NHA1 is a cation/proton antiporter essential for the water-conserving functions of the rectal complex in Tribolium castaneum.

More than half of all extant metazoan species on earth are insects. The evolutionary success of insects is linked with their ability to osmoregulate, suggesting that they have evolved unique physiological mechanisms to maintain water balance. In beetles (Coleoptera)-the largest group of insects-a specialized rectal ("cryptonephridial") complex has evolved that recovers water from the rectum destined for excretion and recycles it back to the body. However, the molecular mechanisms underpinning the remarkable water-conserving functions of this system are unknown. Here, we introduce a transcriptomic resource, BeetleAtlas.org, for the exceptionally desiccation-tolerant red flour beetle Tribolium castaneum, and demonstrate its utility by identifying a cation/H+ antiporter (NHA1) that is enriched and functionally significant in the Tribolium rectal complex. NHA1 localizes exclusively to a specialized cell type, the leptophragmata, in the distal region of the Malpighian tubules associated with the rectal complex. Computational modeling and electrophysiological characterization in Xenopus oocytes show that NHA1 acts as an electroneutral K+/H+ antiporter. Furthermore, genetic silencing of Nha1 dramatically increases excretory water loss and reduces organismal survival during desiccation stress, implying that NHA1 activity is essential for maintaining systemic water balance. Finally, we show that Tiptop, a conserved transcription factor, regulates NHA1 expression in leptophragmata and controls leptophragmata maturation, illuminating the developmental mechanism that establishes the functions of this cell. Together, our work provides insights into the molecular architecture underpinning the function of one of the most powerful water-conserving mechanisms in nature, the beetle rectal complex.

Ameliorating effects of adropin on letrozole-induced polycystic ovary syndrome via regulating steroidogenesis and the microbiota inflammatory axis in rats.

Growing evidence supports the role of gut microbiota in chronic inflammation, insulin resistance (IR) and sex hormone production in polycystic ovary syndrome (PCOS). Adropin plays a pivotal role in the regulation of glucose and lipid metabolism and is negatively correlated with IR, which affects intestinal microbiota and sex hormones. However, the effect of adropin administration in PCOS has yet to be investigated. The present study aimed to assess the effects of adropin on letrozole (LTZ)-induced PCOS in rats and the potential underlying mechanisms. The experimental groups were normal, adropin, letrozole and LTZ + adropin. At the end of the experiment, adropin significantly ameliorated PCOS, as evidenced by restoring the normal ovarian structure, decreasing the theca cell thickness in antral follicles, as well as serum testosterone and luteinizing hormone levels and luteinizing hormone/follicle-stimulating hormone ratios, at the same time as increasing granulosa cell thickness in antral follicles, oestradiol and follicle-stimulating hormone levels. The ameliorating effect could be attributed to its effect on sex hormone-binding globulin, key steroidogenic genes STAR and CYP11A1, IR, lipid profile, gut microbiota metabolites-brain-ovary axis components (short chain fatty acids, free fatty acid receptor 3 and peptide YY), intestinal permeability marker (zonulin and tight junction protein claudin-1), lipopolysaccharides/Toll-like receptor 4/nuclear factor kappa B inflammatory pathway and oxidative stress makers (malondialdehyde and total antioxidant capacity). In conclusion, adropin has a promising therapeutic effect on PCOS by regulating steroidogenesis, IR, lipid profile, the gut microbiota inflammatory axis and redox homeostasis. KEY POINTS: Adropin treatment reversed endocrine and ovarian morphology disorders in polycystic ovary syndrome (PCOS). Adropin regulated the ovarian steroidogenesis and sex hormone-binding globulin in PCOS. Adropin improved lipid profile and decreased insulin resistance in PCOS. Adropin modulated the components of the gut-brain-ovary axis (short chain fatty acids, free fatty acid receptor 3 and peptide YY) in PCOS. Adropin improved intestinal barrier integrity, suppressed of lipopolysaccharides/Toll-like receptor 4/nuclear factor kappa B signalling pathway and oxidative stress in PCOS.

