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Abstract Background Black men consistently have higher rates of prostate cancer (PCA)- related mortality. Advances in PCA treatment, screening, and hereditary cancer assessment center around germline testing (GT). Of concern is the significant under-engagement of Black males in PCA GT, limiting the benefit of precision therapy and tailored cancer screening despite longstanding awareness of these disparities. To address these critical disparities, the Socioecological Model (SEM) was employed to develop comprehensive recommendations to overcome barriers and implement equitable strategies to engage Black males in PCA GT. Methods Clinical/research experts, national organization leaders, and community stakeholders spanning multiple regions in US and Africa participated in developing a framework for equity in PCA GT grounded in the SEM. A novel mixed-methods approach was employed to generate key areas to be addressed and informed statements for consensus consideration utilizing the modified Delphi model. Statements achieving strong consensus (> =75% agreement) were included in final equity frameworks addressing clinical/community engagement and research engagement. Results All societal levels of the SEM (interpersonal, institutional, community, and policy/advocacy) must deliver information about PCA GT to Black males that address benefits/limitations, clinical impact, hereditary cancer implications, with acknowledgment of mistrust (mean scores [MS] 4.57-5.00). Interpersonal strategies for information delivery included engagement of family/friends/peers/Black role models to improve education/awareness and overcome mistrust (MS 4.65-5.00). Institutional strategies included diversifying clinical, research, and educational programs and integrating community liaisons into healthcare institutions (MS 4.57-5.00). Community strategies included partnerships with healthcare institutions and visibility of healthcare providers/researchers at community events (MS 4.65–4.91). Policy/advocacy included improving partnerships between advocacy and healthcare/community organizations while protecting patient benefits (MS 4.57-5.00). Media strategies were endorsed for the first time at every level (MS 4.56-5.00). Conclusion The SEM-based equity frameworks proposed provide the first multidisciplinary strategies dedicated to increase engagement of Black males in PCA GT, which are critical to reduce disparities in PCA-mortality through informing tailored screening, targeted therapy, and cascade testing in families.

Abstract Background The potential association of long‐term oral corticosteroid (OCS) use with adverse events (AEs) in patients with bullous pemphigoid (BP) is not well characterized in a real‐world setting. Objectives To evaluate the effect of OCS use and treatment duration on the incident AEs in patients with BP. Methods This retrospective cohort study used medical and pharmacy claims and patient enrollment data from IQVIA PharMetrics® Plus from 2006−2021. Eligible patients had a diagnosis of BP between 1 January 2006 and 30 June 2020 (≥2 claims for BP ≥ 30 days apart). Patients in the OCS cohort also had a claim for OCS use, ≥7.5 mg daily dose of prednisone or equivalent, and no claims for a nonoral systemic corticosteroid (CS) at any time during the study period. A control cohort of patients with BP not using OCS was also selected. Relative risk ratios were estimated between the incidence of AEs in OCS users with different exposure durations (short‐term, 90 days) and nonusers by Poisson regression, after adjusting for age, sex, prior drug use, and baseline Charlson Comorbidity Index score within the follow‐up period. Results At the 1‐year follow‐up, long‐term OCS users had a higher incidence of infections, cataract, osteoporosis, heart failure, depression or anxiety, and diabetes compared with OCS nonusers (p

Abstract There is growing evidence that a relationship exists between mental and emotional wellbeing and the gut microbiota. Little is known regarding how the microbiota reacts to repeated acute stress events in dogs, and whether it is a predictor of stress response. In this study, we explored the impact on the gut microbiota and digestive health with two common events many pet dogs find stressful. Twenty healthy adult dogs, living within a colony, were exposed to either car travel or separation three times across eight-week intervals. Faecal samples were collected 24 h before, within 24 h, and 24–48 h after. Faecal quality and pH, and microbiota diversity and composition were analysed in context with wider published work on physiological stress measures. No significant changes were observed in faecal quality or pH with either stress event at any timepoint, indicating all pets remained in good digestive health. Microbiota analysis demonstrated no significant impact on alpha or beta diversity with either stressor. Microbial signatures previously linked to stress were not identified in these dogs and no changes were observed in the functional gut composition. Irrespective of whether the pet was considered “stressed” (i.e., exhibited an increase in serum cortisol), there was no effect on the microbiota and no taxa were predictive of stress response. Collectively, this work demonstrates, for this population, certain acute stress events have no meaningful impact on the canine gut microbiota, and it has no impact on the associated stress response.

Partial confinement can provide sufficient reinforcement to enhance the compressive strength and ductility of concrete with lesser confining material. This paper presents the results of an axial compression test conducted on eighteen plain concrete cylinders of 150 mm diameter and 300 mm height partially confined with a Stainless-Steel Wire Mesh (SSWM) strip of different widths. The study included two specimens without wrapping, two fully wrapped specimens, and others wrapped with two SSWM strips of varying widths at both the ends of concrete cylinder. The strain on SSWM up to failure is measured to understand the effectiveness of lateral confining pressure on the behaviour of concrete cylinders. The peak axial compressive strength and corresponding strain of unconfined and SSWM-confined concrete cylinders are compared. The result shows a significant increase in peak confined compressive stress as compared to an unconfined concrete cylinder. However, the confinement efficiency is reduced when the height of the unconfined region exceeds the diameter of the cylinder, and significant strain localisation is detected within the unwrapped region. Based on experimental investigation, a confinement coefficient is suggested for a partial wrapping of SSWM on the concrete cylinder.

Introduction: The present in-vivo experiment was designed to validate newly developed rat models for Rheumatoid Arthritis (RA) as well as cardiovascular complications in RA for translational competence of disease with clinical situation. The FIMD (Framework to Identify Models for Disease) method based on etiology, pathophysiology, symptomatology, and response to therapeutic interventions was used to compare these models sensitized with primary (CFA, bovine collagen type II) and secondary inducing agents (high fat diet, lipopolysaccharide) in different combinations. Materials and Methods: Twenty-four Wistar male rats (four groups/n=6) were taken after prevalidation, where a large dataset was analyzed by using statistical methods (one way ANOVA, repeated Measure ANOVA). Among these groups, two best models from RA representative groups and two best models from cardiovascular complications in RA generated groups were taken for final comparison and validation by the same weight score method for obtaining a percentage similarity and validity score using a radar plot based on FIMD to get the best suited model. Results and Discussion: The findings of this study on the basis of FIMD showed that the collagen (0.1 mL)+lipopolysaccharide (10 µg/mL) induced model is closely fit for preclinical events of RA, with the highest validity score (82%) among all groups and the collagen (0.1 mL)+ lipopolysaccharide (10 µg/mL)+HFD represents a validated model (95%) for co-morbid cardiovascular complications in RA. Conclusion: The developed and validated models were a fresh attempt using different inducers sequentially to culminate the emerging issue of extra organ manifestation in existing RA via a similar pathway, which can be a contributor to future research in drug discoveries in pharmacology.

Abstract Background Excess muscle fat is observed in obesity and associated with greater burden of cardiovascular risk factors and higher risk of mortality. Liraglutide reduces total body weight and visceral fat but its effect on muscle fat and adverse muscle composition is unknown. Methods This is a pre‐specified secondary analysis of a randomized, double‐blind, placebo‐controlled trial that examined the effects of liraglutide plus a lifestyle intervention on visceral adipose tissue and ectopic fat among adults without diabetes with body mass index ≥30 kg/m2 or ≥27 kg/m2 and metabolic syndrome. Participants were randomly assigned to a once‐daily subcutaneous injection of liraglutide (target dose 3.0 mg) or matching placebo for 40 weeks. Body fat distribution and muscle composition was assessed by magnetic resonance imaging at baseline and 40‐week follow‐up. Muscle composition was described by the combination of thigh muscle fat and muscle volume. Treatment difference (95% confidence intervals [CI]) was calculated by least‐square means adjusted for baseline thigh muscle fat. The association between changes in thigh muscle fat and changes in body weight were assessed using Spearman correlation coefficients. The effect of liraglutide versus placebo on adverse muscle composition, denoted by high thigh muscle fat and low thigh muscle volume, was explored. Results Among the 128 participants with follow‐up imaging (92.2% women, 36.7% Black), median muscle fat at baseline was 7.8%. The mean percent change in thigh muscle fat over median follow‐up of 36 weeks was −2.87% among participants randomized to liraglutide (n = 73) and 0.05% in the placebo group (absolute change: −0.23% vs. 0.01%). The estimated treatment difference adjusted for baseline thigh muscle fat was −0.24% (95% CI, −0.41 to −0.06, P‐value 0.009). Longitudinal change in thigh muscle fat was significantly associated with change in body weight in the placebo group but not the liraglutide group. The proportion of participants with adverse muscle composition decreased from 11.0% to 8.2% over follow‐up with liraglutide, but there was no change with placebo. Conclusions In a cohort of predominantly women with overweight or obesity in the absence of diabetes, once‐daily subcutaneous liraglutide was associated with a reduction in thigh muscle fat and adverse muscle composition compared with placebo. The contribution of muscle fat improvement to the cardiometabolic benefits of liraglutide requires further study.

