The effect of alirocumab, a PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor, on coronary plaque burden in patients with familial hypercholesterolemia has not been addressed. Our aim ...was to assess changes in coronary plaque burden and its characteristics after treatment with alirocumab by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of a noninvasive analysis of coronary computed tomographic angiography in asymptomatic subjects with familial hypercholesterolemia receiving optimized and stable treatment with maximum tolerated statin dose with or without ezetimibe.
This study is a phase IV, open-label, multicenter, single-arm clinical trial to assess changes in coronary plaque burden and its characteristics after 78 weeks of treatment with alirocumab in patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent an initial coronary computed tomographic angiography at baseline and another at 78 weeks. Every patient received 150 mg of alirocumab subcutaneiously every 14 days in addition to high-intensity statin therapy. The main outcome was the change on coronary plaque burden and its characteristics by quantification and characterization of atherosclerotic plaque throughout the coronary tree on the basis of analysis of coronary computed tomographic angiography.
The study was completed by 104 patients. The median age was 53.3 (46.2-59.4) years. Of these patients, 54 were women (51.9%). Median low-density lipoprotein cholesterol was 138.9 (117.5-175.3) mg/dL at entry and 45.0 (36.0-65.0) mg/dL at follow-up (
<0.001). Coronary plaque burden changed from 34.6% (32.5%-36.8%) at entry to 30.4% (27.4%-33.4%) at follow-up (
<0.001). A significant change in the characteristics of the coronary atherosclerosis was also found: an increase in the proportion of calcified (+0.3%;
<0.001) and mainly fibrous (+6.2%;
<0.001) plaque, accompanied by a decrease in the percentage of fibro-fatty (-3.9%;
<0.001) and necrotic plaque (-0.6%;
<0.001).
Treatment with alirocumab in addition to high-intensity statin therapy resulted in significant regression of coronary plaque burden and plaque stabilization on coronary computed tomographic angiography over 78 weeks in these groups of patients with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. ARCHITECT (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) could link and explain ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) results.
URL: https://www.
gov; Unique identifier: NCT05465278.
Gamification is increasingly used for better content assimilation. However, it is hardly used in theoretical and technical courses related to building and architecture. This study focuses on ...assessing the use of gamification with Kahoot! to arouse students' interest and to ease content assimilation. Experimentation was undertaken during the 2020/2021 and 2021/2022 academic years. All students enrolled in the course participated in experimentation: 67 and 65 students, respectively. Gamification sessions took place in the middle and at the end of each academic year (the week before partial exams). Students were also surveyed to assess their degree of satisfaction with gamification sessions. The results showed that gamification dynamics improved students' performance in exams, obtaining a lower percentage of failures and increasing higher marks. Cluster analysis results also showed that students' performance in Kahoot! is not a clear indicative of their performance in exams, so it is useful as a self-assessment tool. Moreover, most students positively assessed gamification sessions for better content assimilation. This study stresses the implementation potential of Kahoot! in teaching dynamics in university degrees in architecture and building engineering.
La principal estrategia para el control de la malaria, según la Organización Mundial de la Salud (OMS), es un diagnóstico rápido y adecuado seguido de un tratamiento efectivo. Los laboratorios de ...referencia de microbiología tienen entre sus funciones el desarrollo y validación de nuevas metodologías diagnósticas para ayudar al control y erradicación de la malaria en el mundo y en nuestro caso para evitar la reintroducción en nuestro país. En este trabajo se hace una revisión de los métodos más extendidos para el diagnóstico de malaria: i) métodos clásicos, como son la microscopía y los test de diagnóstico rápido, ii) métodos moleculares, como PCR y LAMP, y, iii) por último, los nuevos avances en microscopía automática e inteligencia artificial.