Isotope-Edited Variable Temperature Infrared Spectroscopy for Measuring Transition Temperatures of Single A-T Watson-Crick Base Pairs in DNA Duplexes.

Experimental methods to determine transition temperatures for individual base pair melting events in DNA duplexes are lacking despite intense interest in these thermodynamic parameters. Here, we determine the dimensions of the thymine (T) C2═O stretching vibration when it is within the DNA duplex via isotopic substitutions at other atomic positions in the structure. First, we determined that this stretching state was localized enough to specific atoms in the molecule to make submolecular scale measurements of local structure and stability in high molecular weight complexes. Next, we develop a new isotope-edited variable temperature infrared method to measure melting transitions at various locations in a DNA structure. As an initial test of this "sub-molecular scale thermometer", we applied our T13C2 difference infrared signal to measure location-dependent melting temperatures (TmL) in a DNA duplex via variable temperature attenuated total reflectance Fourier transform infrared (VT-ATR-FTIR) spectroscopy. We report that the TmL of a single Watson-Crick A-T base pair near the end of an A-T rich sequence (poly T) is ∼34.9 ± 0.7°C. This is slightly lower than the TmL of a single base pair near the middle position of the poly T sequence (TmL ∼35.6±0.2°C). In addition, we also report that the TmL of a single Watson-Crick A-T base pair near the end of a 50% G-C sequence (12-mer) is ∼52.5 ± 0.3°C, which is slightly lower than the global melting Tm of the 12-mer sequence (TmL ∼54.0±0.9°C). Our results provide direct physical evidence for end fraying in DNA sequences with our novel spectroscopic methods.

Genetic Profiling Uncovers Genome-Wide Loss of Heterozygosity and Provides Insight into Mechanisms of Sarcomatoid Transformation in Chromophobe Renal Cell Carcinoma.

Sarcomatoid transformation occurs in ∼8% of chromophobe renal cell carcinoma (chRCC) and is associated with aggressive clinical behavior. In recent years, several studies have identified genomic, transcriptomic, and epigenomic correlates of aggressive behavior in chRCC; however, the molecular mechanisms associated with sarcomatoid transformation remain incompletely understood. In this study, we analyzed paired conventional and sarcomatoid histologic components of individual chRCC to elucidate the genomic alterations that underlie sarcomatoid transformation in this tumor type. Massively parallel sequencing was performed on paired (conventional and sarcomatoid) components from 8 chRCCs. All cases harbored TP53 variants (87.5% showing TP53 variants in both components and 12.5% only in the sarcomatoid component). Intratumor comparisons revealed that TP53 variants were concordant in 71% and discordant in 29% of cases. Additional recurrent single-nucleotide variants were found in RB1 (37.5% of cases) and PTEN (25% of cases), with the remaining single-nucleotide variants detected in these tumors (PBRM1, NF1, and ASXL1) being nonrecurrent. Copy number variant analysis showed the characteristic pattern of chromosomal losses associated with chRCC (1, 2, 6, 10, 13, 17, and 21) in the conventional histologic components only. Interestingly, the sarcomatoid components of these tumors demonstrated widespread loss of heterozygosity but lacked the above chromosomal losses, likely as a consequence of whole-genome duplication/imbalanced chromosomal duplication events. Overall, the findings suggest that TP53 variants followed by whole-genome duplication/imbalanced chromosomal duplication events underlie sarcomatoid transformation in chRCC.

Beta-Catenin Alterations in Postchemotherapy Yolk Sac Tumor, Postpubertal-Type With Enteroblastic Features.

