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Purpose: Non-obstructive azoospermia (NOA) represents the persistent absence of sperm in ejaculate without obstruction, stemming from diverse disease processes. This survey explores global practices in NOA diagnosis, comparing them with guidelines and offering expert recommendations. Materials and Methods:Materials and Methods: A 56-item questionnaire survey on NOA diagnosis and management was conducted globally from July to September 2022. This paper focuses on part 1, evaluating NOA diagnosis. Data from 367 participants across 49 coun-tries were analyzed descriptively, with a Delphi process used for expert recommendations. Results:Results: Of 336 eligible responses, most participants were experienced attending physicians (70.93%). To diagnose azoosper-mia definitively, 81.7% requested two semen samples. Commonly ordered hormone tests included serum follicle-stimulating hormone (FSH) (97.0%), total testosterone (92.9%), and luteinizing hormone (86.9%). Genetic testing was requested by 66.6%, with karyotype analysis (86.2%) and Y chromosome microdeletions (88.3%) prevalent. Diagnostic testicular biopsy, distinguishing obstructive azoospermia (OA) from NOA, was not performed by 45.1%, while 34.6% did it selectively. Differ-entiation relied on physical examination (76.1%), serum hormone profiles (69.6%), and semen tests (68.1%). Expectations of finding sperm surgically were higher in men with normal FSH, larger testes, and a history of sperm in ejaculate. Conclusions:Conclusions: This expert survey, encompassing 367 participants from 49 countries, unveils congruence with recommended guidelines in NOA diagnosis. However, noteworthy disparities in practices suggest a need for evidence-based, international consensus guidelines to standardize NOA evaluation, addressing existing gaps in professional recommendations.

BackgroundAbout 1.35 million deaths annually are attributed to tobacco use in India. The main challenge, given the magnitude of tobacco use and limited resources, is delivering cessation support at scale, low cost, and through a coordinated cross-system effort; one such example being brief advice interventions. However, highly credentialed staff to identify and counsel tobacco users are scarce. Task-shifting is an important opportunity for scaling these interventions. ObjectiveThe LifeFirst SWASTH (Supporting Wellbeing among Adults by Stopping Tobacco Habit) program—adapted from the LifeFirst program (developed by the Narotam Sekhsaria Foundation, Mumbai, India)—is a tobacco cessation program focusing on lower-socioeconomic status patients in Mumbai receiving private health care. This parallel-arm, cluster randomized controlled trial investigates whether the LifeFirst SWASTH program increases tobacco cessation rates in low-resource, high-reach health care settings in Mumbai. MethodsThis study will target tuberculosis-specific nongovernmental organizations (NGOs), dental clinics, and NGOs implementing general health programs serving lower-socioeconomic status patients. Intervention arm patients will receive a pamphlet explaining tobacco’s harmful effects. Practitioners will be trained to deliver brief cessation advice, and interested patients will be referred to a Narotam Sekhsaria Foundation counselor for free telephone counseling for 6 months. Control arm patients will receive the same pamphlet but not brief advice or counseling. Practitioners will have a customized mobile app to facilitate intervention delivery. Practitioners will also have access to a peer network through WhatsApp. The primary outcome is a 30-day point prevalence abstinence from tobacco. Secondary outcomes for patients and practitioners relate to intervention implementation. ResultsThe study was funded in June 2020. Due to the COVID-19 pandemic, the study experienced some delays, and practitioner recruitment commenced in November 2023. As of July 2024, all practitioners have been recruited, and practitioner recruitment and training are complete. Furthermore, 36% (1687/4688) of patients have been recruited. ConclusionsIt is hypothesized that those patients who participated in the LifeFirst SWASTH program will be more likely to have been abstinent from tobacco for 30 consecutive days by the end of 6 months or at least decreased their tobacco use. LifeFirst SWASTH, if found to be effective in terms of cessation outcomes and implementation, has the potential to be scaled to other settings in India and other low- and middle-income countries. The study will be conducted in low-resource settings and will reach many patients, which will increase the impact if scaled. It will use task-shifting and an app that can be tailored to different settings, also enabling scalability. Findings will build the literature for translating evidence-based interventions from high-income countries to low- and middle-income countries and from high- to low-resource settings. Trial RegistrationClinicalTrials.gov NCT05234983; https://clinicaltrials.gov/study/NCT05234983 International Registered Report Identifier (IRRID)DERR1-10.2196/57236

Introduction Hepatic artery complications (HACs), such as a thrombosis or stenosis, are serious causes of morbidity and mortality after paediatric liver transplantation (LT). This study will investigate the incidence, current management practices and outcomes in paediatric patients with HAC after LT, including early and late complications.Methods and analysis The HEPatic Artery stenosis and Thrombosis after liver transplantation In Children (HEPATIC) Registry is an international, retrospective, multicentre, observational study. Any paediatric patient diagnosed with HAC and treated for HAC (at age

Purpose: Sperm DNA fragmentation (SDF) has been associated with male infertility and poor outcomes of assisted reproductive technology (ART). The purpose of this study was to investigate global practices related to the management of elevated SDF in infertile men, summarize the relevant professional society recommendations, and provide expert recommendations for managing this condition. Materials and Methods: An online global survey on clinical practices related to SDF was disseminated to reproductive clinicians, according to the CHERRIES checklist criteria. Management protocols for various conditions associated with SDF were captured and compared to the relevant recommendations in professional society guidelines and the appropriate available evidence. Expert recommendations and consensus on the management of infertile men with elevated SDF were then formulated and adapted using the Delphi method.Results: A total of 436 experts from 55 different countries submitted responses. As an initial approach, 79.1% of reproductive experts recommend lifestyle modifications for infertile men with elevated SDF, and 76.9% prescribe empiric antioxidants. Regarding antioxidant duration, 39.3% recommend 4–6 months and 38.1% recommend 3 months. For men with unexplained or idiopathic infertility, and couples experiencing recurrent miscarriages associated with elevated SDF, most respondents refer to ART 6 months after failure of conservative and empiric medical management. Infertile men with clinical varicocele, normal conventional semen parameters, and elevated SDF are offered varicocele repair immediately after diagnosis by 31.4%, and after failure of antioxidants and conservative measures by 40.9%. Sperm selection techniques and testicular sperm extraction are also management options for couples undergoing ART. For most questions, heterogenous practices were demonstrated. Conclusions: This paper presents the results of a large global survey on the management of infertile men with elevated SDF and reveals a lack of consensus among clinicians. Furthermore, it demonstrates the scarcity of professional society guidelines in this regard and attempts to highlight the relevant evidence. Expert recommendations are proposed to help guide clinicians.

