Quality of Life Questionnaire: Psychometric Properties and Relationships to Healthy Behavioural Patterns

The main purpose of this study is to evaluate the quality of life in a healthy population from Universitat Oberta de Catalunya (UOC) using the 'Quality of life Questionnaire' (QoLQ), which was developed in our cultural context and to examine its psychometric properties. A secondary goal is to explore the relationship between quality of life perception and healthy behavior profiles. Data were obtained from 264 participants with access to the online Campus who answered a web version of the questionnaire (QoLQ). Our results indicate that the psychometric properties of the instrument are satisfactory and the original factorial structure is confirmed: Social Support, General Satisfaction, Physical/Psychological well-being and Absence of work overload/Free time. The Cronbach's alpha coefficients for internal consistency ranged from 0.82 to 0.89 for the subscales and was 0.93 for the total items. A new variable called healthy behavioral pattern was generated from the answers of a chronogram of daily activities. The statistical significant differences (95% CI and t-values) across more healthy and less healthy behavior profiles reveal that the former perceive a higher quality of life

Prediction of Mortality and Major Cardiac Events by Exercise Echocardiography in Patients With Normal Exercise Electrocardiographic Testing

ObjectivesWe sought to assess the value of exercise echocardiography (EE) for predicting outcome in patients with known or suspected coronary artery disease and normal exercise electrocardiogram (ECG) testing.BackgroundThe prognostic value of EE in patients with normal exercise ECG testing has not been characterized.MethodsWe studied 4,004 consecutive patients (2,358 men, mean age [± SD] 59.6 ± 12.5 years) with interpretable ECG who underwent treadmill EE and did not develop chest pain or ischemic ECG abnormalities during the tests. Wall motion score index (WMSI) was evaluated at rest and with exercise, and the difference (ΔWMSI) was calculated. Ischemia was defined as the development of new or worsening wall motion abnormalities with exercise. End points were all-cause mortality and major cardiac events (MACE).ResultsOverall, 669 patients (16.7%) developed ischemia with exercise. During a mean follow-up of 4.5 ± 3.4 years, 313 patients died, and 183 patients had a MACE before any revascularization procedure. The 5-year mortality and MACE rates were 6.4% and 4.2% in patients without ischemia versus 12.1% and 10.1% in those with ischemia, respectively (p < 0.001). In the multivariate analysis, ΔWMSI remained an independent predictor of mortality (hazard ratio [HR]: 2.73, 95% confidence interval [CI]: 1.40 to 5.32, p = 0.003) and MACE (HR: 3.59, 95% CI: 1.42 to 9.07, p = 0.007). The addition of the EE results to the clinical, resting echocardiographic and exercise hemodynamic data significantly increased the global chi-square of the models for the prediction of mortality (p = 0.005) and MACE (p = 0.009).ConclusionsThe use of EE provides significant prognostic information for predicting mortality and MACE in patients with interpretable ECG and normal exercise ECG testing

The causes, consequences, and treatment of left or right heart failure

Chronic heart failure (HF) is a cardiovascular disease of cardinal importance because of several factors: a) an increasing occurrence due to the aging of the population, primary and secondary prevention of cardiovascular events, and modern advances in therapy, b) a bad prognosis: around 65% of patients are dead within 5 years of diagnosis, c) a high economic cost: HF accounts for 1% to 2% of total health care expenditure. This review focuses on the main causes, consequences in terms of morbidity, mortality and costs and treatment of HF

PPAR-γ Gene Expression in Human Adipose Tissue Is Associated with Weight Loss After Sleeve Gastrectomy

Background: The peroxisome proliferator-activated receptor (PPAR)-γ plays a key role in adipose tissue differentiation and fat metabolism. However, it is unclear which factors may regulate its expression and whether obese patients have changes in adipose tissue expression of PPAR-γor potential regulators such as miR-27. Thus, our aims were to analyze PPAR-γ and miR-27 expression in adipose tissue of obese patients, and to correlate their levels with clinical variables. Subjects and methods: We included 43 morbidly obese subjects who underwent sleeve gastrectomy (31 of them completed 1-year follow-up) and 19 non-obese subjects. mRNA expression of PPAR-γ1 and PPAR-γ2, miR-27a, and miR-27b was measured by qPCR in visceral and subcutaneous adipose tissue. Clinical variables and serum adipokine and hormone levels were correlated with PPAR-γ and miR-27 expression. In addition, a systematic review of the literature regarding PPAR-γ expression in adipose tissue of obese patients was performed. Results: We found no differences in the expression of PPAR-γ and miR-27 in adipose tissue of obese patients vs. controls. The literature review revealed discrepant results regarding PPAR-γ expression in adipose tissue of obese patients. Of note, we described a significant negative correlation between pre-operative PPAR-γ1 expression in adipose tissue of obese patients and post-operative weight loss, potentially linked with insulin resistance markers. Conclusion: PPAR-γ1 expression in adipose tissue is associated with weight loss after sleeve gastrectomy and may be used as a biomarker for response to surgeryThis work was funded by the following grants to M.M.: ISCIII and FEDER, PI10/01692, PI16/01548, RD16/0017/0023, and I3SNS-INT12/049, L.H.C.: Junta de Castilla y León GRS 681/A/11, J.-L. T.: GRS 1587/A/17 and GRS1356/A/16, G.S.: ERC 260464, EFSD 2030, MICINNSAF2013-43506-R, and Comunidad de Madrid S2010/BMD-2326. G.S. is an investigator of the Ramón y Cajal Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. ISCIII,PI10/01692,Miguel Marcos,PI16/01548,Miguel Marcos,Gerencia regional de salud,junta de castilla y león,GRS 681/A/11,Lourdes Hernández-Cosido,J.-L. T,Lourdes Hernández-Cosido,Gerencia Regional de Salud,Junta de Castilla y León,GRS 1587/A/17,Jorge-Luis Torres,GRS1356/A/16,Jorge-Luis Torre

