Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Factors Associated with Revision Surgery after Internal Fixation of Hip Fractures

Background: Femoral neck fractures are associated with high rates of revision surgery after management with internal fixation. Using data from the Fixation using Alternative Implants for the Treatment of Hip fractures (FAITH) trial evaluating methods of internal fixation in patients with femoral neck fractures, we investigated associations between baseline and surgical factors and the need for revision surgery to promote healing, relieve pain, treat infection or improve function over 24 months postsurgery. Additionally, we investigated factors associated with (1) hardware removal and (2) implant exchange from cancellous screws (CS) or sliding hip screw (SHS) to total hip arthroplasty, hemiarthroplasty, or another internal fixation device. Methods: We identified 15 potential factors a priori that may be associated with revision surgery, 7 with hardware removal, and 14 with implant exchange. We used multivariable Cox proportional hazards analyses in our investigation. Results: Factors associated with increased risk of revision surgery included: female sex, [hazard ratio (HR) 1.79, 95% confidence interval (CI) 1.25-2.50; P = 0.001], higher body mass index (fo

Controversy referred to the adequate vitamin d levels concerning bone health proposed by the medical institute of medicine and the international medical community

La vitamina D es esencial para la mineralización del esqueleto y el mantenimiento de la masa ósea. El Instituto de Medicina de los Estados Unidos (IOM) realizó recientemente una revisión de las Recomendaciones Dieté- ticas Admitidas o más comúnmente denominadas por su nomenclatura en inglés como RDA (Recommended Dietary Allowance) para mantener las concentraciones séricas de 25-hidroxivitamina D (25OHD) en 20 ng/ml. Dicho valor es considerado por el comité de expertos del IOM como óptimo para mantener la masa ósea, alcanzar una adecuada absorción intestinal de calcio y prevenir la osteomalacia. Las recomendaciones realizadas por el IOM dieron lugar a una importante controversia. La Comunidad Médica Internacional (CMI) especializada en vitamina D considera que la postura del IOM es conservadora ya que estudios epidemiológicos y clínicos muestran que, para mantener una adecuada salud ósea, los niveles de 25OHD deberían ser superiores a 30 ng/ml.Vitamin D is essential for skeletal mineralization and maintenance of bone mass. The Institute of Medicine (IOM) recently revised the recommended dietary allowances (RDA) for vitamin D, to maintain serum 25-hydroxyvitamin D (25OHD) of 20 ng/ml. These values were considered by the IOM committee appropriate to maintain bone mass, achieve adequate intestinal absorption of calcium and avoid osteomalacia. However, these results addressed an important controversy in the International Medical Community (IMC,) especially in the group of experts in vitamin D. IMC argues that IOM has a conservative perspective about desirable levels of 25OHD (20 ng/ml). Epidemiologic and clinical trials showed that the 25OHD levels would be above 30 ng/ml to maintain adequate bone health.Fil: Mastaglia, Silvina Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Watson, Dana Zoe. Fundación de Osteoporosis y Enfermedades Metabólicas Óseas; ArgentinaFil: Oliveri, Maria Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentin

Estudiantes universitarios: ¿Qué comen mientras estudian?

