Facilitating Overdose Risk Mitigation Among Patients Following a Clinician Office Closure: A Connecticut Case Study of the Opioid Rapid Response Program.

The Opioid Rapid Response Program (ORRP) is a federal program designed to support states in mitigating risks to patients who lose access to a prescriber of opioids or other controlled substances. Displaced patients might face risks of withdrawal, overdose, or other harms. Rapid response efforts to mitigate risks require coordination across multiple parts of the health care system.

Phagosomal signalling of the C-type lectin receptor Dectin-1 is terminated by intramembrane proteolysis.

Sensing of pathogens by pattern recognition receptors (PRR) is critical to initiate protective host defence reactions. However, activation of the immune system has to be carefully titrated to avoid tissue damage necessitating mechanisms to control and terminate PRR signalling. Dectin-1 is a PRR for fungal β-glucans on immune cells that is rapidly internalised after ligand-binding.

High Na Environments Impair Phagocyte Oxidase-Dependent Antibacterial Activity of Neutrophils.

Infection and inflammation can augment local Na abundance. These increases in local Na levels boost proinflammatory and antimicrobial macrophage activity and can favor polarization of T cells towards a proinflammatory Th17 phenotype. Although neutrophils play an important role in fighting intruding invaders, the impact of increased Na on the antimicrobial activity of neutrophils remains elusive.

Reduction of Tissue Na Accumulation After Renal Transplantation.

Introduction: Chronic kidney disease (CKD) engenders salt-sensitive hypertension. Whether or not tissue Na accumulation is increased in CKD patients remains uncertain. How tissue Na is affected after renal transplantation has not been assessed.

Effects of mechanical strain on periodontal ligament fibroblasts in presence of Aggregatibacter actinomycetemcomitans lysate.

Purpose: Many adult orthodontic patients suffer from periodontitis, which is caused by oral pathogens such as the gram-negative Aggregatibacter actinomycetemcomitans (Agac). Like orthodontic tooth movement, periodontitis is associated with inflammation and alveolar bone remodelling thereby affecting orthodontic treatment. Interactions of both processes, however, are not sufficiently explored, particularly with regard to oxidative stress.

Differential gene expression response of synovial fibroblasts from temporomandibular joints and knee joints to dynamic tensile stress.

Purpose: Apart from other risk factors, mechanical stress on joints can promote the development of osteoarthritis (OA), which can also affect the temporomandibular joint (TMJ), resulting in cartilage degeneration and synovitis. Synovial fibroblasts (SF) play an important role in upkeeping joint homeostasis and OA pathogenesis, but mechanical stress as a risk factor might act differently depending on the type of joint. We thus investigated the relative impact of mechanical stress on the gene expression pattern of SF from TMJs and knee joints to provide new insights into OA pathogenesis.

Application of Lipid Class Ratios for Sample Stability Monitoring-Evaluation of Murine Tissue Homogenates and SDS as a Stabilizer.

Lipids are a ubiquitous class of structurally complex molecules involved in various biological processes. In the fast-growing field of lipidomics, preanalytical issues are frequently neglected. Here, we investigated the stability of lipid profiles of murine liver, brain, lung, heart, and spleen homogenates by quantitative flow injection analysis using tandem mass spectrometry and high-resolution mass spectrometry.

Novel pathomechanism for spontaneous bacterial peritonitis: disruption of cell junctions by cellular and bacterial proteases.

Objective: Spontaneous bacterial peritonitis (SBP) is a life-threatening complication of liver cirrhosis with a 1-year mortality of 66%. Bacterial translocation (BT) from the intestine to the mesenteric lymph nodes is crucial for the pathogenesis of SBP.

Design: Since BT presupposes a leaky intestinal epithelium, the integrity of mucus and epithelial cell junctions (E-cadherin and occludin) was examined in colonic biopsies from patients with liver cirrhosis and controls.

Mechanical Stress Induce PG-E2 in Murine Synovial Fibroblasts Originating from the Temporomandibular Joint.

Genetic predisposition, traumatic events, or excessive mechanical exposure provoke arthritic changes in the temporomandibular joint (TMJ). We analysed the impact of mechanical stress that might be involved in the development and progression of TMJ osteoarthritis (OA) on murine synovial fibroblasts (SFs) of temporomandibular origin. SFs were subjected to different protocols of mechanical stress, either to a high-frequency tensile strain for 4 h or to a tensile strain of varying magnitude for 48 h.

Dietary Salt Accelerates Orthodontic Tooth Movement by Increased Osteoclast Activity.

Dietary salt uptake and inflammation promote sodium accumulation in tissues, thereby modulating cells like macrophages and fibroblasts. Previous studies showed salt effects on periodontal ligament fibroblasts and on bone metabolism by expression of nuclear factor of activated T-cells-5 (NFAT-5). Here, we investigated the impact of salt and NFAT-5 on osteoclast activity and orthodontic tooth movement (OTM).