Pathogenic variants of DNAJC12 and evaluation of the encoded cochaperone as a genetic modifier of hyperphenylalaninemia

This is the peer reviewed version of the following article: Pathogenic variants of DNAJC12 and evaluation of the encoded cochaperone as a genetic modifier of hyperphenylalaninemia. Human Mutation (2020): 25 April, which has been published in final form at [https://doi.org/10.1002/humu.24026. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived VersionsThe variants identified in this study are openly available at http://www.lovd.nl/ with reference numbers 0000644164, 0000645396, 0000644166, and 0000405673Biallelic variants of the gene DNAJC12, which encodes a cochaperone, were recently described in patients with hyperphenylalaninemia (HPA). This paper reports the retrospective genetic analysis of a cohort of unsolved cases of HPA. Biallelic variants of DNAJC12 were identified in 20 patients (generally neurologically asymptomatic) previously diagnosed with phenylalanine hydroxylase (PAH) deficiency (phenylketonuria [PKU]). Further, mutations of DNAJC12 were identified in four carriers of a pathogenic variant of PAH. The genetic spectrum of DNAJC12 in the present patients included four new variants, two intronic changes c.298‐2A>C and c.502+1G>C, presumably affecting the splicing process, and two exonic changes c.309G>T (p.Trp103Cys) and c.524G>A (p.Trp175Ter), classified as variants of unknown clinical significance (VUS). The variant p.Trp175Ter was detected in 83% of the mutant alleles, with 14 cases homozygous, and was present in 0.3% of a Spanish control population. Functional analysis indicated a significant reduction in PAH and its activity, reduced tyrosine hydroxylase stability, but no effect on tryptophan hydroxylase 2 stability, classifying the two VUS as pathogenic variants. Additionally, the effect of the overexpression of DNAJC12 on some destabilizing PAH mutations was examined and a mutation‐specific effect on stabilization was detected suggesting that the proteostasis network could be a genetic modifier of PAH deficiency and a potential target for developing mutation‐specific treatments for PKUThis work was funded by grant PI16/00573, B2017/BMD-3721, the Fundación Isabel Gemio and the Fundación La Caixa (LCF/PR/PR16/11110018), an institutional grant from the Fundación Ramón Areces to the Centro de Biología Molecular Severo Ochoa, and the European Regional Development Fun

Usefulness of the INTERMACS scale for predicting outcomes after urgent heart transplantation

