Long-term sex differences in atherosclerotic cardiovascular disease in individuals with heterozygous familial hypercholesterolaemia in Spain: a study using data from SAFEHEART, a nationwide, multicentre, prospective cohort study.

BACKGROUND: Sex differences in atherosclerotic cardiovascular disease (ASCVD) in familial hypercholesterolaemia have been reported but are not fully established. We aimed to assess sex differences in the risk of ASCVD and life-time burden of ASCVD in patients with heterozygous familial hypercholesterolaemia. METHODS: SAFEHEART is a nationwide, multicentre, long-term prospective cohort study conducted in 25 tertiary care hospitals and one regional hospital in Spain. Participants in the SAFEHEART study aged 18 years or older with genetically confirmed familial hypercholesterolaemia were included in our analysis. Data were obtained between Jan 26, 2004, and Nov 30, 2022. ASCVD and age at onset were documented at enrolment and at follow-up. Our aim was to investigate the differences by sex in the risk and burden of ASCVD in patients with heterozygous familial hypercholesterolaemia, over the study follow-up and over the life course. The SAFEHEART study is registered with ClinicalTrials.gov, NCT02693548. FINDINGS: Of the 5262 participants in SAFEHEART at the time of analysis, 3506 (1898 [54·1%] female and 1608 [45·9%] male participants) met the inclusion criteria and were included in the current study. Mean age was 46·1 years (SD 15·5) and median follow-up was 10·3 years (IQR 6·4-13·0). Mean on-treatment LDL-cholesterol at follow-up was 3·1 mmol/L (SD 1·4) in females and 3·0 mmol/L (1·5) in males. LDL-cholesterol reductions over time were similar in both sexes (1·39 mmol/L [95% CI 1·30-1·47] absolute reduction in females vs 1·39 mmol/L [1·29-1·48] in males; p=0·98). At enrolment, 130 (6·8%) females and 304 (18·9%) males (p<0·0001) had cardiovascular disease. During follow-up, 134 (7·1%) females and 222 (13·8%) males (p<0·0001) had incident cardiovascular events. Median age at first ASCVD event (mostly due to coronary artery disease) was 61·6 years (IQR 50·0-71·4) in females and 50·6 years (42·0-58·6) in males (p<0·0001). The adjusted hazard ratio for ASCVD in males compared with females during follow-up was 1·90 (95% CI 1·49-2·42) and for cardiovascular death was 1·74 (1·11-2·73). Major adverse cardiovascular disease event (MACE)-free survival from birth was lower in males than females (hazard ratio 3·52 [95% CI 2·98-4·16]; p<0·0001). Median MACE-free survival time was 90·1 years (95% CI 86·5-not estimable) in females and 71·0 years (69·2-74·6) in males. The age at which 25% of female participants have had a MACE event was 74·9 years, this figure was 55·5 years in male participants. INTERPRETATION: Our findings suggest that the burden and risk of ASCVD are markedly lower in females than males with familial hypercholesterolaemia. The impact of sex needs to be considered to improve risk stratification and personalised management in patients with heterozygous familial hypercholesterolaemia. FUNDING: Fundación Hipercolesterolemia Familiar, the Instituto de Salud Carlos III, and Next Generation EU funds from the Recovery and Resilience Mechanism Program. TRANSLATION: For the Spanish translation of the abstract see Supplementary Materials section.

Concepciones y Prácticas Evaluativas en la Formación Inicial del Profesorado en Educación Física

La evaluación ha dejado de ser una instancia que sólo certifica el logro alcanzado a través de una calificación, sino actualmente se entiende como un elemento fundamental para favorecer los procesos de enseñanza-aprendizaje. El objetivo del presente estudio fue "Conocer las concepciones y prácticas evaluativas del alumnado y profesorado de la FIPEF (Formación Inicial del Profesorado en Educación Física) de dos campus universitarios de la zona sur austral de Chile". Para ello, se contó con una muestra de 219 alumnos y alumnas (edad M = 21.6 y dt. = 2.8) de dos campus universitarios que cursaban Formación Inicial del Profesorado en Educación Física (FIPEF) y 21 profesores y profesoras (edad M = 50.3 y dt. = 13.2). Se aplicó el "Cuestionario para el estudio del sistema de evaluación en la formación inicial del profesorado de educación física" de forma virtual, sometiendo los resultados a pruebas estadísticas como la media, desviación típica y pruebas inferenciales. Los principales resultados dejan ver la presencia de metodologías e instrumentos tradicionales de evaluación, así como, una apreciación diferenciada entre alumnado vs. profesorado. Sin embargo, se puede constatar la presencia de intencionalidad formativa en las acciones implementadas por el profesorado.

