Pharmacokinetics of PP353, a formulation of linezolid for intervertebral disc administration, in patients with chronic low back pain and Modic change Type 1: A first-in-human, Phase 1b, open-label, single-dose study.

Background: Bacterial infection of the intervertebral disc is difficult to treat because the tissue is usually not vascularized and systemic antibiotic therapy may not reach optimal antibacterial exposure. Here we characterize the safety, tolerability, and pharmacokinetics of PP353, a suspension of micronized linezolid, formulated for direct intervertebral disc administration.

Methods: The safety, tolerability, and pharmacokinetics of an intradiscal administration of PP353, was assessed in Part A of a Phase 1b study and consisted of a single injection of study drug (3 mL of PP353 and 150 mg linezolid).

Health Insurance Coverage Predicts Health Care Use among Latine Immigrants in Two Policy Contexts.

This study analyzed electronic health record (EHR) data from 2016 through 2019 from a federally qualified health center (FQHC) serving predominantly low-income Latine immigrants in the Washington, D.C. metropolitan area to examine how changes in health insurance coverage relate to changes in health care use.

A randomized, double-blinded, phase 2 trial of EDP1815, an oral immunomodulatory preparation of , in adults with mild-to-moderate plaque psoriasis.

Background: Psoriasis is a chronic inflammatory skin disease. EDP1815 is an oral, gut-restricted preparation of non-live , the first of a new immunomodulatory therapeutic class targeting the small intestine to generate systemic anti-inflammatory responses.

Objective: To evaluate safety and efficacy of EDP1815 in mild-to-moderate psoriasis in a proof-of-concept study.

Immunomodulating effects of the single bacterial strain therapy EDP1815 on innate and adaptive immune challenge responses - a randomized, placebo-controlled clinical trial.

The gut microbiome can modulate systemic inflammation and is therefore target for immunomodulation. Immunomodulating effects of EDP1815, a bacterial commensal strain of Prevotella histicola, were studied in healthy participants. Effects on adaptive immunity were evaluated by a neo-antigen challenge with keyhole limpet haemocyanin (KLH), while effects on innate immunity were evaluated by topical toll-like receptor 7 (TLR7) agonist imiquimod.

Modic changes as seen on MRI are associated with nonspecific chronic lower back pain and disability.

Background: Estimating the contribution of endplate oedema known as Modic changes to lower back pain (LBP) has been the subject of multiple observational studies and reviews, some of which conclude that the evidence for an association of Modic change with LBP is uncertain while others demonstrate a clear link. The clinical trials demonstrating the benefit of basivertebral nerve ablation, a therapeutic intervention, in a tightly defined homogenous patient group with chronic LBP and Modic changes type 1 or type 2, provides further evidence for the contribution of Modic changes to LBP and shows that in these subjects, nerve ablation substantially reduces pain and disability. These interventional studies provide direct evidence that Modic changes can be associated with lower back pain and disability.

Impact of oral administration of single strain spp. on immune responses to keyhole limpet hemocyanin immunization and gut microbiota: A randomized placebo-controlled trial in healthy volunteers.

Introduction: spp. has been associated with promising immunomodulatory results in preclinical trials. The aim of this study was to investigate the pharmacodynamic (PD) effects of three monoclonal microbial formulations of spp.

A genome-wide screen for variants influencing certolizumab pegol response in a moderate to severe rheumatoid arthritis population.

Certolizumab pegol (CZP) is a PEGylated Fc-free tumor necrosis factor (TNF) inhibitor antibody approved for use in the treatment of rheumatoid arthritis (RA), Crohn's disease, psoriatic arthritis, axial spondyloarthritis and psoriasis. In a clinical trial of patients with severe RA, CZP improved disease symptoms in approximately half of patients. However, variability in CZP efficacy remains a problem for clinicians, thus, the aim of this study was to identify genetic variants predictive of CZP response.

Clinical spectrum of -related epileptic disorders.

Objective: The aim of this study was to expand the spectrum of epilepsy syndromes related to , encoding the presynaptic protein syntaxin-1B, and establish genotype-phenotype correlations by identifying further disease-related variants.

Methods: We used next-generation sequencing in the framework of research projects and diagnostic testing. Clinical data and EEGs were reviewed, including already published cases.

Human biallelic MFN2 mutations induce mitochondrial dysfunction, upper body adipose hyperplasia, and suppression of leptin expression.

MFN2 encodes mitofusin 2, a membrane-bound mediator of mitochondrial membrane fusion and inter-organelle communication. MFN2 mutations cause axonal neuropathy, with associated lipodystrophy only occasionally noted, however homozygosity for the p.Arg707Trp mutation was recently associated with upper body adipose overgrowth.

The Deubiquitinase OTULIN Is an Essential Negative Regulator of Inflammation and Autoimmunity.

Methionine-1 (M1)-linked ubiquitin chains regulate the activity of NF-κB, immune homeostasis, and responses to infection. The importance of negative regulators of M1-linked chains in vivo remains poorly understood. Here, we show that the M1-specific deubiquitinase OTULIN is essential for preventing TNF-associated systemic inflammation in humans and mice.

Dominant Splice Site Mutations in PIK3R1 Cause Hyper IgM Syndrome, Lymphadenopathy and Short Stature.

The purpose of this research was to use next generation sequencing to identify mutations in patients with primary immunodeficiency diseases whose pathogenic gene mutations had not been identified. Remarkably, four unrelated patients were found by next generation sequencing to have the same heterozygous mutation in an essential donor splice site of PIK3R1 (NM_181523.2:c.

Towards the taxonomy of human disease.

Consortia have begun to establish 'mechanism-based taxonomies' for inflammatory and neurodegenerative diseases that could aid drug development and personalized therapy.

Whole-exome sequencing in undiagnosed genetic diseases: interpreting 119 trios.

Purpose: Despite the recognized clinical value of exome-based diagnostics, methods for comprehensive genomic interpretation remain immature. Diagnoses are based on known or presumed pathogenic variants in genes already associated with a similar phenotype. Here, we extend this paradigm by evaluating novel bioinformatics approaches to aid identification of new gene-disease associations.

Pain perception is altered by a nucleotide polymorphism in SCN9A.

The gene SCN9A is responsible for three human pain disorders. Nonsense mutations cause a complete absence of pain, whereas activating mutations cause severe episodic pain in paroxysmal extreme pain disorder and primary erythermalgia. This led us to investigate whether single nucleotide polymorphisms (SNPs) in SCN9A were associated with differing pain perception in the general population.

Association between neprilysin polymorphisms and sporadic Alzheimer's disease.

The deposition of amyloid beta peptide (Abeta) in the form of plaques in the brain is a hallmark of Alzheimer's disease (AD). Neprilysin is the major Abeta-degradating enzyme and reduction in neprilysin activity could contribute to Alzheimer's by increasing the steady-state level of Abeta. To provide further evidence for the role of neprilysin in AD we genotyped 22 polymorphisms, 21 SNPs and the GT repeat in the promoter region, across the neprilysin gene in 298 Caucasian sporadic Alzheimer's patients and 298 age-matched controls.

An SCN9A channelopathy causes congenital inability to experience pain.

The complete inability to sense pain in an otherwise healthy individual is a very rare phenotype. In three consanguineous families from northern Pakistan, we mapped the condition as an autosomal-recessive trait to chromosome 2q24.3.