Structural Analysis of Human IgE Monoclonal Antibody Epitopes on Dust Mite Allergen Der p 2.

BACKGROUND: Human IgE monoclonal antibodies (hIgE mAb) against major mite allergen Der p 2 developed using human hybridoma technology, were used for IgE epitope mapping and analysis of epitopes associated with the human IgE repertoire. OBJECTIVE: To elucidate the new hIgE mAb 4C8 epitope on Der p 2 and compare it to the hIgE mAb 2F10 epitope in the context of the allergenic structure of Der p 2. METHODS: X-ray crystallography was utilized to determine the epitope of anti-Der p 2 hIgE mAb 4C8. Epitope mutants created by targeted mutagenesis were analyzed by immunoassays and in vivo using a human FcεRIα-transgenic mouse model of passive systemic anaphylaxis. RESULTS: The structure of recombinant Der p 2 with hIgE mAb 4C8 Fab was determined at 3.05 Å. The newly identified epitope region does not overlap with the hIgE mAb 2F10 epitope or the region recognized by three overlapping hIgE mAb (1B8, 5D10, and 2G1). Compared to wildtype Der p 2, single or double 4C8 and 2F10 epitope mutants bound less IgE antibodies from allergic patients by as much as 93%. Human FcεRIα-transgenic mice sensitized by hIgE mAb, which were susceptible to anaphylaxis when challenged with wildtype Der p 2, could no longer cross-link FcεRI to induce anaphylaxis when challenged with the epitope mutants. CONCLUSION: These data establish the structural basis of allergenicity of two hIgE mAb non-overlapping epitopes on Der p 2, which appear to make important contributions to the hIgE repertoire against Der p 2 and provide molecular targets for future design of allergy therapeutics.

Immune system dysregulation preceding a case of laboratory-confirmed zoster/dermatitis on board the International Space Station.

A case report detailing, for the first time, a case of laboratory-confirmed zoster in an astronaut on board the International Space Station is presented. The findings of reduced T-cell function, cytokine imbalance, and increased stress hormones which preceded the event are detailed. Relevance for deep space countermeasures is discussed.

Myeloablative Vs. Non-Myeloablative Consolidation for Primary Central Nervous System Lymphoma: Results of Alliance 51101.

While it is evident that standard dose whole brain radiotherapy as consolidation is associated with significant neurotoxicity, the optimal consolidative strategy for primary central nervous system lymphoma (PCNSL) is not defined. We performed a randomized phase 2 clinical trial via the U.S. Alliance cancer cooperative group to compare myeloablative consolidation supported by autologous stem cell transplantation with non-myeloablative consolidation after induction therapy for PCNSL. This is the first randomized trial to be initiated that eliminates whole brain radiotherapy as a consolidative approach in newly-diagnosed PCNSL. Patients, age 18-75 years, were randomly assigned in a 1:1 manner to induction therapy (methotrexate, temozolomide, rituximab and cytarabine) followed by consolidation with either thiotepa plus carmustine and autologous stem cell rescue versus induction followed by non-myeloablative, infusional etoposide plus cytarabine (EA) The primary endpoint was progression-free survival (PFS). 113 patients were randomized and 108 (54 in each arm) were evaluable. More patients in the non-myeloablative arm experienced progressive disease or death during induction (28% versus 11%, p = 0.05). Thirty-six patients received autologous stem cell transplant and 34 received non-myeloablative consolidation. The estimated 2-year PFS was higher in the myeloablative versus non-myeloablative arm (73% versus 51%; p= 0.02). However, a planned secondary analysis, landmarked at start of consolidation, revealed that the estimated 2-year PFS in those who completed consolidation therapy was not significantly different between the arms (86% versus 71%; p = 0.21). Both consolidative strategies yielded encouraging efficacy and similar toxicity profiles. Clinicaltrials.gov (NCT01511562).

HDL-C and apolipoprotein A-I are independently associated with skeletal muscle mitochondrial function in healthy humans.