Postchemotherapy postpubertal-type yolk sac tumors (YST) with glandular and solid phenotypes are aggressive and commonly resistant to systemic chemotherapy. These neoplasms show morphologic features that significantly overlap with those of somatic carcinomas with "enteroblastic" or "fetal" phenotype (the preferred terminology depends on the site of origin). They often present as late or very late recurrences, and their diagnosis is challenging because they frequently affect patients in an age group at risk for carcinomas of somatic origin. Recently, we incidentally identified examples of postchemotherapy glandular and solid YST with "enteroblastic" phenotypes and nuclear expression of beta-catenin, prompting us to further evaluate the prevalence of this phenomenon. We found nuclear expression of beta-catenin in 10 (29%) of 34 such tumors. A subset of cases with nuclear beta-catenin expression was further analyzed with a DNA sequencing panel (n = 6) and fluorescence in situ hybridization for isochromosome 12p [i(12p); n = 5]. Sequencing identified exon 3 CTNNB1 variants in 3 (50%) of 6 analyzed cases, and fluorescence in situ hybridization was positive for i(12p) in 5 of 5 cases. In conclusion, a significant subset of postchemotherapy YST with glandular or solid architecture and "enteroblastic" phenotype demonstrates beta-catenin alterations, suggesting that activation of Wnt signaling may play a role in the progression of these neoplasms. Moreover, nuclear beta-catenin expression in these tumors represents a potential diagnostic pitfall given that carcinomas of true somatic origin with overlapping morphology may also be positive for this marker.

Carcinoma arising in ileal conduit or orthotopic ileal neobladder reconstruction: A 20-year single institute experience.

CONTEXT: Carcinomas found in urinary diversion specimens are uncommon, particularly new primary tumours. New primary tumours primarily occur when the large intestine is utilised, whereas the occurrence is infrequent with the use of the ileum. These tumours include both the recurrence of primary malignancy or the development of a new primary malignancy originating from the small intestine. DESIGN: A search was performed within the pathology laboratory system to identify cases of malignancies involving ileal conduit/reconstruction from 2002 to 2022. Data on demographics, clinical details, pathology and management was recorded. RESULTS: A total of 13 male patients, with a mean age of 67 years (range = 49-81 years) were included in the study. The initial procedure performed included cystoprostatectomy (n = 10, including one case with right nephroureterectomy) and cystectomy (n = 3, including one case for bladder exstrophy) for initial diagnoses including urothelial carcinoma (n = 11; conventional, 6; sarcomatoid, 1; glandular 1; plasmacytoid, 1; micropapillary, 2) and adenocarcinoma (n = 1). The initial management included radical surgery with neoadjuvant chemotherapy/immunotherapy (n = 1), adjuvant chemotherapy (n = 3), intravesical adjuvant BCG (n = 2) and intravesical adjuvant chemotherapy (n = 1). Malignancies in ileal conduit or orthotopic ileal neobladder included recurrent urothelial carcinoma (n = 10) and new secondary adenocarcinomas (n = 3), which developed as early as 3 months (usually recurrence) and up to 13, 33 and 45 years (new primary malignancy) following primary resection. CONCLUSIONS: Utilising the ileum as conduit/neobladder presents a viable alternative for urinary diversion with a reduced malignancy risk compared to using a segment of the large intestine. However, there remains a potential for malignancy, either tumour recurrence or a new primary malignancy. In our study, tumour recurrence occurred up to 4 years following the initial diagnosis and the development of a new primary malignancy occurred up to 45 years after the initial diagnosis. Consequently, it is crucial to prioritise long-term follow-up for these patients undergoing this procedure.

ß-Catenin alterations in testicular Leydig cell tumour: a immunohistochemical and molecular analysis.

BACKGROUND: Testicular Leydig cell tumours (LCTs) are the most common type of sex cord-stromal tumour in men, representing 1%-3% of all testicular neoplasms. Among testicular sex cord-stromal tumours, CTNNB1 mutations and nuclear expression of ß-catenin have been typically associated with Sertoli cell tumour. Recent genomic analyses have shown that CTNNB1 variants are also identified in a subset of LCTs; however, the frequency and clinicopathologic associations of ß-catenin alterations remain incompletely understood in this tumour type. METHODS: In this study, we evaluated 32 LCTs (five malignant/metastasizing, 27 nonmetastasizing) using ß-catenin immunohistochemistry and DNA sequencing. RESULTS: Immunohistochemistry revealed focal or multifocal nuclear ß-catenin expression in 47% of the tumours. Diffuse nuclear ß-catenin expression (in >50% of the tumour cells) was not detected in any of the cases analysed herein. Comparison of ß-catenin-positive and ß-catenin-negative cases did not show significant differences in the frequency of adverse histopathologic findings or malignant clinical behaviour. DNA sequencing performed de novo on a subset of seven cases revealed the presence of exon 3 CTNNB1 variants in four of them (4/7, 57%), with variant allele frequencies (VAF) ranging from 7 to 33%. Two additional ß-catenin-positive cases that had been sequenced as part of a previous study harboured exon 3 CTNNB1 variants at VAF of 28% and 7%, respectively. CONCLUSION: These results demonstrate that ß-catenin alterations are relatively common in LCT, most likely occurring as subclonal events that are not enriched in cases with aggressive features. Further studies are needed to clarify the oncogenic role of ß-catenin in this tumour type.

