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Abstract The manuscript summarizes the outcomes of a one-day conference by the South Asian College of American College of Clinical Pharmacology (SAC-ACCP) in July 2023, at Bhopal. The theme of the conference was "Advancing pediatric drug development in South Asia." SAC-ACCP organized this event in Bhopal to foster the discipline of clinical pharmacology and to motivate researchers and physicians in the in the central part of India. The conference featured presentations on regional approaches to pediatric drug development in Asia by pediatric scientific experts from the pharmaceutical industry, regulatory agencies, as well as independent consultancies. The speakers highlighted several important aspects of the evolving regulatory landscape in India and proposed numerous actionable steps in acceleration of pediatric drug development. This commentary provides insights from presentations and the panel discussion at this conference and also makes an attempt to connect to similar discussions that occurred at the SAC-ACCP drug development conference in 2017. Keywords: Clinical pharmacology, drug development, essential medicines, India, innovation, pediatrics, South Asia, Author(s): Rajesh Krishna [1]; Manoj Jadhav (corresponding author) [2]; Rama Sivasubramanian [3]; Gangadhar Sunkara [4]; Vikram Gota [5]; Vis Niranjan [6]; Vipin Dhote [7]; Nidhi Sapkal [8]; Nirmala N Rege [...]

Slender structures often lead to vibration discomfort for occupants when exposed to wind forces. This study proposes an innovative method for assessing comfort against wind-induced vibrations for slender structures that combines field monitoring, numerical simulations, codal provisions, and Chang's comfort chart. The method utilizes ambient vibration tests (AVT) and operational modal analysis (OMA) to create a reliable finite element (FE) model for the structure. It involves analyzing the time history and calculating the peak acceleration values at various points within the structure using synthetic ambient wind forces derived from superposing waves. The comfort assessment compares peak acceleration values estimated from time history analysis against those provided in Chang's chart for different comfort levels. The effectiveness of the proposed method is demonstrated through a case study on a tall, slender reinforced concrete (RC) staircase structure, confirming its suitability for practical applications.

India, owing to its population structure, faces an enormous burden of children born with congenital heart disease (CHD). Systematic challenges such as limited public health infrastructure, a shortage of trained specialists, and high out-of-pocket expenditures hinder uniform access to comprehensive CHD care. Despite these limitations, Indian pediatric cardiologists have delivered innovative and often cost-effective solutions to challenging clinical problems. Indigenous devices such as the MyVal transcatheter heart valve, Konar-MF (multifunction) occluder, and Zephyr large-diameter stents are significant achievements in their respective fields. Static balloon dilatation of interatrial septum and balloon-assisted atrial septal defect (ASD) device implantation are prime examples of many innovations that were established by Indians and followed across the world. India also helped consolidate significant interventions in children, such as percutaneous transvenous mitral commissurotomy and interventions for aortoarteritis. Notably, Indian centers have published some of the largest series on transcatheter closure of sinus venosus ASD and ruptured sinus of Valsalva aneurysm. Close collaboration with adult coronary interventionalists has facilitated innovations borrowed from coronary chronic total occlusion hardware and techniques to recanalize ductus arteriosus or membranous-type pulmonary atresia. This manuscript discusses some of India’s innovative contributions to the field of pediatric cardiac interventions.

Transcatheter pulmonary valve implantation (TPVI) is the standard of care in patients with repaired tetralogy of Fallot (rTOF) presenting with right ventricular outflow tract (RVOT) dysfunction. However, the feasibility of TPVI is limited by the high cost and nonavailability of larger-sized valves for dilated native RVOT of rTOF patients. We report the first successful TPVI with a custom-made 35 mm balloon-expandable valve (Myval™) in a 30-year-old rTOF patient with severe pulmonary regurgitation and RV dysfunction.

