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Abstract Hypertension poses a critical threat to health in India, being the predominant risk factor for mortality and disability. With over 70% of outpatient care being provided by the private sector, our study investigated the practices and incentives of private health providers in screening, diagnosing, treating, monitoring, and counseling hypertension patients in rural and peri-urban India. Conducted from April 2020 to February 2021, the qualitative study involved 46 participants, including various healthcare professionals and patients in three Telangana state districts. Analysis revealed a lack of recognition of hypertension’s gravity among private providers in these areas, leading to inconsistent screening practices and varied diagnostic thresholds, particularly among rural medical practitioners. Both formal and informal providers lacked standardized protocols and follow-up mechanisms, with limited technical knowledge about hypertension observed, especially among rural practitioners who were often the first point of contact. Drug effectiveness, and incentives from pharmaceutical sales representatives influenced prescribing practices. Diagnostic labs also offered financial incentives for patient referrals. Thus, aligning providers’ objectives with patient preferences and public health goals is crucial. To encourage evidence-based hypertension care, the government and NGOs could implement strategies such as tailored incentives, financial rewards, tax benefits, accreditation, and recognition for private healthcare providers. Professional bodies in the private sector should establish programs emphasizing quality assurance and certifications. Future research should focus on designing and testing new models for private sector hypertension service delivery, coupled with targeted interventions to enhance care in rural and peri-urban settings.

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.

Abstract Background Microbial biopolymers such as poly-3-hydroxybutyrate (PHB) are emerging as promising alternatives for sustainable production of biodegradable bioplastics. Their promise is heightened by the potential utilisation of photosynthetic organisms, thus exploiting sunlight and carbon dioxide as source of energy and carbon, respectively. The cyanobacterium Synechocystis sp. B12 is an attractive candidate for its superior ability to accumulate high amounts of PHB as well as for its high-light tolerance, which makes it extremely suitable for large-scale cultivation. Beyond its practical applications, B12 serves as an intriguing model for unravelling the molecular mechanisms behind PHB accumulation. Results Through a multifaceted approach, integrating physiological, genomic and transcriptomic analyses, this work identified genes involved in the upregulation of chlorophyll biosynthesis and phycobilisome degradation as the possible candidates providing Synechocystis sp. B12 an advantage in growth under high-light conditions. Gene expression differences in pentose phosphate pathway and acetyl-CoA metabolism were instead recognised as mainly responsible for the increased Synechocystis sp. B12 PHB production during nitrogen starvation. In both response to strong illumination and PHB accumulation, Synechocystis sp. B12 showed a metabolic modulation similar but more pronounced than the reference strain, yielding in better performances. Conclusions Our findings shed light on the molecular mechanisms of PHB biosynthesis, providing valuable insights for optimising the use of Synechocystis in economically viable and sustainable PHB production. In addition, this work supplies crucial knowledge about the metabolic processes involved in production and accumulation of these molecules, which can be seminal for the application to other microorganisms as well.

Recent decades have witnessed transformative advances in radiation physics and computer technology, revolutionizing the precision of radiation therapy. The adoption of intricate treatment techniques such as three-dimensional conformal radiotherapy, intensity-modulated radiotherapy, volumetric-modulated arc therapy, and image-guided radiotherapy necessitates robust quality assurance (QA) programs. This study introduces the SunCHECK™ Machine (SCM), a web-based QA platform, presenting early results from its integration into a comprehensive QA program. linear accelerators (LINAC) demand QA programs to uphold machine characteristics within accepted tolerances. The increasing treatment complexity underscores the need for streamlined procedures. The selection of QA tools is vital, requiring efficiency, accuracy, and alignment with clinic needs, as per recommendations such as the AAPM task group 142 report. The materials and methods section details SCM implementation in various QA aspects, encompassing daily QA (DQA), imaging QA with Catphan, conventional output assessment with a water phantom, and LINAC isocenter verification through the Winston–Lutz test. Challenges in QA processes, such as manual data transcription and limited device integration, are highlighted. Early results demonstrate SCM’s significant reduction in QA time, ensuring accuracy and efficiency. Its automation eliminates interobserver variation and human errors, contributing to time savings and near-immediate result publication. SCM’s role in consolidating and storing DQA data within a single platform is emphasized, offering potential in resource optimization, especially in resource-limited settings. In conclusion, SCM shows promise for efficient and accurate mechanical and dosimetric QA in radiation therapy. The study underscores SCM’s potential to address contemporary QA challenges, contributing to improved resource utilization without compromising quality and safety standards.

