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Objective: To translate and culturally adapt the Telugu version of Quality-of-Life tool among Spinal Cord Injury patients. Method: It's a prospective cross-sectional study conducted at a tertiary neuro centre care hospital. The English version was translated into Telugu by two expert medical professionals and cross-checked by three experts in Telugu vocabulary. Nursing students who had good proficiency in reading and writing in English and Telugu languages were chosen for checking tool reliability. Initially English language was administered on the satisfaction domain followed by the importance domain one month apart. After two months Telugu version was administered in the same way as the English version. The reliability analysis was done. Results: The tool was administered to 50 nursing students. The Cronbach's alpha for the satisfaction domain was 0.97 and the importance domain was 0.91, indicating excellent reliability. Conclusion: The Telugu version of the QOL tool had excellent reliability. Therefore it can be administered in the Telugu language for evaluating the quality of life of people with spinal cord injury. [ABSTRACT FROM AUTHOR]

The longevity of people with intellectual disabilities is increasing in developing nations. However, developing nations lack a proper system of care for aging persons with intellectual disabilities. Until now the care has been provided by parents and relatives in the home environment in developing countries, but this scenario is also changing; therefore, there is a strong need to explore a plan of care for this population which is also feasible and replicable. The National Trust is an autonomous body of the Government of India which has developed a comprehensive plan of care for adults with intellectual disabilities. In this article, the National Trust is discussed using a socioecological model. The replicability and suitability of this model for other developing countries are discussed. [ABSTRACT FROM AUTHOR]

Background: Despite ongoing improvements to regimens preventing allograft rejection, most cardiac and other organ grafts eventually succumb to chronic vasculopathy, interstitial fibrosis, or endothelial changes, and eventually graft failure. The events leading to chronic rejection are still poorly understood and the gut microbiota is a known driving force in immune dysfunction. We previously showed that gut microbiota dysbiosis profoundly influences the outcome of vascularized cardiac allografts and subsequently identified biomarker species associated with these differential graft outcomes., Methods: In this study, we further detailed the multifaceted immunomodulatory properties of protolerogenic and proinflammatory bacterial species over time, using our clinically relevant model of allogenic heart transplantation., Results: In addition to tracing longitudinal changes in the recipient gut microbiome over time, we observed that Bifidobacterium pseudolongum induced an early anti-inflammatory phenotype within 7 d, whereas Desulfovibrio desulfuricans resulted in a proinflammatory phenotype, defined by alterations in leukocyte distribution and lymph node (LN) structure. Indeed, in vitro results showed that B pseudolongum and D desulfuricans acted directly on primary innate immune cells. However, by 40 d after treatment, these 2 bacterial strains were associated with mixed effects in their impact on LN architecture and immune cell composition and loss of colonization within gut microbiota, despite protection of allografts from inflammation with B pseudolongum treatment., Conclusions: These dynamic effects suggest a critical role for early microbiota-triggered immunologic events such as innate immune cell engagement, T-cell differentiation, and LN architectural changes in the subsequent modulation of protolerant versus proinflammatory immune responses in organ transplant recipients., Competing Interests: This work was supported by the National Institute of Health (NIH), National Heart, Lung, and Blood Institute award R01HL148672 (J.S.B./B.M.), U01AI170050 (B.M./J.S.B.), and National Institute of Allergy and Infectious Diseases training grant T32AI95190-10 (S.J.G.). An earlier version of this article has been released as a preprint on bioRxiv ( https://doi.org/10.1101/2022.10.13.511915 ). E.F.M. contributed to this work as an employee of the University of Maryland School of Medicine. The views expressed in this article are his own and do not necessarily represent the views of the NIH or the US Government. The other authors declare no conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Intrinsic metabolism shapes the immune environment associated with immune suppression and tolerance in settings such as organ transplantation and cancer. However, little is known about the metabolic activities in an immunosuppressive environment. In this study, we employed metagenomic, metabolomic, and immunological approaches to profile the early effects of the immunosuppressant drug tacrolimus, antibiotics, or both in gut lumen and circulation using a murine model. Tacrolimus induced rapid and profound alterations in metabolic activities within two days of treatment, prior to alterations in gut microbiota composition and structure. The metabolic profile and gut microbiome after seven days of treatment was distinct from that after two days of treatment, indicating continuous drug effects on both gut microbial ecosystem and host metabolism. The most affected taxonomic groups are Clostriales and Verrucomicrobiae (i.e., Akkermansia muciniphila ), and the most affected metabolic pathways included a group of interconnected amino acids, bile acid conjugation, glucose homeostasis, and energy production. Highly correlated metabolic changes were observed between lumen and serum metabolism, supporting their significant interactions. Despite a small sample size, this study explored the largely uncharacterized microbial and metabolic events in an immunosuppressed environment and demonstrated that early changes in metabolic activities can have significant implications that may serve as antecedent biomarkers of immune activation or quiescence. To understand the intricate relationships among gut microbiome, metabolic activities, and immune cells in an immune suppressed environment is a prerequisite for developing strategies to monitor and optimize alloimmune responses that determine transplant outcomes., Competing Interests: Disclosure statement No potential conflict of interest was reported by the authors.

