Critical Care Requirements Under Uncontrolled Transmission of SARS-CoV-2

Objectives. To estimate the critical care bed capacity that would be required to admit all critical COVID-19 cases in a setting of unchecked SARS-CoV-2 transmission, both with and without elderly-specific protection measures. Methods. Using electronic health records of all 2432 COVID-19 patients hospitalized in a large hospital in Madrid, Spain, between February 28 and April 23, 2020, we estimated the number of critical care beds needed to admit all critical care patients. To mimic a hypothetical intervention that halves SARS-CoV-2 infections among the elderly, we randomly excluded 50% of patients aged 65 years and older. Results. Critical care requirements peaked at 49 beds per 100 000 on April 1-2 weeks after the start of a national lockdown. After randomly excluding 50% of elderly patients, the estimated peak was 39 beds per 100 000. Conclusions. Under unchecked SARS-CoV-2 transmission, peak critical care requirements in Madrid were at least fivefold higher than prepandemic capacity. Under a hypothetical intervention that halves infections among the elderly, critical care peak requirements would have exceeded the prepandemic capacity of most high-income countries. Public Health Implications. Pandemic control strategies that rely exclusively on protecting the elderly are likely to overwhelm health care systems.S

Phosphatidylinositol 3-Kinase Regulates the CD4/CD8 T Cell Differentiation Ratio

AbstractThe signaling pathways that control T cell differentiation have only begun to be elucidated. Using T cell lines, it has been shown that class IA phosphatidylinositol 3-kinase (PI3K), a heterodimer composed of a p85 regulatory and a p110 catalytic subunit, is activated after TCR stimulation. Nonetheless, the contribution of p85/p110 PI3K isoforms in T cell development has not been described. Mice deficient in the other family of class I PI3K, p110γ, which is regulated by G protein-coupled receptors, exhibit reduced thymus size. Here we examine T cell development in p110γ-deficient mice and in mice expressing an activating mutation of the p85 regulatory subunit, p65PI3K, in T cells. We show that p110γ-deficient mice have a partial defect in pre-TCR-dependent differentiation, which is restored after expression of the p65PI3K activating mutation. Genetic alteration of both PI3K isoforms also affects positive selection; p110γ deletion decreased and p65PI3K expression augmented the CD4+/CD8+ differentiation ratio. Finally, data are presented showing that both PI3K isoforms influenced mature thymocyte migration to the periphery. These observations underscore the contribution of PI3K in T cell development, as well as its implication in determining the CD4+/CD8+ T cell differentiation ratio in vivo

Personal body ornamentation on the Southern Iberian Meseta: An archaeomineralogical study

Beads and pendants from the Castillejo del Bonete (Terrinches, Ciudad Real) and Cerro Ortega (Villanueva de la Fuente, Ciudad Real) burials were analysed using XRD, micro-Raman and XRF in order to contribute to the current distribution map of green bead body ornament pieces on the Iberian Peninsula which, so far, remain undetailed for many regions. XRD, micro-Raman and XRF analyses showed that most of the beads from Castillejo del Bonete (Late 3rd millennium cal. BC) were made from variscite or green phyllosilicates, while Cerro Ortega's (Late 4th millenniumcal. BC) beads were made out of fossil wood or Clinochlore. Significantly enough,while XRD pointed to variscite as the main crystallo-graphic phase, the elemental composition did not match any elemental compositions of known and characterised sources, thus suggesting an unknown south-eastern source or an extra-peninsular origin of these ornamental pieces

El estudio PROPRESE: resultados de un nuevo modelo organizativo en atención primaria para pacientes con cardiopatía isquémica crónica basado en una intervención multifactorial