Purpose: Sperm DNA fragmentation (SDF) testing was recently added to the sixth edition of the World Health Organization laboratory manual for the examination and processing of human semen. Many conditions and risk factors have been associated with elevated SDF; therefore, it is important to identify the population of infertile men who might benefit from this test. The purpose of this study was to investigate global practices related to indications for SDF testing, compare the relevant professional society guideline recommendations, and provide expert recommendations. Materials and Methods: Clinicians managing male infertility were invited to take part in a global online survey on SDF clinical practices. This was conducted following the CHERRIES checklist criteria. The responses were compared to professional society guideline recommendations related to SDF and the appropriate available evidence. Expert recommendations on indications for SDF testing were then formulated, and the Delphi method was used to reach consensus. Results: The survey was completed by 436 experts from 55 countries. Almost 75% of respondents test for SDF in all or some men with unexplained or idiopathic infertility, 39% order it routinely in the work-up of recurrent pregnancy loss (RPL), and 62.2% investigate SDF in smokers. While 47% of reproductive urologists test SDF to support the decision for varicocele repair surgery when conventional semen parameters are normal, significantly fewer general urologists (23%; p=0.008) do the same. Nearly 70% would assess SDF before assisted reproductive technologies (ART), either always or for certain conditions. Recurrent ART failure is a common indication for SDF testing. Very few society recommendations were found regarding SDF testing. Conclusions: This article presents the largest global survey on the indications for SDF testing in infertile men, and demonstrates diverse practices. Furthermore, it highlights the paucity of professional society guideline recommendations. Expert recommendations are proposed to help guide clinicians.

Abstract Diabetes mellitus (DM) increases tuberculosis (TB) severity. We compared blood gene expression in adults with pulmonary TB, with or without diabetes mellitus (DM) from sites in Brazil and India. RNA sequencing (RNAseq) performed at baseline and during TB treatment. Publicly available baseline RNAseq data from South Africa and Romania reported by the TANDEM Consortium were also analyzed. Across the sites, differentially expressed genes varied for each condition (DM, TB, and TBDM) and no pattern classified any one group across all sites. A concise signature of TB disease was identified but this was expressed equally in TB and TBDM. Pathway enrichment analysis failed to distinguish TB from TBDM, although there was a trend for greater neutrophil and innate immune pathway activation in TBDM participants. Pathways associated with insulin resistance, metabolic dysfunction, diabetic complications, and chromosomal instability were positively correlated with glycohemoglobin. The immune response to pulmonary TB as reflected by whole blood gene expression is substantially similar with or without comorbid DM. Gene expression pathways associated with the microvascular and macrovascular complications of DM are upregulated during TB, supporting a syndemic interaction between these coprevalent diseases.

Several hepatitis A outbreaks have recently been reported in Kerala state, India. To inform coverage decision of hepatitis A vaccine in Kerala, this study aimed to examine the cost-effectiveness of 1) hepatitis A vaccination among children aged 1 year and individuals aged 15 years, and 2) serological screening of individuals aged 15 years and vaccination of susceptible as compared to no vaccination or vaccination without serological screening. Both live attenuated hepatitis A vaccine and inactivated hepatitis A vaccine were considered in the analysis. A combination of decision tree and Markov models with a cycle length of one year was employed to estimate costs and benefits of different vaccination strategies. Analysis were based on both societal and payer perspectives. The lifetime costs and outcomes were discounted by 3%. Our findings indicated that all strategies were cost-saving for both societal and payer perspectives. Moreover, budget impact analysis revealed that vaccination without screening among individuals aged 15 years could save the government's budget by reducing treatment cost of hepatitis A. Our cost-effectiveness evidence supports the inclusion of hepatitis A vaccination into the vaccination program for children aged 1 year and individuals aged 15 years in Kerala state, India.

Sebaceous carcinoma of the eyelid frequently presents with metastatic disease involving regional lymph nodes. However, metastasis to parotid gland is very rare and can be mistaken for a primary parotid gland tumor. We present a case of a 53-year-old female who presented with right parotid swelling. MRI of the head and neck with contrast was suggestive of a pleomorphic adenoma. She was operated on for sebaceous carcinoma of the eyelid four years back. Characteristic cytological findings of a mixture of high-grade malignant cells with vacuolated cells along with clinical correlation were helpful in the diagnosis of this tumor following which the patient underwent parotidectomy.

Animal sociality emerges from individual decisions on how to balance the costs and benefits of being sociable. Novel pathogens introduced into wildlife populations should increase the costs of sociality, selecting against gregariousness. Using an individual-based model that captures essential features of pathogen transmission among social hosts, we show how novel pathogen introduction provokes the rapid evolutionary emergence and coexistence of distinct social movement strategies. These strategies differ in how they trade the benefits of social information against the risk of infection. Overall, pathogen-risk-adapted populations move more and have fewer associations with other individuals than their pathogen-risk-naive ancestors, reducing disease spread. Host evolution to be less social can be sufficient to cause a pathogen to be eliminated from a population, which is followed by a rapid recovery in social tendency. Our conceptual model is broadly applicable to a wide range of potential host–pathogen introductions and offers initial predictions for the eco-evolutionary consequences of wildlife pathogen spillover scenarios and a template for the development of theory in the ecology and evolution of animals’ movement decisions.