Background: Deletion of SMARCB1/loss of INI is a well-known association in atypical rhabdoid teratoid tumors (ATRT) in the brain, rhabdoid tumors in the kidney, and less common tumors, including sinonasal INI1 deficient carcinoma, gastric undifferentiated carcinoma, undifferentiated uterine sarcomas, and poorly differentiated chordomas. Case report: We describe homozygous deletion of the SMARCB1 gene in a patient diagnosed with pineal yolk sac tumor, which is a rare entity. The association highlights the importance of INI1 staining when the clinical course is not progressing as expected and raises a critical management question: should this rare entity be treated aggressively, like ATRT, versus the conventional approach to intracranial yolk sac tumor? Conclusion: This case highlights the importance of INI1 staining in pediatric primitive central nervous system tumors as some germ cell markers are expressed in rhabdoid tumors at the stem cell level, implicating the germ cell origin of ATRT, which can complicate the diagnosis.

Background G6PD (glucose‐6‐phosphate‐dehydrogenase) is a key enzyme in the glycolytic pathway and has been implicated in the pathogenesis of cancer and pulmonary hypertension‐associated vascular remodeling. Here, we investigated the role of an X‐linked G6pd mutation (N126D polymorphism), which is known to increase the risk of cardiovascular disease in individuals from sub‐Saharan Africa and many others with African ancestry, in the pathogenesis of pulmonary hypertension induced by a vascular endothelial cell growth factor receptor blocker used for treating cancer. Methods and Results CRISPR‐Cas9 genome editing was used to generate the G6pd variant (N126D; G6pdN126D) in rats. A single dose of the vascular endothelial cell growth factor receptor blocker sugen‐5416 (SU; 20 mg/kg in DMSO), which is currently in a Phase 2/3 clinical trial for cancer treatment, was subcutaneously injected into G6pdN126D rats and their wild‐type littermates. After 8 weeks of normoxic conditions, right ventricular pressure and hypertrophy, pulmonary artery remodeling, the metabolic profile, and cytokine expression were assessed. Right ventricular pressure and pulmonary arterial wall thickness were increased in G6PDN126D+SU/normoxic rats. Simultaneously, levels of oxidized glutathione, inositol triphosphate, and intracellular Ca2+ were increased in the lungs of G6PDN126D+SU/normoxic rats, whereas nitric oxide was decreased. Also increased in G6PDN126D+SU/normoxic rats were pulmonary levels of plasminogen activator inhibitor‐1, thrombin‐antithrombin complex, and expression of proinflammatory cytokines CCL3 (chemokine [C‐C motif] ligand), CCL5, and CCL7. Conclusions Our results suggest G6PDN126D increases inositol triphosphate‐Ca2+ signaling, inflammation, thrombosis, and hypertrophic pulmonary artery remodeling in SU‐treated rats. This suggests an increased risk of vascular endothelial cell growth factor receptor blocker‐induced pulmonary hypertension in those carrying this G6PD variant.

Background and aimsUltrasound derived carotid intima-media thickness (cIMT) is valuable for cardiovascular risk stratification. We assessed the relative importance of traditional atherosclerosis risk factors and plasma proteins in predicting cIMT measured nearly a decade later.MethodWe examined 6,136 UK Biobank participants with 1,461 proteins profiled using the proximity extension assay applied to their baseline blood draw who subsequently underwent a cIMT measurement. We implemented linear regression, stepwise Akaike Information Criterion-based, and the least absolute shrinkage and selection operator (LASSO) models to identify potential proteomic as well as non-proteomic predictors. We evaluated our model performance using the proportion variance explained (R2).ResultThe mean time from baseline assessment to cIMT measurement was 9.2 years. Age, blood pressure, and anthropometric related variables were the strongest predictors of cIMT with fat-free mass index of the truncal region being the strongest predictor among adiposity measurements. A LASSO model incorporating variables including age, assessment center, genetic risk factors, smoking, blood pressure, trunk fat-free mass index, apolipoprotein B, and Townsend deprivation index combined with 97 proteins achieved the highest R2 (0.308, 95% C.I. 0.274, 0.341). In contrast, models built with proteins alone or non-proteomic variables alone explained a notably lower R2 (0.261, 0.228–0.294 and 0.260, 0.226–0.293, respectively). Chromogranin b (CHGB), Cystatin-M/E (CST6), leptin (LEP), and prolargin (PRELP) were the proteins consistently selected across all models.ConclusionPlasma proteins add to the clinical and genetic risk factors in predicting a cIMT measurement. Our findings implicate blood pressure and extracellular matrix-related proteins in cIMT pathophysiology.