Hydrodynamics in stirred vessels is vital for transport phenomena for various applications in chemical and environmental systems like aerobic and anaerobic systems, effluent treatment and biological applications like bioreactors. Design of efficient impellers reduces power consumption which contributes to reduction in greenhouse gases especially power obtained from thermal power plants thus decreasing the carbon footprint. In the present work, Computational Fluid Dynamics (CFD) simulations have been carried out for two different Rushton turbines (one axial and one radial flow) for two different height to diameter (H/T) ratio. The model is first validated for a Pitched Blade Turbine Downflow (PBTD) impeller with data available in the literature. A qualitative study of the flow patterns in stirred tanks shows good axial and radial flow profiles for the respective impellers. A decrease in H/T showed higher power consumption for both impellers. The power number (Np) for these impellers has also been calculated for two H/T ratio and Reynolds number (Re) in the range (2500 < Re < 1000. Np was found to be a strong function of liquid level for both impellers considered in the study. Interesting trends of variation of Np with Re have been observed which suggest there is a critical Re where the impellers have least power consum

It is well established that hearing loss can lead to widespread plasticity within the central auditory pathway, which is thought to contribute to the pathophysiology of audiological conditions such as tinnitus and hyperacusis. Emerging evidence suggests that hearing loss can also result in plasticity within brain regions involved in higher-level cognitive functioning like the prefrontal cortex; findings which may underlie the association between hearing loss and cognitive impairment documented in epidemiological studies. Using the 40-Hz auditory steady state response to assess sound-evoked gamma oscillations, we previously showed that noise-induced hearing loss results in impaired gamma phase coherence within the prefrontal but not the auditory cortex. To determine whether region-specific structural or molecular changes accompany this differential plasticity following hearing loss, in the present study we utilized Golgi-Cox staining to assess dendritic organization and synaptic density, as well as Western blotting to measure changes in synaptic signaling proteins in these cortical regions. We show that following noise exposure, impaired gamma phase coherence within the prefrontal cortex is accompanied by alterations in pyramidal cell dendritic morphology and decreased expression of proteins involved in GABAergic (GAD65) and glutamatergic (NR2B) neurotransmission; findings that were not observed in the auditory cortex, where gamma phase coherence remained unchanged post-noise exposure. In contrast to the noise-induced effects we observed in the prefrontal cortex, plasticity in the auditory cortex was characterized by an increase in NR2B suggesting increased excitability, as well as increases in the synaptic proteins PSD95 and synaptophysin within the auditory cortex. Overall, our results highlight the disparate effect of noise-induced hearing loss on auditory and higher-level brain regions as well as potential structural and molecular mechanisms by which hearing loss may contribute to impaired cognitive and sensory functions mediated by the prefrontal and auditory cortices.

Scleroderma, an autoimmune connective tissue disorder, leads to skin and tissue thickening. In this autoimmune disease condition, the defense mechanism works against the body itself and mistakenly attacks normal cells. Ayurveda links it to vatarakta, initially affecting tvak, rakta, and mamsa. Vata is primarily involved, but as the disease progresses, all doshas and dhatu get involved.A 45-year-old woman presented with skin hardening, skin depigmentation all over her body, limb stiffness, weakness, arthralgia, anorexia, constipation and burning in the chest region for the last three years.She was diagnosed with diffuse systemic sclerosis (SSc) but as per Ayurveda we can correlate with aamvata and vatarakta based on her lakshanas(symptoms).Ayurvedic treatment commenced with vardhamana pippali(Piper longum)rasayan, svedana karma, and virechan karma, followed by basti(enema) chikitsa (pathyadi kvath niruh basti) and oral ayurvedic medication viz., Manjisthadi kvatha, kaishora guggulu, Jatamansi(Nardostachys Jatamansi) churna, mishreya(Foeniculum vulgare) arka, dashang churna with water for local application and daily shamanarth panchtikta ghrit.After 8 weeks, depigmentation was reduced, new hair growth emerged, mild skin softening occured, chest burning, anorexia, sleeplessness was decreased and enhanced mental well-being.The treatment aimed to balance vitiated doshas and dhatu while alleviating symptoms, and enhancing overall well-being, demonstrating the efficacy of the holistic approach in managing scleroderma through Ayurveda.Auto-immune disorder, scleroderma, chronic complications, skin tightness, salt pepper depigmentation, sclerodactyly.

Since CD4+ T cells are essential for regulating adaptive immune responses and for long lasting mucosal protection, changes in CD4+ T cell numbers and function are likely to affect protective immunity. What remains unclear is whether CD4+ T cell composition and function in the female reproductive tract (FRT) changes as women age. Here we investigated the changes in the composition and function of CD4+ T cells in the endometrium (EM), endocervix (CX), and ectocervix (ECX) with aging. We observed a significant decrease in both the total number and percentage of CD4+ T cells in the EM with increasing age, particularly in the years following menopause. CD4+ T cells within the FRT predominantly expressed CD69. The proportion of CD69+CD4+ T cells increased significantly with increasing age in the EM, CX and ECX. The composition of T helper cell subsets within the EM CD4+ T cell population also showed age-related changes. Specifically, there was a significant increase in the proportion of Th1 cells and a significant decrease in Th17 and Treg cells with increasing age. Furthermore, the production of IFNγ by CD4+ T cells in the EM, CX, and ECX significantly decreased with increasing age upon activation. Our findings highlight the complex changes occurring in CD4+ T cell frequency, phenotype, and function within the FRT as women age. Understanding these age-related immune changes in the FRT is crucial for enhancing our knowledge of reproductive health and immune responses in women.

BackgroundLarge language models including GPT-4 (OpenAI) have opened new avenues in health care and qualitative research. Traditional qualitative methods are time-consuming and require expertise to capture nuance. Although large language models have demonstrated enhanced contextual understanding and inferencing compared with traditional natural language processing, their performance in qualitative analysis versus that of humans remains unexplored. ObjectiveWe evaluated the effectiveness of GPT-4 versus human researchers in qualitative analysis of interviews with patients with adult-acquired buried penis (AABP). MethodsQualitative data were obtained from semistructured interviews with 20 patients with AABP. Human analysis involved a structured 3-stage process—initial observations, line-by-line coding, and consensus discussions to refine themes. In contrast, artificial intelligence (AI) analysis with GPT-4 underwent two phases: (1) a naïve phase, where GPT-4 outputs were independently evaluated by a blinded reviewer to identify themes and subthemes and (2) a comparison phase, where AI-generated themes were compared with human-identified themes to assess agreement. We used a general qualitative description approach. ResultsThe study population (N=20) comprised predominantly White (17/20, 85%), married (12/20, 60%), heterosexual (19/20, 95%) men, with a mean age of 58.8 years and BMI of 41.1 kg/m2. Human qualitative analysis identified “urinary issues” in 95% (19/20) and GPT-4 in 75% (15/20) of interviews, with the subtheme “spray or stream” noted in 60% (12/20) and 35% (7/20), respectively. “Sexual issues” were prominent (19/20, 95% humans vs 16/20, 80% GPT-4), although humans identified a wider range of subthemes, including “pain with sex or masturbation” (7/20, 35%) and “difficulty with sex or masturbation” (4/20, 20%). Both analyses similarly highlighted “mental health issues” (11/20, 55%, both), although humans coded “depression” more frequently (10/20, 50% humans vs 4/20, 20% GPT-4). Humans frequently cited “issues using public restrooms” (12/20, 60%) as impacting social life, whereas GPT-4 emphasized “struggles with romantic relationships” (9/20, 45%). “Hygiene issues” were consistently recognized (14/20, 70% humans vs 13/20, 65% GPT-4). Humans uniquely identified “contributing factors” as a theme in all interviews. There was moderate agreement between human and GPT-4 coding (κ=0.401). Reliability assessments of GPT-4’s analyses showed consistent coding for themes including “body image struggles,” “chronic pain” (10/10, 100%), and “depression” (9/10, 90%). Other themes like “motivation for surgery” and “weight challenges” were reliably coded (8/10, 80%), while less frequent themes were variably identified across multiple iterations. ConclusionsLarge language models including GPT-4 can effectively identify key themes in analyzing qualitative health care data, showing moderate agreement with human analysis. While human analysis provided a richer diversity of subthemes, the consistency of AI suggests its use as a complementary tool in qualitative research. With AI rapidly advancing, future studies should iterate analyses and circumvent token limitations by segmenting data, furthering the breadth and depth of large language model–driven qualitative analyses.