Context: Clinical study for immunity. Aims: The present study aimed to assess the effect of proprietary polyherbal formulation (PPHF), labelled as Kofol immunity tablets (KIT) on innate and adaptive immune responses in healthy individuals, on the backdrop of COVID-19 pandemic. Settings and Design: Single-blind, randomized, placebo-controlled, exploratory study in institutional setting. Materials and Methods: Post Ethics Committee permission, screened healthy individuals of either sex aged 18–35 years were randomized to PPHF/Placebo for 2 months. Major assessment variables included peak expiratory flow rate (PEFR), questionnaire-based immune status, perceived stress, and quality of life (QOL) with immune-specific cell counts (CD4+, CD8+), cytokines (interferon gamma [IFN-γ], tumor necrosis factor-alpha [TNF-α], interleukin 10 [IL-10]), and oxidative stress in red blood cells (RBCs) (malondialdehyde (MDA), glutathione peroxidase [GPx]), done at day 60. Statistical Analysis Used: Mean ± standard deviation and paired/unpaired t-test for parametric data analysis while median (range) and Wilcoxon Rank sum test/Mann–Whitney test for nonparametric data analysis, were done. Categorical data was analyzed using Chi-square test. GraphPad InStat software, version 9 was used with p < 0.05, as the level of statistical significance. Results: Of 52 recruited, 28 individuals completed the study. PPHF significantly increased PEFR, improved immune status along with QOL compared to baseline. It also decreased perceived stress from moderate and severe grade to mild. Serum IFN-γ levels remained almost constant post-PPHF treatment. PPHF significantly decreased MDA and increased GPx in RBCs. Significant decrease and increase in TNF-α and IL-10, respectively, were seen in PPHF group. The safety parameters post-PPHF treatment remained within normal reference ranges. Conclusions: PPHF is an efficacious and safe formulation with immunomodulatory potential.

Introduction Portal vein obstruction (PVO) consists of anastomotic stenosis and thrombosis, which occurs due to a progression of the former. The aim of this large-scale international study is to assess the prevalence, current management practices and efficacy of treatment in patients with PVO.Methods and analysis The Portal vein Obstruction Revascularisation Therapy After Liver transplantation registry will facilitate an international, retrospective, multicentre, observational study, with 25 centres around the world already actively involved. Paediatric patients (aged

Immune checkpoint inhibitors (ICIs) are a relatively new class of immunotherapy which bolsters the host immune system by “turning off the brakes” of effector cells (e.g., CTLA-4, PD-1, PD-L1). Although their success in treating adult malignancy is well documented, their utility in pediatric cancer has not yet been shown to be as fruitful. We review ICIs, their use in pediatric malignancies, and active pediatric clinical trials, exemplifying some of adult efforts that could be related to pediatric future trials and complications of ICI therapy. Through our review, we propose the consideration of ICI as standard therapy in lymphoma and various solid tumor types, especially in relapsed or refractory (R/R) disease. However, further studies are needed to demonstrate ICI effectiveness in pediatric leukemia.

Abstract Assessing the impact of lockdowns on COVID-19 incidence may provide important lessons for management of pandemic in resource-limited settings. We examined growth of incident confirmed COVID-19 patients before, during and after lockdowns during the first wave in Pune city that reported the largest COVID-19 burden at the peak of the pandemic. Using anonymized individual-level data captured by Pune’s public health surveillance program between February 1st and September 15th 2020, we assessed weekly incident COVID-19 patients, infection rates, and epidemic curves by lockdown status (overall and by sex, age, and population density) and modelled the natural epidemic using the compartmental model. Effect of lockdown on incident patients was assessed using multilevel Poisson regression. We used geospatial mapping to characterize regional spread. Of 241,629 persons tested for SARS-CoV-2, 64,526 (26%) were positive, contributing to an overall rate of COVID-19 disease of 267·0 (95% CI 265·3–268·8) per 1000 persons. The median age of COVID-19 patients was 36 (interquartile range [IQR] 25–50) years, 36,180 (56%) were male, and 9414 (15%) were children

Abstract Background Dislocation of the knee is a serious and potentially limb-threatening injury. There are three types of dislocation around the knee joint: patellofemoral, tibiofemoral, and tibiofibular. Tibiofemoral dislocation is the variant that is deemed the most serious, with a higher risk of compromise to the popliteal artery and common peroneal nerve. Although simultaneous dislocations of two types have been described, there has been no such description of all three types occurring simultaneously. Case presentation We present a case of a 40-year-old hairdresser who suffered a fall off her moped in Spain, and simultaneously dislocated all three articulations around the knee. Diagnosis was achieved with clinical examination, plain films, and computed tomography and magnetic resonance imaging scans. Management consisted of initial surgical debridement and reduction with stabilization of the affected joints. Conclusion Dislocation of the knee is an uncommon but life changing and potentially limb-threatening injury. It should always be suspected in trauma patients who present with multiligamentous knee injuries. The main concern is of neurovascular compromise to the lower leg, namely, the popliteal artery and common peroneal nerve. The treatment of multiligamentous knee injuries for most patients is surgical treatment with physiotherapy and adequate stabilization of the knee joint. Close monitoring of progress of the knee in terms of persistent laxity, range of movement, and functional status is required for at least 1-year post injury. Current evidence suggests that, despite good functional outcomes for knee dislocations in the short term, the prevalence of post-traumatic osteoarthritis is high in the long term.

