 neutralizing antibodies in 7 asymptomatic persons and 11 patients with pneumonia. The geometric mean titer of neutralizing antibodies declined from 219.4 at 2 months to 143.7 at 5 months after infection, indicating a waning antibody response.     

Determinants and Consequences of Adolescent Fatherhood: A Longitudinal Study in Ethiopia,India, Peru,and Vietnam

PurposeAdolescent parenthood is a major challenge in low- and middle-income countries (LMICs). However, the vast majority of the evidence has focused on adolescent motherhood. Little is known about adolescent fatherhood in LMICs. The aim of this study was to examine the determinants of early fatherhood and its consequences on a range of outcomes among adolescent males.MethodsThis study used three waves of longitudinal data from the multicountry Young Lives cohort study, specifically following a sample of 1,779 adolescent boys at ages 15, 19, and 22 years in Ethiopia, India, Peru, and Vietnam. Individual fixed effects models were conducted to investigate the sociodemographic determinants of adolescent fatherhood and the consequences of adolescent fatherhood on males' education, health, psychosocial well-being, and time use outcomes.ResultsThe results indicated that lower educational attainment, absence of the adolescent's mother and father from the home, larger household size, and poverty increased the likelihood of becoming an adolescent father by age 22 years. The results revealed that becoming an adolescent father was associated with a higher likelihood of school dropout, being overweight, smoking, greater internalizing problems, and less time spent on leisure activities and more time spent on caregiving responsibilities.ConclusionsHighlighting the experiences of young men as adolescent parents in LMICs, findings underscore the importance of prevention strategies to delay early parenthood for adolescent boys and multicomponent interventions to support young fathers and their unique health, socioeconomic, psychosocial, and behavioral needs.     

Comparison of renal function after open radical cystectomy,extracorporeal robot assisted radical cystectomy,and intracorporeal robot assisted radical cystectomy

PurposeRenal function outcomes following robot-assisted radical cystectomy (RARC) have not been well established. We sought to compare long-term renal function outcomes between open radical cystectomy, RARC with extracorporeal urinary diversion and intracorporeal urinary diversion at a high volume institution.Materials and MethodsWe retrospectively reviewed our institutional bladder cancer database for patients who underwent RC from 2010 to 2019 with pre-operative estimated glomerular filtration rate (eGFR) > 45 ml/min/1.73m². Changes in renal function were assessed through locally weighted scatter plot smoothing and comparison of median eGFR between surgical groups. Chronic Kidney Disease Stage 3B was defined as eGFR < 45 ml/min/1.73m². Renal function decline was defined as a ≥10 ml/min/1.73m² drop in eGFR. Kaplan Meier method with log-rank was used to compare CKD 3B-free survival and renal function decline. Cox Proportional Hazards model was used to identify predictors of CKD 3B.ResultsSix hundred and forty four patients were included with median follow-up of 32 months (IQR 12–56). Preoperative characteristics were similar among the groups with no differences in median pre-operative eGFR (ORC: 74.6, extracorporeal urinary diversion: 74.3, intracorporeal urinary diversion: 71.6 ml/min/1.73m², P = 0.15). Median postoperative eGFR on follow up was not different between groups (P = 0.56). 33% of patients developed CKD 3B. There were no differences in CKD 3B-free survival by surgical approach (P = 0.23) or urinary diversion (P = 0.09). 64% of patients experienced renal function decline with a median time of 2.4 years (P 0.23). Predictors of CKD were pathologic T3 disease or greater (HR: 1.77, P = 0.01), ureteroenteric anastomotic stricture (HR: 2.80, P < 0.001), preoperative CKD Stage 2 (HR: 1.81, P =0.02), and preoperative CKD Stage 3A (HR: 5.56, P < 0.001).ConclusionRenal function decline is common after RC. Tumor stage, pre-operative eGFR, and ureteral stricture development, not surgical approach, influence renal function decline.     

Differential contribution of the factors determining long-term renal function after partial nephrectomy over time

PurposeTo define how much of renal function was determined by the preserved renal parenchymal volume and the ischemic insult during partial nephrectomy (PN) long after surgery.MethodsWe analyzed the data of 530 consecutive patients who had undergone PN. For all patients, renal function was measured preoperatively and again at 3 postoperative months, then annually using ^99mTc-diethylenetriaminepentaacetic acid renal scan. Perioperative variables potentially affecting the long-term ipsilateral glomerular filtration rate (GFR) and their time-varying contribution were assessed using a linear mixed model.ResultsThe mean preoperative ipsilateral GFR was 42.9 ml/min, which decreased by 27.3% at 3 months but began to recover thereafter continuing until 4 years (Δ% GFR at 1, 2, 3, 4, and 5 years: 22.3%, 18.5%, 14.7%, 10.0%, and 9.6%, respectively). Parenchymal volume reduction and ischemic time were significantly associated with postoperative ipsilateral GFR throughout observation period unvarying with time. Diabetes and proteinuria were not significant determinants of ipsilateral function at 3 months but became significant at 5 years. In multivariate analysis regarding recovery slope, volume reduction (β = ?0.026, SE 0.006, P < 0.0001), preoperative ipsilateral GFR (β = ?0.021, SE 0.007, P = 0.0012), proteinuria (β = ?0.942, SE 0.372, P = 0.0116), and diabetes (β = ?0.396, SE 0.197, P = 0.0447) were independently significant.ConclusionIpsilateral renal function continued to improve until 5 years after PN. Parenchymal volume loss was the major determinant and its impact on long-term ipsilateral renal function remained constant while ischemic time affected early GFR reduction with its impact diminishing over time. Patient-related factors including diabetes and proteinuria gained significance over time and became independent determinants of recovery slope.     

A prognostic immune predictor,HLA-DRA,plays diverse roles in non-muscle invasive and muscle invasive bladder cancer

BackgroundThere is an increasing demand for prognostic immune biomarkers of cancer. The prognostic significance of immune markers has been shown for various cancers, but biomarkers of bladder cancer (BCa) have not been fully evaluated. To clarify the role of human leukocyte antigen DR alpha chain (HLA-DRA) in BCa development, we examined expression of HLA-DRA mRNA in tissue samples of non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC).Materials and MethodsTissues of 96 NMIBC, 43 MIBC and 59 controls comprising noncancerous BCa surrounding tissues were used to examine the expression of HLA-DRA gene by real-time polymerase chain reaction. The expression of up-stream genes regulating HLA-DRA were also measured to explain the role of HLA-DRA in BCa.ResultsPatients with high grade NMIBC showed higher expression of HLA-DRA than those with low grade NMIBC (P < 0.05). In addition, NMIBC patients who progressed to MIBC showed high expression of HLA-DRA mRNA. Kaplan-Meier analysis showed that NMIBC patients with low expression of HLA-DRA had better progression-free survival than those with high expression (P = 0.004). Moreover, the expression of genes regulating HLA-DRA varied in NMIBC and MIBC, indicating a different immunoregulation effect of HLA-DRA in both cancers.ConclusionsHigh expression of HLA-DRA in NMIBC patients has implications for patient stratification strategies, as well as for BCa tumor immunology.