Elevated LPS is largely driven by time since symptom onset in acute ischemic stroke: the impact on clinical outcomes.

BACKGROUND: Gut dysbiosis leading to increased intestinal barrier permeability and translocation of lipopolysaccharide (LPS) in the circulation has been demonstrated in patients with acute myocardial infarction and pulmonary embolism. OBJECTIVES: We investigated changes in circulating LPS concentrations in acute ischemic stroke (AIS) and their consequences, including prognosis. PATIENTS/METHODS: We studied 98 AIS patients, aged 74±12 years, including 74 (75.5%) thrombolysed individuals. We determined serum LPS and zonulin, a marker of gut permeability, along with protein carbonylation (PC), fibrin clot properties, and thrombin generation on admission, at 24 hours and 3 months. Stroke severity was assessed using the NIH Stroke Scale (NIHSS). Stroke functional outcome using modified Rankin Scale (mRS) and stroke-related mortality were evaluated at 3 months. RESULTS: Serum LPS and zonulin on admission were associated with time since symptom onset (r=0.57, p<0.0001 and r=0.40, p<0.0001). Baseline LPS correlated with PC (r=0.51, p<0.0001) but not with coagulation and fibrinolysis markers. LPS levels increased at 24 hours in thrombolysed patients (p<0.001) and correlated with the NIHSS score (r=0.31, p=0.002) and PC (r=0.32, p=0.0057). Both LPS and zonulin levels measured at 24 hours increased the odds of having unfavorable mRS (OR=1.22, 95%CI, 1.04-1.42 and 2.36, 95%CI, 1.24-4.49 per unit). Elevated LPS, but not zonulin, was associated with stroke-related mortality (OR=1.26, 95%CI, 1.02-1.55 per unit). CONCLUSIONS: In AIS patients intestinal permeability is mainly driven by increasing time since the symptom onset. Our findings suggest that LPS with a trend toward its further rise following thrombolysis adversely affect neurological functional outcomes and 3-month mortality.

Changes in the exposure to cardiovascular disease risk factors in an 18 year follow-up study of a cohort of middle age urban residents. The Polish arm of the HAPIEE study.

BACKGROUND: Cross-sectional studies revealed that risk factor exposure increases with age but after reaching its peak decreases. This decline may be attributed to higher mortality among exposed individuals, lifestyle, or natural physiological changes related to age. Only prospective observations at the individual level provide credible insights of exposure during the transition from middle to old age. This study addresses changes in cardiovascular risk factors among older urban residents in Poland over an 18-year period. METHODS: The study analyzed data from the Polish arm of the Health, Alcohol and Psychosocial factors In Eastern Europe (HAPIEE) project, a prospective cohort study investigating cardiovascular disease determinants. The sample included 312 participants (46-69 years). Data on demographic characteristics, blood lipids, blood pressure, body mass index (BMI), fasting glucose, and smoking status were collected at baseline and during re-examination. RESULTS: The analysis yielded a decrease in diastolic blood pressure, total cholesterol, LDL-cholesterol, and non-HDL cholesterol concentrations. However, BMI and fasting glucose levels increased. The decrease in blood pressure was mainly attributed to treatment effects, while the reduction in lipid concentrations was observed regardless of treatment. In addition, smoking prevalence decreased over the course of 18 years. CONCLUSIONS: The results of the prospective nearly 20 year observation at the individual level confirm findings from repeated cross-sectional studies on decrease in lipid concentrations, blood pressure and prevalence of smoking in older individuals.

Association between dietary (poly)phenol intake and the ATHLOS Healthy Ageing Scale in the Polish arm of the HAPIEE study.

