Mutational Landscape of Patients with Wiskott Aldrich Syndrome: Update from India.

Purpose: Wiskott-Aldrich syndrome (WAS) is an X-linked genetic disorder characterized by distinctive features including microthrombocytopenia, eczema and recurrent infections. In the present study we report clinical, immunological and molecular spectrum of 41 WAS patients diagnosed over last five years.

Methods: Clinical and family history was collected from case records.

Validation of reference genes for cardiac RT-qPCR studies spanning the fetal to adult period.

Many genes used as internal controls for mRNA expression studies are unstable (change) over development. This study determined an approach to validate reference genes for mRNA studies spanning the fetal period to adulthood in sheep hearts.•We determined the mRNA expression of 12 candidate reference genes (ACTB, GAPDH, H3-3A, HYAL2, PPIA, RNA18S1, RPL32, RPL37A, RPL41, RPLP0, RPS15, and YWHAZ) via RT-qPCR.

Comparative analysis of canine and human HtrA2 to delineate its role in apoptosis and cancer.

Therapeutically, targeting the pro- and anti-apoptotic proteins has been one of the major approaches behind devising strategies to combat associated diseases. Human high-temperature requirement serine protease A2 (hHtrA2), which induces apoptosis through both caspase-dependent and independent pathways is implicated in several diseases including cancer, ischemic heart diseases, and neurodegeneration, thus making it a promising target molecule. In the recent past, the canine model has gained prominence in the understanding of human pathophysiology that was otherwise limited to the rodent system.

Heterocyclic Compounds as CDK9 Inhibitors: Structural Diversity, Mechanism of Action, and Therapeutic Potential in Cancer and Beyond.

Cyclin-dependent kinases (CDKs) are crucial proteins involved in key cellular processes, such as cell division and transcription. Their dysregulation plays a significant role in cancer development. Inhibiting cyclin-dependent kinase 9 (CDK9) impacts several survival pathways in cancer cells, presenting a promising therapeutic approach for various cancers.

FDA-approved drugs containing dimethylamine pharmacophore: a review of the last 50 years.

Dimethylamine (DMA) derivatives represent a promising class of compounds with significant potential in the field of medicinal chemistry. DMA derivatives exhibit a diverse range of pharmacological activities, including antimicrobial, antihistaminic, anticancer, and analgesic properties. Their unique chemical structure allows for the modulation of various biological targets, making them valuable candidates for the treatment of numerous diseases.

Targeting type I DED interactions at the DED filament serves as a sensitive switch for cell fate decisions.

Activation of procaspase-8 in the death effector domain (DED) filaments of the death-inducing signaling complex (DISC) is a key step in apoptosis. In this study, a rationally designed cell-penetrating peptide, DEDid, was engineered to mimic the h2b helical region of procaspase-8-DED2 containing a highly conservative FL motif. Furthermore, mutations were introduced into the DEDid binding site of the procaspase-8 type I interface.

Assessment of Body Frame Size by Elbow Breadth and Frame Index and Its Relation to Body Composition Parameters among Tribal Preschool Children in West Bengal, India.

In children, body frame size estimation is used to interpret body mass and evaluate growth patterns. The present study aims to assess the body frame size by elbow breadth and frame index and its relation to body composition parameters among tribal preschool children (1-5 years of age). In the present study, 848 preschool children (430 boys and 418 girls) were included.

Exploring a Preliminary Set of Indicators to Measure Adolescent Health: Results From a 12-Country Feasibility Study.

Purpose: To explore data availability, perceived relevance, acceptability and feasibility of implementing 52 draft indicators for adolescent health measurement in different countries globally.

Methods: A mixed-methods, sequential explanatory study was conducted in 12 countries. An online spreadsheet was used to assess data availability and a stakeholder survey to assess perceived relevance, acceptability, and feasibility of implementing each draft indicator proposed by the Global Action for Measurement of Adolescent health (GAMA).

Marine seaweed endophytic fungi-derived active metabolites promote reactive oxygen species-induced cell cycle arrest and apoptosis in human breast cancer cells.

