Adverse Drug Reactions to Guideline-Recommended Heart Failure Drugs in Women: A Systematic Review of the Literature.

Objectives: This study sought to summarize all available evidence on sex differences in adverse drug reactions (ADRs) to heart failure (HF) medication.

Background: Women are more likely to experience ADRs than men, and these reactions may negatively affect women's immediate and long-term health. HF in particular is associated with increased ADR risk because of the high number of comorbidities and older age.

Age and sex in drug development and testing for adults.

Individualization of drug therapy requires that the right drug be administered at the correct dose to patients who are likely to achieve the highest benefit and lowest risk. Female sex and age comprise two important risk factors for altered drug exposure and response. This review summarizes the current state of science for considering age and sex-related factors along the drug development pipeline, from cell culture and animal research through all phases of clinical trials in humans.

The Absence of Fever Is Associated With Higher Mortality and Decreased Antibiotic and IV Fluid Administration in Emergency Department Patients With Suspected Septic Shock.

Objective: This study evaluates whether emergency department septic shock patients without a fever (reported or measured) receive less IV fluids, have decreased antibiotic administration, and suffer increased in-hospital mortality.

Design: This was a secondary analysis of a prospective, observational study of patients with shock.

Setting: The study was conducted in an urban, academic emergency department.

Serum Lactate Predicts Adverse Outcomes in Emergency Department Patients With and Without Infection.

Introduction: Lactate levels are increasingly used to risk stratify emergency department (ED) patients with and without infection. Whether a serum lactate provides similar prognostic value across diseases is not fully elucidated. This study assesses the prognostic value of serum lactate in ED patients with and without infection to both report and compare relative predictive value across etiologies.

Derivation and Validation of Predictive Factors for Clinical Deterioration after Admission in Emergency Department Patients Presenting with Abnormal Vital Signs Without Shock.

Introduction: Strategies to identify high-risk emergency department (ED) patients often use markedly abnormal vital signs and serum lactate levels. Risk stratifying such patients without using the presence of shock is challenging. The objective of the study is to identify independent predictors of in-hospital adverse outcomes in ED patients with abnormal vital signs or lactate levels, but who are not in shock.

Assessing The Predictive Value of Clinical Factors Used to Determine The Presence of Sepsis Causing Shock in the Emergency Department.

Introduction: Differentiating shock etiologies is a challenging task in the Emergency Department (ED); even the strongest clinical predictors leave some diagnostic uncertainty. This study sought to establish an evidence base for using clinical covariates in the diagnostic evaluation of septic shock.

Methods: We conducted a prospective, observational study of consecutive ED patients with shock from November 11, 2012 to September 23, 2013.

The Utility of Inflammatory and Endothelial Markers to Identify Infection in Emergency Department Patients.

Background: Identifying infection in emergency department (ED) patients can be challenging. This study assesses the value that inflammatory and endothelial biomarkers add to clinical data when predicting infectious etiologies of abnormal vital signs (AVSs) in ED patients.

Methods: This study was a prospective, observational cohort study of ED patients with AVSs at an urban, academic tertiary-care hospital, identified from March 1, 2013, to April 15, 2013.

Effects of a classroom-based yoga intervention on cortisol and behavior in second- and third-grade students: a pilot study.

This uncontrolled pilot study examined the effects of a classroom-based yoga intervention on cortisol concentrations and perceived behavior in children. A 10-week Yoga 4 Classrooms intervention was implemented in one second-grade and one third-grade classroom. Students' salivary cortisol responses were assessed at 3 time points.

Zonulin as prehaptoglobin2 regulates lung permeability and activates the complement system.

Zonulin is a protein involved in the regulation of tight junctions (TJ) in epithelial or endothelial cells. Zonulin is known to affect TJ in gut epithelial cells, but little is known about its influences in other organs. Prehaptoglobin2 has been identified as zonulin and is related to serine proteases (MASPs, C1qrs) that activate the complement system.

Acute sex hormone suppression reduces skeletal muscle sympathetic nerve activity.

Objectives: Comparisons of sympathetic nervous system activity (SNA) between young and older women have produced equivocal results, in part due to inadequate control for potential differences in sex hormone concentrations, age, and body composition. The aim of the present study was to determine the effect of a short-term reduction in sex hormones on tonic skeletal muscle sympathetic nerve activity (MSNA), an indirect measure of whole body SNA, using an experimental model of sex hormone deficiency in young women. We also assessed the independent effects of estradiol and progesterone add-back therapy on MSNA.

Cross-talk between TLR4 and FcgammaReceptorIII (CD16) pathways.

Pathogen-pattern-recognition by Toll-like receptors (TLRs) and pathogen clearance after immune complex formation via engagement with Fc receptors (FcRs) represent central mechanisms that trigger the immune and inflammatory responses. In the present study, a linkage between TLR4 and FcgammaR was evaluated in vitro and in vivo. Most strikingly, in vitro activation of phagocytes by IgG immune complexes (IgGIC) resulted in an association of TLR4 with FcgammaRIII (CD16) based on co-immunoprecipitation analyses.