Abstract Introduction People with low income have worse outcomes throughout the cancer care continuum; however, little is known about income and the diagnostic interval. We described diagnostic pathways by neighborhood income and investigated the association between income and the diagnostic interval. Methods This was a retrospective cohort study of colon cancer patients diagnosed 2007–2019 in Ontario using routinely collected data. The diagnostic interval was defined as the number of days from the first colon cancer encounter to diagnosis. Asymptomatic pathways were defined as first encounter with a colonoscopy or guaiac fecal occult blood test not occurring in the emergency department and were examined separately from symptomatic pathways. Quantile regression was used to determine the association between neighborhood income quintile and the conditional 50th and 90th percentile diagnostic interval controlling for age, sex, rural residence, and year of diagnosis. Results A total of 64,303 colon cancer patients were included. Patients residing in the lowest income neighborhoods were more likely to be diagnosed through symptomatic pathways and in the emergency department. Living in low‐income neighborhoods was associated with longer 50th and 90th‐percentile symptomatic diagnostic intervals compared to patients living in the highest income neighborhoods. For example, the 90th percentile diagnostic interval was 15 days (95% CI 6–23) longer in patients living in the lowest income neighborhoods compared to the highest. Conclusion These findings reveal income inequities during the diagnostic phase of colon cancer. Future work should determine pathways to reducing inequalities along the diagnostic interval and evaluate screening and diagnostic assessment programs from an equity perspective.

Patients with type 2 diabetes face an elevated risk of cardiovascular disease. This review centers on sodium-glucose cotransporter-2 (SGLT2) inhibitors, a class of drugs that, according to a growing body of evidence, may have major potential for managing cardiovascular disease in patients with type 2 diabetes. This review presents findings from multiple clinical trials suggesting that SGLT2 inhibitors can not only serve as preventive therapeutic agents but also play a role in the active management of heart failure. The discussion includes the mechanism of action of SGLT2 inhibitors, emphasizing that they enhance urinary glucose excretion, which could lead to improved glycemic control and contribute to metabolic shifts beneficial to cardiac function. Alongside these cardiometabolic effects, safety concerns and practical considerations for prescribing these agents are addressed, taking into account potential adverse effects such as genitourinary infections and diabetic ketoacidosis as well as the financial implications for patients. Despite these drawbacks, therapeutic indications for SGLT2 inhibitors continue to expand, including for kidney protection, although further research is necessary to fully understand the mechanisms driving the cardioprotective and kidney-protective effects of SGLT2 inhibitors. By synthesizing current knowledge, this review intends to inform and guide clinical decision-making, thereby enhancing cardiovascular disease outcomes in patients with type 2 diabetes.

Abstract Indirect Drive Inertial Confinement Fusion Experiments on the National Ignition Facility (NIF) have achieved a burning plasma state with neutron yields exceeding 170 kJ, roughly 3 times the prior record and a necessary stage for igniting plasmas. The results are achieved despite multiple sources of degradations that lead to high variability in performance. Results shown here, for the first time, include an empirical correction factor for mode-2 asymmetry in the burning plasma regime in addition to previously determined corrections for radiative mix and mode-1. Analysis shows that including these three corrections alone accounts for the measured fusion performance variability in the two highest performing experimental campaigns on the NIF to within error. Here we quantify the performance sensitivity to mode-2 symmetry in the burning plasma regime and apply the results, in the form of an empirical correction to a 1D performance model. Furthermore, we find the sensitivity to mode-2 determined through a series of integrated 2D radiation hydrodynamic simulations to be consistent with the experimentally determined sensitivity only when including alpha-heating.

Background: Distal radius fractures are the most common fractures of upper limb. It accounts nearly 15- 20% of all fractures. Many surgical modalities are available for treatment of the same. It ranges from closed reduction &K-wiring to open reduction & fixation using plates. Objectives: To compare the radiological outcomes of distal radius fractures treated with various operative interventions by parameters like radial inclination, radial height and radial tilt. To find out appropriate modality of management for all varieties of distal end radius fracture. Correlation of the functional and radiological outcomes of various operative modalities and its comparison between different types of fractures. Methods: 110 patients were called for functional and radiological assessment. All the cases were classified according to fracture patterns for comparison of x-rays of operated and opposite wrist joint to analyse the radiological and functional outcomes. Result: Overall 110 patients were operated with slightly male preponderance, 62 male patients (56%) and 48 female patients (44%).Plating had superior outcomes followed by K-wiring. Conclusion: Distal radius fractures are increasingly common. Goal of treating distal radius fracture should be to achieve a painless, congruous wrist joint with anatomic reduction of the fracture along with faster and optimum recovery of functions which can be effectively assessed by radiological parameters.

inadequate intake leads to haematological and neurological disorders. Objective:To determine the symptoms and signs associated with Vitamin B12 deficiency. Method: A case control study was conducted at the medicine department of tertiary care hospital. Patients visiting hospital with serum Vitamin B12 level below 200pg/ml were labelled as cases and more than 200 pg/ml were labelled as controls, irrespective of signs and symptoms of Vitamin B 12 deficiency.Controls were matched for age to minimize confounding. 160 cases and 160 controls were selected. Pretested semi structured questionnaire was used to identify signs and symptoms of Vitamin B12 deficiency among cases and controls. Chi square test was applied for each symptom between cases and control, of which 10 were significant (p0.05).Conclusion: Presence of knuckle pigmentation, poor memory, tingling and numbness, and dizziness can be defined as hallmarks of Vitamin B12 deficiency and can be used to predict and start Vitamin B12 supplementation.

Objective: To determine the appropriateness of ophthalmology recommendations from an online chat-based artificial intelligence model to ophthalmology questions. Patients and Methods: Cross-sectional qualitative study from April 1, 2023, to April 30, 2023. A total of 192 questions were generated spanning all ophthalmic subspecialties. Each question was posed to a large language model (LLM) 3 times. The responses were graded by appropriate subspecialists as appropriate, inappropriate, or unreliable in 2 grading contexts. The first grading context was if the information was presented on a patient information site. The second was an LLM-generated draft response to patient queries sent by the electronic medical record (EMR). Appropriate was defined as accurate and specific enough to serve as a surrogate for physician-approved information. Main outcome measure was percentage of appropriate responses per subspecialty. Results: For patient information site-related questions, the LLM provided an overall average of 79% appropriate responses. Variable rates of average appropriateness were observed across ophthalmic subspecialties for patient information site information ranging from 56% to 100%: cataract or refractive (92%), cornea (56%), glaucoma (72%), neuro-ophthalmology (67%), oculoplastic or orbital surgery (80%), ocular oncology (100%), pediatrics (89%), vitreoretinal diseases (86%), and uveitis (65%). For draft responses to patient questions via EMR, the LLM provided an overall average of 74% appropriate responses and varied by subspecialty: cataract or refractive (85%), cornea (54%), glaucoma (77%), neuro-ophthalmology (63%), oculoplastic or orbital surgery (62%), ocular oncology (90%), pediatrics (94%), vitreoretinal diseases (88%), and uveitis (55%). Stratifying grades across health information categories (disease and condition, risk and prevention, surgery-related, and treatment and management) showed notable but insignificant variations, with disease and condition often rated highest (72% and 69%) for appropriateness and surgery-related (55% and 51%) lowest, in both contexts. Conclusion: This LLM reported mostly appropriate responses across multiple ophthalmology subspecialties in the context of both patient information sites and EMR-related responses to patient questions. Current LLM offerings require optimization and improvement before widespread clinical use.

