Novel loci and Mapuche genetic ancestry are associated with pubertal growth traits in Chilean boys

Puberty is a complex developmental process that varies considerably among individuals and populations. Genetic factors explain a large proportion of the variability of several pubertal traits. Recent genome-wide association studies (GWAS) have identified hundreds of variants involved in traits that result from body growth, like adult height. However, they do not capture many genetic loci involved in growth changes over distinct growth phases. Further, such GWAS have been mostly performed in Europeans, but it is unknown how these findings relate to other continental populations. In this study, we analyzed the genetic basis of three pubertal traits; namely, peak height velocity (PV), age at PV (APV) and height at APV (HAPV). We analyzed a cohort of 904 admixed Chilean children and adolescents with European and Mapuche Native American ancestries. Height was measured on roughly a 6−month basis from childhood to adolescence between 2006 and 2019. We predict that, in average, HAPV is 4.3 cm higher in European than in Mapuche adolescents (P = 0.042), and APV is 0.73 years later in European compared with Mapuche adolescents (P = 0.023). Further, by performing a GWAS on 774, 433 single-nucleotide polymorphisms, we identified a genetic signal harboring 3 linked variants significantly associated with PV in boys (P <5×10−8). This signal has never been associated with growth-related traits

Identification and functional analysis of missense mutations in the lecithin cholesterol acyltransferase gene in a Chilean patient with hypoalphalipoproteinemia

Lecithin-cholesterol acyltransferase (LCAT) is a plasma enzyme that esterifies cholesterol in high- and low-density lipoproteins (HDL and LDL). Mutations in LCAT gene causes familial LCAT deficiency, which is characterized by very low plasma HDL-cholesterol levels (Hypoalphalipoproteinemia), corneal opacity and anemia, among other lipid-related traits. Our aim is to evaluate clinical/biochemical features of a Chilean family with a proband showing clinical signs of familial LCAT deficiency, as well as to identify and assess the functional effects of LCAT mutations. LCAT sequencing identified rare p.V333 M and p.M404 V missense mutations in compound heterozygous state in the proband, as well the common synonymous p.L363 L variant. LCAT protein was detected in proband’s plasma, but with undetectable enzyme activity compared to control relatives. HEK-293 T transfected cells with vector expression plasmids containing either p.M404 V or p.V333 M cDNA showed detectable LCAT protein expression both in supernatants and lysates from cultured cells, but with much lower enzyme activity compared to cells transfected with the wild-type sequence. Bioinformatic analyses also supported a causal role of such rare variations in LCAT lack of function. Additionally, the proband carried the minor allele of the synonymous p.L363 L variant. However, this variant is unlikely to affect the clinical phenotype of the proband given its relatively high frequency in the Chilean population (4%) and its small putative effect on plasma HDL-cholesterol levels. Conclusion: Genetic, biochemical, in vitro and in silico analyses indicate that the rare mutations p.M404 V and p. V333 M in LCAT gene lead to suppression of LCAT enzyme activity and cause clinical features of familial LCAT deficiency.This work was supported by Proyecto FONDECYT 1150416 and Proyecto Interdisciplina VRI-PUC II15024 from the Dirección de Investigación, Pontificia Universidad Católica de Chile. Genotyping of GOCS was performed in the in the Human Genotyping laboratory at the Spanish National Cancer Research Centre, a member of CeGen (PRB2-ISCIII), and was supported by grant PT13/ 0001/0005 of PE I + D + i 2013-2016 funded by ISCIII and ERDF (Fondo Europeo de Desarrollo Regional). This research was partially supported by the supercomputing infrastructure of the NLHPC (ECM-02). L.V. and C.B. were supported by VRI, Pontificia Universidad Católica de Chile (Proyecto Investigación Interdisciplinaria VRI-PUC II15024). TG was supported by “Beca de Magíster Nacional” CONICYT. L.V. was additionally supported by FONDECYT postdoctoral grant 3170038. We express our gratitude to the proband and relatives