Inverse association between (poly)phenol intake and age-related disorders has been demonstrated; however, little is known whether they affect comprehensively assessed healthy aging. The aim of this study was to evaluate the associations between the intake of (poly)phenol (including selected classes and subclasses) and healthy aging scores related to biopsychosocial aspects of health and functioning. A cross-sectional study was performed using data on 9774 randomly selected citizens of Krakow (Poland) who were 45-69 years of age. Dietary (poly)phenol intake was evaluated using a food frequency questionnaire and matching food consumption data with the Phenol-Explorer database. The healthy aging scores were estimated from the ATHLOS Healthy Ageing Scale (HAS) developed by the Ageing Trajectories of Health-Longitudinal Opportunities and Synergies (ATHLOS) consortium. Beta coefficients were calculated using multivariable linear regression models. In multivariable adjusted models, there were significant positive associations between the ATHLOS HAS score and intake of total (poly)phenols (b per increase of 100 mg/day = 0.081; 95% CI, 0.050; 0.112) and among main classes of (poly)phenols with phenolic acids (b = 0.139; 95% CI, 0.098; 0.180). Intake of remaining classes of (poly)phenols (flavonoids, lignans, stilbenes, and others) was not related to the ATHLOS HAS score. Among individual classes studied, hydroxycinnamic acids, flavonols, flavones, and dihydrochalcones were associated with better healthy aging. The findings suggest the beneficial effect of total dietary (poly)phenol and some classes and subclasses of (poly)phenol intake in terms of healthy aging in Poland. These findings should be confirmed in other settings and with prospective data.

Comparison of anthropometric indicators related to overweight and obesity by place of residence in a local community with a high social deprivation rate - a cross-sectional study.

INTRODUCTION AND OBJECTIVE: Obesity is considered a major public health concern. The aim of the study is to compare anthropometric indicators related to overweight and obesity by place of residence in a local community with a high social deprivation rate, based on the example of residents of the Janów District in eastern Poland, taking into account gender strata differences. MATERIAL AND METHODS: The cross-sectional epidemiological study was carried out in a study group of 3,752 individuals. The following anthropometric measurements and laboratory tests were performed to identify the anthropometric indicators related to overweight and obesity: body mass index (BMI), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) and body adiposity index (BAI). RESULTS: Mean age of the study group was 51.92 ± 8.15. Overweight and obesity-related indicators were more prevalent in rural than urban areas among women, and were as follows: BMI (28.77 ± 5.37 vs. 27.62 ± 5.09; p < 0.001), WHR (0.87 ± 0.07 vs. 0.85 ± 0.07; p < 0.001), WHtR (0.57 ± 0.09 vs. 0.57 ± 0.08; p < 0.001) and BAI (33.58 ± 5.48 vs. 32.82 ± 5.4; p = 0.002). Men's mean WHR was higher in rural than in urban areas (0.96 ± 0.07 vs. 0.95 ± 0.62; p < 0.001). CONCLUSIONS: The study shows that women living in rural areas had a mean BMI that was 1.1 higher than that of women living in urban areas, as well as 0.02 higher WHR and WHtR and 0.8 higher BAI. In contrast, men living in rural areas had a 0.001 higher WHtR and WHR than men living in urban areas. In the multivariable models, after having considered potential confounding variables, women living in rural areas had approximately a 60% higher probability of being obese, while men had approximately a 30% higher probability of being obese.

Challenges of Diphtheria Toxin Detection.

Diphtheria toxin (DT) is the main virulence factor of Corynebacterium diphtheriae, C. ulcerans and C. pseudotuberculosis. Moreover, new Corynebacterium species with the potential to produce diphtheria toxin have also been described. Therefore, the detection of the toxin is the most important test in the microbiological diagnosis of diphtheria and other corynebacteria infections. Since the first demonstration in 1888 that DT is a major virulence factor of C. diphtheriae, responsible for the systemic manifestation of the disease, various methods for DT detection have been developed, but the diagnostic usefulness of most of them has not been confirmed on a sufficiently large group of samples. Despite substantial progress in the science and diagnostics of infectious diseases, the Elek test is still the basic recommended diagnostic test for DT detection. The challenge here is the poor availability of an antitoxin and declining experience even in reference laboratories due to the low prevalence of diphtheria in developed countries. However, recent and very promising assays have been developed with the potential for use as rapid point-of-care testing (POCT), such as ICS and LFIA for toxin detection, LAMP for tox gene detection, and biosensors for both.

The whole genome sequence of Polish vaccine strain Mycobacterium bovis BCG Moreau.