Abstract Antibiotic resistance is recognised as one of the biggest global threats to human and animal health. Understanding the influence of antibiotics on the canine microbiome is important to know the potential mid-to-long term effects on dysbiosis and mitigate side-effects such as antibiotic-associated diarrhoea. In this study, metronidazole was prescribed to 22 dogs for suspected giardiasis after exhibiting gastrointestinal symptoms such as diarrhoea and/or vomiting. Faecal samples were collected before, during seven days of treatment, and six months post-cessation. Faecal microbiota was assessed with 16S rRNA sequencing. Shannon diversity was reduced for up to three days after the treatment ended, and an altered community persisted for four to six weeks. All dogs recovered to a similar microbiome composition as pre-treatment. Immediately after receiving metronidazole, an increase in the relative abundance of the genera Lactobacillus, Bifidobacterium, and Enterococcus was observed. This may be due to antibiotic resistance commonly exhibited by these organisms. One-to-two weeks post-cessation, several other genera that were sensitive to the antibiotic recovered in abundances, with taxa belonging to the Erysipelotrichaceae family particularly driving composition change. Many of the bacteria initially reduced were associated with carbohydrate fermentation. This suggests scope exists to explore interventions to augment gastrointestinal health and support the re-establishment of the microbiome.

Viral vector mediated gene therapies for neurodegenerative and neurodevelopmental conditions that require neurosurgical administration continue to expand. We systematically reviewed the National Institutes of Health (NIH) ClinicalTrials.gov database to identify all clinical trials studying in-vivo viral vector mediated gene therapies targeted to the CNS for neurodegenerative and neurodevelopmental diseases. We isolated studies which delivered therapies using neurosurgical approaches: intracisternal, intraventricular, and/or intraparenchymal. Clinical trials primarily registered in international countries were included if they were referenced by an NIH registered clinical trial. We performed a scoping review to identify the preclinical studies that supported each human clinical trial. Key preclinical and clinical data were aggregated to characterize vector capsid design, delivery methods, gene expression profile, and clinical benefit. A total of 64 clinical trials were identified in active, completed, terminated, and long-term follow-up stages. A range of CNS conditions across pediatric and adult populations are being studied with CNS targeted viral vector gene therapy, including Alzheimer's disease, Parkinson's disease, AADC deficiency, sphingolipidoses, mucopolysaccharidoses, neuronal ceroid lipofuscinoses, spinal muscular atrophy, adrenoleukodystrophy, Canavan disease, frontotemporal dementia, Huntington's disease, Rett syndrome, Dravet syndrome, mesial temporal lobe epilepsy, and glutaric acidemia. Adeno-associated viral vectors (AAVs) were utilized by the majority of tested therapies, with vector serotypes, regulatory elements, delivery methods, and vector monitoring varying based on the disease being studied. Intraparenchymal delivery has evolved significantly, with MRI-guided convection-enhanced delivery established as a gold standard method for pioneering novel gene targets.

IntroductionIntracranial hemorrhages present across a spectrum of clinical phenotypes, with many patients transferred across hospitals to access higher levels of neurocritical care. We sought to characterize patient dispositions following intracranial hemorrhage and examine disparities associated with interhospital transfers.MethodsUsing the Healthcare Cost and Utilization Project database, we mapped and identified factors influencing the likelihood of patient transfers and receipt of specialist interventional procedures following intracranial hemorrhage.ResultsOf 11,660 patients with intracranial hemorrhage, 59.4% had non-traumatic and 87.5% single compartment bleeds. After presentation, about a quarter of patients were transferred to another facility either directly from the ED (23.0%) or after inpatient admission (1.8%). On unadjusted analysis, patients who were white, in the upper income quartiles, with private insurance, or resided in suburban areas were more frequently transferred. After adjusting for patient-and hospital-level variables, younger and non-white patients had higher odds of transfer. Hospital capabilities, residence location, insurance status, and prior therapeutic relationship remained as transfer predictors. Transferred patients had a similar hospital length of stay compared to admitted patients, with 43.1% having no recorded surgical or specialist interventional procedure after transfer.DiscussionOur analysis reveals opportunities for improvement in risk stratification guiding transfers, as well as structural challenges likely impacting transfer decisions.

This study evaluates the biocontrol efficacy of three bacterial strains (Pseudomonas fluorescens DTPF-3, Bacillus amyloliquefaciens DTBA-11, and Bacillus subtilis DTBS-5) and two fungal strains (Trichoderma harzianum Pusa-5SD and Aspergillus niger An-27) antagonists, along with their combinations at varying doses (5.0, 7.5, and 10.0 g/kg of seeds), against wheat powdery mildew. The most effective dose (10 g/kg seeds) was further analyzed for its impact on induced resistance and plant growth promotion under greenhouse conditions. The study measured defense enzyme activities, biochemical changes, and post-infection plant growth metrics. All tested microbial antagonists at 10 g/kg significantly reduced PM severity, with B. subtilis strain DTBS-5 outperforming others in reducing PM severity and achieving the highest biocontrol efficacy. It was followed by B. amyloliquefaciens strain DTBA-11 and P. fluorescens strain DTPF-3, with the fungal antagonists showing no significant effect. Wheat crops treated with B. subtilis strain DTBS-5 exhibited substantial increases in defense-related enzyme activities and biochemicals, suggesting an induced resistance mechanism. The study found a 45% increase in peroxidase (POD) activity, a 50% increase in catalase (CAT) activity, a 30% increase in phenolic content, and a 25% increase in soluble protein content in the wheat plants treated with microbial antagonists. The study highlights the effectiveness of microbial antagonists, particularly B. subtilis strain DTBS-5, in managing wheat PM through biocontrol, induced resistance, and enhanced plant growth, offering a sustainable alternative to chemical treatments.

ABSTRACT Introduction Community‐based cohort studies of HIV seroconversion can identify important avenues for enhancing HIV prevention efforts in the era of pre‐exposure prophylaxis (PrEP). Within individuals, one can assess exposure and outcome variables repeatedly and with increased certainty regarding temporal ordering. This cohort study examined the association of several risk factors with subsequent HIV seroconversion. Methods We report data from a 4‐year study (2017−2022) of 6059 HIV seronegative sexual and gender minority individuals who have sex with men who had indications for‐, but were not using‐, PrEP at enrolment. Participants completed repeat exposure assessments and self‐collection of biospecimens for HIV testing. We examined the roles of race and ethnicity, socio‐economic status, methamphetamine use and PrEP uptake over the course of follow‐up in relation to HIV seroconversion. Results Over 4 years, 303 of the participants seroconverted across 18,421 person‐years (incidence rate = 1.64 [95% CI: 1.59−1.70] per 100 person‐years). In multivariable discrete‐time survival analysis, factors independently associated with elevated HIV seroconversion risk included being Black/African American (adjusted risk ratio [aRR]: 2.44, 1.79−3.28), Hispanic/Latinx (1.53, 1.19−1.96), housing instability (1.58, 1.22−2.05) and past year methamphetamine use (3.82, 2.74−5.33). Conversely, time since study enrolment (24 vs. 12 months, 0.67, 0.51−0.87; 36 months, 0.60, 0.45−0.80; 48 months, 0.48, 0.35−0.66) and higher education (master's degree or higher vs. less than or equal to high school, 0.36, 0.17−0.66) were associated with reduced seroconversion risk. Compared to non‐PrEP users in the past 2 years without a current clinical indication, those who started PrEP but then discontinued had higher seroconversion risk, irrespective of clinical indication (3.23, 1.74−6.46) or lack thereof (4.30, 1.85−9.88). However, those who initiated PrEP in the past year (0.14, 0.04−0.39) or persistently used PrEP in the past 2 years (0.33, 0.14−0.74) had a lower risk of seroconversion. Of all HIV seroconversions observed during follow‐up assessments (12, 24, 36 and 48 months), methamphetamine was reported in the 12 months prior 128 (42.2%) times (overall). Conclusions Interventions that acknowledge race and ethnicity, economic variables such as education and housing instability, and methamphetamine use are critically needed. Not only are interventions to engage individuals in PrEP care needed, but those that retain them, and re‐engage those who may fall out of care are essential, given the exceptionally high risk of seroconversion in these groups.