The evaluation has ceased to be a mere instance that only certifies the achievement through a grade; rather, it is currently understood as a fundamental element to promote teaching and learning processes. The objective of the present study was to "Understand the conceptions and evaluative practices of students and faculty in the FIPEF (Initial Teacher Education in Physical Education) of two university campuses in the southernmost region of Chile." For this purpose, a sample of 219 students (age M = 21.6 and SD = 2.8) from two university campuses undergoing Initial Teacher Education in Physical Education (FIPEF) and 21 teachers (age M = 50.3 and SD = 13.2) was used. The "Questionnaire for the study of the evaluation system in the initial teacher education of physical education" was administered in a virtual manner, subjecting the results to statistical tests such as mean, standard deviation, and inferential tests. The main results reveal the presence of traditional evaluation methodologies and instruments, as well as a differentiated perception between students and faculty. However, there is evidence of formative intent in the actions implemented by the faculty.

A avaliação deixou de ser apenas uma instância que certifica a conquista por meio de uma nota; atualmente, é compreendida como um elemento fundamental para promover os processos de ensino e aprendizagem. O objetivo do presente estudo foi "Compreender as concepções e práticas avaliativas dos estudantes e professores da FIPEF (Formação Inicial de Professores de Educação Física) de dois campi universitários na região sul-austral do Chile." Para isso, contamos com uma amostra de 219 alunos (idade M = 21,6 e dp. = 2,8) de dois campi universitários que cursavam a Formação Inicial de Professores de Educação Física (FIPEF) e 21 professores (idade M = 50,3 e dp. = 13,2). Foi aplicado o "Questionário para o estudo do sistema de avaliação na formação inicial de professores de educação física" de forma virtual, sujeitando os resultados a testes estatísticos como média, desvio padrão e testes inferenciais. Os principais resultados revelam a presença de metodologias e instrumentos tradicionais de avaliação, bem como uma percepção diferenciada entre alunos e professores. No entanto, há evidências de intencionalidade formativa nas ações implementadas pelos professores.

North American pitseed goosefoot (Chenopodium berlandieri) is a genetic resource to improve Andean quinoa (C. quinoa).

Pitseed goosefoot (Chenopodium berlandieri) is a free-living North American member of an allotetraploid complex that includes the Andean pseudocereal quinoa (C. quinoa). Like quinoa, pitseed goosefoot was domesticated, possibly independently, in eastern North America (subsp. jonesianum) and Mesoamerica (subsp. nuttaliae). To test the utility of C. berlandieri as a resource for quinoa breeding, we produced the whole-genome DNA sequence of PI 433,231, a huauzontle from Puebla, México. The 1.295 Gb genome was assembled into 18 pseudomolecules and annotated using RNAseq data from multiple tissues. Alignment with the v.2.0 genome of Chilean-origin C. quinoa cv. 'QQ74' revealed several inversions and a 4A-6B reciprocal translocation. Despite these rearrangements, some quinoa x pitseed goosefoot crosses produce highly fertile hybrids with faithful recombination, as evidenced by a high-density SNP linkage map constructed from a Bolivian quinoa 'Real-1' × BYU 937 (Texas coastal pitseed goosefoot) F2 population. Recombination in that cross was comparable to a 'Real-1' × BYU 1101 (Argentine C. hircinum) F2 population. Furthermore, SNP-based phylogenetic and population structure analyses of 90 accessions supported the hypothesis of multiple independent domestications and descent from a common 4 × ancestor, with a likely North American Center of Origin.

Circulating miR-6821-5p levels and coronary calcification in asymptomatic familial hypercholesterolemia patients.

BACKGROUND AND AIMS: Premature atherosclerotic cardiovascular disease (CVD) is a clinic characteristic of familial hypercholesterolemia (FH). Coronary calcium score (CCS) is a highly used imaging modality to evidence atherosclerotic plaque burden. microRNAs (miRNAs) are non-coding RNAs that epigenetically regulate gene expression. Here, we investigated whether CCS associates with a specific miRNA-signature in FH-patients. METHODS: Patients with genetic diagnosis of FH (N = 86) from the nationwide SAFEHEART-cohort were investigated by computed tomography angiography imaging and classified depending on the presence of coronary calcification in FH-CCS (+) and FH-CCS (-) groups by the Agatston score. Differential miRNA profiling was performed in two stages: first by Affymetrix microarray technology (high-throughput differential profiling-studies) and second by RT-PCR using TaqMan-technology (analytical RT-qPCR study) in plasma of the two patient groups. RESULTS: miR-193a-5p, miR-30e-5p and miR-6821-5p levels were significantly higher in FH-CCS (+) compared to FH-CCS (-). miR-6821-5p was the best miRNA to discriminate FH-patients CCS(+), according to receiver operating characteristic (ROC) analysis (AUC: 0.70 ± 0.06, p = 0.006). High miR-6821-5p levels were associated with older age (p = 0.03) and high LDL-burden (p = 0.014) using a ROC-derived cut-off value. However, miR-6821-5p did not correlate with age in either the CCS- or CCS + group. Genes involved in calcification processes were identified by in silico analysis. The relation of cell-calcification and expression levels of miR-6821-5p, BMP2 and SPP1 was validated experimentally in human vascular smooth muscle cell cultures. CONCLUSIONS: Up-regulated levels of miR-6821-5p are found in the plasma of asymptomatic FH-patients with coronary calcified atherosclerotic plaques, as well as in isolated human vascular smooth muscle cells expressing the pro-calcification genes BMP2 and SPP1. These findings highlight the impact of epigenetic regulation on the development of subclinical atherosclerosis.

