Serie patrimonial de casonas italianizantes, Angaco - San Juan - Argentina

La época en que Argentina recibió el mayor volumen de inmigración italiana (1870-1914). Fue una época de crecimiento económico, cuyos aspectos más notables se dieron en el sector agropecuario, aumentando los cultivos llegando a los 24 millones de hectáreas en 1914. En San Juan el proceso más importante fue en el gobierno de Domingo Faustino Sarmiento y la llegada del ferrocarril en 1885, factores que atrajeron a españoles, italianos, franceses y otros futuros grandes empresarios de la región. El Departamento Angaco inicialmente tenía 700 Km2, llegando en la actualidad a 1865 km2. Sus límites son Jáchal al norte, Ullúm al oeste, río San Juan al sur y al este las sierras de Pie de Palo. El inicio del siglo comenzó con la iniciación de las grandes bodegas y la inmigración masiva a San Juan. En 1977 es el epicentro de uno de los terremotos más devastadores de la provincia que dejó gran número de víctimas y dañó casi la totalidad de la construcción existente en el departamento. Se propone, la realización del inventario y catalogación de las 4 viviendas del departamento que resistieron el terremoto y su declaratoria como Serie Patrimonial de Casonas Italianizantes para su preservación. Ya que son testimonio de la historia de la comunidad y en la actualidad reflejan los cambios que el departamento vive, que influyen en los modos de vida y el modo de uso de los espacios. Se da así una mayor preocupación por el contacto social y la búsqueda de confort, que produce cambios en la organización funcional espacial de estas tipologías

5è audit clínic de l'ictus: Catalunya 2018-2019

Audit clínic; Ictus; AvaluacióAudit clínico; Ictus; EvaluaciónClinical audit; Stroke; EvaluationAquest document de la cinquena edició de l'Audit Clínic de l‟ictus, realitzat l'any 2021, descriu les dades globals de Catalunya, així com una part de les dades desagregades per hospital, totes obtingudes de manera prospectiva. Igual que a la resta d‟edicions, les dades dels hospitals de cada àmbit territorial s‟han tramés a la Regió Sanitària corresponent i als professionals dels hospitals implicats, per a poder iniciar els processos de millora adients a partir de la comparació dels resultats amb la mitjana de Catalunya i amb els anteriors Audits

5È. Audit clínic de l'ictus. Catalunya 2018/19

La millora i el manteniment continu de la qualitat de l’atenció als malalts amb ictus agut requereix una avaluació periòdica de la pràctica clínica. Els Audits de l’Ictus són l’instrument avaluatiu del PDMVC. La millora dels seus resultats pretén garantir la millora dels resultats dels pacients.S’han auditat 4.008 casos ingressats per ictus agut entre 2018 i 2019. El període d’estudi s’ha ampliat a 6 mesos, en períodes de 1 mes i mig al llarg de 12 mesos, similars per a tots els centres. L’obtenció prospectiva de dades s’ha realitzat majoritàriament per infermeres de cada hospital. La mediana del temps entre l’inici dels símptomes i l’arribada a urgències va ser de 2,1 hores. El 72% dels casos van arribar a l’hospital dins les primeres quatre hores i mitja. Respecte al 4t Audit: * Augmenten els ingressos en Unitat d’ictus agut (44,2% a 61,3%), les activacions del Codi Ictus (42,9 a 61,4; realitzades pel SEM de 43,4 a 67,8%) i els tractaments de reperfusió (16% a 30% dels ictus isquèmics) * Augmenta el nombre de pacients en els que es diagnostica durant l’ingrés una fibril·lació auricular no coneguda prèviament (7% a 18,8%). * Hi ha un lleuger augment de les pneumònies(6% a 8%)ibaixa la mor talitat intrahospitalària (12% a 9%). * Sis indicadors de qualitat milloren significativament, tres 3 indicadors es mantenen i 3 indicadors empitjoren. Destaca una important millora en alguns indicadors de qualitat rellevants com són la realització del test de disfàgia, l’avaluació del perfil lipídic, l’educació sanitària als pacients i familiars, el registre de l’etiologia de l’ictus i la utilització d’escales neurològiques. Es necessiten accions de milloradels indicadors següents: pauta d’antitrombòtics abans de 48 hores, mobilització precoç i avaluació de l’estat d’ànim. L’estat d’ànim s’avalua en un baix percentatge i es fa servir una gran variabilitat d’eines de mesura.Preprin

Response to fluoxetine in children and adolescents: a weighted gene co-expression network analysis of peripheral blood