Abstract Background Currently recommended cancer screening programs address only part of the overall population cancer burden. Even populations deemed high‐risk for certain individual cancers experience a considerable potential burden of other cancers. However, few published cancer screening trials report the incidence of untargeted cancers. Methods The National Lung Screening Trial (NLST), initiated in 2002–2004, was a randomized controlled trial of lung cancer screening in adults with ≥30 pack‐years of smoking. Active follow‐up for incident invasive cancers continued through 2009. Results Among 53,229 NLST subjects (median follow‐up 6.5 years after randomization), the incidence of lung cancer was 615 per 100,000 person‐years (32% of 6142 overall first primary incident invasive cancers), and that of non‐lung cancer was 1327 per 100,000 (68%). Non‐lung cancer incidence exceeded that for lung cancer in all 5‐year age categories and all quintiles of smoking pack‐years. Besides lung cancer, the most common cancers were prostate, breast, colon/rectum, bladder, and head/neck; 23% were smoking‐related cancers, and 54% were cancer types lacking recommended population‐based screening modalities (32% excluding prostate). Non‐lung cancer comprised 48% of 1793 cancer deaths. Conclusions In the NLST, only 32% of first primary cancer incidence after study entry was lung, compared with 68% non‐lung. Even in a population at high risk for lung cancer, a single‐cancer screening test misses most cancers. Thus, in combination with existing single‐cancer screening modalities, multi‐cancer screening tests—which address many of the incident non‐lung cancers in this trial—have potential to address a currently inaccessible portion of cancer morbidity and mortality.

Abstract Objectives With the legalization of cannabis in New Jersey on April 21, 2022, including the licensing of cannabis dispensaries, concerns have arisen about potential adverse events related to cannabis use. Here, we explore temporal trends and risk factors for cannabis‐related harm in both adult and pediatric cannabis‐related visits at a tertiary care academic institution. Methods We performed a retrospective chart review and temporal trend analysis via the electronic health record from May 1, 2019 to October 31, 2022, covering 2 years before, and 6 months after, cannabis legalization in New Jersey. The pediatric charts identified were analyzed for root causes of adverse events, and changes in the frequency of specific unsafe practices since cannabis legalization were tracked. Results We found that adult cannabis ED‐related visits significantly increased during the COVID‐19 pandemic and remained higher than pre‐pandemic levels for the remainder of the study periods, without a significant change upon legalization. Pediatric rates of cannabis‐related ED visits did not vary significantly during the study period. The vast majority of visits for children aged 0–12 years were related to accidental cannabis exposures—often a household member's edibles—whereas most visits for older children stemmed from intentional cannabis use. Conclusion This project highlights the unintended consequences of wider cannabis access in New Jersey. Notably, cannabis use increased even before its legalization, presumably in response to the COVID‐19 pandemic and its attendant mental health effects. Rates of cannabis use disorder and its highlight of other concurrent psychiatric disorders are important topics for both clinicians and lawmakers to consider.

Background: Avascular necrosis (AVN) is a common occurrence following solid organ transplant (SOT) due to chronic steroid use. We report on three shoulders of humeral head hemiarthroplasty (HHA) in the setting of AVN after SOT. This topic is an important issue to study as there is limited literature on AVN requiring shoulder arthroplasty following SOT. As the prevalence of SOT continues to rise, it is important to study this population before making guidelines in the future. Case presentations: In one shoulder, a 51-year-old male presented with AVN of the left shoulder three years after undergoing a lung transplant and taking 5mg oral prednisone daily. In the second and third shoulder, a 61-year-old female presented with AVN of bilateral shoulders two years after undergoing a kidney transplant and taking 7.5mg oral prednisone daily. All three shoulders went on to have HHA with improved outcomes after surgery at a mean follow-up of 4.6 years. Conclusion: Shoulder arthroplasty is safe and effective for patients with avascular necrosis after a SOT.

Summary: Background: Syringe services programmes (SSPs) are an evidence-based strategy to reduce infectious diseases and deliver overdose prevention interventions for people who use drugs. They face regulatory, administrative, and funding barriers that limit their implementation in the US, though the federal government recently began providing funding to support these efforts. In this study we aim to understand whether the organisational characteristics of SSPs are associated with the provision of syringe and other overdose response strategies. Methods: We examine four outcomes using the National Survey of Syringe Services Programs (NSSSP) (N = 472): syringe distribution, naloxone distribution, fentanyl test strip (FTS) availability, and buprenorphine implementation. These outcomes are assessed across three organizational categories of SSPs—those operated by public health departments (DPH), community-based organizations (CBOs) with government funding, and CBOs without government funding—while adjusting for community-level confounders. Findings: The proportion of SSPs by organizational category was 36% DPH, 42% CBOs with government funding, and 22% CBOs without government funding. Adjusting for community-level differences, we found that CBO SSPs with government funding had significantly higher provision of all four syringe and overdose response services as compared to DPH SSPs and across three of the four services as compared to CBO SSPs without government funding. CBO SSPs without government funding still had significantly higher provision of three of the four services as compared to programmes maintained by the DPH. Interpretation: CBO SSPs have strong potential to expand overdose response services nationally, particularly if provided with sustained and adequate funding. Communities should aim to provide funding that does not hinder SSP innovation so they can remain flexible in responding to local needs. Funding: This study was supported by Arnold Ventures (20-05172).

Connections are important elements of precast structures as they introduce discontinuity between the elements affecting strength and stiffness. In the present study, locally available SSWM 40 × 32 is explored as a strengthening material for precast beam column connections. Experiments are conducted on test specimens to evaluate their performance under monotonic vertical loading applied using hydraulic actuator. Various wet precast connections with different location of connections and detailing of beam column reinforcement are considered for this investigation. Two novel SSWM configurations like enclosure of junction with box shape strip and diagonal strips of SSWM are used for strengthening of precast beam column connections. Experimental study is conducted on twelve test specimens to measure their performance in terms of ultimate load capacity, displacement profile, ductility, failure pattern and energy dissipation. SSWM strengthened specimens show 8–43 % improvement in load carrying capacity along with better ductility and energy dissipation. For the precast connections at junction, box shape SSWM strip configuration is recommended while for the connection at the face of column, diagonal strip configuration of SSWM is recommended. Overall, SSWM can be effectively used for strengthening of precast connections.

Background: Total knee arthroplasty (TKA) has become a common surgical intervention for human immunodeficiency virus (HIV)-positive patients who develop osteonecrosis of the knee. This paper summarized existing literature regarding the outcomes of HIV-positive patients undergoing TKA in 4 subsections: (1) complications; (2) survivorship analyses; (3) patient-reported outcomes; and (4) infections. Methods: A review of PubMed was performed, searching for articles focused on HIV-positive patients undergoing TKA. There were 6 reports selected, containing 4765 HIV-positive patients, and data regarding the various domains was tabulated and analyzed. To ensure article quality, a methodology score and level of evidence were determined for selected studies. Results: Complication rates for HIV-positive patients were low, with a larger study reporting that 7.8% of HIV-positive patients developed a complication in comparison to 8% of HIV-negative patients. Survivorship analyses showed similar results, with a study reporting implant survivorship of 98% for HIV-positive and 99% for HIV-negative patients. There were no differences in patient-reported outcomes; HIV-positive patients improved from baseline with respect to the mean Knee Society objective and mean Knee Society functional scores, and the University of California, Los Angeles self-reported activity levels. The infection rate for HIV-positive patients was low, with a larger database study reporting that 0.6% of HIV-positive patients developed a wound infection in comparison to 0.4% of HIV-negative patients. Conclusions: A TKA is an effective treatment for HIV-positive patients who develop osteonecrosis of the knee. Results showed similar patient-reported outcomes, implant survivorships, revisions, and complication rates when compared to non-HIV patients.

