PPARγ Pro12Ala and ACE ID polymorphisms are associated with BMI and fat distribution, but not metabolic syndrome

<p>Abstract</p> <p>Background</p> <p>Metabolic Syndrome (MetS) results from the combined effect of environmental and genetic factors. We investigated the possible association of peroxisome proliferator-activated receptor-γ2 (PPARγ2) Pro12Ala and Angiotensin Converting Enzyme (ACE) I/D polymorphisms with MetS and interaction between these genetic variants.</p> <p>Methods</p> <p>Three hundred sixty four unrelated Caucasian subjects were enrolled. Waist circumference, blood pressure, and body mass index (BMI) were recorded. Body composition was estimated by impedance analysis; MetS was diagnosed by the NCEP-ATPIII criteria. A fasting blood sample was obtained for glucose, insulin, lipid profile determination, and DNA isolation for genotyping.</p> <p>Results</p> <p>The prevalence of MetS did not differ across PPARγ2 or ACE polymorphisms. Carriers of PPARγ2 Ala allele had higher BMI and fat-mass but lower systolic blood pressure compared with Pro/Pro homozygotes. A significant PPARγ2 gene-gender interaction was observed in the modulation of BMI, fat mass, and blood pressure, with significant associations found in women only. A PPARγ2-ACE risk genotype combination for BMI and fat mass was found, with ACE DD/PPARγ2 Ala subjects having a higher BMI (p = 0.002) and Fat Mass (p = 0.002). Pro12Ala was independently associated with waist circumference independent of BMI and gender.</p> <p>Conclusions</p> <p>Carriers of PPARγ2 Ala allele had higher BMI and fat-mass but not a worse metabolic profile, possibly because of a more favorable adipose tissue distribution. A gene interaction exists between Pro12Ala and ACE I/D on BMI and fat mass. Further studies are needed to assess the contribution of Pro12Ala polymorphism in adiposity distribution.</p

Prevención en salud bucodental escuela 196 aeropuerto. Paso de los libres. Corrientes.

Fundamentación: Con el equipo  Unne - Salud se realizaron visitas a la localidad de  Paso de los Libres con la finalidad de realizar tareas de atención primaria en las escuelas, en las que se brindan las primeras armas en educación y promoción de la salud buco dental, logrando la mayor cantidad de altas básicas. Objetivos: Informar la importancia del cuidado de sus dientes basado en una correcta higiene bucal. Otorgar Altas Básicas al mayor porcentaje de los alumnos atendidos. Recomendar una adecuada alimentación. Promover la participación comunitaria. Destinatarios: alumnos de Escuela 196 Aeropuerto. Paso de los Libres. Corrientes. Actividades: Charlas informativas, proyección de diapositivas acerca de promoción y prevención de la salud bucal. Confección de Historias Clínicas. Odontograma. Índice de O´leary. Índices CPOD – Ceod. Inactivación de caries. Sellantes de Fosas y fisuras. Exodoncias dentarias. Resultados: Total de pacientes atendidos 150: al 92% se realizaron historias clínicas, enseñanza de técnicas de cepillado, entrega de cepillos dentales y topicaciones con flúor. Del total al 25% se le practicaron exodoncias dentarias, al 40% inactivaciones de caries y a un 50% selladores de fosas y fisuras.

Increased p53 gene dosage reduces neointimal thickening induced by mechanical injury but has no effect on native atherosclerosis

