Relationship between the Soluble F11 Receptor and Annexin A5 in African Americans Patients with Type-2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is characterized by endothelial dysfunction, increased thrombogenicity, and inflammation. The soluble human F11 receptor (sF11R) and annexin A5 (ANXA5) play crucial roles in inflammatory thrombosis and atherosclerosis. We examined the relationship between circulating sF11R and ANXA5 and their impact on endothelial function. The study included 125 patients with T2DM. Plasma levels of sF11R and ANXA5 were quantified by ELISA. Microvascular function was assessed using the vascular reactivity index (VRI). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Carotid intima-media thickness (CIMT) was assessed by B-mode ultrasound imaging. The mean age of patients in the study was 59.7 ± 7.8 years, 78% had hypertension, 76% had dyslipidemia, and 12% had CKD. sF11R correlated positively with ANXA5 levels (ß = 0.250, p = 0.005), and correlated inversely with VRI and total nitic oxide (NO), (ß = −0.201, p = 0.024; ß = −0.357, p = 0.0001, respectively). Multivariate regression analysis revealed that sF11R was independently associated with ANXA5 in the total population and in patients with HbA1c > 6.5% (ß = 0.366, p = 0.007; ß = 0.425, p = 0.0001, respectively). sF11R and ANXA5 were not associated with vascular outcome, suggesting that they may not be reliable markers of vascular dysfunction in diabetes. The clinical significance of sF11R/ANXA5 association in diabetes warrants further investigation in a larger population.

Changes in Opioid Therapy Use by an Interprofessional Primary Care Team: A Descriptive Study of Opioid Prescription Data.

OBJECTIVE: The purpose of this study was to describe changes in opioid-therapy prescription rates after a family medicine practice included on-site chiropractic services. METHODS: The study design was a retrospective analysis of opioid prescription data. The database included opioid prescriptions written for patients seeking care at the family medicine practice from April 2015 to September 2018. In June 2016, the practice reviewed and changed its opioid medication practices. In April 2017, the practice included on-site chiropractic services. Opiod-therapy use was defined as the average rate of opioid prescriptions over all medical providers at the practice. RESULTS: There was a significant decrease of 22% in the average monthly rate of opioid prescriptions after the inclusion of chiropractic services (F1,40 = 10.69; P < .05). There was a significant decrease of 32% in the prescribing rate of schedule II opioids after the inclusion of chiropractic services (F2,80 = 6.07 for the Group × Schedule interaction; P < .05). The likelihood of writing schedule II opioid prescriptions decreased by 27% after the inclusion of chiropractic services (odds ratio, 0.73; 95% confidence interval, 0.59-0.90). Changes in opioid medication practices by the medical providers included prescribing a schedule III or IV opioid rather than a schedule II opioid (F6,76 = 29.81; P < .05) and a 30% decrease in the daily doses of opioid prescriptions (odds ratio, 0.70; 95% confidence interval, 0.50-0.98). CONCLUSION: This study demonstrates that there were decreases in opioid-therapy prescribing rates after a family medicine practice included on-site chiropractic services. This suggests that inclusion of chiropractic services may have had a positive effect on prescribing behaviors of medical physicians, as they may have been able to offer their patients additional nonpharmaceutical options for pain management.

Association between nitrated lipoproteins and vascular function in type 2 diabetes.

Higher levels of nitrated lipoproteins (NT-HDL and NT-LDL) were found in blood and atherosclerotic plaques of patients with coronary artery disease. We aimed to examine the relationship between plasma NT-HDL and NT-LDL and diabetic vascular dysfunction. The study included 125 African-American patients with T2DM. NT-HDL and NT-LDL were quantified by ELISA. Microvascular function was assessed by vascular reactivity index (VRI). Large artery stiffness was assessed by carotid-femoral pulse wave velocity (PWV). Carotid intima-media thickness (CIMT) was assessed by B-mode ultrasound imaging. In univariate analysis, NT-HDL was associated with VRI in total population and in patients with HbA1c more than or equal to 7.0 percent (beta= -0.178, p= 0.034; beta = -0.265, p= 0.042; respectively). In contrast, NT-LDL was associated with CIMT in total population and in patients with HbA1c more than 7.0 percent (beta = -0.205, p= 0.022; beta = -0.244, p= 0.042; respectively). Multivariable-adjusted regression analysis demonstrated that NT-HDL independently predicted VRI outcome in total population and in well-controlled patients (beta = -0.282, p= 0.014; beta = -0.400, p= 0.035, respectively). These results suggest that NT-HDL could be used as marker to identify diabetic patients at risk of developing early microvascular complications.

The Impact of Di-2-Ethylhexyl Phthalate on Sperm Fertility.

A growing number of studies point to reduced fertility upon chronic exposure to endocrine-disrupting chemicals (EDCs) such as phthalates and plasticizers. These toxins are ubiquitous and are often found in food and beverage containers, medical devices, as well as in common household and personal care items. Animal studies with EDCs, such as phthalates and bisphenol A have shown a dose-dependent decrease in fertility and embryo toxicity upon chronic exposure. However, limited research has been conducted on the acute effects of these EDCs on male fertility. Here we used a murine model to test the acute effects of four ubiquitous environmental toxins: bisphenol A (BPA), di-2-ethylhexyl phthalate (DEHP), diethyl phthalate (DEP), and dimethyl phthalate (DMP) on sperm fertilizing ability and pre-implantation embryo development. The most potent of these toxins, di-2-ethylhexyl phthalate (DEHP), was further evaluated for its effect on sperm ion channel activity, capacitation status, acrosome reaction and generation of reactive oxygen species (ROS). DEHP demonstrated a profound hazardous effect on sperm fertility by producing an altered capacitation profile, impairing the acrosome reaction, and, interestingly, also increasing ROS production. These results indicate that in addition to its known chronic impact on reproductive potential, DEHP also imposes acute and profound damage to spermatozoa, and thus, represents a significant risk to male fertility.

