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This mini-review provides a detailed outline of studies that have used multimodal approaches in non-invasive brain stimulation to investigate the pathophysiology of the three common movement disorders, namely, essential tremor, Parkinson’s disease, and dystonia. Using specific search terms and filters in the PubMed ® database, we finally shortlisted 27 studies in total that were relevant to this review. While two-thirds ( Brittain et al., 2013 ) of these studies were performed on Parkinson’s disease patients, we could find only three studies that were conducted in patients with essential tremor. We clearly show that although multimodal non-invasive brain stimulation holds immense potential in unraveling the physiological mechanisms that are disrupted in movement disorders, the technical challenges and pitfalls of combining these methods may hinder their widespread application by movement disorder specialists. A multidisciplinary team with clinical and technical expertise may be crucial in reaping the fullest benefits from such novel multimodal approaches.

Numerous neurological disorders are linked to sequences rich in guanine repeats found in introns, exons, and regulatory regions of genes. These sequences have been observed to form stable G-quadruplex (GQ) structures both in vitro and in vitro. Cerebellar Ataxia with Neuropathy and Vestibular Areflexia Syndrome (CANVAS), a slowly progressive neurodegenerative disorder, is associated with the biallelic expansion of (AAGGG) n pathogenic repeats in the second intron of the RFC1 gene. Though these G-rich pathogenic repeats in other neurological diseases are associated with protein loss of function, RNA gain of function, and/or protein gain of function, not much is known about the pathological mechanism associated with CANVAS. Herein, we report the formation of stable GQ conformations in the CANVAS-associated repeats i.e., r(AAGGG) n , where ‘r’ stands for RNA. These GQs are critical regulators in neurological disorders leading to RNA foci formation and RNA binding protein sequestration. They also alter other causative processes like intron retention, which leads us to hypothesize a toxic Proteinopathy mechanism in CANVAS. Various biophysical and biomolecular assays characterized the interactions of three aggregation-prone RNA-binding proteins (RBPs): heterogeneous nuclear ribonucleoprotein H1/F (hnRNP H1/F), and DGCR8 with different pathogenic repeats [(AAGGG) 9 ] in vitro, further affirming the hypothesis. The biophysical observations are further supported by molecular dynamics analysis and cell-based studies, putting us a step closer to elucidating the pathological mechanism(s) in CANVAS neuropathy, paving the way for the development of innovative therapeutic interventions.

This article investigates comparative intersections of gender and family sociology internationally, with a specific focus on urban Germany and urban India. In particular, this research examines a central dynamic that informs family and marriage relations globally, and for this research context, in Germany and India: What are the nuanced ways of conceptualizing changing gender roles in marriage and in family in Germany and India? Bringing together a robust understanding of the theoretical frameworks of Intersectionality and of Mobility as large bodies of scholarship that examine geographic and symbolic power geometries, we adopt the lens of Intersectional Im/Mobilities to explore changing gender roles in family and marriage in Germany and India. We particularly focus on an intersectionality-based analysis of two primary themes that arise out of our primary and secondary data: (1) Women’s employment and impact on family life/work–life balance; and (2) Changing gender roles in marriage (through the lens of the division of household labor and aspects of agency and decision making), questions which influence and inflect complex intersectional realities.

A surge of COVID-19 occurred from March to June 2021, in New Delhi, India, linked to the B.1.617.2 (Delta) variant of SARS-CoV-2. COVID-19 vaccines were rolled out for health care workers (HCWs) starting in January 2021. To assess the incidence density of reinfection among a cohort of HCWs and estimate the effectiveness of the inactivated whole virion vaccine BBV152 against reinfection. This was a retrospective cohort study among HCWs working at a tertiary care center in New Delhi, India. Vaccination with 0, 1, or 2 doses of BBV152. The HCWs were categorized as fully vaccinated (with 2 doses and ≥15 days after the second dose), partially vaccinated (with 1 dose or 2 doses with <15 days after the second dose), or unvaccinated. The incidence density of COVID-19 reinfection per 100 person-years was computed, and events from March 3, 2020, to June 18, 2021, were included for analysis. Unadjusted and adjusted hazard ratios (HRs) were estimated using a Cox proportional hazards model. Estimated vaccine effectiveness (1 - adjusted HR) was reported. Among 15 244 HCWs who participated in the study, 4978 (32.7%) were diagnosed with COVID-19. The mean (SD) age was 36.6 (10.3) years, and 55.0% were male. The reinfection incidence density was 7.26 (95% CI: 6.09-8.66) per 100 person-years (124 HCWs [2.5%], total person follow-up period of 1696 person-years as time at risk). Fully vaccinated HCWs had lower risk of reinfection (HR, 0.14 [95% CI, 0.08-0.23]), symptomatic reinfection (HR, 0.13 [95% CI, 0.07-0.24]), and asymptomatic reinfection (HR, 0.16 [95% CI, 0.05-0.53]) compared with unvaccinated HCWs. Accordingly, among the 3 vaccine categories, reinfection was observed in 60 of 472 (12.7%) of unvaccinated (incidence density, 18.05 per 100 person-years; 95% CI, 14.02-23.25), 39 of 356 (11.0%) of partially vaccinated (incidence density 15.62 per 100 person-years; 95% CI, 11.42-21.38), and 17 of 1089 (1.6%) fully vaccinated (incidence density 2.18 per 100 person-years; 95% CI, 1.35-3.51) HCWs. The estimated effectiveness of BBV152 against reinfection was 86% (95% CI, 77%-92%); symptomatic reinfection, 87% (95% CI, 76%-93%); and asymptomatic reinfection, 84% (95% CI, 47%-95%) among fully vaccinated HCWs. Partial vaccination was not associated with reduced risk of reinfection. These findings suggest that BBV152 was associated with protection against both symptomatic and asymptomatic reinfection in HCWs after a complete vaccination schedule, when the predominant circulating variant was B.1.617.2.