Upregulation of phagocyte-derived catecholamines augments the acute inflammatory response.

Following our recent report that phagocytic cells (neutrophils, PMNs, and macrophages) are newly discovered sources of catecholamines, we now show that both epinephrine and norepinephrine directly activate NFkappaB in macrophages, causing enhanced release of proinflammatory cytokines (TNFalpha, IL-1beta, IL-6). Both adrenal-intact (AD+) and adrenalectomized (ADX) rodents were used, because ADX animals had greatly enhanced catecholamine release from phagocytes, facilitating our efforts to understand the role of catecholamines released from phagocytes. Phagocytes isolated from adrenalectomized rats displayed enhanced expression of tyrosine-hydroxylase and dopamine-beta-hydroxylase, two key enzymes for catecholamine production and exhibited higher baseline secretion of norepinephrine and epinephrine.

The complement anaphylatoxin C5a induces apoptosis in adrenomedullary cells during experimental sepsis.

Sepsis remains a poorly understood, enigmatic disease. One of the cascades crucially involved in its pathogenesis is the complement system. Especially the anaphylatoxin C5a has been shown to have numerous harmful effects during sepsis.

Functions of the complement components C3 and C5 during sepsis.

Activation of the complement system is a key event in the pathogenesis of sepsis. Nevertheless, the exact mechanisms remain inadequately understood. In the current study, we examined the role of complement C3 and C5 in sepsis in wild-type and C3- or C5-deficient mice induced by cecal ligation and puncture.

Acute lung injury induced by lipopolysaccharide is independent of complement activation.

Although acute lung injury (ALI) is an important problem in humans, its pathogenesis is poorly understood. Airway instillation of bacterial LPS, a known complement activator, represents a frequently used model of ALI. In the present study, pathways in the immunopathogenesis of ALI were evaluated.

Functional roles for C5a receptors in sepsis.

The function of the C5a receptors, C5ar (encoded by C5ar) and C5l2 (encoded by Gpr77), especially of C5l2, which was originally termed a 'default receptor', remains a controversial topic. Here we investigated the role of each receptor in the setting of cecal ligation and puncture-induced sepsis by using antibody-induced blockade of C5a receptors and knockout mice. In 'mid-grade' sepsis (30-40% survival), blockade or absence of either C5ar or C5l2 greatly improved survival and attenuated the buildup of proinflammatory mediators in plasma.

Exercise physiologists talk about sex differences.

The number of publications addressing sex differences and exercise physiology has increased from 12, before 1970, to as many as 1344 through October 2007, according to a recent PubMed search. The following symposium represents three distinct examples of how exercise physiologists are approaching the issue of sex differences in various aspects of physiology. Tarnapolsky presents data from studies of sex and sex hormone effects on substrate use, a factor that may distinguish between the capacities of women and men to excel at exercise performance at different durations and intensities.

Adverse functions of IL-17A in experimental sepsis.

IL-17A is a proinflammatory cytokine produced by a variety of cells. In the current study, we examined the role of IL-17A in sepsis induced in mice by cecal ligation and puncture (CLP). IL-17A levels, which rose time-dependently in plasma after CLP, were not affected in the absence of alphabeta T cells or neutrophils.

Phagocyte-derived catecholamines enhance acute inflammatory injury.

It is becoming increasingly clear that the autonomic nervous system and the immune system demonstrate cross-talk during inflammation by means of sympathetic and parasympathetic pathways. We investigated whether phagocytes are capable of de novo production of catecholamines, suggesting an autocrine/paracrine self-regulatory mechanism by catecholamines during inflammation, as has been described for lymphocytes. Here we show that exposure of phagocytes to lipopolysaccharide led to a release of catecholamines and an induction of catecholamine-generating and degrading enzymes, indicating the presence of the complete intracellular machinery for the generation, release and inactivation of catecholamines.

Sex hormone suppression reduces resting energy expenditure and {beta}-adrenergic support of resting energy expenditure.

Resting energy expenditure (REE) decreases with aging and may decrease in women as a result of the menopause, potentially contributing to weight gain. REE has been observed to fluctuate during the menstrual cycle, suggesting regulation by sex hormones. The aim of the present study was to determine the effects of suppressing estrogen and progesterone on REE.

High energy flux mediates the tonically augmented beta-adrenergic support of resting metabolic rate in habitually exercising older adults.

The sympathetic nervous system contributes to resting metabolic rate (RMR) via beta-adrenergic receptor (beta-AR) stimulation of energy metabolism. RMR and beta-AR support of RMR are greater in habitually exercising compared with sedentary older adults possibly due to greater energy flux (magnitude of energy intake and energy expenditure during energy balance). In 10 older adults regularly performing aerobic endurance exercise (mean +/- se, 66 +/- 1 yr) compared with baseline, a reduction in energy flux (via abstention of exercise and proportional reduction in dietary intake) decreased (P < 0.