ResumenObjetivoComparando los resultados obtenidos en los estudios EUROASPIRE I y EUROASPIRE III en pacientes con cardiopatía isquémica se muestra que el grado de control de los factores de riesgo mayores es mejorable. El objetivo de este estudio es evaluar la eficacia de una intervención multifactorial orientada a la mejora del grado de control en estos pacientes en el ámbito de la atención primaria.MétodosEn este estudio de intervención aleatorizado, con 1 año de seguimiento, se reclutó a pacientes con diagnóstico de cardiopatía isquémica (145 en el grupo de intervención y 1.461 en el grupo control). Se aplicó una intervención organizativa mixta basada en la mejora de la relación profesional sanitario-paciente (de acuerdo a los modelos del Chronic Care, el Stanford Expert Patient Programme y el Kaiser Permanente) y en la formación profesional continuada. Los principales resultados fueron el efecto sobre el tabaquismo, el colesterol unido a lipoproteínas de baja densidad (cLDL), la presión arterial sistólica (PAS) y la presión arterial diastólica (PAD) a través de un análisis multivariable.ResultadosLas características de los pacientes fueron: edad (68,4±11,8 años), varones (71,6%), diabetes mellitus (51,3%), dislipemia (68,5%), hipertensión arterial (76,7%), no fumadores (76,1%); cLDL < 100mg/dl (46,9%); PAS < 140mmHg (64,5%); PAD < 90 (91,2%). El análisis multivariable mostró que el riesgo para el buen control en el grupo de intervención fue tabaquismo, riesgo relativo ajustado (RRa): 15,7 (intervalo de confianza del 95% [IC95%], 4,2–58,7); p < 0,001; cLDL, RRa: 2,98 (IC95%, 1,48–6,02); p < 0,002; PAS, RRa: 1.97 (IC95%, 1,21–3,23); p < 0,007, y PAD; RRa: 1,51 (IC95%, 0,65–3,50); p < 0,342.ConclusionesUna intervención multifactorial basada en el modelo de paciente crónico centrada en atención primaria y que facilite la toma de decisiones compartidas con los pacientes y la formación de los profesionales mejora el grado de control de los factores de riesgo cardiovascular (tabaquismo, cLDL y PAS). Las estrategias de mejora en la atención de la cronicidad pueden ser una herramienta eficaz para conseguir mejores resultados.AbstractObjectiveComparison of the results from the EUROASPIRE I to the EUROASPIRE III, in patients with coronary heart disease, shows that the prevalence of uncontrolled risk factors remains high. The aim of the study was to evaluate the effectiveness of a new multifactorial intervention in order to improve health care for chronic coronary heart disease patients in primary care.MethodsIn this randomized clinical trial with a 1-year follow-up period, we recruited patients with a diagnosis of coronary heart disease (145 for the intervention group and 1461 for the control group). An organizational intervention on the patient-professional relationship (centered on the Chronic Care Model, the Stanford Expert Patient Programme and the Kaiser Permanente model) and formative strategy for professionals were carried out. The main outcomes were smoking control, low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP). A multivariate analysis was performed.ResultsThe characteristics of patients were: age (68.4±11.8 years), male (71.6%), having diabetes mellitus (51.3%), dyslipidemia (68.5%), arterial hypertension (76.7%), non-smokers (76.1%); LDL-C < 100mg/dL (46.9%); SBP < 140mmHg (64.5%); DBP < 90 (91.2%). The multivariable analysis showed the risk of good control for intervention group to be: smoking, adjusted relative risk (aRR): 15.70 (95% confidence interval [95%CI], 4.2–58.7); P < .001; LDL-C, aRR: 2.98 (95%CI, 1.48–6.02); P < .002; SPB, aRR: 1.97 (95%CI, 1.21–3.23); P < .007, and DBP: aRR: 1.51 (95%CI, 0.65–3.50); P < .342.ConclusionsAn intervention based on models for chronic patients focused in primary care and involving patients in medical decision making improves cardiovascular risk factors control (smoking, LDL-C and SBP). Chronic care strategies may be an efficacy tool to help clinicians to involve the patients with a diagnosis of CHD to reach better outcomes

Birth weight and blood lipid levels in Spanish adolescents: Influence of selected APOE, APOC3 and PPARgamma2 gene polymorphisms. The AVENA Study

Es reproducción del documento publicado en http://dx.doi.org/10.1186/1471-2350-9-98Background: There is increasing evidence indicating that genes involved in certain metabolic processes of cardiovascular diseases may be of particular influence in people with low body weight at birth. We examined whether the apolipoprotein (APO) E, APOC3 and the peroxisome proliferator-activated receptor-gamma-2 (PPAR gamma 2) polymorphisms influence the association between low birth weight and blood lipid levels in healthy adolescents aged 13-18.5 years. Methods: A cross-sectional study of 502 Spanish adolescents born at term was conducted. Total (TC) and high density lipoprotein cholesterol (HDLc), triglycerides (TG), apolipoprotein (apo) A and B, and lipoprotein(a) [ Lp(a)] were measured. Low density lipoprotein cholesterol (LDLc), TC-HDLc, TC/HDLc and apoB/apoA were calculated. Results: Low birth weight was associated with higher levels of TC, LDLc, apoB, Lp(a), TC-HDLc, TC/HDLc and apoB/apoA in males with the APOE epsilon 3 epsilon 4 genotype, whereas in females, it was associated with lower HDLc and higher TG levels. In males with the APOC3 S1/S2 genotype, low birth weight was associated with lower apoA and higher Lp(a), yet this association was not observed in females. There were no associations between low birth weight and blood lipids in any of the PPAR gamma 2 genotypes. Conclusion: The results indicate that low birth weight has a deleterious influence on lipid profile particularly in adolescents with the APOE epsilon 3/epsilon 4 genotype. These findings suggest that intrauterine environment interact with the genetic background affecting the lipid profile in later life.Instituto de Salud Carlos III (FIS PI021830), the Spanish Ministry of Health, FEDER-FSE funds FIS n 00/0015, CSD grants 05/UPB32/0, 109/UPB31/03 and 13/UPB20/04, Ministerio de Educación (AP-2004-2745; EX2007-1124

