Durvalumab-Induced Triple-M Syndrome.

Background: While the use of immunotherapy has revolutionised the treatment of various cancers, it is often associated with a myriad of immune-related adverse effects.

Case Presentation: In this article, we report a rare case of durvalumab-induced triple-M syndrome in a 69-year-old woman with stage III lung adenocarcinoma. She was admitted with profound generalised muscle weakness, myalgia, and exertional breathlessness, about a week into her second cycle of durvalumab, an immune checkpoint inhibitor.

pH regulating mechanisms of astrocytes: A critical component in physiology and disease of the brain.

Strict homeostatic control of pH in both intra- and extracellular compartments of the brain is fundamentally important, primarily due to the profound impact of free protons ([H]) on neuronal activity and overall brain function. Astrocytes, crucial players in the homeostasis of various ions in the brain, actively regulate their intracellular [H] (pH) through multiple membrane transporters and carbonic anhydrases. The activation of astroglial pH regulating mechanisms also leads to corresponding alterations in the acid-base status of the extracellular fluid.

Defining the T cell transcriptional landscape in pediatric liver transplant rejection at single cell resolution.

Acute cellular rejection (ACR) affects >80% of pediatric liver transplant recipients within 5 years, and late ACR is associated with graft failure. Traditional anti-rejection therapy for late ACR is ineffective and has remained unchanged for six decades. Although CD8+ T cells promote late ACR, little has been done to define their specificity and gene expression.

Dysregulation of Ion Channels and Transporters and Blood-Brain Barrier Dysfunction in Alzheimer's Disease and Vascular Dementia.

The blood-brain barrier (BBB) plays a critical role in maintaining ion and fluid homeostasis, essential for brain metabolism and neuronal function. Regulation of nutrient, water, and ion transport across the BBB is tightly controlled by specialized ion transporters and channels located within its unique cellular components. These dynamic transport processes not only influence the BBB's structure but also impact vital signaling mechanisms, essential for its optimal function.

Transient ischemic stroke triggers sustained damage of the choroid plexus blood-CSF barrier.

Neuroinflammation is a pathological event associated with many neurological disorders, including dementia and stroke. The choroid plexus (ChP) is a key structure in the ventricles of the brain that secretes cerebrospinal fluid (CSF), forms a blood-CSF barrier, and responds to disease conditions by recruiting immune cells and maintaining an immune microenvironment in the brain. Despite these critical roles, the exact structural and functional changes to the ChP over post-stroke time remain to be elucidated.

Navigating post COVID-19 education: an investigative study on students' attitude and perception of their new normal learning environment.

Background: The incidence and aftermath of the COVID-19 pandemic brought about a drastic change in health professional education around the world. Traditional classrooms made way for online classrooms in order to ensure that learning continued in a safe and secure environment. However, how well health professional students perceived and accepted these changes have not been fully gauged yet.

Systems genetics identifies miRNA-mediated regulation of host response in COVID-19.

Background: Individuals infected with SARS-CoV-2 vary greatly in their disease severity, ranging from asymptomatic infection to severe disease. The regulation of gene expression is an important mechanism in the host immune response and can modulate the outcome of the disease. miRNAs play important roles in post-transcriptional regulation with consequences on downstream molecular and cellular host immune response processes.

Construction of copy number variation landscape and characterization of associated genes in a Bangladeshi cohort of neurodevelopmental disorders.

Copy number variations (CNVs) play a critical role in the pathogenesis of neurodevelopmental disorders (NDD) among children. In this study, we aim to identify clinically relevant CNVs, genes and their phenotypic characteristics in an ethnically underrepresented homogenous population of Bangladesh. We have conducted chromosomal microarray analysis (CMA) for 212 NDD patients with male to female ratio of 2.

T-cell infiltrate intensity is associated with delayed response to treatment in late acute cellular rejection in pediatric liver transplant recipients.

Background: Late acute cellular rejection (ACR) is associated with donor-specific antibodies (DSA) development, chronic rejection, and allograft loss. However, accurate predictors of late ACR treatment response are lacking. ACR is primarily T-cell mediated, yet B cells and plasma cells (PC) also infiltrate the portal areas during late ACR.

Knowledge, Awareness, and Perception of Common Eye Diseases and Eye Donation Among People Seeking Healthcare in a Tertiary Hospital in Telangana, South India.

Background Globally billions of people have vision impairment (VI) or blindness, and at least half of the VI could have been prevented or has yet to be addressed. With the policies focused exclusively on treating ailments, we need to recognize the need to educate the country's population regarding diseases and their outcomes. This is evident in the poor eye donation rates, as documented by the Eye Bank Association of India (EBAI).

Amelioration of bleomycin induced pulmonary fibrosis by administration of Salvianolic acid B in mice.

Pulmonary fibrosis is the end‑stage manifestation of wide range of respiratory diseases and during pulmonary fibrosis, pulmonary inflammation and epithelial‑mesenchymal transition (EMT) play important roles. Salvianolic acid B (SAB) from the herb Salviae miltiorrhiza has been reported to possess an excellent anti‑inflammatory, antifibrotic and antioxidant activity. The present study aimed to investigate the ameliorative effect of SAB on bleomycin induced pulmonary fibrosis in mice.

World Health Organization Versus Diabetes in Pregnancy Study Group India Approaches in the Screening of Gestational Diabetes Among Pregnant Women With Risk Factors: A Study Among Rural Population of Telangana, South India.

Background Gestational diabetes mellitus (GDM) represents a pathological condition wherein pregnant women (PW) suffer from glycemic dysregulation, which predisposes them to an increased risk of developing complications related to pregnancy and childbirth. The most commonly used guidelines to screen for GDM include those provided by the World Health Organization (WHO), the American Congress of Obstetricians and Gynecologists, the Canadian Diabetes Association, and the International Association of Diabetes and Pregnancy Study Group. The Diabetes in Pregnancy Study Group India (DIPSI) guidelines are national-level recommendations to screen for GDM in India.

Assessment of Breastfeeding, Weaning, and Complementary Feeding Practices Among Women Attending a Tertiary Care Teaching Hospital in South India.

Introduction Infants depend exclusively on mothers' milk for nutrition in their early months of life. However, some infants are given cow/buffalo milk during insufficiency. After six months, the children are supplemented with complementary food, including solid food, to meet the nutritional requirements of a growing infant, a process known as weaning.

Polycystic Ovarian Syndrome: Prevalence, Predisposing Factors, and Awareness Among Adolescent and Young Girls of South India.

Introduction Polycystic ovarian syndrome (PCOS) is a leading cause of infertility among women throughout the world. PCOS is an endocrine abnormality that presents as hyperandrogenemia, anovulation, and/or polycystic ovaries. The exact causes of PCOS are not entirely understood.

Analyzing single cell transcriptome data from severe COVID-19 patients.

We describe the protocol for identifying COVID-19 severity specific cell types and their regulatory marker genes using single-cell transcriptomics data. We construct COVID-19 comorbid disease-associated gene list using multiple databases and literature resources. Next, we identify specific cell type where comorbid genes are upregulated.

NOX activation in reactive astrocytes regulates astrocytic LCN2 expression and neurodegeneration.

Reactive astrocytes (RA) secrete lipocalin-2 (LCN2) glycoprotein that regulates diverse cellular processes including cell death/survival, inflammation, iron delivery and cell differentiation. Elevated levels of LCN2 are considered as a biomarker of brain injury, however, the underlying regulatory mechanisms of its expression and release are not well understood. In this study, we investigated the role of astrocytic Na/H exchanger 1 (NHE1) in regulating reactive astrocyte LCN2 secretion and neurodegeneration after stroke.

Role of SPAK-NKCC1 signaling cascade in the choroid plexus blood-CSF barrier damage after stroke.