Currently, tuberculosis immunoprophylaxis is based solely on Bacillus Calmette-Guérin (BCG) vaccination, and some of the new potential tuberculosis vaccines are based on the BCG genome. Therefore, it is reasonable to analyze the genomes of individual BCG substrains. The aim of this study was the genetic characterization of the BCG-Moreau Polish (PL) strain used for the production of the BCG vaccine in Poland since 1955. Sequencing of different BCG lots showed that the strain was stable over a period of 59 years. As a result of comparison, BCG-Moreau PL with BCG-Moreau Rio de Janeiro (RDJ) 143 single nucleotide polymorphisms (SNPs) and 32 insertion/deletion mutations (INDELs) were identified. However, the verification of these mutations showed that the most significant were accumulated in the BCG-Moreau RDJ genome. The mutations unique to the Polish strain genome are 1 SNP and 2 INDEL. The strategy of combining short-read sequencing with long-read sequencing is currently the most optimal approach for sequencing bacterial genomes. With this approach, the only available genomic sequence of BCG-Moreau PL was obtained. This sequence will primarily be a reference point in the genetic control of the stability of the vaccine strain in the future. The results enrich knowledge about the microevolution and attenuation of the BCG vaccine substrains. IMPORTANCE: The whole genome sequence obtained is the only genomic sequence of the strain that has been used for vaccine production in Poland since 1955. Sequencing of different BCG lots showed that the strain was stable over a period of 59 years. The comprehensive genomic analysis performed not only enriches knowledge about the microevolution and attenuation of the BCG vaccine substrains but also enables the utilization of identified markers as a reference point in the genetic control and identity tests of the stability of the vaccine strain in the future.

Extracting accurate materials data from research papers with conversational language models and prompt engineering.

There has been a growing effort to replace manual extraction of data from research papers with automated data extraction based on natural language processing, language models, and recently, large language models (LLMs). Although these methods enable efficient extraction of data from large sets of research papers, they require a significant amount of up-front effort, expertise, and coding. In this work, we propose the ChatExtract method that can fully automate very accurate data extraction with minimal initial effort and background, using an advanced conversational LLM. ChatExtract consists of a set of engineered prompts applied to a conversational LLM that both identify sentences with data, extract that data, and assure the data's correctness through a series of follow-up questions. These follow-up questions largely overcome known issues with LLMs providing factually inaccurate responses. ChatExtract can be applied with any conversational LLMs and yields very high quality data extraction. In tests on materials data, we find precision and recall both close to 90% from the best conversational LLMs, like GPT-4. We demonstrate that the exceptional performance is enabled by the information retention in a conversational model combined with purposeful redundancy and introducing uncertainty through follow-up prompts. These results suggest that approaches similar to ChatExtract, due to their simplicity, transferability, and accuracy are likely to become powerful tools for data extraction in the near future. Finally, databases for critical cooling rates of metallic glasses and yield strengths of high entropy alloys are developed using ChatExtract.

Elevated factor XI is associated with increased risk of recurrent cerebral venous sinus thrombosis: a cohort study.

Cerebral venous sinus thrombosis (CVST) has no identified cause in 15% of cases. Elevated factors (F) VIII and FXI have been associated with thromboembolism, but data on CVST are limited. We hypothesized that elevated plasma FVIII and FXI predispose to first and recurrent CVST. In 50 CVST survivors aged < 60 years, following anticoagulant cessation and in 50 controls, we determined plasma FVIII and FXI, along with fibrin clot properties: lysis time, permeability, maximum D-dimer (D-Dmax), and maximum rate of D-dimer increase (D-Drate). We recorded CVST recurrence during a follow-up of 58.5 (55.0-60.0) months. Plasma FVIII was 22.7% higher in CVST than in controls, with elevated FVIII > 150% in 13 (26%) vs. 4 (8%) patients, respectively (p = 0.02). Median FXI tended to be higher in CVST vs. controls (110.5 [99.0-117-0]% vs. 104.5 [97.0-116.0]%, p = 0.07), while FXI > 120% was observed more commonly in the former group (12 [24%] vs. 4 [8%], respectively, p = 0.03). Patients with FVIII > 150% were less likely to achieve complete recanalization compared with the remainder (2 [15.4%] vs. 28 [75.7%], respectively; p < 0.001). Eight patients (16%) experienced CVST recurrence. They had higher baseline FXI, but not FVIII, as compared with the remainder (125.5 [114.5-140.0]% vs. 107.5 [102.0-117.0]%, respectively, p = 0.01). Patients with FXI > 120% were four times more likely to have recurrent CVST (5 [62.5%] vs. 7 [16.7%], respectively; p = 0.01). Plasma FXI > 120% could represent a novel risk factor for first and recurrent CVST. Given advances in anti-FXI agents, CVST might be another indication for this emerging treatment.