Inter-regional patient mobility in decentralised Spain: Explaining regional budget imbalances.

Inter-regional patient mobility represents both a resource and a challenge for the organization and financing of health systems, particularly in decentralised countries. We use cross-sectional time series regression analysis to test the determinants of imbalances in regional funds to finance inter-regional patient mobility for the 17 Spanish regions for the period 2014-2020. The findings indicate that highly specialised health centres and bilateral agreements partly explain the budget imbalance from inter-regional patient referrals, while local tourism partly explains the budget imbalance from non-referred patient mobility. Developing effective national schemes to compensate net patient recipient regions would be fundamental to addressing territorial imbalances.

Characteristics of Coronary Atherosclerosis Related to Plaque Burden Regression During Treatment With Alirocumab: The ARCHITECT Study.

BACKGROUND: Intensive lipid-lowering therapy may induce coronary atherosclerosis regression. Nevertheless, the factors underlying the effect of lipid-lowering therapy on disease regression remain poorly characterized. Our aim was to determine which characteristics of atherosclerotic plaque are associated with a greater reduction in coronary plaque burden (PB) after treatment with alirocumab in patients with familial hypercholesterolemia. METHODS: The ARCHITECT study (Effect of Alirocumab on Atherosclerotic Plaque Volume, Architecture and Composition) is a phase IV, open-label, multicenter, single-arm clinical trial to assess the effect of the treatment with alirocumab for 78 weeks on the coronary atherosclerotic PB and its characteristics in subjects with familial hypercholesterolemia without clinical atherosclerotic cardiovascular disease. Participants underwent a coronary computed tomographic angiography at baseline and a final one at 78 weeks. Every patient received alirocumab 150 mg subcutaneously every 14 days in addition to high-intensity statin therapy. RESULTS: One hundred and four patients were enrolled. Median age was 53.3 (46.2-59.4) years and 54 were women (51.9%). The global coronary PB changed from 34.6% (32.5%-36.8%) at entry to 30.4% (27.4%-33.4%) at follow-up, which is -4.6% (-7.7% to -1.9%; P<0.001) reduction. A decrease in the percentage of unstable core (fibro-fatty+necrotic plaque; from 14.1 [7.9-22.3] to 8.0 [6.4-10.6]; -6.6%; P<0.001) was found. A greater PB (ß, 0.36 [0.13-0.59]; P=0.002) and a higher proportion of unstable core (ß, 0.15 [0.08-0.22]; P<0.001) were significantly related to PB regression. CONCLUSIONS: Treatment with alirocumab in addition to high-intensity statin therapy might produce a greater PB regression in patients with familial hypercholesterolemia with higher baseline PB and in those with larger unstable core. Further studies are needed to corroborate the hypothesis raised by these results. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT05465278.

Left atrial strain in adults after the arterial switch operation for transposition of the great arteries.

BACKGROUND: No study has focused on left atrial (LA) function assessed by echocardiography in adult patients with simple D-TGA after arterial switch operation (ASO). We aimed to describe LA strain parameters in these patients. METHODS: A prospective cohort study including 42 adult patients with simple D-TGA after ASO and 33 aged-matched controls. Phasic LA and LV global longitudinal strain (GLS) were obtained by transthoracic 2D-speckle tracking echocardiography (STE). Volumetric and functional analysis of LA and LV were also evaluated by 2D and 3D analysis. A multivariable model was performed to investigate the variables that best differentiate patients with D-TGA from healthy controls. RESULTS: LA strain parameters in D-TGA patients were within the normal range described for healthy subjects. However, the three LA strain parameters (Reservoir, Conduit, and Contraction) were lower in patients (LASr: 31.13 ± 7.67 vs. 49.71 ± 8.38; LAS cd: -22.91 ± 5.69 vs. -34.55 ± 6.54; LASct: -8.14 ± 4.93 vs. -15.15 ± 6.07, p < .001 for all three comparisons). LA volumes were similar between patients and controls. LV-GLS remained significantly lower in the D-TGA group than in controls (-17.29 ± 2.68 vs. -21.98 ± 1.84, p < .001). D-TGA patients had evidence of worse LV ejection fraction measured by the Teichholz method (63.38 ± 8.23 vs. 69.28 ± 5.92, p = .001) and 3D analysis (57.97% ± 4.16 vs. 60.67 ± 3.39, p = .011) and diastolic dysfunction as compared to healthy controls. LV-GLS and conduit LAS were the variables best differentiating patients with D-TGA from healthy controls. CONCLUSIONS: LA strain is impaired in young adults with simple D-TGA late after the ASO, probably in agreement with some degree of LV dysfunction previously described.