Genomic analysis of primary epithelial neoplasms of the seminal vesicle identifies a subset of mucinous cystic tumours driven by KRAS mutations.

BACKGROUND: Carcinomas of the seminal vesicle are exceedingly rare, with a limited number of cases described in the literature. Reported cases span a relatively wide morphological spectrum, and their genomic features remain unexplored. DESIGN: In this study, we interrogated five primary epithelial neoplasms of the seminal vesicle using a targeted DNA sequencing platform (OncoPanel, 447 genes). RESULTS: The tumours included one adenocarcinoma with intestinal phenotype presenting after external beam radiation (for prostatic adenocarcinoma), one carcinoma with Müllerian-type clear cell phenotype, two mucinous tumours resembling low-grade mucinous neoplasms of the appendix (LAMN) and one mucinous cystadenoma. The post-radiation mucinous adenocarcinoma had genomic findings consistent with bi-allelic inactivation of TP53, as well as multiple copy-number changes with regional and chromosomal arm-level copy-number losses. The Müllerian-type clear cell carcinoma exhibited a complex copy-number profile with numerous regional and arm-level copy-number changes, as well as focal amplification events, including copy-number gain of 8q and amplification of a region within 20q13. Both low-grade mucinous tumours resembling LAMN harboured hot-spot gain-of-function KRAS variants (p.G12V and p.G13D) as the only genomic alteration. No genomic alterations were detected inthe lesion diagnosed as mucinous cystadenoma. CONCLUSION: Our results suggest that primary low-grade mucinous neoplasms of the seminal vesicle may represent a distinct entity equivalent to appendiceal counterparts, driven by gain-of-function variants of RAS GTPases. The remaining tumours showed genomic features that closely resembled those of neoplasms with comparable phenotypes and/or biological characteristics arising in other sites, suggesting that they could be managed similarly, with special considerations related to their anatomical location.

Evolution of Testicular Germ Cell Tumors in the Molecular Era With Histogenetic Implications.

The current WHO classification of testicular germ cell tumors is based on the pathogenesis of the tumors driven by different genomic events. The germ cell neoplasia in situ is the precursor lesion for all malignant germ cell tumors. The current understanding of pathogenesis is that the developmental and environmental factors with the erasure of parental genomic imprinting lead to the development of abnormal gonocytes that settle in the "spermatogonial Niche" in seminiferous tubules. The abnormal primordial germ cells in the seminiferous tubules give rise to pre-GCNIS cells under the influence of TPSY and OCT4 genes. The whole genome duplication events give rise to germ cell neoplasia in situ, which further acquires alterations in 12p along with NRAS and KRAS mutations to produce seminoma. A subset of seminomas acquires KIT mutation and does not differentiate further. The remaining KIT-stable seminomas differentiate to nonseminomatous GCTs after obtaining recurrent chromosomal losses, epigenetic modification, and posttranscriptional regulation by multiple genes. Nonseminomatous germ cell tumors also develop directly from differentiated germ cell neoplasia in situ. TP53 pathway with downstream drivers may give rise to somatic-type malignancies of GCT. The GCTs are remarkably sensitive to cisplatin-based combination chemotherapy; however, resistance to cisplatin develops in up to 8% of tumors and appears to be driven by TP53/MDM2 gene mutations. Serum and Plasma miRNAs show promise in diagnosing, managing, and following up on these tumors. The mechanisms underlying the development of most tumors have been elucidated; however, additional studies are required to pinpoint the events directing specific characteristics. Advances in identifying specific molecular markers have been seen recently and may be adopted as gold standards in the future.