Strong Room-Temperature Ferromagnetism in Ultrathin NiOOH Nanosheets through Surfactant Manipulation.

Two-dimensional (2D) ferromagnetic (FM) materials with nanoscale thickness and spontaneous net magnetization have emerged as a promising class of functional materials for applications in next-generation spintronics, quantum processing, and data storage devices. However, most 2D materials exhibit weak FM even at low temperatures, limiting their potential applications in many technological fields. The fabrication of strong room-temperature FM 2D materials is highly desirable for the development of practical applications. Here, we demonstrate an ionic layer epitaxy strategy to synthesize few-layered NiOOH nanosheets with strong room-temperature FM and a saturation magnetization up to 409.86 emu cm-3 at 300 K. The results are consistent with the ab initio predictions of a stable FM NiOOH nanolayer structure with an FM configuration. The FM strength of the NiOOH nanosheets can be tuned by controlling the surfactant monolayer density and annealing. This work offers a promising strategy for achieving strong high-temperature FM in 2D materials for spintronic applications.

Protein Carbonylation Contributes to Prothrombotic Fibrin Clot Phenotype in Acute Ischemic Stroke: Clinical Associations.

BACKGROUND: Acute ischemic stroke (AIS) is associated with enhanced oxidative stress and unfavorably altered fibrin clot properties. We investigated determinants of plasma protein carbonylation (PC) in AIS, its impact on the prothrombotic state, and prognostic value during follow-up. METHODS: We included 98 consecutive AIS patients aged 74±12 years (male:female ratio, 50:48 [51%:49%]) at the Neurology Center in Warsaw, Poland, between January and December 2014. As many as 74 (75.5%) patients underwent thrombolysis, and 24 were unsuitable for thrombolysis. We determined plasma PC, along with thrombin generation, fibrin clot permeability, and clot lysis time on admission, at 24 hours, and 3 months. Stroke severity was assessed using the National Institutes of Health Stroke Scale and stroke outcome with the modified Rankin Scale. Hemorrhagic transformation was assessed on the computed tomography scan within 48 hours from the symptom onset, while stroke-related mortality was evaluated at 3 months. RESULTS: On admission, PC levels (median, 4.61 [3.81-5.70] nM/mg protein) were associated with the time since symptom onset (r=0.41; P<0.0001) and with the National Institutes of Health Stroke Scale score (P=0.36; P=0.0003). Higher PC levels on admission correlated with denser fibrin clot formation and prolonged clot lysis time but not with thrombin generation. In thrombolysed patients, lower PC levels were observed after 24 hours (-34%) and at 3 months (-23%; both P<0.001). PC levels at baseline and after 24 hours predicted the modified Rankin Scale score >2 at 3 months (OR, 1.90 [95% CI, 1.21-3.00]; OR, 2.19 [95% CI, 1.39-3.44], respectively). Higher PC at baseline predicted hemorrhagic transformation of stroke (OR, 1.95 [95% CI, 1.02-3.74]) and stroke-related mortality (OR, 2.02 [95% CI, 1.08-3.79]), while higher PC at 24 hours predicted solely stroke-related mortality (OR, 2.11 [95% CI, 1.28-3.46]). CONCLUSIONS: Elevated plasma PC levels in patients with AIS, related to prothrombotic fibrin clot properties, are associated with stroke severity. Thrombolysis reduces the extent of PC. The current study suggests a prognostic value of PC in AIS.

The Relationship between Diet and the Occurrence of Depressive Symptoms in a Community Example with High Rates of Social Deprivation: A Cross-Sectional Study.

