Systemic Character of Legionnaires’ Disease – A Murine Model

In contrast to lung infection caused by Legionella pneumophila, little is known about the pathogenesis of this disease in other organs. In this study, we analyzed the number of colony forming units (CFU) of legionellae not only in lungs but also in EDTA plasma, liver, spleen and kidneys. The number of CFU was determined 2, 24, 48, 72 and 168 h after intratracheal inoculation. Results showed that the inflammatory response was mostly pronounced in lungs. Legionellae, however, were also found in EDTA plasma and all the other investigated organs. The duration of infection was most protracted in lungs, with persistence for at least 168 h. In the remaining organs, legionellae were found for a maximum of 72 h after inoculation. Besides the culture methods used for detection of CFU we also used LightCycler (LC) PCR to confirm the presence of bacteria in the blood of intratracheally infected mice. By this method the bacterial DNA could be detected during the first two days of post infection

Sequencing of 53,831 diverse genomes from the NHLBI TOPMed Program

The Trans-Omics for Precision Medicine (TOPMed) programme seeks to elucidate the genetic architecture and biology of heart, lung, blood and sleep disorders, with the ultimate goal of improving diagnosis, treatment and prevention of these diseases. The initial phases of the programme focused on whole-genome sequencing of individuals with rich phenotypic data and diverse backgrounds. Here we describe the TOPMed goals and design as well as the available resources and early insights obtained from the sequence data. The resources include a variant browser, a genotype imputation server, and genomic and phenotypic data that are available through dbGaP (Database of Genotypes and Phenotypes)1. In the first 53,831 TOPMed samples, we detected more than 400 million single-nucleotide and insertion or deletion variants after alignment with the reference genome. Additional previously undescribed variants were detected through assembly of unmapped reads and customized analysis in highly variable loci. Among the more than 400 million detected variants, 97% have frequencies of less than 1% and 46% are singletons that are present in only one individual (53% among unrelated individuals). These rare variants provide insights into mutational processes and recent human evolutionary history. The extensive catalogue of genetic variation in TOPMed studies provides unique opportunities for exploring the contributions of rare and noncoding sequence variants to phenotypic variation. Furthermore, combining TOPMed haplotypes with modern imputation methods improves the power and reach of genome-wide association studies to include variants down to a frequency of approximately 0.01%

Internet interventions for mental health in university students:A systematic review and meta-analysis

OBJECTIVES: Mental health disorders are highly prevalent among university students. Universities could be an optimal setting to provide evidence-based care through the Internet. As part of the World Mental Health International College Student initiative, this systematic review and meta-analysis synthesizes data on the efficacy of Internet-based interventions for university students' mental health. METHOD: A systematic literature search of bibliographical databases (CENTRAL, MEDLINE, and PsycINFO) for randomized trials examining psychological interventions for the mental health (depression, anxiety, stress, sleep problems, and eating disorder symptoms), well-being, and functioning of university students was performed through April 30, 2018. RESULTS: Forty-eight studies were included. Twenty-three studies (48%) were rated to have low risk of bias. Small intervention effects were found on depression (g = 0.18, 95% confidence interval [CI; 0.08, 0.27]), anxiety (g = 0.27, 95% CI [0.13, 0.40]), and stress (g = 0.20, 95% CI [0.02, 0.38]). Moderate effects were found on eating disorder symptoms (g = 0.52, 95% CI [0.22-0.83]) and role functioning (g = 0.41, 95% CI [0.26, 0.56]). Effects on well-being were non-significant (g = 0.15, 95% CI [-0.20, 0.50]). Heterogeneity was moderate to substantial in many analyses. After adjusting for publication bias, effects on anxiety were not significant anymore. DISCUSSION: Internet interventions for university students' mental health can have significant small-to-moderate effects on a range of conditions. However, more research is needed to determine student subsets for which Internet-based interventions are most effective and to explore ways to increase treatment effectiveness. © 2018 John Wiley & Sons, Ltd. KEYWORDS: Internet; college; mental disorders; meta-analysis; psychotherap

