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Objective: To describe patient characteristics and pathological stage at bladder cancer (BCa) diagnosis in a diverse population within a national, equal‐access healthcare system. Methods: This retrospective cohort study identified 15 966 men diagnosed with BCa in the Veterans Affairs (VA) healthcare system from 2000 to 2020. The primary outcome was pathological stage at diagnosis, determined by index transurethral resection of bladder tumour. Logistic regression was used to assess the relationship between race and stage. Competing risk models tested the association between race and BCa‐specific mortality with cumulative incidence estimates. Results: Of 15 966 BCa patients, 12 868 (81%), 1726 (11%), 493 (3%) and 879 (6%) were White, Black, Hispanic and Other race, respectively. Black patients had significantly higher muscle‐invasive bladder cancer (MIBC) rates than White patients (35% vs 32%; P = 0.009). In multivariable analysis, the odds of presenting with MIBC did not differ significantly between Black and White patients (odds ratio [OR] 1.10, 95% confidence interval [CI] 0.98–1.22) or between Hispanic patients (OR 0.82, 95% CI 0.67–1.01) and White patients. Compared to White patients, Black patients had a similar risk of BCa‐specific mortality (hazard ratio [HR] 0.89, 95% CI 0.75–1.06), whereas Hispanic patients had a lower risk (HR 0.56, 95% CI 0.38–0.82). Conclusions: Black patients presented with the highest rates of de novo MIBC. However, in a large, equal‐access healthcare system, this did not result in a difference in BCa‐specific mortality. In contrast, Hispanic patients had lower risks of MIBC and BCa‐specific mortality. [ABSTRACT FROM AUTHOR]

Introduction: We previously reported that cholesterol homeostasis in prostate cancer (PC) is regulated by 27-hydroxycholesterol (27HC) and that CYP27A1, the enzyme that converts cholesterol to 27HC, is frequently lost in PCs. We observed that restoring the CYP27A1/27HC axis inhibited PC growth. In this study, we investigated the mechanism of 27HC-mediated anti-PC effects. Methods: We employed in vitro models and human transcriptomics data to investigate 27HC mechanism of action in PC. LNCaP (AR+) and DU145 (AR-) cells were treated with 27HC or vehicle. Transcriptome profiling was performed using the Affymetrix GeneChip™ microarray system. Differential expression was determined, and gene set enrichment analysis was done using the GSEA software with hallmark gene sets from MSigDB. Key changes were validated at mRNA and protein levels. Human PC transcriptomes from six datasets were analyzed to determine the correlation between CYP27A1 and DNA repair gene expression signatures. DNA damage was assessed via comet assays. Results: Transcriptome analysis revealed 27HC treatment downregulated Hallmark pathways related to DNA damage repair, decreased expression of FEN1 and RAD51, and induced "BRCAness" by downregulating genes involved in homologous recombination regulation in LNCaP cells. Consistently, we found a correlation between higher CYP27A1 expression (i.e., higher intracellular 27HC) and decreased expression of DNA repair gene signatures in castration-sensitive PC (CSPC) in human PC datasets. However, such correlation was less clear in metastatic castration-resistant PC (mCRPC). 27HC increased expression of DNA damage repair markers in PC cells, notably in AR+ cells, but no consistent effects in AR- cells and decreased expression in non-neoplastic prostate epithelial cells. While testing the clinical implications of this, we noted that 27HC treatment increased DNA damage in LNCaP cells via comet assays. Effects were reversible by adding back cholesterol, but not androgens. Finally, in combination with olaparib, a PARP inhibitor, we showed additive DNA damage effects. Discussion: These results suggest 27HC induces "BRCAness", a functional state thought to increase sensitivity to PARP inhibitors, and leads to increased DNA damage, especially in CSPC. Given the emerging appreciation that defective DNA damage repair can drive PC growth, future studies are needed to test whether 27HC creates a synthetic lethality to PARP inhibitors and DNA damaging agents in CSPC. [ABSTRACT FROM AUTHOR]

Sodium boiling in a fuel subassembly of a sodium-cooled fast breeder reactor is a very critical phenomenon as void propagation may lead to loss of heat removal and increase in reactivity. Hence, sodium boiling behavior from the incipient stage and evolution of bubble dynamics need to be thoroughly understood toward validating various thermal-hydraulic models pertaining to safety analysis of fast reactors. An experimental program has been taken up at Indira Gandhi Centre for Atomic Research to investigate incipient sodium boiling toward spatiotemporal evaluation of bubble characteristics in sodium. Real-time X-ray radioscopy has been employed for in-sodium visualization of bubbles generated during sodium boiling. The raw images obtained during the experiment were processed using an in-house–developed image processing algorithm that includes background subtraction, noise filtering, and segmentation techniques for enhancement of foreground features. A max filter–based tracker is also devised for clear depiction of bubble boundary and motion with time during the boiling process. Attributes like bubble diameter, nucleation site density, and bubble velocity are determined effectively from the captured images using the algorithm. The paper focuses on the experiment, imaging technique using X-ray radioscopy, and image processing toward depicting the bubble characteristics during sodium boiling in a vertical channel. [ABSTRACT FROM AUTHOR]