Research suggests that various biological and psychosocial mechanisms are involved in the heterogeneous and complex relationship between dietary patterns and depressive symptoms. The occurrence of depressive symptoms is thought to be related to socioeconomic status (SES), with those with lower SES being more likely to experience persistent depression. The aim of the undertaken study was to investigate whether socioeconomic and health variables are associated with dietary assessment in a population with high rates of social deprivation and whether a relationship exists between dietary assessment and depressive symptoms (DS). The respondents' nutrition was evaluated through a qualitative method, using the Perinumeric Periodic Table questionnaire by Starzynska. At the same time, the prevalence of DS was assessed employing the Patient Health Questionnaire-9 (PHQ-9). In the DS screening (PHQ-9 ≥ 10), in the entire study population, the risk of DS was 16.1% (n = 605). In our entire study population, up to 61.2% (n = 2297) of the respondents exhibited poor dietary patterns. In the multivariate model, women with almost adequate or poor dietary assessment were 1.62 and 2.18 times more likely to score at least 10 on the PHQ-9 questionnaire, as compared to women whose dietary assessment was good or adequate. In conclusion, it was determined that sociodemographic variables affect nutritional habits. Women who lived in rural areas limited to a vocational education had significantly poorer diets. Moreover, men, younger men, smokers, and those without chronic diseases were characterized by a poorer dietary assessment. Additionally, women who had a better dietary assessment were significantly more likely to have lower scores on the questionnaire assessing the occurrence of DS (PHQ-9 10).

Trajectories in physical functioning at older age in relation to childhood and adulthood SES and social mobility: a population-based cohort study.

Introduction: Older age is associated with the deterioration of physical functioning (PF), and low PF is strongly related to poor quality of life among older people. We conducted a study to examine the trajectories of PF between middle and old age, considering sex differences as well as the association between socioeconomic status (SES) at different life stages and changes in PF. Methods: We analyzed data from the Polish arm of the HAPIEE (Health, Alcohol and Psychosocial factors In Eastern Europe) study, including 1,116 men and 1,178 women aged 45-64 years at baseline. Adult and childhood SES and social mobility were assessed using a retrospectively focused questionnaire. PF was assessed using the 10-question SF-36 scale at baseline examination, face-to-face re-examination, and three postal surveys, covering up to 20 years (on average, 18 years). We employed Generalized Estimating Equations models to assess changes in PF scores over time and compare PF trajectories across different SES categories. Results: After adjusting for age and other covariates, we found that, in both sexes, participants with always middle or high SES, as well as those who reported upward mobility, had higher PF scores at baseline compared to those with always low SES. A decline in PF between middle and old age was observed in all SES groups; however, the decline was slower in participants with always middle or high SES compared to those with always low SES. Conclusion: This cohort study revealed that lower SES and downward social mobility were cross-sectionally associated with poorer PF, while upward social mobility seemed to largely reverse the effect of low childhood SES. In addition to the cross-sectional associations observed at baseline, advantaged SES was also significantly associated with a slower decline in PF over an 18-year follow-up period.

Elevated plasma factor XI predicts cardiovascular events in patients with type 2 diabetes: a long-term observational study.

BACKGROUND: Type 2 diabetes mellitus (T2DM) patients are at high risk of cardiovascular (CV) events. Factor XI (FXI) is associated with arterial thromboembolism, including myocardial infarction (MI), stroke, and CV mortality. The role of FXI in T2DM is unknown. We investigated whether plasma FXI is associated with CV events in T2DM patients in long-term observation. METHODS: In 133 T2DM patients (aged 66 ± 8 years, 40.6% women, median T2DM duration 5 [2-10] years) we assessed plasma FXI levels, along with fibrin clot properties, thrombin generation, and fibrinolysis proteins. A composite endpoint of MI, stroke, or CV death, as well as CV mortality alone were assessed during a median follow-up of 72 months. RESULTS: Plasma FXI above the 120% upper normal limit was detected in 25 (18.8%) patients and showed positive association with LDL cholesterol and thrombin activatable fibrinolysis inhibitor, but not glycated hemoglobin, inflammatory markers or thrombin generation. The composite endpoint (n = 21, 15.8%) and CV death alone (n = 16, 12%) were more common in patients with elevated FXI (hazard ratio [HR] 10.94, 95% confidence interval [CI] 4.46-26.87, p < 0.001 and HR 7.11, 95% CI 2.61-19.31, p < 0.001, respectively). On multivariable analysis, FXI remained an independent predictor of the composite endpoint and CV death, regardless of concomitant coronary artery disease. CONCLUSIONS: To our knowledge, this study is the first to show that in T2DM patients, elevated FXI could predict major CV events, including mortality, which suggest that anti-FXI agents might be a potential novel antithrombotic option in this disease.

