Single-cell multiomics reveals the complexity of TGFβ signalling to chromatin in iPSC-derived kidney organoids.

TGFβ1 plays a regulatory role in the determination of renal cell fate and the progression of renal fibrosis. Here we show an association between SMAD3 and the histone methyltransferase, EZH2, during cell differentiation; ChIP-seq revealed that SMAD3 and EZH2 co-occupy the genome in iPSCs and in iPSC-derived nephron progenitors. Through integration of single cell gene expression and epigenome profiling, we identified de novo ACTA2/POSTN myofibroblasts in kidney organoids treated with TGFβ1, characterised by increased SMAD3-dependent cis chromatin accessibility and gene expression associated with fibroblast activation.

Long-term outcomes of the arthroscopic Bankart repair: a systematic review of studies at 10-year follow-up.

Background: The purpose of this study was to systematically review the evidence in the literature to ascertain the functional outcomes and recurrences rates, as well as subsequent revision rates, following arthroscopic Bankart repair at a minimum of 10 years' follow-up.

Methods: Two independent reviewers performed a literature search based on Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines, using the Embase, MEDLINE, and Cochrane Library databases. Studies were included if they were clinical studies on arthroscopic Bankart repair with a minimum of 10 years' follow-up.

Defens-IN! Human α-Defensin 5 Acts as an Unwitting Double Agent to Promote Shigella Infection.

Shigella pathogenesis has confounded researchers for years because of its narrow host selectivity and extraordinary infectious capability. In this issue of Immunity, Xu et al. (2018) identify a cunning mechanism whereby Shigella hijacks human α-defensin 5 to enhance its adhesion and subsequent invasion.

Transcriptional profiling of PBMCs unravels B cell mediated immunopathogenic imprints of HCV vasculitis.

B cell depletion therapy using rituximab has been shown to be effective in achieving remission in patients with HCV-mixed cryoglobulinemic (MC) vasculitis. Previously, we have demonstrated abnormalities in peripheral immune cells involving neutrophils, chemotaxis, and innate immune activation among patients with HCV-MC vasculitis when compared to HCV patients without vasculitis. In this study, we evaluated the effect of B cell depletion therapy on transcriptional profiles of peripheral blood mononuclear cells before and after riruximab therapy, in order to unravel the pathogenic mechanism involved in HCV-MC vasculitis induced by abnormal B cell proliferation.

Epithelial Cell Inflammasomes in Intestinal Immunity and Inflammation.

Pattern recognition receptors (PRR), such as NOD-like receptors (NLRs), sense conserved microbial signatures, and host danger signals leading to the coordination of appropriate immune responses. Upon activation, a subset of NLR initiate the assembly of a multimeric protein complex known as the inflammasome, which processes pro-inflammatory cytokines and mediates a specialized form of cell death known as pyroptosis. The identification of inflammasome-associated genes as inflammatory bowel disease susceptibility genes implicates a role for the inflammasome in intestinal inflammation.

Identifying patient-related information problems: A study of information use by patient-care teams during morning rounds.

Objective: This study identifies the types of patient-related information problems (PIPs) that patient-care teams encounter during morning rounds, and how those PIPs are identified and managed. PIPs are any issues related to patient information (e.g.

Mitral valve prolapse is associated with altered extracellular matrix gene expression patterns.

Mitral valve prolapse (MVP) is the leading indication for isolated mitral valve surgery in the United States. Disorganization of collagens and glycosaminoglycans in the valvular extracellular matrix (ECM) are histological hallmarks of MVP. We performed a transcriptome analysis to study the alterations in ECM-related gene expression in humans with sporadic MVP.

Memory Th1 Cells Are Protective in Invasive Staphylococcus aureus Infection.

Mechanisms of protective immunity to Staphylococcus aureus infection in humans remain elusive. While the importance of cellular immunity has been shown in mice, T cell responses in humans have not been characterised. Using a murine model of recurrent S.

Genome sequencing of the extinct Eurasian wild aurochs, Bos primigenius, illuminates the phylogeography and evolution of cattle.

