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Background: Radiation-induced oral mucositis is one of the most critical dose-limiting toxicities associated with radiation therapy for oral cancer which can result in treatment interruption and compromise the quality of the life of cancer patients. Jati (Jasminum grandiflorum) is used in Ayurveda to treat oral conditions like stomatitis and mouth ulcers., Objective: To test the feasibility of Jati oral gel as an add on therapy in grade 2 radiation-induced oral mucositis., Materials and Methods: A prospective, open-label, non-randomised pilot trial was conducted on 20 patients with grade 2 radiation-induced oral mucositis at a tertiary cancer hospital. The control group received sodium bicarbonate mouthwash 4-5 times daily as the standard of care, while the intervention arm also received Jati oral gel twice daily. We used the ImageJ software for objective assessment and the Visual Analogue Scale for subjective pain assessment. The study was continued for 15 days or until the mucositis progressed to grade 3 or resolved to grade 1., Result: There was a significant reduction in the mean pain score and mean area of mucositis in the intervention group compared to the control group., Conclusion: Jati oral gel is a suitable medicament as an add-on therapy in managing grade 2 radiation-induced oral mucositis., Competing Interests: Declaration of Competing Interest Nil., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Transient receptor potential melastatin 8 (TRPM8) is a temperature- and menthol-sensitive ion channel that contributes to diverse physiological roles, including cold sensing and pain perception. Clinical trials targeting TRPM8 have faced repeated setbacks predominantly due to the knowledge gap in unraveling the molecular underpinnings governing polymodal activation. A better understanding of the molecular foundations between the TRPM8 activation modes may aid the development of mode-specific, thermal-neutral therapies. Ancestral sequence reconstruction was used to explore the origins of TRPM8 activation modes. By resurrecting key TRPM8 nodes along the human evolutionary trajectory, we gained valuable insights into the trafficking, stability, and function of these ancestral forms. Notably, this approach unveiled the differential emergence of cold and menthol sensitivity over evolutionary time, providing a fresh perspective on complex polymodal behavior. These studies provide a paradigm for understanding polymodal behavior in TRPM8 and other proteins with the potential to enhance our understanding of sensory receptor biology and pave the way for innovative therapeutic interventions.

Background: Porcine reproductive and respiratory syndrome virus 2 (PRRSV-2) infection during late gestation substantially lowers fetal viability and survival. In a previous genome-wide association study, a single nucleotide polymorphism on chromosome 7 was significantly associated with probability of fetuses being viable in response to maternal PRRSV-2 infection at 21 days post maternal inoculation. The iodothyronine deiodinase 2 (DIO2) gene, located ~ 14 Kilobase downstream of this SNP, was selected as a priority candidate related to fetal susceptibility following maternal PRRSV-2 infection. Our objectives were to identify mutation(s) within the porcine DIO2 gene and to determine if they were associated with fetal outcomes after PRRSV-2 challenge. Sequencing of the DIO2, genotyping identified variants, and association of DIO2 genotypes with fetal phenotypes including DIO2 mRNA levels, viability, survival, viral loads, cortisol and thyroid hormone levels, and growth measurements were conducted., Results: A missense variant (p.Asn91Ser) was identified in the parental populations from two independent PRRSV-2 challenge trials. This variant was further genotyped to determine association with fetal PRRS outcomes. DIO2 mRNA levels in fetal heart and kidney differed by the genotypes of Asn91Ser substitution with significantly greater DIO2 mRNA expression in heterozygotes compared with wild-type homozygotes (P < 0.001 for heart, P = 0.002 for kidney). While Asn91Ser did not significantly alter fetal viability and growth measurements, interaction effects of the variant with fetal sex or trial were identified for fetal viability or crown rump length, respectively. However, this mutation was not related to dysregulation of the hypothalamic-pituitary-adrenal and thyroid axis, indicated by no differences in circulating cortisol, T4, and T3 levels in fetuses of the opposing genotypes following PRRSV-2 infection., Conclusions: The present study suggests that a complex relationship among DIO2 genotype, DIO2 expression, fetal sex, and fetal viability may exist during the course of fetal PRRSV infection. Our study also proposes the increase in cortisol levels, indicative of fetal stress response, may lead to fetal complications, such as fetal compromise, fetal death, or premature farrowing, during PRRSV infection., (© 2024. The Author(s).)

