Neutrophil-derived microparticles are released into the coronary circulation following percutaneous coronary intervention in acute coronary syndrome patients.

To evaluate (i) local coronary and systemic levels of microparticles (MP) in acute coronary syndrome (ACS) and stable angina pectoris (SAP) patients and (ii) their release after plaque disruption with percutaneous coronary intervention (PCI). MP are small vesicles originating from plasma membranes of cells after activation or apoptosis and are implicated in the pathogenesis of atherosclerosis. Neutrophils play a role in plaque destabilization and shed neutrophil-derived MP that have the potential to drive significant proinflammatory and thrombotic downstream effects. Eight ACS and eight SAP patients were included. Coronary sinus (CS) samples pre-intervention (CS1), 45 s following balloon angioplasty (CS2) and at 45 s intervals following stent deployment (CS3, CS4 and CS5), together with peripheral vein samples, pre- and post-PCI were analysed for neutrophil-derived (CD66b+), endothelial-derived (CD144+), platelet-derived (CD41a+), monocyte-derived (CD14+) and apoptotic (Annexin V+) MP. ELISA for interleukin (IL)-6, myeloperoxidase (MPO) and P-selectin was also performed. CD66b+ MP levels were similar in both groups pre-intervention. Post-PCI, CS levels rose significantly in ACS but not SAP patients (ACS area under the curve (AUC): 549 ± 83, SAP AUC: 24 ± 29, P<0.01). CS CD41a+, CD144+, CD14+ and Annexin V+ MP levels did not differ between groups. Acute neutrophil-derived MP release post-PCI occurs in ACS compared with stable patients, likely to be reflective of plaque MP content in vulnerable lesions

Analysis of the reported risk situations for the nutrition service in a hospital in Southern Brazil

Objetivo: Analisar as situações de risco notificadas para o serviço de nutrição em um hospital público do sul do Brasil. Método: Estudo retrospectivo das situações de risco, de acordo com a Classificação Internacional de Segurança do Paciente (CISP), registradas no ano de 2017 no sistema de notificações do hospital. As análises foram realizadas no programa estatístico SPSS versão 21.0. Resultados: Das 172 notificações, 70,3% envolveram pacientes adultos. A maioria aconteceu em dias úteis (84,9%); no turno da manhã (39,5%). Foram mais frequentes os incidentes (62,2%) que causaram danos leves (68,6%). As principais dietas envolvidas nas notificações foram as normais (33,1%), enterais (15,1%) e para Diabetes Mellitus (9,9%). As principais causas de notificação foram atribuídas a falhas no cumprimento das rotinas (61,6%), envolvendo atraso na entrega das refeições (15,1%) e falha de comunicação (13,9%). Conclusão: Verificou-se um grande número de situações de risco, ocorrendo nos momentos e tipos de dietas mais frequentes na realidade hospitalar, sinalizando a necessidade de melhoria na cultura de segurança do paciente, visando a aperfeiçoar a qualidade da assistência nutricional hospitalar.Objective: To analyze the reported risk situations for the nutrition service in a public hospital in southern Brazil. Method: Retrospective study of risk situations, according to the International Patient Safety Classification (CISP), registered in 2017 in the hospital's notification system. The analyzes were performed using the statistical program SPSS version 21.0. Results: Of the 172 reports, 70.3% involved adult patients. The majority happened on working days (84.9%); in the morning shift (39.5%). Incidents were more frequent (62.2%) causing mild damage (68.6%). The main diets involved in the reports were normal (33.1%), enteral (15.1%), and Diabetes Mellitus (9.9%). The main causes of notification were attributed to failure to comply with routines (61.6%), involving delayed meal delivery (15.1%) and communication failure (13.9%). Conclusion: There was a large number of risk situations, occurring in the most frequent moments and types of diets in the hospital, signaling the need for improvement in the patient safety culture, aiming to improve the quality of hospital nutritional assistance

Análise das situações de risco notificadas para o serviço de nutrição em um hospital do sul do Brasil / Analysis of the reported risk situations for the nutrition service in a hospital in southern Brazil

Objetivo: Analisar as situações de risco notificadas para o serviço de nutrição em um hospital público do sul do Brasil. Método: Estudo retrospectivo das situações de risco, de acordo com a Classificação Internacional de Segurança do Paciente (CISP), registradas no ano de 2017 no sistema de notificações do hospital. As análises foram realizadas no programa estatístico SPSS versão 21.0. Resultados: Das 172 notificações, 70,3% envolveram pacientes adultos. A maioria aconteceu em dias úteis (84,9%); no turno da manhã (39,5%). Foram mais frequentes os incidentes (62,2%) que causaram danos leves (68,6%). As principais dietas envolvidas nas notificações foram as normais (33,1%), enterais (15,1%) e para Diabetes Mellitus (9,9%). As principais causas de notificação foram atribuídas a falhas no cumprimento das rotinas (61,6%), envolvendo atraso na entrega das refeições (15,1%) e falha de comunicação (13,9%). Conclusão: Verificou-se um grande número de situações de risco, ocorrendo nos momentos e tipos de dietas mais frequentes na realidade hospitalar,  sinalizando a necessidade de melhoria na cultura de segurança do paciente, visando a aperfeiçoar a qualidade da assistência nutricional hospitalar

