Determination of G and P genotypes of bovine group A rotavirus with emergence of unusual G- and P-type combinations from neonatal calf diarrhea in Kashmir, India.

A total of 490 diarrhoeic samples from calves aged between 0 and 6 months were screened for the presence of different G- and P-genotypes of rotavirus circulating in bovines in the Kashmir Valley. Of the 490 diarrhoeic samples, Group A rotavirus was detected in 68 (13.87%) samples by polymerase chain reaction (PCR) followed by RNA-PAGE. Genotyping analysis revealed G10, G6, G3, P[11] and P[5] to be the predominant types. The most common types of combinations detected were G10P[11] (27.90%) and G6P[11] (20.60%). The prevalence rate of G10 and P[11] decreased from 60% to 36.76% and 100%-69.11%, respectively. Genotypes G6, G3, P[1] and P[5], which were not previously reported, were detected and unusual combinations such as G6P[11], G3P[11], G10P[5], G3P[5], G6P[1], G6P[5], G6+G8P[11] were also observed for the first time. Fluctuations in the predominant types, emergence of new types and possible genetic reassortment events suggest an unstable epidemiological situation and the need for continuous surveillance of the circulating types to ensure the suitability of the vaccination programme. The present data suggests G10, G6, P[11] and P[5] genotypes could be incorporated in the polyvalent vaccine to offer increased protection against bovine rotavirus infection in India.

Exploring rehabilitation providers' perspectives of assistive technology access after the implementation of a paediatric AT provision program in rural South India.

A paediatric Assistive Technology (AT) Provision Program was implemented by a non-governmental rehabilitation facility in rural South India to support rehabilitation providers in providing needed AT access for children with disabilities. Capacity-building measures for providers and other supports based on the AT needs, barriers, and facilitators to AT access were implemented that aligned with the AT global report for low-middle income countries (LMIC). This study explores how the initiatives from the AT Provision Program have influenced the perspectives of rehabilitation providers on AT access.Using a qualitative design eight paediatric rehabilitation providers were purposively sampled for virtual semi-structured interviews. Findings were analysed using thematic analysis.Six overarching themes were identified: (1) Stigma associated with AT use, (2) Organisational response to changing needs, (3) Financial factors related to family socioeconomic status and the organisation providing AT services, (4) Inequity of AT service access in rural areas, (5) Provider AT awareness and confidence and, (6) Quality assurance. Rehabilitation providers' experiences informed future AT capacity-building strategies within a low-resource context. Our findings provide valuable insights for the development of comprehensive AT Provision Program initiatives to provide AT access for children with disabilities in LMIC settings.

The perspectives of rehabilitation providers in low- and middle-income countries are important to expand the limited research in understanding Assistive Technology (AT) provision in these countries to advance program development and planning.Organized access to AT in rural communities, particularly in developing countries such as India, enables children with disabilities to improve their participation in social, recreational, and educational opportunities.Exploring rehabilitation providers' perspectives gives insight into barriers and opportunities surrounding AT access within their cultural context, and how it influences their clinical practice.Integrating the AT Access Principle framework from the 2022 WHO-UNICEF Global Report on AT, this study evaluates the current AT systems in rural south India and can further inform strategic planning in low-middle income countries to mitigate access barriers encountered along the AT access pathway.

Aged garlic extract preserves beta-cell functioning via modulation of nuclear factor kappa-B (NF-κB)/Toll-like receptor (TLR)-4 and sarco endoplasmic reticulum calcium ATPase (SERCA)/Ca2+ in diabetes mellitus.