Background & Aims: With change of posture from quadrupeds to bipeds, a shift of body weight from appendicular skeleton to the axial skeleton (spine) occurs. As a result, various changes in the spine took place and the human spine became more prone to diseases such as scoliosis, spondylolisthesis, osteoporosis of vertebrae and many more. Over the past decade, a number of corrective surgeries have been designed but trans-pedicular screw fixation in spondylosyndesis remains the gold standard for the correcting spinal deformities. Hence, the current study was designed to frame out the morphometric measurements of the pedicle of lumbar vertebrae so that guidelines can be delineated for the manufacturers of lumbar screw implants. Materials and Methods: The present cross-sectional descriptive study was conducted on 100 lumbar vertebrae of unknown age and sex obtained from the Department of Anatomy Govt. Medical College (GMC) Jammu. All the measurements were taken twice on both right and left side with the help of sliding vernier calipers, averaged out and then tabulated in Microsoft Excel spreadsheet. Results: The dimensions of the pedicle height of the lumbar vertebrae on the right side were recorded to be from 20.05 to 10.32mm with mean of 13.83±2.08mm. However, mean of the pedicle height on left side was 13.71± 2.09mm with the range of 20.01 to 10.22mm with statistically significant p- value of 0.025. Further, the range of pedicular width of lumbar vertebrae on the right side was 17.71 to 5.38mm with a mean of 10.8±2.73mm and on left side was from 17.69 to 5.37 mm with mean of 9.77±2.57 mm with statistically significant p value of 0.037. The mean inter-pedicular distance of lumbar vertebrae was 21.73±2.62mm with a range of 11-28mm. Conclusions: The results of the present study concluded that mean pedicular width and mean pedicular height are more on right side and mean inter- pedicular distance was 21.73±2.62mm. Hence, it was concluded that measurements should be taken before designing the lumbar screws for North Indian population.

Background and aim: Arsenic is a common pollutant of water in developing counties, leads to major health problems, and affects all body organs. The current study aimed to evaluate the histopathological effects of arsenic on the liver and kidney of albino rats.Materials and methods: A total of 18 Wistar rats were divided into 3 groups (n = 6). The control group received only distilled water, ARS 50 Group received 50ppm of arsenic in drinking water as a daily oral dose for 4 weeks, and ARS 100 group received 100ppm of arsenic in drinking water as a daily oral dose, each day for 4 weeks. After experimentation, the rats were euthanized and tissues procured, treated, slides were prepared, and observational analysis was done.Results: The liver of rats exposed to low dose showed mild central venous dilatation and congestion, portal haemorrhage, and dilated portal vein. However, the liver of rats exposed to higher doses revealed distortion of tissue architecture, haemorrhage, necrosis, vacuolated cytoplasm, mononuclear infiltrate. These changes were more pronounced in the high dose group, and rats in the control group showed normal tissue architecture. The kidneys of rats exposed to arsenic revealed disrupted architecture, increased or decreased periglomerular space, eosinophilic casts, and mononuclear infiltrate in a dose-dependent manner compared to the control group, which revealed normal renal function architecture.Conclusion: According to the research results, even smaller doses of 50ppm of arsenic potentially induce pathological effects on the liver and kidney. Hence, the amount of arsenic should be checked in drinking water.

Objectives To perform a mixed-methods study identifying motivators and deterrents to female doctors interested in core surgical training (CST). To provide tangible implementations based on the findings.Design This study used quantitative (questionnaires) and qualitative (semistructured interviews (SSIs)) analyses. Participants completed online questionnaires on Qualtrics and SSIs were conducted remotely on Microsoft Teams. Questions were derived from previous studies and a novel term, the gender impact rating (GIR), was coined to assess the impact of gender on opportunities available during CST application.Setting Participants were working in the UK National Health Service and data collected from December 2020 to January 2021.Participants A total of 100 female surgical trainees in the UK ranging from Foundation Year 2 to Core Training Year 2.Main outcome measures Participants ranked factors by their influence on their CST application. Of the 100 trainees, 21 were randomly selected for an SSI to explore their questionnaire responses. Statistical analyses were performed using MATLAB and SPSS, alongside a thematic analysis of the interviews.Results A total of 44 out of 100 questionnaire respondents ranked early exposure to surgery as the most influential motivator, while 43% selected work-life balance as the greatest deterrent and 33% suggested mentoring schemes to encourage women to apply to CST. The median GIR was 3 out of 5, indicating a moderate perceived impact of gender on opportunities available during CST application. Qualitative analysis found four overarching themes: institutional factors (including mentorship schemes), organisational culture (including active engagement), social factors and personal factors.Conclusion Thematic analysis suggested that seniors involving women in theatre and a supportive work environment would encourage entry of more female surgeons. Therefore, the proposed implementations are the active engagement of women in theatre and destigmatising less than full-time training. Further research into ethnicity and personality on motivations to enter surgery is advised.

Background and aim: The harmful effects of nicotine have been reported on the lungs and cardiovascular system in many studies, but the most unexplored profile of the effect of nicotine has been the genitourinary organs. In the current study, we planned to evaluate the effects of nicotine smoke on one of the important genitourinary organs, i.e., the testes and kidneys.Materials and methods: The study was conducted on 12 inbred adult Wistar albino rats; 6 animals acting as a control, and the remaining six acting as a test group. The control group animals were given only sterile water, whereas animals of the test group were exposed to smoke produced from the nicotine wrapped in cotton wool in the dose of 6mg/day three times a day for each session of 5 minutes each for five days. Each rat was exposed to the smoke produced due to nicotine separately in a closed inhalational chamber and not in groups. The rats were euthanized after experimentation, and testis and kidneys were removed and subjected further to tissue processing for histological examination.Results: The histological examination of tissue sections of the test group revealed marked distortion and degeneration of seminiferous tubules and germ cell lineage and distorted and widened interstitial spaces with loss of Leydig cells. On the other hand, the tissue sections of the control group showed normal histological architecture of testes with normal interstitial spaces and Leydig cells. Additionally, the renal sections of the test group showed dilation of urinary space, shrunken and distorted glomeruli. On the contrary, the renal specimens of the control group also demonstrated normal renal architectural patterns.Conclusion: the results of the present study concluded that even passive smoke exposure has drastic effects on the genitourinary organs, and hence, its use in public places should be checked.