Corazón univentricular sin cirugía de Fontan: el tipo de paliación importa / Univentricular hearts not undergoing Fontan: the type of palliation matters

Introducción y objetivos: La información sobre pacientes con fisiología univentricular (FU) y flujo pulmonar restrictivo no sometidos a cirugía de Fontan es escasa. El objetivo de este estudio es comparar la supervivencia y los eventos cardiovasculares en estos pacientes según el tipo de paliación.MétodosLos datos de pacientes con FU se obtuvieron de las bases de datos de 7 centros con unidades de cardiopatías congénitas del adulto. Se excluyó a los pacientes que completaron la circulación de Fontan o desarrollaron un síndrome de Eisenmenger. Se crearon 3 grupos según la fuente de flujo pulmonar: G1, flujo anterógrado pulmonar restrictivo; G2, shunt cavopulmonar, y G3, shunt aortopulmonar±shunt cavopulmonar. El objetivo principal fue la muerte.ResultadosSe identificó a 120 pacientes. La media de edad en la primera visita fue 32,2 años. El seguimiento medio fue de 7,1 años. Se asignó a 55 pacientes (45,8%) al G1, 30 (25%) al G2 y 35 (29,2%) al G3. Los pacientes del G3 tenían peores función renal, clase funcional y fracción de eyección en la primera visita y mostraron una disminución más marcada de la fracción de eyección durante el seguimiento, especialmente en comparación con el G1. Veinticuatro pacientes (20%) fallecieron, 38 (31,7%) ingresaron por insuficiencia cardiaca y 21 (17,5%) presentaron aleteo/fibrilación auricular durante el seguimiento. Estos eventos fueron más frecuentes en el G3 y al compararlos con los del G1 se encontraron diferencias significativas en muerte (HR=2,9; IC95%, 1,14-7,37; p=0,026) y aleteo/fibrilación auricular (HR=2,9; IC95%, 1,11-7,68; p=0,037).ConclusionesEl tipo de paliación de los pacientes con FU y flujo pulmonar restrictivo no sometidos a cirugía de Fontan identifica distintos perfiles. Los pacientes paliados con derivaciones aortopulmonares presentan un peor pronóstico, con más morbilidad y mortalidad. (AU)

Introduction and objectives: There is scarce information on patients with single ventricle physiology (SVP) and restricted pulmonary flow not undergoing Fontan circulation. This study aimed to compare survival and cardiovascular events in these patients according to the type of palliation.MethodsSVP patient data were obtained from the databases of the adult congenital heart disease units of 7 centers. Patients completing Fontan circulation or developing Eisenmenger syndrome were excluded. Three groups were created according to the source of pulmonary flow: G1 (restrictive pulmonary forward flow), G2 (cavopulmonary shunt), and G3 (aortopulmonary shunts±cavopulmonary shunt). The primary endpoint was death.ResultsWe identified 120 patients. Mean age at the first visit was 32.2 years. Mean follow-up was 7.1 years. Fifty-five patients (45.8%) were assigned to G1, 30 (25%) to G2, and 35 (29.2%) to G3. Patients in G3 had worse renal function, functional class, and ejection fraction at the first visit and a more marked ejection fraction decline during follow-up, especially when compared with G1. Twenty-four patients (20%) died, 38 (31.7%) were admitted for heart failure, and 21 (17.5%) had atrial flutter/fibrillation during follow-up. These events were more frequent in G3 and significant differences were found compared with G1 in terms of death (HR, 2.9; 95%CI, 1.14-7.37; P=.026) and atrial flutter/fibrillation (HR, 2.9; 95%CI, 1.11-7.68; P=.037).ConclusionsThe type of palliation in patients with SVP and restricted pulmonary flow not undergoing Fontan palliation identifies distinct profiles. Patients palliated with aortopulmonary shunts have an overall worse prognosis with higher morbidity and mortality. (AU)

Univentricular hearts not undergoing Fontan: the type of palliation matters.