Prior animal and cell studies have demonstrated a direct role of high-density lipoprotein (HDL) and apolipoprotein A-I (ApoA-I) in enhancing skeletal muscle mitochondrial function and exercise capacity. However, the relevance of these animal and cell investigations in humans remains unknown. Therefore, a cross-sectional study was conducted in 48 adults (67% female, 8% Black participants, age 39 ± 15.4 yr old) to characterize the associations between HDL measures, ApoA-I, and muscle mitochondrial function. Forearm muscle oxygen recovery time (tau) from postexercise recovery kinetics was used to assess skeletal muscle mitochondrial function. Lipoprotein measures were assessed by nuclear magnetic resonance. HDL efflux capacity was assessed using J774 macrophages, radiolabeled cholesterol, and apolipoprotein B-depleted plasma both with and without added cyclic adenosine monophosphate. In univariate analyses, faster skeletal muscle oxygen recovery time (lower tau) was significantly associated with higher levels of HDL cholesterol (HDL-C), ApoA-I, and larger mean HDL size, but not HDL cholesterol efflux capacity. Slower recovery time (higher tau) was positively associated with body mass index (BMI) and fasting plasma glucose (FPG). In multivariable linear regression analyses, higher levels of HDL-C and ApoA-I, as well as larger HDL size, were independently associated with faster skeletal muscle oxygen recovery times that persisted after adjusting for BMI and FPG (all P < 0.05). In conclusion, higher levels of HDL-C, ApoA-I, and larger mean HDL size were independently associated with enhanced skeletal muscle mitochondrial function in healthy humans.NEW & NOTEWORTHY Our study provides the first direct evidence supporting the beneficial role of HDL-C and ApoA-I on enhanced skeletal muscle mitochondrial function in healthy young to middle-aged humans without cardiometabolic disease.

Identification and characterization of a novel nematode pan allergen (NPA) from Wuchereria bancrofti and their potential role in human filarial tropical pulmonary eosinophilia (TPE).

BACKGROUND: Tropical pulmonary eosinophilia (TPE) is a chronic respiratory syndrome associated with Lymphatic Filariasis (LF), a tropical parasitic infection of the human, transmitted by mosquitoes. The larval form of LF (microfilariae) are trapped in the lungs of TPE subjects have a major role in initiating the TPE syndrome. To date, there are no reports on the potential allergen that is responsible for generating parasite-specific IgE in TPE. METHODOLOGY/PRINCIPAL FINDINGS: In this project, we screened a cDNA expression library of the microfilarial stages of Wuchereria bancrofti with monoclonal IgE antibodies prepared from subjects with clinical filarial infections. Our studies identified a novel molecule that showed significant sequence similarity to an allergen. A blast analysis showed the presence of similar proteins in a number of nematodes parasites. Thus, we named this molecule as Nematode Pan Allergen (NPA). Subsequent functional analysis showed that NPA is a potent allergen that can cause release of histamine from mast cells, induce secretion of proinflammatory cytokines from alveolar macrophages and promote accumulation of eosinophils in the tissue, all of which occur in TPE lungs. CONCLUSIONS/SIGNIFICANCE: Based on our results, we conclude that the NPA protein secreted by the microfilariae of W. bancrofti may play a significant role in the pathology of TPE syndrome in LF infected individuals. Further studies on this molecule can help design an approach to neutralize the NPA in an attempt to reduce the pathology associated with TPE in LF infected subjects.

Precision engineering for localization, validation, and modification of allergenic epitopes.

