Familial hypercholesterolaemia in children and adolescents from 48 countries: a cross-sectional study

Background: Approximately 450 000 children are born with familial hypercholesterolaemia worldwide every year, yet only 2·1% of adults with familial hypercholesterolaemia were diagnosed before age 18 years via current diagnostic approaches, which are derived from observations in adults. We aimed to characterise children and adolescents with heterozygous familial hypercholesterolaemia (HeFH) and understand current approaches to the identification and management of familial hypercholesterolaemia to inform future public health strategies. Methods: For this cross-sectional study, we assessed children and adolescents younger than 18 years with a clinical or genetic diagnosis of HeFH at the time of entry into the Familial Hypercholesterolaemia Studies Collaboration (FHSC) registry between Oct 1, 2015, and Jan 31, 2021. Data in the registry were collected from 55 regional or national registries in 48 countries. Diagnoses relying on self-reported history of familial hypercholesterolaemia and suspected secondary hypercholesterolaemia were excluded from the registry; people with untreated LDL cholesterol (LDL-C) of at least 13·0 mmol/L were excluded from this study. Data were assessed overall and by WHO region, World Bank country income status, age, diagnostic criteria, and index-case status. The main outcome of this study was to assess current identification and management of children and adolescents with familial hypercholesterolaemia. Findings: Of 63 093 individuals in the FHSC registry, 11 848 (18·8%) were children or adolescents younger than 18 years with HeFH and were included in this study; 5756 (50·2%) of 11 476 included individuals were female and 5720 (49·8%) were male. Sex data were missing for 372 (3·1%) of 11 848 individuals. Median age at registry entry was 9·6 years (IQR 5·8-13·2). 10 099 (89·9%) of 11 235 included individuals had a final genetically confirmed diagnosis of familial hypercholesterolaemia and 1136 (10·1%) had a clinical diagnosis. Genetically confirmed diagnosis data or clinical diagnosis data were missing for 613 (5·2%) of 11 848 individuals. Genetic diagnosis was more common in children and adolescents from high-income countries (9427 [92·4%] of 10 202) than in children and adolescents from non-high-income countries (199 [48·0%] of 415). 3414 (31·6%) of 10 804 children or adolescents were index cases. Familial-hypercholesterolaemia-related physical signs, cardiovascular risk factors, and cardiovascular disease were uncommon, but were more common in non-high-income countries. 7557 (72·4%) of 10 428 included children or adolescents were not taking lipid-lowering medication (LLM) and had a median LDL-C of 5·00 mmol/L (IQR 4·05-6·08). Compared with genetic diagnosis, the use of unadapted clinical criteria intended for use in adults and reliant on more extreme phenotypes could result in 50-75% of children and adolescents with familial hypercholesterolaemia not being identified. Interpretation: Clinical characteristics observed in adults with familial hypercholesterolaemia are uncommon in children and adolescents with familial hypercholesterolaemia, hence detection in this age group relies on measurement of LDL-C and genetic confirmation. Where genetic testing is unavailable, increased availability and use of LDL-C measurements in the first few years of life could help reduce the current gap between prevalence and detection, enabling increased use of combination LLM to reach recommended LDL-C targets early in life

Evolving trends in the management of acute appendicitis during COVID-19 waves. The ACIE appy II study

Background: In 2020, ACIE Appy study showed that COVID-19 pandemic heavily affected the management of patients with acute appendicitis (AA) worldwide, with an increased rate of non-operative management (NOM) strategies and a trend toward open surgery due to concern of virus transmission by laparoscopy and controversial recommendations on this issue. The aim of this study was to survey again the same group of surgeons to assess if any difference in management attitudes of AA had occurred in the later stages of the outbreak. Methods: From August 15 to September 30, 2021, an online questionnaire was sent to all 709 participants of the ACIE Appy study. The questionnaire included questions on personal protective equipment (PPE), local policies and screening for SARS-CoV-2 infection, NOM, surgical approach and disease presentations in 2021. The results were compared with the results from the previous study. Results: A total of 476 answers were collected (response rate 67.1%). Screening policies were significatively improved with most patients screened regardless of symptoms (89.5% vs. 37.4%) with PCR and antigenic test as the preferred test (74.1% vs. 26.3%). More patients tested positive before surgery and commercial systems were the preferred ones to filter smoke plumes during laparoscopy. Laparoscopic appendicectomy was the first option in the treatment of AA, with a declined use of NOM. Conclusion: Management of AA has improved in the last waves of pandemic. Increased evidence regarding SARS-COV-2 infection along with a timely healthcare systems response has been translated into tailored attitudes and a better care for patients with AA worldwide