BACKGROUND: Peripheral insulin resistance and compromised insulin secretion from pancreatic ß-cells are significant factors and pathogenic hallmarks of diabetes mellitus (DM). NF-κß/TLR-4 and SERCA/Ca2+ pathways have been identified as potential pathways regulating insulin synthesis by preserving pancreatic ß-cell functioning. The current study aimed to evaluate the therapeutic effect of aged garlic extract (AGE) against DM in a streptozotocin (STZ)-induced rat model with particular emphasis on pancreatic ß-cell functioning. METHODS: AGE was characterized by gas chromatography-mass spectrometry (GC-MS), Fourier-transform infrared spectroscopy (FTIR), and scanning electron microscopy (SEM) to evaluate its physio-chemical characteristics followed by in-vitro anti-diabetic and antioxidant potential. This was followed by the induction of DM in laboratory animals for investigating the therapeutic action of AGE by evaluating the role of NF-κß/TLR-4 and the SERCA/Ca2+ pathway. The parameters assessed in the present experimental setup encompassed antioxidant parameters, metabolic indicators, insulin concentration, intracellular calcium levels, apoptotic markers (CCK-8 and Caspase Glo-8), and protein expression (P-62 and APACHE-II). RESULTS: AGE characterization by SEM, GC-MS, and X-ray diffraction (XRD) revealed the presence of phenylalanine, alliin, S-allylmercaptocysteine (SAMC), tryptophan, 1-methyl-1,2,3,4-tetrahydro-ß-carboline-3-carboxylic acid as major bioactive constituents of AGE. Metabolic studies, including intraperitoneal glucose tolerance test (IPGTT), revealed significantly lower blood glucose levels in the AGE group compared to the disease control group. In contrast, the intraperitoneal insulin tolerance test (ITT) exhibited no significant difference in insulin sensitivity between the AGE supplementation group and the DM control group. Interestingly, AGE was found to have no significant effect on fasting glucose and serum insulin levels. In contrast, AGE supplementation was found to cause significant hypoglycaemia in postprandial blood glucose and insulin levels. Importantly, AGE causes restoration of intracellular Ca2+ levels by modulation of SERCA/Ca2 functioning and inhibition NF-κB/TLR-4 pathway. AGE was found to interact with and inhibit the DR-5/ caspase-8/3 apoptotic complex. Furthermore, microscopic studies revealed degeneration and apoptotic changes in pancreatic ß-cells of the DM control group, while supplementation of AGE resulted in inhibition of apoptotic pathway and regeneration of pancreatic ß-cells. CONCLUSION: The current study suggests that AGE enhance glucose homeostasis by exerting their effects on pancreatic ß-cells, without ameliorating peripheral sensitivity. Moreover, AGEs promote an increase in ß-cell mass by mitigating the apoptosis of pancreatic ß-cells. These findings suggest that AGE could aid in developing a viable alternative therapy for diabetes mellitus (DM).

The critical impacts of cytokine storms in respiratory disorders.

Cytokine storm (CS) refers to the spontaneous dysregulated and hyper-activated inflammatory reaction occurring in various clinical conditions, ranging from microbial infection to end-stage organ failure. Recently the novel coronavirus involved in COVID-19 (Coronavirus disease-19) caused by SARS-CoV-2 (Severe Acute Respiratory Syndrome Coronavirus 2) has been associated with the pathological phenomenon of CS in critically ill patients. Furthermore, critically ill patients suffering from CS are likely to have a grave prognosis and a higher case fatality rate. Pathologically CS is manifested as hyper-immune activation and is clinically manifested as multiple organ failure. An in-depth understanding of the etiology of CS will enable the discovery of not just disease risk factors of CS but also therapeutic approaches to modulate the immune response and improve outcomes in patients with respiratory diseases having CS in the pathogenic pathway. Owing to the grave consequences of CS in various diseases, this phenomenon has attracted the attention of researchers and clinicians throughout the globe. So in the present manuscript, we have attempted to discuss CS and its ramifications in COVID-19 and other respiratory diseases, as well as prospective treatment approaches and biomarkers of the cytokine storm. Furthermore, we have attempted to provide in-depth insight into CS from both a prophylactic and therapeutic point of view. In addition, we have included recent findings of CS in respiratory diseases reported from different parts of the world, which are based on expert opinion, clinical case-control research, experimental research, and a case-controlled cohort approach.

Modulation of immune cum inflammatory pathway by earthworm granulation tissue extract in wound healing of diabetic rabbit model.

