Vat Photopolymerization of Reinforced Styrene-Butadiene Elastomers: A Degradable Scaffold Approach.

Vat photopolymerization (VP) is a high-throughput additive manufacturing modality that also offers exceptional feature resolution and surface finish; however, the process is constrained by a limited selection of processable photocurable resins. Low resin viscosity (<10 Pa·s) is one of the most stringent process-induced constraints on resin processability, which in turn limits the mechanical performance of printed resin systems. Recently, the authors created a VP-processable photosensitive latex resin, where compartmentalization of the high molecular weight polymer chains into discrete particles resulted in the decoupling of viscosity from molecular weight.

Expanding the drug discovery space with predicted metabolite-target interactions.

Metabolites produced in the human gut are known modulators of host immunity. However, large-scale identification of metabolite-host receptor interactions remains a daunting challenge. Here, we employed computational approaches to identify 983 potential metabolite-target interactions using the Inflammatory Bowel Disease (IBD) cohort dataset of the Human Microbiome Project 2 (HMP2).

Inflammatory Endotype-associated Airway Microbiome in Chronic Obstructive Pulmonary Disease Clinical Stability and Exacerbations: A Multicohort Longitudinal Analysis.

Understanding the role of the airway microbiome in chronic obstructive pulmonary disease (COPD) inflammatory endotypes may help to develop microbiome-based diagnostic and therapeutic approaches. To understand the association of the airway microbiome with neutrophilic and eosinophilic COPD at stability and during exacerbations. An integrative analysis was performed on 1,706 sputum samples collected longitudinally from 510 patients with COPD recruited at four UK sites of the BEAT-COPD (Biomarkers to Target Antibiotic and Systemic COPD), COPDMAP (Chronic Obstructive Pulmonary Disease Medical Research Council/Association of the British Pharmaceutical Industry), and AERIS (Acute Exacerbation and Respiratory Infections in COPD) cohorts.

Multi-omic meta-analysis identifies functional signatures of airway microbiome in chronic obstructive pulmonary disease.

The interaction between airway microbiome and host in chronic obstructive pulmonary disease (COPD) is poorly understood. Here we used a multi-omic meta-analysis approach to characterize the functional signature of airway microbiome in COPD. We retrieved all public COPD sputum microbiome datasets, totaling 1640 samples from 16S rRNA gene datasets and 26 samples from metagenomic datasets from across the world.

The sputum microbiome is distinct between COPD and health, independent of smoking history.

Background: Airway bacterial dysbiosis is a feature of chronic obstructive pulmonary disease (COPD). However, there is limited comparative data of the lung microbiome between healthy smokers, non-smokers and COPD.

Methods: We compared the 16S rRNA gene-based sputum microbiome generated from pair-ended Illumina sequencing of 124 healthy subjects (28 smokers and 96 non-smokers with normal lung function), with single stable samples from 218 COPD subjects collected from three UK clinical centres as part of the COPDMAP consortium.

Microbiome Metabolite Mimics Accelerate Drug Discovery.

A recent study by Dvořák et al. supports metabolite mimicry as a drug development strategy. A potent agonist of the human pregnane X receptor (hPXR) was designed from two ligands that are products of the microbial catabolism of tryptophan.

Obesity and disease severity magnify disturbed microbiome-immune interactions in asthma patients.

In order to improve targeted therapeutic approaches for asthma patients, insights into the molecular mechanisms that differentially contribute to disease phenotypes, such as obese asthmatics or severe asthmatics, are required. Here we report immunological and microbiome alterations in obese asthmatics (n = 50, mean age = 45), non-obese asthmatics (n = 53, mean age = 40), obese non-asthmatics (n = 51, mean age = 44) and their healthy counterparts (n = 48, mean age = 39). Obesity is associated with elevated proinflammatory signatures, which are enhanced in the presence of asthma.

Activity and Microbiological Efficacy of Gepotidacin from a Phase 2, Randomized, Multicenter, Dose-Ranging Study in Patients with Acute Bacterial Skin and Skin Structure Infections.