Contemporary Updates on Sex Cord-stromal Tumors of the Testis.

Testicular sex cord-stromal tumors (TSCSTs) are relatively rare, representing ~5% of testicular neoplasms overall. Historically, TSCSTs have been classified into 3 major entities: Leydig cell tumor, Sertoli cell tumor, and granulosa cell tumor. In recent years, immunophenotypic and molecular analyses have led to a more detailed understanding of the biological and genomic features of these neoplasms, resulting in the description of new entities, some of which have been included in the latest WHO classification. This review summarizes novel histopathologic, clinical, and molecular findings that may lead to a reappraisal of established concepts and help improve the diagnosis and clinical management of TSCSTs in the coming years.

Vertical transmission of SARS-CoV-2 delta-variant in a preterm infant.

BACKGROUND: As SARS-CoV-2 continues to be relevant and cause illnesses, the effect of emerging virus variants on perinatal health remains to be elucidated. It was demonstrated that vertical transmission of SARS-CoV-2 is a relatively rare event in the original SARS-CoV-2 strain. However, very few reports describe vertical transmission related to the delta-variant. CASE PRESENTATION: We report a case of a preterm male neonate born to a mother with positive SARS-CoV-2 and mild respiratory complications. The neonate was born by cesarean section due to fetal distress. The rupture of the amniotic membrane was at delivery. The neonate had expected prematurity-related complications. His nasopharyngeal swabs for RT-PCR were positive from birth till three weeks of age. RT-ddPCR of the Placenta showed a high load of the SARS-CoV-2 virus with subgenomic viral RNA. RNAscope technique demonstrated both the positive strand of the S gene and the orf1ab negative strand. Detection of subgenomic RNA and the orf1ab negative strand indicats active viral replication in the placenta. CONCLUSIONS: Our report demonstrates active viral replication of the SARS-CoV-2 delta-variant in the placenta associated with vertical transmission in a preterm infant.

Decomposing the rural-urban differences in depression among multimorbid older patients in India: evidence from a cross-sectional study.

BACKGROUND: In India, the prevalence of depression among older adults dealing with multiple health conditions varies between rural and urban areas due to disparities in healthcare access and cultural factors. The distinct patterns observed underscore the necessity for tailored research and interventions to address mental health inequalities among multimorbid older patients in diverse geographic contexts. METHODS: This study used data from the Longitudinal Ageing Study in India (LASI) wave 1 (2017-18). A total of 7,608 adults aged ≥ 60 years who were diagnosed with two or more chronic conditions (such as hypertension, diabetes, cancer, chronic lung disease, chronic heart diseases, stroke, bone/joint disease, any neurological or psychiatric diseases, and high cholesterol) were included in this study. Descriptive statistics, bivariate analysis, logistic regression estimates, and Fairlie decomposition method were used to accomplish the study's objectives. RESULTS: The prevalence of depression among older adults with multimorbidity was 9.48% higher in rural areas (38.33%) than in urban areas (28.85%).. Older adults with multimorbidity belonging to the scheduled caste group were 40% more likely to experience depression. Moreover, those with multimorbidity and any form of disability in activities of daily living (ADL) were 93% more likely to experience depression than those without disability, whereas those with multimorbidity and perceived good general health were 65% less likely to suffer from depression than those with poor self-perceived health. Additionally, decomposition analysis revealed that education (35.99%), caste status (10.30%), IADL disability (19.30%), and perceived discrimination (24.25%) were the primary factors contributing to the differences in depression prevalence among older adults with multimorbidity between rural and urban areas. CONCLUSIONS: We found significant rural-urban differences in depression among older Indians with multimorbidity. The findings underscore the need for targeted interventions that address the unique challenges faced by older patients in rural areas, including lack of social capital, discrimination, and limited resources that enable access to healthcare services. Policymakers and healthcare professionals must collaboratively design and implement effective strategies to improve the mental health and overall well-being of rural older adults, particularly those with multiple comorbidities.

