Use and Cost of Low-Value Services Among Veterans Dually Enrolled in VA and Medicare.

Background: Over half of veterans enrolled in the Veterans Health Administration (VA) are also enrolled in Medicare, potentially increasing their opportunity to receive low-value health services within and outside VA.

Objectives: To characterize the use and cost of low-value services delivered to dually enrolled veterans from VA and Medicare.

Design: Retrospective cross-sectional.

Care cascades following low-value cervical cancer screening in dually enrolled Veterans.

Background: Veterans dually enrolled in the Veterans Health Administration (VA) and Medicare commonly experience downstream services as part of a care cascade after an initial low-value service. Our objective was to characterize the frequency and cost of low-value cervical cancer screening and subsequent care cascades among Veterans dually enrolled in VA and Medicare.

Methods: This retrospective cohort study used VA and Medicare administrative data from fiscal years 2015 to 2019.

Effects of HLA single chain trimer design on peptide presentation and stability.

MHC class I "" molecules, coupling MHC heavy chain, β-microglobulin, and a specific peptide into a single polypeptide chain, are widely used in research. To more fully understand caveats associated with this design that may affect its use for basic and translational studies, we evaluated a set of engineered single-chain trimers with combinations of stabilizing mutations across eight different classical and non-classical human class I alleles with 44 different peptides, including a novel human/murine chimeric design. While, overall, single-chain trimers accurately recapitulate native molecules, care was needed in selecting designs for studying peptides longer or shorter than 9-mers, as single-chain trimer design could affect peptide conformation.

Variation in Low-Value Service Use Across Veterans Affairs Facilities.

Background: It is unclear whether extensive variation in the use of low-value services exists even within a national integrated delivery system like the Veterans Health Administration (VA).

Objective: To quantify variation in the use of low-value services across VA facilities and examine associations between facility characteristics and low-value service use.

Design: In this retrospective cross-sectional study of VA administrative data, we constructed facility-level rates of low-value service use as the mean count of 29 low-value services per 100 Veterans per year.

Frailty predicts referral for elder abuse evaluation in a nationwide healthcare system-Results from a case-control study.

Background: Elder abuse (EA) is common and has devastating health impacts. Frailty may increase susceptibility to and consequences of EA for older adults, making healthcare system detection more likely, but this relationship has been difficult to study. We examined the association between a recently validated frailty index and referral to social work (SW) for EA evaluation in the Veterans Administration (VA) healthcare system.

Assessment of Care Cascades Following Low-Value Prostate-Specific Antigen Testing Among Veterans Dually Enrolled in the US Veterans Health Administration and Medicare Systems.

Importance: Older US veterans commonly receive health care outside of the US Veterans Health Administration (VHA) through Medicare, which may increase receipt of low-value care and subsequent care cascades.

Objective: To characterize the frequency, cost, and source of low-value prostate-specific antigen (PSA) testing and subsequent care cascades among veterans dually enrolled in the VHA and Medicare and to determine whether receiving a PSA test through the VHA vs Medicare is associated with more downstream services.

Design, Setting, And Participants: This retrospective cohort study used VHA and Medicare administrative data from fiscal years (FYs) 2017 to 2018.

Prevalence and Cost of Care Cascades Following Low-Value Preoperative Electrocardiogram and Chest Radiograph Within the Veterans Health Administration.

Background: Low-value care cascades, defined as the receipt of downstream health services potentially related to a low-value service, can result in harm to patients and wasteful healthcare spending, yet have not been characterized within the Veterans Health Administration (VHA).

Objective: To examine if the receipt of low-value preoperative testing is associated with greater utilization and costs of potentially related downstream health services in Veterans undergoing low or intermediate-risk surgery.

Design: Retrospective cohort study using VHA administrative data from fiscal years 2017-2018 comparing Veterans who underwent low-value preoperative electrocardiogram (EKG) or chest radiograph (CXR) with those who did not.

Medical and Social Factors Associated With Referral for Elder Abuse Services in a National Health Care System.

Background: Elder abuse (EA) is common and has devastating health consequences yet is not systematically assessed or documented in most health systems, limiting efforts to target health care-based interventions. Our objective was to examine sociodemographic and medical characteristics associated with documented referrals for EA assessment or services in a national U.S.

Silymarin suppresses basal and stimulus-induced activation, exhaustion, differentiation, and inflammatory markers in primary human immune cells.

Silymarin (SM), and its flavonolignan components, alter cellular metabolism and inhibit inflammatory status in human liver and T cell lines. In this study, we hypothesized that SM suppresses both acute and chronic immune activation (CIA), including in the context of HIV infection. SM treatment suppressed the expression of T cell activation and exhaustion markers on CD4+ and CD8+ T cells from chronically-infected, HIV-positive subjects.

Uncovering biologically significant lipid isomers with liquid chromatography, ion mobility spectrometry and mass spectrometry.

Understanding how biological molecules are generated, metabolized and eliminated in living systems is important for interpreting processes such as immune response and disease pathology. While genomic and proteomic studies have provided vast amounts of information over the last several decades, interest in lipidomics has also grown due to improved analytical technologies revealing altered lipid metabolism in type 2 diabetes, cancer, and lipid storage disease. Mass spectrometry (MS) measurements are currently the dominant approach for characterizing the lipidome by providing detailed information on the spatial and temporal composition of lipids.

Natural Products as Tools for Defining How Cellular Metabolism Influences Cellular Immune and Inflammatory Function during Chronic Infection.

