The process of aging in the brain is reflective of various factors including the environment, lifestyle, genetics, and management of concurrent chronic conditions. Aging in the brain leads to observable structural changes on neuroimaging, such as brain volume reduction, neuronal atrophy, and synaptic loss, which affect higher cognitive functions. Positron emission tomography imaging can help visualize these changes earlier before structural changes even take place and the associated decline in brain function, revealing important insights into how the brain ages and the impact on neural connectivity and cognitive abilities.
View Article and Find Full Text PDFDespite major advances in neonatal care, oxygen remains the most commonly used medication in the neonatal intensive care unit (NICU). Supplemental oxygen can be life-saving for term and preterm neonates in the resuscitation period and beyond, however use of oxygen in the neonatal period must be judicious as there can be toxic effects. Newborns experience substantial hemodynamic changes at birth, rapid energy consumption, and decreased antioxidant capacity, which requires a delicate balance of sufficient oxygen while mitigating reactive oxygen species causing oxidative stress.
View Article and Find Full Text PDFBackground: India accounts for the largest number of global neonatal deaths with around 20 per 1000 live births. To improve the utilization of government services for institutional deliveries, Augmented Arogya Laxmi Scheme (ALS) was launched in Telangana state of southern India. This study assessed the effectiveness of the Janani Suraksha Yojana (JSY), which combines cash assistance with delivery and post-delivery care, in comparison to ALS in improving the outcomes related to antenatal, natal, and postnatal care in urban settlements of Hyderabad, Telangana, southern India.
View Article and Find Full Text PDFPurpose Of Review: The treatment of stage III N2 non-small cell lung cancer (NSCLC) remains debated. There is an absence of a universally agreed definition of resectability for this heterogeneous group and a lack of trial data.
Recent Findings: We reviewed and compared current international guidelines and evidence surrounding management of stage III N2 NSCLC.
J Neonatal Perinatal Med
December 2023
Background: The standard of care for respiratory support of preterm infants is nasal continuous positive airway pressure (CPAP), yet practices are not standardized. Our aim was to survey CPAP practices in infants < 32 weeks gestation among the American Academy of Pediatrics Neonatal-Perinatal section.
Methods: A US, web-based survey inquired about the initiation, management, and discontinuation of CPAP, and chinstrap use and oral feedings on CPAP.
Background: SARS-CoV-2 infection during pregnancy may cause adverse maternal, neonatal and placental outcomes. While tissue hypoxia is often reported in COVID-19 patients, pregnant women with anemia are suspected to be more prone to placental hypoxia-related injuries.
Methods: This hospital-based cross-sectional study was conducted between August-November 2021, during COVID-19 second wave in India.
Objectives: HIV affects 36 million people globally with prevalence decreasing due to antiretroviral therapy (ART) and social awareness; transmission occurs during substance use. Cocaine usage independently affects brain activity and may result in reduced ART adherence. This study evaluates brain glucose metabolism measured by 18 F-fluorodeoxyglucose positron emission tomography/computed tomography ( 18 F-FDG PET/CT) in cocaine users with HIV infection.
View Article and Find Full Text PDFBackground/objectives: Globally, the COVID-19 pandemic and its prevention and control policies have impacted maternal and child health (MCH) services. This study documents the challenges faced by patients in accessing MCH services, and the experiences of health care providers in delivering those services during the COVID-19 outbreak, explicitly focusing on the lockdown period in India.
Methods: A cross-sectional study (rapid survey) was conducted in 18 districts from 6 states of India during March to June, 2020.
Maternal nutritional status and care during pregnancy are essential for adequate birth weight. In this prospective cohort study (N = 1061) in an urban slum, we investigated the association of maternal anthropometry, body composition, gestational weight gain and dietary intakes with low birthweight (LBW, <2.5 kg).
View Article and Find Full Text PDFPatients with prostate cancer whose tumors bear deleterious mutations in DNA-repair pathways often respond to PARP inhibitors. Studies were conducted to compare the activity of several PARP inhibitors in vitro and their tissue exposure and in vivo efficacy in mice bearing PC-3M-luc-C6 prostate tumors grown subcutaneously or in bone. Niraparib, olaparib, rucaparib, and talazoparib were compared in proliferation assays, using several prostate tumor cell lines and in a cell-free PARP-trapping assay.
View Article and Find Full Text PDFIntroduction: The central C4 and C5 domains (C4C5) of cardiac myosin binding protein C (cMyBPC) contain a flexible interdomain linker and a cardiac-isoform specific loop. However, their importance in the functional regulation of cMyBPC has not been extensively studied.
Methods And Results: We expressed recombinant C4C5 proteins with deleted linker and loop regions and performed biophysical experiments to determine each of their structural and dynamic roles.
Objective: To compare the acceptability of a locally produced ready-to-use therapeutic food (L-RUTF) with the standard ready-to-use therapeutic food (S-RUTF).
Methods: It was a single-center, randomized, double-blind, two-way crossover study. The participants were 6-59-mo-old children residing in an urban slum, with weight-for-height z score (WHZ) < -2SD.
