“Dermal Dendritic Cells” Comprise Two Distinct Populations: CD1+ Dendritic Cells and CD209+ Macrophages

A key cell type of the resident skin immune system is the dendritic cell (DC), which in normal skin is located in two distinct microanatomical compartments: Langerhans cells (LCs), mainly in the epidermis, and dermal DCs (DDCs), in the dermis. Here, the lineage of DDCs was investigated using monoclonal antibodies and immunohistology. We provide evidence that “DDC” comprise at least two major phenotypic populations of dendritic-appearing cells, immature DC expressing CD1, CD11c and CD208; and macrophages expressing CD209, CD206, CD163, and CD68. These data suggest that dermal dendritic-appearing macrophages comprise a novel part of the innate immune response in the resident skin immune system

Evaluation of the relationship between pharmacokinetics and the safety of aripiprazole and its cardiovascular effects in healthy volunteers

The aim of this study was the evaluation of the possible relationship between pharmacokinetics and the safety of aripiprazole as well as its influence on blood pressure (BP), heart rate (HR), and corrected QT (QTc) interval. Methods: The study population comprised 157 healthy volunteers from 6 bioequivalence clinical trials. Subjects were administered a single 10-mg oral dose of each formulation separated by a 28-day washout period. Plasma concentrations were measured using high-performance liquid chromatography coupled to mass spectrometry. Blood pressure was measured at the following times: predose and 0.5, 2, 4, 6, and 8 hours postdose. An electrocardiogram was recorded at predose, 4, and 8 hours postdose. Results: Area under the curve (AUC), maximum plasma concentration, half-life, and distribution volume corrected for weight were higher in women. Aripiprazole treatment produced a decrease of BP (9.3 mm Hg on systolic and 6.2 mm Hg on diastolic pressure) and an increase in HR (12.1 beats per minute) and QTc interval (9.1 milliseconds). There were sex differences in BP, HR, and QTc interval. Women and subjects with higher AUC and maximum plasma concentration values were more prone to experience adverse drug reactions and gastrointestinal adverse reactions. The AUC was related with systolic BP and diastolic BP decrease and HR increase but there was no relationship between aripiprazole concentrations and QTc increase. Conclusions: Aripiprazole decreases BP and increases HR and QTc interval. Pharmacokinetics, pharmacodynamics, and safety of aripiprazole are affected by sex. There is a directly proportional relationship between pharmacokinetic parameters and adverse drug reactions and effect on BP and HRThis study was partially funded by Fundación Teófilo Hernando and Foundation for Biomedical Research at Hospital Universitario de La Princes

Measuring eating habits and physical activity in children: Synthesis of information using indexes and clusters / Medición de hábitos saludables y no saludables en niños: Síntesis de la información utilizando indicadores y conglomerados

Abstract Assessing healthy habits related to child overweight and obesity is important concerning the prevention efforts. A variety of measures to assess eating habits and physical activity are available, being the self-report frequency questionnaires the most common and cost-efficient. Nevertheless, those questionnaires generate a large amount of data. Considering this, the purpose of the study was to develop a proposal to synthesize information from the Child Overweight/Obesity Healthy related Habits Questionnaire (CHS-SO), through the creation of indexes and a combination of a factorial method and cluster analysis. Nine indexes were created to assess eating habits, physical activity, and digital entertainment use, allowing to classify children into healthy or unhealthy in each index. The CHS-SO was administered to 239 children between 8 and 12 years old from Cali, Colombia. Data obtained from the indexes were analyzed using a multiple correspondence analysis and cluster analysis. Results show that most of the children have healthy eating habits, physical activity was lower in girls and digital entertainment use was high.Resumen Evaluar los hábitos de salud relacionados con el sobrepeso y la obesidad infantil resulta fundamental para la prevención de estas problemáticas. Existe una amplia variedad de instrumentos para medir dichos hábitos, siendo más comunes y costo-eficientes los cuestionarios de autorreporte, sin embargo estos generan información demasiado extensa y difícil de analizar. Por tanto, este estudio tuvo como objetivo desarrollar una propuesta de síntesis de la información obtenida del  Cuestionario de Hábitos de Salud relacionados con el Sobrepeso/Obesidad Infantil (CHS-SO), a partir de la construcción de indicadores de hábitos de alimentación, de actividad física y de consumo de entretenimiento digital que permitan clasificar a los niños como saludables o no saludables. Participaron 239 niños y niñas de 8 a 12 años de edad, quienes completaron el CHS-SO. La combinación del análisis de correspondencias múltiples con el de conglomerados arrojó dos clústers. Los hábitos de alimentación fueron saludables en la mayoría de los niños, sin embargo fueron identificadas diferencias en función del sexo y el nivel socioeconómico. Por el contrario, los dos hábitos menos saludables fueron el comer mientras se emplean dispositivos de entretenimiento digital y el tiempo destinado a estos últimos.