Calorie restriction improves physical performance and modulates the antioxidant and inflammatory responses to acute exercise

Our aim was to characterize the effects of calorie restriction on the anthropometric characteristics and physical performance of sportsmen and to evaluate the effects of calorie restriction and acute exercise on mitochondria energetics, oxidative stress, and inflammation. Twenty volunteer taekwondo practitioners undertook a calorie restriction of 30-40% on three alternate days a week for one month. Eleven volunteer sportsmen participated as controls. Both groups performed an energy effciency test to evaluate physical performance, and samples were taken before and after exercise. The total weight of participants significantly decreased (5.9%) after calorie restriction, while the effciency of work and the contributions of fat to obtain energy were enhanced by calorie restriction. No significant differences induced by acute exercise were observed in individual non-esterified fatty acid percentage or oxidative stress markers. Calorie restriction downregulated the basal gene expression of nitric oxide synthase, antioxidant enzymes, mitochondrial uncoupling proteins, and repairing stress proteins, but it enhanced the expression of sirtuins in peripheral blood mononuclear cells. In conclusion, one month of calorie restriction decreases body weight and increases physical performance, enhancing energy effciency, moderating the antioxidant and inflammatory basal gene expression, and influencing its response to acute exercise

Assessment of VINO filters for correcting redgreen Color Vision Deficiency

In our ongoing research on the effectiveness of different passive tools for aiding Color Vision Deficiency (CVD) subjects, we have analyzed the VINO 02 Amp Oxy-Iso glasses using two strategies: 1) 52 observers were studied using four color tests (recognition, arrangement, discrimination, and color-naming); 2) the spectral transmittance of the lenses were used to model the color appearance of natural scenes for different simulated CVD subjects. We have also compared VINO and EnChroma glasses. The spectral transmission of the VINO glasses significantly changed color appearance. This change would allow some CVD subjects, above all the deutan ones, to be able to pass recognition tests but not the arrangement tests. To sum up, our results support the hypothesis that glasses with filters are unable to effectively resolve the problems related to color vision deficiency.The Spanish State Agency of Research (AEI); the Ministry for Economy, Industry and Competitiveness (MIMECO) (Grant numbers FIS2017-89258-P and DPI 2015-64571-R); European Union FEDER (European Regional Development Funds)

Resumen ejecutivo del documento de consenso sobre el manejo de la patología renal en pacientes con infección por VIH

El objetivo de este documento es actualizar las recomendaciones sobre la evaluación y el manejo de la afectación renal en pacientes con infección por el VIH del año 2010. La función renal debe monitorizarse en todos los pacientes e incluir la medida de la concentración sérica de creatinina, la estimación del filtrado glomerular (ecuación CKD-EPI), la medida del cociente proteína/creatinina en orina y un sedimento urinario. El estudio básico de la función tubular ha de incluir la concentración sérica de fosfato y la tira reactiva de orina (glucosuria). En ausencia de alteraciones, el cribado será anual. En pacientes tratados con tenofovir o con factores de riesgo para el desarrollo de enfermedad renal crónica (ERC), se recomienda una evaluación más frecuente. Se debe evitar el uso de antirretrovirales potencialmente nefrotóxicos en pacientes con ERC o factores de riesgo para evitar su progresión. También se revisan las indicaciones de la biopsia renal, cuándo enviar el paciente al nefrólogo y las indicaciones, evaluación y manejo del paciente en diálisis o del trasplante renal

Análisis de Costes y de Coste/Eficacia de las Pautas Recomendadas por GESIDA/Plan Nacional sobre el Sida en 2018 Para el Tratamiento Antirretroviral Inicial en Adultos Infectados Por el VIH

