Safety and efficacy of selective RIPK1 inhibitor SIR1-365 in hospitalized patients with severe COVID-19: A multicenter, randomized, double-blind, phase 1b trial.

Background: Receptor-interacting protein kinase 1 (RIPK1), a serine/threonine protein kinase, is mainly activated by pro-inflammatory cytokines and pathogens, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and its activation could result in apoptosis, necroptosis, or inflammation. This study was conducted to evaluate the safety and efficacy of a potent and selective inhibitor of RIPK1, SIR1-365, in hospitalized patients with severe coronavirus disease 2019 (COVID-19).

Methods: This multicenter, randomized, double-blind, phase 1b study screened patients from December 18, 2020 until November 27, 2021.

Consensus statements for influenza awareness, prevention, and vaccination in Pakistan.

Introduction: Influenza is a serious underestimated viral infection in Pakistan and influenza vaccination and vaccination awareness are low. The current work aimed to develop consensus on influenza epidemiology, prevention, vaccination, and awareness in Pakistan.

Methodology: A systematic literature search was conducted to develop recommendations on influenza vaccines in Pakistan.

Cilia Provide a Platform for the Generation, Regulated Secretion, and Reception of Peptidergic Signals.

Cilia are microtubule-based cellular projections that act as motile, sensory, and secretory organelles. These structures receive information from the environment and transmit downstream signals to the cell body. Cilia also release vesicular ectosomes that bud from the ciliary membrane and carry an array of bioactive enzymes and peptide products.

Home Isolated COVID-19 Patients Adhering To Recommended Guidelines: A Cross Sectional Survey In Karachi.

Objectives: To assess compliance level of coronavirus disease-2019 patients with recommended isolation guidelines.

Methods: The cross-sectional phone-based survey was conducted in Karachi, from March to October 2020 after approval from the ethics review board of Dow University of Health Sciences, Karachi, and comprised patients of either gender who had been tested positive and were advised home isolation due to mild/asymptomatic nature of their infection. Data was collected using a predesigned 42-item questionnaire in the light of the guidelines issued by the National Institutes of Health, Islamabad, Pakistan.

An assessment of the physicochemical characteristics and essential oil composition of (L.) Huds. exposed to different salt stress conditions.

Salt stress adversely influences growth, development, and productivity in plants, resulting in a limitation on agriculture production worldwide. Therefore, this study aimed to investigate the effect of four different salts, i.e.

Flood 2022 in Pakistan: Managing medical flood relief camps in a developing country.

Floods are the most common natural disasters in the world. Currently Pakistan is in an acute emergency situation due to the recent flood that occurred as a result of the monsoon rains in July-August 2022. Unfortunately, the country was already under an economic crisis and was just recovering from the COVID pandemic when this devastating calamity struck.

Isolation of ciliary ectosomes and analysis of amidated peptide-mediated chemotaxis in Chlamydomonas.

Ciliary ectosomes are vesicles that bud from the ciliary membrane. Isolation and analysis of these structures can shed light on their bioactive cargoes and identify proteins and biomolecules involved in intercellular communication and various physiological processes. Most published methods to isolate ciliary ectosomes are based on their size (100nm to 1μm) to separate cilia-derived vesicles from isolated cilia and/or intact cells.

Phase II/III trial of hyperimmune anti-COVID-19 intravenous immunoglobulin (C-IVIG) therapy in severe COVID-19 patients: study protocol for a randomized controlled trial.

Background: COVID-19 poses a global health challenge with more than 325 million cumulative cases and above 5 million cumulative deaths reported till January 17, 2022, by the World Health Organization. Several potential treatments to treat COVID-19 are under clinical trials including antivirals, steroids, immunomodulators, non-specific IVIG, monoclonal antibodies, and passive immunization through convalescent plasma. The need to produce anti-COVID-19 IVIG therapy must be continued, alongside the current treatment modalities, considering the virus is still mutating into variants of concern.

Regulated processing and secretion of a peptide precursor in cilia.

Cilia are sensory and secretory organelles that both receive information from the environment and transmit signals. Cilia-derived vesicles (ectosomes), formed by outward budding of the ciliary membrane, carry enzymes and other bioactive products; this process represents an ancient mode of regulated secretion. Peptidergic intercellular communication controls a wide range of physiological and behavioral responses and occurs throughout eukaryotes.

Efficacy of heterologous boosting against SARS-CoV-2 using a recombinant interferon-armed fusion protein vaccine (V-01): a randomized, double-blind and placebo-controlled phase III trial.