Chronic viral infections like those caused by hepatitis C virus (HCV) and human immunodeficiency virus (HIV) cause disease that establishes an ongoing state of chronic inflammation. While there have been tremendous improvements towards curing HCV with directly acting antiviral agents (DAA) and keeping HIV viral loads below detection with antiretroviral therapy (ART), there is still a need to control inflammation in these diseases. Recent studies indicate that many natural products like curcumin, resveratrol and silymarin alter cellular metabolism and signal transduction pathways via enzymes such as adenosine monophosphate kinase (AMPK) and mechanistic target of rapamycin (mTOR), and these pathways directly influence cellular inflammatory status (such as NF-κB) and immune function.

Phylogenetic and ecological factors impact the gut microbiota of two Neotropical primate species.

Recent studies suggest that variation in diet across time and space results in changes in the mammalian gut microbiota. This variation may ultimately impact host ecology by altering nutritional status and health. Wild animal populations provide an excellent opportunity for understanding these interactions.

Silymarin Suppresses Cellular Inflammation By Inducing Reparative Stress Signaling.

Silymarin, a characterized extract of the seeds of milk thistle (Silybum marianum), suppresses cellular inflammation. To define how this occurs, transcriptional profiling, metabolomics, and signaling studies were performed in human liver and T cell lines. Cellular stress and metabolic pathways were modulated within 4 h of silymarin treatment: activation of Activating Transcription Factor 4 (ATF-4) and adenosine monophosphate protein kinase (AMPK) and inhibition of mammalian target of rapamycin (mTOR) signaling, the latter being associated with induction of DNA-damage-inducible transcript 4 (DDIT4).

Engineered calcium-precipitable restriction enzyme.

We have developed a simple system for tagging and purifying proteins. Recent experiments have demonstrated that RTX (Repeat in Toxin) motifs from the adenylate cyclase toxin gene (CyaA) of B. pertussis undergo a conformational change upon binding calcium, resulting in precipitation of fused proteins and making this method a viable alternative for bioseparation.

Independent, parallel pathways to CXCL10 induction in HCV-infected hepatocytes.

Background & Aims: The pro-inflammatory chemokine CXCL10 is induced by HCV infection in vitro and in vivo, and is associated with outcome of IFN (interferon)-based therapy. We studied how hepatocyte sensing of early HCV infection via TLR3 (Toll-like receptor 3) and RIG-I (retinoic acid inducible gene I) led to expression of CXCL10.

Methods: CXCL10, type I IFN, and type III IFN mRNAs and proteins were measured in PHH (primary human hepatocytes) and hepatocyte lines harboring functional or non-functional TLR3 and RIG-I pathways following HCV infection or exposure to receptor-specific stimuli.

The role of amino acid changes in the human immunodeficiency virus type 1 transmembrane domain in antibody binding and neutralization.

The detailed interactions between antibodies and the HIV-1 envelope protein that lead to neutralization are not well defined. Here, we show that several conservative substitutions in the envelope gp41 led to a ~100 fold increase in neutralization sensitivity to monoclonal antibodies (MAbs) that target gp41: 4E10 and 2F5. Substitution at position 675 alone did not impact neutralization susceptibility to MAbs that recognize more distal sites in gp120 (b12, VRC01, PG9).

Stabilization of α-conotoxin AuIB: influences of disulfide connectivity and backbone cyclization.

α-Conotoxins are peptides isolated from the venom ducts of cone snails that target nicotinic acetylcholine receptors (nAChRs). They are valuable pharmacological tools and have potential applications for treating a range of conditions in humans, including pain. However, like all peptides, conotoxins are susceptible to degradation, and to enhance their therapeutic potential it is important to elucidate the factors contributing to instability and to develop approaches for improving stability.

Differential effects of selective HDAC inhibitors on macrophage inflammatory responses to the Toll-like receptor 4 agonist LPS.

Broad-spectrum inhibitors of HDACs are therapeutic in many inflammatory disease models but exacerbated disease in a mouse model of atherosclerosis. HDAC inhibitors have anti- and proinflammatory effects on macrophages in vitro. We report here that several broad-spectrum HDAC inhibitors, including TSA and SAHA, suppressed the LPS-induced mRNA expression of the proinflammatory mediators Edn-1, Ccl-7/MCP-3, and Il-12p40 but amplified the expression of the proatherogenic factors Cox-2 and Pai-1/serpine1 in primary mouse BMM.

Selective induction of the Notch ligand Jagged-1 in macrophages by soluble egg antigen from Schistosoma mansoni involves ERK signalling.

Soluble egg antigen (SEA) from the helminth Schistosoma mansoni promotes T helper type 2 (Th2) responses by modulating antigen-presenting cell function. The Jagged/Notch pathway has recently been implicated in driving Th2 development. We show here that SEA rapidly up-regulated mRNA and protein expression of the Notch ligand Jagged-1 in both murine bone marrow-derived macrophages (BMMs) and human monocyte-derived macrophages (HMDMs).

Cyclic MrIA: a stable and potent cyclic conotoxin with a novel topological fold that targets the norepinephrine transporter.

Conotoxins, disulfide-rich peptides from the venom of cone snails, have created much excitement over recent years due to their potency and specificity for ion channels and their therapeutic potential. One recently identified conotoxin, MrIA, a 13-residue member of the chi-conotoxin family, inhibits the human norepinephrine transporter (NET) and has potential applications in the treatment of pain. In the current study, we show that the beta-hairpin structure of native MrIA is retained in a synthetic cyclic version, as is biological activity at the NET.