Background: Early identification of overweight and obesity with the help of simple anthropometric tests can prevent from development of metabolic complications in these children. Body mass index (BMI) is the most commonly used parameter but, measurements such as waist circumference (WC), waist-to-height ratio (WHtR) and wrist circumference (WrC) have also been studied and found to have a better correlation with visceral fat., Objective: To correlate WC, WHtR and WrC with BMI among overweight and obese children. The secondary objective was to estimate the proportion of metabolic syndrome among obese and overweight children., Methods: A single-centre, cross-sectional study involving 80 overweight and obese children aged 3-15 years. Anthropometric measures such as WC, WHtR and WrC of the study subjects were correlated with BMI and investigated for metabolic syndrome., Results: Statistically significant and moderate positive correlation was found between BMI and WC, r (80)=0.45 and p<0.001 with WC explaining 20% of the variation of BMI. There was a statistically significant, moderate positive correlation between WHtR and BMI r (80)=0.34 and p<0.001 with 11% of the variation in BMI. There was a statistically significant strong positive correlation between WC and WrC (80)=0.61 and p<0.001, and WrC explains 37.2% of the variation in WC. However, there was no statistically significant correlation between BMI and WrC. Metabolic syndrome was found in 13 (16.25%) children., Conclusion: Alternative anthropometric measurements such as WC and WHtR have a significant correlation with BMI and may be of help in defining overweight and obesity in children. There was a statistically significant strong positive correlation between WC and WrC among obese children. Metabolic syndrome is common in these children., Competing Interests: Competing interests: No, there are no competing interests., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Food production must undergo systems change to meet the sustainable development goals (SDGs). For example, organic farming can be empowered by soil microorganisms with plant growth promotion (PGP) and biocontrol features. In this context, there have been limited studies on pomegranate. We investigated microbial diversity in rhizosphere of the pomegranate "Bhagwa" variety and its potential role in PGP and biocontrol. Both bulk and rhizosphere soil samples were analyzed for their physicochemical properties. Whole metagenome sequencing was conducted using the Illumina NovaSeq6000 platform. Surprisingly, we found that bulk and rhizosphere soil samples had comparable microbial diversity. Metagenome sequencing revealed the abundance of Streptomyces indicus, Bradyrhizobium kalamazoonesis, and Pseudomonas cellulosum in the rhizosphere that are reported here for the first time in agricultural literature. Pathway prediction analysis using KEGG (Kyoto Encyclopedia for Genes and Genomes) and COG (clusters of orthologous genes) databases identified metabolic pathways associated with biocontrol properties against pathogens. We confirmed the metagenome data in vitro , which demonstrated their PGP potential and antimicrobial properties. For instance, S. indicus produced high concentration of indole-3-acetic acid, a PGP phytohormone, that can stimulate plant growth. In addition, an antimicrobial susceptibility assay suggested that bacterial extracts displayed activity against Xanthomonas , a primary pathogen causing the pomegranate wilt disease. In conclusion, this study suggests that S. indicus, B. kalamazoonesis , and P. cellulosum can potentially be PGP and biocontrol agents that may contribute to increased crop productivity in pomegranate cultivation. These agents and their combinations warrant future research with an eye on SDGs and so as to enable and innovate organic farming and pomegranate agricultural practices.