Programmed death-1 (PD-1) and its ligand PD-L1 are checkpoint molecules which regulate immune responses. Little is known about their functions in T cell migration and there are contradictory data about their roles in regulatory T cell (Treg) function. Here we show activated Tregs and CD4 effector T cells (Teffs) use PD-1/PD-L1 and CD80/PD-L1, respectively, to regulate transendothelial migration across lymphatic endothelial cells (LECs). Antibody blockade of Treg PD-1, Teff CD80 (the alternative ligand for PD-L1), or LEC PD-L1 impairs Treg or Teff migration in vitro and in vivo. PD-1/PD-L1 signals through PI3K/Akt and ERK to regulate zipper junctional VE-cadherin, and through NFκB-p65 to up-regulate VCAM-1 expression on LECs. CD80/PD-L1 signaling up-regulates VCAM-1 through ERK and NFκB-p65. PD-1 and CD80 blockade reduces tumor egress of PD-1 high fragile Tregs and Teffs into draining lymph nodes, respectively, and promotes tumor regression. These data provide roles for PD-L1 in cell migration and immune regulation., (© 2022. The Author(s).)

Regulatory T cell (Treg) lymphatic migration is required for resolving inflammation and prolonging allograft survival. Focusing on Treg interactions with lymphatic endothelial cells (LECs), we dissect mechanisms and functional consequences of Treg transendothelial migration (TEM). Using three genetic mouse models of pancreatic islet transplantation, we show that Treg lymphotoxin (LT) αβ and LEC LTβ receptor (LTβR) signaling are required for efficient Treg migration and suppressive function to prolong allograft survival. Inhibition of LT signaling increases Treg conversion to Foxp3 lo CD25 lo exTregs. In a transwell-based model of TEM across polarized LECs, non-migrated Tregs become exTregs. Such conversion is regulated by LTβR nuclear factor κB (NF-κB) signaling in LECs, which increases interleukin-6 (IL-6) production and drives exTreg conversion. Migrating Tregs are ectonucleotidase CD39 hi and resist exTreg conversion in an adenosine-receptor-2A-dependent fashion. Human Tregs migrating across human LECs behave similarly. These molecular interactions can be targeted for therapeutic manipulation of immunity and suppression., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

In the realm of behavioral interventions, a combined approach of yoga and a cognitive-behavioral strategy in the form of introspective meditation ( manan-dhyana ) may offer benefits as a stress management tool. This pilot study focuses on introspective meditation performed before seeking pleasurable activities, which is a self-reflection about whether to pursue a goal that will bring sensory pleasure in life. A non-probability sample of college students was recruited from a mid-sized Southern University of the United States using a 52-items web-based survey built in Qualtrics. Univariate, bivariate, and multivariate statistics were used to analyze data. Of total 65 students, only 21.5% students reported being engaged in the introspective meditation. The sample constituted predominantly females (75.4%), White (64.6%), and undergraduate students (87.7%). The proportions of anxiety, depression, and moderate/high stress were 50.8%, 40.0%, 86.1% respectively. In the hierarchical regression for initiation, the final model explained nearly 21.1% of variance in initiating introspective meditation among participants ( n = 51) who had not been practicing it. With each unit increment in subscales of initiation (i.e., changes in physical environment), the conditional mean for initiating introspective meditation behavior increased by 0.373 units. In the hierarchical regression for sustenance, the final model explained nearly 50.5% of variance in sustaining introspective meditation behavior among participants ( n = 51) who had not been practicing it. With each unit increment in subscales of sustenance (i.e., emotional transformation), the conditional mean for sustaining introspective meditation behavior increased by 0.330 units. This study can pave a way for designing interventions for college students to promote introspective meditation directed toward seeking pleasurable activities before engaging in them. This has implications for the reduction of stress as well as a preemptive measure for sexual risk-taking, indulgence in maladaptive behaviors such as smoking, vaping, alcohol, and substance use.

