Molecular basis of CRX/DNA recognition and stoichiometry at the Ret4 response element.

Two retinal transcription factors, cone-rod homeobox (CRX) and neural retina leucine zipper (NRL), cooperate functionally and physically to control photoreceptor development and homeostasis. Mutations in CRX and NRL cause severe retinal diseases. Despite the roles of NRL and CRX, insight into their functions at the molecular level is lacking.

Reconstitution of the phosphodiesterase 6 maturation process important for photoreceptor cell function.

The sixth family phosphodiesterases (PDE6) are principal effector enzymes of the phototransduction cascade in rods and cones. Maturation of nascent PDE6 protein into a functional enzyme relies on a coordinated action of ubiquitous chaperone HSP90, its specialized cochaperone aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1), and the regulatory Pγ-subunit of PDE6. Deficits in PDE6 maturation and function underlie severe visual disorders and blindness.

Barriers of household toilet utilization among toilet owners in a rural area of Northern India: An analytical cross-sectional study.

Background: Open defecation continues to prevail among toilet owners despite effective implementation of the Swachh Bharat Mission (Gramin). We conducted this study to determine toilet utilization rates and learn about the barriers to toilet use in the rural areas. By understanding the barriers, physicians can provide targeted education and become better equipped to manage their patients' conditions and advocate for their demands.

Estimation of Access to Safe Drinking Water to Households in Etawah District: A Cross-Sectional Study.

Context: Unsafe drinking water causes diarrheal disease and environmental enteropathy. The quality of water is determined by its physical, chemical, and biological characteristics. Water sources have a significant impact on household members' health, particularly children.

Insulin sensitization by small molecules enhancing GLUT4 translocation.

Insulin resistance (IR) is the root cause of type II diabetes, yet no safe treatment is available to address it. Using a high throughput compatible assay that measures real-time translocation of the glucose transporter glucose transporter 4 (GLUT4), we identified small molecules that potentiate insulin action. In vivo, these insulin sensitizers improve insulin-stimulated GLUT4 translocation, glucose tolerance, and glucose uptake in a model of IR.

Unique interface and dynamics of the complex of HSP90 with a specialized cochaperone AIPL1.

Photoreceptor phosphodiesterase PDE6 is central for visual signal transduction. Maturation of PDE6 depends on a specialized chaperone complex of HSP90 with aryl hydrocarbon receptor-interacting protein-like 1 (AIPL1). Disruption of PDE6 maturation underlies a severe form of retina degeneration.

Frmpd1 Facilitates Trafficking of G-Protein Transducin and Modulates Synaptic Function in Rod Photoreceptors of Mammalian Retina.

Trafficking of transducin (Gα) in rod photoreceptors is critical for adaptive and modulatory responses of the retina to varying light intensities. In addition to fine-tuning phototransduction gain in rod outer segments (OSs), light-induced translocation of Gα to the rod synapse enhances rod to rod bipolar synaptic transmission. Here, we show that the rod-specific loss of Frmpd1 (FERM and PDZ domain containing 1), in the retina of both female and male mice, results in delayed return of Gα from the synapse back to outer segments in the dark, compromising the capacity of rods to recover from light adaptation.

Modified Bain's Circuit as an Alternate to Non-invasive Ventilation in COVID 19.

Introduction COVID-19 is a pandemic that severely affects the lungs. Symptomatically affected individuals often become severely hypoxic, requiring non-invasive ventilation. The scarcity of resources in resource-compromised countries like India led to the adoption of novel strategies like using Bain's circuit for assisting spontaneous ventilation.

Assessment of knowledge and their practices regarding malaria among members of Village Health Sanitation Committee in rural Uttar Pradesh: A cross-sectional study.

Background: In 2019, the global number of malaria cases was estimated at 229 million. An estimated 409,000 deaths were attributed to malaria in 2019. Under-five children are the most susceptible to malaria, accounting for 67% (274,000) of all malaria deaths worldwide in 2019.

Are the labour rooms of primary healthcare facilities capable of providing basic delivery and newborn services? A cross-sectional study.

Objectives: The study aimed to assess the functionality of labour rooms by evaluating the labour room infrastructure with reference to the standard guidelines, the status of the availability of human resources, the availability of essential equipment and consumables in the labour room and by documenting the knowledge of the healthcare provider in terms of labour room practices. The study also explored the facility parameters associated with its delivery load taking the facility as a unit of analysis.

Design: A cross-sectional analytical study.

Pregnancy outcomes and vertical transmission capability of SARS-CoV-2 infection among asymptomatic females: A cross-sectional study in a tertiary care rural hospital.

Background: The COVID-19 pandemic is still spreading throughout the world along with its strange and frightening mutations, and the World Health Organization (WHO) has declared it as a global pandemic.

Objective: The present investigation aims to evaluate the effect of SARS-CoV-2 infection on mother and newborn outcomes and the vertical transmission potential of this virus.

Study Design: This was a cross-sectional study conducted at a tertiary care dedicated COVID-19 hospital.

Retrospective sequential trend analysis of neoplasms reported in a tertiary care hospital of district Etawah, Uttar Pradesh.

Introduction: An estimated 2.25 million new cancer cases with 7 lakh cancer deaths were reported, according to GLOBOCAN 2018 in India. There is a steady rise in cancer cases, but trends and patterns vary within the state depending on the geographic region.

Epidemiological characteristics, reinfection possibilities and vaccine development of SARS CoV2: A global review.

According to the World Health Organization (WHO), there are 37,704,153 cases and 10,79,029 deaths due to COVID-19 till the 13th October 2020 in the world. Day by day, rise in the number of COVID-19 deaths has created great pressure on health facilities, governmental bodies, and health workers. There is a need for knowledge regarding lifecycle, transmission, and different strains of SARSCoV2, so that countries can stop the disease as early as possible.