The allergen-IgE interaction is essential for the genesis of allergic responses, yet investigation of the molecular basis of these interactions is in its infancy. Precision engineering has unveiled the molecular features of allergen-antibody interactions at the atomic level. High-resolution technologies, including x-ray crystallography, nuclear magnetic resonance spectroscopy, and cryo-electron microscopy, determine allergen-antibody structures. X-ray crystallography of an allergen-antibody complex localizes in detail amino acid residues and interactions that define the epitope-paratope interface. Multiple structures involving murine IgG mAbs have recently been resolved. The number of amino acids forming the epitope broadly correlates with the epitope area. The production of human IgE mAbs from B cells of allergic subjects is an exciting recent development that has for the first time enabled an actual IgE epitope to be defined. The biologic activity of defined IgE epitopes can be validated in vivo in animal models or by measuring mediator release from engineered basophilic cell lines. Finally, gene-editing approaches using the Clustered Regularly Interspaced Short Palindromic Repeats technology to either remove allergen genes or make targeted epitope engineering at the source are on the horizon. This review presents an overview of the identification and validation of allergenic epitopes by precision engineering.

Reduced resting beat-to-beat blood pressure variability in females with relapsing-remitting multiple sclerosis.

BACKGROUND: Relapsing-remitting multiple sclerosis (RRMS) is a demyelinating disease of the central nervous system and cardiovascular autonomic dysfunction has been well documented in this population. The sympathetic nervous system contributes to beat-to-beat blood pressure regulation primarily by baroreflex control of the peripheral vasculature which may be impaired in females with RRMS. Even at rest, attenuated sympathetic control of vasomotor tone may result in large and frequent blood pressure excursions (i.e., greater blood pressure variability). Therefore, the primary purpose of this investigation was to test the following hypotheses; (1) females with RRMS have augmented beat-to-beat blood pressure variability compared to healthy controls and (2) reduced sympathetic baroreflex sensitivity in females with RRMS is related to augmented blood pressure variability. METHODS: Electrocardiogram and beat-to-beat blood pressure were continuously recorded during 8-10 min of supine rest in 26 females with clinically definite RRMS and 24 sex-, age- and BMI- matched healthy controls. Muscle sympathetic nerve activity (MSNA) was recorded in a subset of participants (MS, n = 15; CON, n = 14). Traditional statistical measurements of dispersions were used to index beat-to-beat blood pressure variability. Spontaneous sympathetic baroreflex sensitivity was quantified by sorting diastolic blood pressures into 3 mmHg bins and calculating MSNA burst incidence within each bin. Weighted linear regression was then used to account for the number of cardiac cycles in each bin and calculate slopes. Spontaneous cardiac baroreflex sensitivity was determined using the sequence method. RESULTS: Groups had similar resting mean arterial pressure (MAP), systolic blood pressure (SBP), diastolic blood pressure (DBP), MSNA burst frequency and MSNA burst incidence (All P > 0.05). The standard deviation and interquartile range of MAP, SBP and DBP were less in females with RRMS compared to healthy controls (All P < 0.05). There were no between groups differences in sympathetic baroreflex sensitivity or cardiac baroreflex sensitivity (Both P > 0.05) and baroreflex sensitivity measures were not related to any indices of blood pressure variability (Both P > 0.05). CONCLUSION: These data suggest that females with RRMS have reduced beat-to-beat blood pressure variability. However, this does not appear to be related to changes in sympathetic or cardiac baroreflex sensitivity.

The Humira in Ocular Inflammations Taper (HOT) Study.

PURPOSE: To assess factors that impact the risk of relapse in patients with noninfectious uveitis (NIU) who undergo adalimumab tapering after achieving remission. DESIGN: Retrospective study. METHODS: In this multicenter study, patients with NIU were treated with adalimumab and subsequently tapered. Patient demographics, type of NIU, onset and duration of disease, the period of inactivity before tapering adalimumab, and the tapering schedule were collected. The primary outcome measures were independent predictors of the rate of uveitis recurrence after adalimumab tapering. RESULTS: Three hundred twenty-eight patients were included (54.6% female) with a mean age of 34.3 years. The mean time between disease onset and initiation of adalimumab therapy was 35.2 ± 70.1 weeks. Adalimumab tapering was commenced after a mean of 100.8 ± 69.7 weeks of inactivity. Recurrence was observed in 39.6% of patients at a mean of 44.7 ± 61.7 weeks. Patients who experienced recurrence were significantly younger than those without recurrence (mean 29.4 years vs 37.5 years, P = .0005), and the rate of recurrence was significantly higher in younger subjects (hazard ratio [HR] = 0.88 per decade of increasing age, P = .01). The lowest rate of recurrence was among Asian subjects. A faster adalimumab taper was associated with an increased recurrence rate (HR = 1.23 per unit increase in speed, P < .0005). Conversely, a more extended period of remission before tapering was associated with a lower rate of recurrence (HR = 0.97 per 10-weeks longer period of inactivity, P = .04). CONCLUSIONS: When tapering adalimumab, factors that should be considered include patient age, race, and duration of disease remission on adalimumab. A slow tapering schedule is advisable.

