The nuclear receptor LXRα controls the functional specialization of splenic macrophages.

Macrophages are professional phagocytic cells that orchestrate innate immune responses and have considerable phenotypic diversity at different anatomical locations. However, the mechanisms that control the heterogeneity of tissue macrophages are not well characterized. Here we found that the nuclear receptor LXRα was essential for the differentiation of macrophages in the marginal zone (MZ) of the spleen. LXR-deficient mice were defective in the generation of MZ and metallophilic macrophages, which resulted in abnormal responses to blood-borne antigens. Myeloid-specific expression of LXRα or adoptive transfer of wild-type monocytes restored the MZ microenvironment in LXRα-deficient mice. Our results demonstrate that signaling via LXRα in myeloid cells is crucial for the generation of splenic MZ macrophages and identify an unprecedented role for a nuclear receptor in the generation of specialized macrophage subsets

Climatization, energy efficiency and environmental protection

It is known that approximately 15% of the energy consumed in Ecuador is used for the operation of climate conditioning equipment and, on the other hand, most of the existing technology operates on the basis of the use of refrigerant gases Are invasive to the ozone layer. In the work, a case study is shown that allows the identification of a relevant result linked to an action of technological innovation based on the conversion of the R-22 gas by the R-290 gas, thus reducing the consumption of electric energy and reducing the Environmental inventory of the institution, achieving a better performance of the technology

Placebo-controlled trial of nimodipine in the treatment of acute ischemic cerebral infarction

Nimodipine is a 1,4-dihydropyridine derivative that shows a preferential cerebrovascular activity in experimental animals. Clinical data suggest that nimodipine has a beneficial effect on the neurologic outcome of patients suffering an acute ischemic stroke. Our double-blind placebo-controlled multicenter trial was designed to assess the effects of oral nimodipine on the mortality rate and neurologic outcome of patients with an acute ischemic stroke. One hundred sixty-four patients were randomly allocated to receive either nimodipine tablets (30 mg q.i.d.) or identical placebo tablets for 28 days. Treatment was always started less than or equal to 48 hours after the acute event. The Mathew Scale, slightly modified by Gelmers et al, was used for neurologic assessment. Mortality rate and neurologic outcome after 28 days were used as evaluation criteria. We considered 123 patients to be valid for the analysis of efficacy. Mortality rates did not differ significantly between groups. Neurologic outcome after 28 days of therapy did not differ between groups. However, when only those patients most likely to benefit from any intervention (Mathew Scale sum score of less than or equal to 65 at baseline) were analyzed separately in post hoc-defined subgroups, the nimodipine-treated subgroups showed a significantly better neurologic outcome. This result suggests that some patients with acute ischemic stroke will benefit from treatment with nimodipine tablets

