Prospective Trial on the Pharmacokinetics of Clopidogrel in Hemodialysis Patients.

Introduction: Hemodialysis patients (HDPs) exhibit extensive cardiovascular risk. The widely prescribed anti-platelet agent clopidogrel is metabolically activated by cytochrome enzymes, which may be impaired by uremia and chronic low-grade inflammation, typically present in HDPs. We conducted a prospective multicenter study to investigate the pharmacokinetics and pharmacodynamics of clopidogrel in HDPs and healthy volunteers (HVs).

Investigating a New Way to Assess Metabolic Risk in Pregnant Females with Prior RYGB Surgery.

Background: Obesity in pregnancy is linked to adverse clinical outcomes such as gestational diabetes. Recently, a risk score calculated by different ceramide concentrations was recognized as a new way to investigate cardiovascular risk. The aim was to analyze if the ceramide risk score and cardiometabolic risk vary between normal-weight, obese, and females with prior Roux-en-Y bypass surgery (RYGB) during pregnancy.

The disrupted molecular circadian clock of monocytes and macrophages in allergic inflammation.

Introduction: Macrophage dysfunction is a common feature of inflammatory disorders such as asthma, which is characterized by a strong circadian rhythm.

Methods And Results: We monitored the protein expression pattern of the molecular circadian clock in human peripheral blood monocytes from healthy, allergic, and asthmatic donors during a whole day. Monocytes cultured of these donors allowed us to examine circadian protein expression in human monocyte-derived macrophages, M1- and M2- polarized macrophages.

Association of HbA1c and utilization of internal mammary arteries with wound infections in CABG.

Background: Deep sternal wound infection (DSWI) remains a serious complication after coronary artery bypass grafting (CABG). We herein aimed to stratify diabetic patients who underwent CABG using bilateral internal mammary artery (BIMA) for levels of glycated hemoglobin A1C (HbA1c) and compare postoperative outcomes.

Methods: Between January 2010 and August 2020, 4,186 consecutive patients underwent isolated CABG at our center.

Pharmacokinetics of isavuconazole at different target sites in healthy volunteers after single and multiple intravenous infusions.

Background: Invasive aspergillosis is a severe fungal infection that affects multiple organ systems including the CNS and the lungs. Isavuconazole, a novel triazole antifungal agent, has demonstrated promising activity against Aspergillus spp. However, data on the penetration of isavuconazole into the CNS and ELF and intracellular accumulation remain limited.

Recombinant human diamine oxidase prevents hemodynamic effects of continuous histamine infusion in guinea pigs.

Objective: To test whether recombinant human diamine oxidase (rhDAO) with a mutated heparin-binding motif (mHBM), which shows an increased alpha-distribution half-life, prevents histamine-induced hemodynamic effects.

Material: Thirty-eight female guinea pigs were either pretreated with rhDOA_mHBM or buffer.

Treatment And Methods: Guinea pigs received a continuous infusion of histamine.

Switching From Cangrelor to Prasugrel in Patients Undergoing Percutaneous Coronary Intervention: The Switching Antiplatelet-6 (SWAP-6) Study.

Background: A drug-drug interaction (DDI) may occur when transitioning from intravenous P2Y inhibition with cangrelor to oral P2Y inhibition with prasugrel. However, this has never been tested in patients undergoing percutaneous coronary intervention (PCI).

Objectives: This study sought to rule out a DDI when cangrelor and prasugrel are concomitantly administered in PCI patients.

Plasma and intraperitoneal pharmacokinetics of ceftazidime/avibactam in peritoneal dialysis patients.

Objectives: Peritonitis is a serious complication in patients undergoing automated peritoneal dialysis (APD) that increases morbidity and frequently disqualifies patients from the peritoneal dialysis programme. Ceftazidime/avibactam (CAZ/AVI) is a potential treatment option for APD patients with peritonitis caused by resistant Gram-negative bacteria, but limited data exist on systemic and target-site pharmacokinetics (PK) in patients undergoing APD. This study set out to investigate the PK of CAZ/AVI in plasma and peritoneal dialysate (PDS) of patients undergoing APD.

"Courage to cobble something new": Women's queer and creative narratives of bisexuality and ageing.

Critical gerontologists have called for more diverse and inclusive visions of a good old age, and especially for imaginings that do not depend on health, wealth and heterosexuality. They have suggested that LGBTQ people, alongside other marginalized groups, may have particular contributions to make to the project of reimagining ageing. In this paper, we bring together this work with Jose Muñoz's concept of 'cruising utopia' to examine possibilities for imagining a more utopian, queer life course.

Catch Recognition in Automated American Football Training Using Machine Learning.

In order to train receivers in American football in a targeted and individual manner, the strengths and weaknesses of the athletes must be evaluated precisely. As human resources are limited, it is beneficial to do it in an automated way. Automated passing machines are already given, therefore the motivation is to design a computer-based system that records and automatically evaluates the athlete's catch attempts.

Simvastatin therapy in higher dosages deteriorates bone quality: Consistent evidence from population-wide patient data and interventional mouse studies.

Background: Combining mouse experiments with big data analysis of the Austrian population, we investigated the association between high-dose statin treatment and bone quality.

Methods: The bone microarchitecture of the femur and vertebral body L4 was measured in male and ovariectomized female mice on a high-fat diet containing simvastatin (1.2 g/kg).

A multi-omics based anti-inflammatory immune signature characterizes long COVID-19 syndrome.