Bandgap Pressure Coefficient of a CH3NH3PbI3 Thin Film Perovskite.

Recent scientific interest in examining the bandgap evolution of a MAPbI3 hybrid perovskite by applying hydrostatic pressure has mostly focused on a room-temperature tetragonal phase. In contrast, the pressure response of a low-temperature orthorhombic phase (OP) of MAPbI3 has not been explored and understood. In this research, we investigate for the first time how hydrostatic pressure alters the electronic landscape of the OP of MAPbI3. Pressure studies using photoluminescence combined with calculations within density functional theory at zero temperature allowed us to identify the main physical factors affecting the bandgap evolution of the OP of MAPbI3. The negative bandgap pressure coefficient was found to be strongly dependent on the temperature (α120K = -13.3 ± 0.1 meV/GPa, α80K = -29.8 ± 0.1 meV/GPa, and α40K = -36.3 ± 0.1 meV/GPa). Such dependence is related to the changes in the Pb-I bond length and geometry in the unit cell as the atomic configuration approaches the phase transition as well as the increasing phonon contribution to octahedral tilting as the temperature increases.

Determinants of body weight changes during COVID-19 pandemic in older urban residents.

INTRODUCTION: COVID­19 pandemic is associated with unfavorable body weight changes. However, little is known about these changes in older individuals, a particularly vulnerable group with limited representation in both direct and online research. OBJECTIVES: The aims of the study were to assess changes in body weight and determinants of thesechanges, and to evaluate the prevalence of COVID­19 history and its impact on the changes in body weight in older individuals. PATIENTS AND METHODS: The analysis included 2076 residents of Kraków, aged 60 to 84 years. Data on sociodemographic factors, lifestyle, history of COVID­19, and changes in body weight were collected in 2021 and 2022 by a postal survey. Multinomial logistic regression analysis was used. RESULTS: COVID­19 tests were performed in 29.3% of the participants, with one­third of them being positive. A total of 14.3% of the participants had any history of COVID­19. Almost two­thirds of the study participants declared no change in their body weight during the pandemic, while 26.2% gained weight. The weight gain was associated with unfavorable sociodemographic and lifestyle conditions. Weight loss was reported by 11.3% of the participants, and it was associated with poor perceived health and a history of COVID­19. After adjusting for covariates, the history of COVID­19 was associated with about 4 times higher odds of weight loss in any case (odds ratio [OR], 2.69; 95% CI, 1.59-4.57 for nonhospitalized, and OR, 18.96; 95% CI, 5.64-63.73 for hospitalized individuals). CONCLUSIONS: Most people with a change in their body weight gained weight due to unfavorable lifestyle modifications, but the history of COVID­19, especially hospitalization, was a strong determinant of body weight loss.

ATHLOS Healthy Aging Scale score as the predictor of all-cause mortality in Poland and Czechia.