Abstract Therapeutic deep eutectic solvents (THEDES) are a type of deep eutectics that can be used as active pharmaceutical ingredients (APIs) by enhancing the drug bioavailability, by increasing the solubility of APIs in aqueous solutions or by increasing their permeability through biological barriers. In this study, we demonstrate the utility of designer THEDES, based on Quillaja Saponin (SAP), a triterpene natural product to unravel the antimicrobial potential of such THEDES. THEDES were prepared by gently mixing and heating five different α- hydroxy acids- malic, citric, tartaric, glycolic, lactic acids and SAP with water as a third component in the THEDES. The antimicrobial assays were performed with the as-prepared SAP-THEDES and among the panel of bacterial strains, saponin-malic acid THEDES [SMA-THEDES] displayed potent activity in disassembling PA biofilms, demonstrating that the SMA-THEDES can serve as therapeutic antibacterial biomaterials. To further optimize, a Box-Behnken- response surface methodology (RSM) experimental design was done and at the optimum conditions of SAP (1.014 m.mol), Malic acid (1.003 m.mol), Water (0.117 m.mol), SMA-THEDES exhibited maximum MIC of P. aeruginosa with the minimum absorbance at 590 nm of 0.105. The effectiveness of SMA-THEDES as antibiofilm agents on P. aeruginosa with the mechanism studies have been explored. The colony count from the in vivo infection zebrafish model in the treatment group showed a decline of > 2 fold for SMA-THEDES. Toxicity studies did not reveal any abnormality in liver and brain enzyme levels. Liver morphology images show no severe cytological alterations when treated with SMA-THEDES and were almost similar to the normal liver.

Abstract In this article, a 12 switch 31 L multi-level inverter (MLI) is proposed with the benefits of least switching devices for electric vehicle applications. In most electric vehicles (EV), conventional inverters are utilized so the lifetime of electric vehicle induction motors is reduced due to the high THD level and high voltage stress. To rectify this, a new inverter topology is proposed with minimum switching devices by increasing the level to 31, and also the THD should be maintained within IEEE standards. This inverter topology is constructed with variable DC sources (PV system) along with required capacitors and a polarity changer. The specific feature of this topology is that it can generate any level of voltage with minimum switching devices, less voltage stress, minimum THD, and less cost are tabulated in the comparison. This type of inverter can also applicable for high voltage (HV) applications and grid-connected systems. Furthermore, the proposed topology is simulated with MATLAB software and the downscale prototype model is developed using the DSPIC30f2010 controller.

The emergence of checkpoint inhibitors targeting the PD-1/PD-L1 axis marks a paradigm shift in cancer therapy, offering a novel avenue for enhancing patient outcomes. This review examines the structural and functional dynamics of PD-1 and PD-L1 while exploring the clinical implications of current PD-1/PD-L1 monoclonal antibodies. Highlighting recent advancements, this paper delves into the promising results from combination therapies that present a multifaceted attack on tumor progression. Despite the success observed across various cancer types, challenges such as immune resistance remain. Future considerations are discussed with an emphasis on the need for further clinical studies, aiming to refine and broaden the curative potential of PD-1/PD-L1 inhibitors in oncology. This review postulates that ongoing research and innovative approaches could significantly enhance cancer care, making immunotherapy an even more central strategy in the fight against cancer.

Background The mortality risks of children undergoing various cardiac surgeries for congenital heart disease (CHD) in India are not well defined. We conducted a systematic review and meta-analysis to estimate the inhospital mortality of various common CHD surgeries reported in India and compared it to representative data from established Western databases. Methods and Results We searched four bibliographic databases for studies published in India over the last 25 years. In total, 135 studies met the inclusion criteria and included 30,587 patients aged from 1 day to 65 years. The pooled mortality rate of 43 Indian studies reporting multiple CHD surgical outcomes is 5.63% (95% confidence interval [CI]: 4.26–7.16; I2 = 93.9%), whereas the Western data showed a pooled mortality rate of 2.65% (P value for comparison

Partial cavopulmonary shunt is an established procedure for patients with abnormal right ventricular (RV) physiology. Late failure of the Glenn shunt is usually due to further progression of the primary disease process. However, there may be surprises, as in our patient. We report an 8-year-old child who was diagnosed with tricuspid valve (TV) dysplasia with borderline RV hypoplasia. He underwent TV repair with a right cavopulmonary shunt. He presented with features of heart failure after 6 years of the surgery. An echocardiographic evaluation suggested a restrictive filling pattern of the RV with preserved size and function. Computed tomography and cardiac magnetic resonance imaging revealed a normal pericardial thickness with no evidence of myocardial involvement. Despite the contradicting clinical and imaging features, endomyocardial biopsy confirmed a diagnosis of desmin cardiomyopathy. Restrictive cardiomyopathy may remain an elusive diagnosis despite extensive imaging. In our case, the altered loading conditions due to a cavopulmonary shunt further masked pathophysiological hemodynamic changes.