INTRODUCTION AND OBJECTIVES: There is scarce information on patients with single ventricle physiology (SVP) and restricted pulmonary flow not undergoing Fontan circulation. This study aimed to compare survival and cardiovascular events in these patients according to the type of palliation. METHODS: SVP patient data were obtained from the databases of the adult congenital heart disease units of 7 centers. Patients completing Fontan circulation or developing Eisenmenger syndrome were excluded. Three groups were created according to the source of pulmonary flow: G1 (restrictive pulmonary forward flow), G2 (cavopulmonary shunt), and G3 (aortopulmonary shunts±cavopulmonary shunt). The primary endpoint was death. RESULTS: We identified 120 patients. Mean age at the first visit was 32.2 years. Mean follow-up was 7.1 years. Fifty-five patients (45.8%) were assigned to G1, 30 (25%) to G2, and 35 (29.2%) to G3. Patients in G3 had worse renal function, functional class, and ejection fraction at the first visit and a more marked ejection fraction decline during follow-up, especially when compared with G1. Twenty-four patients (20%) died, 38 (31.7%) were admitted for heart failure, and 21 (17.5%) had atrial flutter/fibrillation during follow-up. These events were more frequent in G3 and significant differences were found compared with G1 in terms of death (HR, 2.9; 95%CI, 1.14-7.37; P=.026) and atrial flutter/fibrillation (HR, 2.9; 95%CI, 1.11-7.68; P=.037). CONCLUSIONS: The type of palliation in patients with SVP and restricted pulmonary flow not undergoing Fontan palliation identifies distinct profiles. Patients palliated with aortopulmonary shunts have an overall worse prognosis with higher morbidity and mortality.

Diminished criminal responsibility: A multinational comparative review.

This article reviews the legal frameworks of diminished criminal responsibility in eighteen civil law jurisdictions across the globe-Brazil, Chile, China, the Czech Republic, Finland, France, Germany, Greece, Italy, Japan, Luxembourg, Poland, Portugal, Russia, Spain, Switzerland, Taiwan, and Turkey. Specifically, it reports the legal standards and main features of partial responsibility, associated penalty reductions, and potential dispositions following a partial responsibility finding. It also surveys empirical data on the prevalence of diminished responsibility as compared to criminal nonresponsibility. This article, which reflects contemporary penal codes and draws from both English and non-English sources, is the only known existing source to compile these partial responsibility standards or to delineate their precise sentencing consequences. It is also the only known source in English to describe Portugal's and Chile's treatment of diminished responsibility. Providing a comparative overview of graduated responsibility in nearly twenty countries invites global discussion on whether and how society should recognize partial responsibility, as well as the punitive and therapeutic consequences that should attend this finding.

Neutralizing Antibodies against the SARS-CoV-2 Ancestral Strain and Omicron BA.1 Subvariant in Dogs and Cats in Mexico.

SARS-CoV-2 mainly affects humans; however, it is important to monitor the infection of companion and wild animals as possible reservoirs of this virus. In this sense, seroprevalence studies in companion animals, such as dogs and cats, provide important information about the epidemiology of SARS-CoV-2. This study aimed to evaluate the seroprevalence of neutralizing antibodies (nAbs) against the ancestral strain and the Omicron BA.1 subvariant in dogs and cats in Mexico. Six hundred and two samples were obtained from dogs (n = 574) and cats (n = 28). These samples were collected from the end of 2020 to December 2021 from different regions of Mexico. The presence of nAbs was evaluated using a plaque reduction neutralization test (PRNT) and microneutralization (MN) assays. The results showed that 14.2% of cats and 1.5% of dogs presented nAbs against the ancestral strain of SARS-CoV-2. The analysis of nAbs against Omicron BA.1 in cats showed the same percentage of positive animals but a reduced titer. In dogs, 1.2% showed nAbs against Omicron BA.1. These results indicate that nAbs were more frequent in cats than in dogs and that these nAbs have a lower capacity to neutralize the subvariant Omicron BA.1.

Incidence and Risk Factors for Development of Cardiac Toxicity in Adult Patients with Newly Diagnosed Acute Myeloid Leukemia.