Abstract Tuberculosis (TB) and atherosclerotic cardiovascular disease (ASCVD) have a close epidemiological and pathogenetic overlap. Thus, it becomes essential to understand the relationship between ASCVD and TB outcomes. From our retrospective cohort on drug-susceptible TB patients at the National Taiwan University Hospital, we assessed the association of pre-existing ASCVD (coronary artery disease (CAD) and atherothrombotic stroke (ATS)) with 9-month all-cause and infection-related mortality and the extent of mediation by systemic inflammatory markers. We determined the effect of pre-existing ASCVD on 2-month sputum microbiological status. Among ASCVD patients, we assessed the association of statin use on mortality. Nine-month all-cause mortality was higher in CAD patients with prior acute myocardial infarction (CAD+AMI+) (adjusted HR 2.01, 95%CI 1.38–3.00) and ATS patients (aHR 2.79, 95%CI 1.92–4.07) and similarly, for infection-related mortality was higher in CAD+AMI+ (aHR 1.95, 95%CI 1.17–3.24) and ATS (aHR 2.04, 95%CI 1.19–3.46) after adjusting for confounding factors. Pre-existing CAD (AMI- or AMI+) or ATS did not change sputum culture conversion or sputum smear AFB positivity at 2 months. The CAD+AMI+ group had significantly higher levels of CRP at TB diagnosis in the multivariable linear regression analysis (Adjusted B(SE) 1.24(0.62)). CRP mediated 66% (P = 0.048) and 25% (P = 0.033) of the association all-cause mortality with CAD+AMI− and CAD+AMI+, respectively. In summary, patients with ASCVD have higher hazards of 9-month all-cause and infection-related mortality, with elevated serum inflammation mediating one to three-quarters of this association when adjusted for confounders. Statin use was associated with lower all-cause mortality among patients with ASCVD.

Introduction India has 267 million adult tobacco users, the majority of whom are part of the economically productive workforce. Workplaces are ideal settings to influence tobacco use behavior. A 6-month tobacco cessation program was implemented in five workplaces in Maharashtra, India. The study aimed to describe 6-month tobacco cessation outcomes and to identify promoters and barriers for implementing the program. Methods This is an explanatory mixed methods study. Quantitative part involved analysis of routinely collected program data from January 2016 to June 2017 to describe the sociodemographic characteristics, tobacco use patterns and 6-month cessation outcomes. Qualitative part consisted of one-to-one interviews with employees who had enrolled for cessation services (n=16) and one group interview with the counseling service providers (n=5). Results A total of 331 current tobacco users voluntarily enrolled in this program and used predominantly (78%) smokeless tobacco. The self-reported 7-day point prevalence abstinence at the end of six months was 66%. Employees who used smokeless forms of tobacco, had low levels of nicotine dependence, and attended 4 or more counseling sessions, were more likely to quit tobacco use. Support from the management and multiple counseling sessions were described as promoters. Peer pressure, work stress, and inability to quit without medication were the major barriers. Formulating tobacco-free workplace policy was suggested for reducing tobacco use at workplaces. Conclusions The core activities of the program, which included awareness sessions, individual counseling sessions and repeated follow-up sessions as well as support received from the workplace management, played a major role in achieving good cessation outcomes.

Introduction The youth are a vulnerable populationgroup for tobacco-related harms. Schools are an excellent setting for health promotion; yet there is a dearth of schoolbased cessation interventions, rarely evaluated for their impact. Here, we assess the impact of the LifeFirst program: an ongoing tobacco and supari (areca nut) cessation intervention delivered to students from corporation schools in Mumbai city. Methods We used a prospective quasi-experimental design with an intervention and a control arm embedded within an ongoing LifeFirst program in select schools. We used a difference-in-difference analysis with baseline and endline surveys to assess the program’s impact on students’ knowledge about harms, students’ refusal skills, and prevalence of tobacco/supari use. We report our work using the TREND statement checklist. Results A total of 959 students registered in the LifeFirst program. In our analysis, we included 827 students who completed both the baseline and end-line surveys. Postintervention, we found both tobacco and supari use reduced substantially among the intervention group while tobacco use increased among the control group. The difference-indifference estimates show a statistically significant reduction of 17.9 and 38.1 percentage points in the intervention group for tobacco and supari use respectively, beyond the reduction in the control group. Conclusions The LifeFirst program was successful in reducing tobacco and supari use among the study participants and protected students in the intervention group against new uptake of tobacco. It helped improve knowledge score and refusal skills among students. Implementation and evaluation of similar school-based programs should be considered as part of a multi-strategy approach to reducing tobacco use among young people.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic affected the pediatric oncology population globally. Over the course of 2 years, increasing reports have been made to better understand this entity and its pathologic complications on these patients. The pandemic has allowed healthcare providers, hospital systems, and leading oncologic societies to quickly adapt and formulate new guidelines for the effective understanding, management, and treatment of patients with pediatric malignancy.

Conjunctival myxomas are very rare benign tumours of mesenchymal origin which pose a diagnostic challenge clinically and radiologically. They usually present as asymptomatic slowly growing cystic lesions involving the bulbar conjunctiva. Two cases were with usual presentation while one was with unusual presentation. Two cases of conjunctival myxoma (59-year-old female patient and 65-year-old male patient) involving the bulbar conjunctiva and one (56-year-old female patient) in the palpebral conjunctiva are reported. Anterior segment examination and fundoscopy were within normal limits. A clinical diagnosis of conjunctival cyst, pinguecula and pyogenic granuloma was made in the three cases, respectively. Excision was done in all the cases and a diagnosis of myxoma was made based on the characteristic histological and immunohistochemical features. No systemic involvement was seen. The authors hereby report the present cases because of their rarity and to emphasise that, histopathology is required to distinguish it from other conjunctival lesions.

IntroductionIn India, smokeless tobacco (SLT) is a predominant form of tobacco used among people living with HIV (PLHIV). Despite SLT being a risk factor for oral potentially malignant disorders (OPMDs), no prior studies have quantified the association of OPMDs with SLT use among PLHIV. This limits the planning of preventive and control strategies for oral cancer among PLHIV, who are at higher risk for the disease.MethodsWe enrolled 601 PLHIV and 633 HIV-uninfected individuals in an oral cancer screening study at BJ Government Medical College, Pune, India. Oral cavity images were collected using an m-Health application and reviewed by three clinicians. Participants with two clinician positive diagnoses were deemed to have suspected OPMDs. Prevalence ratios (PRs) were used to quantify the association between suspected OPMDs and SLT use among PLHIV. PRs for current SLT users, across HIV status and use duration were also estimated. Corrected PRs were obtained by modifying the maximum likelihood estimation. Models were adjusted for age, smoking, alcohol use and CD4 counts.ResultsOf those enrolled, 61% were men, median age was 36 years (IQR: 28-44), and 33% currently use SLT. Proportion of current SLT users was similar across PLHIV and HIV-uninfected groups but use duration for current SLT use was higher among PLHIV(pConclusionPLHIV that are current SLT users are at high risk of OPMDs and potentially oral cancer. The development of strategies for screening, early detection, and management of OPMDs must be considered for this group.

