Medication-induced fractures: Screening and treatment strategies.

Medication-induced osteoporosis leads to substantial fracture morbidity. With polypharmacy and the aging population in the United States, significant increases in medication-associated fractures are predicted. The most common medication to cause osteoporosis and increase fractures is glucocorticoids.

SHIP inhibition mediates select TREM2-induced microglial functions.

Microglia play a pivotal role in the pathology of Alzheimer's Disease (AD), with the Triggering Receptor Expressed on Myeloid cells 2 (TREM2) central to their neuroprotective functions. The R47H variant of TREM2 has emerged as a significant genetic risk factor for AD, leading to a loss-of-function phenotype in mouse AD models. This study elucidates the roles of TREM2 in human microglia-like HMC3 cells and the regulation of these functions by SH2-containing inositol-5'-phosphatase 1 (SHIP1).

HIV-Associated Rheumatic Diseases: A Narrative Review.

Human immunodeficiency virus (HIV) is widely prevalent among the world population. Although, historically, it has been linked to opportunistic infections in keeping with immunodeficiency and immune dysregulation, it has also been associated with a wide variety of autoimmune manifestations. With the introduction of highly active antiretroviral therapy and subsequent restoration of immunity, there have been multiple immune-mediated diseases that have resurfaced in the HIV population.

The inhibitor of MyoD Family A (I-MFA) regulates megakaryocyte lineage commitment and terminal differentiation.

Hematopoiesis and lineage commitment are regulated by several conserved cell-intrinsic signaling pathways, including MAPKs and β-catenin/TCF/LEF. The Inhibitor of MyoD Family A (I-MFA), a transcriptional repressor and tumor suppressor gene, interacts with these pathways and is dysregulated in chronic and acute myeloid leukemias, suggesting it may play a role in development and differentiation during hematopoiesis. To study this, immune cell populations in the bone marrow (BM) and periphery were analyzed in mice lacking Mdfi, encoding I-MFA (I-MFA-/-), and wild type (WT) controls.

Development of SARS-CoV-2 infection in patients with rheumatic conditions on hydroxychloroquine monotherapy vs. patients without rheumatic conditions: A retrospective, propensity-matched cohort study.

Background: The primary purpose of the current study was to examine whether patients with rheumatologic conditions receiving only chronic hydroxychloroquine therapy for their disease are at less risk of developing SARS-CoV-2 infection than a comparative group of patients without rheumatologic conditions.

Methods: A retrospective, observational, nationwide stratified propensity analysis was conducted comparing patients only on chronic treatment with hydroxychloroquine for their rheumatologic condition to a random sample of patients without rheumatologic conditions and not receiving hydroxychloroquine, utilizing a Veterans Health Administration nationwide clinical administrative database.

Results: The 1-to-1 stratified propensity analysis was undertaken using a random sample of patients without rheumatoid conditions and not receiving hydroxychloroquine (n  33,081) and patients with rheumatoid conditions receiving hydroxychloroquine as the lone medication for their condition (n  6047).

Transcutaneous Vagus Nerve Stimulation Ameliorates the Phenotype of Heart Failure With Preserved Ejection Fraction Through Its Anti-Inflammatory Effects.

Background: A systemic proinflammatory state plays a central role in the development of heart failure with preserved ejection fraction (HFpEF). Low-level transcutaneous vagus nerve stimulation (LLTS) suppresses inflammation in animals and humans, mediated by an α7nAchR (alpha7 nicotinic acetylcholine receptor)-dependent pathway. We examined the effects of LLTS on cardiac function, inflammation, and fibrosis in the presence of α7nAchR pharmacological blockade in a rat model of HFpEF.

Neuromodulation of Inflammation to Treat Heart Failure With Preserved Ejection Fraction: A Pilot Randomized Clinical Trial.

Background A systemic proinflammatory state plays a central role in the development of heart failure with preserved ejection fraction. Low-level transcutaneous vagus nerve stimulation suppresses inflammation in humans. We conducted a sham-controlled, double-blind, randomized clinical trial to examine the effect of chronic low-level transcutaneous vagus nerve stimulation on cardiac function, exercise capacity, and inflammation in patients with heart failure with preserved ejection fraction.

