Viral-mediated Oct4 overexpression and inhibition of Notch signaling synergistically induce neurogenic competence in mammalian Müller glia.

Retinal Müller glia in cold-blooded vertebrates can reprogram into neurogenic progenitors to replace neurons lost to injury, but mammals lack this ability. While recent studies have shown that transgenic overexpression of neurogenic bHLH factors and glial-specific disruption of NFI family transcription factors and Notch signaling induce neurogenic competence in mammalian Müller glia, induction of neurogenesis in wildtype glia has thus far proven elusive. Here we report that viral-mediated overexpression of the pluripotency factor ( ) induces transdifferentiation of wildtype mouse Müller glia into bipolar neurons and stimulates this process synergistically in parallel with Notch loss of function.

Robust reprogramming of glia into neurons by inhibition of Notch signaling and nuclear factor I (NFI) factors in adult mammalian retina.

Generation of neurons through direct reprogramming has emerged as a promising therapeutic approach for treating neurodegenerative diseases. In this study, we present an efficient method for reprogramming retinal glial cells into neurons. By suppressing Notch signaling by disrupting either or , we induced mature Müller glial cells to reprogram into bipolar- and amacrine-like neurons.

International Nosocomial Infection Control Consortium (INICC) report of health care-associated infections, data summary of 25 countries for 2014 to 2023, Surgical Site Infections Module.

Background: Surgical site infection (SSI) rates are higher in low-resource countries (LRC) than in high-income counterparts.

Methods: Prospective cohort study using the INICC Surveillance Online System, from 116 hospitals in 75 cities across 25 Latin-American, Asian, Eastern-European, and Middle-Eastern countries: Argentina, Bahrain, Brazil, Colombia, Costa Rica, Dominican Republic, Ecuador, Egypt, Honduras, India, Kosovo, Kuwait, Lebanon, Mexico, Mongolia, Pakistan, Papua New Guinea, Philippines, Poland, Romania, Saudi Arabia, Thailand, Turkey, Venezuela, Vietnam. CDC/NHSN definitions were applied.

Robust reprogramming of glia into neurons by inhibition of Notch signaling and NFI factors in adult mammalian retina.

Generation of neurons through direct reprogramming has emerged as a promising therapeutic approach for neurodegenerative diseases. Despite successful applications , implementation has been hampered by low efficiency. In this study, we present a highly efficient strategy for reprogramming retinal glial cells into neurons by simultaneously inhibiting key negative regulators.

NARF is a hypoxia-induced coactivator for OCT4-mediated breast cancer stem cell specification.

Hypoxia is a key characteristic of the breast cancer microenvironment that promotes expression of the transcriptional activator hypoxia-inducible factor 1 (HIF-1) and is associated with poor patient outcome. HIF-1 increases the expression or activity of stem cell pluripotency factors, which control breast cancer stem cell (BCSC) specification and are required for cancer metastasis. Here, we identify nuclear prelamin A recognition factor () as a hypoxia-inducible, HIF-1 target gene in human breast cancer cells.

Ectopic insert-dependent neuronal expression of GFAP promoter-driven AAV constructs in adult mouse retina.

Direct reprogramming of retinal Müller glia is a promising avenue for replacing photoreceptors and retinal ganglion cells lost to retinal dystrophies. However, questions have recently been raised about the accuracy of studies claiming efficient glia-to-neuron reprogramming in retina that were conducted using GFAP mini promoter-driven adeno-associated virus (AAV) vectors. In this study, we have addressed these questions using GFAP mini promoter-driven AAV constructs to simultaneously overexpress the mCherry reporter and candidate transcription factors predicted to induce glia-to-neuron conversion, in combination with prospective genetic labeling of retinal Müller glia using inducible Cre-dependent GFP reporters.

Gene regulatory networks controlling temporal patterning, neurogenesis, and cell-fate specification in mammalian retina.

Gene regulatory networks (GRNs), consisting of transcription factors and their target sites, control neurogenesis and cell-fate specification in the developing central nervous system. In this study, we use integrated single-cell RNA and single-cell ATAC sequencing (scATAC-seq) analysis in developing mouse and human retina to identify multiple interconnected, evolutionarily conserved GRNs composed of cell-type-specific transcription factors that both activate genes within their own network and inhibit genes in other networks. These GRNs control temporal patterning in primary progenitors, regulate transition from primary to neurogenic progenitors, and drive specification of each major retinal cell type.