Calcium signaling in the brain is fundamental to the learning and memory process and there is evidence to suggest that its dysfunction is involved in the pathological pathways underlying Alzheimer's ...disease (AD). Recently, the calcium hypothesis of AD has received support with the identification of the non-selective Ca(2+)-permeable channel CALHM1. A genetic polymorphism (p. P86L) in CALHM1 reduces plasma membrane Ca(2+) permeability and is associated with an earlier age-at-onset of AD. To investigate the role of CALHM1 variants in early-onset AD (EOAD), we sequenced all CALHM1 coding regions in three independent series comprising 284 EOAD patients and 326 controls. Two missense mutations in patients (p.G330D and p.R154H) and one (p.A213T) in a control individual were identified. Calcium imaging analyses revealed that while the mutation found in a control (p.A213T) behaved as wild-type CALHM1 (CALHM1-WT), a complete abolishment of the Ca(2+) influx was associated with the mutations found in EOAD patients (p.G330D and p.R154H). Notably, the previously reported p. P86L mutation was associated with an intermediate Ca(2+) influx between the CALHM1-WT and the p.G330D and p.R154H mutations. Since neither expression of wild-type nor mutant CALHM1 affected amyloid ß-peptide (Aß) production or Aß-mediated cellular toxicity, we conclude that rare genetic variants in CALHM1 lead to Ca(2+) dysregulation and may contribute to the risk of EOAD through a mechanism independent from the classical Aß cascade.
To assess the associations between eating speed, adiposity, cardiometabolic risk factors, and diet quality in a cohort of Spanish preschool-children.
A cross-sectional study in 1371 preschool age ...children (49% girls; mean age, 4.8 ± 1.0 years) from the Childhood Obesity Risk Assessment Longitudinal Study (CORALS) cohort was conducted. After exclusions, 956 participants were included in the analyses. The eating speed was estimated by summing the total minutes used in each of the 3 main meals and then categorized into slow, moderate, or fast. Multiple linear and logistic regression models were fitted to assess the β-coefficient, or OR and 95% CI, between eating speed and body mass index, waist circumference, fat mass index (FMI), blood pressure, fasting plasma glucose, and lipid profile.
Compared with participants in the slow-eating category, those in the fast-eating category had a higher prevalence risk of overweight/obesity (OR, 2.9; 95% CI, 1.8-4.4; P < .01); larger waist circumference (β, 2.6 cm; 95% CI, 1.5-3.8 cm); and greater FMI (β, 0.3 kg/m2; 95% CI, 0.1-0.5 kg/m2), systolic blood pressure (β, 2.8 mmHg; 95% CI, 0.6-4.9 mmHg), and fasting plasma glucose levels (β, 2.7 mg/dL, 95% CI, 1.2-4.2 mg/dL) but lower adherence to the Mediterranean diet (β, −0.5 points; 95% CI, −0.9 to −0.1 points).
Eating fast is associated with higher adiposity, certain cardiometabolic risk factors, and lower adherence to a Mediterranean diet. Further long-term and interventional studies are warranted to confirm these associations.
To estimate the infection fatality risk for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), based on deaths with confirmed coronavirus disease 2019 (covid-19) and excess deaths from all ...causes.
Nationwide seroepidemiological study.
First wave of covid-19 pandemic in Spain.
Community dwelling individuals of all ages.
The main outcome measure was overall, and age and sex specific, infection fatality risk for SARS-CoV-2 (the number of covid-19 deaths and excess deaths divided by the estimated number of SARS-CoV-2 infections) in the community dwelling Spanish population. Deaths with laboratory confirmed covid-19 were obtained from the National Epidemiological Surveillance Network (RENAVE) and excess all cause deaths from the Monitoring Mortality System (MoMo), up to 15 July 2020. SARS-CoV-2 infections in Spain were derived from the estimated seroprevalence by a chemiluminescent microparticle immunoassay for IgG antibodies in 61 098 participants in the ENE-COVID nationwide seroepidemiological survey between 27 April and 22 June 2020.
The overall infection fatality risk was 0.8% (19 228 of 2.3 million infected individuals, 95% confidence interval 0.8% to 0.9%) for confirmed covid-19 deaths and 1.1% (24 778 of 2.3 million infected individuals, 1.0% to 1.2%) for excess deaths. The infection fatality risk was 1.1% (95% confidence interval 1.0% to 1.2%) to 1.4% (1.3% to 1.5%) in men and 0.6% (0.5% to 0.6%) to 0.8% (0.7% to 0.8%) in women. The infection fatality risk increased sharply after age 50, ranging from 11.6% (8.1% to 16.5%) to 16.4% (11.4% to 23.2%) in men aged 80 or more and from 4.6% (3.4% to 6.3%) to 6.5% (4.7% to 8.8%) in women aged 80 or more.