Regeneration is a rare occurrence in the animal kingdom, but the earthworm stands out as a remarkable example of this phenomenon. Recent research has highlighted the promising wound healing properties of extracts derived from earthworms. Therefore, we propose that earthworm granulation tissue extract (EGTE) may facilitate wound healing by regulating immune responses in a rabbit diabetic wound model. Electron microscopy reveals that 70 % EGTE possesses noteworthy porosity with spherical to irregularly oval configuration. Gas chromatography-mass spectrometry (GC-MS) Characterization of EGTE revealed higher levels of ergosta-5,7,22-trien-3-ol, (3. beta.,22E). In-Vitro studies revealed significant anti-oxidant, anti-inflammatory and anti-bacterial properties in dose dependent manner. Likewise, cytotoxicity assessments reveal that 70 % EGTE exhibits minimal harm to cells while displaying substantial antioxidant and anti-inflammatory activities. For In-Vivo studies excision wounds were created on the dorsal regions of the experimental animals and were divided as Group I (50 % EGTE), Group II (70 % EGTE), Group III (vehicle) and Group IV (distilled water). Over a 21-day observation period 70 % EGTE facilitated the early healing of wounds in the experimental animals, evident through prompt wound closure, granulation tissue formation, increased DNA content, enhanced tensile strength of the wound area and enhanced the expression/synthesis of wound healing markers/proteins. From these results it can be postulated that EGTE accelerates wound healing by immune modulation, dampening of inflammatory pathway and enhanced expression of growth markers. Henceforth making it promising candidate for therapeutic use in diabetic wound healing.

Novel Therapeutic Agents for Management of Diabetes Mellitus: A Hope for Drug Designing against Diabetes Mellitus.

Diabetes mellitus (DM) is characterized by an absolute decline in insulin secretion and peripheral resistance and is the most prevalent metabolic and endocrine disorder. However, the pathogenesis of DM also includes adipocyte insulin resistance, increased glucagon secretion, increased renal glomerular glucose absorption, and neurotransmitter dysfunction. Although there is a wide spectrum of therapeutics available for glycemic control, owing to the identification of various pathogenic determinants of DM, management of DM remains challenging and complex. Current therapeutic interventions against DM focus mostly on glycemic control without considering the other pathological determinants that eventually lead to treatment failure and the progression of DM. Furthermore, long-term use of these conventionally available anti-diabetic drugs leads to various side effects, henceforth development of novel drugs against DM remains an unending search strategy for researchers. Various studies conducted in various parts of the world have proposed that these novel therapeutic interventions target multiple and alternate pathogenic hotspots involved in DM. The current review article discusses novel therapeutic options that hold particular promise to support their safety and discuss the side effects resulting from their use so that these novel candidate drugs can be effectively fabricated into potential drugs for the treatment of DM.

Early Results of Internal Fixation with Femoral Neck System in Young Patients with Femoral Neck Fracture.

BACKGROUND: Femoral neck fractures are intracapsular hip fractures. There are several surgical implants that have been used to treat femoral neck fractures. Depuy Synthes Products and the lower extremity expert group have developed an innovative femoral neck system (FNS) for fixing femoral neck fractures. With minimally invasive procedures, FNS can provide angular stability. MATERIALS AND METHODS: A non-randomized single centre prospective study was conducted in 30 patients of less than 60 years of age at Maharishi Markandeshwar Institute of Medical Sciences and Research between August 2020 to May 2022. All patients underwent internal fixation with FNS within 48 hours of presentation. RESULTS: Although blood loss and operative time in our operated group was more than that in conventional fixation by cannulated screws, our group had better VAS scores, better Harris scores and lower complication rates. CONCLUSIONS: 1. The Femoral Neck System resulted in better biomechanical properties and good early results in femoral neck fractures. FNS gives both angular stability and rotational stability. The last follow-up in our study showed Harris score to be significantly higher, and the incidence of complications were lower. 2. The combination of FNS bolts with anti-rotation screws avoids the "Z" effect and improves the overall stability and anti-rotation effect. 3. In addition, the novel sliding compression mechanism of FNS allows the fracture ends to come in close contact with each other, benefitting fracture healing.

Self-Administration of Right Vagus Nerve Stimulation Activates Midbrain Dopaminergic Nuclei.