European multicenter evaluation of Xpert® Xpress SARS-CoV-2/Flu/RSV test

Rapid diagnostics for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are paramount for reducing the spread of the current pandemic. During additional seasonal epidemics with influenza A/B and respiratory syncytial virus (RSV), the clinical signs and symptoms cannot be distinguished easily from SARS-CoV-2. Therefore, a new assay combining four targets in the form of the new Xpert Xpress SARS-CoV-2/Flu/RSV assay was evaluated. The assay was compared to the Xpert Xpress SARS-CoV-2, Xpert Xpress Flu/RSV, Seegene Flu/RSV, influenza A/B r-gene® and RSV/hMPV r-gene®. A total of 295 nasopharyngeal and throat swabs were tested at four institutes throughout Europe including 72 samples positive for SARS-CoV-2, 65 for influenza A, 47 for influenza B, and 77 for RSV. The sensitivity of the new assay was above 95% for all targets, with the highest for SARS-CoV-2 (97.2%). The overall correlation of SARS-CoV-2 Ct values between Xpert Xpress SARS-CoV-2 assay and Xpert Xpress SARS-CoV-2/Flu/RSV assay was high. The agreement between Ct values above 30 showed the multiplex giving higher Ct values for SARS-CoV-2 on average than the singleplex assay. In conclusion, the new assay is a rapid and reliable alternative with less hands-on time for the detection of not one, but four upper respiratory tract pathogens that may circulate at the same time

Relationship between Endothelial Function, Antiretroviral Treatment and Cardiovascular Risk Factors in HIV Patients of African Descent in South Africa: A Cross-Sectional Study

Limited information on the effect of antiretroviral treatment (ART) on vascular function in South Africans of African descent living with human immunodeficiency virus (HIV) is available. The relationship between ART, vascular function and cardiovascular risk factors in South Africans of African ancestry with HIV was therefore studied. This cross-sectional study recruited 146 HIV-positive individuals on ART (HIV+ART+), 163 HIV-positive individuals not on ART (HIV+ART−) and 171 individuals without HIV (HIV−) in Mthatha, Eastern Cape Province of South Africa. Flow-mediated dilation (FMD) test was performed to assess endothelial function. Anthropometry and blood pressure parameters were measured. Lipid profile, glycaemic indices, serum creatinine as well as CD4 count and viral load were assayed in blood. Urinary albumin to creatinine ratio (ACR) was determined as a marker of cardiovascular risk. Obesity and albuminuria were positively associated with HIV, and HIV+ART+ participants had significantly higher HDL cholesterol. Dyslipidaemia markers were significantly higher in hypertensive HIV+ART+ participants compared with the controls (HIV+ART− and HIV− participants). FMD was not different between HIV+ART+ participants and the controls. Moreover, HIV+ART+ participants with higher FMD showed lower total cholesterol and LDL cholesterol comparable to that of HIV− and HIV+ART− participants. A positive relationship between FMD and CD4 count was observed in HIV+ART+ participants. In conclusion, antiretroviral treatment was associated with cardiovascular risk factors, particularly dyslipidaemia, in hypertensive South Africans of African ancestry with HIV. Although, ART was not associated with endothelial dysfunction, flow-mediated dilatation was positively associated with CD4 count in HIV-positive participants on ART

A telephone- and text-message based telemedical care concept for patients with mental health disorders - study protocol for a randomized, controlled study design