FBW7 couples structural integrity with functional output of primary cilia.

Structural defects in primary cilia have robust effects in diverse tissues and systems. However, how disorders of ciliary length lead to functional outcomes are unknown. We examined the functional role of a ciliary length control mechanism of FBW7-mediated destruction of NDE1, in mesenchymal stem cell (MSC) differentiation.

Sex differences in the incidence and mode of death in rats with heart failure with preserved ejection fraction.

New Findings: What is the central question of this study? Prior studies failed to address the role of sex in modifying the pathophysiology and response to therapy in heart failure with preserved ejection fraction (HFpEF), potentially introducing bias into translational findings. We aimed to explore sex differences in outcomes and sought to identify the underlying mechanisms in a well-established rat model of HFpEF. What is the main finding and its importance? Male rats with HFpEF exhibited worse survival compared with females and were at a higher risk for sudden death, attributable in part to QT prolongation, autonomic dysregulation and enhanced inflammation.

Long-term hydroxychloroquine use in patients with rheumatic conditions and development of SARS-CoV-2 infection: a retrospective cohort study.

Background: Hydroxychloroquine is one of several agents being evaluated in the treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to examine whether patients with rheumatological conditions receiving chronic hydroxychloroquine therapy are at less risk of developing SARS-CoV-2 infection than those not receiving hydroxychloroquine.

Methods: This retrospective cohort study included de-identified information of all veterans in the US Veterans Health Administration clinical administrative database aged 18 years or older with rheumatoid arthritis, systemic lupus erythematosus, or associated rheumatological conditions (based on International Classification of Diseases, 10th edition, diagnostic codes) who were alive on March 1, 2020.

Inhibition of γ-secretase in adipocytes leads to altered IL-6 secretion and adipose inflammation.

Adipocyte-mediated inflammatory signalling has been proposed to alter adipose physiology in obesity and Type 2 diabetes mellitus. Novel targets for alteration of inflammatory signalling are needed to improve obesity-related outcomes. The γ-secretase enzyme complex has been suggested to play a role both in adipocyte function as well as in immune regulation.

Control of PTH secretion by the TRPC1 ion channel.

Familial hypocalciuric hypercalcemia (FHH) is a genetic condition associated with hypocalciuria, hypercalcemia, and, in some cases, inappropriately high levels of circulating parathyroid hormone (PTH). FHH is associated with inactivating mutations in the gene encoding the Ca2+-sensing receptor (CaSR), a GPCR, and GNA11 encoding G protein subunit α 11 (Gα11), implicating defective GPCR signaling as the root pathophysiology for FHH. However, the downstream mechanism by which CaSR activation inhibits PTH production/secretion is incompletely understood.

TREAT AF (Transcutaneous Electrical Vagus Nerve Stimulation to Suppress Atrial Fibrillation): A Randomized Clinical Trial.

Objectives: This study was a sham-controlled, double-blind, randomized clinical trial to examine the effect of chronic low level tragus stimulation (LLTS) in patients with paroxysmal AF.

Background: Low-level transcutaneous electrical stimulation of the auricular branch of the vagus nerve at the tragus (LLTS) acutely suppresses atrial fibrillation (AF) in humans, but the chronic effect remains unknown.

Methods: LLTS (20 Hz, 1 mA below the discomfort threshold) was delivered using an ear clip attached to the tragus (active arm) (n = 26) or the ear lobe (sham control arm) (n = 27) for 1 h daily over 6 months.

TLR4 Promotes and DAP12 Limits Obesity-Induced Osteoarthritis in Aged Female Mice.

Aging and female sex are the strongest risk factors for nontraumatic osteoarthritis (OA); whereas obesity is a modifiable risk factor accelerating OA. Prior studies indicate that the innate immune receptor toll-like receptor 4 (TLR4) mediates obesity-induced metabolic inflammation and cartilage catabolism via recognition of damage-associated molecular patterns and is increased with aging in OA joints. TLR4 responses are limited by innate immunoreceptor adapter protein DNAX-activating protein of 12kDA (DAP12).