Engineering therapeutic monoclonal antibodies.

The use of human antibodies as biologic therapeutics has revolutionized patient care throughout fields of medicine. As our understanding of the many roles antibodies play within our natural immune responses continues to advance, so will the number of therapeutic indications for which an mAb will be developed. The great breadth of function, long half-life, and modular structure allow for nearly limitless therapeutic possibilities. Human antibodies can be rationally engineered to enhance their desired immune functions and eliminate those that may result in unwanted effects. Antibody therapeutics now often start with fully human variable regions, either acquired from genetically engineered humanized mice or from the actual human B cells. These variable genes can be further engineered by widely used methods for optimization of their specificity through affinity maturation, random mutagenesis, targeted mutagenesis, and use of in silico approaches. Antibody isotype selection and deliberate mutations are also used to improve efficacy and tolerability by purposeful fine-tuning of their immune effector functions. Finally, improvements directed at binding to the neonatal Fc receptor can endow therapeutic antibodies with unbelievable extensions in their circulating half-life. The future of engineered antibody therapeutics is bright, with the global mAb market projected to exhibit compound annual growth, forecasted to reach a revenue of nearly half a trillion dollars in 2030.

Pharmacotherapy for the Prevention of Depression and Behavioral Side Effects in Hematopoietic Stem Cell Transplantation Patients.

Depression and decreased quality of life (QoL) develop in approximately 30% of nondepressed hematopoietic stem cell transplantation (HSCT) recipients early after transplantation. To potentially prevent this complication, we conducted a prospective randomized trial to assess whether prophylaxis of nondepressed HSCT patients with the antidepressant sertraline (SER) in addition to supportive psychotherapy starting at admission for transplantation decreases the risk of depression and improves QoL. The primary objective of the study was to evaluate whether there was an added benefit of SER versus placebo along with routine supportive psychotherapy on the development of depression in patients receiving HSCT. A secondary objective was to analyze the impact on patient-reported QoL and survival. The study was conducted at a single-site academic medical center. We randomized 123 nondepressed HSCT recipients (1:1) in a phase III double-blind study to receive SER starting at a dose of 50 mg/day, with possible dose escalations to 200 mg per day, or placebo beginning on admission for HSCT and continuing for 12 weeks. Supportive psychotherapy was provided for both groups. Depression (Beck Depression Inventory II [BDI-II]) and QoL (Functional Assessment of Cancer Therapy-Bone Marrow Transplantation [FACT-BMT]) were assessed prior to HSCT and then weekly to week 12 post-HSCT. A multivariable linear mixed-effects model was used to estimate the mean change in BDI-II scores as a function of elapsed time since baseline, treatment assignment, and their interaction. The same process was used to assess treatment effects on all QoL scores from the FACT-BMT assessment. A Kaplan-Meier curve was used to estimate the probability of survival for each group following initiation of treatment. A follow-up Cox proportional hazards model was used to estimate the mortality rate in the 2 groups. Our results do not indicate a benefit of SER in either a diminished risk of depression or improved QoL or survival outcomes. Based on our findings, we can only recommend early evaluation of HSCT recipients for depression, with antidepressant use reserved for patients with evidence of clinical depression, unless additional randomized trials can confirm the effects of early antidepressant therapy on mood and QoL in this vulnerable group. Future research in this area would be improved by systematic monitoring of medication adherence, identification of the optimal dose of SER (or other antidepressant), and inclusion of psychotherapy outcomes when relevant, the absence of which are limitations of this study.