Background: The ATHLOS consortium (Aging Trajectories of Health-Longitudinal Opportunities and Synergies) used data from several aging cohorts to develop a novel scale measuring healthy aging comprehensively and globally (ATHLOS Healthy Aging Scale). In the present study, we assessed the predictive performance of the ATHLOS Healthy Aging Scale for all-cause mortality in middle-aged and older adults. Methods: Data from the Polish and Czech HAPIEE (Health Alcohol and Psychosocial factors In Eastern Europe) prospective cohorts were used. There were 10,728 Poles and 8,857 Czechs recruited. The ATHLOS Healthy Aging Scale score was calculated for all participants using data from the baseline examination carried out from 2002 to 2005. The follow-up for all-cause mortality was completed over 14 years. The associations between quintiles of the ATHLOS Healthy Aging Scale and all-cause mortality were estimated using Cox proportional hazards models. Results: A total of 9,922 Polish and 8,518 Czech participants contributed ATHLOS Healthy Aging Scale and mortality data with 1,828 and 1,700 deaths, respectively. After controlling for age, the ATHLOS Healthy Aging Scale score was strongly associated with mortality in a graded fashion for both genders and countries (hazard ratios for lowest vs. highest quintile were 2.98 and 1.96 for Czech and Polish women and 2.83 and 2.66 for Czech and Polish men, respectively). The associations were only modestly attenuated by controlling for education, economic activity, and smoking, and there was further modest attenuation after additional adjustment for self-rated health. Conclusion: The novel ATHLOS Healthy Aging Scale is a good predictor of all-cause mortality in Central European urban populations, suggesting that this comprehensive measure is a useful tool for the assessment of the future health trajectories of older persons.

Therapy with high-dose statins reduces soluble P-selectin: The impact on plasma fibrin clot properties.

OBJECTIVE: Studies on the effect of statins on platelets in patients with coronary artery disease (CAD) yielded inconsistent results. We sought to investigate whether high-dose statin therapy reduces plasma concentrations of soluble P-selectin (sP-selectin), a well-established platelet activation marker and if such changes can affect fibrin clot properties, which are unfavorably altered in CAD patients. METHODS: We studied 130 consecutive patients with advanced CAD who did not achieve the target LDL cholesterol on statins. At baseline and after 6-12 months of treatment with atorvastatin 80 mg/day or rosuvastatin 40 mg/day, soluble plasma sP-selectin, along with plasma fibrin clot permeability (Ks), clot lysis time (CLT), thrombin generation and fibrinolysis proteins were determined. RESULTS: Before high-intensity statin treatment, lower Ks and longer CLT values were associated with increased sP-selectin (ß -0.27 [95% CI -0.44 to -0.10] and ß 0.21 [95% CI 0.01 to 0.41]; both p < 0.05, respectively) also after adjustment for potential confounders. sP-selectin, alongside fibrin features and other variables at baseline showed no association with lipid profile. On high-dose statin therapy, there was 32% reduction in sP-selectin levels (p < 0.001). On-treatment change (Δ) in sP-selectin correlated with ΔKs and ΔCLT (r = -0.32, p < 0.001 and r = 0.22, p = 0.011, respectively), but not with cholesterol and C-reactive protein lowering. We did not observe any associations between post-treatment sP-selectin levels and lipids, fibrin clot properties or thrombin generation. CONCLUSIONS: High-dose statin therapy reduces markedly sP-selectin levels in association with improved fibrin clot phenotype, which highlights the contribution of platelet-derived proteins to a prothrombotic state in hypercholesterolemia and statin-induced antithrombotic effects.

Competition for recruitment in SARS-CoV-2 Trials in the United States: a longitudinal cohort analysis.

OBJECTIVE: Competition among trials for patient enrollment can impede recruitment. We hypothesized that this occurred early in the COVID-19 pandemic, when an unprecedented number of clinical trials were launched. We performed a simple and multivariable regression analysis evaluating the relationship between the proportion of SARS-CoV-2 investigational trial sites within each USA state with unsuccessful patient-participant recruitment and: (i) the proportion of cases required to reach state recruitment goals; (ii) state population based on data from the US Census; and, (iii) number of trial sites per state. RESULTS: Our study included 151 clinical trials. The proportion of trials with successful recruitment was 72.19% (109 of 151 trials). We did not find a significant relationship between unsuccessful patient-participant recruitment, state recruitment goals, state population or the number of trial sites per state in both our simple and multivariable regression analyses. Our results do not suggest that early in the COVID-19 pandemic, competition for patient-participants impeded successful recruitment in SARS-CoV-2 trials. This may reflect the unique circumstances of the first few months of the pandemic in the United States, in which the number and location of SARS-CoV-2 cases was sufficient to meet trial recruitment requirements, despite the large number of trials launched.