IntroductionThe COVID-19 pandemic has been recognized as an unprecedented global health crisis. Over 7 million mortalities have been documented with many paediatric fatalities. Trauma and orthopaedic care, much like other specialities, were marginalized due to resource allocation during the pandemic which affected paediatric care. This is the first systematic review to centralise and compile the recommended published guidelines from professional bodies in principally English speaking countries on managing paediatric trauma and orthopaedic care. These guidelines will be required to be implemented sooner and more effectively in case of future pandemics with similar impact.MethodsA search was conducted on PubMed/MedLine, Cochrane Library and Embase using terms including p(a)ediatric or child* and/or COVID* or coronavirus or SARS-CoV-2 and/or trauma and/or orthop(a)edic* with a simplified MeSH heading [mh] in order to make the search as comprehensive as possible. General terminology was utilized to make the search as exhaustive as possible for this systematic review. Another search was conducted on resources available in the public domain from professional bodies publishing on consensus statements and clinical practice guidelines in countries where English is the principal language managing pediatric trauma and orthopedics. The review adhered to PRISMA guidance.ResultsThe search revealed a total of 62 results from both databases and professional bodies. Duplicates were removed. This was then reviewed to identify a total of 21 results which fit the inclusion criteria and included within the main analysis. The guidelines from professional bodies were outlined and categorized into aspects of clinical care.DiscussionThe impact of COVID-19 pandemic has compelled for changes in clinical practice and pediatric management. The systematic review highlights the relevant guidelines on service provision for pediatric patients including indications for urgent referrals, surgical prioritization, reasons for follow-up and trauma guidelines. The rationale for care during the unpredictable evolution of the COVID-19 pandemic may have the potential to be translated and replicated in future pandemics of similar significance.

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

Abstract OpenDengue is a global database of dengue case data collated from public sources and standardised and formatted to facilitate easy reanalysis. Dataset version 1.2 of this database contains information on over 56 million dengue cases from 102 countries between 1924 and 2023, making it the largest and most comprehensive dengue case database currently available. Over 95% of records are at the weekly or monthly temporal resolution and subnational data is available for 40 countries. To build OpenDengue we systematically searched databases, ministry of health websites, peer reviewed literature and Pro-MED mail reports and extracted denominator-based case count data. We undertake standardisation and error checking protocols to ensure consistency and resolve discrepancies. We meticulously documented the extraction process to ensure records are attributable and reproducible. The OpenDengue database remains under development with plans for further disaggregation and user contributions are encouraged. This new dataset can be used to better understand the long-term drivers of dengue transmission, improve estimates of disease burden, targeting and evaluation of interventions and improving future projections.

Huntington's disease (HD) is caused by an expanded CAG repeat in the huntingtin gene, yielding a Huntingtin protein with an expanded polyglutamine tract. While experiments with patient-derived induced pluripotent stem cells (iPSCs) can help understand disease, defining pathological biomarkers remains challenging. Here, we used cryogenic electron tomography to visualize neurites in HD patient iPSC-derived neurons with varying CAG repeats, and primary cortical neurons from BACHD, deltaN17-BACHD, and wild-type mice. In HD models, we discovered sheet aggregates in double membrane-bound organelles, and mitochondria with distorted cristae and enlarged granules, likely mitochondrial RNA granules. We used artificial intelligence to quantify mitochondrial granules, and proteomics experiments reveal differential protein content in isolated HD mitochondria. Knockdown of Protein Inhibitor of Activated STAT1 ameliorated aberrant phenotypes in iPSC- and BACHD neurons. We show that integrated ultrastructural and proteomic approaches may uncover early HD phenotypes to accelerate diagnostics and the development of targeted therapeutics for HD.

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

Abstract Objective: We conducted a meta-analysis of randomized clinical trials evaluating the clinical effects of ferric carboxymaltose therapy compared to other intravenous iron in improving hemoglobin and serum ferritin in pregnant women. We also assessed the safety of ferric carboxymaltose vs. other intravenous iron. Data source: EMBASE, PubMed, and Web of Science were searched for trials related to ferric carboxymaltose in pregnant women, published between 2005 and 2021. We also reviewed articles from google scholar. The keywords "ferric carboxymaltose," "FCM," "intravenous," "randomized," "pregnancy," "quality of life," and "neonatal outcomes" were used to search the literature. The search was limited to pregnant women. Selection of studies: Studies related to ferric carboxymaltose in pregnancy were scanned. Observational studies, review articles, and case reports were excluded. Randomized studies in pregnant women involving ferric carboxymaltose and other intravenous iron formulations were shortlisted. Of 256 studies, nine randomized control trials were selected. Data collection: Two reviewers independently extracted data from nine selected trials Data synthesis: The final effect size for increase in hemoglobin after treatment was significant for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 0.89g/dl [95% confidence interval 0.27,1.51]). The final effect size for the increase in ferritin after treatment was more for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 22.53µg/L [-7.26, 52.33]). No serious adverse events were reported with ferric carboxymaltose or other intravenous iron. Conclusion: Ferric carboxymaltose demonstrated better efficacy than other intravenous iron in increasing hemoglobin and ferritin levels in treating iron deficiency anemia in pregnant women.