Antigen-specific memory NK cell responses against HIV and influenza use the NKG2/HLA-E axis.

Multiple studies have broadened the roles of natural killer (NK) cells functioning as purely innate lymphocytes by demonstrating that they are capable of putative antigen-specific immunological memory against multiple infectious agents including HIV-1 and influenza. However, the mechanisms underlying antigen specificity remain unknown. Here, we demonstrate that antigen-specific human NK cell memory develops upon exposure to both HIV and influenza, unified by a conserved and epitope-specific targetable mechanism largely dependent on the activating CD94/NKG2C receptor and its ligand HLA-E. We validated the permanent acquisition of antigen specificity by individual memory NK cells by single-cell cloning. We identified elevated expression of KLRG1, α4ß7, and NKG2C as biomarkers of antigen-specific NK cell memory through complex immunophenotyping. Last, we uncovered individual HLA-E-restricted peptides that may constitute the dominant NK cell response in HIV-1- and influenza-infected persons in vivo. Our findings clarify the mechanisms contributing to antigen-specific memory NK cell responses and suggest that they could be potentially targeted therapeutically for vaccines or other therapeutic interventions.

Cheminformatics and artificial intelligence for accelerating agrochemical discovery.

The global cost-benefit analysis of pesticide use during the last 30 years has been characterized by a significant increase during the period from 1990 to 2007 followed by a decline. This observation can be attributed to several factors including, but not limited to, pest resistance, lack of novelty with respect to modes of action or classes of chemistry, and regulatory action. Due to current and projected increases of the global population, it is evident that the demand for food, and consequently, the usage of pesticides to improve yields will increase. Addressing these challenges and needs while promoting new crop protection agents through an increasingly stringent regulatory landscape requires the development and integration of infrastructures for innovative, cost- and time-effective discovery and development of novel and sustainable molecules. Significant advances in artificial intelligence (AI) and cheminformatics over the last two decades have improved the decision-making power of research scientists in the discovery of bioactive molecules. AI- and cheminformatics-driven molecule discovery offers the opportunity of moving experiments from the greenhouse to a virtual environment where thousands to billions of molecules can be investigated at a rapid pace, providing unbiased hypothesis for lead generation, optimization, and effective suggestions for compound synthesis and testing. To date, this is illustrated to a far lesser extent in the publicly available agrochemical research literature compared to drug discovery. In this review, we provide an overview of the crop protection discovery pipeline and how traditional, cheminformatics, and AI technologies can help to address the needs and challenges of agrochemical discovery towards rapidly developing novel and more sustainable products.

Medicare Data Linkages for Conducting Patient-Centered Outcomes Research on Economic Outcomes.

BACKGROUND: Medicare patients and other stakeholders often make health care decisions that have economic consequences. Research on economic variables that patients have identified as important is referred to as patient-centered outcomes research (PCOR) and can generate evidence that informs decision-making. Medicare fee-for-service (FFS) claims are widely used for research and are a potentially valuable resource for studying some economic variables, particularly when linked to other datasets. OBJECTIVE: The aim of this study was to identify and assess the characteristics of federally funded administrative and survey data sources that can be linked to Medicare claims for conducting PCOR on some economic outcomes. RESEARCH DESIGN: A targeted internet search was conducted to identify a list of relevant data sources. A technical panel and key informant interviews were used for guidance and feedback. RESULTS: We identified 12 survey and 6 administrative sources of linked data for Medicare FFS beneficiaries. A majority provide longitudinal data and are updated annually. All linked sources provide some data on social determinants of health and health equity-related factors. Fifteen sources capture direct medical costs (beyond Medicare FFS payments); 5 capture indirect costs (eg, lost wages from absenteeism), and 7 capture direct nonmedical costs (eg, transportation). CONCLUSIONS: Linking Medicare FFS claims data to other federally funded data sources can facilitate research on some economic outcomes for PCOR. However, few sources capture direct nonmedical or indirect costs. Expanding linkages to include additional data sources, and reducing barriers to existing data sources, remain important objectives for increasing high-quality, patient-centered economic research.