Low-level transcutaneous vagus nerve stimulation attenuates cardiac remodelling in a rat model of heart failure with preserved ejection fraction.

New Findings: What is the central question of this study? What is the effect of chronic intermittent low-level transcutaneous vagus nerve stimulation on cardiac inflammation, fibrosis and diastolic dysfunction in a rat model of heart failure with preserved ejection fraction? What is the main finding and its importance? In salt-sensitive rats fed with high salt diet, low-level transcutaneous vagus nerve stimulation significantly attenuated blood pressure elevation, ameliorated diastolic function, and attenuated left ventricular inflammation and fibrosis compared to the sham group. Further studies to examine the efficacy of this novel treatment in humans are warranted.

Abstract: Inflammation and fibrosis play a central role in the development of heart failure with preserved ejection fraction (HFpEF).

Low-Level Vagus Nerve Stimulation Suppresses Post-Operative Atrial Fibrillation and Inflammation: A Randomized Study.

Objectives: This study sought to examine the efficacy of low-level vagus nerve stimulation (LLVNS) in suppressing post-operative atrial fibrillation (POAF) and inflammatory cytokines in patients undergoing cardiac surgery.

Background: POAF often complicates cardiac surgery.

Methods: Patients undergoing cardiac surgery were randomized to active or sham LLVNS.

Immune Contributions to Osteoarthritis.

Purpose Of The Review: Mounting evidence supports a role of low-grade inflammation in the pathophysiology of osteoarthritis (OA). We review and discuss the role of synovitis, complement activation, cytokines, and immune cell population in OA.

Recent Findings: Using newer imaging modalities, synovitis is found in the majority of knees with OA.

Corrigendum to "Utilization of Preventive Measures for Glucocorticoid-Induced Osteoporosis among Veterans with Inflammatory Bowel Disease".

[This corrects the article DOI: 10.1155/2013/862312.].

A functional genomics predictive network model identifies regulators of inflammatory bowel disease.

A major challenge in inflammatory bowel disease (IBD) is the integration of diverse IBD data sets to construct predictive models of IBD. We present a predictive model of the immune component of IBD that informs causal relationships among loci previously linked to IBD through genome-wide association studies (GWAS) using functional and regulatory annotations that relate to the cells, tissues, and pathophysiology of IBD. Our model consists of individual networks constructed using molecular data generated from intestinal samples isolated from three populations of patients with IBD at different stages of disease.

Innate Immune Responses and Osteoarthritis.

Purpose Of The Review: Osteoarthritis (OA) is a chronic, painful joint disease that affects approximately 40% of adults over 70 year. Age is the strongest predictor of OA, while obesity is considered the primary preventable risk factor for OA. Both conditions are associated with abnormal innate immune inflammatory responses that contribute to OA progression and are the focus of this review.

DOK3 Modulates Bone Remodeling by Negatively Regulating Osteoclastogenesis and Positively Regulating Osteoblastogenesis.

Osteoclastogenesis is essential for bone remodeling and normal skeletal maintenance. Receptor activator of NF-κB ligand (RANKL) promotes osteoclast differentiation and function but requires costimulation of immunoreceptor tyrosine-based activation motif (ITAM)-coupled immunoreceptors. Triggering receptor expressed on myeloid cells-2 (TREM2) coupled to ITAM-adaptor protein DNAX activation protein 12kDA (DAP12) provides costimulation of intracellular calcium signaling during osteoclastogenesis.

2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis.

Objective: To develop recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP).

Methods: We conducted a systematic review to synthesize the evidence for the benefits and harms of GIOP prevention and treatment options. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence.

2017 American College of Rheumatology Guideline for the Prevention and Treatment of Glucocorticoid-Induced Osteoporosis.

Objective: To develop recommendations for prevention and treatment of glucocorticoid-induced osteoporosis (GIOP).

Methods: We conducted a systematic review to synthesize the evidence for the benefits and harms of GIOP prevention and treatment options. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to rate the quality of evidence.