Waning of neutralizing titres along with decline of protection efficacy after the second dose of COVID-19 vaccines was observed, including China-made inactivated vaccines. Efficacy of a heterologous boosting using one dose of a recombinant SARS-CoV-2 fusion protein vaccine (V-01) in inactivated vaccine-primed population was studied, aimed to restore the immunity. A randomized, double-blind and placebo-controlled phase III trial was conducted in healthy people aged 18 years or older in Pakistan and Malaysia.

Cilia-derived vesicles: An ancient route for intercellular communication.

Extracellular vesicles (EVs) provide a mechanism for intercellular communication that transports complex signals in membrane delimited structures between cells, tissues and organisms. Cells secrete EVs of various subtypes defined by the pathway leading to release and by the pathological condition of the cell. Cilia are evolutionarily conserved organelles that can act as sensory structures surveilling the extracellular environment.

Hyperimmune anti-COVID-19 IVIG (C-IVIG) treatment in severe and critical COVID-19 patients: A phase I/II randomized control trial.

Background: Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG) is an unexplored therapy amidst the rapidly evolving spectrum of medical therapies for COVID-19 and is expected to counter the three most life-threatening consequences of COVID-19 including lung injury by the virus, cytokine storm and sepsis.

Methods: A single center, phase I/II, randomized controlled, single-blinded trial was conducted at Dow University of Health Sciences, Karachi, Pakistan. Participants were COVID-19 infected individuals, classified as either severely or critically ill with Acute Respiratory Distress Syndrome (ARDS).

Successful desensitization and kidney transplantation in the presence of donor-specific anti-human leukocyte antigen antibodies in kidney transplant recipients.

Kidney transplantation has indisputably revamped renal medicine and restored hope among patients coming across fatal end-stage renal disease. However, sensitization of human leukocyte antigen (HLA) triggers extensive immunological fences to successful kidney transplantation and henceforth, transplant candidates are frequently demoted to the ever-growing waiting list owing to preformed donor specific antibodies (DSAs). Over the past few years, the advent of desensitization protocols has significantly overpowered the immunological barriers and enhanced the outcomes of kidney transplant recipients with DSAs against HLA.

Production of hyperimmune anti-SARS-CoV-2 intravenous immunoglobulin from pooled COVID-19 convalescent plasma.

This study assesses the feasibility of producing hyperimmune anti-COVID-19 intravenously administrable immunoglobulin (C-IVIG) from pooled convalescent plasma (PCP) to provide a safe and effective passive immunization treatment option for COVID-19. PCP was fractionated by modified caprylic acid precipitation followed by ultrafiltration/diafiltration to produce hyperimmune C-IVIG. In C-IVIG, the mean SARS-CoV-2 antibody level was found to be threefold (104 ± 30 cut-off index) that of the PCP (36 ± 8.

Multiple Drug Resistant Urinary Tract Infection in Kidney Transplant Recipients: A Retrospective Cohort Study.

Urinary tract infection (UTI) is the most common infectious disease in post-kidney transplantation patients. The objective of the study was to investigate the prevalence, impact and risk factors of multiple drug resistant (MDR) UTI in kidney transplant recipients. This retrospective cohort study recruited 72 kidney transplant recipients between March 2017 and February 2018.

Hyperimmune anti-COVID-19 IVIG (C-IVIG) Therapy for Passive Immunization of Severe and Critically Ill COVID-19 Patients: A structured summary of a study protocol for a randomised controlled trial.

Objectives: The aim of this trial is to investigate the safety and clinical efficacy of passive immunization therapy through Hyperimmune anti-COVID-19 Intravenous Immunoglobulin (C-IVIG: 5% liquid formulation), on severe and critically ill patients with COVID-19.

Trial Design: This is a phase I/II single centre, randomised controlled, single-blinded, superiority trial, through parallel-group design with sequential assignment. Participants will be randomised either to receive both C-IVIG and standard care or only standard care (4:1).

Peptidylglycine α-amidating monooxygenase is required for atrial secretory granule formation.

The discovery of atrial secretory granules and the natriuretic peptides stored in them identified the atrium as an endocrine organ. Although neither atrial nor brain natriuretic peptide (ANP, BNP) is amidated, the major membrane protein in atrial granules is peptidylglycine α-amidating monooxygenase (PAM), an enzyme essential for amidated peptide biosynthesis. Mice lacking cardiomyocyte PAM () are viable, but a gene dosage-dependent drop in atrial ANP and BNP content occurred.