Unique allergen-specific human IgE monoclonal antibodies derived from patients with allergic disease.

Introduction: Allergic reactions are mediated by human IgE antibodies that bind to and cross-link allergen molecules. The sites on allergens that are recognized by IgE antibodies have been difficult to investigate because of the paucity of IgE antibodies in a human serum. Here, we report the production of unique human IgE monoclonal antibodies to major inhaled allergens and food allergens that can be produced at scale in perpetuity. Materials and methods: The IgE antibodies were derived from peripheral blood mononuclear cells of symptomatic allergic patients, mostly children aged 3-18 years, using hybridoma fusion technology. Total IgE and allergen-specific IgE was measured by ImmunoCAP. Their specificity was confirmed through ELISA and immunoblotting. Allergenic potency measurements were determined by ImmunoCAP inhibition. Biological activity was determined in vitro by comparing ß-hexosaminidase release from a humanized rat basophilic cell line. Results: Human IgE monoclonal antibodies (n = 33) were derived from 17 allergic patients with symptoms of allergic rhinitis, asthma, atopic dermatitis, food allergy, eosinophilic esophagitis, or red meat allergy. The antibodies were specific for five inhaled allergens, nine food allergens, and alpha-gal and had high levels of IgE (53,450-1,702,500 kU/L) with ratios of specific IgE to total IgE ranging from <0.01 to 1.39. Sigmoidal allergen binding curves were obtained through ELISA, with low limits of detection (<1 kU/L). Allergen specificity was confirmed through immunoblotting. Pairs of IgE monoclonal antibodies to Ara h 6 were identified that cross-linked after allergen stimulation and induced release of significant levels of ß-hexosaminidase (35%-80%) from a humanized rat basophilic cell line. Conclusions: Human IgE monoclonal antibodies are unique antibody molecules with potential applications in allergy diagnosis, allergen standardization, and identification of allergenic epitopes for the development of allergy therapeutics. The IgE antibody probes will enable the unequivocal localization and validation of allergenic epitopes.

Corrigendum: Biological activity of human IgE monoclonal antibodies targeting Der p 2, Fel d 1, Ara h 2 in basophil mediator release assays.

[This corrects the article DOI: 10.3389/fimmu.2023.1155613.].

Utility of standing office blood pressure in detecting hypertension in healthy adults.

Current guidelines recommend office blood pressures (BP) be taken in a seated position when screening for hypertension (HTN). Seated BP is known to have limited accuracy in detecting high BP, while the utility of standing BP in diagnosing HTN is unknown. We conducted a cross-sectional study to determine the incremental value of standing BP in diagnosing HTN. Seated, standing, and 24-h ambulatory BPs (ABPM) were obtained in adults without known cardiovascular disease, HTN, or BP medication use. Presence of HTN was defined by the 2017 ACC/AHA and the 2023 ESH HTN guidelines based on ABPM. Area under the receiver-operating-characteristic curve (AUROC) was used to evaluate the diagnostic accuracy of seated and standing BP. Sensitivity and specificity of standing BP was determined using cut-offs derived from Youden's Index, while sensitivity and specificity of seated BP was determined using the cut-off of 130/80 mmHg and by 140/90 mmHg. Among 125 participants (mean age 49 ± 17 years; 62% female; 24% Black), 33.6% of them had HTN. Sensitivity and specificity of seated systolic BP (SBP) was 43% and 92%, respectively. Cut-offs selected by Youden's index for standing SBP/diastolic BP (DBP) were 124/81 mmHg according to the 2017 ACC/AHA HTN guidelines, and 123.5/83.5 mmHg according to the 2023 ESH HTN guidelines. Sensitivity and specificity of standing SBP was 71% and 67%, respectively. The AUROC of standing SBP (0.81 [0.71-0.92]) was significantly higher than seated SBP (0.70 [0.49-0.91]), when HTN was defined as average 24-h SBP ≥ 125 mmHg. Moreover, the addition of standing to seated SBP (0.80 [0.68-0.92]) improved HTN detection when compared to seated SBP. These patterns were consistent for both the 2017 ACC/AHA and the 2023 ESH definitions for HTN. In summary, standing BP, alone or in combination with seated BP, outperformed seated BP alone in diagnosing HTN in adults.