The IL-6 response to Chlamydia from primary reproductive epithelial cells is highly variable and may be involved in differential susceptibility to the immunopathological consequences of chlamydial infection

Background Chlamydia trachomatis infection results in reproductive damage in some women. The process and factors involved in this immunopathology are not well understood. This study aimed to investigate the role of primary human cellular responses to chlamydial stress response proteases and chlamydial infection to further identify the immune processes involved in serious disease sequelae. Results Laboratory cell cultures and primary human reproductive epithelial cultures produced IL-6 in response to chlamydial stress response proteases (CtHtrA and CtTsp), UV inactivated Chlamydia, and live Chlamydia. The magnitude of the IL-6 response varied considerably (up to 1000 pg ml-1) across different primary human reproductive cultures. Thus different levels of IL-6 production by reproductive epithelia may be a determinant in disease outcome. Interestingly, co-culture models with either THP-1 cells or autologous primary human PBMC generally resulted in increased levels of IL-6, except in the case of live Chlamydia where the level of IL-6 was decreased compared to the epithelial cell culture only, suggesting this pathway may be able to be modulated by live Chlamydia. PBMC responses to the stress response proteases (CtTsp and CtHtrA) did not significantly vary for the different participant cohorts. Therefore, these proteases may possess conserved innate PAMPs. MAP kinases appeared to be involved in this IL-6 induction from human cells. Finally, we also demonstrated that IL-6 was induced by these proteins and Chlamydia from mouse primary reproductive cell cultures (BALB/C mice) and mouse laboratory cell models. Conclusions We have demonstrated that IL-6 may be a key factor for the chlamydial disease outcome in humans, given that primary human reproductive epithelial cell culture showed considerable variation in IL-6 response to Chlamydia or chlamydial proteins, and that the presence of live Chlamydia (but not UV killed) during co-culture resulted in a reduced IL-6 response suggesting this response may be moderated by the presence of the organism

Moderate‐ and High‐Intensity Exercise Improves Lipoprotein Profile and Cholesterol Efflux Capacity in Healthy Young Men

Background Exercise is associated with a reduced risk of cardiovascular disease. Increased high‐density lipoprotein cholesterol (HDL‐C) levels are thought to contribute to these benefits, but much of the research in this area has been limited by lack of well‐controlled subject selection and exercise interventions. We sought to study the effect of moderate and high‐intensity exercise on HDL function, lipid/lipoprotein profile, and other cardiometabolic parameters in a homogeneous population where exercise, daily routine, sleep patterns, and living conditions were carefully controlled. Methods and Results Male Army recruits (n=115, age 22±0.3 years) completed a 12‐week moderate‐intensity exercise program. A subset of 51 subsequently completed a 15‐week high‐intensity exercise program. Fitness increased and body fat decreased after moderate‐ and high‐intensity exercise (P<0.001). Moderate‐intensity exercise increased HDL‐C and apolipoprotein A‐I levels (6.6%, 11.6% respectively), and decreased low‐density lipoprotein cholesterol and apolipoprotein B levels (7.2%, 4.9% respectively) (all P<0.01). HDL‐C and apolipoprotein A‐I levels further increased by 8.2% (P<0.001) and 6.3% (P<0.05) after high‐intensity exercise. Moderate‐intensity exercise increased ABCA‐1 (ATP‐binding cassette transporter A1) mediated cholesterol efflux by 13.5% (P<0.001), which was sustained after high‐intensity exercise. In a selected subset the ability of HDLs to inhibit ICAM‐1 (intercellular adhesion molecule‐1) expression decreased after the high (P<0.001) but not the moderate‐intensity exercise program. Conclusions When controlling for exercise patterns, diet, and sleep, moderate‐intensity exercise improved HDL function, lipid/lipoprotein profile, fitness, and body composition. A sequential moderate followed by high‐intensity exercise program showed sustained or incremental benefits in these parameters. Improved HDL function may be part of the mechanism by which exercise reduces cardiovascular disease risk

β3 adrenergic agonism: A novel pathway which improves right ventricular‐pulmonary arterial hemodynamics in pulmonary arterial hypertension