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Documentos de Trabajo, no.31

El presente trabajo, es el segundo de la Serie Estudios de Trayectorias Sociolaborales, en el marco del proyecto UBACyT “El núcleo duro de la desocupación en los ’90. Los diferentes trabajos, que se exponen a continuación nos muestran analíticamente el segmento de los varones adultos, en particular los jefes de familia, que han constituido y siguen constituyendo –aunque cada vez menos- el núcleo central del mundo del trabajo, especialmente si se trata de trabajo asalariado registrado. De hecho, gran parte de la literatura occidental que ha abordado la dimensión social del problema del desempleo -durante el siglo XX- ha tenido a esta población como su principal objeto implícito o explícito de estudio y de propuestas de políticas.UT Librarie

Trayectorias laborales masculinas : estudios diacrónicos de varones beneficiarios del Seguro de Desempleo y del Pago Único. Trayectorias laborales No. 2

Resumen: El presente trabajo, es el segundo de la Serie Estudios de Trayectorias Sociolaborales, en el marco del proyecto UBACyT El núcleo duro de la desocupación en los 90. Los diferentes trabajos, que se exponen a continuación nos muestran analíticamente el segmento de los varones adultos, en particular los jefes de familia, que han constituido y siguen constituyendo -aunque cada vez menos- el núcleo central del mundo del trabajo, especialmente si se trata de trabajo asalariado registrado. De hecho, gran parte de la literatura occidental que ha abordado la dimensión social del problema del desempleo -durante el siglo XX- ha tenido a esta población como su principal objeto implícito o explícito de estudio y de propuestas de políticas.\nAl respecto, creemos que del mismo modo en que los estudios de género, juventud o gerontología se han difundido a partir de desarrollar modelos, categorías e indicadores específicos, acordes con los nuevos procesos sociales de exclusión o discriminación que afectan a esos sectores, es fundamental abordar el desempleo en los hombres adultos y su relación con el mundo laboral, familiar y socio-institucional, redescubriendo su especificidad en cuanto a su relevancia económica, social y política.Fil: Chávez Molina, Eduardo. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones Gino Germani; Argentina.Fil: Salvia, Agustín. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones Gino Germani; Argentina.Fil: Gómez, Florencia. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones Gino Germani; Argentina.Fil: De Gainza, Mariana. Universidad de Buenos Aires. Facultad de Ciencias Sociales. Instituto de Investigaciones Gino Germani; Argentina.Fil: Salvia, Victoria. Universidad de Buenos Aires. Facultad de Filosofía y Letras; Argentina.Fil: Persia, Juliana. Universidad de Buenos Aires. Facultad de Ciencias Sociales; Argentina.Fil: Ferro, Mariano. Universidad de Buenos Aires. Facultad de Ciencias Sociales; Argentina.Fil: Austral, Rosario. Universidad de Buenos Aires. Facultad de Ciencias Sociales; Argentina.Fil: Herrera Gallo, Gonzalo. Universidad de Buenos Aires. Facultad de Ciencias Sociales; Argentina

Trayectorias laborales masculinas: Estudios diacrónicos de varones beneficiarios del Seguro de Desempleo y del Pago Único