Manejo actual de los pólipos vesiculares en Chile

Introduction: Gallbladder polyps are a mucosal projection into the gallbladder lumen and an increasingly frequent diagnosis, due to radiologic advances. In Chile, the incidence of gallbladder cancer reaches 12,8 per 100.000 habitants. Materials and Methods: A review of 20 papers (national and international) was carried out on platforms like PubMed, UpToDate and google Scholar. Results: Mostly asymptomatic, a minority evolves to a malignant neoplasia. There is no consensus between the studies about all management criteria, being the most accepted one to an active treatment, a size ≥10mm. Other factors include association with primary sclerosing cholangitis (PSC) or cholelithiasis, sessile morphology, older age, and single polyps. Discussion: Given de incidence of incidental finding of polyps and the difficulty in differentiating potentially malignant polyps through images, associated with the high incidence of gallbladder cancer in Chile; active management with cholecystectomy is recommended for those measuring 10mm or more, associated with symptoms, cholelithiasis or PSC or growth in follow-up, age older than 50 years, sessile morphology, and Indian ethnicity. Due to the malignant potential of gallbladder polyps, their frequently asymptomatic presentation and the importance of gallbladder cancer in Chile, this review has the objective of making explicit the currently accepted risk factors and propose a management algorithm for gallbladder polyps in Chile.Introducción: Los pólipos de vesícula son proyecciones de la mucosa vesicular hacia su lumen (1,2), siendo un diagnóstico cada vez más frecuente, debido a los avances imagenológicos (3,4). En Chile, la incidencia de cáncer de vesícula alcanza 12,8 por 100.000 habitantes (6). Material y métodos: Se realizó una revisión de 20 revistas (nacionales e internacionales), en plataformas PubMed, UpToDate y Google académico. Resultados: Se presentan principalmente asintomáticos y una parte menor de ellos progresa a neoplasia maligna (5). No existe consenso entre los diversos estudios respecto a los criterios de manejo de estos, siendo el más aceptado para un manejo activo con colecistectomía un tamaño ≥10mm. Entre otros factores se nombran: asociación a colangitis esclerosante primaria (CEP), morfología sésil, mayor edad, pólipos únicos y asociados a colelitiasis. Discusión: Dado la frecuencia del hallazgo incidental de pólipos y la dificultad para diferenciar los potencialmente malignos mediante imágenes, asociado a la alta prevalencia de cáncer vesicular en Chile, se recomienda el uso de un manejo activo con colecistectomía a aquellos que se caractericen por medir 10mm o más, asociarse a síntomas, colelitiasis, CEP o crecimiento en seguimiento, edad mayor a 50 años, morfología sésil y etnicidad india. Debido al potencial maligno de los pólipos vesiculares, su presentación frecuentemente asintomática y la importancia del cáncer de vesícula en Chile, esta revisión tiene por objetivo explicitar los factores de riesgo actualmente aceptados y proponer un algoritmo de manejo para los pólipos vesiculares en Chile

Cuerpos extraños rectales. Revisión bibliográfica actualizada

Introduction: Rectal foreign bodies (REC) have increased in incidence in recent years, however, there are few epidemiological data to this date. Its management generally represents a challenge for surgeons due to the variability of clinical presentations. The goal of this review is to describe and analyze national and international publications on CER during the last decade. Materials and methods: A bibliographic review was carried out in Medline (PubMed) and Scholar Google databases, including publications from 2010 to 2021. Results: 29 results were obtained, eliminating those focused on extra-rectal foreign bodies and rectal lesions of other etiologies. There is a male predominance in CER cases, with a ratio of up to 28: 1 and a higher incidence between 20-40 years. 35.8% of the cases were secondary to sexual stimulation, 50.6% had no reported cause and 5.2% were due to third-party aggression. The cardinal symptoms are anal pain or constipation. Most CERs can be diagnosed by abdominal and pelvic radiographs (Rx), however, a negative Rx does not rule it out. Multiple extraction techniques are described, depending on the type of object and the risk or suspicion of complications; being the most frequent ones sphincter and / or anal mucosa lacerations, intestinal obstruction and perforation. Discussion: The bibliography regarding CER is currently scarce, however, its incidence is expected to increase; therefore, it is important that health care professionals take into consideration its diagnostic possibility and learn management options.Introducción: Los cuerpos extraños rectales (CER) han aumentado en incidencia durante los últimos años, sin embargo, existen escasos datos epidemiológicos a la fecha. Su manejo representa en general un desafío para el cirujano por la variabilidad de presentaciones. El objetivo de esta revisión es describir y analizar las publicaciones nacionales e internacionales sobre CER durante la última década. Materiales y métodos: Se realizó una revisión bibliográfica en las bases de datos Medline (PubMed) y Google Académico, incluyendo publicaciones desde el año 2010 al 2021. Resultados: Se obtuvieron 29 resultados, eliminando aquellas enfocadas en cuerpos extraños extra-rectales y lesiones rectales de otras etiologías. Existe un predominio masculino en casos de CER, con una relación de hasta 28:1 y mayor incidencia entre 20- 40 años. Un 35.8% de los casos fueron secundarios a estimulación sexual, 50,6% con causa no informada y 5.2% por agresión de terceros. Los síntomas cardinales son dolor anal o constipación. La mayoría de los CER pueden ser diagnosticados mediante radiografías (Rx) de abdomen y pelvis, sin embargo, una Rx negativa no lo descarta. Se describen múltiples técnicas de extracción, dependiendo del tipo de objeto y del riesgo o sospecha de complicaciones; siendo las más frecuentes laceraciones de esfínter y/o mucosa anal, obstrucción intestinal y perforación. Discusión: La bibliografía respecto a CER es escasa actualmente, sin embargo, se espera que su incidencia aumente; por lo que es importante que el personal de salud tenga en consideración su posibilidad diagnóstica conozca las opciones de manejo