Background: Domestication of the now-extinct wild aurochs, Bos primigenius, gave rise to the two major domestic extant cattle taxa, B. taurus and B. indicus.

Designing for privacy management in hospitals: Understanding the gap between user activities and IT staff's understandings.

Purpose: We examined the role of privacy in collaborative clinical work and how it is understood by hospital IT staff. The purpose of our study was to identify the gaps between hospital IT staff members' perceptions of how electronic health record (EHR) users' protect the privacy of patient information and how users actually protect patients' private information in their daily collaborative activities. Since the IT staff play an important role in implementing and maintaining the EHR, any gaps that exist between the IT staff's perceptions of user work practices and the users' actual work practices can result in a number of problems in the configuration, implementation, or customization of the EHR, which can lead to collaboration challenges, interrupted workflow, and privacy breaches.

Manipulation of Autophagy in Phagocytes Facilitates Staphylococcus aureus Bloodstream Infection.

The capacity for intracellular survival within phagocytes is likely a critical factor facilitating the dissemination of Staphylococcus aureus in the host. To date, the majority of work on S. aureus-phagocyte interactions has focused on neutrophils and, to a lesser extent, macrophages, yet we understand little about the role played by dendritic cells (DCs) in the direct killing of this bacterium.

Hepatitis C-associated mixed cryoglobulinemic vasculitis induces differential gene expression in peripheral mononuclear cells.

This study examines the distinct gene expression profile of peripheral blood mononuclear cells from patients with chronic hepatitis C infection and mixed cryoglobulinemic (MC) vasculitis. Our DNA microarray analysis indicates that hepatitis C virus (HCV)-associated MC vasculitis is characterized by compromised neutrophil function, impaired chemotaxis, and increased interferon-stimulated gene (ISG) expression, contributing to overall MC pathogenesis and end-organ damage. Increased ISG expression is suggestive of an enhanced endogenous interferon gene signature.

Staphylococcus aureus infection of mice expands a population of memory γδ T cells that are protective against subsequent infection.

The development of vaccines against Staphylococcus aureus has consistently failed in clinical trials, likely due to inefficient induction of cellular immunity. T cell-derived IL-17 is one of the few known correlates of antistaphylococcoal immunity, conferring protection against S. aureus infections through its ability to promote phagocytic cell effector functions.

A survey of rural hospitals' perspectives on health information technology outsourcing.

A survey of rural hospitals was conducted in the spring of 2012 to better understand their perspectives on health information technology (HIT) outsourcing and the role that hospital-to-hospital HIT partnerships (HHPs) can play as an outsourcing mechanism. The survey sought to understand how HHPs might be leveraged for HIT implementation, as well as the challenges with forming them. The results suggest that HHPs have the potential to address rural hospitals' slow rate of HIT adoption, but there are also challenges to creating these partnerships.

Identification and management of information problems by emergency department staff.

Patient-care teams frequently encounter information problems during their daily activities. These information problems include wrong, outdated, conflicting, incomplete, or missing information. Information problems can negatively impact the patient-care workflow, lead to misunderstandings about patient information, and potentially lead to medical errors.

Targeted nasal vaccination provides antibody-independent protection against Staphylococcus aureus.

Despite showing promise in preclinical models, anti-Staphylococcus aureus vaccines have failed in clinical trials. To date, approaches have focused on neutralizing/opsonizing antibodies; however, vaccines exclusively inducing cellular immunity have not been studied to formally test whether a cellular-only response can protect against infection. We demonstrate that nasal vaccination with targeted nanoparticles loaded with Staphylococcus aureus antigen protects against acute systemic S.

Impaired HCV clearance in HIV/HCV coinfected subjects treated with PegIFN and RBV due to interference of IFN signaling by IFNαR2a.