A phase 2 study of gepotidacin demonstrated the safety and efficacy of 3 gepotidacin doses (750 mg every 12 h [q12h], 1,000 mg q12h, and 1,000 mg every 8 h [q8h]) in hospitalized patients with suspected/confirmed Gram-positive acute bacterial skin and skin structure infections (ABSSSIs). Evaluating microbiology outcomes and responses were secondary endpoints. Pretreatment isolates recovered from infected lesions underwent susceptibility testing per Clinical and Laboratory Standards Institute guidelines.

The Microbiome Factor in Drug Discovery and Development.

Here we review recent studies that illustrate three areas where the microbiome directly impacts drug development: (1) microbial effects on drug safety and efficacy, (2) the effects of drugs on causing collateral restructuring of microbiome communities, and (3) the potential side-effects of novel therapies targeting the microbiome. On the basis of the findings of these and other studies, we advocate the systematic incorporation of microbiome analyses in early to late stage clinical trials as a strategy to increase the overall success rate of the drug discovery and development process.

Shared Molecular Signatures Across Neurodegenerative Diseases and Herpes Virus Infections Highlights Potential Mechanisms for Maladaptive Innate Immune Responses.

Growing evidence suggests that peripheral factors to the brain driving neuro-inflammation could affect Alzheimer's Disease (AD) and Parkinson's Disease (PD) severity. Herpes simplex virus type 1 (HSV1) infection has been associated with AD while other related viruses, including cytomegalovirus (CMV), Epstein-Bar virus and human herpesvirus 6 (HHV6), are known to infect neurons. Here we compare gene expression profiles between AD or PD patients to those afflicted with herpes viral infections as to discover novel potential neuro-inflammation pathways.

Airway host-microbiome interactions in chronic obstructive pulmonary disease.

Background: Little is known about the interactions between the lung microbiome and host response in chronic obstructive pulmonary disease (COPD).

Methods: We performed a longitudinal 16S ribosomal RNA gene-based microbiome survey on 101 sputum samples from 16 healthy subjects and 43 COPD patients, along with characterization of host sputum transcriptome and proteome in COPD patients.

Results: Dysbiosis of sputum microbiome was observed with significantly increased relative abundance of Moraxella in COPD versus healthy subjects and during COPD exacerbations, and Haemophilus in COPD ex-smokers versus current smokers.

Left Off the Route: A Qualitative Examination of Urban Bus Drivers Wanting to be Players in the Bully Prevention Solution.

Every school day millions of children board the bus from home and school oftentimes with 90 others including a bus driver. Perhaps not found in a bus drivers' job description are the details to monitor and respond to all suspected bullying behaviors. Being bullied can have long-term negative consequences for both bullies and victims.

Longitudinal profiling of the lung microbiome in the AERIS study demonstrates repeatability of bacterial and eosinophilic COPD exacerbations.

Background: Alterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in COPD.

Objective: To characterise longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory InfectionS in COPD) and their relationship with associated COPD outcomes.

Methods: We surveyed 584 sputum samples from 101 patients with COPD to analyse the lung microbiome at both stable and exacerbation time points over 1 year using high-throughput sequencing of the 16S ribosomal RNA gene.

Meta-analysis of human gene expression in response to Mycobacterium tuberculosis infection reveals potential therapeutic targets.

Background: With the global emergence of multi-drug resistant strains of Mycobacterium tuberculosis, new strategies to treat tuberculosis are urgently needed such as therapeutics targeting potential human host factors.

Results: Here we performed a statistical meta-analysis of human gene expression in response to both latent and active pulmonary tuberculosis infections from nine published datasets. We found 1655 genes that were significantly differentially expressed during active tuberculosis infection.

Gut microbiome differences between metformin- and liraglutide-treated T2DM subjects.

