Reproductive disorders induced by Chlamydophila spp. infections in an italian mediterranean buffalo (bubalus bubalis) herd

The Italian Mediterranean Buffalo (Bubalus bubalis) has low fecundity and high incidence of abortion. Several studies have associated reproductive failure of water buffalo with viral infections but there is limited information on the role of chlamydial infections. To investigate the presence and the role of Chlamydiaceae in water buffalo a retrospective study was performed in a farm where, in the arch of 11 months, the pregnant heifers suffered an abortion rate of 36.8% in the 3rd and 5th month of pregnancy. Antibodies to Chlamydiaceae were detected in 57% of the aborted cows, while the rate of positivity was 0% in overtly healthy cows used as control. By a PCR assay 3 of 14 vaginal swabs from aborted animals tested positive for Chlamydophila agents and, additionally, 3 out of 7 aborted foetuses tested positive for Chlamydophila spp., with two being co-infections by Cp. abortus and Cp. pecorum and one being characterised as Cp. abortus. The presence of anti-Chlamydiaceae antibodies in 57% of the aborted animals and the detection of Chlamydophila agents in foetal organs and in vaginal swabs is consistent with the history of abortions (P<0.002) observed in the herd and may suggest a pathogenic role by Chlamydophila spp. in water buffalo

(13C)-Methacetin breath test provides evidence of subclinical liver dysfunction linked to fat storage but not lifestyle

Background &amp; Aims: Non-alcoholic fatty liver disease (NAFLD) is characterised by the presence of hepatic steatosis in the absence of other causes of secondary hepatic fat accumulation, and is usually associated with visceral, metabolically active obesity. However, the subclinical effects of body and liver fat accumulation on liver function are still unclear. Methods: We used orally administered (13C)-methacetin and breath test to quantify the efficiency of hepatic extraction from portal blood flow and liver microsomal function in 81 participants, in relation to presence/absence of ultrasonographic NAFLD, extent of body fat accumulation, insulin resistance, dietary models, and lifestyle. Results: NAFLD was present in 23% of participants with normal weight, and prevalence increased with body fat and insulin resistance. Fat accumulation, NAFLD, and insulin resistance were associated with decreased hepatic extraction efficiency, and liver microsomal function was impaired in moderate-to-severe NAFLD. Caloric intake, dietary models, and lifestyles had a minor role in promoting functional changes. Conclusions: The interplay between body fat accumulation, insulin resistance, and NAFLD is linked with altered hepatic extraction efficiency from blood flow and deranged microsomal function. Non-invasive diagnosis of subclinical alterations of liver function is relevant for primary and secondary prevention measures. Furthermore, the occurrence of NAFLD in lean individuals and the evidence that caloric intake, dietary models, and lifestyle played a minor role require further studies exploring the role of environmental factors in the natural history of these diseases. Lay summary: Obesity is progressively increasing worldwide and is paralleled by fat accumulation in the liver (non-alcoholic fatty liver disease [NAFLD]), the most common chronic liver disease worldwide. NAFLD can alter liver structure and function, with a variety of consequences ranging from asymptomatic and subclinical alterations to cirrhosis and cancer. (13C)-Methacetin breath test, a non-invasive diagnostic tool, can reveal early subclinical alterations of liver dynamic function in individuals with obesity and in patients with NAFLD

Effect of lifestyle changes on erectile dysfunction in obese men: a randomized controlled trial