Abstract Efficacy of therapies that target the downstream nitric oxide (NO) pathway in pulmonary arterial hypertension (PAH) depends on the bioavailability of NO. Reduced NO level in PAH is secondary to “uncoupling” of endothelial nitric oxide synthase (eNOS). Stimulation of β3 adrenergic receptors (β3 ARs) may lead to the recoupling of NOS and therefore be beneficial in PAH. We aimed to examine the efficacy of β3 AR agonism as a novel pathway in experimental PAH. In hypoxia (5 weeks) and Sugen hypoxia (hypoxia for 5 weeks + SU5416 injection) models of PAH, we examined the effects of the selective β3 AR agonist CL316243. We measured echocardiographic indices and invasive right ventricular (RV)–pulmonary arterial (PA) hemodynamics and compared CL316243 with riociguat and sildenafil. We assessed treatment effects on RV–PA remodeling, oxidative stress, and eNOS glutathionylation, an oxidative modification that uncouples eNOS. Compared with normoxic mice, RV systolic pressure was increased in the control hypoxic mice (p < 0.0001) and Sugen hypoxic mice (p < 0.0001). CL316243 reduced RV systolic pressure, to a similar degree to riociguat and sildenafil, in both hypoxia (p < 0.0001) and Sugen hypoxia models (p < 0.03). CL316243 reversed pulmonary vascular remodeling, decreased RV afterload, improved RV–PA coupling efficiency and reduced RV stiffness, hypertrophy, and fibrosis. Although all treatments decreased oxidative stress, CL316243 significantly reduced eNOS glutathionylation. β3 AR stimulation improved RV hemodynamics and led to beneficial RV–PA remodeling in experimental models of PAH. β3 AR agonists may be effective therapies in PAH

Military medicine : the official journal of AMSUS

Biomarkers of the age of mosquitoes are required to determine the risk of transmission of various pathogens as each pathogen undergoes a period of extrinsic incubation in the mosquito host. Using the 2-D Difference Gel Electrophoresis (2-D DIGE) procedure, we investigated the abundance of up to 898 proteins from the Yellow Fever and dengue virus vector, Aedes aegypti, during ageing. By applying a mixed-effects model of protein expression, we identified five common patterns of abundance change during ageing and demonstrated an age-related decrease in variance for four of these. This supported a search for specific proteins with abundance changes that remain tightly associated with ageing for use as ageing biomarkers. Using MALDI-TOF/TOF mass spectrometry we identified ten candidate proteins that satisfied strict biomarker discovery criteria (identified in two out of three multivariate analysis procedures and in two cohorts of mosquitoes). We validated the abundances of the four most suitable candidates (Actin depolymerising factor; ADF, Eukaryotic initiation factor 5A; eIF5A, insect cuticle protein Q17LN8, and Anterior fat body protein; AFP) using semi-quantitative Western analysis of individual mosquitoes of six ages. The redox-response protein Manganese superoxide dismutase (SOD2) and electron shuttling protein Electron transfer oxidoreductase (ETO) were subject to post-translational modifications affecting their charge states with potential effects on function. For the four candidates we show remarkably consistent decreases in abundance during ageing, validating initial selections. In particular, the abundance of AFP is an ideal biomarker candidate for whether a female mosquito has lived long enough to be capable of dengue virus transmission. We have demonstrated proteins to be a suitable class of ageing biomarkers in mosquitoes and have identified candidates for epidemiological studies of dengue and the evaluation of new disease reduction projects targeting mosquito longevity

Low doses of killed parasite in CpG elicit vigorous CD4+ T cell responses against blood-stage malaria in mice

Development of a vaccine that targets blood-stage malaria parasites is imperative if we are to sustainably reduce the morbidity and mortality caused by this infection. Such a vaccine should elicit long-lasting immune responses against conserved determinants in the parasite population. Most blood-stage vaccines, however, induce protective antibodies against surface antigens, which tend to be polymorphic. Cell-mediated responses, on the other hand, offer the theoretical advantage of targeting internal antigens that are more likely to be conserved. Nonetheless, few of the current blood-stage vaccine candidates are able to harness vigorous T cell immunity. Here, we present what we believe to be a novel blood-stage whole-organism vaccine that, by combining low doses of killed parasite with CpG-oligodeoxynucleotide (CpG-ODN) adjuvant, was able to elicit strong and cross-reactive T cell responses in mice. Our data demonstrate that immunization of mice with 1,000 killed parasites in CpG-ODN engendered durable and cross-strain protection by inducing a vigorous response that was dependent on CD4+ T cells, IFN-γ, and nitric oxide. If applicable to humans, this approach should facilitate the generation of robust, cross-reactive T cell responses against malaria as well as antigen availability for vaccine manufacture