Kanchi Kamakoti CHILDS Trust Hospital

Objectives: The study aims to provide evidence for the compressed progress of puberty in affluent South Indian girls from Chennai. Material and Methods: This is a cross-sectional school-based study. Data collected as part of these two surveys which were conducted within 2 weeks’ time during July 1981 and 1998. Tanner staging was used. The first survey was in the year 1981, designated as Group 1. The year of the second survey was 1998, designated as Group 2. Results: Results showed the following: The number of subjects was 1976 in Group 1 (1981) and 1520 in Group 2 (1998). Mean values at 50 th percentile: Time taken to move from P2 to P4, 1981 = 3.2 years and time taken to move from P2 to P4, 1998 = 2.1 years. Menarche mean/median age of attainment in year 1981 versus 1998 was 12.4 (SD 1.I) and 12.1 (SD 1.07) years respectively ( P < 0.05). Conclusion: Time taken to complete all the breast and PH stages was compressed from 4.8 years to 3.4 years in the two studies. The Thelarche-menarche duration also was compressed from 1.2 years to 0.9 years in the two studies. Early menarche in South Indian girls is associated with compressed progression of sexual maturity ratings.

Primary immune regulatory disorders (PIRDs) are a group of conditions characterised by a loss of immune tolerance. Two such disorders, CHAI and LATAIE, share common molecular mechanisms, leading to significant clinical overlap. Here, we report demographic, clinical, immunological, and molecular findings in 29 patients referred from different parts of India with a diagnosis of CHAI or LATAIE. LATAIE patients demonstrated a higher prevalence of consanguinity, while CHAI patients more often had a positive family history. Both disorders presented with overlapping clinical features, predominately autoimmune cytopenias, benign lymphoproliferation, and inflammatory bowel disease (IBD). However, the incidence of recurrent infections, otitis media, bronchiectasis, and hypogammaglobulinemia was higher among LATAIE patients as compared to CHAI. Flow cytometry analysis revealed significant differences in T cell subsets, particularly in percentages of CD4+ naïve cells and T regulatory cells (Treg), between the two disorders. B cell abnormalities were also observed. Molecular diagnosis was achieved using targeted or clinical exome sequencing, and specific protein expression was employed to validate the novel variants.

Streptococcus pneumoniae poses a significant public health burden, particularly in India, where invasive and non-invasive forms contribute to high morbidity and mortality. Rapid disease progression and limitations of antimicrobial therapy underscore the need for preventive strategies. Pneumococcal vaccines, especially the 20-valent conjugate vaccine (PCV20), offer robust protection against diverse serotypes, reduce nasopharyngeal carriage, and promote herd immunity. To understand the epidemiology of the pneumococcal disease and establish the evidence for the use of higher valent pneumococcal conjugate vaccines in Indian adults. This paper describes the epidemiology of pneumococcal disease, urgency of pneumococcal vaccination, serotype replacement dynamics, and the advantages of PCV20 over PPSV23. In India, delayed vaccine adoption and unique serotype profiles necessitate targeted strategies, including catch-up campaigns and enhanced surveillance, to achieve herd immunity and mitigate the disease burden within 5-10 years.

BackgroundThere is significant overlap in clinical features between multisystem inflammatory syndrome in children (MIS‐C) and Kawasaki disease (KD). We sought to compare the prevalence, severity, and associated factors for coronary artery (CA) involvement.Methods and ResultsFrom January 1, 2020 through January 31, 2023, 1191 patients with MIS‐C and 554 patients contemporaneously diagnosed with KD were enrolled into the International Kawasaki Disease Registry. Demographic and clinical features, laboratory values, maximum Z score in any CA branch at any time point, and worst left ventricular ejection fraction, were compared between groups. Factors associated with CA aneurysms (maximum Z score in any CA branch +2.5 or greater) were determined separately for each diagnosis using multivariable logistic regression analyses. The prevalence of CA aneurysms was lower for MIS‐C versus KD (16% versus 25%, respectively; P<0.001) and less severe by size category (1.2% with medium/large CA aneurysm versus 9.6%, respectively). Male sex and lower nadir hemoglobin levels were associated with greater odds of CA aneurysms for both groups. Additional associated factors for KD patients included age<6 months, fewer clinical KD criteria (more incomplete presentation), presentation with shock, and greater total days of fever. There were no additional associated factors for patients with MIS‐C. Using exploratory splines, there was a trend of improvement in Z scores within 30 days of illness for both MIS‐C and KD for CA involvement other than large aneurysms.ConclusionsCA involvement for patients with MIS‐C was less prevalent and milder in severity compared with contemporaneous patients with KD, with fewer associated factors, and a high prevalence of regression to a normal luminal dimension.

Pune, western India, was earlier identified as hyperendemic for hepatitis A. Subsequently, we noted age and socio-economic status-dependent reduction in hepatitis A virus (HAV) prevalence. To assess the situation in different parts of India, this multicentric, hospital-based, cross-sectional study was conducted in four metropolitan cities in the northern/southern/eastern/western regions. As per age group-anti-HAV-positivity-specific sample size calculations (1-40years), 496 samples/centre were collected from Pune, Kolkata, Chennai and Ludhiana. All samples were tested for anti-HAV antibodies using enzyme-linked immunosorbent assay (ELISA). Overall, 44.9% of children up to fiveyears of age were anti-HAV antibody-positive (ELISA), with a steady increase reaching 92.9% by the age of 26-40years. Importantly, 782/1756 (44.5%) of the total population ≤ 15years was anti-HAV negative and hence susceptible to HAV. The city-wise analysis documented similar patterns with afew differences. According to theWorld Health Organization (WHO) classification of HAV endemicity, Pune, Chennai and Ludhiana were classified as cities with intermediate endemicity, whereas Kolkata with lower seroprevalence had low endemicity. Compared to the 2011-2012 survey anti-HAV positivity remained unchanged in the other cities except for the rise in Chennai. Apart from age, other risk factors varied in different cities. A comparison of socio-economic-dependent, age-stratified serosurveys conducted during 1982, 1992, 1998,2017 and 2022 in Pune documented the shift from high to intermediate endemicity in the population with high socio-economic status in 1998 and lower-middle socio-economic strata in 2017. The lowering of anti-HAV positivity reflects a definite improvement in sanitation and voluntary vaccination, but seems to have slowed down during recent years. Additional, well-defined efforts are necessary.