The World Health Organization (WHO) recently changed its guidance for tuberculosis (TB) preventive treatment (TPT) recommending TPT for all pulmonary TB (PTB) exposed household contacts (HHC) to prevent incident TB disease (iTBD), regardless of TB infection (TBI) status. However, this recommendation was conditional as the strength of evidence was not strong. We assessed risk factors for iTBD in recently-exposed adult and pediatric Indian HHC, to determine which HHC subgroups might benefit most from TPT. We prospectively enrolled consenting HHC of adult PTB patients in Pune and Chennai, India. They underwent clinical, microbiologic and radiologic screening for TB disease (TBD) and TBI, at enrollment, 4-6, 12 and 24 months. TBI testing was performed by tuberculin skin test (TST) and Quantiferon®- Gold-in-Tube (QGIT) assay. HHC without baseline TBD were followed for development of iTBI and iTBD. Using mixed-effect Poisson regression, we assessed baseline characteristics including TBI status, and incident TBI (iTBI) using several TST and/or QGIT cut-offs, as potential risk factors for iTBD. Of 1051 HHC enrolled, 42 (4%) with baseline TBD and 12 (1%) with no baseline TBI test available, were excluded. Of the remaining 997 HHC, 707 (71%) had baseline TBI (TST #x2265; 5 mm or QGIT #x2265; 0.35 IU/ml). Overall, 20 HHC (2%) developed iTBD (12 cases/1000 person-years, 95%CI: 8-19). HIV infection (aIRR = 29.08, 95% CI: 2.38-355.77, p = 0.01) and undernutrition (aIRR = 6.16, 95% CI: 1.89-20.03, p = 0.003) were independently associated with iTBD. iTBD was not associated with age, diabetes mellitus, smoking, alcohol, and baseline TBI, or iTBI, regardless of TST (#x2265; 5 mm, #x2265; 10 mm, #x2265; 6 mm increase) or QGIT (#x2265; 0.35 IU/ml, #x2265; 0.7 IU/ml) cut-offs. Given the high overall risk of iTBD among recently exposed HHCs, and the lack of association between TBI status and iTBD, our findings support the new WHO recommendation to offer TPT to all HHC of PTB patients residing in a high TB burden country such as India, and do not suggest any benefit of TBI testing at baseline or during follow-up to risk stratify recently-exposed HHC for TPT.

BackgroundViolence against women has been one of the most prominent issue and a major public health concern. It is a principle violation of basic human rights and has both physical and mental effect on the victim. This study focuses on married and unmarried girls aged 15 to 19 years, belonging to Uttar Pradesh and Bihar, India. This study attempts to examine depression level among married and unmarried girls who have faced violence against them. With the unprecedented growth in social networking, online digital platform and its accessibility, the study also brings out the pertinent aspect of internet based violence and its psychological outcome on adolescent girls. Hence, the study can be seen as an important and needed value addition to the existing pool of knowledge on the subject.MethodsThe study uses Understanding the lives of adolescents and young adults (UDAYA) project data for Uttar Pradesh and Bihar. Depressive symptoms among adolescent girl is the outcome variable of the study. Descriptive statistic and bivariate analysis has been used to get to preliminary results. Chi-squared test is used to test the significant of variables. Further, multi-variate analysis (logistic regression) was used.ResultsAlmost 29, 23 and 26 percent of married adolescent girls had faced emotional, physical and sexual violence respectively. It was found that about five per cent of unmarried and eight per cent of married girls had high depressive symptoms. It was found that unmarried adolescent girls who had witnessed their father beating mother were 71 percent more likely to suffer from higher depressive symptoms [OR: 1.71, 1.09-2.69]. Adolescents who faced perpetrated bullying had 90 per cent [OR: 1.90, 1.32-2.72] and 86 per cent [OR: 1.86, 0.98-3.52] higher likelihood to suffer from higher depressive symptoms.ConclusionThe study goes beyond intimate partner violence and includes various covariates to explain the association between violence and depressive symptoms among married and unmarried adolescents. Hence, more inclusive policies are needed to address the issue of violence against women as the spectrum of the violence is expanding with time.

Studies of the outcome of Pseudomonas aeruginosa bacteremia (Pab) have focused mainly on antibiotic appropriateness. However, P. aeruginosa possesses many virulence factors whose roles in outcomes have not been examined in humans, except for the type III secretion system (T3SS) toxins. The purpose of this study was to examine the role of virulence factors other than the T3SS toxins. Bacterial isolates were collected from 75 patients who suffered from Pa blood stream infections. Host factors such as neutropenia, immunosuppression, comorbidities, time to effective antibiotics, source of bacteremia, and presence of multidrug resistant (MDR) isolate were studied. The isolates were analyzed for the presence of toxin genes, proteolytic activity, swimming and twitching motility, and pyocyanin production. The data were analyzed to ascertain which virulence factors correlated with poor outcomes defined as septic shock or death (SS) within 7 days. Septic shock or death occurred in 25/75 patients. Univariate analysis identified age as a host factor that exerted a significant effect on these outcomes. Ineffective antibiotics administered during the first 24 hours of treatment or MDR P. aeruginosa did not influence the frequency of SS, nor did the presence of lasB, exoA, exoS exoU, plcH genes and proteolytic activity. However, 6/8 patients infected with non-motile isolates, developed SS, p = 0.014 and 5/6 isolates that produced large amounts of pyocyanin (>18ug/ml), were associated with SS, p = 0.014. Multivariate analysis indicated that the odds ratio (OR) for development of SS with a non-motile isolate was 6.8, with a 95% confidence interval (CI) (1.37, 51.5), p = 0.030 and with high pyocyanin producing isolates, an OR of 16.9, 95% CI = (2.27, 360), p = .017. This study evaluating the role of microbial factors that significantly effect outcomes following Pa bloodstream infection suggests that P. aeruginosa strains showing high pyocyanin production and the lack of motility independently increase the risk of SS.