Subjective social status and socio-demographic correlates of perceived discrimination among older adults in India.

BACKGROUND: Considering India's diversity, marked by differences in caste, class, ethnicity, religion, region, and language, discrimination can take on varying forms across social-structural locations. We examined the association between subjective social status (SSS) and perceived discrimination, and assessed the sociodemographic correlates of perceived discrimination among older persons in India. METHODS: Data come from the 2017-18 wave 1 of the Longitudinal Aging Study in India (LASI) with a sample of 30,253 adults 60 years or older. SSS was examined using the Macarthur scale with a ladder technique. Perceived discrimination was evaluated with the Everyday Discrimination Scale. Multivariable logistic regression models examined the odds of reporting discrimination by its types and attributions. RESULTS: 39% of older adults reported low SSS, whereas 7.3% reported high SSS. Older adults with low SSS had significantly higher odds of experiencing some discrimination than those with high SSS. Compared to high-SSS peers, low-SSS individuals attributed age, gender, caste, financial, and health status as reasons for discrimination. Older women attributed gender as a reason for discrimination. Caste was reported as a reason for discrimination by rural but not urban dwellers. Relative to northerners, those from southern India reported age, financial, and health statuses as reasons for discrimination. CONCLUSIONS: That low-SSS older adults reported age, gender, caste, financial status, and health status as reasons for discrimination and that this association persisted after considering objective indicators of socioeconomic status (SES) is suggestive of SSS as independently consequential for perceived discrimination. These findings are useful for care providers and practitioners as they encourage older patients -- especially those with low SSS who may feel stigmatized -- to seek care, comply with care regimen, and engage in behaviors that protect and promote health.

Interaction between depressive symptoms and obesity-related anthropometric measures on multimorbidity among community-dwelling older adults: evidence from India.

BACKGROUND: This study aimed to examine the associations between depressive symptoms, body mass index (BMI), waist circumference, waist-hip ratio and multimorbidity among community-dwelling older adults. We also examine the interaction effects between depressive symptoms, BMI, waist circumference and waist-hip ratio on multimorbidity among older adults in India. METHODS: A cross-sectional study was conducted, and the data were obtained from the Longitudinal Ageing Study in India (LASI) wave-1, with a sample of 31,464 older adults aged 60 years and above (men-15,098 and women-16,366). We used multinomial logistic regression to explore the independent associations between depressive symptoms, obesity-measures, and single and multimorbidity. We also estimated the interaction effects of depressive symptoms and obesity-measures on multimorbidity. RESULTS: The prevalence of multimorbidity was higher among individuals with depressive symptoms (39.22%) than individuals with no depressive symptoms (29.94%). Adjusted models indicated that older adults with depressive symptoms had higher odds of single and multimorbidity [(AOR = 1.40, 95% CI: 1.17-1.68) and (AOR = 1.85, 95% CI: 1.58-2.16), respectively]. Similarly, in comparison to the normal BMI category, overweight and obese older adults were more likely to report single morbidity [(AOR = 1.62, 95% CI: 1.37-1.92 and (AOR = 2.14, 95% CI: 1.67-2.75), respectively] and multimorbidity [(AOR = 2.00, 95% CI: 1.72-2.33) and (AOR = 3.77, 95% CI: 2.94-4.82), respectively]. CONCLUSION: The findings revealed that the presence of depressive symptoms, overweight or obesity, and high-risk anthropometric measures such as high-risk waist circumference and high-risk waist to hip ratio significantly increased the risk of morbidity among older adults in India. Thus, it is suggested to adopt an integrated public health policy approach to control depressive symptoms and high-risk body composition to strategically prepare against the elevated risk of multimorbidity among ageing populations.

Factors associated with public and private healthcare utilization for outpatient care among older adults in India: A Wagstaff's decomposition of Anderson's behavioural model.