The increase in SARS-CoV-2 infection fatality risk after age 50 appeared to be more noticeable in men than in women. Based on the results of this study, fatality from covid-19 was greater than that reported for other common respiratory diseases, such as seasonal influenza.
Objective
To compare the efficacy of infliximab (IFX) versus adalimumab (ADA) as a first‐line biologic drug over 1 year of treatment in a large series of patients with refractory uveitis due to ...Behçet's disease (BD).
Methods
We conducted an open‐label multicenter study of IFX versus ADA for BD‐related uveitis refractory to conventional nonbiologic treatment. IFX or ADA was chosen as the first‐line biologic agent based on physician and patient agreement. Patients received 3–5 mg/kg intravenous IFX at 0, 2, and 6 weeks and every 4–8 weeks thereafter, or 40 mg subcutaneous ADA every other week without a loading dose. Ocular parameters were compared between the 2 groups.
Results
The study included 177 patients (316 affected eyes), of whom 103 received IFX and 74 received ADA. There were no significant baseline differences between treatment groups in main demographic features, previous therapy, or ocular sign severity. After 1 year of therapy, we observed an improvement in all ocular parameters in both groups. However, patients receiving ADA had significantly better outcomes in some parameters, including improvement in anterior chamber inflammation (92.31% versus 78.18% for IFX; P = 0.06), improvement in vitritis (93.33% versus 78.95% for IFX; P = 0.04), and best‐corrected visual acuity (mean ± SD 0.81 ± 0.26 versus 0.67 ± 0.34 for IFX; P = 0.001). A nonsignificant difference was seen for macular thickness (mean ± SD 250.62 ± 36.85 for ADA versus 264.89 ± 59.74 for IFX; P = 0.15), and improvement in retinal vasculitis was similar between the 2 groups (95% for ADA versus 97% for IFX; P = 0.28). The drug retention rate was higher in the ADA group (95.24% versus 84.95% for IFX; P = 0.042).
Conclusion
Although both IFX and ADA are efficacious in refractory BD‐related uveitis, ADA appears to be associated with better outcomes than IFX after 1 year of follow‐up.
The eukaryotic chaperonin CCT (chaperonin containing TCP-1) uses cavities built into its double-ring structure to encapsulate and to assist folding of a large subset of proteins. CCT can inhibit ...amyloid fibre assembly and toxicity of the polyQ extended mutant of huntingtin, the protein responsible for Huntington's disease. This raises the possibility that CCT modulates other amyloidopathies, a still-unaddressed question. We show here that CCT inhibits amyloid fibre assembly of α-synuclein A53T, one of the mutants responsible for Parkinson's disease. We evaluated fibrillation blockade in α-synuclein A53T deletion mutants and CCT interactions of full-length A53T in distinct oligomeric states to define an inhibition mechanism specific for α-synuclein. CCT interferes with fibre assembly by interaction of its CCTζ and CCTγ subunits with the A53T central hydrophobic region (NAC). This interaction is specific to NAC conformation, as it is produced once soluble α-synuclein A53T oligomers form and blocks the reaction before fibres begin to grow. Finally, we show that this association inhibits α-synuclein A53T oligomer toxicity in neuroblastoma cells. In summary, our results and those for huntingtin suggest that CCT is a general modulator of amyloidogenesis via a specific mechanism.
El objetivo del presente estudio fue analizar la relación entre la cohesión grupal de los jugadores del equipo con la intención de persistencia en el equipo. Para ello, un total de 271 jugadores/as ...de balonmano, baloncesto y fútbol con edades comprendidas entre 15 y 43 años (M = 21.43; DT = 5.31), completaron las medidas de cohesión grupal y la persistencia al equipo. Se trata de un estudio transversal donde el modelado de ecuaciones estructurales fue utilizado para testar las relaciones entre ambas variables. Los resultados revelaron correlaciones positivas de los factores de cohesión tarea y social con la persistencia en el equipo. Además, el análisis de regresión mostró una predicción positiva y significativa entre la cohesión tarea y la intención de persistir en el equipo. Sin embargo, la cohesión social no mostró una predicción significativa respecto al sentimiento de persistencia al equipo. Por lo tanto, la unión de los jugadores en las tareas de entrenamiento y durante el desarrollo de la competición, podría contribuir al sentimiento de persistir en un equipo, aumentando el bloque de jugadores durante varias temporadas.
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