The incidence of cardiac morbimortality in acute myeloid leukemia (AML) is not well known. We aim to estimate the cumulative incidence (CI) of cardiac events in AML patients and to identify risk factors for their occurrence. Among 571 newly diagnosed AML patients, 26 (4.6%) developed fatal cardiac events, and among 525 treated patients, 19 (3.6%) experienced fatal cardiac events (CI: 2% at 6 months; 6.7% at 9 years). Prior heart disease was associated with the development of fatal cardiac events (hazard ratio (HR) = 6.9). The CI of non-fatal cardiac events was 43.7% at 6 months and 56.9% at 9 years. Age ≥ 65 (HR = 2.2), relevant cardiac antecedents (HR = 1.4), and non-intensive chemotherapy (HR = 1.8) were associated with non-fatal cardiac events. The 9-year CI of grade 1-2 QTcF prolongation was 11.2%, grade 3 was 2.7%, and no patient had grade 4-5 events. The 9-year CI of grade 1-2 cardiac failure was 1.3%, grade 3-4 was 15%, and grade 5 was 2.1%; of grade 1-2, arrhythmia was 1.9%, grade 3-4 was 9.1%, and grade 5 was 1%. Among 285 intensive therapy patients, median overall survival decreased in those experiencing grade 3-4 cardiac events (p < 0.001). We observed a high incidence of cardiac toxicity associated with significant mortality in AML.

Alirocumab and Coronary Atherosclerosis in Asymptomatic Patients with Familial Hypercholesterolemia: The ARCHITECT Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (P<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 (P<0.001). A significant change in the characteristics of the coronary atherosclerosis was also found: an increase in the proportion of calcified (+0.3%; P<0.001) and mainly fibrous (+6.2%; P<0.001) plaque, accompanied by a decrease in the percentage of fibro-fatty (-3.9%; P<0.001) and necrotic plaque (-0.6%; P<0.001). CONCLUSIONS: 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. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT05465278.

After-school sports programmes and social inclusion processes in culturally diverse contexts: Results of an international multicase study.

This research aimed to understand the role of after-school sports programs in social inclusion processes in culturally diverse contexts through a multicase study within two locations. The first location was in Spain where immigrant and Spanish students were enrolled, and the other was in Chile with Mapuche-Huilliche students, immigrant and Chilean students. The implemented programs at both sites were similar in their educational focus on socio-educational values, and teaching models (hybridization of teaching games for understanding and cooperative learning) that enhance social inclusion. Using individual and group interviews with teachers, sports coordinators, parents, and students, a qualitative approach was used to identify the factors that facilitate or hinder the social inclusion processes. In addition, the researchers used qualitative observations of the programs over six months using "notes logbook" to record their impressions during the observation process. Results indicated that the implemented sports programs successfully facilitated social inclusion processes, enabling the development of interpersonal skills and relationships between students from different cultural backgrounds. The previous training and experiences of teachers in culturally diverse contexts, and incorporation of traditional sporting games from all cultures, seems to be an important facilitator factor for the inclusion potential of the implemented programs.

Detection of reassortant influenza B strains from 2004 to 2015 seasons in Barcelona (Catalonia, Spain) by whole genome sequencing.

BACKGROUND: Influenza B viruses (FLUBV) have segmented genomes which enables the virus to evolve by segment reassortment. Since the divergence of both FLUBV lineages, B/Victoria/2/87 (FLUBV/VIC) and B/Yamagata/16/88 (FLUBV/YAM), PB2, PB1 and HA have kept the same ancestor, while some reassortment events in the other segments have been reported worldwide. The aim of the present study was to find out reassortment episodes in FLUBV strains detected in cases attended at Hospital Universitari Vall d'Hebron and Hospital de la Santa Creu i Sant Pau (Barcelona, Spain) from 2004 to 2015 seasons. METHODS: From October 2004 to May 2015, respiratory specimens were received from patients with respiratory tract infection suspicion. Influenza detection was carried out by either cell culture isolation, immunofluorescence or PCR-based assays. A RT-PCR was performed to distinguish both lineages by agarose gel electrophoresis. Whole genome amplification was performed using the universal primer set by Zhou et al. in 2012, and subsequently sequenced using Roche 454 GS Junior platform. Bioinformatic analysis was performed to characterise the sequences with B/Malaysia/2506/2007 and B/Florida/4/2006 corresponding sequences as reference of (B/VIC) and (B/YAM), respectively. RESULTS: A total of 118 FLUBV (75 FLUBV/VIC and 43 FLUBV/YAM), from 2004 to 2006, 2008-2011 and 2012-2015 seasons, were studied. The whole genome of 58 FLUBV/VIC and 42 FLUBV/YAM viruses was successfully amplified. Based on HA sequences, most FLUBV/VIC viruses (37; 64%) belonged to clade 1A (B/Brisbane/60/2008) except to 11 (19%), which fell within clade 1B (B/HongKong/514/2009) and 10 (17%) to B/Malaysia/2506/2004. Nine (20%) FLUBV/YAM viruses belonged to clade 2 (B/Massachusetts/02/2012), 18 (42%) to clade 3 (B/Phuket/3073/2013) and 15 (38%) fell within Florida/4/2006. Numerous intra-lineage reassortments in PB2, PB1, NA and NS were found in 2 2010-2011 viruses. An important inter-lineage reassortment event from 2008 to 2009 (11), 2010-2011 (26) and 2012-2013 (3) FLUBV/VIC (clade 1) strains to FLUBV/YAM (clade 3) was found, in addition to 1 reassortant NS in 2010-2011 B/VIC virus. CONCLUSIONS: Intra- and inter-lineage reassortment episodes were revealed by WGS. While PB2-PB1-HA remained in complex, NP and NS reassortant viruses were found in both lineages. Despite reassorment events are not often, the characterisation only by HA and NA sequences might be underestimating their detection.

