Loss of synovial tissue macrophage homeostasis precedes rheumatoid arthritis clinical onset.

This study performed an in-depth investigation into the myeloid cellular landscape in the synovium of patients with rheumatoid arthritis (RA), "individuals at risk" of RA, and healthy controls (HC). Flow cytometric analysis demonstrated the presence of a CD40-expressing CD206CD163 macrophage population dominating the inflamed RA synovium, associated with disease activity and treatment response. In-depth RNA sequencing and metabolic analysis demonstrated that this macrophage population is transcriptionally distinct, displaying unique inflammatory and tissue-resident gene signatures, has a stable bioenergetic profile, and regulates stromal cell responses.

Enhancing Return to Alpine Skiing: Integrating Perceptual-Motor-Cognitive Considerations in Testing and Progressions: A Clinical Commentary.

Unlabelled: Alpine skiing poses significant risks for anterior cruciate ligament (ACL) injury at both recreational and professional levels, which is compounded by high rates of re-injury. Despite the existence of return to sport (RTS) and return to snow protocols, the frequency of ACL re-injury has not been mitigated, raising doubts about protocol effectiveness. Current RTS protocols primarily focus on biomechanical and neuromuscular factors in isolation, neglecting the important perceptual-motor-cognitive changes associated with ACL injuries and the high cognitive demands of skiing.

Two-Portal Arthroscopic Knotless All-Suture Anchor Posterior Labral Repair.

Isolated posterior shoulder instability accounts for approximately 10% of shoulder instability cases. Patients may present after an acute trauma or with insidious onset and associated posterior shoulder pain. Knotless and all-suture anchor devices have become increasing popular and are often used in arthroscopic shoulder instability cases to avoid knot stacks and allow for the ability to re-tension the fixation.

Metformin has anti-inflammatory effects and induces immunometabolic reprogramming via multiple mechanisms in hidradenitis suppurativa.

Background: Targeting immunometabolism has shown promise in treating autoimmune and inflammatory conditions. Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease involving painful lesions in apocrine gland-bearing skin. Therapeutic options for HS are limited and often ineffective; thus, there is a pressing need for improved treatments.

Effect of making skin incision with electrocautery on positive Cutibacterium acnes culture rates in shoulder arthroplasty: a prospective randomized clinical trial.

Background: Cutibacterium acnes remains the most commonly detected organism in shoulder arthroplasty. C acnes infection is thought to occur during shoulder arthroplasty through contamination of the surgical field with C acnes from the incised dermis. The purpose of this study was to examine whether using electrocautery for making skin incisions would decrease C acnes culture rates at the incised dermis compared to using scalpels during shoulder arthroplasty.

Targeting the NLRP3 inflammasome reduces inflammation in hidradenitis suppurativa skin.

Background: Treatment for the debilitating disease hidradenitis suppurativa (HS) is inadequate in many patients. Despite an incidence of approximately 1%, HS is often under-recognized and underdiagnosed, and is associated with a high morbidity and poor quality of life.

Objectives: To gain a better understanding of the pathogenesis of HS, in order to design new therapeutic strategies.

The mammalian target of rapamycin contributes to synovial fibroblast pathogenicity in rheumatoid arthritis.

Objectives: The mammalian target of Rapamycin (mTOR) is a metabolic master regulator of both innate and adaptive immunity; however, its exact role in stromal cell biology is unknown. In this study we explored the role of the mTOR pathway on Rheumatoid Arthritis synovial fibroblast (RASF) metabolism and activation and determined if crosstalk with the Hippo-YAP pathway mediates their effects.

Methods: Primary RA synovial fibroblasts (RASF) were cultured with TNFα alone or in combination with the mTOR inhibitor Rapamycin or YAP inhibitor Verteporfin.

Innate lymphoid cell (ILC) subsets are enriched in the skin of patients with hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic relapsing inflammatory skin disease manifested as painful inflamed lesions including deep-seated nodules, abscesses and sinus tracts. The exact aetiology of HS is unclear. Recent evidence suggests that immune dysregulation plays a crucial role in pathogenesis and disease progression.