In India, an expanding ageing population will become a public health alarm, putting additional pressure on the healthcare system. Therefore, the current study aimed to examine the factors associated with outpatient healthcare choices among older Indian adults. We used data from the first wave of the Longitudinal Ageing Study in India (LASI, 2017-2018). A total of 34,588 individuals (age 45 years and over) who accessed outpatient healthcare services in the last 12 months during the survey were included in this research. A bivariate chi-square test was used to present the percentage distribution of types of outpatient healthcare utilisation by background characteristics. Multinomial logistic regression and Wagstaff's decomposition analyses were employed to explore the interplay of outpatient healthcare utilisation and allied predisposing, enabling, and need factors and examine these factors' contributions to the wealth-based inequalities in public, private, and other healthcare utilisation. Outpatient healthcare utilisation varied significantly according to socioeconomic and demographic factors. The findings suggest that consumption quintiles, place of residence, education, and health insurance were significant determinants of private and public healthcare utilisation and contributed to wealth-based inequalities in healthcare choices. The current study emphasises the need to strengthen and promote public healthcare services.

Separate and combined associations of cognitive impairment and body pain with functional and mobility disabilities among older women and men in India.

This study examined the separate and combined associations of cognitive impairment and body pain with functional and mobility disabilities (FMDs) among older women and men in India. Multivariable linear regression models were applied using data from the Longitudinal Aging Study in India (2017-18) comprising 31,464 adults aged 60+. Older adults with cognitive impairment and pain reported higher levels of FMDs than peers without any pain and cognitive impairment. The likelihood of FMDs was significantly greater among older Indians enduring both cognitive impairment and pain (p < 0.05). Moreover, the association between cognitive impairment and functional disability was noticeably stronger in older women, particularly those with frequent pain, while the link between cognitive impairment and mobility disability was more pronounced in men with pain. Integrated cognitive rehabilitation and pain management programs, along with guided physical therapy, gender-specific support groups, and community-based health promotion activities, should be considered to reduce FMDs in older Indians.

Associations between neighbourhood safety, social cohesion, sleep quality and sleep duration among older adults in India: Findings from the Study on Global Aging and Adult Health (WHO-SAGE), 2015.

BACKGROUND: Most studies on later-life health in India focus on families, with far less attention given to the health repercussions of neighbourhood conditions among older Indians. We address this limitation in existing research by examining the associations between perceptions of neighbourhood safety and social cohesion and sleep duration and sleep quality among older adults in India. METHODS: Data come from the Study on Global Aging and Adult Health (WHO-SAGE), India 2015 wave 2, with a sample of 7118 adults aged 50 years and above. Sleep quality and duration were assessed using subjective responses. Multivariable logistic and linear regression analyses were employed to test the research hypotheses. RESULTS: Prevalence of poor sleep quality was higher among older adults living in unsafe neighbourhoods (4.46%) than peers residing in safe neighbourhoods (3.52%), and it was also higher among those living in neighbourhoods with poor social cohesion (5.31%) than counterparts who lived in socially cohesive communities (3.10%). Older adults in neighbourhoods with poor social cohesion had higher odds of reporting compromised sleep quality (adjusted odds ratio 1.75, CI: 1.22-2.51) than those living in socially cohesive neighbourhoods. Moreover, compared to those who perceived they were living in safe neighbourhoods, their peers who perceived their neighbourhoods as unsafe reported shorter sleep duration, with a negative beta coefficient of -0.27 (CI: -0.45 to -0.085). CONCLUSION: That perceived unsafety and poor social cohesion within one's neighbourhood are associated with compromised sleep reflects the significance of making neighbourhoods safer and more integrated for later-life sleep health. In addition to micro-level strategies (e.g., balanced nutrition and physical activity), efforts to improve sleep health should optimise macro-level opportunities, such as rehabilitating and revitalising neighbourhoods, which may alleviate sleep disturbances and improve sleep outcomes among older adults.

Explaining the Urban-Rural Difference in Late-Life Depression in India: Evidence from a Multivariate Decomposition Analysis Based on Longitudinal Aging Study in India, Wave 2017-18.