Introduction: Metformin and glucagon-like peptide-1 (GLP-1) agonists are widely used for treating type two diabetes mellitus (T2DM). While recent studies suggest these drugs might modify the gastrointestinal tract (GIT) microbiome, further confirmation is required from human clinical trials.

Materials And Methods: Here, we compare, in patients with T2DM, the effects of metformin (n=18 subjects) and liraglutide (n=19), a GLP-1 agonist, on their GIT microbiomes over a 42 day period (n=74 samples) using 16S ribosomal RNA (rRNA) sequencing.

Sputum microbiome temporal variability and dysbiosis in chronic obstructive pulmonary disease exacerbations: an analysis of the COPDMAP study.

Background: Recent studies suggest that lung microbiome dysbiosis, the disease associated disruption of the lung microbial community, might play a key role in chronic obstructive pulmonary disease (COPD) exacerbations. However, characterising temporal variability of the microbiome from large longitudinal COPD cohorts is needed to better understand this phenomenon.

Methods: We performed a 16S ribosomal RNA survey of microbiome on 716 sputum samples collected longitudinally at baseline and exacerbations from 281 subjects with COPD at three UK clinical centres as part of the COPDMAP consortium.

Preparing Nursing and Social Work Students to Care for Patients in Acute Alcohol Withdrawal.

Alcohol and other drug abuse has become a national crisis with approximately 26% of general medical patients having alcohol-related problems. New nurses and social workers are often not prepared to care for patients with severe alcohol withdrawal symptoms because they lack experience in actual crisis situations. The purpose of this study was to prepare nursing and social work students to care for a patient undergoing an acute alcohol withdrawal process.

SUMO Ligase Protein Inhibitor of Activated STAT1 (PIAS1) Is a Constituent Promyelocytic Leukemia Nuclear Body Protein That Contributes to the Intrinsic Antiviral Immune Response to Herpes Simplex Virus 1.

Unlabelled: Aspects of intrinsic antiviral immunity are mediated by promyelocytic leukemia nuclear body (PML-NB) constituent proteins. During herpesvirus infection, these antiviral proteins are independently recruited to nuclear domains that contain infecting viral genomes to cooperatively promote viral genome silencing. Central to the execution of this particular antiviral response is the small ubiquitin-like modifier (SUMO) signaling pathway.

Novel Role for Protein Inhibitor of Activated STAT 4 (PIAS4) in the Restriction of Herpes Simplex Virus 1 by the Cellular Intrinsic Antiviral Immune Response.

Unlabelled: Small ubiquitin-like modifier (SUMO) is used by the intrinsic antiviral immune response to restrict viral pathogens, such as herpes simplex virus 1 (HSV-1). Despite characterization of the host factors that rely on SUMOylation to exert their antiviral effects, the enzymes that mediate these SUMOylation events remain to be defined. We show that unconjugated SUMO levels are largely maintained throughout infection regardless of the presence of ICP0, the HSV-1 SUMO-targeted ubiquitin ligase.

Lung microbiome dynamics in COPD exacerbations.

Increasing evidence suggests that the lung microbiome plays an important role in chronic obstructive pulmonary disease (COPD) severity. However, the dynamics of the lung microbiome during COPD exacerbations and its potential role in disease aetiology remain poorly understood.We completed a longitudinal 16S ribosomal RNA survey of the lung microbiome on 476 sputum samples collected from 87 subjects with COPD at four visits defined as stable state, exacerbation, 2 weeks post-therapy and 6 weeks recovery.

Human microbial metabolites as a source of new drugs.

Crosstalk between the microbiome and the human host is mediated by specific ligand-receptor interactions involving microbially generated metabolites that can be either agonists or antagonists of human proteins. The evolved co-compatibility of gut microbiota with human systems points to a potentially rich area for discovering new drug-like molecules that are both highly specific modulators of human pathways and derisked for adverse effects. In this review, we discuss the rapidly growing research into the role of microbial metabolites in human health and suggest potential strategies for developing these molecules into therapeutic agents.