Purpose of Review: The microbiota plays an important role in health and disease. During organ transplantation, perturbations in microbiota influence transplant outcome. We review recent advances in characterizing microbiota and studies on regulation of intestinal epithelial barrier function and mucosal and systemic immunity by microbiota and their metabolites. We discuss implications of these interactions on transplant outcomes., Recent Findings: Metagenomic approaches have helped the research community identify beneficial and harmful organisms. Microbiota regulates intestinal epithelial functions. Signals released by epithelial cells or microbiota trigger pro-inflammatory or anti-inflammatory effects on innate and adaptive immune cells, influencing the structure and function of the immune system. Assessment and manipulation of microbiota can be used for biomarkers for diagnosis, prognosis, and therapy., Summary: The bidirectional dialogue between the microbiota and immune system is a major influence on immunity. It can be targeted for biomarkers or therapy. Recent studies highlight a close association of transplant outcomes with microbiota, suggesting exciting potential avenues for management of host physiology and organ transplantation., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Behaviour problems are most common in people with intellectual disabilities. Nature of behaviour problems can vary depending upon the age, sex and intellectual level (IQ)., Objectives: This study examined the distribution of behaviour problems across intellectual disability categories and their association with IQ age and sex in children with intellectual disabilities., Methods: This is a cross-sectional study design. A total of 104 participants (57 males and 47 females), aged 3-18 years, with intellectual disabilities were administered The Behavioural Assessment Scale for Indian Children with Mental Retardation (BASIC-MR)., Results: It was found that violent and destructive, temper tantrum and self-injurious behaviours were differently distributed with reference to intellectual disability levels (P > 0.05) but cumulative scores per se problem behaviours did not vary with the level of intellectual disabilities. IQ showed a significant positive correlation with destructive and violent and misbehaves with other; and a significant negative correlation with temper tantrums and self-injurious behaviours. Age was significantly, positively associated with violent and destructive, odd, and hyperactive behaviours and inversely with self-injurious problem behaviours. There was no significant relationship between the sex of the child and problem behaviours. There was no significant interactive effect of sex and level of intellectual disabilities of the child on problem behaviours., Conclusion: Behaviour problems, in general, are not equally distributed in all categories of intellectual disabilities. Relationship between behaviour problems and age, sex and IQ may not be uniform. But specific behaviours are more associated with specific age group and intellectual disability levels., (© 2016 John Wiley & Sons Ltd.)

Riboflavin (RF) is essential for normal cellular functions and health. Humans obtain RF from exogenous sources via intestinal absorption that involves a highly specific carrier-mediated process. We have recently established that the riboflavin transporter-3 (RFVT3) is vital for the normal intestinal RF uptake process and have characterized certain aspects of its transcriptional regulation. Little is known, however, about how this transporter is regulated at the posttranscriptional level. We address this issue by focusing on the role of microRNAs. Using bioinformatics, we identified two potential interacting miRNAs with the human (h) RFVT3-3'-UTR, and showed (using pmirGLO-hRFVT3-3'-UTR) that the hRFVT3-3'-UTR is, indeed, a target for miRNA effect. Of the two putative miRNAs identified, miR-423-5p was found to be highly expressed in intestinal epithelial cells and that its mimic affected luciferase reporter activity of the pmirGLO-hRFVT3-3'-UTR construct, and also led to inhibition in RF uptake by intestinal epithelial Caco-2 and HuTu-80 cells. Furthermore, cells transfected with mutated seed sequences for miR-423-5p showed an abrogation in inhibitory effect of the miR-423-5p mimic on luciferase activity. While miR-423-5p did not affect the level of expression of the hRFVT3 mRNA, it did lead to a significant inhibition in the level of expression of its protein. Similarly, miR-423-5p was found to affect the level of expression of the mouse RFVT3 in cultured intestinal enteroids. These findings demonstrate, for the first time, that the RFVT3 is a target for posttranscriptional regulation by miRNAs in intestinal epithelial cells and that this regulation has functional consequences on intestinal RF uptake. NEW & NOTEWORTHY Our findings show for the first time that RFVT3 is a target for posttranscriptional regulation by miR-423-5p in intestinal epithelial cells, and this regulation has functional consequences on intestinal riboflavin (RF) uptake process.