[Background]: The GESIDA/National AIDS Plan expert panel recommended preferred regimens (PR), alternative regimens (AR) and other regimens (OR) for antiretroviral treatment (ART) as initial therapy in HIV-infected patients for 2018. The objective of this study was to evaluate the costs and the efficiency of initiating treatment with PR and AR. [Methods]: Economic assessment of costs and efficiency (cost-effectiveness) based on decision tree analyses. Effectiveness was defined as the probability of reporting a viral load <50 copies/mL at week 48, in an intention-to-treat analysis. Cost of initiating treatment with an ART regimen was defined as the costs of ART and its consequences (adverse effects, changes of ART regimen, and drug-resistance studies) over the first 48 weeks. The payer perspective (National Health System) was applied considering only differential direct costs: ART (official prices), management of adverse effects, studies of resistance, and HLA B*5701 testing. The setting was Spain and the costs correspond to those of 2018. A deterministic sensitivity analysis was conducted, building three scenarios for each regimen: base case, most favourable and least favourable. [Results]: In the base-case scenario, the cost of initiating treatment ranges from 6788 euros for TAF/FTC/RPV (AR) to 10,649 euros for TAF/FTC + RAL (PR). The effectiveness varies from 0.82 for TAF/FTC + DRV/r (AR) to 0.91 for TAF/FTC + DTG (PR). The efficiency, in terms of cost-effectiveness, ranges from 7814 to 12,412 euros per responder at 48 weeks, for ABC/3TC/DTG (PR) and TAF/FTC + RAL (PR), respectively. [Conclusion]: Considering ART official prices, the most efficient regimen was ABC/3TC/DTG (PR), followed by TAF/FTC/RPV (AR) and TAF/FTC/EVG/COBI (AR).[Introducción]: El panel de expertos de GESIDA/Plan Nacional del Sida ha recomendado pautas preferentes (PP), pautas alternativas (PA) y otras pautas (OP) para el tratamiento antirretroviral (TAR) como terapia de inicio en pacientes infectados por VIH para 2018. El objetivo de este estudio es evaluar los costes y la eficiencia de iniciar tratamiento con PP y PA. [Métodos]: Evaluación económica de costes y eficiencia (coste/eficacia) mediante construcción de árboles de decisión. Se definió eficacia como la probabilidad de tener carga viral <50 copias/ml en la semana 48 en análisis por intención de tratar. Se definió coste de iniciar tratamiento con una pauta como los costes del TAR y de todas sus consecuencias (efectos adversos, cambios de pauta y estudio de resistencias) que se producen en las siguientes 48 semanas. Se utilizó la perspectiva del Sistema Nacional de Salud, considerando solo costes directos diferenciales: TAR (a precio oficial), manejo de efectos adversos, estudios de resistencias y determinación de HLA-B*5701. El ámbito es España, con costes de 2018. Se realizó un análisis de sensibilidad determinista construyendo 3 escenarios para cada pauta: basal, más favorable y más desfavorable. [Resultados]: En el escenario basal, los costes de iniciar tratamiento oscilaron entre 6.788 para TAF/FTC/RPV (PA) y 10.649 para TAF/FTC + RAL (PP). La eficacia osciló entre 0,82 para TAF/FTC + DRV/r (PA) y 0,91 para TAF/FTC + DTG (PP). La eficiencia, en términos de coste/eficacia, osciló entre 7.814 y 12.412 por respondedor a las 48 semanas, para ABC/3TC/DTG (PP) y TAF/FTC + RAL (PP), respectivamente. [Conclusión]: Considerando el precio oficial del TAR, la pauta más eficiente fue ABC/3TC/DTG (PP), seguida de TAF/FTC/RPV (PA) y TAF/FTC/EVG/COBI (PA)

Genomic transformation and social organization during the Copper Age-Bronze Age transition in southern Iberia

The emerging Bronze Age (BA) of southeastern Iberia saw marked social changes. Late Copper Age (CA) settlements were abandoned in favor of hilltop sites, and collective graves were largely replaced by single or double burials with often distinctive grave goods indirectly reflecting a hierarchical social organization, as exemplified by the BA El Argar group. We explored this transition from a genomic viewpoint by tripling the amount of data available for this period. Concomitant with the rise of El Argar starting ~2200 cal BCE, we observe a complete turnover of Y-chromosome lineages along with the arrival of steppe-related ancestry. This pattern is consistent with a founder effect in male lineages, supported by our finding that males shared more relatives at sites than females. However, simple two-source models do not find support in some El Argar groups, suggesting additional genetic contributions from the Mediterranean that could predate the BA