Peroxisome proliferator activated receptor gamma 2 modulates late pregnancy homeostatic metabolic adaptations.

Pregnancy requires the adaptation of maternal energy metabolism including expansion and functional modifications of adipose tissue. Insulin resistance (IR), predominantly during late gestation, is a physiological metabolic adaptation that serves to support the metabolic demands of fetal growth. The molecular mechanisms underlying these adaptations are not fully understood and may contribute to gestational diabetes mellitus. Peroxisome proliferator-activated receptor gamma (PPARγ) controls adipogenesis, glucose and lipid metabolism and insulin sensitivity. The PPARγ2 isoform is mainly expressed in adipocytes and is thus likely to contribute to adipose tissue adaptation during late pregnancy. In the present study, we investigated the contribution of PPARγ2 to the metabolic adaptations occurring during the late phase of pregnancy in the context of IR. Using a model of late pregnancy in PPARγ2 knockout (KO) mice, we found that deletion of PPARγ2 exacerbated IR in association with lower serum adiponectin levels, increased body weight and enhanced lipid accumulation in liver. Lack of PPARγ2 provoked changes in the distribution of fat mass and preferentially prevented the expansion of the perigonadal depot while at the same time exacerbating inflammation. PPARγ2KO pregnant mice presented adipose tissue depot-dependent decreased expression of genes involved in lipid metabolism. Collectively, these data indicate that PPARγ2 is essential to promote healthy adipose tissue expansion and immune and metabolic functionality during pregnancy, contributing to the physiological adaptations that lead gestation to term.This work was supported by grants from the Spanish Ministry of Economy and Competitiveness: BFU2012-33594 and BFU2013-47384-R to GMG; SAF2015- 64287-R to M. Ricote; and SAF2014-56671-R to MPR; predoctoral fellowship BES-2010- 038107 to YV; and grants S2010/BMD-2423 from the Community of Madrid to MPR and GMG. The authors thank Saverio Cinti for his helpful comments with histological samples, Antonio Vidal-Puig for his help in discussion and Lucia Torres for technical assistance.S

The effectiveness of peer health coaching in improving glycemic control among low-income patients with diabetes: protocol for a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Although self-management support improves diabetes outcomes, it is not consistently provided in health care settings strained for time and resources. One proposed solution to personnel and funding shortages is to utilize peer coaches, patients trained to provide diabetes education and support to other patients. Coaches share similar experiences about living with diabetes and are able to reach patients within and beyond the health care setting. Given the limited body of evidence that demonstrates peer coaching significantly improves chronic disease care, this present study examines the impact of peer coaching delivered in a primary care setting on diabetes outcomes.</p> <p>Methods/Design</p> <p>The aim of this multicenter, randomized control trial is to evaluate the effectiveness of utilizing peer coaches to improve clinical outcomes and self-management skills in low-income patients with poorly controlled diabetes. A total of 400 patients from six primary health centers based in San Francisco that serve primarily low-income populations will be randomized to receive peer coaching (n = 200) or usual care (n = 200) over 6 months. Patients in the peer coach group receive coaching from patients with diabetes who are trained and mentored as peer coaches. The primary outcome is change in HbA1c. Secondary outcomes include change in: systolic blood pressure, body mass index (BMI), LDL cholesterol, diabetes self-care activities, medication adherence, diabetes-related quality of life, diabetes self-efficacy, and depression. Clinical values (HbA1c, LDL cholesterol and blood pressure) and self-reported diabetes self-efficacy and self-care activities are measured at baseline and after 6 months for patients and coaches. Peer coaches are also assessed at 12 months.</p> <p>Discussion</p> <p>Patients with diabetes, who are trained as peer health coaches, are uniquely poised to provide diabetes self management support and education to patients. This study is designed to investigate the impact of peer health coaching in patients with poorly controlled diabetes. Additionally, we will assess disease outcomes in patients with well controlled diabetes who are trained and work as peer health coaches.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov identifier: <a href="http://www.clinicaltrials.gov/ct2/show/NCT01040806">NCT01040806</a></p

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research

Design and Preliminary Analysis of a Taxonomic Conceptual Relations Assessment Tool in Spanish-speaking Clinical Population

En este trabajo se presentan los resultados psicométricos preliminares de un instrumento para evaluar relaciones conceptuales taxonómicas. El instrumento está conformado por una escala verbal y una pictórica y ofrece cuatro opciones de respuesta. Se evaluó a 43 participantes, mayores de 60 años, con y sin patología neurológica. Se realizó una regresión logística binaria que indicó una sensibilidad del 90.9% para la escala verbal y 96.8% para la pictórica y una especificidad del 96.8% para la escala verbal y 100% para la pictórica. El análisis de confiabilidad arrojó valores de alfa ordinales de .99 para la escala verbal y .98 para la escala pictórica. A su vez, se obtuvieron evidencias de validez convergente mediante la correlación con el subtest de Analogías del WAIS, Clasificación de imágenes de la EMSDA y emparejamiento palabra-dibujo de la BEA.This paper presents the design and preliminary psychometric analysis of a scale to assess taxonomic conceptual relations. The instrument consists of a verbal and a pictorial scale and offers four answer choices. We assessed 43 participants with and without neurological disease over 60 years. A discriminant analysis was conducted and it indicated a sensitivity of 90.9 % for the verbal scale and 91 % for the pictorial and a specificity of 100 % for both scales. Reliability analysis yielded ordinal alpha values of .985 for the verbal scale and .983 for the pictorial scale. In turn, evidences of convergent validity were obtained by correlating with WAIS´ Analogies subtest, Picture sorting from the EMSDA and word-picture matching from the BEA.Fil: Vivas, Leticia Yanina. Universidad Nacional de Mar del Plata. Facultad de Psicologia; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Fernandez Liporace, Maria Mercedes. Universidad de Buenos Aires. Facultad de Psicología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

TAXON: A new tool to assess semantic deficits

Introducción: La memoria semántica es un constructo multidimensional, por lo tanto, su evaluación requiere incluir tareas que abarquen los diversos aspectos que pueden verse afectados en distintos síndromes neuropsicológicos. Objetivo: El propósito de este trabajo es presentar una nueva herramienta de evaluación de la memoria semántica destinada a medir una dimensión específica: la capacidad para reconocer relaciones taxonómicas. Materiales y método: En su versión inicial el test contaba con 2 escalas, verbal y pictórica, con 60 ítems cada una. Fue administrada a una muestra de 67 participantes (grupos clínico y control). Se realizaron análisis psicométricos para eliminar aquellos ítems que no aportaran a la discriminación de los participantes según grupo. Luego se estudiaron las propiedades psicométricas de la versión final (21 ítems por escala). Resultados: Se realizó un análisis de curvas ROC que arrojó valores aceptables de sensibilidad y especificidad del instrumento. Se obtuvieron evidencias de validez externa mediante el análisis de la correlación con pruebas reconocidas de evaluación de memoria semántica. Se analizó la consistencia interna mediante el cálculo del alfa para respuestas ordinales. Discusión: Se obtuvieron evidencias de validez del instrumento y de consistencia de las puntuaciones, mostrando a la vez una buena capacidad de discriminación. Esto indica que se trata de una prueba apropiada para uso clínico neuropsicológico, que puede incluirse en una batería más amplia de evaluación de la memoria semántica como instrumento para examinar relaciones conceptuales taxonómicas.Introduction: Semantic memory is a multidimensional concept and, as such, its assessment requires the inclusion of diverse tasks involving the different aspects that could be adversely affected in neuropsychological syndromes. Aim: This study introduces a new semantic memory test to assess a specific dimension: the ability to identify taxonomic relations. Materials and method: In the initial version, the test included 2 scales, verbal and pictorial, with 60 items each. Psychometric analyses were carried out in a sample of 67 participants (clinical and control groups), in order to eliminate those items with no discrimination power between groups. The psychometric features ofthe final version were analyzed (21 items each scale) at a later stage. Results: An analysis employing ROC curves was conducted, finding acceptable values of sensitivity and specificity. External validity evidences were obtained by correlating the test scores with the scores of well-known tools used to assess semantic memory. Internal consistency was examined using alphas for ordinal responses. Discussion: Validity evidences and internal consistency of scores were obtained and showed a good discrimination capacity. This indicates that this is an adequate test to be used in neuropsychological assessment, which could be included in a broader assessment battery to measure the ability to identify taxonomic conceptual relations.Fil: Vivas, Leticia Yanina. Universidad Nacional de Mar del Plata. Facultad de Psicología. Instituto de Psicología Básica, Aplicada y Tecnología. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Psicología Básica, Aplicada y Tecnología; ArgentinaFil: Fernandez Liporace, Maria Mercedes. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Psicología. Instituto de Investigaciones; Argentin