Satisfacción laboral y factores de mejora en profesionales de atención primaria

Fundamento. La calidad de los servicios en un sistema sanitario está relacionada con el nivel de satisfacción de sus profesionales. El objetivo de este trabajo es conocer la satisfacción laboral y jerarquizar aquellos factores capaces de mejorarla, en profesionales de atención primaria. Metodología. Estudio descriptivo realizado en 2010 en Navarra. Se remitió por correo un cuestionario validado a la población de estudio: médicos, pediatras y enfermería de atención primaria. Se recogen variables de datos sociodemográficos y autocalificación de su satisfacción laboral en escala de 1 a 10. Se solicita la jerarquización de 10 factores que puedan mejorar la satisfacción previa señalada. Se realizó comparación de medias y análisis bivariante mediante el test de la Chi cuadrado, estudiando la asociación entre variables mediante la Odds Ratio (OR). El análisis ajustado se realizó mediante regresión logística no condicional. Resultados. Se recogieron 432 cuestionarios (77,5%). La satisfacción media fue 6,7 (escala 1 a 10), más alta en enfermería. Las mujeres presentaron una media superior a los hombres (6,90: 6,34). Los trabajadores de centros de salud urbanos (OR:1,71; IC:1,10-2,65) presentaron un mayor riesgo de insatisfacción respecto a los profesionales de centros rurales. Las actividades formativas de los profesionales es el ítem más valorado, seguido de razones económicas y de presión asistencial, no encontrándose diferencias por profesión. Conclusión. La satisfacción laboral es una dimensión de la gestión de calidad en atención primaria y su estudio permite identificar problemas u oportunidades de mejora con impacto en la calidad de los servicios que se ofertan.Background. The quality of services in a health system is related to the level of satisfaction of its professionals. The aim of this article is to determine job satisfaction in primary care professionals and rank those factors capable of improving it. Methodology. Descriptive study carried out in Navarre in 2010. A validated questionnaire was sent by post to the population of the study: primary care doctors, pediatricians and nurses. Variables on socio-demographic data were collected and job satisfaction was self-evaluated on a scale of 1 to 10. Respondents were asked to rank 10 factors that could improve the previously mentioned satisfaction. Averages were compared and bivariate analysis was carried out using the chi-square test, studying the association between variables through the Odds Ratio (OR). The adjusted analysis was realized through unconditional logistic regression. Results. We collected 432 questionnaires (77.5%). Average satisfaction was 6.7 (scale of 1 to 10), higher in nursing. Women showed a higher average than men (6.90:6.34). The workers at urban health centers (OR: 1.71; CI: 1.10- 2.65) showed a higher risk of dissatisfaction with respect to professionals at rural centers. The training activities of the professional is the most highly valued item, followed by economic questions and questions of care pressure, with no differences found by profession. Conclusion. Job satisfaction is a dimension of quality management in primary care and its study enables identification of problems or opportunities for improvement with an impact on the quality of the services offered

Validación de un cuestionario de mejora de la satisfacción laboral (CMSL) en profesionales de atención primaria

Fundamento. La satisfacción laboral de los profesionales sanitarios se considera un indicador de calidad en la gestión del sistema, estando relacionado con la eficacia de los servicios ofrecidos. El objetivo del estudio es la validación de un cuestionario para evaluar la mejora de la satisfacción laboral (CMSL) en una población de profesionales sanitarios de atención primaria en Navarra. Metodología. Se realizó un estudio descriptivo con cuestionarios autocumplimentados, siendo la población diana todos los profesionales de atención primaria (médicos, pediatras y personal de enfemería) de los centros de salud de Navarra. Se utilizó la escala Lickert para la medición de los ítems. Se recogieron datos descriptivos de sexo, años de ejercicio profesional, satisfacción laboral, estamento profesional, centro de salud y 47 ítems sobre mejora de satisfacción laboral. Se calculó la fiabilidad mediante el coeficiente alfa de Cronbach y se halló la validez de constructo mediante un análisis factorial con rotación varimax, agrupando los ítems en 9 dimensiones. Resultados. Se recogieron un total de 414 cuestionarios. Se obtuvo el coeficiente alfa de Cronbach, con un valor global de 0,933. Entre 5 dimensiones se explica el 41,287% de la varianza total. La dimensión “relaciones con los pacientes” presentó la media (4,087) más alta de mejora de la satisfacción laboral y el ítem “Si pudiera eliminar la demanda injustificada” presentó una media de 4,21. Conclusiones. El cuestionario diseñado es un instrumento válido para la evaluación integral de la mejora de la satisfacción laboral de los profesionales de atención primaria. Los resultados obtenidos pueden orientar sobre qué áreas de mejora se deben implantar para mejorar la satisfacción de los profesionales.Background. Job satisfaction of health professionals is considered to be a quality indicator, as it is related to the efficacy of the services. The aim of the study is to validate a questionnaire for evaluating job satisfaction improvement in a population of health professionals in primary care in Navarre. Methodology. Descriptive study with self-completed questionnaires; the target population was all health care professionals (family doctors, pediatricians and nurses) of primary health centers of Navarre. A Lickert scale was used for measuring the items. Other variables measured were: sex, years in the profession, job satisfaction, professional status, health center, and 47 items on improving job satisfaction. Cronbach’s alpha coefficient was used to evaluate reliability, and to evaluate construct validity factor analysis with varimax rotation, grouping the items in 9 dimensions was used. Results. A total of 414 questionnaires were collected. Cronbach’s alpha coefficient was 0.933. Forty-one point two eight seven percent (41.287%) of total variance was explained by five dimensions. The dimension “relations with patients” presented the highest average (4.087) of improvement in job satisfaction, and the item “If it were possible to eliminate unjustified demand” showed an average of 4.21. Conclusions. The questionnaire designed is a valid instrument for a comprehensive evaluation of the improvement in the job satisfaction of primary care professionals. The results obtained can indicate which areas of improvement should be implemented in order to improve the satisfaction of the professionals