Dearomatized 1,4‐dihydropyridyl motifs are significant in both chemistry and biology for their potential abilities to deliver the stored hydride, driven by rearomatization. Biological cofactors like nicotinamide adenine dinucleotide (NADH) and organic 'hydride sources' like Hantzsch esters are prime examples. An organoaluminum chemistry on a 2‐anilidomethylpyridine framework is reported, where such hydride storage and transfer abilities are displayed by the ligand's pyridyl unit. The pyridylmethylaniline proligand (NNLH) is simultaneously deprotonated and 1,4‐hydroaluminated by AlH3(NMe2Et) to [(NNLde)AlH(NMe2Et)] (1; NNLde=hydride‐inserted dearomatized version of NNL). A hydride abstraction by B(C6F5)3 rearomatizes the pyridyl moiety to give the cationic aluminum hydride [(NNL)AlH(NMe2Et)][HB(C6F5)3] (6). Notably, such chemical non‐innocence is priorly unseen in this established ligand class. The hydroalumination mechanism is investigated by isolating the intermediate [(NNL)AlH2] (2) and by control experiments, and is also analyzed by DFT calculation. The results advocate an intriguing 'self‐promoting' pathway, which underlines alane's Lewis acid/Brønsted base duality. NMe2Et carrying the alane also plays a crucial role. In contrast, the chemistry between NNLH and AlMe3 is much different, giving only [(NNL)AlMe2] (4) from the adduct [(NNLH)AlMe3] (3) by deprotonation but not a subsequent pyridyl dearomatization in the presence or absence of NMe2Et. This divergence is also justified by DFT analyses. [ABSTRACT FROM AUTHOR]

The dopamine transporter (DAT) plays an integral role in dopamine neurotransmission through the clearance of dopamine from the extracellular space. Dysregulation of DAT is central to the pathophysiology of numerous neuropsychiatric disorders and as such is an attractive therapeutic target. DAT belongs to the solute carrier family 6 (SLC6) class of Na+/Cl-dependent transporters that move various cargo into neurons against their concentration gradient. This review focuses on DAT (SCL6A3 protein) while extending the narrative to the closely related transporters for serotonin and norepinephrine where needed for comparison or functional relevance. Cloning and site-directed mutagenesis experiments provided early structural knowledge of DAT but our contemporary understanding was achieved through a combination of crystallization of the related bacterial transporter LeuT, homology modeling, and subsequently the crystallization of drosophila DAT. These seminal findings enabled a better understanding of the conformational states involved in the transport of substrate, subsequently aiding state-specific drug design. Posttranslational modifications to DAT such as phosphorylation, palmitoylation, ubiquitination also influence the plasma membrane localization and kinetics. Substrates and drugs can interact with multiple sites within DAT including the primary S1 and S2 sites involved in dopamine binding and novel allosteric sites. Major research has centered around the question what determines the substrate and inhibitor selectivity of DAT in comparison to serotonin and norepinephrine transporters. DAT has been implicated in many neurological disorders and may play a role in the pathology of HIV and Parkinson's disease via direct physical interaction with HIV-1 Tat and a-synuclein proteins respectively. [ABSTRACT FROM AUTHOR]

Background: Chronic kidney disease is now a global burden with an increased grade of morbidity and mortality due to the unavailability of particular medicines except for high-cost treatments like dialysis or kidney transplantation. Tribal people use their own indigenous preparation of medicinal plants for the prevention and treatment of kidney ailments. The present study was aimed at preparing Arjunakwaatha and Arjunasheeta, an indigenous preparation of the bark of Terminalia arjuna (TA) and its supplementation in the kidney injury rat model. Materials and Methods: In this study, rats were induced to kidney injury (KI) by intraperitoneal injection of paracetamol 15 mg/kg b. w. for 14 days and supplementation of Arjunakwaatha and Arjunasheeta with various doses continued the experimentation for 28 days. Results: Results showed that urea, creatinine, C-reactive protein (CRP), glutamine oxalic transaminase (GOT), glutamate pyruvate transaminase (GPT) in plasma, and malondialdehyde (MDA) in kidney tissue, urinary protein, and KIM-1 were significantly (p<0.05) increased in kidney injury rats when compared to normal control rats. Supplementation of Arjunakwaatha and Arjunasheeta with kidney injury rats significantly (p<0.05) decreased urea, creatinine, CRP, GOT, GPT, MDA, SOD, CAT, and GSH levels as compared to kidney injury rats. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis showed new low molecular weight urinary protein bands in kidney injury rats. The protective effects of Arjunakwaatha and Arjunasheeta present no band at this molecular level in normal rats. Conclusion: It has been concluded that Arjunakwaatha is the best indigenous preparation for kidney protection. [ABSTRACT FROM AUTHOR]