Context: Healthy lifestyle factors are associated with maintenance of erectile function in men. Objective: To determine the effect of weight loss and increased physical activity on erectile and endothelial functions in obese men. Design, Setting, and Patients: Randomized, single-blind trial of 110 obese men (body mass index ≥30) aged 35 to 55 years, without diabetes, hypertension, or hyperlipidemia, who had erectile dysfunction that was determined by having a score of 21 or less on the International Index of Erectile Function (IIEF). The study was conducted from October 2000 to October 2003 at a university hospital in Italy. Interventions: The 55 men randomly assigned to the intervention group received detailed advice about how to achieve a loss of 10% or more in their total body weight by reducing caloric intake and increasing their level of physical activity. Men in the control group (n=55) were given general information about healthy food choices and exercise. Main Outcomes Measures: Erectile function score, levels of cholesterol and tryglycerides, circulating levels of interleukin 6, interleukin 8, and C-reactive protein, and endothelial function as assessed by vascular responses to L-arginine. Results: After 2 years, body mass index decreased more in the intervention group (from a mean [SD] of 36.9 [2.5] to 31.2 [2.1]) than in the control group (from 36.4 [2.3] to 35.7 [2.5]) (P<.001), as did serum concentrations of interleukin 6 (P=.03), and C-reactive protein (P=.02). The mean (SD) level of physical activity increased more in the intervention group (from 48 [10] to 195 [36] min/wk; P<.001) than in the control group (from 51 [9] to 84 [28] min/wk; P<.001). The mean (SD) IIEF score improved in the intervention group (from 13.9 [4.0] to 17 [5]; P<.001), but remained stable in the control group (from 13.5 [4.0] to 13.6 [4.1]; P=.89). Seventeen men in the intervention group and 3 in the control group (P=.001) reported an IIEF score of 22 or higher. In multivariate analyses, changes in body mass index (P=.02), physical activity (P=.02), and C-reactive protein (P=.03) were independently associated with changes in IIEF score. Conclusion: Lifestyle changes are associated with improvement in sexual function in about one third of obese men with erectile dysfunction at baseline

Effects of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 in IBS patients

Background: Irritable bowel syndrome (IBS) is a common gastrointestinal disorder, which still lacks effective therapy. We aimed to investigate the effects of a novel formulation of Bifidobacterium longum BB536 and Lactobacillus rhamnosus HN001 with vitamin B6 (LBB) on symptoms, intestinal permeability, cultivable bacteria and metabolome in IBS subjects. Materials and methods: Twenty-five IBS patients (Rome IV criteria) (M:F&nbsp;=&nbsp;8:17; age 48&nbsp;years&nbsp;±&nbsp;11 SD) were randomized to treatment (LBB) or placebo (one month each) in a crossover randomized double-blind controlled trial. Symptoms, intestinal habits, disease severity, intestinal permeability and intestinal microbiota were analysed at 0, 30, 45 and 60&nbsp;days. Results: Percentage decrease from baseline of abdominal pain (−48.8% vs −3.5%), bloating (−36.35% vs +7.35%) and severity of disease (−30.1% vs −0.4%) was significantly (P&nbsp;&lt;.0001) greater with LBB than placebo, respectively. In IBS-D patients, the improvement from baseline of Bristol score was more consistent with LBB (from 6&nbsp;±&nbsp;0.4 to 4.3&nbsp;±&nbsp;1.1, P&nbsp;&lt;.00001) than placebo (from 6.2&nbsp;±&nbsp;0.7 to 5.3&nbsp;±&nbsp;1.1, P&nbsp;=.04). In IBS-C patients, Bristol score tended to improve from baseline after LBB (2.6&nbsp;±&nbsp;1.1 vs 3.2&nbsp;±&nbsp;0.5, P&nbsp;=.06). LBB significantly improved the percentage of sucralose recovery (colonic permeability) (1.86&nbsp;±&nbsp;0.1 vs 1.1&nbsp;±&nbsp;0.2, P&nbsp;=.01). During treatment, presumptive lactic acid bacteria and bifidobacteria, relative abundance of propanoic, butanoic, pentanoic acids and hydrocarbons increased, while phenol decreased. Conclusions: The novel formulation of B. longum BB536 and L. rhamnosus HN001 with B6 vitamin improves symptoms and severity of disease, restores intestinal permeability and gut microbiota in IBS patients

Effective action for Superconductors and BCS-Bose crossover

A standard perturbative expansion around the mean-field solution is used to derive the low-energy effective action for superconductors at T=0. Taking into account the density fluctuations at the outset we get the effective action where the density $\rho$ is the conjugated momentum to the phase $\theta$ of the order parameter. In the hydrodynamic regime, the dynamics of the superconductor is described by a time dependent non-linear Schr\"odinger equation (TDNLS) for the field $\Psi(x)=\sqrt{\rho/2} e^{i\theta}$. The evolution of the density fluctuations in the crossover from weak-coupling (BCS) to strong-coupling (Bose condensation of localized pairs) superconductivity is discussed for the attractive Hubbard model. In the bosonic limit, the TDNLS equation reduces to the the Gross-Pitaevskii equation for the order parameter, as in the standard description of superfluidity. The conditions under which a phase-only action can be derived in the presence of a long-range interaction to describe the physics of the superconductivity of ``bad metals'' are discussed.Comment: 13 pages, accepted for publication on Phys. Rev.