To investigate long COVID-19 syndrome (LCS) pathophysiology, we performed an exploratory study with blood plasma derived from three groups: 1) healthy vaccinated individuals without SARS-CoV-2 exposure; 2) asymptomatic recovered patients at least three months after SARS-CoV-2 infection and; 3) symptomatic patients at least 3 months after SARS-CoV-2 infection with chronic fatigue syndrome or similar symptoms, here designated as patients with long COVID-19 syndrome (LCS). Multiplex cytokine profiling indicated slightly elevated pro-inflammatory cytokine levels in recovered individuals in contrast to patients with LCS. Plasma proteomics demonstrated low levels of acute phase proteins and macrophage-derived secreted proteins in LCS.

Cangrelor in Patients With Coronary Artery Disease Pretreated With Ticagrelor: The Switching Antiplatelet (SWAP)-5 Study.

Background: There are no studies specifically designed to rule out a drug-drug interaction (DDI) when cangrelor is used among patients who have been pretreated with ticagrelor.

Objectives: This study sought to rule out a DDI among cangrelor-treated patients who have been pretreated with ticagrelor.

Methods: In this prospective, randomized, double-blind, placebo-controlled, crossover, pharmacokinetic (PK) and pharmacodynamic (PD) study, patients with coronary artery disease (N = 20) were pretreated with a 180-mg ticagrelor loading dose and after 1 hour randomized to placebo or cangrelor (bolus and infusion for 2 hours).

Comparison of pharmacokinetics and stability of generics of cefepime, linezolid and piperacillin/tazobactam with their respective originator drugs: an intravenous bioequivalence study in healthy volunteers.

Objectives: The efficacy and quality of generic antibacterial drug formulations are often questioned by both healthcare specialists and patients. Therefore, the present study investigated the interchangeability of generic drugs with their originators by comparing bioequivalence parameters and stability data of generic cefepime, linezolid and piperacillin/tazobactam with their respective originator drugs.

Methods: In this open-label, randomized, crossover bioequivalence study, three groups of 12 healthy volunteers each received a single intravenous infusion of either 2 g of cefepime or 4.

Commonalities and specialties in photosynthetic functions of PROTON GRADIENT REGULATION5 variants in Arabidopsis.

The PROTON GRADIENT REGULATION5 (PGR5) protein is required for trans-thylakoid proton gradient formation and acclimation to fluctuating light (FL). PGR5 functionally interacts with two other thylakoid proteins, PGR5-like 1 (PGRL1) and 2 (PGRL2); however, the molecular details of these interactions are largely unknown. In the Arabidopsis (Arabidopsis thaliana) pgr5-1 mutant, the PGR5G130S protein accumulates in only small amounts.

Right ventricular and pulmonary artery pulse pressure variation and systolic pressure variation for the prediction of fluid responsiveness: an interventional study in coronary artery bypass surgery patients.

Purpose: Predicting fluid responsiveness is essential when treating surgical or critically ill patients. When using a pulmonary artery catheter, pulse pressure variation and systolic pressure variation can be calculated from right ventricular and pulmonary artery pressure waveforms.

Methods: We conducted a prospective interventional study investigating the ability of right ventricular pulse pressure variation (PPV) and systolic pressure variation (SPV) as well as pulmonary artery pulse pressure variation (PPV) and systolic pressure variation (SPV) to predict fluid responsiveness in coronary artery bypass (CABG) surgery patients.

Microdosing as a Potential Tool to Enhance Clinical Development of Novel Antibiotics: A Tissue and Plasma PK Feasibility Study with Ciprofloxacin.

Background And Objective: In microdose studies, drug pharmacokinetics is measured in humans after administration of subtherapeutic doses. While previous microdose studies focused primarily on plasma pharmacokinetics, we set out to evaluate the feasibility of microdosing for a pharmacokinetic assessment in subcutaneous tissue and epithelial lining fluid.

Methods: Healthy subjects received a single intravenous bolus injection of a microdose of [C]ciprofloxacin (1.

Targeted temperature management after cardiac arrest is associated with reduced metabolism of pantoprazole - A probe drug of CYP2C19 metabolism.

Objective: Targeted temperature management (TTM) is part of standard post-resuscitation care. TTM may downregulate cytochrome enzyme activity and thus impact drug metabolism. This study compared the pharmacokinetics (PK) of pantoprazole, a probe drug of CYP2C19-dependent metabolism, at different stages of TTM following cardiac arrest.

Rise of cGMP by partial phosphodiesterase-3A degradation enhances cardioprotection during hypoxia.

3',5'-cyclic guanosine monophosphate (cGMP) is a druggable second messenger regulating cell growth and survival in a plethora of cells and disease states, many of which are associated with hypoxia. For example, in myocardial infarction and heart failure (HF), clinical use of cGMP-elevating drugs improves disease outcomes. Although they protect mice from ischemia/reperfusion (I/R) injury, the exact mechanism how cardiac cGMP signaling is regulated in response to hypoxia is still largely unknown.

PGRL2 triggers degradation of PGR5 in the absence of PGRL1.

In plants, inactivation of either of the thylakoid proteins PGR5 and PGRL1 impairs cyclic electron flow (CEF) around photosystem I. Because PGR5 is unstable in the absence of the redox-active PGRL1, but not vice versa, PGRL1 is thought to be essential for CEF. However, we show here that inactivation of PGRL2, a distant homolog of PGRL1, relieves the need for PGRL1 itself.