Syringe Services Programs (SSPs) provide evidence-based services like drug use equipment to prevent infectious disease, overdose prevention education, and naloxone distribution to people who use drugs (PWUD). However, inadequate funding threatens provision of these interventions. This study aimed to document how the current funding landscape impacted determinants of SSP implementation, particularly describing financial and staffing barriers, facilitators, and proposed strategies, using qualitative methods informed by three implementation research frameworks. We interviewed 20 leaders of SSPs in the United States using a semi-structured interview guide. Participants described how structural stigma against PWUD led to insufficient and restrictive funding, and burdensome reporting for SSPs. This resulted in harming program implementation outcomes like reach, fidelity, and sustainability. Inadequate funding also led to insufficient staffing and subsequent staff stress, burnout, and turnover. Taken together, these barriers threatened the implementation of evidence-based interventions that SSPs provided, ultimately harming their ability to effectively address health outcomes like infectious disease transmission and opioid overdose mortality within their communities. Interviewees described how upstream policy strategies like political advocacy might address structural stigma at the federal level. Participants also highlighted state-level efforts like harm reduction–centered funding, technical assistance and capacity-building, and clearinghouse programs that may facilitate better implementation and health outcomes. A more robust understanding of the relationship between financial barriers, facilitators, and strategies on implementation and health outcomes represents a novel and vital area of research within harm reduction literature.

Purpose: Trabeculectomy surgery is a commonly performed procedure for treatment of glaucoma. While the goal is to lower intraocular pressure, over-filtration may cause hypotony with ocular structural changes and vision loss. Observations: A 53-year-old woman with primary open-angle glaucoma was referred to our service for further evaluation. The patient previously underwent trabeculectomy 9 years prior and was found to have a cataract and hypotony maculopathy in the right eye. Treatment options included cataract surgery alone, bleb revision alone, or combined cataract extraction and bleb revision. Biometry revealed corneal astigmatism in the right eye, and significant disparity in axial length between the two eyes. Since the axial length and corneal astigmatic changes were presumed to be at least partially reversible, measurements from the non-operative left eye influenced the lens selection for the hypotonous right eye. The patient underwent combined phacoemulsification and bleb revision. While IOP increased and hypotony was partly reversed, there was hyperopic and astigmatic refractive surprise after surgery.The patient subsequently underwent intraocular lens exchange using biometric values of the previously hypotonous eye and met the target post-operative refractive goal. Conclusions and importance: This case demonstrates changes to the axial length and ocular structure following longstanding hypotony maculopathy may be permanent, even after restoration of normotensive intraocular pressure.

Background: Resection arthroplasty is an option for patients with multiple previous failed arthroplasties due to periprosthetic joint infection. Case details: We report on 3 patients (4 shoulders) who were resected and followed for a decade on average. These patients had postoperative ASES scores in alignment with their preoperative baseline and a mean forward elevation of 155°. All patients reported being satisfied with their shoulder function at final follow-up. Conclusion: Resection arthroplasty is an option for patients with risk factors for failed shoulder arthroplasty. While outcomes are moderate, they can be satisfactory if patients are counseled beforehand about realistic expectations.

A 33-year-old female was admitted for community-acquired pneumonia. On presentation, she was tachypneic and tachycardic and leukocytosis at 28,900/µL. Chest imaging showed dense consolidation on the right upper lobe. Due to refractory worsening respiratory failure, she was intubated with mechanical ventilation. Initial bronchoscopy with culture data was negative. Extracorporeal membrane oxygenation was pursued on the fourth day. Repeat bronchoscopy revealed targetoid ulcerative lesions with erythema in the right middle, lower lobes and left lower lobe. We describe a case of herpes simplex virus pneumonia in an immunocompetent patient that occurred in the setting of acute bacterial infection.

Fabric defects can significantly impact the quality of a textile product. By analyzing the types and frequencies of defects, manufacturers can identify process inefficiencies, equipment malfunctions, or operator errors. Although deep learning networks are accurate in classification applications, some defects may be subtle and difficult to detect, while others may have complex patterns or occlusions. CNNs may struggle to capture a wide range of defect variations and generalize well to unseen defects. Discriminating between genuine defects and benign variations requires sophisticated feature extraction and modeling techniques. This paper proposes a residual network-based CNN model to enhance the classification of fabric defects. A pretrained residual network, ResNet50, is fine-tuned to classify fabric defects into four categories: holes, objects, oil spots, and thread errors on the fabric surface. The fine-tuned network is further optimized via cuckoo search optimization using classification error as a fitness function. The network is systematically analyzed at different layers, and the investigation of classification results are reported using a confusion matrix and classification accuracy for each class. The experimental results confirm that the proposed model achieved superior performance with 95.36% accuracy and a 95.35% F1 score for multiclass classification. In addition, the proposed model achieved higher accuracy with similar or fewer trainable parameters than traditional deep CNN networks.

Parkinson’s Disease (PD) has been found to cause force control deficits in upper and lower limbs. About 50% of patients with advanced PD develop a debilitating symptom called freezing of gait (FOG), which has been linked to force control problems in the lower limbs, and some may only have a limited response to the gold standard pharmaceutical therapy, levodopa, resulting in partially levodopa-responsive FOG (PLR-FOG). There has been limited research on investigating upper-limb force control in people with PD with PLR-FOG, and without FOG. In this pilot study, force control was explored using an upper-and-lower-limb haptics-enabled robot in a reaching task while people with PD with and without PLR-FOG were on their levodopa medication. A healthy control group was used for reference, and each cohort completed the task at three different levels of assistance provided by the robot. Similar significant proportional force control deficits were found in the upper and lower limbs in patients with PLR-FOG versus those without FOG. Some aspects of force control were found to be retained, including an ability to increase or decrease force in response to changes in resistance while completing a reaching task. Overall, these results suggest there are force control deficits in both the upper and lower limbs in people with PLR-FOG.

Introduction: Total Intravenous Anaesthesia (TIVA) with propofol is gaining acceptance for day care surgeries due to its advantages over inhalational agents. Opioids administered as premedication are known to enhance the hypnotic effect of propofol and provide intraoperative and postoperative analgesia. Aim: To compare the effectiveness of Nalbuphine and Fentanyl for postoperative analgesia in short surgical procedures. Materials and Methods: In present double-blinded randomised controlled trail conducted in the Department of Anaesthesia at the Gujarat Cancer and Research Institute, Ahmedabad, Gujarat, India, 60 patients aged 18 to 60 years, classified as American Soceity of Anaesthesiologists (ASA) Grade-I or II, and scheduled for elective short surgical procedures under TIVA were randomly assigned to two groups. Group N received Nalbuphine 0.05 mg/kg, and control Group F received 0.001 mg/ kg Fentanyl intravenously before induction. Parameters studied included pain scores, first rescue analgesia, haemodynamics, and side effects. Statistical analysis was performed using the Statistical Package for Social Sciences (SPSS Inc., Chicago, IL, USA, version 19.0 for Windows). Parametric data were analysed using paired and unpaired t-tests. Results: Data from a total of 60 patients (Group N mean age: 46.9±9.96 years and Group F mean age: 46.6±10.44 years) were collected and analysed. Both groups were comparable in terms of age, Body Mass Index (BMI), mean duration of surgery, and type of surgery (p > 0.05). Pain scores on the Visual Analogue Scale (VAS) were not significant upto 15 minutes after surgery, but thereafter, the VAS score was significantly lower in the Nalbuphine group (p-value < 0.05). Intraoperative episodes of significant hypotension were observed only in the Fentanyl group (p-value < 0.05). The total dose of propofol required was significantly lower in the Fentanyl group (p-value < 0.001). The time to the first rescue analgesia requirement (in minutes) was significantly shorter in the Fentanyl group (32.83±28.43) compared to the Nalbuphine group (56.37±25.31). Side effects such as postoperative sedation, nausea, and vomiting were observed in the Fentanyl group (p-value >0.05). Conclusion: Nalbuphine provided superior postoperative analgesic effects compared to Fentanyl when used as an analgesic component in TIVA. Postoperatively, pain scores were lower, and the time to the first rescue analgesia was longer in the Nalbuphine group.