[Abstract] Introduction and objectives. Our aim was to assess the prognostic value of the INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) scale in patients undergoing urgent heart transplantation (HT). Methods. Retrospective analysis of 111 patients treated with urgent HT at our institution from April, 1991 to October, 2009. Patients were retrospectively assigned to three levels of the INTERMACS scale according to their clinical status before HT. Results. Patients at the INTERMACS 1 level (n = 31) more frequently had ischemic heart disease (p = 0.03) and post-cardiothomy shock (p = 0.02) than patients at the INTERMACS 2 (n = 55) and INTERMACS 3-4 (n = 25) levels. Patients at the INTERMACS 1 level showed higher preoperative catecolamin doses (p = 0.001), a higher frequency of use of mechanical ventilation (p < 0.001), intraaortic balloon (p = 0.002) and ventricular assist devices (p = 0.002), and a higher frequency of preoperative infection (p = 0.015). The INTERMACS 1 group also presented higher central venous pressure (p = 0.02), AST (p = 0.002), ALT (p = 0.006) and serum creatinine (p < 0.001), and lower hemoglobin (p = 0.008) and creatinine clearance (p = 0.001). After HT, patients at the INTERMACS 1 level had a higher incidence of primary graft failure (p = 0.03) and postoperative need for renal replacement therapy (p = 0.004), and their long-term survival was lower than patients at the INTERMACS 2 (log rank 5.1, p = 0.023; HR 3.1, IC 95% 1.1-8.8) and INTERMACS 3-4 level (log rank 6.1, p = 0.013; HR 6.8, IC 95% 1.2-39.1). Conclusions. Our results suggest that the INTERMACS scale may be a useful tool to stratify postoperative prognosis after urgent HT.[Resumen] Introducción y objetivos. Analizar el valor pronóstico de la escala INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) en pacientes tratados con trasplante cardiaco urgente. Métodos. Análisis retrospectivo de 111 pacientes tratados con trasplante cardiaco urgente en nuestro centro entre abril de 1991 y octubre de 2009. Se asignó retrospectivamente a los pacientes a tres niveles de la escala INTERMACS en función de su situación clínica previa al trasplante cardiaco. Resultados. Los pacientes del grupo INTERMACS 1 (n = 31) presentaban mayor frecuencia de cardiopatía isquémica (p = 0,03) y shock tras cardiotomía (p = 0,02) que los pacientes del grupo INTERMACS 2 (n = 55) y los pacientes del grupo INTERMACS 3-4 (n = 25), así como mayores dosis de catecolaminas (p = 0,001), mayor empleo de ventilación mecánica (p < 0,001), balón de contrapulsación (p = 0,002) y dispositivos de asistencia ventricular (p = 0,002) y mayores tasas de infección preoperatoria (p = 0,015). El grupo INTERMACS 1 también mostraba mayores cifras de presión venosa central (p = 0,02), GOT (p = 0,002), GPT (p = 0,006) y creatinina (p < 0,001) y menores cifras de hemoglobina (p = 0,008) y aclaramiento de creatinina (p = 0,001). Tras el trasplante cardiaco, los pacientes del grupo INTERMACS 1 presentaron mayores incidencias de fracaso primario del injerto (p = 0,03) y necesidad de terapia de sustitución renal (p = 0,004), y su supervivencia a largo plazo fue menor que la de los pacientes de los grupos INTERMACS 2 (log rank = 5,1; p = 0,023; razón de riesgos [HR] = 3,1; intervalo de confianza [IC] del 95%, 1,4-6,8) e INTERMACS 3-4 (log rank = 6,1; p = 0,013; HR = 4; IC del 95%, 1,3-12,3). Conclusiones. Nuestros resultados indican que la escala INTERMACS resulta útil para estratificar el pronóstico postoperatorio tras el trasplante cardiaco urgente

Macrophages direct cancer cells through a LOXL2-mediated metastatic cascade in pancreatic ductal adenocarcinoma

[Objective]: The lysyl oxidase-like protein 2 (LOXL2) contributes to tumour progression and metastasis in different tumour entities, but its role in pancreatic ductal adenocarcinoma (PDAC) has not been evaluated in immunocompetent in vivo PDAC models.[Design]: Towards this end, we used PDAC patient data sets, patient-derived xenograft in vivo and in vitro models, and four conditional genetically-engineered mouse models (GEMMS) to dissect the role of LOXL2 in PDAC. For GEMM-based studies, K-Ras +/LSL-G12D;Trp53 LSL-R172H;Pdx1-Cre mice (KPC) and the K-Ras +/LSL-G12D;Pdx1-Cre mice (KC) were crossed with Loxl2 allele floxed mice (Loxl2Exon2 fl/fl) or conditional Loxl2 overexpressing mice (R26Loxl2 KI/KI) to generate KPCL2KO or KCL2KO and KPCL2KI or KCL2KI mice, which were used to study overall survival; tumour incidence, burden and differentiation; metastases; epithelial to mesenchymal transition (EMT); stemness and extracellular collagen matrix (ECM) organisation.[Results]: Using these PDAC mouse models, we show that while Loxl2 ablation had little effect on primary tumour development and growth, its loss significantly decreased metastasis and increased overall survival. We attribute this effect to non-cell autonomous factors, primarily ECM remodelling. Loxl2 overexpression, on the other hand, promoted primary and metastatic tumour growth and decreased overall survival, which could be linked to increased EMT and stemness. We also identified tumour-associated macrophage-secreted oncostatin M (OSM) as an inducer of LOXL2 expression, and show that targeting macrophages in vivo affects Osm and Loxl2 expression and collagen fibre alignment.[Conclusion]: Taken together, our findings establish novel pathophysiological roles and functions for LOXL2 in PDAC, which could be potentially exploited to treat metastatic disease.JCL-G received support from a 'la Caixa' Foundation (ID 100010434) fellowship (LCF/BQ/DR21/11880011). This study was supported by ISCIII FIS grants PI18/00757 and PI21/01110 (BSJ) and PI18/00267 (LG-B), and grants from the Spanish Ministry of Economy and Innovation SAF2016-76504-R (ACan and FP), PID2019-111052RB-I00 (FP), PID2019-104644RB-I00 (GM-B), a Ramón y Cajal Merit Award RYC-2012–12104 (BSJ) and ISCIII, CIBERONC, CB16/12/00446 (ACar) and CB16/12/00295 (ACan and GM-B), all of them co-financed through Fondo Europeo de Desarrollo Regional (FEDER) 'Una manera de hacer Europa'; a Fero Foundation Grant (BSJ); a Coordinated grant (GC16173694BARB) from the Fundación Científica Asociación Española Contra el Cáncer (FC-AECC) (BSJ); a Miguel Servet award (CP16/00121) (PS); a DFG, German Research Foundation Grant—Project no: 492 436 553 (KG); and a Max Eder Fellowship of the German Cancer Aid (111746) (PCH