Toward an international consensus-Integrating lipoprotein apheresis and new lipid-lowering drugs

Background: Despite advances in pharmacotherapy of lipid disorders, many dyslipidemic patients do not attain sufficient lipid lowering to mitigate risk of atherosclerotic cardiovascular disease. Several classes of novel lipid-lowering agents are being evaluated to reduce atherosclerotic cardiovascular disease risk. Lipoprotein apheresis (LA) is effective in acutely lowering the plasma concentrations of atherogenic lipoproteins including low-density lipoprotein cholesterol and lipoprotein(a), and novel lipid-lowering drugs may dampen the lipid rebound effect of LA, with the possibility that LA frequency may be decreased, in some cases even be discontinued. Sources of material: This document builds on current American Society for Apheresis guidelines and, for the first time, makes recommendations from summarized data of the emerging lipid-lowering drug classes (inhibitors of proprotein convertase subtilisin/kexin type 9 or microsomal triglyceride transfer protein, high-density lipoprotein mimetic), including the available evidence on combination therapy with LA with respect to the management of patients with dyslipidemia. Abstract of findings: Recommendations for different indications are given based on the latest evidence. However, except for lomitapide in homozygous familial hypercholesterolemia and alirocumab/evolocumab in heterozygous familial hypercholesterolemia subjects, limited data are available on the effectiveness and safety of combination therapy. More studies on combining LA with novel lipid-lowering drugs are needed. Conclusion: Novel lipid-lowering agents have potential to improve the performance of LA, but more evidence is needed. The Multidisciplinary International Group for Hemapheresis TherapY and Metabolic DIsturbances Contrast scientific society aims to establish an international registry of clinical experience on LA combination therapy to expand the evidence on this treatment in individuals at high cardiovascular disease risk

DISC1 genetics, biology and psychiatric illness

Psychiatric disorders are highly heritable, and in many individuals likely arise from the combined effects of genes and the environment. A substantial body of evidence points towards DISC1 being one of the genes that influence risk of schizophrenia, bipolar disorder and depression, and functional studies of DISC1 consequently have the potential to reveal much about the pathways that lead to major mental illness. Here, we review the evidence that DISC1 influences disease risk through effects upon multiple critical pathways in the developing and adult brain

Geoeconomic variations in epidemiology, ventilation management, and outcomes in invasively ventilated intensive care unit patients without acute respiratory distress syndrome: a pooled analysis of four observational studies