MYH10 activation rescues contractile defects in arrhythmogenic cardiomyopathy (ACM).

The most prevalent genetic form of inherited arrhythmogenic cardiomyopathy (ACM) is caused by mutations in desmosomal plakophilin-2 (PKP2). By studying pathogenic deletion mutations in the desmosomal protein PKP2, here we identify a general mechanism by which PKP2 delocalization restricts actomyosin network organization and cardiac sarcomeric contraction in this untreatable disease. Computational modeling of PKP2 variants reveals that the carboxy-terminal (CT) domain is required for N-terminal domain stabilization, which determines PKP2 cortical localization and function. In mutant PKP2 cells the expression of the interacting protein MYH10 rescues actomyosin disorganization. Conversely, dominant-negative MYH10 mutant expression mimics the pathogenic CT-deletion PKP2 mutant causing actin network abnormalities and right ventricle systolic dysfunction. A chemical activator of non-muscle myosins, 4-hydroxyacetophenone (4-HAP), also restores normal contractility. Our findings demonstrate that activation of MYH10 corrects the deleterious effect of PKP2 mutant over systolic cardiac contraction, with potential implications for ACM therapy.This study was supported by MCIU grant BFU2016-75144-R and PID2020- 116935RB-I00, and by a “la Caixa” Banking Foundation grant under the project code HR18-00304” to J.A.B.; The study was also supported by the “Ayudas a la Investigación Cátedra Real Madrid-Universidad Europea” (2017/RM01). C.M.-L. and S.S. hold MCIU predoctoral contracts BES-2017-079715, and BES-2017-079707 respectively. R.G. acknowledges funding from the European Research Council under grant ERCAG-340177 (3DNanoMech) and from the MCIU under grant MAT2016- 76507-R. The CNIC is supported by the Instituto de Salud Carlos III (ISCIII), the Ministerio de Ciencia e Innovación (MCIN) and the Pro CNIC Foundation and is a Severo Ochoa Center of Excellence, grant CEX2020-001041-S funded by MICIN/AEI/10.13039/501100011033. The microscopy experiments were carried out at the Dynamic Microscopy and Image Unit, CNIC, ICTS-ReDib, co-financed by MCIN/AEI /10.13039/ 501100011033 and FEDER “A way of making Europe” (#ICTS-2018-04- CNIC-16). Imaris full analysis were carried out at the Microscopy & Dynamic Imaging, CNIC, ICTS-ReDib, co-funded by MCIN/AEI /10.13039/501100011033. Biomedical Imaging has been conducted at the Advanced Imaging Unit of the CNIC (Centro Nacional de Investigaciones Cardiovasculares Carlos III), Madrid, Spain. This project used the ReDIB ICTS infrastructure TRIMA@CNIC, Ministerio de Ciencia e Innovación (MCIN).S

Height and timing of growth spurt during puberty in young people living with vertically acquired HIV in Europe and Thailand.