The study aim was to develop an age-appropriate definition of sport and exercise in children and adolescents for use in concussion research and management. A modified Delphi methodology, with three rounds and consensus defined a priori as ≥ 80% agreement. Thirty-one participants (13 male, 18 female) from 13 countries, including clinical psychologists, epidemiologists, implementation scientists, neurologists, neuropsychologists, neurosurgeons, paediatric emergency physicians, paediatricians, physiotherapists, rehabilitation physicians, speech-language pathologists, and sports medicine physicians came to a consensus that sport-related paediatric concussion extends beyond the sporting arena, and includes the school yard, playground, park, street, recreational site, and home; excludes non-accidental violence, assault, and passenger vehicle road trauma; may include falls; and age-group terminology includes Toddlers and Young Children (1-4 years), Children (5-12 years), and Adolescents (13 to < 18 years). Sport and exercise categories and individual examples are provided. This consensus definition of sport and exercise in paediatrics for concussion research and management will enable researchers and guideline development groups to expand paediatric concussion research and management guidelines to encompass the broad range of activities commonly associated with sport- and exercise-related concussion in children and adolescents and thus limit exclusion of relevant studies from systematic reviews and guideline development.

Introduction: Non-coronary artery systemic arterial aneurysms (SAA) are a rare and under-reported sequelae of Kawasaki disease (KD), for which data and guidance are limited. Methods: A survey was sent to members of the International KD Registry (IKDR) regarding their experiences and practices with SAA in KD patients. For comparison, a systematic review was conducted following PRISMA methodology; after evaluation, a total of 21 studies with 75 patients total were included. Results were compared qualitatively. Results: Surveys were completed by 48 (56%) of 86 IKDR investigators; 35 (73%) respondents had &gt;10 years of experience caring for KD patients. Experience with SAA was limited, with 33% not having cared for a patient with SAA. Reported screening practices included 81% screening only patients with coronary artery (CA) involvement, 8% reporting screening all patients with KD, and with 11% using other criteria. The degree of CA involvement influenced screening, with 56% screening only those with giant CA aneurysms, 20% also small/medium aneurysms, 6% included dilation and 18% not using any specific CA criteria. Additional factors reported included multiple or rapidly expanding CA aneurysms, clinical features such as prolonged/persistent fever, progressing/persistent elevation of inflammatory markers, and resistance to standard treatment. These screening practices were somewhat concordant with the characteristics of patients with SAA reported in the literature (FIGURE). Initial preferred assessment method was CT angiography for 48%, ultrasound 28% and MRI for 24% of respondents. In contrast, SAA reported in the review were most commonly assessed with conventional coronary artery angiography. From the review, SAA were associated with a high rate of regression (62-93%). Longer-term complications reported included SAA thrombosis, calcification, stenosis, occlusion and collateral formation. Clinical and management factors associated with SAA outcomes were not defined. Conclusion: While the development of SAA is a known but rare complication of acute KD, there remains a gap in evidence as to which patients are at risk, best practices for screening and management, and outcomes. Protocol driven cohort studies are needed.

FtsZ, a bacterial cell division protein, is essential for assembling the contractile Z-ring crucial in bacterial cytokinesis. Consequently, inhibiting FtsZ could impede proto-filaments, disrupting FtsZ and other associated proteins vital for cell division machinery. Conduct an in-silico drug interaction study to identify novel drug candidates that inhibit the FtsZ protein, aiming to prevent Multi-Drug Resistant (MDR) Salmonella Typhi. Data mining was performed based on piperidine compounds, which were subsequently screened for safe pharmacokinetic profiles. Compounds that met favorable drug-likeness criteria underwent virtual screening against the FtsZ drug target. Two compounds were chosen for molecular docking and molecular dynamic simulation to verify the binding affinity and stability between the target protein and the potential compounds. The 400 isoforms of piperidine analogues were curated, among them potent compound ZINC000000005416 found to possess high binding affinity (-8.49 kcal/mol) and low dissociation constant (0.597 µM). The highest binding affinity shown by ZINC000000005416 was validated by hydrogen bonds, hydrophobic interaction, and salt bridges with the functional domain of the cell division regulatory protein. Docking profiles, when correlated with molecular dynamic simulation (MDS) depicted stable trajectories and compatible conformational changes in the FtsZ-ZINC000000005416 complex. The stable simulated trajectories were validated through free-energy calculations using the Molecular Mechanics-Poisson Boltzmann Surface Area (MM/PBSA) module. Low energy conformations, although the simulation trajectory confirmed the stable ZINC000000005416-FtsZ interaction, which encouraged experimental validations. This study encourages further exploration of the compound ZINC000000005416 as a drug candidate inhibiting FtsZ protein against MDR Salmonella Typhi.