Proximal Humerus Fractures: Leave It Alone, Fix It, Replace It?

Proximal humerus fractures are common injuries that account for 10% of all fractures in the elderly. Several options are available for the management of proximal humerus fractures. Optimal treatment is based on the fracture pattern and the patient characteristics.

Functional biomechanical comparison of Latarjet vs. distal tibial osteochondral allograft for anterior glenoid defect reconstruction.

Introduction: Glenoid reconstruction is indicated for recurrent glenohumeral instability with significant glenoid bone deficiency. Coracoid autograft (Latarjet) and distal tibial osteochondral allograft (DTA) reconstructions have been used to successfully restore glenohumeral stability. Relative advantages and disadvantages associated with each reconstruction technique have been described.

Extracranial arteriovenous malformations demonstrate dysregulated TGF-β/BMP signaling and increased circulating TGF-β1.

Extracranial arteriovenous malformations (AVMs) are characterized by anomalous arterial-to-venous connections, aberrant angiogenesis, local inflammation and hypoxia, and disorganized histological architecture; however, the precise molecular perturbations leading to this phenotype remain elusive. We hypothesized that extracranial AVM tissue would demonstrate deregulation of the TGF-β/BMP signaling pathway, which may serve as a potential target in the development of molecular-based therapies for AVMs. AVM tissue was harvested during resection from 10 patients with AVMs and compared to control tissue.

Distinct stromal and immune cell interactions shape the pathogenesis of rheumatoid and psoriatic arthritis.

Objectives: Immune and stromal cell communication is central in the pathogenesis of rheumatoid arthritis (RA) and psoriatic arthritis (PsA), however, the nature of these interactions in the synovial pathology of the two pathotypes can differ. Identifying immune-stromal cell crosstalk at the site of inflammation in RA and PsA is challenging. This study creates the first global transcriptomic analysis of the RA and PsA inflamed joint and investigates immune-stromal cell interactions in the pathogenesis of synovial inflammation.

The impact of stress on social behavior in adult zebrafish (Danio rerio).

Stress has adverse effects on social behavior that is mediated by dopamine circuits in the midbrain. The purpose of this research is to examine the effect of chronic stress and dopamine signals on social behavior in zebrafish (Danio rerio). Chronic stress was induced chemically with low dosage of ethanol (0.

Rexinoids as Therapeutics for Alzheimer's Disease: Role of APOE.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by amyloid plaques, composed of amyloid-beta peptide (Aβ) and neurofibrillary tangles, composed of aberrantly phosphorylated tau. APOE4 is the greatest genetic risk factor for AD, increasing risk up to 12- fold with a double allele compared to APOE3. In contrast, APOE2 reduces AD risk ~2-fold per allele.

The APOE4 allele shows opposite sex bias in microbleeds and Alzheimer's disease of humans and mice.

The apolipoprotein APOE4 allele confers greater risk of Alzheimer's disease (AD) for women than men, in conjunction with greater clinical deficits per unit of AD neuropathology (plaques, tangles). Cerebral microbleeds, which contribute to cognitive dysfunctions during AD, also show APOE4 excess, but sex-APOE allele interactions are not described. We report that elderly men diagnosed for mild cognitive impairment and AD showed a higher risk of cerebral cortex microbleeds with APOE4 allele dose effect in 2 clinical cohorts (ADNI and KIDS).

Genetics ignite focus on microglial inflammation in Alzheimer's disease.

In the past five years, a series of large-scale genetic studies have revealed novel risk factors for Alzheimer's disease (AD). Analyses of these risk factors have focused attention upon the role of immune processes in AD, specifically microglial function. In this review, we discuss interpretation of genetic studies.

A role for picomolar concentrations of pregnenolone sulfate in synaptic activity-dependent Ca2+ signaling and CREB activation.