OBJECTIVE: The aim of this study was to describe growth during puberty in young people with vertically acquired HIV. DESIGN: Pooled data from 12 paediatric HIV cohorts in Europe and Thailand. METHODS: One thousand and ninety-four children initiating a nonnucleoside reverse transcriptase inhibitor or boosted protease inhibitor based regimen aged 1-10 years were included. Super Imposition by Translation And Rotation (SITAR) models described growth from age 8 years using three parameters (average height, timing and shape of the growth spurt), dependent on age and height-for-age z-score (HAZ) (WHO references) at antiretroviral therapy (ART) initiation. Multivariate regression explored characteristics associated with these three parameters. RESULTS: At ART initiation, median age and HAZ was 6.4 [interquartile range (IQR): 2.8, 9.0] years and -1.2 (IQR: -2.3 to -0.2), respectively. Median follow-up was 9.1 (IQR: 6.9, 11.4) years. In girls, older age and lower HAZ at ART initiation were independently associated with a growth spurt which occurred 0.41 (95% confidence interval 0.20-0.62) years later in children starting ART age 6 to 10 years compared with 1 to 2 years and 1.50 (1.21-1.78) years later in those starting with HAZ less than -3 compared with HAZ at least -1. Later growth spurts in girls resulted in continued height growth into later adolescence. In boys starting ART with HAZ less than -1, growth spurts were later in children starting ART in the oldest age group, but for HAZ at least -1, there was no association with age. Girls and boys who initiated ART with HAZ at least -1 maintained a similar height to the WHO reference mean. CONCLUSION: Stunting at ART initiation was associated with later growth spurts in girls. Children with HAZ at least -1 at ART initiation grew in height at the level expected in HIV negative children of a comparable age

The role of a firm's absorptive capacity and the technology transfer process in clusters: How effective are technology centres in low-tech clusters?

This paper analyses how the internal resources of small- and medium-sized enterprises determine access (learning processes) to technology centres (TCs) or industrial research institutes (innovation infrastructure) in traditional low-tech clusters. These interactions basically represent traded (market-based) transactions, which constitute important sources of knowledge in clusters. The paper addresses the role of TCs in low-tech clusters, and uses semi-structured interviews with 80 firms in a manufacturing cluster. The results point out that producer–user interactions are the most frequent; thus, the higher the sector knowledge-intensive base, the more likely the utilization of the available research infrastructure becomes. Conversely, the sectors with less knowledge-intensive structures, i.e. less absorptive capacity (AC), present weak linkages to TCs, as they frequently prefer to interact with suppliers, who act as transceivers of knowledge. Therefore, not all the firms in a cluster can fully exploit the available research infrastructure, and their AC moderates this engagement. In addition, the existence of TCs is not sufficient since the active role of a firm's search strategies to undertake interactions and conduct openness to available sources of knowledge is also needed. The study has implications for policymakers and academia

Lipid profile, cardiovascular disease and mortality in a Mediterranean high-risk population: the ESCARVAL-RISK study

The potential impact of targeting different components of an adverse lipid profile in populations with multiple cardiovascular risk factors is not completely clear. This study aims to assess the association between different components of the standard lipid profile with all cause mortality and hospitalization due to cardiovascular events in a high-risk population. Methods This prospective registry included high risk adults over 30 years old free of cardiovascular disease (2008±2012). Diagnosis of hypertension, dyslipidemia or diabetes mellitus was inclusion criterion. Lipid biomarkers were evaluated. Primary endpoints were all-cause mortality and hospital admission due to coronary heart disease or stroke. We estimated adjusted rate ratios (aRR), absolute risk differences and population attributable risk associated with adverse lipid profiles. Results 51,462 subjects were included with a mean age of 62.6 years (47.6% men). During an average follow-up of 3.2 years, 919 deaths, 1666 hospitalizations for coronary heart disease and 1510 hospitalizations for stroke were recorded. The parameters that showed an increased rate for total mortality, coronary heart disease and stroke hospitalization were, respectively, low HDL-Cholesterol: aRR 1.25, 1.29 and 1.23; high Total/HDL-Cholesterol: aRR 1.22, 1.38 and 1.25; and high Triglycerides/HDL-Cholesterol: aRR 1.21, 1.30, 1.09. The parameters that showed highest population attributable risk (%) were, respectively, low HDL-Cholesterol: 7.70, 11.42, 8.40; high Total/HDL-Cholesterol: 6.55, 12.47, 8.73; and high Triglycerides/ HDL-Cholesterol: 8.94, 15.09, 6.92. Conclusions In a population with cardiovascular risk factors, HDL-cholesterol, Total/HDL-cholesterol and triglycerides/HDL-cholesterol ratios were associated with a higher population attributable risk for cardiovascular disease compared to other common biomarkers