A Look at the Interconnection of Dimensions of Knowledge in Physical Education Teacher Training in Chile.

The massive fragmentation of knowledge that exists in the current field of physical education enables us to research pedagogical and disciplinary aspects in the educational processes of teachers in training, as this has significant implications for future educational practices. This study proposes to assess the dimensions of knowledge (conceptual, procedural and attitudinal) that stem from the learnings that emerge in physical education teacher training in terms of the disciplinary standards proposed by the Chilean Education Ministry for the Preservice Teacher Education. The study methodology was descriptive and inferential, and the cohort was cross-sectional. A total of 750 fourth- and fifth-year students in training from 13 Chilean universities participated. Of these, 619 subjects were considered: 54.6% (338) men and 45.4% (281) women between the ages of 21 and 25. The questionnaire used for data collection was the "Questionnaire on Conceptual, Procedural and Attitudinal Learning in Preservice Teacher Education in Physical Education" (CACPA-FIDEF), prepared as part of Fondecyt project No. 11190537. The main results indicate that there are no statistically significant differences in the three dimensions in terms of students' sex and type of schooling, with p values > 0.05. In conclusion, the study observed a weak conceptual management of the discipline in future teachers, revealing once again the need to seek out didactic alternatives that enable teachers in training to understand the importance of the conceptual dimension in their learning and teaching processes.

CA125 como nuevo biomarcador en pacientes con circulación de Fontan / CA125: a new biomarker in patients with Fontan circulation

Introducción y objetivos Los pacientes con circulación de Fontan (CF) presentan una gran incidencia de complicaciones y ningún biomarcador estratifica el riesgo. El objetivo es analizar la asociación de biomarcadores con un perfil clínico de disfunción de la CF, incluyendo por primera vez el antígeno carbohidrato 125 (CA125), y proponer una estimación del riesgo basada en la combinación de biomarcadores. Métodos Estudio transversal de adultos con CF. Se consideró perfil clínico desfavorable el combinado de insuficiencia cardiaca, arritmias auriculares, fístulas venovenosas, enteropatía pierdeproteínas o bronquitis plástica. Se analizaron variables clínicas y analíticas, incluidos CA125, NT-proBNP, función renal y hepática y amplitud de distribución eritrocitaria (ADE). Se realizó un estudio univariado y multivariado de la relación de dichas complicaciones clínicas y curvas ROC para obtener puntos de corte. Resultados Se incluyó a 56 pacientes (media de edad, 27,4±7,8 años). El 34% tenía un perfil clínico desfavorable, con valores de CA125 significativamente mayores (30,1 frente a 12,6 UI/ml; p=0,001). LnCA125 (OR=5,1; IC95%, 1,2-22), ADE (OR=1,8; IC95%, 1,1-3.1) y FIB4 (OR=38; IC95%, 1,7-855) se asociaron con un perfil de disfunción clínica. Los puntos de corte fueron CA125 ≥ 20 U/ml, FIB4 ≥ 0,75 y ADE ≥ 14,5%, y la probabilidad de un perfil clínico desfavorable fue del 81% con 2 o más biomarcadores elevados. Conclusiones El aumento de CA125 se asocia con mayor prevalencia de complicaciones en pacientes con CF. Los valores de CA125 ≥ 20 U/ml, FIB4 ≥ 0,75 y ADE ≥ 14,5% identifican con alta probabilidad fracaso clínico de la CF. (AU)