Galectin-8 binds to LFA-1, blocks its interaction with ICAM-1 and is counteracted by anti-Gal-8 autoantibodies isolated from lupus patients

Galectin-8 belongs to a family of mammalian lectins that recognize glycoconjugates present on different cell surface components and modulate a variety of cellular processes. A role of Gal-8 in the immune system has been proposed based on its effects in immune cells, including T and B lymphocytes, as well as the presence of anti-Gal-8 autoantibodies in the prototypic autoimmune disease systemic lupus erythematosus (SLE). We have previously described that Gal-8 induces apoptosis in activated T cells interacting with certain β1 integrins and this effect is counteracted by the anti-Gal-8 autoantibodies. Given that Gal-8 can potentially interact with several glycoproteins, here we analyzed the β2 integrin Lymphocyte Function-Associated Antigen-1 (LFA-1), which is involved in leukocyte cell adhesion and immunological synapses. We show by GST-pull down assays that Gal-8 interacts with LFA-1 and this interaction is inhibited by anti-Gal-8 autoantibodies isolated from SLE patients. In cell adhesion assays, Gal-8 precluded the interaction of LFA-1 with its ligand Intracellular Adhesion Molecule-1 (ICAM-1). These results suggest that Gal-8 can exert immunosuppressive action not only by inducing apoptosis in activated T cells but also by negatively modulating the crucial function of LFA-1 in the immune system, while function-blocking autoantibodies counteract these effects

New insights from GWAS on BMI-related growth traits in a longitudinal cohort of admixed children with Native American and European ancestry.

Body-mass index (BMI) is a hallmark of adiposity. In contrast with adulthood, the genetic architecture of BMI during childhood is poorly understood. The few genome-wide association studies (GWAS) on children have been performed almost exclusively in Europeans and at single ages. We performed cross-sectional and longitudinal GWAS for BMI-related traits on 904 admixed children with mostly Mapuche Native American and European ancestries. We found regulatory variants of the immune gene HLA-DQB3 strongly associated with BMI at 1.5 - 2.5 years old. A variant in the sex-determining gene DMRT1 was associated with the age at adiposity rebound (Age-AR) in girls (P = 9.8 × 10 - 9 ). BMI was significantly higher in Mapuche than in Europeans between 5.5 and 16.5 years old. Finally, Age-AR was significantly lower (P = 0.004 ) by 1.94 years and BMI at AR was significantly higher (P = 0.04 ) by 1.2 kg/ m 2 , in Mapuche children compared with Europeans

“Compassionate City” in Patients with Advanced Illnesses and at the End of Life: A Pilot Study

Objectives: To evaluate, in a Compassionate City pilot experience (Sevilla), the impact results on health in a population of people with advanced illness and at the end of life. Methods: The project was undertaken in Sevilla, Spain, between January 2019 and June 2020. A longitudinal, descriptive study was conducted using a longitudinal cohort design with two cross-sectional measurements, pre and post intervention. All patients who entered the program on the start date were included. The networks of care around people with advanced illness and at the end of life, palliative care needs, quality of life, loneliness, anxiety, depression, caregivers’ burden and family satisfaction were evaluated. The interventions were conducted by community promoters assigned to the “Sevilla Contigo, Compassionate City” program. Results: A total of 83 people were included in the program. The average number of people involved in care at the beginning of the evaluations was 3.6, increasing to 6.1 at the end of the interventions. The average number of needs detected at the beginning was 15.58, and at the end of interventions, it was 16.56 out of 25. The unmet needs were those related to last wishes (40.7%), emotional relief (18.5%), entertainment (16%), help to walk up and down stairs (8.6%) and help to walk (6.2%). A total of 54.2% showed improved loneliness in the final evaluation. Out of 26 people evaluated for pre and post quality of life, 7 (26.9%) improved their quality of life in the general evaluation and 5 (19.2%) displayed improved anxiety/depression. A total of 6 people (28.6%) improved their quality-of-life thermometer scores. A total of 57.7% of caregivers improved their burden with a mean score of 17.8