Glial Factors Regulating White Matter Development and Pathologies of the Cerebellum.

The cerebellum is a brain region that undergoes extremely dynamic growth during perinatal and postnatal development which is regulated by the proper interaction between glial cells and neurons with a complex concert of growth factors, chemokines, cytokines, neurotransmitters and transcriptions factors. The relevance of cerebellar functions for not only motor performance but also for cognition, emotion, memory and attention is increasingly being recognized and acknowledged. Since perturbed circuitry of cerebro-cerebellar trajectories can play a role in many central nervous system pathologies and thereby contribute to neurological symptoms in distinct neurodevelopmental and neurodegenerative diseases, is it the aim with this mini-review to highlight the pathways of glia-glia interplay being involved.

Elevated circulating CD14CD16 intermediate monocytes are independently associated with extracardiac complications after cardiac surgery.

Elective cardiac surgery has low procedural complications. However, about 40% of patients develop extracardiac complications including delirium and acute kidney injury. We hypothesized that inflammatory processes and immune cell activation might be associated with these complications.

Global, regional, and national sepsis incidence and mortality, 1990-2017: analysis for the Global Burden of Disease Study.

Background: Sepsis is life-threatening organ dysfunction due to a dysregulated host response to infection. It is considered a major cause of health loss, but data for the global burden of sepsis are limited. As a syndrome caused by underlying infection, sepsis is not part of standard Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) estimates.

Cenicriviroc Treatment for Adults With Nonalcoholic Steatohepatitis and Fibrosis: Final Analysis of the Phase 2b CENTAUR Study.

Background And Aims: Cenicriviroc (CVC) is a C-C chemokine receptors type 2 and 5 dual antagonist under evaluation for treating liver fibrosis in adults with nonalcoholic steatohepatitis (NASH). Year 1 primary analysis of the 2-year CENTAUR study showed that CVC had an antifibrotic effect without impacting steatohepatitis. Herein, we report the final data from year 2 exploratory analyses.

Loss of cytoplasmic survivin expression is an independent predictor of poor prognosis in radically operated prostate cancer patients.

Survivin is an inhibitor of apoptosis. Aberrant survivin expression occurs in malignant tumors and has often been linked to unfavorable patient outcome. Here we analyzed 12 432 prostate cancers by immunohistochemistry.

Cenicriviroc for the treatment of liver fibrosis in adults with nonalcoholic steatohepatitis: AURORA Phase 3 study design.

Introduction: Nonalcoholic steatohepatitis (NASH) is a sub-classification of nonalcoholic fatty liver disease (NAFLD) characterized by increased risk of progressive liver fibrosis. Cenicriviroc (CVC) is a novel, orally administered, potent chemokine 2 and 5 receptor antagonist currently in development for the treatment of liver fibrosis in adults with NASH.

Methods And Analysis: Efficacy and safety of CVC will be comprehensively evaluated in a global, Phase 3, multicenter, randomized, double-blind, placebo-controlled study (AURORA, NCT03028740) of subjects with NASH and Stage F2 or F3 fibrosis.

Elevated MR-proANP plasma concentrations are associated with sepsis and predict mortality in critically ill patients.

Background And Aims: Mid-regional pro atrial natriuretic peptide (MR-proANP) is an established biomarker for heart failure, based on its key role in regulating homeostasis of water balance and blood pressure. The aim of the study was to determine the value of MR-proANP as a clinical biomarker in critical illness and/or sepsis. Upon admission to the medical intensive care unit (ICU), we investigated MR-proANP plasma concentrations in 217 critically ill patients (144 with sepsis, 73 without sepsis).

The transcriptional coactivator and histone acetyltransferase CBP regulates neural precursor cell development and migration.

CREB (cyclic AMP response element binding protein) binding protein (CBP, CREBBP) is a ubiquitously expressed transcription coactivator with intrinsic histone acetyltransferase (KAT) activity. Germline mutations within the CBP gene are known to cause Rubinstein-Taybi syndrome (RSTS), a developmental disorder characterized by intellectual disability, specific facial features and physical anomalies. Here, we investigate mechanisms of CBP function during brain development in order to elucidate morphological and functional mechanisms underlying the development of RSTS.

New drugs for NAFLD: lessons from basic models to the clinic.

The term nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of increasingly harmful conditions ranging from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH) to liver fibrosis and end-stage cirrhosis. NAFLD is the currently most common form of chronic liver disease in both adults and children worldwide. As NAFLD evolves as a global pandemic alongside the still growing prevalence of metabolic syndrome, obesity, and diabetes, it is inevitable to develop effective counterstrategies.

The Treatment of Proximal Humerus Fracture Using Internal Fixation with Fixed-angle Plates.

Background: Implants made of various types of material can be used for the internal fixation of fractures. Carbon fiber reinforced polyetheretherketone (CFR-PEEK) is a radiolucent material that may have advantageous handling properties compared with titanium implants.

Methods: Seventy-six patients with proximal humerus fractures requiring surgery were randomized to receive a fixed-angle plate made out of either titanium or CFR- PEEK.

Serum Levels of miR-143 Predict Survival in Critically Ill Patients.