Resumen Al momento no se disponen de suficientes datos sobre las elecciones alimentarias de los estudiantes universitarios. Las técni-cas proyectivas permiten recabar información que no se conseguiría mediante un interrogatorio directo ni por otros medios. El presente trabajo intenta conocer localmente la preferencia y motivos de la elección de alimentos o preparaciones alimenticias de los estudiantes durante su estadía en las facultades de la Universidad de Buenos Aires. Palabras clave: Elecciones alimentarias, Técnicas proyectivas, Estudiantes universitarios. Abstract At the moment there is insufficient data on food choices of university students. Projective techniques help to gather information that would not be achieved by direct examination or by other means. This paper attempts to locally know the preference and reasons for the choice of foods or food preparations of the students during their stay in the faculties of the University of Buenos Aires Keywords: Food choices, Projective Techniques, University students. Estudiantes universitarios: ¿Qué comen mientras estudian? University students: What do they eat while studying? Introducción Los factores que influyen en los consumidores para la elección de sus comidas son diversos, incluyendo entre otros: la tradición culinaria, la educación nutricional, el precio, la disponibilidad en comercios cercanos, la facilidad de preparación, las características sensoriales y la información de medios masivos de comunicación, entre otros (1, 2). Elorriaga y col aplicaron un cuestionario que evaluaba motivos de elección de comidas en estudiantes universitarios de carreras relacionadas con las ciencias de la salud. En la elección de sus comidas, los estudiantes asignaron mayor importancia al atractivo sensorial (sabor y aroma), seguido por los motivos relacionados con la salud y el contenido natural de los alimentos, el precio y la accesibilidad en los comercios, así como a la apariencia y los aspectos extrínsecos (3). Por otra parte, se reconoce que la alimentación tiene una importancia crucial como factor de riesgo de enfermedades crónicas. Entre otras, el exceso de grasas, azúcares y sodio, así como una alimentación con escasa cantidad de fibra se han asociado en forma convincente con un aumento del riesgo de obesidad, enfermedad cardiovascular y enfermedades dentales (4). Algunos trabajos locales y de otros países han observado las principales tendencias alimentarias en adultos jóvenes universitarios (5-8). En los mismos se estudiaron sus hábitos alimentarios y factores de riesgo presentes que, en conjunto, caracterizaron el estilo de vida. El trabajo realizado por Karleny et al encontró que los estudiantes universitarios que no desayunaban tendían a consumir luego más alimentos con alta densida

Vitamin D levels and their impact on mineral metabolism in HIV infected patients: An exploratory study

Vitamin D has immunomodulating properties. The nuclear receptor for vitamin D is expressed in several immune cells, which convert 25-hydroxyvitamin D(25OHD) to the active form 1,25 hydroxyvitamin D (1,25(OH)2 D). Under conditions of infection, 1,25(OH)2 D promotes production of cathelicidin (an antimicrobial peptide) in monocytes and activated macrophages. In vitro studies have shown the ability of cathelicidin to inhibit replication of human immunodeficiency virus (HIV-1) in T CD4 lymphocytes and macrophages. Objective: To evaluate vitamin D levels and their impact on mineral metabolism in HIV infected patients. Materials and Methods: Seventy-four clinical records of HIV/AIDS patients seen at the outpatients clinic were reviewed. The following data were collected: age, sex, time since diagnosis of HIV, HIV-1 viral load, CD4 counts (absolute value and percentage), and mineral metabolism determinations: 25OHD, intact parathormone (iPTH); serum calcium (sCa); serum phosphorus (sP) and serum crosslaps (sCTX). Vitamin D levels were stratified as follows: optimal: ≥30ng/ml; insufficient: 21-29ng/ml; moderately deficient: 20 -25OHD- >10 ng/ml and severely deficient ≤10 ng/ml. Results: Fifty-five clinical records were included; 82% of patients had 25OHD levels below 30ng/ml (insufficient: 23.6%, moderately deficient: 36.4%; and severely deficient: 21.8%). A significantly higher serum PTH levels in the moderately and severely deficient groups than in the optimal and insufficient groups was observed (p<0.05 and p<0.03 respectively). A weak negative correlation was observed between serum 25OHD and PTH levels (r=-0.268; p<0.004). Conclusion: Sub-optimal vitamin D levels are frequently observed in HIV/AIDS patients on antiretroviral therapy (ART). Systematic assessment of mineral metabolism is considered necessary in HIV/AIDS positive patients.Fil: Mastaglia, Silvina Rosana. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Watson, Dana Zoe. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; ArgentinaFil: Bellotti, Natalia. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Fridman, Vanesa. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Stecher, Daniel. Universidad de Buenos Aires. Facultad de Medicina. Hospital de Clínicas General San Martín; ArgentinaFil: Oliveri, María Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentin

Estimación de umbral sensorial en agua potable con calcio agregado: Primeros avances en el desarrollo de un agua enriquecida