Argentinean Psycholinguistic Image Naming Test (PAPDI). Part 2. Study of the psychometric properties

En el presente trabajo se detallan los análisisrealizados con el fin de estudiar las propiedadespsicométricas la Prueba Argentina Psicolingüística de Denominación de Imágenes(PAPDI). La misma cuenta con dos cualidadesque representan un valor agregado frente a laspruebas actualmente disponibles en nuestro país:a) los estímulos fueron seleccionados controlando las variables que afectan las etapas deanálisis visual y de representación conceptual dela imagen del objeto y se manipularon las variables que afectan la selección y recuperaciónde la etiqueta léxica, en base a valores normativos de población argentina; y b) las claves semánticas se elaboraron de acuerdo con normasde producción de atributos semánticos tambiénrecolectadas en nuestro país. En este trabajo seanalizaron las propiedades psicométricas mediante el estudio de pacientes con demencia tipoAlzheimer, con lesiones cerebrales focales yparticipantes sin patología neurológica. Se buscaron evidencias de validez de criterio medianteel análisis de grupos contrastados y la correlación con el test de Boston. A su vez, se estudióla confiabilidad de las puntuaciones por dos métodos: consistencia interna y test-retest. Tambiénse analizó la capacidad de discriminación entrepacientes con y sin anomia mediante curvasROC. Se estudiaron además los efectos de lasvariables manipuladas, se realizó un análisiscualitativo de los errores y se examinó el desempeño en función del uso de las claves. Los resultados de los análisis aportan evidencia de quepresenta cualidades psicométricas sumamenteaceptables para su uso en nuestra población.In the current paper we present the psychometric analysis of the Argentinean Psycholinguistic Image Naming Test (PAPDI). This test has two characteristics that makes it different 262 Vivas, Andreini, Linares, Fuentes Leiza, Del Boca y Segui from those currently available in our country: a) the stimuli has been chosen and ordered controlling certain psycholinguistic variables proven to have influence on this task, such as Visual Complexity, Image Agreement, Image Variability, Familiarity, Name Agreement, Age of Acquisition and Frequency of Use, following Argentinean normative data base; and b) semantic cues were elaborated according to semantic feature production norms also from Argentina. We present here the psychometric analysis of its properties. There were analyzed through the study of patients with Alzheimer Disease (n = 25) and focal brain lesions (n = 27) and healthy participants (n = 125). On the first place, in order to study criteria validity a group comparison analysis was carried out. On the one hand Alzheimer Disease patients were compared with healthy participants. On the other hand, two focal brain damaged patients were compared: with and without aphasia. Convergent validity was also stu- died through the correlation with Boston naming test. In the third place, scores reliability was studied through two methods: internal consistency analysis, for Alzheimer, focal and healthy groups, and test-retest for focal brain damage group. Forth, it was analyzed the capacity to discriminate between patient with and without aphasia through ROC curves analysis. The respective sensitivity and specificity values to detect anomia were established. Fifth, the demographic variables ́ influence was analyzed through a regression analysis. Moreover, there were analyzed the effects of two psycholinguistic variables that were taken into account to order the images but were not normalized: Lexical Frequency and Age of Acquisition. Finally, type of errors and response to cues were studied for focal brain damaged patients. The results indicated that the PAPDI presents acceptable psychometric properties to be used as a tool in neuropsychological assessment. It showed evidence of internal and external validity and it was observed scores reliability through internal consistency and test-retest. A suggested cutting point was established to detect anomia. Furthermore a main influence of educational level was reported. There were also detected effects of Lexical Frequency and Age of Acquisition which were observed for Alzheimer and aphasic patients groups. Moreover it was illustrated the response profile analysis for aphasic and non aphasic focal brain damaged patients regarding a proposed taxonomy of error types. It was also studied the response to semantic and phonological cues and it was observed that both contributed to improve patients ́ performance.Fil: Manoiloff, Laura Maria Victoria. Universidad Nacional de Córdoba. Facultad de Psicología; ArgentinaFil: Vivas, Leticia Yanina. Universidad Nacional de Mar del Plata. Facultad de Psicología. Instituto de Psicología Básica, Aplicada y Tecnología. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Psicología Básica, Aplicada y Tecnología; ArgentinaFil: Andreini, C.. Universidad Nacional de Córdoba. Facultad de Psicología; ArgentinaFil: Linares, N.. Hospital Interzonal General de Agudos `oscar Alende´; ArgentinaFil: Fuentes, M.. Universidad Nacional de Córdoba. Facultad de Psicología; ArgentinaFil: Del Boca, M. L.. Universidad Nacional de Córdoba. Facultad de Psicología; ArgentinaFil: Segui, Juan. Universidad René Descartes; Franci