Background And Aims: Recent data suggested a potential role of miR-143 as a biomarker for systemic inflammation and infection. However, its role in critical illness and sepsis is only poorly understood.

Methods: We determined circulating levels of miR-143 in 218 critically ill patients, of which 135 fulfilled sepsis criteria, and compared them to 76 healthy controls.

More precisely defining risk peri-HCT in pediatric ALL: pre- vs post-MRD measures, serial positivity, and risk modeling.

Detection of minimal residual disease (MRD) pre- and post-hematopoietic cell transplantation (HCT) for pediatric acute lymphoblastic leukemia (ALL) has been associated with relapse and poor survival. Published studies have had insufficient numbers to: (1) compare the prognostic value of pre-HCT and post-HCT MRD; (2) determine clinical factors post-HCT associated with better outcomes in MRD+ patients; and (3) use MRD and other clinical factors to develop and validate a prognostic model for relapse in pediatric patients with ALL who undergo allogeneic HCT. To address these issues, we assembled an international database including sibling (n = 191), unrelated (n = 259), mismatched (n = 56), and cord blood (n = 110) grafts given after myeloablative conditioning.

Cellular Senescence: Defining a Path Forward.

Cellular senescence is a cell state implicated in various physiological processes and a wide spectrum of age-related diseases. Recently, interest in therapeutically targeting senescence to improve healthy aging and age-related disease, otherwise known as senotherapy, has been growing rapidly. Thus, the accurate detection of senescent cells, especially in vivo, is essential.

Prediction of lithium response using clinical data.

Objective: Promptly establishing maintenance therapy could reduce morbidity and mortality in patients with bipolar disorder. Using a machine learning approach, we sought to evaluate whether lithium responsiveness (LR) is predictable using clinical markers.

Method: Our data are the largest existing sample of direct interview-based clinical data from lithium-treated patients (n = 1266, 34.

Elevated blood glucose is associated with aggravated brain edema in acute stroke.

Background And Purpose: Clinical outcome after endovascular thrombectomy in patients with acute ischemic stroke still varies significantly. Higher blood glucose levels (BGL) have been associated with worse clinical outcome, but the pathophysiological causes are not yet understood. We hypothesized that higher levels of BGL are associated with more pronounced ischemic brain edema and worse clinical outcome mediated by cerebral collateral circulation.

Association of serum albumin level with incidence and mortality of overt hepatic encephalopathy in cirrhosis during hospitalization.

Background: Hepatic encephalopathy (HE) is a serious complication of cirrhosis. Decreased serum albumin (ALB) level may facilitate the development of HE and accelerate the death of cirrhotic patients with HE. Recent evidence also suggests that human albumin infusion may reduce the incidence of HE and improve the outcomes of cirrhotic patients.

Is a vegan or a vegetarian diet associated with the microbiota composition in the gut? Results of a new cross-sectional study and systematic review.

It is assumed that diet influences the composition of gut microbiota, which in turn may affect human health status. This systematic review aimed to summarize associations of a vegan or vegetarian diet with the composition of microbiota. A literature search was conducted in PubMed and Embase for eligible human studies with vegan or vegetarian diets as an exposure and microbiota composition as an outcome in healthy adults.

Hospitalization and Intensive Therapy at the End of Life.

Background: Germany has more intensive care unit (ICU) beds per capita than the USA, but the utilization of these resources at the end of life is unknown.

Methods: Retrospective observational study using nationwide German hospital discharge data (DRG statistics; DRG, diag- nosis-related groups) from 2007 to 2015. We investigated hospital deaths and use of intensive care services during terminal hospitalizations.

Resolving the fibrotic niche of human liver cirrhosis at single-cell level.

Liver cirrhosis is a major cause of death worldwide and is characterized by extensive fibrosis. There are currently no effective antifibrotic therapies available. To obtain a better understanding of the cellular and molecular mechanisms involved in disease pathogenesis and enable the discovery of therapeutic targets, here we profile the transcriptomes of more than 100,000 single human cells, yielding molecular definitions for non-parenchymal cell types that are found in healthy and cirrhotic human liver.

Reinfection With the Hepatitis C Virus in Men Who Have Sex With Men After Successful Treatment With Direct-acting Antivirals in Germany: Current Incidence Rates, Compared With Rates During the Interferon Era.

Background: Micro-elimination of the hepatitis C virus (HCV) includes treatment in populations at risk of ongoing HCV transmission, such as men who have sex with men (MSM) or people who inject drugs (PWID). We analyzed the HCV reinfection incidence rates of participants in the German hepatitis C cohort (GECCO) and compared our data to previous findings from the interferon era.

Methods: Patients with HCV reinfections in the multi-centric GECCO cohort were compared to patients in whom no reinfection occurred.

CXCR1 Mediates the Development of Monocyte-Derived Dendritic Cells during Hepatic Inflammation.

Recent evidence suggests that hepatic dendritic cells (HDCs) contribute to the evolution of chronic liver diseases. However, the HDC subsets involved and the mechanisms driving these responses are still poorly understood. In this study, we have investigated the role of the fractalkine receptor CXCR1 in modulating monocyte-derived dendritic cell (moDC) differentiation during liver inflammation.