Abstract Objective: Despite the literature on dydrogesterone, studies on dydrogesterone utilization patterns are largely lacking in Indian patients. Methods: This was a multi-center, retrospective, observational, cross-sectional, and descriptive study across 817 centers in India. Data of patients who received dydrogesterone in past and provided consent for future use of their medical record for research purpose was were retrieved and analyzed. Results: Data of 7287 subjects (aged 29.55±4.84 years) was analyzed. Threatened abortion was the most common indication for which the subjects received dydrogesterone (46.9%) followed by recurrent pregnancy loss. Polycystic ovary syndrome (PCOS), thyroid disorders and anemia were the most common comorbid conditions and prior pregnancy loss, advanced maternal age and obesity were the most common risk factors seen in subjects who received dydrogesterone. Total 27.5% of subjects received a loading dose of dydrogesterone, and majority (64%) received 40 mg as loading dose. 10 mg dose was used as maintenance or regular dose in 81.4% of the subjects. Twice daily (BID) was the most common dosing frequency (66.6%). The most common concomitant medications being taken by the subjects on dydrogesterone included folic acid (45.1%), iron supplements (30.3%) and calcium and vitamin D3 supplements (25.5%). Another progesterone preparation (oral, injection, vaginal, tubal) other than dydrogesterone was used concurrently in 7.8% of subjects. Conclusion: The study helped to identify the patient population that is benefitted by dydrogesterone and the preferred indications, risk factors, comorbid conditions and concomitant medication used in this patient population at real-life scenario.

BackgroundPediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM.MethodsTBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL).ResultsOf 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P

The current survey was conducted to assess the knowledge, awareness and perception of platelet-rich plasma (PRP) on accelerated tooth movement among dentist present in the state of Tamil Nadu. Tamil Nadu dentists were the subjects of the cross-sectional questionnaire survey. 500 participants completed self-administered questionnaires about their knowledge, awareness, and perception of PRP’s effect on accelerated tooth movement. The Statistical Package for the Social Sciences (SPSS) (V 22.0) was used to do the statistical analysis. It computed the frequency distribution.The result showed that 466 (93.2%) had prior knowledge of PRP, whereas 34 (6.4%) had no previous experience with it. A total of 156 (31.2%) dentists were aware that PRP procedures are used for teeth rotation and canine retraction.15.2% of participants stated that PRP facilitates accelerated tooth movement.Therefore, results of the study show that the dentists were a little aware of PRP as an additional therapeutic strategy for accelerating tooth movement.More awareness required among the dentist regarding application and its benefits of PRP in accelerated tooth movement.

IntroductionHost lipids play important roles in tuberculosis (TB) pathogenesis. Whether host lipids at TB treatment initiation (baseline) affect subsequent treatment outcomes has not been well characterised. We used unbiased lipidomics to study the prospective association of host lipids with TB treatment failure.MethodsA case-control study (n=192), nested within a prospective cohort study, was used to investigate the association of baseline plasma lipids with TB treatment failure among adults with pulmonary TB. Cases (n=46) were defined as TB treatment failure, while controls (n=146) were those without failure. Complex lipids and inflammatory lipid mediators were measured using liquid chromatography mass spectrometry techniques. Adjusted least-square regression was used to assess differences in groups. In addition, machine learning identified lipids with highest area under the curve (AUC) to classify cases and controls.ResultsBaseline levels of 32 lipids differed between controls and those with treatment failure after false discovery rate adjustment. Treatment failure was associated with lower baseline levels of cholesteryl esters and oxylipin, and higher baseline levels of ceramides and triglycerides compared to controls. Two cholesteryl ester lipids combined in a unique classifier model provided an AUC of 0.79 (95% CI 0.65-0.93) in the test dataset for prediction of TB treatment failure.ConclusionsWe identified lipids, some with known roles in TB pathogenesis, associated with TB treatment failure. In addition, a lipid signature with prognostic accuracy for TB treatment failure was identified. These lipids could be potential targets for risk-stratification, adjunct therapy and treatment monitoring.