Nuclear factor erythroid-2-related factor 2 (Nrf2) is a stress-activated transcription factor regulating antioxidant genes, and a deficiency thereof, slowing lymphangiogenesis, has been reported in diabetic foot ulcer (DFU). The mode of Nrf2 regulation in DFU has been less explored. Emerging studies on miRNA-mediated target regulation show miRNA to be the leading player in the pathogenesis of the disease. In the present study, we demonstrated the role of miR-27b in regulating Nrf2-mediated angiogenesis in DFU. A lower expression of mRNA targets, such as Nrf2, HO-1, SDF-1α, and VEGF, was observed in tissue biopsied from chronic DFU subjects, which was in line with miR-27b, signifying a positive correlation with Nrf2. Similarly, we found significantly reduced expression of miR-27b and target mRNAs Nrf2, HO-1, SDF-1α, and VEGF in endothelial cells under a hyperglycemic microenvironment (HGM). To confirm the association of miR-27b on regulating Nrf2-mediated angiogenesis, we inhibited its expression through RNA interference-mediated knockdown and observed disturbances in angiogenic signaling with reduced endothelial cell migration. In addition, to explore the role of miR-27b and angiogenesis in the activation of Nrf2, we pretreated the endothelial cells with two well-known pharmacological compounds—pterostilbene and resveratrol. We observed that activation of Nrf2 through these compounds ameliorates impaired angiogenesis on HGM-induced endothelial cells. This study suggests a positive role of miR-27b in regulating Nrf2, which seems to be decreased in DFU and improves on treatment with pterostilbene and resveratrol.

An amendment to this paper has been published and can be accessed via the original article.

Proliferation of specific nucleotide sequences within the coding and non-coding regions of numerous genes has been implicated in approximately 40 neurodegenerative disorders. Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS), a neurodegenerative disorder, is distinguished by a pathological triad of sensory neuropathy, bilateral vestibular areflexia and cerebellar impairments. It manifests in adults gradually and is autosomal recessive and multi-system ataxia. Predominantly, CANVAS is associated with biallelic AAGGG repeat expansions in intron 2 of the RFC1 gene. Although various motifs have been identified, only a subset induces pathological consequences, by forming stable secondary structures that disrupt gene functions both in vitro and in vivo. The pathogenesis of CANVAS remains a subject of intensive research, yet its precise mechanisms remain elusive. Herein, we aim to comprehensively review the epidemiology, clinical ramifications, molecular mechanisms, genetics, and potential therapeutics in light of the current findings, extending an overview of the most significant research on CANVAS.

In the present work, we aim to study collectivity in the Pb isotopes in the framework of nuclear shell model. We have performed shell-model calculations using KHH7B effective interaction. The model space of KHH7B interaction consists of 14 orbitals. We have reported results for even-even 196 - 206 Pb isotopes for spectra and electromagnetic properties. The shell model results for isomeric states are also reported. Our results will be useful to compare upcoming experimental data.

Background Bariatric surgery can alleviate cardiovascular risk via effects on cardiovascular disease (CVD) risk factors such as diabetes mellitus, hypertension, and dyslipidemia. Our study aimed to assess the cholesterol efflux capacity (CEC) of HDL as a negative risk factor for CVD in individuals with obesity and identify the factors associated with improvement in CEC 3 months following bariatric surgery. Methods We recruited 40 control individuals (mean BMI of 22.2 kg/m 2 ) and 56 obese individuals (mean BMI of 45.9 kg/m 2 ). The biochemical parameters, inflammatory status and CEC of HDL was measured for the obese individuals before bariatric surgery and at 3 months after surgery. The CEC was measured using a cell-based cholesterol efflux system of BODIPY-cholesterol-labelled THP-1 macrophages. Results A significant reduction in BMI (− 17%, p < 0.001), resolution of insulin sensitivity (HOMA2-IR = − 23.4%, p = 0.002; Adipo IR = − 16%, p = 0.009) and inflammation [log resistin = − 6%, p = 0.07] were observed 3 months post-surgery. CEC significantly improved 3 months after surgery [Pre: 0.91 ± 0.13; Post: 1.02 ± 0.16; p = 0.001] despite a decrease in HDL-C levels. The change in CEC correlated with the change in apo A-I (r = 0.39, p = 0.02) and adiponectin levels (r = 0.35, p = 0.03). Conclusion The results suggest that improvements in CEC, through improvement in adipose tissue health in terms of adipokine secretion and insulin sensitivity could be an important pathway in modulating obesity-related CVD risk.

An in-silico approach was implemented to develop a multi-epitope subunit vaccine construct against the recent outbreak of the Monkeypox virus. The contribution of 10 different antigenic proteins based on their antigenicity led to the selection of 10 HTL, 9 CTL, and 6 BCL epitopes. The construct was further investigated for its allergenicity, antigenicity, and physio-chemical properties using servers such as AllerTOP and Allergen FP, VaxiJen and ANTIGENPro, and ProtParam respectively. The secondary structure of the vaccine was predicted using the SOPMA server followed by I-TASSER for the 3D structure. After refinement and validation of structural stability of the modelled vaccine, a molecular docking assay was implemented to study the interaction of the known TLR4 receptor with that of the constructed vaccine using the ClusPro server. The docked vaccine and TLR4 receptor were studied using the molecular dynamics (MD) simulation to validate the stability of the complex. After codon optimization the cDNA was constructed and in-silico cloning of the vaccine construct was carried out. The vaccine was also subjected to computational immune assay which predicted a powerful immune response against the Monkeypox virus validating that the developed multi-epitope vaccine construct can be a potent vaccine candidate.