Enhanced endogenous interferon (IFN) stimulated gene (ISG) signature has been associated with nonresponsiveness to hepatitis C treatment using pegylated-IFNα (pegIFNα) and ribavirin (RBV) in human immunodeficiency virus/hepatitis C virus (HIV/HCV) coinfected patients. Using a proteomic approach, we identified high levels of IFNα receptor 2a (IFNαR2a) in the serum of null responders to pegIFNα/RBV. IFNαR2a inhibited antiviral activity of all formulations of IFNα in JFH/Huh7.

Nlrp-3-driven interleukin 17 production by γδT cells controls infection outcomes during Staphylococcus aureus surgical site infection.

Recent work has identified T cells and the cytokines they produce as important correlates of immune protection during Staphylococcus aureus infections through the ability of these T cells to regulate local neutrophil responses. However, the specific T-cell subsets that are involved in coordinating protection at distinct sites of infection remains to be established. In this study, we identify for the first time an important role for γδT cells in controlling S.

Outcome of pure mucocele-like lesions diagnosed on breast core biopsy.

Aim: Current guidelines recommend that mucocele-like lesions (MLL) of the breast diagnosed on needle core biopsy (NCB) should be categorized as a lesion of uncertain malignant potential (B3). However, data on the outcome of MLL diagnosed on NCB remains limited due to the rarity of this lesion. The aim of this study was to assess the outcome of pure MLL without atypia diagnosed on NCB using a large series of cases and a review of the literature to provide evidence that can guide management.

Critical procedures in pediatric emergency medicine.

Children comprise approximately one-quarter of all visits to most emergency departments. Children are generally healthier than adults, yet there are similar priorities in assessment and management of pediatric patients. The initial approach to airway, breathing, and circulation still applies and is first and foremost in the evaluation of young infants and children.

Gene expression profiles predict emergence of psychiatric adverse events in HIV/HCV-coinfected patients on interferon-based HCV therapy.

Background: The efficacy of pegylated interferon-α and ribavirin (pegIFN/RBV) in the treatment of Hepatitis C infection is limited by psychiatric adverse effects (IFN-PE). Our study examined the ability of differential gene expression patterns before therapy to predict emergent IFN-PE among 28 HIV/HCV-coinfected patients treated with pegIFN-α2b/RBV.

Methods: Patients dually infected with HIV and HCV were evaluated at baseline and during treatment by board-certified psychiatrists who classified patients into 2 groups: those who developed IFN-PE and those who did not (IFN-NPE).

Ribavirin enhances IFN-α signalling and MxA expression: a novel immune modulation mechanism during treatment of HCV.

The nucleoside analogue Ribavirin significantly increases patient response to IFN-α treatment of HCV, by directly inhibiting viral replication. Recent studies indicate that Ribavirin also regulates immunity and we propose that Ribavirin enhances specific interferon sensitive gene (ISG) expression by amplifying the IFN-α-JAK/STAT pathway. We found that IFN-α-induced STAT1 and STAT3 phosphorylation was increased in hepatocytes co-treated with Ribavirin and IFN-α, compared to IFN-α alone.

Twice-weekly pegylated interferon-α-2a and ribavirin results in superior viral kinetics in HIV/hepatitis C virus co-infected patients compared to standard therapy.

Background: Hepatitis C virus (HCV)/HIV co-infected patients have more rapid progression of liver fibrosis and only modest cure rates (sustained virologic responses, SVRs) when compared to HCV monoinfected patients.

Method: We compared the virologic responses of either twice-weekly peginterferon-α-2a 180 μg/week (for 4 weeks, followed by weekly dosing) or weekly peginterferon-α-2a 180 μg/week, and weight-based ribavirin (1-1.2 g/day), among HIV/HCV co-infected genotype-1 individuals.

Characterization and outcome of breast needle core biopsy diagnoses of lesions of uncertain malignant potential (B3) in abnormalities detected by mammographic screening.

In the setting of breast cancer screening, 5-9% of needle core biopsies are diagnosed as lesions of uncertain malignant potential (B3). The management of these lesions is potentially problematic as the data on their outcome remains limited. In our study, we aim to assess the outcome of screen-detected lesions diagnosed as B3 in a large series to validate previous studies and to characterize the malignant lesions detected after a B3 diagnosis.