This is a pre-copy-editing, author-produced PDF of an article accepted for publication in Cardiovascular Research following peer review. The definitive publisher-authenticated version Cardiovasc Res. 75 (4):803-12. is available online at: http://cardiovascres.oxfordjournals.org/cgi/content/full/75/4/803OBJECTIVE: The tumor suppressor p53 regulates cell proliferation and apoptosis, two key processes in the pathogenesis of occlusive vascular disease. Here, we examined the consequences of heightening p53 function on neointimal lesion formation in the setting of atherosclerosis and mechanical injury. METHODS: (1) Immunohistopathological characterization of neointimal lesions in atherosclerosis-prone apolipoprotein E-null mice with normal p53 gene dosage (apoEKO) and carrying a p53 transgene (Super-p53/apoE-KO); (2) molecular studies in macrophages and smooth muscle cells (SMCs) obtained from these mice. RESULTS: The p53 transgene conferred p53 gain-of-function in cultured cells and mice. In vitro, survival of irradiated Super-p53 macrophages and femoral SMCs was reduced, but only Super-p53 SMCs exhibited attenuated proliferation. In vivo, whereas the size of spontaneously formed and diet-induced aortic atheromas was undistinguishable in apoE-KO and Super-p53/apoE-KO mice, the latter exhibited attenuated neointimal thickening in mechanically-injured femoral artery. In both models, neither apoptosis nor cell proliferation were affected by additional p53 gene dosage when examined in established neointimal lesions. However, at 2 days after mechanical injury when neointimal lesions were not formed yet, cell proliferation was significantly attenuated within medial SMCs of Super-p53/apoEKO mice. CONCLUSION: Heightening p53 function has differential effects on in vitro proliferation of macrophages (unaffected) versus SMCs (reduced), and on native atherosclerosis (unaffected) versus mechanically-induced neointimal thickening (reduced) in apoE-KO mice. The protective effect of p53 in mechanically-injured femoral artery coincided with limited medial SMC proliferation at early time points preceding neointima formation, but neither medial nor neointimal cell proliferation was affected in vessels with established occlusive lesions. These findings corroborate p53 gain-of-function as a promising therapeutic strategy to limit post-angioplasty restenosis but not native atherosclerosis.Work financed by grants from Ministerio de Sanidad y Consumo/Instituto de Salud Carlos III (Red Temática de Investigación Cooperativa en Enfermedades Cardiovasculares, RECAVA), from the Regional Government of Valencia (GV04B-288) and from Ministerio de Educación y Ciencia and the European Regional Development Fund (SAF2004-03057). S.M.S.-G. and J.M.G received salary support from Instituto de Salud Carlos III, and J.J.F. from CSIC-I3P predoctoral fellowship program cosponsored by the European Social Fund.Peer reviewe

Promoviendo la Salud Buco-Dental en la Escuela 692 Corrientes.

El trabajo que se lleva a cabo en una Escuela rural ubicada en Bella Vista, provincia de Corrientes a través del equipo de UNNE-Salud, es interdisciplinario para contribuir por medio de la Promoción, Prevención y Educación de la Salud Bucal al desarrollo sustentable y saludable de la región, reconociendo la realidad de las comunidades y las necesidades que ellas plantean, permitiendo a su vez el continuo crecimiento mutuo que favorece al desarrollo social. Numerosos estudios confirman que la mala higiene bucal y el consumo excesivo de hidratos de carbono, constituyen un factor de riesgo primordial en la caries dental. El incremento de la prevalencia de la caries dental se presenta en este grupo de niños, por lo que resulta necesario minimizar el riesgo de Enfermedades Bucales. La implementación de programas preventivos y/o atención a escolares ha señalado variaciones en la comparación de los índices, mejorando en un 90% la salud comparado con el primer índice registrado. El objetivo de los Programas Preventivos es lograr disminuir el riesgo y la actividad de enfermedades bucales a niveles compatibles con Salud, y de esta manera lograr el Alta Básica para los destinatarios. En este caso se pretendió informar a los niños sobre la importancia del cuidado de la salud bucal, brindar recursos necesarios para la atención, y aplicar técnicas de motivación para lograr una adecuada atención. Los destinatarios fueron niños de Escuela Rural 692, en Colonia 3 de abril, Bella Vista (Corrientes). Las actividades comprendieron: charlas informativas, proyección de diapositivas acerca de promoción y prevención de la salud bucal, confección de historias clínicas, odontograma, índice de O´Leary, índices CPOD – Ceod, inactivación de caries, sellantes de fosas y fisuras, exodoncias dentarias. Como resultado, a todos los integrantes de la comunidad educativa se les brindó información a través de charlas de promoción y educación para la salud bucodental, y se atendió a un total de 72 pacientes. Se realizaron historias clínicas, enseñanza de técnicas de cepillado, entrega de cepillos dentales y topicaciones con flúor. A 20% del total se les practicaron exodoncias dentarias; a 50% inactivaciones de caries y a 45% selladores de fosas y fisuras. Conclusión: con la información brindada se formaron Agentes Multiplicadores de Salud Bucal, donde personal auxiliar, maestros, padres y/o tutores actuarán sobre todo en su ambiente familiar. Se ha logrado reducir las enfermedades producidas por la placa bacteriana, caries y gingivitis por medio de tratamientos preventivos realizados, así como también se ha logrado la modificación de los hábitos de higiene bucal para reservar y mantener la salud de la misma, sobre todo teniendo en cuenta que son comunidades rurales, que se encuentran alejadas de los centros de salud. 