[This corrects the article DOI: 10.1371/journal.pone.0217289.].

[This corrects the article DOI: 10.1371/journal.pone.0220507.].

BackgroundMore than 20% of tuberculosis (TB) disease worldwide may be attributable to smoking and alcohol abuse. India is the second largest consumer of tobacco products, a major consumer of alcohol particularly among males, and has the highest burden of TB globally. The impact of increasing tobacco dose, relevance of alcohol misuse and past versus current or never smoking status on TB treatment outcomes remain inadequately defined.MethodsWe conducted a multi-centric prospective cohort study of newly diagnosed adult pulmonary TB patients initiated on TB treatment and followed for a minimum of 6 months to assess the impact of smoking status with or without alcohol abuse on treatment outcomes. Smokers were defined as never smokers, past smokers or current smokers. Alcohol Use Disorder Identification Test (AUDIT) scores were used to assess alcohol misuse. The association between smoking status and treatment outcomes was assessed in univariate and multivariate random effects poisson regression models.ResultsOf 455 enrolled, 129 (28%) had a history of smoking with 94 (20%) current smokers and 35 (8%) past smokers. Unfavourable treatment outcomes were significantly higher among past and current smokers as compared to never smokers. Specifically, the risk of treatment failure was significantly higher among past smokers (aIRR = 2.66, 95% CI: 1.41-4.90, p = 0.002), recurrent TB among current smokers (aIRR = 2.94, 95% CI: 1.30-6.67, p = 0.010) and death among both past (2.63, 95% CI: 1.11-6.24, p = 0.028) and current (aIRR = 2.59, 95% CI: 1.29-5.18, p = 0.007) smokers. Furthermore, the combined effect of alcohol misuse and smoking on unfavorable treatment outcomes was significantly higher among past smokers (aIRR: 4.67, 95% CI: 2.17-10.02, pConclusionPast and current smoking along with alcohol misuse have combined effects on increasing the risk of unfavourable TB treatment outcomes. Innovative interventions that can readily address both co-morbidities are urgently needed.

Despite substantial exposure to infectious pulmonary tuberculosis (TB) cases, some household contacts (HHC) never acquire latent TB infection (LTBI). Characterizing these "resisters" can inform who to study immunologically for the development of TB vaccines. We enrolled HHCs of culture-confirmed adult pulmonary TB in India who underwent LTBI testing using tuberculin skin test (TST) and QuantiFERON TB Gold Test-in-tube (QFT-GIT) at baseline and, if negative by both (

BackgroundBurden, phenotype and risk-factors of lung function defects in successfully treated tuberculosis cases are unclear.MethodsWe performed spirometry with bronchodilators in new drug-sensitive adult (≥18 years) pulmonary tuberculosis cases during the 12 months following successful treatment in India. Airflow obstruction was defined as pre-bronchodilator FEV1/FVCResultsOf the 172 participants included in the analysis, 82 (48%) were female, 22 (13%) had diabetes and 34 (20%) ever-smoked with a median (IQR) exposure of 3.5 (0.2-9.9) pack-years. Median (IQR) age and body-mass index (BMI) at enrollment was 32 (23-39) years and 18.1 (16.0-20.5) kg/m2 respectively. Airflow obstruction was detected in 42 (24%) participants; of whom 9 (21%) responded to short-acting bronchodilators and 25 (56%) had COPD; and was associated with duration of illness prior to treatment (aOR = 1.32 per 30-days, 95%CI 1.04-1.68, p = 0.02). A restrictive spirometry pattern was detected in 89 (52%) participants and was associated with female sex (aOR = 3.73, 95%CI 1.51-9.17, p = 0.004) and diabetes (aOR = 4.06, 95%CI 1.14-14.42, p = 0.03). Higher HbA1c at treatment initiation was associated with greater odds of a restrictive spirometry pattern (aOR = 1.29 per unit higher HbA1c, 95%CI 1.04 to 1.60, p = 0.02).ConclusionWe found a high burden of lung function defects and COPD in tuberculosis cases who successfully completed treatment. Screening for chronic lung diseases following treatment and linkage to respiratory health clinics should be included in the routine management plan of all tuberculosis cases in India, regardless of conventional COPD risk-factors such as older age and smoking.

Pharmacological doses of fibroblast growth factor (FGF) 21 effectively normalize glucose, lipid and energy homeostasis in multiple animal models with many benefits translating to obese humans with type 2 diabetes. However, a role for FGF21 in the regulation of bile acid metabolism has not been reported. Herein, we demonstrate AAV-mediated FGF21 overexpression in mice increases liver expression of the key bile acid producing enzyme, Cyp7a1, resulting in an increased bile acid pool. Furthermore, in cholecystectomized mice, FGF21-mediated bile acid pool increase led to increased transit of bile acids into colon. We elucidate that the mechanism of FGF21 induced bile acid changes is mainly through antagonizing FGF15/19 function on liver βKlotho/FGFR4 receptor complex; thus inhibiting FGF15/19-mediated suppression of Cyp7a1 expression. In conclusion, these data reveal a previously unidentified role for FGF21 on bile acid metabolism and may be relevant to understand the effects of FGF21 analogs in clinical studies.