<p>Abstract</p> <p>Background</p> <p>As in other countries worldwide, the prevalence of mental disorders in Germany is high. Although numerically a dense network of in- and outpatient psychiatric health services exists, the availability in rural and remote regions is insufficient.</p> <p>In rural regions, telemedical concepts can be a chance to unburden and complement the existing healthcare system. Telemedical concepts consisting of video or telephone consulting show first positive results, but there are only a few studies with a randomized controlled design.</p> <p>To improve the treatment of patients with mental disorders in rural regions, we developed a telemedical care concept based on telephone contacts and text-messages. The primary objective of this study is to evaluate the effects of the telemedical interventions on psychopathological outcomes, e. g. anxiety, depressive symptoms, and somatisation. Secondary objective of the study is the analysis of intervention effects on the frequency of medical contacts with healthcare services. Furthermore, the frequency of patients' crises and the frequency and kind of interventions, initiated by the project nurses will be evaluated. We will also evaluate the acceptance of the telemedical care concept by the patients.</p> <p>Methods/Design</p> <p>In this paper we describe a three-armed, randomized, controlled study. All participants are recruited from psychiatric day hospitals. The inclusion criteria are a specialist-diagnosed depression, anxiety disorder, adjustment disorder or a somatoform disorder and eligibility to participate in the study. Exclusion criteria are ongoing outpatient psychotherapy, planned interval treatment at the day clinic and expected recurrent suicidality and self-injuring behaviour.</p> <p>The interventions consist of regular patient-individual telephone consultations or telephone consultations with complementing text-messages on the patients' mobile phone. The interventions will be conducted during a time period of 6 months.</p> <p>Trial registration</p> <p>This study is registered in the German Clinical Trials Register (DRKS00000662).</p

Cardiovascular risk and endothelial function in people living with HIV/AIDS: design of the multi-site, longitudinal EndoAfrica study in the Western Cape Province of South Africa

CITATION: Strijdom, H., et al. 2017. Cardiovascular risk and endothelial function in people living with HIV/AIDS: design of the multi-site, longitudinal EndoAfrica study in the Western Cape Province of South Africa. BMC Infectious Diseases, 17:41, doi:10.1186/s12879-016-2158-y.The original publication is available at http://bmcinfectdis.biomedcentral.comBackground: There is growing evidence of an interaction between HIV-infection, anti-retroviral therapy (ART) and cardiovascular diseases (CVD). Epidemiological studies in Europe and North America have been observing a shift towards an increased incidence of coronary heart disease and acute myocardial infarctions in HIV-infected populations compared to the general population even after adjusting for traditional cardiovascular risk factors. Despite South Africa (and sub-Saharan Africa, SSA) being regarded as the epicentre of the global HIV epidemic, very little is known about the prevalence of cardiovascular risk factors and precursors of vascular disease in HIV-infected populations in this region. The knowledge gap is further widened by the paucity of data from prospective studies. We present the rationale, objectives and key methodological features of the EndoAfrica study, which aims to determine whether HIVinfection and ART are associated with altered cardiovascular risk and changes in vascular endothelial structure and function in adults living in the Western Cape Province of South Africa. Methods: In this longitudinal study, comprehensive cardiovascular assessments of HIV-negative and HIV-positive (with and without ART) study participants are performed by clinical and biochemical screening for traditional cardiovascular risk factors and biomarkers of CVD. Vascular and endothelial function is determined by brachial artery flow-mediated dilatation (FMD), carotid-intima-thickness (IMT) measurements and quantitative retinal blood vessel analyses, complemented by vascular endothelial biomarker assays. Finally, we aim to statistically determine whether HIVinfection and/or ART are associated with increased cardiovascular risk and vascular endothelial dysfunction, and determine whether there is progression/regression in these endpoints 18 months after the baseline assessments. Discussion: The EndoAfrica study provides a unique opportunity to recruit a cohort of HIV-infected patients and HIVnegative controls who will be comprehensively and longitudinally assessed for cardiovascular risk and disease profile with vascular endothelial function as a potentially important intermediate cardiovascular phenotype. To our knowledge, it is the first time that such a systematic study has been established in the context of SSA and South Africa.http://bmcinfectdis.biomedcentral.com/articles/10.1186/s12879-016-2158-yPublisher's versio