Introduction and objectives Patients with Fontan circulation (FC) have a high incidence of clinical complications. However, no biomarker is able to accurately stratify risk. The aim of this study was to analyze the relationship between biomarkers and clinical complications, including carbohydrate antigen 125 (CA125) for the first time, and to propose a risk estimation based on a combination of biomarkers. Methods Cross-sectional study of patients with FC. The clinical endpoint was the combination of heart failure, atrial arrhythmias, veno-venous fistulae, protein-losing enteropathy, or plastic bronchitis. Demographic, clinical, and laboratory variables were analyzed, including CA125, NT-proBNP, renal and liver function, and red cell distribution width (RDW). We performed univariate and multivariate analyses of the relationship between these variables and the composite endpoint. Cutoff values were calculated by ROC curves. Results We included 56 patients (27.4±7.8 years). A total of 34% showed the composite endpoint, with significantly higher CA125 levels (30.1 IU/mL vs 12.6 IU/mL; P=.001). In the multivariate model, the biomarkers related to the endpoint were LnCA125 (OR, 5.1; 95%CI, 1.2-22), RDW (OR, 1.8; 95%CI, 1.1-3.1), and FIB4 (OR, 38, 95%CI, 1.7-855). The cutoff points were CA125 ≥ 20 U/mL, FIB4 ≥ 0.75, and RDW ≥ 14.5%, and the probability of the occurrence of the endpoint was 81% if ≥ 2 biomarkers were elevated. Conclusions CA125 elevation is associated with a higher prevalence of complications in patients with Fontan-type circulation. CA125 levels ≥ 20U/mL, FIB4 ≥ 0.75 and RDW ≥ 14.5% identify with a high probability the clinical failure of FC. (AU)

Spatiotemporal Complexity of Vena Contracta and Mitral Regurgitation Grading Using Three-Dimensional Echocardiographic Analysis.

BACKGROUND: Spatiotemporal complexity of the color Doppler vena contracta challenging the assumption of a circular and constant orifice may lead to mitral regurgitation (MR) grading inconsistencies. Using 3D transesophageal echocardiography, we characterized spatiotemporal vena contracta complexity and its impact on MR severity grading. METHODS: In 192 patients with suspected moderate or severe MR (100 primary MR [PMR]; 92 secondary MR [SMR]), we performed three-dimensional vena contracta area (VCA) quantification using single-frame (midsystolic or VCAmid, maximum or VCAmax) and multiframe (VCAmean) methods, as well as measures of orifice shape (shape index) and systolic variation of VCA. Vena contracta complexity and intermethod discrepancies were analyzed and correlated with functional class and pulmonary vein flow (PVF) patterns and with cardiac magnetic resonance (CMR) in a subset of cases (n = 20). RESULTS: The vena contracta was noncircular (shape index > 1.5) in 90% of patients. Severe noncircularity (shape index > 3) was more prevalent in SMR than in PMR (32.4% vs 14.6%). Variations of the VCA were more prominent in SMR than in PMR. VCAmid showed a low grading agreement with VCAmax (62%) and high grading agreement with VCAmean (83.3%). Pulmonary vein flow systolic reversal was associated with MR severity by VCA in SMR but not in PMR. VCAmid and VCAmean showed a stronger association with systolic flow reversal than VCAmax (area under the curve, 0.88, 0.86, and 0.79, respectively). In the subset of patients with CMR quantification, severe MR by VCAmax was graded as nonsevere by CMR more frequently compared with VCAmid and VCAmean. CONCLUSIONS: Highly prevalent spatiotemporal vena contracta complexity features in MR challenge the assumption of a circular and constant orifice. VCAmid seems the best single-frame approximation to multiframe quantification, and VCAmax may lead to severity overestimation.

CA125: a new biomarker in patients with Fontan circulation.

INTRODUCTION AND OBJECTIVES: Patients with Fontan circulation (FC) have a high incidence of clinical complications. However, no biomarker is able to accurately stratify risk. The aim of this study was to analyze the relationship between biomarkers and clinical complications, including carbohydrate antigen 125 (CA125) for the first time, and to propose a risk estimation based on a combination of biomarkers. METHODS: Cross-sectional study of patients with FC. The clinical endpoint was the combination of heart failure, atrial arrhythmias, veno-venous fistulae, protein-losing enteropathy, or plastic bronchitis. Demographic, clinical, and laboratory variables were analyzed, including CA125, NT-proBNP, renal and liver function, and red cell distribution width (RDW). We performed univariate and multivariate analyses of the relationship between these variables and the composite endpoint. Cutoff values were calculated by ROC curves. RESULTS: We included 56 patients (27.4±7.8 years). A total of 34% showed the composite endpoint, with significantly higher CA125 levels (30.1 IU/mL vs 12.6 IU/mL; P=.001). In the multivariate model, the biomarkers related to the endpoint were LnCA125 (OR, 5.1; 95%CI, 1.2-22), RDW (OR, 1.8; 95%CI, 1.1-3.1), and FIB4 (OR, 38, 95%CI, 1.7-855). The cutoff points were CA125 ≥ 20 U/mL, FIB4 ≥ 0.75, and RDW ≥ 14.5%, and the probability of the occurrence of the endpoint was 81% if ≥ 2 biomarkers were elevated. CONCLUSIONS: CA125 elevation is associated with a higher prevalence of complications in patients with Fontan-type circulation. CA125 levels ≥ 20U/mL, FIB4 ≥ 0.75 and RDW ≥ 14.5% identify with a high probability the clinical failure of FC.