Fish spawning locations are a crucial input into fisheries management and conservation plans, and many stocks are especially sensitive to the environmental conditions within these localized zones. Globally collated data on spawning locations across many species has been unavailable, hindering global stock assessments and analyses of sustainable development and global environmental change. To address this, we created a geocoded fish spawning dataset using qualitative spawning information from FishBase and Science and Conservation of Fish Aggregations (SCRFA). We cleaned and geocoded the spawning locations of 1,045 marine fish species into 2,931 regions. Each spawning region is defined by one or more polygons, and most spawning regions are associated with spawning months. The resulting dataset covers oceans globally. This dataset will be useful to scientists studying marine fish population dynamics and their interactions with the physical environment on regional to large scales., (© 2024. The Author(s).)

In pancreatic ductal adenocarcinoma (PDAC), no recurrent metastasis-specific mutation has been found, suggesting that epigenetic mechanisms, such as DNA methylation, are the major contributors of late-stage disease progression. Here, we performed the first whole-genome bisulfite sequencing (WGBS) on mouse and human PDAC organoid models to identify stage-specific and molecular subtype-specific DNA methylation signatures. With this approach, we identified thousands of differentially methylated regions (DMRs) that can distinguish between the stages and molecular subtypes of PDAC. Stage-specific DMRs are associated with genes related to nervous system development and cell-cell adhesions, and are enriched in promoters and bivalent enhancers. Subtype-specific DMRs showed hypermethylation of GATA6 foregut endoderm transcriptional networks in the squamous subtype and hypermethylation of EMT transcriptional networks in the progenitor subtype. These results indicate that aberrant DNA methylation contributes to both PDAC progression and subtype differentiation, resulting in significant and reoccurring DNA methylation patterns with diagnostic and prognostic potential., Competing Interests: The authors declare no competing interests., (© 2024 The Author(s).)

Hydroxyapatite is widely used in bone implantation because of its similar mineral composition to natural bone, allowing it to serve as a biocompatible osteoconductive support. A bovine-derived hydroxyapatite (BHA) scaffold was developed through an array of defatting and deproteinization procedures. The BHA scaffold was substituted with fluoride ions using a modified sol-gel method to produce a bovine-derived fluorapatite (BFA) scaffold. Fourier-transform infrared spectroscopy and X-ray diffraction analysis showed that fluoride ions were successfully substituted into the BHA lattice. According to energy dispersive X-ray analysis, the main inorganic phases contained calcium and phosphorus with a fluoride ratio of ~1-2 wt%. Scanning electron microscopy presented a natural microporous architecture for the BFA scaffold with pore sizes ranging from ~200-600 μm. The BHA scaffold was chemically stable and showed sustained degradation in simulated-body fluid. Young's modulus and yield strength were superior in the BFA scaffold to BHA. In vitro cell culture studies showed that the BFA was biocompatible, supporting the proliferative growth of Saos-2 osteoblast cells and exhibiting osteoinductive features. This unique technique of producing hydroxyapatite from bovine bone with the intent of producing high performance biomedically targeted materials could be used to improve bone repair.