Empoderamiento del alumnado adulto y de las personas mayores para una ciudadanía activa

Esta obra reúne iniciativas y experiencias de sensibilización y formación del profesorado y del alumnado adulto y mayor hacia una educación en competencias que contribuya a desarrollar la práctica de una ciudadanía activa compartiendo el tiempo libre, los conocimientos y las experiencias en proyectos sociales que consoliden y mejoren el entramado social de la ciudad, de las personas que la habitan y de la atención a sus necesidades. Su origen fue el proyecto CiudAct cofinanciado por el Programa Erasmus+ de la Unión Europea y en su desarrollo ha intervenido un equipo interinstitucional liderado por el Aula de Mayores+55 de la Universidad de Málaga y participado por el Centro de Profesorado «José Rodríguez Galán» de Antequera, la Asociación Cívica para la Prevención (ACP), la Asociación de Igualdad de Género Universitario (AIGU), y el Ayuntamiento de Faraján (Málaga). Con ellos, y con otras tantas instituciones y sus respectivos consorcios locales en toda Europa, se participa en la red supranacional Ciudades en Crecimiento.Programa Erasmus+ de la Unión Europea (referencia de proyecto 2015-1-ES01-KA104-014944

Metodología para la creación y gestión de un sistema de seguimiento de egresados de la Facultad de Ciencias Matemáticas y su aplicación en la mejora de los títulos

Fac. de Ciencias MatemáticasFALSEUCMsubmitte

Frequency and Characteristics of familial melanoma in Spain: the FAM-GEM-1 Study.

Familial history of melanoma is a well-known risk factor for the disease, and 7% melanoma patients were reported to have a family history of melanoma. Data relating to the frequency and clinical and pathological characteristics of both familial and non-familial melanoma in Spain have been published, but these only include patients from specific areas of Spain and do not represent the data for the whole of Spain. PATIENTS AND METHODS: An observational study conducted by the Spanish Group of Melanoma (GEM) analyzed the family history of patients diagnosed with melanoma between 2011 and 2013 in the dermatology and oncology departments. RESULTS: In all, 1047 patients were analyzed, and 69 (6.6%) fulfilled criteria for classical familial melanoma (two or more first-degree relatives diagnosed with melanoma). Taking into account other risk factors for familial melanoma, such as multiple melanoma, pancreatic cancer in the family or second-degree relatives with melanoma, the number of patients fulfilling the criteria increased to 165 (15.8%). Using a univariate analysis, we determined that a Breslow index of less than 1 mm, negative mitosis, multiple melanoma, and a history of sunburns in childhood were more frequent in familial melanoma patients, but a multivariate analysis revealed no differences in any pathological or clinical factor between the two groups. CONCLUSIONS: Similar to that observed in other countries, familial melanoma accounts for 6.6% of melanoma diagnoses in Spain. Although no differences in the multivariate analysis were found, some better prognosis factors, such as Breslow index, seem more frequent in familial melanoma, which reflect a better early detection marker and/or a different biological behavior

Phase I prognostic online (PIPO): A web tool to improve patient selection for oncology early phase clinical trials