Fast excitatory synaptic transmission that is contingent upon N-methyl d-aspartate receptor (NMDAR) function contributes to core information flow in the central nervous system and to the plasticity of neural circuits that underlie cognition. Hypoactivity of excitatory NMDAR-mediated neurotransmission is hypothesized to underlie the pathophysiology of schizophrenia, including the associated cognitive deficits. The neurosteroid pregnenolone (PREG) and its metabolites pregnenolone sulfate (PregS) and allopregnanolone in serum are inversely associated with cognitive improvements after oral PREG therapy, raising the possibility that brain neurosteroid levels may be modulated therapeutically.

Pregnenolone sulfate as a modulator of synaptic plasticity.

Rationale: The neurosteroid pregnenolone sulfate (PregS) acts as a cognitive enhancer and modulator of neurotransmission, yet aligning its pharmacological and physiological effects with reliable measurements of endogenous local concentrations and pharmacological and therapeutic targets has remained elusive for over 20 years.

Objectives: New basic and clinical research concerning neurosteroid modulation of the central nervous system (CNS) function has emerged over the past 5 years, including important data involving pregnenolone and various neurosteroid precursors of PregS that point to a need for a critical status update.

Results: Highly specific actions of PregS affecting excitatory N-methyl-D-aspartate receptor (NMDAR)-mediated synaptic transmission and the pharmacological effects of PregS on various receptors and ion channels are discussed.

Alkane hydroxylase gene (alkB) phylotype composition and diversity in northern Gulf of Mexico bacterioplankton.

Natural and anthropogenic activities introduce alkanes into marine systems where they are degraded by alkane hydroxylases expressed by phylogenetically diverse bacteria. Partial sequences for alkB, one of the structural genes of alkane hydroxylase, have been used to assess the composition of alkane-degrading communities, and to determine their responses to hydrocarbon inputs. We present here the first spatially extensive analysis of alkB in bacterioplankton of the northern Gulf of Mexico (nGoM), a region that experiences numerous hydrocarbon inputs.

The neuroactive steroid pregnenolone sulfate stimulates trafficking of functional N-methyl D-aspartate receptors to the cell surface via a noncanonical, G protein, and Ca2+-dependent mechanism.

N-methyl D-aspartate (NMDA) receptors (NMDARs) mediate fast excitatory synaptic transmission and play a critical role in synaptic plasticity associated with learning and memory. NMDAR hypoactivity has been implicated in the pathophysiology of schizophrenia, and clinical studies have revealed reduced negative symptoms of schizophrenia with a dose of pregnenolone that elevates serum levels of the neuroactive steroid pregnenolone sulfate (PregS). This report describes a novel process of delayed-onset potentiation whereby PregS approximately doubles the cell's response to NMDA via a mechanism that is pharmacologically and kinetically distinct from rapid positive allosteric modulation by PregS.

Analysis of composition and structure of coastal to mesopelagic bacterioplankton communities in the northern gulf of Mexico.

16S rRNA gene amplicons were pyrosequenced to assess bacterioplankton community composition, diversity, and phylogenetic community structure for 17 stations in the northern Gulf of Mexico (nGoM) sampled in March 2010. Statistical analyses showed that samples from depths ≤100 m differed distinctly from deeper samples. SAR 11 α-Proteobacteria and Bacteroidetes dominated communities at depths ≤100 m, which were characterized by high α-Proteobacteria/γ-Proteobacteria ratios (α/γ > 1.

Analysis of stomach and gut microbiomes of the eastern oyster (Crassostrea virginica) from coastal Louisiana, USA.

We used high throughput pyrosequencing to characterize stomach and gut content microbiomes of Crassostrea virginica, the Easter oyster, obtained from two sites, one in Barataria Bay (Hackberry Bay) and the other in Terrebonne Bay (Lake Caillou), Louisiana, USA. Stomach microbiomes in oysters from Hackberry Bay were overwhelmingly dominated by Mollicutes most closely related to Mycoplasma; a more rich community dominated by Planctomyctes occurred in Lake Caillou oyster stomachs. Gut communities for oysters from both sites differed from stomach communities, and harbored a relatively diverse assemblage of phylotypes.