El objetivo de este estudio fue estimar el umbral sensorial de agua potable con diferentes sales de calcio añadidas: cloruro de calcio, gluconato de calcio y lactato de calcio. Se utilizó la metodología de prueba del triángulo, y el umbral se estimó utilizando estadística de supervivencia. El valor de umbral sensorial de gluconato de calcio para un 25% de discriminación fue 587 ± 131 mg/l de agua, para el lactato de calcio a un 50% de discriminación fue de 676 ± 186 mg/l y para cloruro de calcio a un 50% de discriminación fue de 291 ± 73 mg/l. Los resultados muestran la factibilidad del enriquecimiento de agua con calcio utilizando diferentes sales y hasta una concentración de 500 mg de calcio/l de agua. La sal que permitió la mayor concentración con menos cambios sensoriales percibidos fue gluconato de calcio.The objective of this study was to estimate the sensory threshold of drinking water with different added calcium salts: calcium chloride, calcium gluconate and calcium lactate. The triangle test methodology was used, and the threshold was estimated using survival statistics. The sensory threshold value of calcium gluconate for 25% discrimination was 587 ± 131 mg/l of water, for calcium lactate at 50% discrimination it was 676 ± 186 mg/l and for calcium chloride at a 50% discrimination was 291 ± 73 mg/l. The results show the feasibility of enriching water with calcium using different salts and up to a concentration of 500 mg of calcium/l of water. The salt that allowed the highest concentration with the least perceived sensory changes was calcium gluconate.Fil: Cormick, Gabriela. Universidad Nacional de La Matanza; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Instituto de Efectividad Clínica y Sanitaria; ArgentinaFil: Matamoros, Natalia. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; Argentina. Provincia de Buenos Aires. Ministerio de Salud. Hospital de Niños "Sor María Ludovica" de La Plata; ArgentinaFil: Romero, Iris Beatriz. Universidad Nacional de La Matanza; ArgentinaFil: Perez, Surya Macarena. Universidad Nacional de La Matanza; ArgentinaFil: White, Cintia. Universidad Nacional de La Matanza; ArgentinaFil: Watson, Dana Zoe. Universidad Nacional de La Matanza; ArgentinaFil: Belizan, Jose. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Parque Centenario. Centro de Investigaciones en Epidemiología y Salud Pública. Instituto de Efectividad Clínica y Sanitaria. Centro de Investigaciones en Epidemiología y Salud Pública; ArgentinaFil: Sosa, Miriam Patricia. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Dirección General de Cultura y Educación. Instituto Superior Experimental de Tecnología Alimentaria; ArgentinaFil: Gugole Ottaviano, Maria Fernanda. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Dirección General de Cultura y Educación. Instituto Superior Experimental de Tecnología Alimentaria; Argentina. Provincia de Buenos Aires. Gobernación. Comisión de Investigaciones Científicas; ArgentinaFil: Elizagoyen, Eliana Soledad. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Dirección General de Cultura y Educación. Instituto Superior Experimental de Tecnología Alimentaria; ArgentinaFil: Garitta, Lorena Garitta. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Provincia de Buenos Aires. Dirección General de Cultura y Educación. Instituto Superior Experimental de Tecnología Alimentaria; Argentin

Fracture fixation in the operative management of hip fractures (FAITH): an international, multicentre, randomised controlled trial

Background Reoperation rates are high after surgery for hip fractures. We investigated the effect of a sliding hip screw versus cancellous screws on the risk of reoperation and other key outcomes. Methods For this international, multicentre, allocation concealed randomised controlled trial, we enrolled patients aged 50 years or older with a low-energy hip fracture requiring fracture fixation from 81 clinical centres in eight countries. Patients were assigned by minimisation with a centralised computer system to receive a single large-diameter screw with a side-plate (sliding hip screw) or the present standard of care, multiple small-diameter cancellous screws. Surgeons and patients were not blinded but the data analyst, while doing the analyses, remained blinded to treatment groups. The primary outcome was hip reoperation within 24 months after initial surgery to promote fracture healing, relieve pain, treat infection, or improve function. Analyses followed the intention-to-treat principle. This study was registered with ClinicalTrials.gov, number NCT00761813. Findings Between Mar

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease