Expanded carrier screening for inherited genetic disease using exome and genome sequencing.

The goal of this study was to assess the feasibility of using exome (ES) and genome sequencing (GS) in guiding preconception genetic screening (PCGS) for couples who are planning to conceive by creating a workflow for identifying risk alleles for autosomal recessive (AR) and X-linked (XL) disorders without the constraints of a predetermined, targeted gene panel. There were several limitations and challenges related to reporting and the technical aspects of ES and GS, which are listed in the discussion. We selected 150 couples from a cohort of families (trios) enrolled in a research protocol where the goal was to define the genetic etiology of disease in an affected child.

Amelioration of experimental autoimmune encephalomyelitis by gemfibrozil in mice via PPARβ/δ: implications for multiple sclerosis.

It is important to describe effective and non-toxic therapies for multiple sclerosis (MS), an autoimmune demyelinating disease. Experimental autoimmune encephalomyelitis (EAE) is an immune-mediated inflammatory disease that serves as a model for MS. Earlier we and others have shown that, gemfibrozil, a lipid-lowering drug, exhibits therapeutic efficacy in EAE.

Snyder-Robinson syndrome presenting with learning disability, epilepsy, and osteoporosis: a novel gene variant.

Snyder-Robinson syndrome (SRS) is a rare X-linked recessive disorder characterized by a collection of clinical features including mild to severe intellectual disability, hypertonia, marfanoid habitus, facial asymmetry, osteoporosis, developmental delay and seizures. Whole genome sequencing (WGS) identified a mutation in the spermine synthase () gene (c.746 A>G, p.

FGF12 copy number variant associated with epileptic encephalopathy.

FGF12 related epilepsy presents with variable phenotypes. We report another patient with a duplication involving the FGF12 gene who presented similar to other published cases having normal early development and responded to phenytoin.

Impact of regenerative farming practices on soil quality and yield of cotton-sorghum system in semi arid Indian conditions.

Regenerative agricultural practices, i.e. organic and natural farming, are rooted in India since ancient times.

Therapeutic efficacy of cinnamein, a component of balsam of Tolu/Peru, in controlled cortical impact mouse model of TBI.

Traumatic brain injury (TBI) remains a major health concern which causes long-term neurological disability particularly in war veterans, athletes and young adults. In spite of intense clinical and research investigations, there is no effective therapy to cease the pathogenesis of the disease. It is believed that axonal injury during TBI is potentiated by neuroinflammation and demyelination and/or failure to remyelination.

Nebulization of low-dose aspirin ameliorates Huntington's pathology in N171-82Q transgenic mice.

Huntington Disease (HD), a devastating hereditary neurodegenerative disorder, is caused by expanded CAG trinucleotide repeats in the huntingtin gene () on chromosome 4. Currently, there is no effective therapy for HD. Although aspirin, acetylsalicylic acid, is one of the most widely-used analgesics throughout the world, it has some side effects.

Nuclease-free precise genome editing corrects MECP2 mutations associated with Rett syndrome.

Rett syndrome is an acquired progressive neurodevelopmental disorder caused by mutations in the X-linked MECP2 gene which encodes a pleiotropic protein that functions as a global transcriptional regulator and a chromatin modifier. Rett syndrome predominantly affects heterozygous females while affected male hemizygotes rarely survive. Gene therapy of Rett syndrome has proven challenging due to a requirement for stringent regulation of expression with either over- or under-expression being toxic.

Defining levels of care in cardiogenic shock.

Background: Expert opinion and professional society statements have called for multi-tier care systems for the management of cardiogenic shock (CS). However, little is known about how to pragmatically define centers with different levels of care (LOC) for CS.

Methods: Eleven of 23 hospitals within our healthcare system sharing a common electronic health record were classified as different LOC according to their highest mechanical circulatory support (MCS) capabilities: Level 1 (L-1)-durable left ventricular assist device, Level 1A (L-1A)-extracorporeal membrane oxygenation, Level 2 (L-2)-intra-aortic balloon pump and percutaneous ventricular assist device; and Level 3 (L-3)-no MCS.

Acute exposure to tenorite nanoparticles induces phenotypic and behavior alterations in zebrafish larvae.

Tenorite or copper oxide nanoparticles (CuO NPs) are extensively used in biomedical fields due to their unique physicochemical properties. Increased usage of these NPs leads to release in the environment, affecting varied ecosystems and the biota within them, including humans. The effect of these NPs can be evaluated with zebrafish, an excellent complementary model for nanotoxicity studies.

Inherited CSNK2A1 variants in families with Okur-Chung neurodevelopmental syndrome.

Pedigree showing the autosomal dominant inheritance pattern of CSNK21 variants in families presenting with OCNDS. (A) Maternal inheritance to two daughters in Family 1, (B) Paternal inheritance to a daughter in Family 2, and (C) Maternal inheritance to two sons in Family 3.

Suppression of Experimental Autoimmune Encephalomyelitis in Mice by β-Hydroxy β-Methylbutyrate, a Body-Building Supplement in Humans.

Although several immunomodulatory drugs are available for multiple sclerosis (MS), most present significant side effects with long-term use. Therefore, delineation of nontoxic drugs for MS is an important area of research. β-Hydroxy β-methylbutyrate (HMB) is accessible in local GNC stores as a muscle-building supplement in humans.

Bi-allelic SNAPC4 variants dysregulate global alternative splicing and lead to neuroregression and progressive spastic paraparesis.

The vast majority of human genes encode multiple isoforms through alternative splicing, and the temporal and spatial regulation of those isoforms is critical for organismal development and function. The spliceosome, which regulates and executes splicing reactions, is primarily composed of small nuclear ribonucleoproteins (snRNPs) that consist of small nuclear RNAs (snRNAs) and protein subunits. snRNA gene transcription is initiated by the snRNA-activating protein complex (SNAPc).

Protection of Mice from Controlled Cortical Impact Injury by Food Additive Glyceryl Tribenzoate.

Despite intense investigations, no effective therapy is available to halt the pathogenesis of traumatic brain injury (TBI), a major health concern, which sometimes leads to long-term neurological disability, especially in war veterans and young adults. This study highlights the use of glyceryl tribenzoate (GTB), a flavoring ingredient, in ameliorating the disease process of controlled cortical impact (CCI)-induced TBI in mice. Oral administration of GTB decreased the activation of microglia and astrocytes to inhibit the expression of inducible nitric oxide synthase (iNOS) in hippocampus and cortex of TBI mice.

Protection of dopaminergic neurons in hemiparkinsonian monkeys by flavouring ingredient glyceryl tribenzoate.

Parkinson's disease (PD) is the second most prevalent neurodegenerative disease and this study underlines the significance of a small molecule glyceryl tribenzoate (GTB), a FDA approved food additive, in preventing parkinsonian pathologies in MPTP-induced animal models. The study conducted in MPTP-induced mice demonstrated dose-dependent protection of nigral tyrosine hydroxylase (TH) and striatal dopamine level by GTB oral treatment and the optimum dose was found to be 50 mg/kg/d. In the next phase, the study was carried out in MPTP-injected hemiparkinsonian monkeys, which recapitulate better clinical parkinsonian syndromes.

An empirical investigation of investor sentiment and volatility of realty sector market in India: an application of the DCC-GARCH model.

Understanding how an irrational investors' sentiment affects the realty market returns, especially during the pandemic, is imperative to take any financial decisions. The effect of investor sentiment on the movement of the realty market leading to market volatility is dynamically represented in a numerical form. The study incorporates daily market data and their implicit indices to construct a sector-specific investor sentiment index by using the principal component analysis method.

Treadmill workout activates PPARα in the hippocampus to upregulate ADAM10, decrease plaques and improve cognitive functions in 5XFAD mouse model of Alzheimer's disease.

Although liver is rich in peroxisome proliferator-activated receptor α (PPARα), recently we have described the presence of PPARα in hippocampus where it is involved in non-amyloidogenic metabolism of amyloid precursor protein (APP) via ADAM10, decreasing amyloid plaques and improving memory and learning. However, mechanisms to upregulate PPARα in vivo in the hippocampus are poorly understood. Regular exercise has multiple beneficial effects on human health and here, we describe the importance of regular mild treadmill exercise in upregulating PPARα in vivo in the hippocampus of 5XFAD mouse model of Alzheimer's disease.

Design and Testing of a Smartphone Application for Real-Time Tracking of CSII and CGM Site Rotation Compliance in Patients With Type 1 Diabetes.

Introduction: Glycemic control in patients with type 1 diabetes can be difficult to achieve. One critical aspect of insulin delivery is site rotation, which is necessary to reduce dermatologic complications of repeated insulin infusion. No current application is designed to help patients track sites and instruct on overused sites.

Effect of webinars in teaching-learning process in medical and allied health science students during COVID-19 pandemic: A cross-sectional study.

Background: COVID-19 pandemic lockdown has brought all sectors to be dwindled with no exception of the academic system. Even professional courses like medical and allied health academic courses were also not spared. The academic requirements were not met as required to do so.

Generation of an iPSC line from a Pontocerebellar Hypoplasia 1B patient harboring a homozygous c.395 A > C mutation in EXOSC3 along with a family matched control.

Pontocerebellar Hypoplasia 1B (PCH1B) is a severe autosomal recessive neurological disorder that is associated with mutations in the exosome complex component RRP40 (EXOSC3) gene. We generated and characterized an iPSC line from an individual with PCH1B that harbors a recessive homozygous c.395 A > C mutation in EXOSC3 and a family matched control from the probands unaffected mother.

Antibacterial Photodynamic Therapy in the Near-Infrared Region with a Targeting Antimicrobial Peptide Connected to a π-Extended Porphyrin.

The increase of antimicrobial resistance to conventional antibiotics is worldwide a major health problem that requires the development of new bactericidal strategies. Antimicrobial photodynamic therapy (a-PDT) that generates reactive oxygen species acting on multiple cellular targets is unlikely to induce bacterial resistance. This localized treatment requires, for safe and efficient treatment of nonsuperficial infections, a targeting photosensitizer excited in the near IR.

Sodium Benzoate, a Metabolite of Cinnamon and a Food Additive, Improves Cognitive Functions in Mice after Controlled Cortical Impact Injury.

Traumatic brain injury (TBI) is a major health concern, sometimes leading to long-term neurological disability, especially in children, young adults and war veterans. Although research investigators and clinicians have applied different treatment strategies or neurosurgical procedures to solve this health issue, we are still in need of an effective therapy to halt the pathogenesis of brain injury. Earlier, we reported that sodium benzoate (NaB), a metabolite of cinnamon and a Food and Drug Administration-approved drug against urea cycle disorders and glycine encephalopathy, protects neurons in animal models of Parkinson's disease and Alzheimer's disease.