BackgroundFew studies have evaluated the association between preexisting vitamin D deficiency and incident tuberculosis (TB). We assessed the impact of baseline vitamins D levels on TB disease risk.Methods and findingsWe assessed the association between baseline vitamin D and incident TB in a prospective cohort of 6,751 HIV-negative household contacts of TB patients enrolled between September 1, 2009, and August 29, 2012, in Lima, Peru. We screened for TB disease at 2, 6, and 12 months after enrollment. We defined cases as household contacts who developed TB disease at least 15 days after enrollment of the index patient. For each case, we randomly selected four controls from among contacts who did not develop TB disease, matching on gender and year of age. We also conducted a one-stage individual-participant data (IPD) meta-analysis searching PubMed and Embase to identify prospective studies of vitamin D and TB disease until June 8, 2019. We included studies that assessed vitamin D before TB diagnosis. In the primary analysis, we defined vitamin D deficiency as 25-(OH)D < 50 nmol/L, insufficiency as 50-75 nmol/L, and sufficiency as >75nmol/L. We estimated the association between baseline vitamin D status and incident TB using conditional logistic regression in the Lima cohort and generalized linear mixed models in the meta-analysis. We further defined severe vitamin D deficiency as 25-(OH)D < 25 nmol/L and performed stratified analyses by HIV status in the IPD meta-analysis. In the Lima cohort, we analyzed 180 cases and 709 matched controls. The adjusted odds ratio (aOR) for TB risk among participants with baseline vitamin D deficiency compared to sufficient vitamin D was 1.63 (95% CI 0.75-3.52; p = 0.22). We included seven published studies in the meta-analysis and analyzed 3,544 participants. In the pooled analysis, the aOR was 1.48 (95% CI 1.04-2.10; p = 0.03). The aOR for severe vitamin D deficiency was 2.05 (95% CI 0.87-4.87; p trend for decreasing 25-(OH)D levels from sufficient vitamin D to severe deficiency = 0.02). Among 1,576 HIV-positive patients, vitamin D deficiency conferred a 2-fold (aOR 2.18, 95% CI 1.22-3.90; p = 0.01) increased risk of TB, and the aOR for severe vitamin D deficiency compared to sufficient vitamin D was 4.28 (95% CI 0.85-21.45; p = 0.08). Our Lima cohort study is limited by the short duration of follow-up, and the IPD meta-analysis is limited by the number of possible confounding covariates available across all studies.ConclusionOur findings suggest vitamin D predicts TB disease risk in a dose-dependent manner and that the risk of TB disease is highest among HIV-positive individuals with severe vitamin D deficiency. Randomized control trials are needed to evaluate the possible role of vitamin D supplementation on reducing TB disease risk.

Foregut cysts of the oral cavity are rare developmental anomalies which are lined by gastric, intestinal, squamous or respiratory epithelium or a mixture of these epithelia. A 10-year-old boy presented with a large cyst in the floor of the mouth and had difficulty in speech and chewing of food. On Magnetic Resonance Imaging (MRI) examination a diagnosis of ranula was given. Surgical excision was done and a diagnosis of foregut cyst lined by respiratory epithelium was given on histopathological examination. Till now only 21 cases of lingual foregut cyst with respiratory lining have been reported. We report the 22nd case for its rarity and because these lesions can pose a diagnostic dilemma and should be included in the differential diagnosis of cystic lesions in the oral cavity especially in paediatric population.

The present study aims to address the problem of chromium (Cr) toxicity by providing important insights into the mechanisms involved in its bioremediation. Among the 22 Rhizobium and Sinorhizobium isolates obtained from Sesbania sesban root nodules, Sinorhizobium sp. SAR1 (JX174035.1) tolerated the maximum Cr concentration (1mM) and hence was used for further studies. The excess secretion of extra polymeric substances, as seen from scanning electron micrographs, could be a probable mechanism of adaptation to the Cr stress. The Energy dispersive X-ray spectroscopy data did not show any peaks of Cr. The biosorption studies done on the isolate gave maximum adsorption capacity as 285.71mg/g. The isotherm studies showed a better fit to Langmuir isotherm. The Weber and Morris plot established that the phenomenon of adsorption was governed by film diffusion mechanism. The FTIR analysis suggested the role of cell wall components and extracellular polymeric substances in Cr adsorption to the biomass of Sinorhizobium. On the basis of these results a compiled mechanism of Cr (VI) adsorption and its biotransformation into Cr (III) by Sinorhizobium sp. SAR1 is explained. This work outlines a comprehensive detail for the exact phenomenon of Cr biotransformation by Sinorhizobium sp. SAR1. These results may further help in developing and enhancing effective bioremediation approaches.

Context: Depression, a sustained mood disorder caused by selective diminution of specialized cells in brain is increasing at an alarming rate. It will be the second largest morbid illness by next decade and is the leading cause of suicidal deaths. The available antidepressant medications benefit only a third of its recipients and have many side effects. Hence, it is imperative to search in Ayurveda for leads. Aim: To evaluate Anti- depressant activity of Hiṅgvādi Ghṛta in vivo. Settings and Design: Comparative preclinical study. Materials and Methods: Hiṅgvādi Ghṛta (HG) was prepared using standard operating procedure, physicochemically analyzed and assessed. Tail Suspension Test (TST) model with Swiss albino mice and Forced Swim Test (FST) model with Wistar albino rats were used to assess anti-depressant activity. Imipramine hydrochloride in dose of 15 mg/kg for TST and 10 mg/kg for FST, was the standard drug and Ghee as vehicle control in dose of 0.1g/20g for TST and 0.72g/200g for FST orally. Hiṅgvādi Ghṛta in doses of 0.05g/20g (x/2), 0.1g/20g (x) and 0.2 g/20g (2x) for TST and 0.36g/200g (x/2), 0.72g/200g (x) and 1.44g/200g (2x) for FST was administered to 3 test groups for 21 days orally except Plain control group which received only distilled water. Duration of immobility in seconds for TST and number of rotations for FST were noted for assessment. Statistical Analysis Used: One way ANOVA followed by Dunnets test and Paired t test. Results: HG was significantly effective at dose of 0.1gm/20gm for TST (P = 0.0037; P < 0.01) and 0.72g/200g for FST (P = 0.0055, P < 0.01) comparable to Imipramine hydrochloride. Conclusions: HG displayed potent anti depressant activity comparable to standard drug Imipramine Hydrochloride.