Immunotherapy; Phase 1 trials; Prognostic modelInmunoterapia; Ensayos de fase 1; Modelo pronósticoImmunoteràpia; Assajos de fase 1; Model pronòsticPurpose Patient selection in phase 1 clinical trials (Ph1t) continues to be a challenge. The aim of this study was to develop a user-friendly prognostic calculator for predicting overall survival (OS) outcomes in patients to be included in Ph1t with immune checkpoint inhibitors (ICIs) or targeted agents (TAs) based on clinical parameters assessed at baseline. Methods Using a training cohort with consecutive patients from the VHIO phase 1 unit, we constructed a prognostic model to predict median OS (mOS) as a primary endpoint and 3-month (3m) OS rate as a secondary endpoint. The model was validated in an internal cohort after temporal data splitting and represented as a web application. Results We recruited 799 patients (training and validation sets, 558 and 241, respectively). Median follow-up was 21.2 months (m), mOS was 10.2 m (95% CI, 9.3–12.7) for ICIs cohort and 7.7 m (95% CI, 6.6–8.6) for TAs cohort. In the multivariable analysis, six prognostic variables were independently associated with OS – ECOG, number of metastatic sites, presence of liver metastases, derived neutrophils/(leukocytes minus neutrophils) ratio [dNLR], albumin and lactate dehydrogenase (LDH) levels. The phase 1 prognostic online (PIPO) calculator showed adequate discrimination and calibration performance for OS, with C-statistics of 0.71 (95% CI 0.64–0.78) in the validation set. The overall accuracy of the model for 3m OS prediction was 87.2% (95% CI 85%–90%). Conclusions PIPO is a user-friendly objective and interactive tool to calculate specific survival probabilities for each patient before enrolment in a Ph1t. The tool is available at https://pipo.vhio.net/.The research leading to these results has received funding from “la Caixa” Foundation (LCF/PR/CE07/50610001). Cellex Foundation for providing research facilities and equipment. This work was supported by the Accelerator Award (UpSMART) from Fundacion Científica – Asociacion Espanola Contra el Cancer (FC -AECC)/ Associazione Italiana per la Ricerca sul Cancro (AIRC) /Cancer Research United Kingdom (CRUK)

Late gadolinium enhancement distribution patterns in non-ischemic dilated cardiomyopathy: Genotype-phenotype correlation.

AIMS Late gadolinium enhancement (LGE) is frequently found in patients with dilated cardiomyopathy (DCM), there is little information about its frequency and distribution pattern according to underlying genetic substrate. We sought to describe LGE patterns according to genotype and to analyze the risk of major ventricular arrhythmias (MVA) according to patterns. METHODS AND RESULTS Cardiac magnetic resonance findings and LGE distribution according to genetics was performed in a cohort of 600 DCM patients followed at 20 Spanish centers. After exclusion of individuals with multiple causative gene variants or with variants in infrequent DCM-causing genes, 577 patients (34% females, mean age 53.5 years, LVEF 36.9 ± 13.9%) conformed the final cohort. A causative genetic variant was identified in 219 (38%) patients and 147 (25.5%) had LGE. Significant differences were found comparing LGE patterns between genes (P < 0.001). LGE was absent or rare in patients with variants in TNNT2, RBM20 and MYH7 (0%, 5% and 20%, respectively). Patients with variants in DMD, DSP and FLNC showed predominance of LGE subepicardial pattern (50%, 41% and 18%, respectively) whereas patients with variants in TTN, BAG3, LMNA and MYBPC3 showed unspecific LGE patterns. Genetic yield differed according to LGE pattern. Patients with subepicardial, lineal midwall, transmural, right ventricular insertion points or with combination of LGE patterns showed increased risk of MVA compared with patients without LGE. CONCLUSION LGE patterns in DCM has a specific distribution according to the affected gene. Certain LGE patterns are associated with increased risk of MVA and with increased yield of genetic testing.This study has been funded by Instituto Salud Carlos III (ISCIII) through the projects ‘PI18/0004, PI19/01283, and PI20/0320’ (co-funded by the European Regional Development Fund/European Social Fund ‘A way to make Europe’/‘Investing in your future’). The Hospital Universitario Puerta de Hierro, the Hospital Universitario Vall Hebrón, the Hospital General Universitario Gregorio Marañón, and the Hospital Universitario Virgen de la Arrixaca are members of the European Reference Network for Rare, Low Prevalence, and Complex Diseases of the Heart (ERN GUARD-Heart). F.d.F. receives grant support from ISCIII (CM20/00101). R.B. receives funding from the Obra Social la Caixa Foundation. M.B. receives funding from ISCIII (PI19/01283). The CNIC is supported by the ISCIII, Ministerio de Ciencia e Innovación of the Spanish Government (MCIN), and Pro CNIC Foundation.S