The inconclusive and non-replicated results of pharmacogenetic studies of antidepressant response could be related to the lack of acknowledgement of its mechanism of action. In this scenario, gene expression studies provide and interesting framework to reveal new candidate genes for pharmacogenetic studies or peripheral biomarkers of fluoxetine response. We propose a system biology approach to analyse changes in gene expression induced by eight weeks of treatment with fluoxetine in peripheral blood. 21 naïve child and adolescents participated in the present study. Our analysis include the identification of gene co-expression modules, using Weighted Gene Co-expression Network Analysis (WGCNA), followed by protein-protein interaction (PPi) network construction coupled with functional annotation. Our results revealed two modules of co-expression genes related to fluoxetine treatment. The constructed networks from these modules were enriched for biological processes related to cellular and metabolic processes, cell communication, immune system processes, cell death, response to stimulus and neurogenesis. Some of these processes, such as immune system, replicated previous findings in the literature, whereas, neurogenesis, a mechanism proposed to be involved in fluoxetine response, had been identified for first time using peripheral tissues. In conclusion, our study identifies several biological processes in relation to fluoxetine treatment in peripheral blood, offer new candidate genes for pharmacogenetic studies and valuable markers for peripheral moderator biomarkers discovery

Regulation of death receptor signaling by the autophagy protein TP53INP2

TP53INP2 positively regulates autophagy by binding to Atg8 proteins. Here, we uncover a novel role of TP53INP2 in death-receptor signaling. TP53INP2 sensitizes cells to apoptosis induced by death receptor ligands. In keeping with this, TP53INP2 deficiency in cultured cells or mouse livers protects against death receptor-induced apoptosis. TP53INP2 binds caspase-8 and the ubiquitin ligase TRAF6, thereby promoting the ubiquitination and activation of caspase-8 by TRAF6. We have defined a TRAF6-interacting motif (TIM) and a ubiquitin-interacting motif in TP53INP2, enabling it to function as a scaffold bridging already ubiquitinated caspase-8 to TRAF6 for further polyubiquitination of caspase-8. Mutations of key TIM residues in TP53INP2 abrogate its interaction with TRAF6 and caspase-8, and subsequently reduce levels of death receptor-induced apoptosis. A screen of cancer cell lines showed that those with higher protein levels of TP53INP2 are more prone to TRAIL-induced apoptosis, making TP53INP2 a potential predictive marker of cancer cell responsiveness to TRAIL treatment. These findings uncover a novel mechanism for the regulation of caspase-8 ubiquitination and reveal TP53INP2 as an important regulator of the death receptor pathway

Educational attainment and mortality in schizophrenia

Background Individuals suffering from schizophrenia have a reduced life expectancy with cardiovascular disease (CVD) as a major contributor. Low educational attainment is associated with schizophrenia, as well as with all-cause and CVD mortality. However, it is unknown to what extent low educational attainment can explain the increased mortality in individuals with schizophrenia. Aim Here, we quantify associations between educational attainment and all-cause and CVD mortality in individuals with schizophrenia, and compare them with the corresponding associations in the general population. Method All Norwegian citizens born between January 1, 1925, and December 31, 1959, were followed up from January 1, 1990, to December 31, 2014. The total sample included 1,852,113 individuals, of which 6548 were registered with schizophrenia. We estimated hazard ratios (HR) for all-cause and CVD mortality with Cox models, in addition to life years lost. Educational attainment for index persons and their parents were included in the models. Results In the general population individuals with low educational attainment had higher risk of all-cause (HR: 1.48 [95% CI: 1.47–1.49]) and CVD (HR: 1.59 [95% CI: 1.57–1.61]) mortality. In individuals with schizophrenia these estimates were substantially lower (all-cause: HR: 1.13 [95% CI: 1.05–1.21] and CVD: HR: 1.12 [95% CI: 0.98–1.27]). Low educational attainment accounted for 3.28 (3.21–3.35) life years lost in males and 2.48 (2.42–2.55) years in females in the general population, but was not significantly associated with life years lost in individuals with schizophrenia. Results were similar for parental educational attainment. Conclusions Our results indicate that while individuals with schizophrenia in general have lower educational attainment and higher mortality rates compared with the general population, the association between educational attainment and mortality is smaller in schizophrenia subjects than in the general population.publishedVersio

Regulation of death receptor signaling by the autophagy protein TP53INP2

TP53INP2 positively regulates autophagy by binding to Atg8 proteins. Here, we uncover a novel role of TP53INP2 in death‐receptor signaling. TP53INP2 sensitizes cells to apoptosis induced by death receptor ligands. In keeping with this, TP53INP2 deficiency in cultured cells or mouse livers protects against death receptor‐induced apoptosis. TP53INP2 binds caspase‐8 and the ubiquitin ligase TRAF6, thereby promoting the ubiquitination and activation of caspase‐8 by TRAF6. We have defined a TRAF6‐interacting motif (TIM) and a ubiquitin‐interacting motif in TP53INP2, enabling it to function as a scaffold bridging already ubiquitinated caspase‐8 to TRAF6 for further polyubiquitination of caspase‐8. Mutations of key TIM residues in TP53INP2 abrogate its interaction with TRAF6 and caspase‐8, and subsequently reduce levels of death receptor‐induced apoptosis. A screen of cancer cell lines showed that those with higher protein levels of TP53INP2 are more prone to TRAIL‐induced apoptosis, making TP53INP2 a potential predictive marker of cancer cell responsiveness to TRAIL treatment. These findings uncover a novel mechanism for the regulation of caspase‐8 ubiquitination and reveal TP53INP2 as an important regulator of the death receptor pathway