Background: Endophytic fungi have an abundant sources rich source of rich bioactive molecules with pivotal pharmacological properties. Several studies have found that endophytic fungi-derived bioactive secondary metabolites have antiproliferative, anti-oxidant, and anti-inflammatory properties, but the molecular mechanism by which they induce cell cycle arrest and apoptosis pathways is unknown. This study aimed to determine the molecular mechanism underlying the anticancer property of the endophytic fungi derived active secondary metabolites on human breast cancer cells.

Sensitivity and activation of endoplasmic reticulum stress response and apoptosis in the perinatal sheep heart.

Although the unfolded protein response (UPR) contributes to survival by removing misfolded proteins, endoplasmic reticulum (ER) stress also activates proapoptotic pathways. Changed sensitivity to normal developmental stimuli may underlie observed cardiomyocyte apoptosis in the healthy perinatal heart. We determined in vitro sensitivity to thapsigargin in sheep cardiomyocytes from four perinatal ages.

Cardiac Surgery-Associated Acute Kidney Injury.

AKI is a common and serious complication of cardiac surgery that has a significant impact on patient morbidity and mortality. The Kidney Disease Improving Global Outcomes definition of AKI is widely used to classify and identify AKI associated with cardiac surgery (cardiac surgery-associated AKI [CSA-AKI]) on the basis of changes in serum creatinine and/or urine output. There are various preoperative, intraoperative, and postoperative risk factors for the development of CSA-AKI which should be recognized and addressed as early as possible to expedite its diagnosis, reduce its occurrence, and prevent or ameliorate its devastating complications.

Short-Term, Mid-Term, and Long-Term Outcomes after Deceased Donor Kidney Transplantation in Patients with AKI: A Systematic Review and Meta-Analysis.

Key Points: This study reviews the willingness to use kidneys from donors who have experienced AKI during transplantation and provides a thorough analysis of the existing literature. While delayed graft function is more common, primary nonfunction and acute rejection rates appear comparable, as do allograft function and graft survival compared with non-AKI donor kidneys. Considering the shortage of available organs and the high mortality rate of patients on dialysis, the use of donors with AKI as a source for kidney transplantation is a viable alternative.

Boosting Contraceptive Uptake in Urban Uganda: Older Women Benefit When Layering Adolescent and Youth Interventions Onto Existing Family Planning Programming.

Introduction: Uganda has a large young population with a high unmet need for family planning (FP). Although there have been many efforts to improve access to and uptake of contraception, improvements have been slow. The Ministry of Health Uganda partnered with The Challenge Initiative (TCI) to implement a novel multipronged approach layering adolescent and youth sexual reproductive health (AYSRH) onto a functioning general FP program for women of reproductive age in 3 local governments of Buikwe, Mukono, and Iganga.

Anthropometric markers and their cut-off point for the prediction of hypertension with lifestyle as a risk factor among Chiru tribe of North East India.

Background: The increased prevalence of obesity, particularly central obesity, is closely associated with many metabolic complexions, including hypertension and diabetes.

Objectives: The present study investigates the cut-off points of some anthropometric measurements such as body mass index [BMI (kg/m)], waist circumference [WC (cm)], waist-hip ratio (WHR), and waist-height ratio (WHtR) associated with high blood pressure. It determines the risk factors among the Chiru tribe of North East India.

Implementing Quality Improvement Initiatives to Improve the Use of Adolescent- and Youth-Friendly Health Services in Zou, Benin.

Introduction: In Benin, the unmet need for family planning services is especially high for adolescent girls and youth aged 15-24 years. The Challenge Initiative (TCI) supported the health system to assess and improve the quality of adolescent and youth sexual reproductive health services and enhance contraceptive uptake in 65 service delivery points (SDPs) of the Zou department.

Program Description: Between June 2019 and March 2021, TCI supported the health districts in Zou to train an assessment team to complete 3 cycles of quality assessments (QAs) using a QA checklist adapted to the local context.

Improving the Quality of Adolescent and Youth-Friendly Health Services Through Integrated Supportive Supervision in Four Nigerian States.