Background: Geoeconomic variations in epidemiology, the practice of ventilation, and outcome in invasively ventilated intensive care unit (ICU) patients without acute respiratory distress syndrome (ARDS) remain unexplored. In this analysis we aim to address these gaps using individual patient data of four large observational studies. Methods: In this pooled analysis we harmonised individual patient data from the ERICC, LUNG SAFE, PRoVENT, and PRoVENT-iMiC prospective observational studies, which were conducted from June, 2011, to December, 2018, in 534 ICUs in 54 countries. We used the 2016 World Bank classification to define two geoeconomic regions: middle-income countries (MICs) and high-income countries (HICs). ARDS was defined according to the Berlin criteria. Descriptive statistics were used to compare patients in MICs versus HICs. The primary outcome was the use of low tidal volume ventilation (LTVV) for the first 3 days of mechanical ventilation. Secondary outcomes were key ventilation parameters (tidal volume size, positive end-expiratory pressure, fraction of inspired oxygen, peak pressure, plateau pressure, driving pressure, and respiratory rate), patient characteristics, the risk for and actual development of acute respiratory distress syndrome after the first day of ventilation, duration of ventilation, ICU length of stay, and ICU mortality. Findings: Of the 7608 patients included in the original studies, this analysis included 3852 patients without ARDS, of whom 2345 were from MICs and 1507 were from HICs. Patients in MICs were younger, shorter and with a slightly lower body-mass index, more often had diabetes and active cancer, but less often chronic obstructive pulmonary disease and heart failure than patients from HICs. Sequential organ failure assessment scores were similar in MICs and HICs. Use of LTVV in MICs and HICs was comparable (42\ub74% vs 44\ub72%; absolute difference \u20131\ub769 [\u20139\ub758 to 6\ub711] p=0\ub767; data available in 3174 [82%] of 3852 patients). The median applied positive end expiratory pressure was lower in MICs than in HICs (5 [IQR 5\u20138] vs 6 [5\u20138] cm H2O; p=0\ub70011). ICU mortality was higher in MICs than in HICs (30\ub75% vs 19\ub79%; p=0\ub70004; adjusted effect 16\ub741% [95% CI 9\ub752\u201323\ub752]; p&lt;0\ub70001) and was inversely associated with gross domestic product (adjusted odds ratio for a US$10 000 increase per capita 0\ub780 [95% CI 0\ub775\u20130\ub786]; p&lt;0\ub70001). Interpretation: Despite similar disease severity and ventilation management, ICU mortality in patients without ARDS is higher in MICs than in HICs, with a strong association with country-level economic status. Funding: No funding

Spontaneous Breathing in Early Acute Respiratory Distress Syndrome: Insights From the Large Observational Study to UNderstand the Global Impact of Severe Acute Respiratory FailurE Study

OBJECTIVES: To describe the characteristics and outcomes of patients with acute respiratory distress syndrome with or without spontaneous breathing and to investigate whether the effects of spontaneous breathing on outcome depend on acute respiratory distress syndrome severity. DESIGN: Planned secondary analysis of a prospective, observational, multicentre cohort study. SETTING: International sample of 459 ICUs from 50 countries. PATIENTS: Patients with acute respiratory distress syndrome and at least 2 days of invasive mechanical ventilation and available data for the mode of mechanical ventilation and respiratory rate for the 2 first days. INTERVENTIONS: Analysis of patients with and without spontaneous breathing, defined by the mode of mechanical ventilation and by actual respiratory rate compared with set respiratory rate during the first 48 hours of mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Spontaneous breathing was present in 67% of patients with mild acute respiratory distress syndrome, 58% of patients with moderate acute respiratory distress syndrome, and 46% of patients with severe acute respiratory distress syndrome. Patients with spontaneous breathing were older and had lower acute respiratory distress syndrome severity, Sequential Organ Failure Assessment scores, ICU and hospital mortality, and were less likely to be diagnosed with acute respiratory distress syndrome by clinicians. In adjusted analysis, spontaneous breathing during the first 2 days was not associated with an effect on ICU or hospital mortality (33% vs 37%; odds ratio, 1.18 [0.92-1.51]; p = 0.19 and 37% vs 41%; odds ratio, 1.18 [0.93-1.50]; p = 0.196, respectively ). Spontaneous breathing was associated with increased ventilator-free days (13 [0-22] vs 8 [0-20]; p = 0.014) and shorter duration of ICU stay (11 [6-20] vs 12 [7-22]; p = 0.04). CONCLUSIONS: Spontaneous breathing is common in patients with acute respiratory distress syndrome during the first 48 hours of mechanical ventilation. Spontaneous breathing is not associated with worse outcomes and may hasten liberation from the ventilator and from ICU. Although these results support the use of spontaneous breathing in patients with acute respiratory distress syndrome independent of acute respiratory distress syndrome severity, the use of controlled ventilation indicates a bias toward use in patients with higher disease severity. In addition, because the lack of reliable data on inspiratory effort in our study, prospective studies incorporating the magnitude of inspiratory effort and adjusting for all potential severity confounders are required

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database

Background: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). Methods: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. Results: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. Conclusions: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. Trial registration: NCT02010073. Registered on 12 December 2013