Cilia-based peptidergic signaling.

Peptide-based intercellular communication is a ubiquitous and ancient process that predates evolution of the nervous system. Cilia are essential signaling centers that both receive information from the environment and secrete bioactive extracellular vesicles (ectosomes). However, the nature of these secreted signals and their biological functions remain poorly understood.

Rapid degradation of progressive ankylosis protein (ANKH) in craniometaphyseal dysplasia.

Mutations in the progressive ankylosis protein (NP_473368, human ANKH) cause craniometaphyseal dysplasia (CMD), characterized by progressive thickening of craniofacial bones and widened metaphyses in long bones. The pathogenesis of CMD remains largely unknown, and treatment for CMD is limited to surgical intervention. We have reported that knock-in mice (Ank) carrying a F377del mutation in ANK (NM_020332, mouse ANK) replicate many features of CMD.

Proteases Shape the Secretome: Comparison to Classical Neuropeptide Processing Machinery.

The recent identification of catalytically active peptidylglycine α-amidating monooxygenase (PAM) in Chlamydomonas reinhardtii, a unicellular green alga, suggested the presence of a PAM-like gene and peptidergic signaling in the last eukaryotic common ancestor (LECA). We identified prototypical neuropeptide precursors and essential peptide processing enzymes (subtilisin-like prohormone convertases and carboxypeptidase B-like enzymes) in the genome. Reasoning that sexual reproduction by C.

The influence of treatment, age at onset, and metabolic control on height in children and adolescents with type 1 diabetes-A SWEET collaborative study.

Objective: To describe the association between height, demographics, and treatment in youths with type 1 diabetes participating in an international network for pediatric diabetes centers (SWEET).

Methods: Data were collected from 55 centers with documented patients' height. All subjects below 20 years of age, diabetes duration >1 year, and without celiac disease were included.

Craniometaphyseal Dysplasia Mutations in ANKH Negatively Affect Human Induced Pluripotent Stem Cell Differentiation into Osteoclasts.

We identified osteoclast defects in craniometaphyseal dysplasia (CMD) using an easy-to-use protocol for differentiating osteoclasts from human induced pluripotent stem cells (hiPSCs). CMD is a rare genetic bone disorder, characterized by life-long progressive thickening of craniofacial bones and abnormal shape of long bones. hiPSCs from CMD patients with an in-frame deletion of Phe377 or Ser375 in ANKH are more refractory to in vitro osteoclast differentiation than control hiPSCs.

Expression of the SIN3 homologue from banana, MaSIN3, suppresses ABA responses globally during plant growth in Arabidopsis.

The SIN3 family of co-repressors is a family of highly conserved eukaryotic repressor proteins that regulates diverse functions in yeasts and animals but remains largely uncharacterized functionally even in plants like Arabidopsis. The sole SIN3 homologue in banana, MaSIN3, was identified as a 1408 amino acids, nuclear localized protein conserved to other SIN3s in the PAH, HID and HCR domains. Interestingly, MaSIN3 over-expression in Arabidopsis mimics a state of reduced ABA responses throughout plant development affecting growth processes such as germination, root growth, stomatal closure and water loss, flowering and senescence.

Synthesis and antimicrobial evaluation of ester-linked 1,4-disubstituted 1,2,3-triazoles with a furyl/thienyl moiety.

Twenty ester-linked 1,4-disubstituted 1,2,3-triazoles having a furyl/thienyl moiety have been synthesized from heteroaryl prop-2-yn-1-yl carboxylate and aromatic azides via a Cu(I) catalyzed 1,3-dipolar cycloaddition. All the synthesized compounds were characterized by FTIR, [Formula: see text]H NMR, [Formula: see text]C NMR spectroscopy and HRMS. Synthesized triazoles were tested in vitro for antimicrobial evaluation against Gram-negative bacteria-Escherichia coli, Enterobacter aerogenes and Klebsiella pneumoniae; Gram-positive bacteria-Staphylococcus aureus and two fungal strains-Candida albicans and Aspergillus niger, reflecting moderate to good activity.

Opportunity for natural selection among five population groups of Manipur, North East India.

Opportunity for natural selection among five population groups of Manipur in comparison with other North East Indian population has been studied. Crow's index as well as Johnston and Kensinger's index for natural selection were calculated based on differential fertility and mortality. The mortality component was found to be lower compared to fertility component in all the populations which may attribute to comparatively improved and easily accessible health care facilities.