Background: Although the unique sexual and reproductive health needs of adolescents and youth (AY) are widely recognized, the challenge remains how to integrate adolescent- and youth-friendly health services (AYFHS) effectively within a systems-based approach that is both feasible and scalable. This article provides preliminary evidence from 4 Nigerian states that sought to overcome this challenge by implementing capacity-strengthening approaches centered around a shortened quality assurance (QA) tool that has become part of the state health system's routine supportive supervision process and follow-up quality improvement (QI) activities.

Methods: A shortened QA tool was administered to assess and track the performance of 130 high-volume health facilities across 5 domains to serve its AY population with quality contraceptive services.

cFLIP - An interacting partner and a novel substrate for pro-apoptotic serine protease HtrA2.

Background: HtrA2, a pro-apoptotic protease, plays a crucial role in apoptosis by cleaving inhibitory and anti-apoptotic proteins by translocating from mitochondria to the cytosol. Prior studies in ischemic cells have indicated that cytosolic HtrA2 triggers cFLIP degradation, plausibly through direct interaction. In this study, we have characterized the cFLIP protein, validated its interaction with HtrA2, and demonstrated that cFLIP is also a substrate of HtrA2.

Improving Contraceptive Service Quality and Accessibility for Adolescents and Youth Through Proprietary Patent Medicine Vendors in Four Nigerian States.

Introduction: In Nigeria, health care services and commodities have increasingly been accessed through private sector entities, including retail pharmacies and drug shops (also called proprietary patent medicine vendors [PPMVs]). However, PPMVs cannot provide long-acting or permanent methods, and concerns have been raised about their quality of services and their need to better comply with government regulations. This article describes how The Challenge Initiative's (TCI) family planning program supported 4 state governments in Nigeria to develop a model to strengthen public-private partnerships between PPMVs and primary health centers (PHCs) to leverage PPMVs to provide adolescents and youth with high-quality contraceptive information, services, and referrals to PHCs.

Correlation between maternal and infant vitamin B12 levels in severe malnutrition in infants under 6 months.

Background: Malnutrition poses a significant global health challenge, affecting various age groups, with infants under 6 months being particularly vulnerable. Vitamin B12, an essential micronutrient critical for neurological development, has been identified as a key player in the overall health of both mothers and infants.

Aim: To find the correlation between serum vitamin B12 levels in infants, 1-6 months of age with severe malnutrition and maternal levels at tertiary care hospitals in western Rajasthan.

Influence of lead-induced toxicity on the inflammatory cytokines.

Lead (Pb) is a hazardous heavy metal that is pervasive in the human environment as a result of anthropogenic activity, and poses serious health risks, particularly in children. Due to its innumerable unique physical and chemical properties, it has various applications; therefore, it has become a common environmental pollutant. Lead may cause oxidative stress, and accumulating evidence indicates that oxidative stress influences the pathophysiology of lead poisoning, also called plumbism.

Sleep fragmentation induces heart failure in a hypertrophic cardiomyopathy mouse model by altering redox metabolism.

Sleep fragmentation (SF) disrupts normal biological rhythms and has major impacts on cardiovascular health; however, it has never been shown to be a risk factor involved in the transition from cardiac hypertrophy to heart failure (HF). We now demonstrate devastating effects of SF on hypertrophic cardiomyopathy (HCM). We generated a transgenic mouse model harboring a patient-specific myosin binding protein C3 (MYBPC3) variant displaying HCM, and measured the progression of pathophysiology in the presence and absence of SF.

"Click Chemistry": An Emerging Tool for Developing a New Class of Structural Motifs against Various Neurodegenerative Disorders.

Click chemistry is a set of easy, atom-economical reactions that are often utilized to combine two desired chemical entities. Click chemistry accelerates lead identification and optimization, reduces the complexity of chemical synthesis, and delivers extremely high yields without undesirable byproducts. The most well-known click chemistry reaction is the 1,3-dipolar cycloaddition of azides and alkynes to form 1,2,3-triazoles.