Background: The mechanisms underlying dysfunction of choroid plexus (ChP) blood-cerebrospinal fluid (CSF) barrier and lymphocyte invasion in neuroinflammatory responses to stroke are not well understood. In this study, we investigated whether stroke damaged the blood-CSF barrier integrity due to dysregulation of major ChP ion transport system, Na-K-Cl cotransporter 1 (NKCC1), and regulatory Ste20-related proline-alanine-rich kinase (SPAK).

Methods: Sham or ischemic stroke was induced in C57Bl/6J mice.

Co-Administration of Iron and Bioavailable Curcumin Reduces Levels of Systemic Markers of Inflammation and Oxidative Stress in a Placebo-Controlled Randomised Study.

Ferrous sulphate (FS) is widely used as an iron supplement to treat iron deficiency (ID), but is known to induce inflammation causing gastric side-effects resulting in poor adherence to supplement regimens. Curcumin, a potent antioxidant, has been reported to suppress inflammation via down regulation of NF-κB. The aim of the present double blind, placebo-controlled randomised trial was to assess whether co-administration of FS with a formulated, bioavailable form of curcumin (HydroCurc™) could reduce systemic inflammation and/or gastrointestinal side-effects.

Mutational Landscape of Autism Spectrum Disorder Brain Tissue.

Rare post-zygotic mutations in the brain are now known to contribute to several neurodevelopmental disorders, including autism spectrum disorder (ASD). However, due to the limited availability of brain tissue, most studies rely on estimates of mosaicism from peripheral samples. In this study, we undertook whole exome sequencing on brain tissue from 26 ASD brain donors from the Harvard Brain Tissue Resource Center (HBTRC) and ascertained the presence of post-zygotic and germline mutations categorized as pathological, including those impacting known ASD-implicated genes.

Traumatic brain Injury related schizophrenia in individuals without family history: A case series.

Traumatic brain injury (TBI) related mental disorder has been hypothesized in the literature before 1969 as the etiology of schizophrenia. TBI has been described as a complex of multiple genetic factors and interacting non-genetic factor influence. Most research on non-genetic factors has focused on the period from conception through childhood.

Co-Expression Analysis of microRNAs and Proteins in Brain of Alzheimer's Disease Patients.

Alzheimer's disease (AD) is the most common form of dementia globally; however, the aetiology of AD remains elusive hindering the development of effective therapeutics. MicroRNAs (miRNAs) are regulators of gene expression and have been of growing interest in recent studies in many pathologies including AD not only for their use as biomarkers but also for their implications in the therapeutic field. In this study, miRNA and protein profiles were obtained from brain tissues of different stage (Braak III-IV and Braak V-VI) of AD patients and compared to matched controls.

Determining the effect of ocular chemical injuries on topical drug delivery.

Ocular chemical injuries (OCIs) commonly cause ocular damage and visual loss and treatment uses topical therapies to facilitate healing and limit complications. However, the impact of chemical injury on corneal barrier function and treatment penetration is unknown. Therefore, the aim of this study was to determine the effect of OCI on drug penetration and absorption.

Single-cell transcriptome identifies upregulated subtype of alveolar macrophages in patients with critical COVID-19.

Understanding host cell heterogeneity is critical for unraveling disease mechanism. Utilizing large-scale single-cell transcriptomics, we analyzed multiple tissue specimens from patients with life-threatening COVID-19 pneumonia, compared with healthy controls. We identified a subtype of monocyte-derived alveolar macrophages (MoAMs) where genes associated with severe COVID-19 comorbidities are significantly upregulated in bronchoalveolar lavage fluid of critical cases.

Attenuating vascular stenosis-induced astrogliosis preserves white matter integrity and cognitive function.

Background: Chronic cerebral hypoperfusion (CCH) causes white matter damage and cognitive impairment, in which astrogliosis is the major pathology. However, underlying cellular mechanisms are not well defined. Activation of Na/H exchanger-1 (NHE1) in reactive astrocytes causes astrocytic hypertrophy and swelling.