Background: Left cervical vagus nerve stimulation (l-VNS) is an FDA-approved treatment for neurological disorders including epilepsy, major depressive disorder, and stroke, and l-VNS is increasingly under investigation for a range of other neurological indications. Traditional l-VNS is thought to induce therapeutic neuroplasticity in part through the coordinated activation of multiple broadly projecting neuromodulatory systems in the brain. Recently, it has been reported that striking lateralization exists in the anatomical and functional connectivity between the vagus nerves and the dopaminergic midbrain. These emerging findings suggest that VNS-driven activation of this important plasticity-promoting neuromodulatory system may be preferentially driven by targeting the right, rather than the left, cervical nerve. Objective: To compare the effects of right cervical VNS (r-VNS) vs. traditional l-VNS on self-administration behavior and midbrain dopaminergic activation in rats. Methods: Rats were implanted with a stimulating cuff electrode targeting either the right or left cervical vagus nerve. After surgical recovery, rats underwent a VNS self-administration assay in which lever pressing was paired with r-VNS or l-VNS delivery. Self-administration was followed by extinction, cue-only reinstatement, and stimulation reinstatement sessions. Rats were sacrificed 90 min after completion of behavioral training, and brains were removed for immunohistochemical analysis of c-Fos expression in the dopaminergic ventral tegmental area (VTA) and substantia nigra pars compacta (SNc), as well as in the noradrenergic locus coeruleus (LC). Results: Rats in the r-VNS cohort performed significantly more lever presses throughout self-administration and reinstatement sessions than did rats in the l-VNS cohort. Moreover, this appetitive behavioral responding was associated with significantly greater c-Fos expression among neuronal populations within the VTA, SNc, and LC. Differential c-Fos expression following r-VNS vs. l-VNS was particularly prominent within dopaminergic midbrain neurons. Conclusion: Our results support the existence of strong lateralization within vagal-mesencephalic signaling pathways, and suggest that VNS targeted to the right, rather than left, cervical nerve preferentially activates the midbrain dopaminergic system. These findings raise the possibility that r-VNS could provide a promising strategy for enhancing dopamine-dependent neuroplasticity, opening broad avenues for future research into the efficacy and safety of r-VNS in the treatment of neurological disease.

Early Results of Bridge Plating of Humerus Diaphyseal Fractures by MIPO Technique.

BACKGROUND: Anterior bridge plating with minimally invasive technique in humeral shaft fractures is reported as an acceptable, less traumatic and reproducible procedure by several authors. We have evaluated the clini-cal, radiological, and functional outcome of such fractures in eleven patients, all of which were managed with dynamic compression plates over an average follow-up period of 22 months. MATERIAL AND METHODS: Forty patients with humerus shaft fractures managed by anterior bridge plating using the MIPO technique between 2014 and 2016 were included in this series. All cases were treated with closed reduction and 10-12 hole 4.5mm dynamic compression plate fixation over anterolateral aspect in bridging mode using the MIPO technique. The UCLA shoulder and Mayo elbow performance scores were used for assessing shoulder and elbow function. RESULTS: Of the forty patients followed up for a minimum of 18 months in the study, 26 were males and 14 were females. The mean age was 34.3 years (range 20 to 53 years). 24 out of the forty patients (60%) had the dominant side fractured. The mean surgical time was 72.5 minutes (range: 45-100 minutes) and mean radiation exposure was 160 seconds (range: 100-220 seconds). The mean radiological fracture union time was 13 weeks (range: 8-18 weeks). Shoulder function based on the UCLA score was excellent to good in 33 cases (82.5%), fair in 6 cases (15%) and one patient (2.5%) developed infection for which the plate was removed prematurely at the 4th month and the wound was meticulously debrided and then managed conservatively. Road traffic accident (RTA) was the most common mode of injury, found in 27 cases; 12 patients sustained blunt trauma due to a fall; one patient sustained an injury following a direct blow by stick. CONCLUSIONS: 1. The mini-incision anterior bridge technique for humeral shaft fractures gives good functional results and should be considered an effective, cosmetically advanced surgical option in the treatment of humeral shaft fractures. 2. The mini-incision anterior bridge technique is a safe and less method for simple types of humeral shaft fractures when the surgeon is experienced in the technique.