Systemic review of CNS involvement and its manifestations in SARS-CoV2 positive patients.

Coronavirus is known to cause various systemic infections both in human and animal which are mostly mild in nature. However, recent years have seen major pandemics caused by coronavirus which are very invasive and virulent in nature. The recent SARS-CoV2 is a new addition to this list of coronavirus pandemics.

Morbidity Patterns among Menopausal Women in Rural Uttar Pradesh, India: A Cross-Sectional Study.

Objectives: The quality of life declines gradually as women enter menopause, owing to the various problems associated with estrogen deficiency and aging, which adds to their morbidities. This study aimed to investigate the patterns of morbidity among rural menopausal women and compare the morbidity patterns among menopausal transition group and post-menopausal women.

Methods: This community-based cross-sectional study included menopausal women aged 45-55 years from rural areas of the Etawah district, Uttar Pradesh, India.

A Randomized Controlled Study Comparing Dexmedetomidine-Midazolam with Fentanyl-Midazolam for Sedation during awake Fiberoptic Intubation in Anticipated Difficult Airway.

Background: Awake fibreoptic nasotracheal intubation is an effective technique for the management of patients with difficult airways. Adequate sedation with effective topicalization of the airway is important to overcome discomfort and achieve intubation successfully.

Aim And Objectives: Our aim was to compare the effectiveness of dexmedetomidine-midazolam with fentanyl-midazolam infusion for providing conscious sedation during fibreoptic intubation in patients with anticipated difficult airway under topical anaesthesia.

Structural basis for allosteric regulation of pyruvate kinase M2 by phosphorylation and acetylation.

Pyruvate kinase muscle isoform 2 (PKM2) is a key glycolytic enzyme and transcriptional coactivator and is critical for tumor metabolism. In cancer cells, native tetrameric PKM2 is phosphorylated or acetylated, which initiates a switch to a dimeric/monomeric form that translocates into the nucleus, causing oncogene transcription. However, it is not known how these post-translational modifications (PTMs) disrupt the oligomeric state of PKM2.

Transducin Partners Outside the Phototransduction Pathway.

Transducin mediates signal transduction in a classical G protein-coupled receptor (GPCR) phototransduction cascade. Interactions of transducin with the receptor and the effector molecules had been extensively investigated and are currently defined at the atomic level. However, partners and functions of rod transducin α (Gα ) and βγ (Gβγ) outside the visual pathway are not well-understood.

Neurological Involvement in COVID-19 Patients: A Narrative Review.

 Coronavirus disease 2019 (COVID-19) is a viral disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) belonging to the coronavirus family. The primary target of SARS-CoV-2 is peripheral mucosal cells of respiratory tract. Recent days have seen few cases where virus has affected extrapulmonary organ such as nervous system.

Hyperbaric oxygen therapy as an adjuvant to standard therapy in the treatment of diabetic foot ulcers.

Background And Aims: Chronic diabetic foot ulcers pose a major problem because of associated limb threatening complications. The aim of the present study was to evaluate the efficacy of hyperbaric oxygen therapy (HBOT) as an adjuvant to standard therapy for treatment of diabetic foot ulcers.

Material And Methods: A total of 54 patients with diabetic foot ulcer of Wagner grade II-IV were recruited in this prospective, randomized, double blind study.

Analysis of risk factors contributing to road traffic accidents in a tertiary care hospital. A hospital based cross-sectional study.

Purpose: Road traffic accidents (RTAs) are a public health issue and cost a lot to individuals, families, communities and nations. Trauma care systems in India are at a nascent stage of development. There is gross disparity between trauma services available in various parts of the country.

Ric-8A, a GEF, and a Chaperone for G Protein α-Subunits: Evidence for the Two-Faced Interface.

Resistance to inhibitors of cholinesterase 8A (Ric-8A) is a prominent non-receptor GEF and a chaperone of G protein α-subunits (Gα). Recent studies shed light on the structure of Ric-8A, providing insights into the mechanisms underlying its interaction with Gα. Ric-8A is composed of a core armadillo-like domain and a flexible C-terminal tail.

Large-scale conformational rearrangement of the α5-helix of Gα subunits in complex with the guanine nucleotide exchange factor Ric8A.

Resistance to inhibitors of cholinesterase 8A (Ric8A) protein is an important G protein-coupled receptor (GPCR)-independent regulator of G protein α-subunits (Gα), acting as a guanine nucleotide exchange factor (GEF) and a chaperone. Insights into the complex between Ric8A and Gα hold the key to understanding the mechanisms underlying noncanonical activation of G-protein signaling as well as the folding of nascent Gα proteins. Here, we examined the structure of the complex of Ric8A with minimized Gα (miniGα) in solution by small-angle X-ray scattering (SAXS) and exploited the scattering profile in modeling of the Ric8A/miniGα complex by steered molecular dynamics (SMD) simulations.

Mechanistic and Structural Insights into Cysteine-Mediated Inhibition of Pyruvate Kinase Muscle Isoform 2.

Cancer cells regulate key enzymes in the glycolytic pathway to control the glycolytic flux, which is necessary for their growth and proliferation. One of the enzymes is pyruvate kinase muscle isoform 2 (PKM2), which is allosterically regulated by various small molecules. Using detailed biochemical and kinetic studies, we demonstrate that cysteine inhibits wild-type (wt) PKM2 by shifting from an active tetramer to a mixture of a tetramer and a less active dimer/monomer equilibrium and that the inhibition is dependent on cysteine concentration.