CPT Pharmacometrics Syst Pharmacol
September 2021
Erdafitinib is a potent oral pan-fibroblast growth factor receptor inhibitor being developed as oncology drug for patients with alterations in the fibroblast growth factor receptor pathway. Erdafitinib binds preferentially to α1-acid glycoprotein (AGP) and is primarily metabolized by cytochrome P450 (CYP) 2C9 and 3A4. This article describes a physiologically based pharmacokinetic (PBPK) model for erdafitinib to assess the drug-drug interaction (DDI) potential of CYP3A4 and CYP2C9 inhibitors and CYP3A4/CYP2C9 inducers on erdafitinib pharmacokinetics (PK) in patients with cancer exhibiting higher AGP levels and in populations with different CYP2C9 genotypes.
View Article and Find Full Text PDFPurpose: To assess the safety and pharmacokinetics and determine the recommended phase 2 dose (RP2D) of niraparib with apalutamide or abiraterone acetate plus prednisone (AAP) in patients with metastatic castration-resistant prostate cancer (mCRPC).
Methods: BEDIVERE was a multicenter, open-label, phase 1b study of niraparib 200 or 300 mg/day with apalutamide 240 mg or AAP (abiraterone acetate 1000 mg; prednisone 10 mg). Patients with mCRPC were previously treated with ≥ 2 lines of systemic therapy, including ≥ 1 androgen receptor-axis-targeted therapy for prostate cancer.
Omecamtiv mecarbil (OM), a direct myosin motor activator, is currently being tested as a therapeutic replacement for conventional inotropes in heart failure (HF) patients. It is known that HF patients exhibit dysregulated β-adrenergic signaling and decreased cardiac myosin-binding protein C (cMyBPC) phosphorylation, a critical modulator of myocardial force generation. However, the functional effects of OM in conditions of altered cMyBPC phosphorylation have not been established.
View Article and Find Full Text PDFMultiple micronutrient deficiencies (MNDs) co-exist, often because of poor intakes and adversely impact health. Habitual diets were assessed in 300 school children (6-17 years old) recruited from two government schools by simple random sampling. Probability of adequacy (PA) for 11 micronutrients and mean probability of adequacy (MPA) was calculated.
View Article and Find Full Text PDFThis article describes biotransformation and disposition of erdafitinib following single oral dose of H-erdafitinib and C-erdafitinib to intact and bile duct-cannulated (BC) rats (4 mg/kg), H-erdafitinib to intact dogs (0.25 mg/kg), and C-erdafitinib to humans (12 mg; NCT02692677). Peak plasma concentrations of total radioactivity were achieved rapidly (: animals, 1 h; humans, 2-3 h).
View Article and Find Full Text PDFDecreased cardiac myosin-binding protein C (cMyBPC) expression due to inheritable mutations is thought to contribute to the hypertrophic cardiomyopathy (HCM) phenotype, suggesting that increasing cMyBPC content is of therapeutic benefit. In vitro assays show that cMyBPC N-terminal domains (NTDs) contain structural elements necessary and sufficient to modulate actomyosin interactions, but it is unknown if they can regulate in vivo myocardial function. To test whether NTDs can recapitulate the effects of full-length (FL) cMyBPC in rescuing cardiac function in a cMyBPC-null mouse model of HCM, we assessed the efficacy of AAV9 gene transfer of a cMyBPC NTD that contained domains C0C2 and compared its therapeutic potential with AAV9-FL gene replacement.
View Article and Find Full Text PDFBackground: Non-healing plantar ulcers are one of the significant causes of disability in leprosy patients. Plantar ulcers often take months or years to heal, affecting the patient's quality of life. Presence of comorbid conditions in these patients can delay wound healing.
View Article and Find Full Text PDFExpert Opin Drug Discov
April 2020
: Heart failure remains one of the largest clinical challenges in the United States. Researchers have continually searched for more effective heart failure treatments that target the cardiac sarcomere but have found few successes despite numerous expensive cardiovascular clinical trials. Among many reasons, the high failure rate of cardiovascular clinical trials may be partly due to incomplete characterization of a drug candidate's complex interaction with cardiac physiology.
View Article and Find Full Text PDFStudies to date demonstrated the relatedness of mid-upper arm circumference (MUAC) measurement of pregnant women to their anthropometry/weight. Hence, the objective was to determine whether maternal MUAC at different gestational age predicted birthweight, and if so, to identify which cut-offs provided the best prediction of low birthweight (LBW) in pregnant women cohort. A total of 928 pregnant women, free of any obstetrical and medical complications known to affect fetal growth, were followed from 20 to 24 weeks' gestation till delivery.
View Article and Find Full Text PDFBackground And Objectives: Erdafitinib, an oral selective pan-fibroblast growth factor receptor (FGFR) kinase inhibitor, is primarily metabolized by cytochrome P450 (CYP) 2C9 and 3A4. The aim of this phase 1 study was to assess the pharmacokinetics and safety of erdafitinib in healthy participants when coadministered with fluconazole (moderate CYP2C9 and CYP3A inhibitor), and itraconazole (a strong CYP3A4 and P-glycoprotein inhibitor). The effect of CYP2C9 genotype variants (*1/*1, *1/*2, *1/*3) on the pharmacokinetics of erdafitinib was also investigated.
View Article and Find Full Text PDFSevere acute malnutrition (SAM) in children under five years is an important public health problem due to associated high mortality and long-term health consequences. Research on the dietary causes of SAM, especially the role and relative importance of dietary protein, in the aetiology of oedematous malnutrition, has led to considerable debates and controversies. The present article revisits some of the debates in this field, where the researchers at the National Institute of Nutrition (NIN), Hyderabad, India, with their pioneering work, have contributed to the global literature on the various facets of the disease.
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