Eicosapentaenoic acid and docosahexaenoic acid are n-3 fatty acids that are highly available in sea-fishes. Many studies have revealed that n-3 fatty acids play antidiabetic activity. In this study antidiabetic activity of the three sea fishes oils, 'volavetki' (Panna microdon, Bleeker 1849), 'ruli' (Coilia dussumieri, Valenciennes 1848), and 'tapra' (Opisthopterus tardoore, Cuvier 1829), as well as three fresh-water fishes oils, 'bata' (Labeo bata, Hamilton 1822), 'folui' (Opisthopterus tardoore, Cuvier 1829), and 'mourala' (Amblypharyngodon mola, Hamilton 1822) evaluated high lipid diet (HLD) and STZ-induced type 2 diabetes mellitus (T2DM) rats. The GC-MS analysis revealed high n-3 fatty acid content in volavetki oil. Supplementation of sea-fish oils and antidiabetic effect was monitored by fasting plasma blood glucose and HbA1c. Also, insulin, c-peptide, glucagon-like peptide-1, dipeptidyl peptidase-4, free fatty acid receptor 1, glucokinase, glucose-6 phosphatase, superoxide dismutase, glutathione peroxidase, catalase, malondialdehyde, plasma total cholesterol, low density lipoprotein, triglycerides, high density lipoprotein, c-reactive protein, total protein, alkaline phosphatase, and histopathology of pancreatic tissues were evaluated. Out of six fish oils, oral supplementation with volavetki oil resulted in significant reduction of plasma blood glucose, HbA1c of T2DM rat. All other parameters in T2DM rats were returned to near normally by treatment of volavetki oil. These findings strongly indicate that volavetki oil possess antidiabetic activity. [ABSTRACT FROM AUTHOR]

Purpose: Indications for germline testing in prostate cancer patients have expanded substantially over the past decade. With a near-universal shortage of genetic counselors and increasing demand, increased access to genetic counseling is crucial. We sought to prospectively implement and assess a clinician-led approach to genetic counseling and testing. Materials and Methods: Patients with metastatic or localized prostate cancer meeting National Comprehensive Cancer Network® criteria for consideration of genetic testing were offered pre-test genetic counseling by their urologist or medical oncologist as part of their routine clinical care and concurrently approached for enrollment in the Germline Genetics in Prostate Cancer Study. Consented patients filled out a post-counseling survey using validated instruments to assess the quality of counseling. For patients who elected to undergo genetic testing, an additional validated questionnaire was completed following disclosure of results. The primary outcome was the proportion of patients undergoing testing, with a target >60% of patients. The secondary outcome was overall satisfaction with counseling, with a target >85% of patients. Results: A total of 275 patients enrolled, and 203 patients elected to undergo genetic testing. Post-counseling surveys were obtained from 265 patients, and post-genetic testing surveys were obtained from 132 patients. Patient satisfaction was high, with 98% of patients reporting being satisfied with the overall quality of pre-test counseling, and 74% of patients elected to undergo genetic testing. Conclusions: These results support the effectiveness of clinician-led genetic counseling in prostate cancer. With clinician training, this approach can be utilized to expand access to appropriate germline genetic testing. [ABSTRACT FROM AUTHOR]

The study is a field note to two tribal villages in Chandaka region of Odisha, namely, Bhagabatipur and Firikinali. Both the villages are devoid of adequate electricity facilities. Although there is a grid connection in both the villages, it suffers from various problems that lead to ultimate darkness. The field visit includes pre and post-pilot installation visits under a DST sponsored project. The fundamental aim of the project is to promote large scale deployment of Micro Solar Domes (MSD) for renewable energy application and social empowerment of rural SC and ST communities through integrated techno-social interventions for addressing energy-poverty holistically. The villagers of Bhagabatipur have benefitted immensely from MSD, and many villagers are interested in installing it for a better lifestyle. [ABSTRACT FROM AUTHOR]

A new species of front-eyed trapdoor spider Heligmomerus jagadishchandra sp. n. is described from the holotype collected in Keshpur (West Medinipur, West Bengal, India). Habitat information of the species is provided too. [ABSTRACT FROM AUTHOR]