This review highlights potential application areas for carbon-based molecular nanoparticles, such as carbon dots, carbon nanotubes, graphene quantum dots, and carbon quantum dots. The success of nano-manufacturing hinges on robust collaboration between academia and industry to advance applicable manufacturing techniques. Choosing the right approach is crucial, one that integrates the carbon base of nanomaterials with the required properties and impurities, as well as the scalability of the process. Molecular, in this context, refers to the nanoscale carbon structures that form the basis of these materials, including their arrangement, bonding, and properties at the molecular level. The article also explores the characterization of different types of molecular nanomaterials. Nanomaterials are increasingly used in almost every contemporary industry, including construction, textiles, manufacturing, and computing. This article reviews the most prominent sectors globally that employ nanomaterials. Biomasses containing lignin, cellulose, and hemicellulose have become some of the most extensively studied. Initially, rice waste was utilized for bulk materials, but lately, the production of multifunctional materials has surged in interest. Carbon nanostructures derived from rice waste offer a broad spectrum of applications and enhanced biocompatibility. Recent advancements, challenges, and trends in the development of multifunctional carbon-based nanomaterials from renewable rice waste resources are considered.

Ghosal hematodiaphyseal dysplasia (GHDD) is a rare autosomal recessive disorder characterized by increased bone density involving diaphyses of long bones and defective hematopoiesis. It is due to biallelic variants in the TBXAS1 (OMIM*274180) gene, which encodes for thromboxane synthase. We present a rare case of a middle-aged woman who presented with chronic anemia and bone pain. About 31-year-old Southeast Asian female with a history of persistent iron deficiency anemia (6.1 gm/dL) presents with bilateral knee pain for 4 years. Autoimmune panel turned out to be negative. CT scan of the lower limbs showed multilamellated endosteal thickening specifically involving diaphyses with severe narrowing of medullary canal. PET CT scan revealed tubular remodeling, intramedullary ground glass matrix, and mild cortical thickening with increased FDG uptake in diaphyseal regions of femur and tibia. Bone marrow biopsy of left tibia revealed fibrocellular marrow with dyserythropoiesis. Considering the slow progression of illness over 4 years and radiological evidence suggestive of bone remodeling with severe narrowing of medullary canal as the cause of anemia, the patient underwent molecular analysis for GHDD. Results revealed homozygous p.Arg412Gln (exon 11) in TBXAS1 gene. Considering the effect of NSAIDs on cyclooxygenase and its downstream metabolites, oral Aspirin 150 mg/day was initiated. Hemoglobin improved to 11 gm/dL at 3-month follow-up visit. The complexity of reaching a diagnosis of GHDD underscores the importance of maintaining a high clinical suspicion and thorough analysis of radiological evidence. The treatment for GHDD involves aspirin, a readily available drug.

High performance and durability are essential for goods to satisfy the needs of the expanding worldwide market. Wood plastic composites (WPCs) are materials made from a combination of wood, polymers, and additives. WPCs can be extruded, injected, compressed, or thermoformed. Presently, WPCs are manufactured using sophisticated processes including as laser sintering, fused layer modeling, and additive manufacturing. Properly managing the melt temperature and pressure is crucial in the manufacturing process of WPCs to ensure effective polymer incorporation. Natural fibers have distinct benefits for polymer composites, but they also have some serious drawbacks, like lower strength properties--especially lower impact strength than synthetic fibers--poor compatibility with hydrophobic polymers, poorer dimensional stability and moisture absorption due to hydroxly groups, a maximum processing temperature that is limited, thermal degradation above 200-220[degrees]C, and lower biological durability. The modification of the surface of the fibers improves the mentioned disadvantages of the natural fibers. High-quality WPCs require the application of chemical or physical treatment to the wood fibers. This extensive review focused on the modification techniques applied to the surface of wood, manufacturing processes, and properties and applications of WPCs. Highlights * Modification methods used in surface treatment of natural fibers was explained. * Properties and recent applications of wood polymer composites were given. * Optimum requirements of natural fibers and polymer matrices are given. * Fabrication methods of natural fiber composites are extensively given. KEYWORDS application, composite preparation, surface treatment, wood flour composites, 1 | INTRODUCTION The use of composite materials is not a new idea worldwide. In the past, builders used to strengthen mud by adding twigs to the mixture when constructing [...]