Diagnostic and prognostic microRNAs in the serum of breast cancer patients measured by droplet digital PCR

Background: Breast cancer circulating biomarkers include carcinoembryonic antigen and carbohydrate antigen 15-3, which are used for patient follow-up. Since sensitivity and specificity are low, novel and more useful biomarkers are needed. The presence of stable circulating microRNAs (miRNAs) in serum or plasma suggested a promising role for these tiny RNAs as cancer biomarkers. To acquire an absolute concentration of circulating miRNAs and reduce the impact of preanalytical and analytical variables, we used the droplet digital PCR (ddPCR) technique. Results: We investigated a panel of five miRNAs in the sera of two independent cohorts of breast cancer patients and disease-free controls. The study showed that miR-148b-3p and miR-652-3p levels were significantly lower in the serum of breast cancer patients than that in controls in both cohorts. For these two miRNAs, the stratification of breast cancer patients versus controls was confirmed by receiver operating characteristic curve analyses. In addition, we showed that higher levels of serum miR-10b-5p were associated with clinicobiological markers of poor prognosis. Conclusions: The study revealed the usefulness of the ddPCR approach for the quantification of circulating miRNAs. The use of the ddPCR quantitative approach revealed very good agreement between two independent cohorts in terms of comparable absolute miRNA concentrations and consistent trends of dysregulation in breast cancer patients versus controls. Overall, this study supports the use of the quantitative ddPCR approach for monitoring the absolute levels of diagnostic and prognostic tumor-specific circulating miRNAs

Computerized cognitive training and brain derived neurotrophic factor during bed rest: Mechanisms to protect individual during acute stress

Acute stress, as bed rest, was shown to increase plasma level of the neurotrophin brain-derived neurotrophic factor (BDNF) in older, but not in young adults. This increase might represent a protective mechanism towards acute insults in aging subjects. Since computerized cognitive training (CCT) is known to protect brain, herein we evaluated the effect of CCT during bed rest on BDNF, muscle mass, neuromuscular function and metabolic parameters. The subjects that underwent CCT did not show an increase of BDNF after bed rest, and showed an anti-insular modification pattern in metabolism. Neuromuscular function parameters, already shown to beneficiate from CCT, negatively correlated with BDNF in research participants undergoing CCT, while positively correlated in the control group. In conclusion, BDNF increase can be interpreted as a standardized protective mechanism taking place whenever an insult occurs; it gives low, but consistent preservation of neuromuscular function. CCT, acting as an external protective mechanism, seems to modify this standardized response, avoiding BDNF increase or possibly modifying its time course. Our results suggest the possibility of differential neuroprotective mechanisms among ill and healthy individuals, and the importance of timing in determining the effects of protective mechanism

Prognostic significance of FLT3-ITD length in AML patients treated with intensive regimens