Background: There are limited global data on head-to-head comparisons of vaccine platforms assessing both humoral and cellular immune responses, stratified by pre-vaccination serostatus. The COVID-19 vaccination drive for the Indian population in the age group 18-45 years began in April 2021 when seropositivity rates in the general population were rising due to the delta wave of COVID-19 pandemic during April-May 2021., Methods: Between June 30, 2021, and Jan 28, 2022, we enrolled 691 participants in the age group 18-45 years across four clinical sites in India. In this non-randomised and laboratory blinded study, participants received either two doses of Covaxin® (4 weeks apart) or two doses of Covishield™ (12 weeks apart) as per the national vaccination policy. The primary outcome was the seroconversion rate and the geometric mean titre (GMT) of antibodies against the SARS-CoV-2 spike and nucleocapsid proteins post two doses. The secondary outcome was the frequency of cellular immune responses pre- and post-vaccination., Findings: When compared to pre-vaccination baseline, both vaccines elicited statistically significant seroconversion and binding antibody levels in both seronegative and seropositive individuals. In the per-protocol cohort, Covishield™ elicited higher antibody responses than Covaxin® as measured by seroconversion rate (98.3% vs 74.4%, p < 0.0001 in seronegative individuals; 91.7% vs 66.9%, p < 0.0001 in seropositive individuals) as well as by anti-spike antibody levels against the ancestral strain (GMT 1272.1 vs 75.4 binding antibody units/ml [BAU/ml], p < 0.0001 in seronegative individuals; 2089.07 vs 585.7 BAU/ml, p < 0.0001 in seropositive individuals). As participants at all clinical sites were not recruited at the same time, site-specific immunogenicity was impacted by the timing of vaccination relative to the delta and omicron waves. Surrogate neutralising antibody responses against variants-of-concern including delta and omicron was higher in Covishield™ recipients than in Covaxin® recipients; and in seropositive than in seronegative individuals after both vaccination and asymptomatic infection (omicron variant). T cell responses are reported from only one of the four site cohorts where the vaccination schedule preceded the omicron wave. In seronegative individuals, Covishield™ elicited both CD4+ and CD8+ spike-specific cytokine-producing T cells whereas Covaxin® elicited mainly CD4+ spike-specific T cells. Neither vaccine showed significant post-vaccination expansion of spike-specific T cells in seropositive individuals., Interpretation: Covishield™ elicited immune responses of higher magnitude and breadth than Covaxin® in both seronegative individuals and seropositive individuals, across cohorts representing the pre-vaccination immune history of most of the vaccinated Indian population., Funding: Corporate social responsibility (CSR) funding from Hindustan Unilever Limited (HUL) and Unilever India Pvt. Ltd. (UIPL)., Competing Interests: The project was fully supported by corporate social responsibility (CSR) funding from Hindustan Unilever Limited (HUL) and Unilever India Pvt. Ltd. (UIPL) and facilitated by the Office of the Principal Scientific Advisor (Government of India). SM is supported by a J.C. Bose Fellowship from the Department of Science and Technology and is a Margadarshi Fellow of the DBT-Wellcome Trust India Alliance (IA/M/15/1/502018). All authors declare no other conflicts of interest., (© 2024 The Authors.)

Whilst surgeons and robotic companies are key stakeholders involved in the adoption of robotic assisted surgery (RS), the public's role is overlooked. However, given that patients hold ultimate power over their healthcare decisions, public acceptance of RS is crucial. Therefore, this study aims to identify public understanding, opinions, and misconceptions about RS. An online questionnaire distributed between February and May 2021 ascertained the views of UK adults on RS. The themes of questions included familiarity, experience and comfort with RS, opinions on its ethical implications, and the impact of factual information provided to the participant. The data were evaluated using thematic and statistical analysis, including assessing for statistical differences in age, gender, education level, and presence in the medical field. Overall, 216 responses were analysed. Participants were relatively uninformed about RS, with a median knowledge score of 4.00(2.00-6.00) on a 10-point Likert scale. Fears surrounding increased risk, reduced precision and technological failure were identified, alongside misconceptions about its autonomous nature. However, providing factual information in the survey about RS statistically increased participant comfort (p = < 0.0001). Most (61.8%) participants believed robot manufacturers were responsible for malfunctions, but doctors were held accountable more by older, less educated, and non-medical participants. Our findings suggest that there is limited public understanding of RS. The numerous common misconceptions identified present a major barrier to the widespread acceptance of RS, since inaccurate fears about its nature could discourage potential patients from engaging with robotic procedures., (© 2024. Crown.)