Blockade of endogenous insulin receptor signaling in the nucleus tractus solitarius potentiates exercise pressor reflex function in healthy male rats.

Insulin not only regulates glucose and/or lipid metabolism but also modulates brain neural activity. The nucleus tractus solitarius (NTS) is a key central integration site for sensory input from working skeletal muscle and arterial baroreceptors during exercise. Stimulation of the skeletal muscle exercise pressor reflex (EPR), the responses of which are buffered by the arterial baroreflex, leads to compensatory increases in arterial pressure to supply blood to working muscle. Evidence suggests that insulin signaling decreases neuronal excitability in the brain, thus antagonizing insulin receptors (IRs) may increase neuronal excitability. However, the impact of brain insulin signaling on the EPR remains fully undetermined. We hypothesized that antagonism of NTS IRs increases EPR function in normal healthy rodents. In decerebrate rats, stimulation of the EPR via electrically induced muscle contractions increased peak mean arterial pressure (MAP) responses 30 min following NTS microinjections of an IR antagonist (GSK1838705, 100 µM; Pre: Δ16 ± 10 mmHg vs. 30 min: Δ23 ± 13 mmHg, n = 11, p = .004), a finding absent in sino-aortic baroreceptor denervated rats. Intrathecal injections of GSK1838705 did not influence peak MAP responses to mechano- or chemoreflex stimulation of the hindlimb muscle. Immunofluorescence triple overlap analysis following repetitive EPR stimulation increased c-Fos overlap with EPR-sensitive nuclei and IR-positive cells relative to sham operation (p < .001). The results suggest that IR blockade in the NTS potentiates the MAP response to EPR stimulation. In addition, insulin signaling in the NTS may buffer EPR stimulated increases in blood pressure via baroreflex-mediated mechanisms during exercise.

Prevalence of Hospital-Onset Bacteremia Pre- and Post-Implementation of a Needleless Blood Sampling Device From Existing Peripheral Catheters.

Repeated access of peripheral intravenous (IV) devices theoretically increases the risk of bacterial exposure. PIVO™ (VelanoVascular) is a needleless, single-use device that enables blood sampling from an existing peripheral IV. The goal of this retrospective observational exploratory study was to evaluate the influence of PIVO use on rates of hospital-onset bacteremia and fungemia (HOB) by comparing HOB rates in the year before and after PIVO introduction in hospitals implementing PIVO and over similar time periods in "control" hospitals with no PIVO. Two hospitals implementing PIVO (Hospital 1, a large community hospital; Hospital 2, a tertiary oncology center), and 71 control hospitals were included. During the 1-year period before and after PIVO introduction, HOB rates decreased in hospitals 1 and 2 by 31.9% and 41.8%, respectively. Control hospitals that did not use PIVO had a 12.4% decrease in HOB rates. Multivariable logistic regression analyses found that PIVO was associated with a lower risk (Hospital 1 odds ratio [OR]: 0.63; 95% CI, 0.42-0.94) or no change (Hospital 2 OR: 1.05; 95% CI, 0.72-1.52) in HOB rates. Control hospitals also showed no change in HOB rates between the 2 time periods. These data do not support concerns about increased risk of bacteremia with PIVO.