Development of de novo donor-specific anti-HLA antibody (dnDSA) is associated with poor graft survival in adults. However, there is a paucity of data about its prevalence and outcome in Indian children. We retrospectively assessed the proportion and spectrum of dnDSA and its outcome on antibody-mediated rejection (ABMR) and graft function. Children ≤18 years who were transplanted between November 2016 and October 2019 were included in this study. Pretransplant donor-specific antibody (DSA) was screened by complement-dependent cytotoxicity, flow cytometry crossmatch, and single antigen bead (SAB) class I and II by Luminex platform. Either antithymocyte globulin or basiliximab was used as induction. Tacrolimus, mycophenolate, and prednisolone were used for the maintenance of immunosuppression. SAB screening was done at 1, 3, 6 months, and yearly in seven children and at the time of acute graft dysfunction in eight. Mean fluorescence intensity ≥1000 was considered positive. Protocol biopsies were done at 3, 6, and 12 months and annually thereafter in seven children. Fifteen children, all males with a median age (interquartile range) of 13 years (11; 15.5) were analyzed. Only one child had pretransplant DSA who developed dnDSA posttransplant. Overall, 8 (53%) developed dnDSA over a median follow-up of 18 months. Seven (87%) had Class II, one Class I and 3 (37%) both Class I and II. Six had dQ and two had DR. All children with dnDSA had ABMR, of these two had subclinical rejection. DSAs persisted despite treatment, though graft function improved. Children with DSA and ABMR had lower graft function than those without DSA. The proportion of dnDSA was high in our study, majority against DQ. The detection of dnDSA prompted early diagnosis and treatment of ABMR.

Introduction: The experience of pain during the neonatal period has short and long-term consequences. The Revised Premature Infant Pain Profile (PIPP-R) is a globally accepted and validated tool for assessing pain in neonates. Adequate pain management measures can be implemented using the PIPP-R, even in the absence of consultants. Aim: To assess the agreement among healthcare providers and laypersons in scoring the PIPP-R. Materials and Methods: A cross-sectional study was conducted at Shree Krishna Hospital, a rural Tertiary Care Teaching Hospital in central Gujarat, India. The duration of the study was one year and six months, from January 2021 to June 2022. The study included 12 volunteers from various fields, such as consultant neonatologists, first year postgraduate students in Department of Paediatrics, neonatal nurses, social workers, Bachelor of Medicine, Bachelor of Surgery (MBBS) interns, and mothers of newborns. A neonatology consultant provided training on the PIPP-R scoring system using handouts and a presentation. The volunteers then evaluated 100 prerecorded videos of newborns undergoing painful procedures. Agreement between volunteers for the total PIPP-R score and its subcomponents was assessed using Bland-Altman analysis and Cohen’s Kappa statistics. Results: A total of 100 videos of newborns (51 girls, 49 boys) undergoing painful procedures were evaluated for the PIPP-R score. The mean age, gestational age, and birth weight of the newborns were 2.21±1.55 days, 37±2.44 weeks, and 2.56±0.72 kg, respectively. The procedures included heel prick for Random Blood Sugar (RBS) (44%), intravenous sampling/insertion (34%), and intramuscular vitamin K injection (22%). The mean difference with 95% Confidence Limits (CL) of total PIPP-R scores between the two consultants (neonatologists) was -0.640 (-5.196, 3.916). The length of the CL was -9.112, which fell outside the defined CL of 4.2 (20% of the total score), indicating unacceptable agreement between the two consultants. Similarly, agreement between each consultant and any of the other participants, including residents, nurses, interns, mothers, and social workers, regarding the total PIPP-R score, as well as its subcomponents, was also deemed unacceptable. Conclusion: The present study concluded that the inter-rater reliability of the PIPP-R score and its subcomponents was unacceptable between consultants and with any of the other participants.

Introduction The global burden associated with common mental disorders is high, especially for people living in low resource settings. Although psychosocial interventions delivered by locally available lay or community health workers are effective, mechanisms of intervention response are poorly understood. One of the greatest barriers is that psychosocial interventions are administered as complex, multi-component “packages of care”. Objectives Our aim is to systematically review all the randomized controlled trials (RCTs) that have tested the efficacy of psychosocial interventions delivered through the task shifting modality to treat people suffering from common mental disorders (depression, anxiety, and related somatic complaints) in low resource settings, dismantle the intervention protocols creating a taxonomy of active intervention components, and re-evaluate their efficacy. Methods We will use the component network meta-analysis (cNMA) methodology. The major benefit of cNMA is the possibility to disentangle intervention components and explore their effectiveness separately or in various combinations (even in disconnected networks). cNMA increases statistical power by combining direct and indirect comparisons while fully respecting the randomized structure of the evidence. According to the additive cNMA model which we will implement, adding a component “c” to a composite intervention “X” will lead to an increase (or decrease) of the effect size by an amount only dependent on “c”, and not on “X”. We will denote the corresponding component specific incremental standard mean difference (iSMD) so that iSMDc = SMD(X+c) v. (X). Combining these component-specific iSMDs will allow the estimation of SMD between any two composite interventions. Results A network of comparisons and a hierarchy that includes all intervention components expressed as iSMD, indicating the added benefit of adding a component to an intervention, will be presented. By selecting the most effective components it will be possible to outline a novel task shifting psychosocial intervention to be tested in future RCTs. Conclusions These findings will set the basis for further investigations in the field of precision medicine. This project is funded by the European Union’s HORIZON EUROPE research programme under grant agreement No 101061648. Disclosure of Interest None Declared

Introduction Generalized anxiety disorder (GAD) is one of the most common mental disorders in adults. Psychotherapies are among the most recommended treatment choices for GAD, but which should be considered as first-line treatment still needs to be clarified. Objectives To examine the most effective and accepted psychotherapy for GAD both in the short and long-term, via a network meta-analysis. Methods We searched MEDLINE, Embase, PsycINFO, and the Cochrane Register of Controlled Trials – CENTRAL, from database inception to January 1st, 2023, to find randomized controlled trials (RCTs) of psychotherapies for GAD. Eight psychotherapies (behaviour therapy, cognitive-behaviour therapy, cognitive restructuring, psychoeducation, psychodynamic therapy, relaxation therapy, supportive psychotherapy, and third-wave CBTs) were compared with each other and two control conditions (treatment as usual, waiting list). We followed Cochrane standards when extracting data and assessing data quality and used PRISMA guidelines for the reporting. We conducted random-effects model pairwise and network meta-analyses. We assessed risk of bias of individual studies through the second version of the Cochrane’s Risk of Bias tool and used the Confidence in Network Meta-Analysis (CINeMA) to rate certainty of evidence for meta-analytical results. Severity of GAD symptoms and acceptability of the psychotherapies were our outcomes of interest. Results We analysed data from 66 RCTs. Effect size estimates on data from 5,597 participants suggest third wave cognitive-behavioural therapies (standardized mean differences [SMDs] =-0.78; 95%CI=-1.19 to -0.37; certainty=moderate), cognitive-behavioural therapy (CBT) (SMD=-0.68; 95%CI=-1.05 to -0.32 certainty=moderate), and relaxation therapy (SMD=-0.54; 95%CI=-1.04 to -0.05; certainty=low) reduced generalized anxiety symptoms more than treatment as usual (TAU). Relative risks for all-cause discontinuation signalled no differences compared with TAU for all psychotherapies. When excluding studies at high risk of bias, relaxation therapy lost its superiority over TAU. When considering anxiety severity at three to twelve months after completion of the intervention only CBT remained significantly more efficacious than TAU (SMD=-0.58; 95%CI=-0.93 to -0.23). Image: Conclusions Given the evidence for both acute and long-term efficacy, CBT may represent the reasonable first-line psychological treatment for GAD. Third-wave CBT and relaxation therapy have short-term efficacy and may also be offered. Results from this investigation should inform patients, clinicians, and guidelines. This project is funded by the European Union’s HORIZON EUROPE research programme under grant agreement No 101061648. Disclosure of Interest None Declared