FLT3-ITD mutations are detected in approximately 25% of newly diagnosed adult acute myeloid leukemia (AML) patients and confer an adverse prognosis. The FLT3-ITD allelic ratio has clear prognostic value. Nevertheless, there are numerous manuscripts with contradictory results regarding the prognostic relevance of the length and insertion site (IS) of the FLT3-ITD fragment. We aimed to assess the prognostic impact of these variables on the complete remission (CR) rates, overall survival (OS) and relapse-free survival (RFS) of AML patients with FLT3-ITDmutations. We studied the FLT3-ITD length of 362 adult AML patients included in the PETHEMA AML registry. We tried to validate the thresholds of ITD length previously published (i.e., 39 bp and 70 bp) in intensively treated AML patients (n = 161). We also analyzed the mutational profile of 118 FLT3-ITD AML patients with an NGS panel of 39 genes and correlated mutational status with the length and IS of ITD. The AUC of the ROC curve of the ITD length for OS prediction was 0.504, and no differences were found when applying any of the thresholds for OS, RFS or CR rate. Only four out of 106 patients had ITD IS in the TKD1 domain. Our results, alongside previous publications, confirm that FLT3-ITD length lacks prognostic value and clinical applicability. © 2021, The Author(s)

Effectiveness of influenza vaccine against laboratory-confirmed influenza, in the late 2011-2012 season in Spain, among population targeted for vaccination

Background: In Spain, the influenza vaccine effectiveness (VE) was estimated in the last three seasons using the observational study cycEVA conducted in the frame of the existing Spanish Influenza Sentinel Surveillance System. The objective of the study was to estimate influenza vaccine effectiveness (VE) against medically attended, laboratory-confirmed influenza-like illness (ILI) among the target groups for vaccination in Spain in the 2011-2012 season. We also studied influenza VE in the early (weeks 52/2011-7/2012) and late (weeks 8-14/2012) phases of the epidemic and according to time since vaccination. Methods: Medically attended patients with ILI were systematically swabbed to collect information on exposure, laboratory outcome and confounding factors. Patients belonging to target groups for vaccination and who were swabbed 4 months, respectively, since vaccination. A decrease in VE with time since vaccination was only observed in individuals aged ≥ 65 years. Regarding the phase of the season, decreasing point estimates were only observed in the early phase, whereas very low or null estimates were obtained in the late phase for the shortest time interval. Conclusions: The 2011-2012 influenza vaccine showed a low-to-moderate protective effect against medically attended, laboratory-confirmed influenza in the target groups for vaccination, in a late season and with a limited match between the vaccine and circulating strains. The suggested decrease in influenza VE with time since vaccination was mostly observed in the elderly population. The decreasing protective effect of the vaccine in the late part of the season could be related to waning vaccine protection because no viral changes were identified throughout the season

Next generation flow for minimally-invasive blood characterization of MGUS and multiple myeloma at diagnosis based on circulating tumor plasma cells (CTPC)

Here, we investigated for the first time the frequency and number of circulating tumor plasma cells (CTPC) in peripheral blood (PB) of newly diagnosed patients with localized and systemic plasma cell neoplasms (PCN) using next-generation flow cytometry (NGF) and correlated our findings with the distinct diagnostic and prognostic categories of the disease. Overall, 508 samples from 264 newly diagnosed PCN patients, were studied. CTPC were detected in PB of all active multiple myeloma (MM; 100%), and smoldering MM (SMM) patients (100%), and in more than half (59%) monoclonal gammopathy of undetermined significance (MGUS) cases (p < 0.0001); in contrast, CTPC were present in a small fraction of solitary plasmacytoma patients (18%). Higher numbers of CTPC in PB were associated with higher levels of BM infiltration and more adverse prognostic features, together with shorter time to progression from MGUS to MM (p < 0.0001) and a shorter survival in MM patients with active disease requiring treatment (p <= 0.03). In summary, the presence of CTPC in PB as assessed by NGF at diagnosis, emerges as a hallmark of disseminated PCN, higher numbers of PB CTPC being strongly associated with a malignant disease behavior and a poorer outcome of both MGUS and MM