Leukocyte Count and Coronary Artery Disease Events in People With Human Immunodeficiency Virus: A Longitudinal Study

BACKGROUND: People with human immunodeficiency virus (HIV; PWH) have increased cardiovascular risk. Higher leukocyte count has been associated with coronary artery disease (CAD) events in the general population. It is unknown whether the leukocyte-CAD association also applies to PWH. METHODS: In a case-control study nested within the Swiss HIV Cohort Study, we obtained uni- and multivariable odds ratios (OR) for CAD events, based on traditional and HIV-related CAD risk factors, leukocyte count, and confounders previously associated with leukocyte count. RESULTS: We included 536 cases with a first CAD event (2000-2021; median age, 56 years; 87% male; 84% with suppressed HIV RNA) and 1464 event-free controls. Cases had higher latest leukocyte count before CAD event than controls (median [interquartile range], 6495 [5300-7995] vs 5900 [4910-7200]; P 11 000/µL) was uncommon (4.3% vs 2.1%; P = .01). In the highest versus lowest leukocyte quintile at latest time point before CAD event, participants had univariable CAD-OR = 2.27 (95% confidence interval, 1.63-3.15) and multivariable adjusted CAD-OR = 1.59 (1.09-2.30). For comparison, univariable CAD-OR for dyslipidemia, diabetes, and recent abacavir exposure were 1.58 (1.29-1.93), 2.19 (1.59-3.03), and 1.73 (1.37-2.17), respectively. Smoking and, to a lesser degree, alcohol and ethnicity attenuated the leukocyte-CAD association. Leukocytes measured up to 8 years before the event were significantly associated with CAD events. CONCLUSIONS: PWH in Switzerland with higher leukocyte counts have an independently increased risk of CAD events, to a degree similar to traditional and HIV-related risk factors

The SARS-Coronavirus-Host Interactome: Identification of Cyclophilins as Target for Pan-Coronavirus Inhibitors

Coronaviruses (CoVs) are important human and animal pathogens that induce fatal respiratory, gastrointestinal and neurological disease. The outbreak of the severe acute respiratory syndrome (SARS) in 2002/2003 has demonstrated human vulnerability to (Coronavirus) CoV epidemics. Neither vaccines nor therapeutics are available against human and animal CoVs. Knowledge of host cell proteins that take part in pivotal virus-host interactions could define broad-spectrum antiviral targets. In this study, we used a systems biology approach employing a genome-wide yeast-two hybrid interaction screen to identify immunopilins (PPIA, PPIB, PPIH, PPIG, FKBP1A, FKBP1B) as interaction partners of the CoV non-structural protein 1 (Nsp1). These molecules modulate the Calcineurin/NFAT pathway that plays an important role in immune cell activation. Overexpression of NSP1 and infection with live SARS-CoV strongly increased signalling through the Calcineurin/NFAT pathway and enhanced the induction of interleukin 2, compatible with late-stage immunopathogenicity and long-term cytokine dysregulation as observed in severe SARS cases. Conversely, inhibition of cyclophilins by cyclosporine A (CspA) blocked the replication of CoVs of all genera, including SARS-CoV, human CoV-229E and -NL-63, feline CoV, as well as avian infectious bronchitis virus. Non-immunosuppressive derivatives of CspA might serve as broad-range CoV inhibitors applicable against emerging CoVs as well as ubiquitous pathogens of humans and livestock

Integration der Flexibilitätsvermarktung

Die Energiesynchronisationsplattform adressiert den gesamten Prozess des automatisierten Energieflexibilitätshandels von der Maschine bis zu den Vermarktungsservices. Sie stellt somit das übergeordnete Gesamtkonzept eines digitalen Ökosystems dar, welches industrielle Nachfrageflexibilität ermöglicht. Die Energiesynchronisationsplattform besteht dabei aus unternehmensindividuellen Unternehmensplattformen und einer zentralen Marktplattform. Der Marktplattform kommt die Rolle der Servicevermittlung zu. Dies ermöglicht es, auf Veränderungen innerhalb der Services bzw. der Marktplattform schnell reagieren zu können. Im vorliegenden Kapitel werden beispielhafte Services der Unternehmens- und Marktplattformen beschrieben. Zudem wird ein Überblick über die Referenzabläufe für den Betrieb und die Vermarktung von Energieflexibilität gegeben. Die Prozesse werden anhand eines möglichen Anwendungsfalls dargestellt. Außerdem wird das weiterentwickelte Energieflexibilitätsdatenmodell vorgestellt und anhand von vier Klassen beschrieben. Zur Bedrohungsanalyse im Kontext der IT-Sicherheit werden Threat Models (Bedrohungsmodelle) angewandt und auf Basis verschiedener Sicherheitslevels vorgestellt. Darüber hinaus werden Rollen- und Rechtedefinitionen beschrieben und Anforderungen an die IT-Sicherheit abgeleitet. Eine Kurzvorstellung entwickelter Demonstratoren schließt das Kapitel ab

Leukocyte Count and Coronary Artery Disease Events in People with HIV: A Longitudinal Study.

BACKGROUND People with HIV (PWH) have increased cardiovascular risk. Higher leukocyte count has been associated with coronary artery disease (CAD) events in the general population. It is unknown whether the leukocyte-CAD association also applies to PWH. METHODS In a case-control study nested within the Swiss HIV Cohort Study, we obtained uni- and multivariable odds ratios (OR) for CAD events, based on traditional and HIV-related CAD risk factors, leukocyte count, and confounders previously associated with leukocyte count. RESULTS We included 536 cases with a first CAD event (2000-2021; median age 56 years, 87% male, 84% with suppressed HIV-RNA) and 1464 event-free controls. Cases had higher latest leukocyte count prior to CAD event than controls (median [interquartile range], 6495 [5300-7995] vs. 5900 [4910-7200]; p 11000/uL) was uncommon (4.3% vs. 2.1%; p = 0.01). In the highest vs. lowest leukocyte quintile at latest time point prior to CAD event, participants had univariable CAD-OR = 2.27 (95% confidence interval, 1.63-3.15) and multivariable adjusted CAD-OR = 1.59 (1.09-2.30). For comparison, univariable CAD-OR for dyslipidemia, diabetes, and recent abacavir exposure were 1.58 (1.29-1.93), 2.19 (1.59-3.03), and 1.73 (1.37-2.17), respectively. Smoking and, to a lesser degree, alcohol and ethnicity attenuated the leukocyte-CAD association. Leukocytes measured up to 8 years pre-event were significantly associated with CAD events. CONCLUSIONS PWH in Switzerland with higher leukocyte counts have an independently increased risk of CAD events, to a degree similar to traditional and HIV-related risk factors