Assessment of platelet function in patients with stroke using multiple electrode platelet aggregometry: a prospective observational study

Background There is a link between high on-treatment platelet reactivity (HPR) and adverse vascular events in stroke. This study aimed to compare multiple electrode platelet aggregometry (MEA), in healthy subjects and ischaemic stroke patients, and between patients naive to antiplatelet drugs (AP) and those on regular low dose AP. We also aimed to determine prevalence of HPR at baseline and at 3–5 days after loading doses of aspirin. Methods Patients with first ever ischaemic stroke were age and sex-matched to a healthy control group. Three venous blood samples were collected: on admission before any treatment given (baseline); at 24 h and 3–5 days after standard treatment. MEA was determined using a Mutliplate® analyser and agonists tested were arachidonic acid (ASPI), adenosine diphosphate (ADP) and collagen (COL). Results Seventy patients (mean age 73 years [SD 13]; 42 men, 28 women) were age and sex-matched to 72 healthy subjects. Thirty-three patients were on antiplatelet drugs (AP) prior to stroke onset and 37 were AP-naive. MEA results for all agonists were significantly increased in AP-naive patients compared to healthy subjects: ADP 98 ± 31 vs 81 ± 24, p < 0.005; ASPI 117 ± 31 vs 98 ± 27, p < 0.005; COL 100 ± 25 vs 82 ± 20, p < 0.005. For patients on long term AP, 33% (10/30) of patients were considered aspirin-resistant. At 3–5 days following loading doses of aspirin, only 11.1% were aspirin resistant based on an ASPI cut-off value of 40 AU*min. Conclusions Many patients receiving low dose aspirin met the criteria of aspirin resistance but this was much lower at 3–5 days following loading doses of aspirin. Future studies are needed to establish the causes of HPR and potential benefits of individualizing AP treatment based on platelet function testing

A global experience‐sampling method study of well‐being during times of crisis: The CoCo project

We present a global experience-sampling method (ESM) study aimed at describing, predicting, and understanding individual differences in well-being during times of crisis such as the COVID-19 pandemic. This international ESM study is a collaborative effort of over 60 interdisciplinary researchers from around the world in the “Coping with Corona” (CoCo) project. The study comprises trait-, state-, and daily-level data of 7490 participants from over 20 countries (total ESM measurements = 207,263; total daily measurements = 73,295) collected between October 2021 and August 2022. We provide a brief overview of the theoretical background and aims of the study, present the applied methods (including a description of the study design, data collection procedures, data cleaning, and final sample), and discuss exemplary research questions to which these data can be applied. We end by inviting collaborations on the CoCo dataset

An 8-week injury prevention exercise program combined with change-of-direction technique training limits movement patterns associated with anterior cruciate ligament injury risk

Abstract Knee ligament sprains are common during change-of-direction (COD) maneuvers in multidirectional team sports. This study aimed to compare the effects of an 8-week injury prevention exercise program containing COD-specific exercises and a similar program containing linear sprint exercises on injury- and performance-related variables during a 135° COD task. We hypothesized that the COD-specific training would lead to (H1) stronger reductions in biomechanical variables associated with anterior cruciate ligament (ACL) injury risk during COD, i.e. knee abduction moment and angle, hip internal rotation angle and lateral trunk lean, and (H2) more effective improvements in COD performance according to the COD completion time, executed angle, ground contact time, and approach speed. Twenty-two sports science students (40% female) completed biomechanical assessments of COD movement strategies before and after participating in two supervised 25-min training sessions per week over 8 weeks. We observed significant ‘training x group’ interaction effects in support of H1: the COD-specific training but not the linear sprint training led to reduced peak knee abduction moments (interaction, p = 0.027), initial knee abduction (interaction, p < 0.001), and initial lateral trunk lean angles (interaction, p < 0.001) compared to baseline. Although the COD-specific training resulted in sharper executed angles (interaction, p < 0.001), the sprint-specific training group showed reduced COD completion (interaction, p = 0.037) and ground contact times (interaction, p < 0.001). In conclusion, a combination of generic and COD-specific injury prevention training resulted in COD technique adaptations that can help to avoid ACL injury-prone COD movements but may negatively affect COD speed

Discovery of All- d -Peptide Inhibitors of SARS-CoV-2 3C-like Protease

During the replication process of SARS-CoV-2, the main protease of the virus [3-chymotrypsin-like protease (3CLpro)] plays a pivotal role and is essential for the life cycle of the pathogen. Numerous studies have been conducted so far, which have confirmed 3CLpro as an attractive drug target to combat COVID-19. We describe a novel and efficient next-generation sequencing (NGS) supported phage display selection strategy for the identification of a set of SARS-CoV-2 3CLpro targeting peptide ligands that inhibit the 3CL protease, in a competitive or noncompetitive mode, in the low μM range. From the most efficient l-peptides obtained from the phage display, we designed all-d-peptides based on the retro-inverso (ri) principle. They had IC50 values also in the low μM range and in combination, even in the sub-micromolar range. Additionally, the combination with Rutinprivir decreases 10-fold the IC50 value of the competitive inhibitor. The inhibition modes of these d-ri peptides were the same as their respective l-peptide versions. Our results demonstrate that retro-inverso obtained all-d-peptides interact with high affinity and inhibit the SARS-CoV-2 3CL protease, thus reinforcing their potential for further development toward therapeutic agents. The here described d-ri peptides address limitations associated with current l-peptide inhibitors and are promising lead compounds. Further optimization regarding pharmacokinetic properties will allow the development of even more potent d-peptides to be used for the prevention and treatment of COVID-19