El presente trabajo, es el segundo de la Serie Estudios de Trayectorias Sociolaborales, en el marco del proyecto UBACyT “El núcleo duro de la desocupación en los ’90. Los diferentes trabajos, que se exponen a continuación nos muestran analíticamente el segmento de los varones adultos, en particular los jefes de familia, que han constituido y siguen constituyendo –aunque cada vez menos- el núcleo central del mundo del trabajo, especialmente si se trata de trabajo asalariado registrado. De hecho, gran parte de la literatura occidental que ha abordado la dimensión social del problema del desempleo -durante el siglo XX- ha tenido a esta población como su principal objeto implícito o explícito de estudio y de propuestas de políticas. Al respecto, creemos que del mismo modo en que los estudios de género, juventud o gerontología se han difundido a partir de desarrollar modelos, categorías e indicadores específicos, acordes con los nuevos procesos sociales de exclusión o discriminación que afectan a esos sectores, es fundamental abordar el desempleo en los hombres adultos y su relación con el mundo laboral, familiar y socio-institucional, redescubriendo su especificidad en cuanto a su relevancia económica, social y política

VIII Semana de la Facultad de Educación : Desafíos de las pedagogías, las prácticas y las perspectivas investigativas en el siglo XXI.

Estas memorias de la viii Semana de la Educación Desafíos de las pedagogías, las prácticas y las perspectivas investigativas en el siglo XXI, publicadas por la editorial de la Corporación Universitaria Minuto de Dios (uniminuto), contienen las ponencias, los talleres y los foros sobre las tendencias actuales de la pedagogía, las prácticas y la investigación que desarrollan los maestros y estudiantes de licenciaturas en las instituciones educativas a nivel preescolar, básica, media y superior. Son ponencias con carácter innovador e incluyente, que responden a los retos actuales de la sociedad y que conducen a la mejora de las condiciones de formación de los ciudadanos que requiere el país, dadas las particularidades de pluralismo propias de nuestras regiones. Durante el encuentro, también se compartieron experiencias artísticas, culturales y deportivas

VIII Semana de la Facultad de Educación : Desafíos de las pedagogías, las prácticas y las perspectivas investigativas en el siglo XXI.

Estas memorias de la viii Semana de la Educación Desafíos de las pedagogías, las prácticas y las perspectivas investigativas en el siglo XXI, publicadas por la editorial de la Corporación Universitaria Minuto de Dios (uniminuto), contienen las ponencias, los talleres y los foros sobre las tendencias actuales de la pedagogía, las prácticas y la investigación que desarrollan los maestros y estudiantes de licenciaturas en las instituciones educativas a nivel preescolar, básica, media y superior. Son ponencias con carácter innovador e incluyente, que responden a los retos actuales de la sociedad y que conducen a la mejora de las condiciones de formación de los ciudadanos que requiere el país, dadas las particularidades de pluralismo propias de nuestras regiones. Durante el encuentro, también se compartieron experiencias artísticas, culturales y deportivas

Immunogenetics of lithium response and psychiatric phenotypes in patients with bipolar disorder

The link between bipolar disorder (BP) and immune dysfunction remains controversial. While epidemiological studies have long suggested an association, recent research has found only limited evidence of such a relationship. To clarify this, we investigated the contributions of immune-relevant genetic factors to the response to lithium (Li) treatment and the clinical presentation of BP. First, we assessed the association of a large collection of immune-related genes (4,925) with Li response, defined by the Retrospective Assessment of the Lithium Response Phenotype Scale (Alda scale), and clinical characteristics in patients with BP from the International Consortium on Lithium Genetics (ConLi + Gen, N = 2,374). Second, we calculated here previously published polygenic scores (PGSs) for immune-related traits and evaluated their associations with Li response and clinical features. We found several genes associated with Li response at p < 1x10 - 4 values, including HAS3 , CNTNAP5 and NFIB . Network and functional enrichment analyses uncovered an overrepresentation of pathways involved in cell adhesion and intercellular communication, which appear to converge on the well-known Li-induced inhibition of GSK-3β. We also found various genes associated with BP's age-at-onset, number of mood episodes, and presence of psychosis, substance abuse and/or suicidal ideation at the exploratory threshold. These included RTN4 , XKR4 , NRXN1 , NRG1/3 and GRK5 . Additionally, PGS analyses suggested serum FAS, ECP, TRANCE and cytokine ligands, amongst others, might represent potential circulating biomarkers of Li response and clinical presentation. Taken together, our results support the notion of a relatively weak association between immunity and clinically relevant features of BP at the genetic level