TAS2R38 polymorphisms, Helicobacter pylori infection and susceptibility to gastric cancer and premalignant gastric lesions

Background: Gastric cancer is worldwide the fourth more common cancer type by incidence, and the third by mortality. We analyzed three missense variants of TAS2R38 gene: rs713598 (A49P), rs1726866 (V262A), and rs10246939 (I296V). These variants and their combination in haplotypes (proline, alanine and valine/tasters or alanine, valine and isoleucine/nontasters) and diplotypes are responsible for individual differences in bitter perception. The single-nucleotide polymorphisms and the related phenotypes are known to be associated with susceptibility to Gram-negative bacterial infections, such as Helicobacter pylori, and with risk of various cancer types. An association between intermediate tasters (as defined by TAS2R38 diplotypes) and increased risk of gastric cancer was reported in a Korean population. Methods: We analyzed 2616 individuals of Latin American origin, representing the whole spectrum of lesions from gastritis to gastric cancer. Results: Comparing cancer cases vs. noncancers we observed a decrease in risk associated with heterozygous carriers of rs10246939 (P = 0.006) and rs1726866 (P = 0.003) when compared with homozygotes of the more common allele. Also, the analysis of diplotypes/phenotypes reflected the same association, with super-tasters showing a borderline increased risk of developing gastric cancer compared to medium-tasters [odds ratio (OR) = 1.63; 95% confidence interval (CI), 1.04-2.56; P = 0.033]. Also, nontasters showed an increased risk when compared to medium-tasters although not reaching statistical significance (OR = 1.58; 95% CI, 0.80-2.87; P = 0.203). We also tested the interactions between the TAS2R38 genotypes and H. pylori cagA status in a subset of samples and found no interaction. Conclusion: In conclusion, our results suggest only a modest contribution of TAS2R38 gene genetic variability in gastric cancer etiology

Investigating the concordance in molecular subtypes of primary colorectal tumors and their matched synchronous liver metastasis

To date, no systematic analyses are available assessing concordance of molecular classifications between primary tumors (PT) and matched liver metastases (LM) of metastatic colorectal cancer (mCRC). We investigated concordance between PT and LM for four clinically relevant CRC gene signatures. Twenty-seven fresh and 55 formalin-fixed paraffin-embedded pairs of PT and synchronous LM of untreated mCRC patients were retrospectively collected and classified according to the MSI-like, BRAF-like, TGFB activated-like and the Consensus Molecular Subtypes (CMS) classification. We investigated classification concordance between PT and LM and association of TGFBa-like and CMS classification with overall survival. Fifty-one successfully profiled matched pairs were used for analyses. PT and matched LM were highly concordant in terms of BRAF-like and MSI-like signatures, (90.2% and 98% concordance, respectively). In contrast, 40% to 70% of PT that were classified as mesenchymal-like, based on the CMS and the TGFBa-like signature, respectively, lost this phenotype in their matched LM (60.8% and 76.5% concordance, respectively). This molecular switch was independent of the microenvironment composition. In addition, the significant change in subtypes was observed also by using methods developed to detect cancer cell-intrinsic subtypes. More importantly, the molecular switch did not influence the survival. PT classified as mesenchymal had worse survival as compared to nonmesenchymal PT (CMS4 vs CMS2, hazard ratio [HR] = 5.2, 95% CI = 1.5-18.5, P = .0048; TGFBa-like vs TGFBi-like, HR = 2.5, 95% CI = 1.1-5.6, P = .028). The same was not true for LM. Our study highlights that the origin of the tissue may have major consequences for precision medicine in mCRC