Predictores de riesgo en una cohorte española con cardiolaminopatías. Registro REDLAMINA

[Abstract] Introduction and objectives. According to sudden cardiac death guidelines, an implantable cardioverter-defibrillator (ICD) should be considered in patients with LMNA-related dilated cardiomyopathy (DCM) and ≥ 2 risk factors: male sex, left ventricular ejection fraction (LVEF) < 45%, nonsustained ventricular tachycardia (NSVT), and nonmissense genetic variants. In this study we aimed to describe the clinical characteristics of carriers of LMNA genetic variants among individuals from a Spanish cardiac-laminopathies cohort (REDLAMINA registry) and to assess previously reported risk criteria. Methods. The relationship between risk factors and cardiovascular events was evaluated in a cohort of 140 carriers (age ≥ 16 years) of pathogenic LMNA variants (54 probands, 86 relatives). We considered: a) major arrhythmic events (MAE) if there was appropriate ICD discharge or sudden cardiac death; b) heart failure death if there was heart transplant or death due to heart failure. Results. We identified 11 novel and 21 previously reported LMNA-related DCM variants. LVEF < 45% (P = .001) and NSVT (P < .001) were related to MAE, but not sex or type of genetic variant. The only factor independently related to heart failure death was LVEF < 45% (P < .001). Conclusions. In the REDLAMINA registry cohort, the only predictors independently associated with MAE were NSVT and LVEF < 45%. Therefore, female carriers of missense variants with either NSVT or LVEF < 45% should not be considered a low-risk group. It is important to individualize risk stratification in carriers of LMNA missense variants, because not all have the same prognosis.[Resumen] Introducción y objetivos. Según las guías de muerte súbita, se debe considerar un desfibrilador automático implantable (DAI) para los pacientes con miocardiopatía dilatada debida a variantes en el gen de la lamina (LMNA) con al menos 2 factores: varones, fracción de eyección del ventrículo izquierdo (FEVI) < 45%, taquicardia ventricular no sostenida (TVNS) y variantes no missense. Nuestro objetivo es describir las características clínicas de una cohorte española de pacientes con cardiolaminopatías (registro REDLAMINA) y evaluar los criterios de riesgo vigentes. Métodos. Se evaluó la relación entre factores de riesgo y eventos cardiovasculares en una cohorte de 140 portadores de variantes en LMNA (54 probandos, 86 familiares, edad ≥ 16 años). Se consideró: a) evento arrítmico mayor (EAM) si hubo descarga apropiada del DAI o muerte súbita, y b) muerte por insuficiencia cardiaca, incluidos los trasplantes. Resultados. Se identificaron 11 variantes nuevas y 21 previamente publicadas. La FEVI < 45% (p = 0,001) y la TVNS (p < 0,001) se relacionaron con los EAM, pero no el sexo o el tipo de variante (missense frente a no missense). La FEVI < 45% (p < 0,001) fue el único factor relacionado con la muerte por insuficiencia cardiaca. Conclusiones. En el registro REDLAMINA, los únicos 2 predictores asociados con EAM fueron la TVNS y la FEVI < 45%. No se debería considerar grupo de bajo riesgo a las portadoras de variantes missense con TVNS o FEVI < 45%. Es importante individualizar la estratificación del riesgo de los portadores de variantes missense en LMNA, porque no todas tienen el mismo pronóstico.This study received a grant from the Proyecto de investigación de la Sección de Insuficiencia Cardiaca 2017 from the Spanish Society of Cardiology and grants from the Instituto de Salud Carlos III (ISCIII) [PI14/0967, PI15/01551, AC16/0014] and ERA-CVD Joint Transnational Call 2016 (Genprovic). Grants from the ISCIII and the Ministerio de Economía y Competitividad de España (Spanish Department of Economy and Competitiveness) are supported by the Plan Estatal de I+D+i 2013-2016: Fondo Europeo de Desarrollo Regional (FEDER) “Una forma de hacer Europa”

Epidemiologic Features and Control Measures during Monkeypox Outbreak, Spain, June 2022

During June 2022, Spain was one of the countries most affected worldwide by a multicountry monkeypox outbreak with chains of transmission without identified links to disease-endemic countries. We provide epidemiologic features of cases reported in Spain and the coordinated measures taken to respond to this outbreak.S