IntroductionPre-exposure Prophylaxis (PrEP) is a daily pill aimed at reducing HIV transmission risk when taken as prescribed. It’s highly recommended for high-risk Men who have sex with Men (MSM). This study aimed to assess PrEP awareness and willingness to use it among Rwandan MSM, a critical aspect given PrEP’s proven effectiveness. The findings are expected to inform policy decisions and further advance the implementation of PrEP strategies.MethodsThis is a cross-sectional study design that utilized a web-based survey conducted between April and June 2019 to assess awareness and willingness to use PrEP among sexually active MSM in Rwanda. A snowball sampling technique was used to recruit participants via social media such as WhatsApp and e-mail. Eligibility criteria included being sexually active, aged ≥18 years, self-identifying as MSM, residing in Rwanda, self-reported engagement in receptive or insertive anal sex in the last 12 months, and self-reported HIV-negative serostatus. We assessed two primary outcomes: PrEP awareness (having ever heard of PrEP) and willingness to use PrEP within one month of completing the survey. Multivariable logistic regression was performed to identify participant characteristics associated with PrEP awareness and willingness to use it.ResultsOut of 521 participants, the majority (73%) demonstrated awareness of PrEP. Factors linked to PrEP awareness included residing outside the capital, Kigali, being in the 18–29 age group, having higher education levels, perceiving a benefit from PrEP, and engaging in vaginal sex with a woman while using a condom in the last year. Additionally, 96% of participants expressed a strong willingness to use PrEP.ConclusionRwandan MSM exhibits a high level of PrEP awareness, notably associated with factors like location, age, education, perceived benefits, and condom use. The study also revealed a strong willingness to use PrEP, indicating promising prospects for its adoption among this group. These findings highlight the need for targeted awareness campaigns, personalized interventions, and comprehensive sexual health education to promote PrEP adoption and strengthen HIV prevention efforts among Rwandan MSM.

Being a pulse crop, green gram has huge scope in crop improvement in terms of productivity and other yield related parameters. Genetic variability is a preferable option for breeders in breeding programme for varietal development programme and others crop improvement aspect. The present investigation was framed to create the variability in mung bean var. GAM 8 during the seedling period through gamma (γ) irradiation. The significant variation was observed in germination percentage and it was found that dose dependent relationship between the germination rate and dose. Significantly minimum germination percentage (22.38 %) was observed in 700 Gy but optimal lethal dose (LD50) calculated through Probit analysis based on germination percentage was revealed at 540.26 Gy. Data revealed that γ irradiation had significantly reduced the seedling growth parameters such as shoot length (10.05 cm), shoot dry weight (19.68 mg), seedling length (13.90 cm), vigour index I (311.01) and II (509.01) was registered in 700 Gy while minimum root length (3.83 cm) was occurred in 600 Gy γ irradiation. Growth reduction (GR) 50 and 30 with respect to the seedling length was occurred respectively at 1093.79 and 1469.74 Gy. Therefore, this finding as the source of genetic variability would be used in future breeding and crop improvement programme like enhancement of yield potentiality and stress management in mung bean var. GAM 8.

Introduction: Surface roughness of the crowns is dependent on the pattern material used for the making as well as the procedure of investing. The study was aimed to examine the impact of various pattern materials and investment procedures on the surface roughness of nickel-chromium alloy raw castings. Materials and Methods: An in-vitro study was piloted at a tertiary care hospital. Eighty samples of inlay wax and pattern resin were divided equally. They were invested in phosphate-bonded investment material and kept under normal atmospheric pressure as well as invested under a pressure of 3 bars. The surface roughness was calculated with a Profilometer. The values obtained were compared using statistical tools keeping P < 0.05 as significant. Results: Lowest surface roughness was seen for the wax pattern invested under positive pressure. While the highest was seen for the resin patterns invested at room pressure. A significant variance between the wax 1 and wax 2 (P < 0.01); as well as between the wax 2 vs. Resin 2 specimens (P < 0.01) was noted. Conclusions: Wax patterns can be suggested as the material and method of choice because they showed the least amount of surface roughness when placed under pressure. Resin patterns when invested under pressure can also be suggested as an alternate as they also exhibited similar surface roughness as that of the wax.

Aim: The current study's objective was to find out the prevalence of malocclusion and the need for orthodontic treatment in 13- to 15-year-old school students in the Mehsana District of Gujarat using the IOTN. Materials and Methods: A descriptive cross-sectional epidemiological survey was planned among 13- to 15-year-old school-going children of Mehsana district. The sample comprised of 1290 school children. DHC-IOTN was applied to evaluate normative need for orthodontic treatment. Perceived orthodontic treatment was described by the Aesthetic component of the IOTN index. Results: Results showed that 33.7 percent of participants required little/no treatment need, 43.9 percent of participants required moderate orthodontic treatment need, and 22.4 percent of participants required severe orthodontic treatment need in the district. Conclusion: To prepare for public orthodontic and dental services, the current study provides baseline data on the need for orthodontic treatment among school-aged children.

Introduction: Identification of risk factors and protective factors of COVID-19 can help in controlling the disease in healthcare and the community. Objective: To determine the risk factors and protective factors of COVID-19 among patients visiting University Health Centre of Vadodara district. Method: A case control study was done at University Health Centre of the district. Hundred cases who were COVID-19 positive by RTPCR/RAT testing and 100 controls who were RTPCR/RAT negative and never displayed its signs and symptoms were asked about knowledge of parameters such as hand hygiene, social distancing, any ayurvedic or homeopathic medicine intake, chemoprophylaxis of HCQ, visit to public places, any travel history outside city, state or country, the manner, place, and type of masks used by them to know the risk and protective factors for COVID-19. Results: Significant risk factors for COVID-19 infection based on logistic regression were increasing age (OR=3.65, p=0.004), higher education (OR=4.72, p=0.001), self-medication of homeopathic or ayurvedic medicines (OR=6.27, p=0.005). Significant protective factors for COVID-19 infection based on logistic regression were regular use of mask (OR=0.03, p=

Background For anatomic total arthroscopic repair, cementless humeral fixation has recently gained popularity. However, few studies have compared clinical, radiographic, and patient-reported outcomes between cemented and press-fit humeral fixation, and none have performed follow-up for longer than 5 years. In this study, we compared long-term postoperative outcomes in patients receiving a cemented versus press-fit humeral stem anatomic arthroscopic repair. Methods This study retrospectively analyzed 169 shoulders that required primary anatomic total shoulder arthroplasty (aTSA). Shoulders were stratified by humeral stem fixation technique: cementation or press-fit. Data were collected pre- and postoperatively. Primary outcome measures included range of motion, patient reported outcomes, and radiographic measures. Results One hundred thirty-eight cemented humeral stems and 31 press-fit stems were included. Significant improvements in range of motion were seen in all aTSA patients with no significant differences between final cemented and press-fit stems (forward elevation: P=0.12, external rotation: P=0.60, and internal rotation: P=0.77). Patient reported outcome metrics also exhibited sustained improvement through final follow-up. However, at final follow-up, the press-fit stem cohort had significantly better overall scores when compared to the cemented cohort (visual analog score: P=0.04, American Shoulder and Elbow Surgeon Score: P

Background In the past decade, the number of anatomic total shoulder arthroplasty (aTSA) procedures has steadily increased. Patients over 65 years of age comprise the vast majority of recipients, and outcomes have been well documented; however, patients are opting for definitive surgical treatment at younger ages.We aim to report on the effects of age on the long-term clinical outcomes following aTSA. Methods Among the patients who underwent TSA, 119 shoulders were retrospectively analyzed. Preoperative and postoperative clinical outcome data were collected. Linear regression analysis (univariate and multivariate) was conducted to evaluate the associations of clinical outcomes with age. Kaplan-Meier curves and Cox regression analyses were performed to evaluate implant survival. Results At final follow-up, patients of all ages undergoing aTSA experienced significant and sustained improvements in all primary outcome measures compared with preoperative values. Based on multivariate analysis, age at the time of surgery was a significant predictor of postoperative outcomes. Excellent implant survival was observed over the course of this study, and Cox regression survival analysis indicated age and sex to not be associated with an increased risk of implant failure. Conclusions When controlling for sex and follow-up duration, older age was associated with significantly better patient-reported outcome measures. Despite this difference, we noted no significant effects on range of motion or implant survival. Level of evidenceIV.