Impact of salt and the osmoprotective transcription factor NFAT-5 on macrophages during mechanical strain.

Myeloid cells regulate bone density in response to increased salt (NaCl) intake via the osmoprotective transcription factor, nuclear factor of activated T cells-5 (NFAT-5). Because orthodontic tooth movement (OTM) is a pseudoinflammatory immunological process, we investigated the influence of NaCl and NFAT-5 on the expression pattern of macrophages in a model of simulated OTM. RAW264.

LARP1 isoform expression in human cancer cell lines.

LARP1 is an oncogenic RNA-binding protein required for ribosome biogenesis and cancer cell survival. From published studies, there is disparity over which of two different LARP1 protein isoforms (termed the long LI-LARP1 and short SI-LARP1) is the canonical. Here, after conducting a series of biochemical and cellular assays, we conclude that LI-LARP1 (NM_033551.

A high-salt diet compromises antibacterial neutrophil responses through hormonal perturbation.

The Western diet is rich in salt, which poses various health risks. A high-salt diet (HSD) can stimulate immunity through the nuclear factor of activated T cells 5 (Nfat5)-signaling pathway, especially in the skin, where sodium is stored. The kidney medulla also accumulates sodium to build an osmotic gradient for water conservation.

Osteoprotective action of low-salt diet requires myeloid cell-derived NFAT5.

Dietary salt consumption leads to cutaneous Na+ storage and is associated with various disorders, including osteopenia. Here, we explore the impact of Na+ and the osmoprotective transcription factor nuclear factor of activated T cell 5 (NFAT5) on bone density and osteoclastogenesis. Compared with treatment of mice with high-salt diet, low-salt diet (LSD) increased bone density, decreased osteoclast numbers, and elevated Na+ content and Nfat5 levels in the BM.

Sodium-chloride-induced effects on the expression profile of human periodontal ligament fibroblasts with focus on simulated orthodontic tooth movement.

Increased salt (NaCl) consumption triggers chronic diseases such as hypertension or osteopenia. Its impact on orthodontic tooth movement and periodontitis, however, has not been investigated, although both processes are related to the immune system, with periodontal ligament fibroblasts (PDLFs) playing a key mediating role. Here, we investigated the impact of NaCl on the expression pattern of PDLFs in a model of simulated compressive orthodontic strain.

Interplay of Na Balance and Immunobiology of Dendritic Cells.

Local Na balance emerges as an important factor of tissue microenvironment. On the one hand, immune cells impact on local Na levels. On the other hand, Na availability is able to influence immune responses.

HIF1A and NFAT5 coordinate Na-boosted antibacterial defense via enhanced autophagy and autolysosomal targeting.

Infection and inflammation are able to induce diet-independent Na-accumulation without commensurate water retention in afflicted tissues, which favors the pro-inflammatory activation of mouse macrophages and augments their antibacterial and antiparasitic activity. While Na-boosted host defense against the protozoan parasite is mediated by increased expression of the leishmanicidal NOS2 (nitric oxide synthase 2, inducible), the molecular mechanisms underpinning this enhanced antibacterial defense of mouse macrophages with high Na (HS) exposure are unknown. Here, we provide evidence that HS-increased antibacterial activity against was neither dependent on NOS2 nor on the phagocyte oxidase.

Monitoring Protein Dynamics in Protein -Mannosyltransferase Mutants In Vivo by Tandem Fluorescent Protein Timers.

For proteins entering the secretory pathway, a major factor contributing to maturation and homeostasis is glycosylation. One relevant type of protein glycosylation is -mannosylation, which is essential and evolutionarily-conserved in fungi, animals, and humans. Our recent proteome-wide study in the eukaryotic model organism revealed that more than 26% of all proteins entering the secretory pathway receive -mannosyl glycans.

Hypertonicity-enforced BCL-2 addiction unleashes the cytotoxic potential of death receptors.

Attempts to exploit the cytotoxic activity of death receptors (DR) for treating cancer have thus far been disappointing. DR activation in most malignant cells fails to trigger cell death and may even promote tumor growth by activating cell death-independent DR-associated signaling pathways. Overcoming apoptosis resistance is consequently a prerequisite for successful clinical exploitation of DR stimulation.

Hypoxia, Hypoxia-Inducible Factor-1α, and Innate Antileishmanial Immune Responses.

Low oxygen environments and accumulation of hypoxia-inducible factors (HIFs) are features of infected and inflamed tissues. Here, we summarize our current knowledge on oxygen levels found in -infected tissues and discuss which mechanisms potentially contribute to local tissue oxygenation in leishmanial lesions. Moreover, we review the role of hypoxia and HIF-1 on innate antileishmanial immune responses.