Differential expression and hypoxia-mediated regulation of the N-myc downstream regulated gene family.

Many organisms rely on oxygen to generate cellular energy (adenosine triphosphate or ATP). During severe hypoxia, the production of ATP decreases, leading to cell damage or death. Conversely, excessive oxygen causes oxidative stress that is equally damaging to cells.

Histone citrullination by PADI4 is required for HIF-dependent transcriptional responses to hypoxia and tumor vascularization.

Hypoxia-inducible factors (HIFs) activate transcription of target genes by recruiting coactivators and chromatin-modifying enzymes. Peptidylarginine deiminase 4 (PADI4) catalyzes the deimination of histone arginine residues to citrulline. Here, we demonstrate that PADI4 expression is induced by hypoxia in a HIF-dependent manner in breast cancer and hepatocellular carcinoma cells.

International Nosocomial Infection Control Consortium (INICC) report, data summary of 45 countries for 2013-2018, Adult and Pediatric Units, Device-associated Module.

Background: We report the results of INICC surveillance study from 2013 to 2018, in 664 intensive care units (ICUs) in 133 cities, of 45 countries, from Latin-America, Europe, Africa, Eastern-Mediterranean, Southeast-Asia, and Western-Pacific.

Methods: Prospective data from patients hospitalized in ICUs were collected through INICC Surveillance Online System. CDC-NHSN definitions for device-associated healthcare-associated infection (DA-HAI) were applied.

Human casualties are the dominant cost of human-wildlife conflict in India.

Reducing the costs from human-wildlife conflict, mostly borne by marginal rural households, is a priority for conservation. We estimate the mean species-specific cost for households suffering damages from one of 15 major species of wildlife in India. Our data are from a survey of 5,196 households living near 11 wildlife reserves in India, and self-reported annual costs include crop and livestock losses and human casualties (injuries and death).

Six-year study on peripheral venous catheter-associated BSI rates in 262 ICUs in eight countries of South-East Asia: International Nosocomial Infection Control Consortium findings.

Background: Short-term peripheral venous catheter-associated bloodstream infection rates have not been systematically studied in Asian countries, and data on peripheral venous catheter-associated bloodstream infections incidence by number of short-term peripheral venous catheter days are not available.

Methods: Prospective, surveillance study on peripheral venous catheter-associated bloodstream infections conducted from 1 September 2013 to 31 May 2019 in 262 intensive care units, members of the International Nosocomial Infection Control Consortium, from 78 hospitals in 32 cities of 8 countries in the South-East Asia Region: China, India, Malaysia, Mongolia, Nepal, Philippines, Thailand, and Vietnam. For this research, we applied definition and criteria of the CDC NHSN, methodology of the INICC, and software named INICC Surveillance Online System.

Does therapeutic plasma exchange have a role in the treatment of prosthetic hip-associated cobalt toxicity? A case report and literature review.

Background: Prosthetic hip-associated cobalt toxicity (PHACT) is an uncommon, but potentially devastating, complication for patients with metal-on-metal hip implants (MoMs). Clinical management of PHACT is poorly defined, with primary intervention being MoM explant followed by chelation therapy. Therapeutic plasma exchange (TPE) in cobalt toxicity has not been previously described.

Safety of a liberal policy for extended-date preadmission testing samples.

Background: Regulations governing pretransfusion testing allow specimen expiration to be extended past 3 days before the transfusion if a patient has not been transfused or pregnant in the preceding 3 months. Our hospital allows extension of the expiration of a presurgical specimen to 28 days if 1) the patient has neither been transfused nor pregnant in the past 3 months, 2) the patient does not have an antibody history, and 3) the current antibody screen (ABSC) is negative. Patients not meeting Criteria 2 and 3 are required to have specimens redrawn on the day of surgery (DOS).

Establishing an antigen-negative red blood cell inventory in a hospital-based blood bank.

Background: Our blood bank is part of a large academic institution with an active sickle cell anemia program. We provide sickle patients with blood phenotypically matched for C/c, E/e, and K antigens. Since licensed reagents are available for phenotyping C/c, E/e, and K on an automated blood analyzer, we decided to evaluate whether establishing our own inventory of blood negative for those antigens would result in cost savings and decreased turnaround time (TAT).