Sex and Gender Differences in Acute Stroke Care: Metrics, Access to Treatment and Outcome. A Territorial Analysis of the Stroke Code System of Catalonia

INTRODUCTION: Previous studies have reported differences in the management and outcome of women stroke patients in comparison with men. We aim to analyze sex and gender differences in the medical assistance, access to treatment and outcome of acute stroke patients in Catalonia. PATIENTS AND METHODS: Data were obtained from a prospective population-based registry of stroke code activations in Catalonia (CICAT) from January/2016 to December/2019. The registry includes demographic data, stroke severity, stroke subtype, reperfusion therapy, and time workflow. Centralized clinical outcome at 90 days was assessed in patients receiving reperfusion therapy. RESULTS: A total of 23,371 stroke code activations were registered (54% men, 46% women). No differences in prehospital time metrics were observed. Women more frequently had a final diagnosis of stroke mimic, were older and had a previous worse functional situation. Among ischemic stroke patients, women had higher stroke severity and more frequently presented proximal large vessel occlusion. Women received more frequently reperfusion therapy (48.2% vs 43.1%, DISCUSSION AND CONCLUSION: We found some differences by sex in that acute stroke was more frequent in older women and the stroke severity was higher. We found no differences in medical assistance times, access to reperfusion treatment and early complications. Worse clinical outcome at 90 days in women was conditioned by stroke severity and older age, but not by sex itself

Deficient endoplasmic reticulum-mitochondrial phosphatidylserine transfer causes liver disease

Non-alcoholic fatty liver is the most common liver disease worldwide. Here, we show that the mitochondrial protein mitofusin 2 (Mfn2) protects against liver disease. Reduced Mfn2 expression was detected in liver biopsies from patients with nonalcoholic steatohepatitis (NASH). Moreover, reduced Mfn2 levels were detected in mouse models of steatosis or NASH, and its re-expression in a NASH mouse model ameliorated the disease. Liver-specific ablation of Mfn2 in mice provoked inflammation, triglyceride accumulation, fibrosis, and liver cancer. We demonstrate that Mfn2 binds phosphatidylserine (PS) and can specifically extract PS into membrane domains, favoring PS transfer to mitochondria and mitochondrial phosphatidylethanolamine (PE) synthesis. Consequently, hepatic Mfn2 deficiency reduces PS transfer and phospholipid synthesis, leading to endoplasmic reticulum (ER) stress and the development of a NASH-like phenotype and liver cancer. Ablation of Mfn2 in liver reveals that disruption of ER-mitochondrial PS transfer is a new mechanism involved in the development of liver disease

Humoral and Cellular Immune Responses After a 3-dose Course of mRNA-1273 COVID-19 Vaccine in Kidney Transplant Recipients: A Prospective Cohort Study.

In kidney transplant recipients, there is discordance between the development of cellular and humoral response after vaccination against SARS-CoV-2. We sought to determine the interplay between the 2 arms of adaptive immunity in a 3-dose course of mRNA-1273 100 μg vaccine. Methods: Humoral (IgG/IgM) and cellular (N- and S-ELISpot) responses were studied in 117 kidney and 12 kidney-pancreas transplant recipients at the following time points: before the first dose, 14 d after the second dose' and before and after the third dose, with a median of 203 and 232 d after the start of the vaccination cycle, respectively. Results: After the second dose, 26.7% of naive cases experienced seroconversion. Before the third dose and in the absence of COVID-19, this percentage increased to 61.9%. After the third dose, seroconversion occurred in 80.0% of patients. Naive patients who had at any time point a detectable positivity for S-ELISpot were 75.2% of the population, whereas patients who maintained S-ELISpot positivity throughout the study were 34.3%. S-ELISpot positivity at 42 d was associated with final seroconversion (odds ratio' 3.14; 95% confidence interval' 1.10-8.96; P = 0.032). Final IgG titer was significantly higher in patients with constant S-ELISpot positivity (P < 0.001). Conclusions: A substantial proportion of kidney transplant recipients developed late seroconversion after 2 doses. Cellular immunity was associated with the development of a stronger humoral respons