The High Content of Fructose in Human Semen Competitively Inhibits Broad and Potent Antivirals That Target High-Mannose Glycans.

Semen is the primary transmission vehicle for various pathogenic viruses. Initial steps of transmission, including cell attachment and entry, likely occur in the presence of semen. However, the unstable nature of human seminal plasma and its toxic effects on cells in culture limit the ability to study in vitro virus infection and inhibition in this medium. We found that whole semen significantly reduces the potency of antibodies and microbicides that target glycans on the envelope glycoproteins (Envs) of HIV-1. The extraordinarily high concentration of the monosaccharide fructose in semen contributes significantly to the effect by competitively inhibiting the binding of ligands to α1,2-linked mannose residues on Env. Infection and inhibition in whole human seminal plasma are accurately mimicked by a stable synthetic simulant of seminal fluid that we formulated. Our findings indicate that, in addition to the protein content of biological secretions, their small-solute composition impacts the potency of antiviral microbicides and mucosal antibodies.IMPORTANCE Biological secretions allow viruses to spread between individuals. Each type of secretion has a unique composition of proteins, salts, and sugars, which can affect the infectivity potential of the virus and inhibition of this process. Here, we describe HIV-1 infection and inhibition in whole human seminal plasma and a synthetic simulant that we formulated. We discovered that the sugar fructose in semen decreases the activity of a broad and potent class of antiviral agents that target mannose sugars on the envelope protein of HIV-1. This effect of semen fructose likely reduces the efficacy of such inhibitors to prevent the sexual transmission of HIV-1. Our findings suggest that the preclinical evaluation of microbicides and vaccine-elicited antibodies will be improved by their in vitro assessment in synthetic formulations that simulate the effects of semen on HIV-1 infection and inhibition.

Indications for cardiovascular magnetic resonance in children with congenital and acquired heart disease: an expert consensus paper of the Imaging Working Group of the AEPC and the Cardiovascular Magnetic Resonance Section of the EACVI.

This article provides expert opinion on the use of cardiovascular magnetic resonance (CMR) in young patients with congenital heart disease (CHD) and in specific clinical situations. As peculiar challenges apply to imaging children, paediatric aspects are repeatedly discussed. The first section of the paper addresses settings and techniques, including the basic sequences used in paediatric CMR, safety, and sedation. In the second section, the indication, application, and clinical relevance of CMR in the most frequent CHD are discussed in detail. In the current era of multimodality imaging, the strengths of CMR are compared with other imaging modalities. At the end of each chapter, a brief summary with expert consensus key points is provided. The recommendations provided are strongly clinically oriented. The paper addresses not only imagers performing CMR, but also clinical cardiologists who want to know which information can be obtained by CMR and how to integrate it in clinical decision-making.

Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials.

BACKGROUND: Whether statin therapy is as effective in women as in men is debated, especially for primary prevention. We undertook a meta-analysis of statin trials in the Cholesterol Treatment Trialists' (CTT) Collaboration database to compare the effects of statin therapy between women and men. METHODS: We performed meta-analyses on data from 22 trials of statin therapy versus control (n=134,537) and five trials of more-intensive versus less-intensive statin therapy (n=39,612). Effects on major vascular events, major coronary events, stroke, coronary revascularisation and mortality were weighted per 1.0 mmol/L reduction in LDL cholesterol and effects in men and women compared with a Cox model that adjusted for non-sex differences. For subgroup analyses, we used 99% CIs to make allowance for the multiplicity of comparisons. FINDINGS: 46,675 (27%) of 174,149 randomly assigned participants were women. Allocation to a statin had similar absolute effects on 1 year lipid concentrations in both men and women (LDL cholesterol reduced by about 1.1 mmol/L in statin vs control trials and roughly 0.5 mmol/L for more-intensive vs less-intensive therapy). Women were generally at lower cardiovascular risk than were men in these trials. The proportional reductions per 1.0 mmol/L reduction in LDL cholesterol in major vascular events were similar overall for women (rate ratio [RR] 0.84, 99% CI 0.78-0.91) and men (RR 0.78, 99% CI 0.75-0.81, adjusted p value for heterogeneity by sex=0.33) and also for those women and men at less than 10% predicted 5 year absolute cardiovascular risk (adjusted heterogeneity p=0.11). Likewise, the proportional reductions in major coronary events, coronary revascularisation, and stroke did not differ significantly by sex. No adverse effect on rates of cancer incidence or non-cardiovascular mortality was noted for either sex. These net benefits translated into all-cause mortality reductions with statin therapy for both women (RR 0.91, 99% CI 0.84-0.99) and men (RR 0.90, 99% CI 0.86-0.95; adjusted heterogeneity p=0.43). INTERPRETATION: In men and women at an equivalent risk of cardiovascular disease, statin therapy is of similar effectiveness for the prevention of major vascular events. FUNDING: UK Medical Research Council, British Heart Foundation, Australian National Health and Medical Research Council, European Community Biomed Program.