Background: Fluid responsiveness should be assessed in patients with septic shock because only 50% of patients are fluid responsive. Dynamic measures of fluid responsiveness, like pulse pressure variation measured after a passive leg raise maneuver, are recommended to guide fluid administration in patients with sepsis after initial fluid resuscitation., Local Problem: The purpose of the project was to evaluate outcomes after implementing a nurse-driven fluid responsiveness evaluation using passive leg raise and pulse pressure variation measurement in patients with septic shock., Methods: The project included 30 adult patients with septic shock in a 24-bed medical-surgical intensive care unit at a community hospital. A new nursing process was initiated for bedside fluid responsiveness evaluation (pulse pressure variation measurement after passive leg raise). Staff members received in-person individual training sessions. Preintervention and 20-week postintervention patient outcomes data were collected to estimate the project's impact on incidence of fluid overload and acute kidney injury, duration of mechanical ventilation, and intensive care unit length of stay. Preintervention and postintervention staff satisfaction surveys assessed nurses' perception of the project's value., Results: Before intervention, 24 of 37 patients (65%) met criteria of fluid overload. The project resulted in a 28% decrease in the incidence of fluid overload. Staff satisfaction surveys revealed a significant increase in nurses' feelings of empowerment to positively affect patient outcomes; all nurses agreed that the new process was efficient., Conclusion: The results indicate that the project had a positive impact on patient outcomes and nurse autonomy., (©2024 American Association of Critical-Care Nurses.)

Nuclear clearance and cytoplasmic accumulations of the RNA-binding protein TDP-43 are pathological hallmarks in almost all patients with amyotrophic lateral sclerosis (ALS) and up to 50% of patients with frontotemporal dementia (FTD) and Alzheimer's disease. In Alzheimer's disease, TDP-43 pathology is predominantly observed in the limbic system and correlates with cognitive decline and reduced hippocampal volume. Disruption of nuclear TDP-43 function leads to abnormal RNA splicing and incorporation of erroneous cryptic exons in numerous transcripts including Stathmin-2 (STMN2, also known as SCG10) and UNC13A, recently reported in tissues from patients with ALS and FTD. Here, we identify both STMN2 and UNC13A cryptic exons in Alzheimer's disease patients, that correlate with TDP-43 pathology burden, but not with amyloid-β or tau deposits. We also demonstrate that processing of the STMN2 pre-mRNA is more sensitive to TDP-43 loss of function than UNC13A. In addition, full-length RNAs encoding STMN2 and UNC13A are suppressed in large RNA-seq datasets generated from Alzheimer's disease post-mortem brain tissue. Collectively, these results open exciting new avenues to use STMN2 and UNC13A as potential therapeutic targets in a broad range of neurodegenerative conditions with TDP-43 proteinopathy including Alzheimer's disease., (© 2024. The Author(s).)

Background: Nursing profession requires strength and resilience not just physically, but emotionally as well which requires them to adapt in stressful situations that they are often exposed to in their work environment., Objective: To determine the prevalence and associated factors of emotional intelligence (EI) and occupational stress (OS) among the nursing professionals from selected tertiary care hospitals in Bangalore, India., Methods: This was a multi-centric, cross-sectional study done among nurses with more than 1year of work experience and they were randomly selected from four tertiary care hospitals in Bangalore. The EI and OS were assessed using the Emotional intelligence scale (EIS) and Occupational Stress Index (OSI). Data was collected, both online and offline, owing to the ongoing COVID-19 pandemic. The data was analyzed using SPSS v21.0 to calculate the mean, associations, and regression., Results: Out of the total 294, the mean age of the study participants was 27±4.92years. A total of 75 (25.5%) nurses had poor EI and 245 (83.3%) had moderate OSI. None of the participants had high OSI. There was a significant association between the severity grades of EI and OSI ( P = 0.010) and a binary logistic regression showed that those staff with high EI had a lesser odd (OR 0.531, 95% CI 0.282-0.999) of developing occupational stress as compared to those with low EI., Conclusion: EI plays a significant role in reversing the effect of one's occupational stress. Thereby, the training curriculum should include skills and measures of resilience to facilitate their EI improvement., Competing Interests: There are no conflicts of interest., (Copyright: © 2024 Indian Journal of Occupational and Environmental Medicine.)