Biotin (vitamin B7), an essential micronutrient for normal cellular functions, is obtained from both dietary sources as well as gut microbiota. Absorption of biotin in both the small and large intestine is via a carrier-mediated process that involves the sodium-dependent multivitamin transporter (SMVT). Although different physiological and molecular aspects of intestinal biotin uptake have been delineated, nothing is known about the effect of LPS on the process. We addressed this issue using in vitro (human colonic epithelial NCM460 cells) and in vivo (mice) models of LPS exposure. Treating NCM460 cells with LPS was found to lead to a significant inhibition in carrier-mediated biotin uptake. Similarly, administration of LPS to mice led to a significant inhibition in biotin uptake by native colonic tissue. Although no changes in total cellular SMVT protein and mRNA levels were observed, LPS caused a decrease in the fraction of SMVT expressed at the cell surface. A role for casein kinase 2 (CK2) (whose activity was also inhibited by LPS) in mediating the endotoxin effects on biotin uptake and on membrane expression of SMVT was suggested by findings that specific inhibitors of CK2, as well as mutating the putative CK2 phosphorylation site (Thr 78 Ala) in the SMVT protein, led to inhibition in biotin uptake and membrane expression of SMVT. This study shows for the first time that LPS inhibits colonic biotin uptake via decreasing membrane expression of its transporter and that these effects likely involve a CK2-mediated pathway.

Background: Low-and middle-income countries (LAMI) lack an integrated and systematic approach to identify people with intellectual disabilities. Screening surveys are considered resource-intensive; therefore, alternative approaches are needed. This study attempted to identify children up to age 18 years with intellectual disabilities through a mixed-method approach involving focus group interviews (FGIs) and door-to-door surveys., Materials and Methods: Focus groups were conducted with the assistance and involvement of local leaders in four villages of Barwani district of Madhya Pradesh with a 99% tribal population in all four villages. A formal survey of the community was then conducted to determine the prevalence of intellectual disabilities based on a standardized screening instrument (NIMH-DDS)., Results: Thirty focus group interviews were conducted involving 387 participants (males 284, females 103) over a period of 13 days. The entire adult population (N = 8797) was then surveyed for intellectual disabilities using a standardized screening instrument. The data revealed a close similarity in the prevalence rates of intellectual disabilities, as determined by the two approaches (Focus Group Interviews, 5.22/1000 versus Survey, 5.57/1000)., Conclusion: A qualitative method using FGIs successfully identified people with intellectual disabilities in an economically deprived tribal area, showing that a community-based approach provides a close estimate of intellectual disabilities based on a formal survey using standard diagnostic criteria. These data suggest that FGI, along with other qualitative data, could be helpful in designing and in serving as an entree for community-based interventions., (© 2015 John Wiley & Sons Ltd.)

Obesity, a global problem, is a multifactorial disorder. The factors are environmental, metabolic and genetic and their interaction with each other regulates the body weight. Imbalance in either of the factors may be responsible for weight gain. With advancement of research techniques in the last decade, genetic studies have been undertaken for several different causative mutations involving obesity loci on different chromosomes. Monogenic and polygenic obesity has been observed however, polygenic forms are more common. So far more than 200 genes in mouse and more than 100 genes in humans have been identified which result in phenotypes that affect body weight regulation. In spite of this knowledge, the field of obesity has still not been explored extensively. There remain a lot of lacuna regarding causes and treatment of obesity. Challenges are still there to identify the exact cause of weight gain and the use of current knowledge for development of anti-obesity drugs targeted for body weight regulation. In this review, we have explained neuropathophysiologic regulation of feeding behaviour and some aspects of obesity-genetics especially with single nucleotide polymorphism of selected candidate genes and their functional aspects mainly in monogenic obesity.