OBJECTIVES: The study explored the associated factors of depression among older Indian adults and the influences of individual and socio-environmental factors in explaining the rural-urban difference in the prevalence of late-life depression. METHODS: Data come from the Longitudinal Aging Study in India, with a sample of 30,637 older adults aged 60 and above. Multivariable logistic regression and nonlinear multivariate decomposition analyses were conducted to fulfill the objectives. RESULTS: About 6.2% older adults in urban areas and 9.5% in rural areas were depressed. Older adults in rural areas had significantly higher likelihood to be depressed than those in urban areas. Poor self-rated health, multiple chronic conditions, functional difficulty, low life satisfaction, social inactivity, low satisfaction with living arrangement, ill-treatment and being widowed increased the risk of depression. Additionally, work status similar to urban older adults, physical activity, living arrangement satisfaction, self-rated health and ill-treatment would decrease the urban-rural difference in depression. CONCLUSIONS: The study showed significant rural-urban difference in late-life depression, with a rural disadvantage. CLINICAL IMPLICATIONS: The findings suggest the need for identifying at-risk populations and developing a framework of targeted policy interventions for mitigating the increased risk of late-life depression among older Indians and in rural areas in particular.

Treatment for Insomnia Symptoms is Associated with Reduced Depression Among Older Adults: A Propensity Score Matching Approach.

OBJECTIVES: The study aimed to investigate the effect of utilization of treatment for insomnia symptoms on the prevalence of major depressive disorder among older adults in India. METHODS: We used the data from the Longitudinal Ageing Study in India (LASI), 2017-18. The sample included 10,911 older individuals who reported insomnia symptoms. The propensity score matching (PSM) approach was used to compare the depressive disorder among those who received vs. not received treatment. RESULTS: Only 5.7% of older adults reporting insomnia symptoms received treatment. On average, prevalence of depressive disorder among men and women who received treatment for insomnia symptoms was lesser by 0.79 and 0.33 points, respectively, than those who did not receive treatment. In the matched sample, treatment for insomnia symptoms was significantly associated with lesser prevalence of depression for both older men (ß= -0.68, p < .001) and older women (ß= -0.62, p < .001). CONCLUSIONS: The current findings suggest that treatment for insomnia symptoms can reduce the risk of depressive disorder among older adults and the effects are higher among older men than women.

Ulinastatin ameliorated streptozotocin-induced diabetic nephropathy: Potential effects via modulating the components of gut-kidney axis and restoring mitochondrial homeostasis.

Growing evidence supports the role of the gut-kidney axis and persistent mitochondrial dysfunction in the pathogenesis of diabetic nephropathy (DN). Ulinastatin (UTI) has a potent anti-inflammatory effect, protecting the kidney and the gut barrier in sepsis, but its effect on DN has yet to be investigated. This study aimed to assess the potential mitigating effect of UTI on DN and investigate the possible involvement of gut-kidney axis and mitochondrial homeostasis in this effect. Forty male Wistar rats were divided equally into four groups: normal; UTI-treated control; untreated DN; and UTI-treated DN. At the end of the experiment, UTI ameliorated DN by modulating the gut-kidney axis as it improved serum and urinary creatinine, urine volume, creatinine clearance, blood urea nitrogen, urinary albumin, intestinal morphology including villus height, crypt depth, and number of goblet cells, with upregulating the expression of intestinal tight-junction protein claudin-1, and counteracting kidney changes as indicated by significantly decreasing glomerular tuft area and periglomerular and peritubular collagen deposition. In addition, it significantly reduced intestinal and renal nuclear factor kappa B (NF-κB), serum Complement 5a (C5a), renal monocyte chemoattractant protein-1 (MCP-1), renal intercellular adhesion molecule 1 (ICAM1), and renal signal transducer and activator of transcription 3 (STAT3), mitochondrial dynamin related protein 1 (Drp1), mitochondrial fission 1 protein (FIS1), mitochondrial reactive oxygen species (ROS), renal hydrogen peroxide (H2O2), and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels. Furthermore, it significantly increased serum short chain fatty acids (SCFAs), and mitochondrial ATP levels and mitochondrial transmembrane potential. Moreover, there were significant correlations between measured markers of gut components of the gut-kidney axis and renal function tests in UTI-treated DN group. In conclusion, UTI has a promising therapeutic effect on DN by modulating the gut-kidney axis and improving renal mitochondrial dynamics and redox equilibrium.