Personalised comfort systems: a novel approach based on localized two-phase water circulation

openThe approach to personal cooling based on liquid circulation has shown promise in literature, but iterations have been limited and often not based on the existing data on local comfort. This work aims to test out the feasibility of using a mixture of ice and water which is circulated in a garment designed to improve the comfort of localized cooling.The approach to personal cooling based on liquid circulation has shown promise in literature, but iterations have been limited and often not based on the existing data on local comfort. This work aims to test out the feasibility of using a mixture of ice and water which is circulated in a garment designed to improve the comfort of localized cooling

a model in the loop application of a predictive controller to a district heating system

Abstract The high weather variability due to climate change and the need to reduce carbon emissions require innovative solutions for energy systems and grids. In particular, improvements in control strategies allow to increase efficiency without changing the system configuration. Adaptive controllers, as currently proposed, base the management of the system on its past behavior. The main drawback of these methods is the lack of flexibility required to face the mentioned scenario. This paper presents a Model Predictive Control approach which, instead, is based on the prediction of the future evolution of the controlled system. Since it allows to consider the external conditions variability, a more resilient way to manage District Heating and Cooling networks can be achieved. The novel control strategy is developed and tested through a Model-in-the-Loop application to a thermal energy network. This latter is composed by combining physics-based dynamic models from a dedicated library of energy systems components developed by the authors in the Matlab®/Simulink® environment. The network model is controlled by the MPC controller model, which shows to be flexible and reliable in the optimization and management of energy systems

Emerging concepts in heart failure management and treatment: focus on SGLT2 inhibitors in heart failure with preserved ejection fraction

Dapagliflozin; Empagliflozin; Heart failureDapagliflozina; Empagliflozina; Atac de corDapagliflozina; Empagliflozina; Insuficiencia cardiacaThe role of sodium-glucose cotransporter 2 inhibitors (SLTG2i), developed initially as glucose-lowering agents, has represented a novelty in patients with heart failure (HF) and reduced ejection fraction (HFrEF) since dapagliflozin (DAPA-HF study) and empagliflozin (EMPEROR-Reduced study) were able to reduce morbidity and mortality in this setting regardless of the presence or absence of diabetes. In previous large clinical trials (EMPA-REG OUTCOME study, CANVAS, DECLARE-TIMI 58), SGLT2i have been shown to attenuate HF progression expressed by reducing the risk of HF hospitalizations in patients with type 2 diabetes mellitus mostly without HF at baseline. This benefit was then corroborated with positive results in HF outcomes (cardiovascular mortality and HF hospitalizations) in patients with HF with preserved ejection fraction (HFpEF) in the EMPEROR-Preserved (empagliflozin) and DELIVER (dapagliflozin) trials. Several biological mechanisms apart from the glycosuria are attributed to these agents in this last context, including anti-inflammatory effects, reduction of fibrosis and apoptosis, improvement of myocardial metabolism, mitochondrial function optimization, and oxidative stress protection. Moreover, SGLT2i can also improve ventricular loading conditions by forcing diuresis and natriuresis, and by enhancing vascular and renal function. In addition, SGLT2i can reduce myocardial passive stiffness (diastolic function) by enforcing the phosphorylation of myofilament modulatory proteins. This article provided an overview of the main pathophysiological characteristics of HFpEF and of the diverse mechanisms of action of SGLT2i in this setting. The supporting clinical evidence of SGLT2i in HFpEF (EMPEROR-Preserved and DELIVER trials) is also reviewed. This article is part of the Emerging concepts in heart failure management and treatment Special Issue: https://www.drugsincontext.com/special_issues/emerging-concepts-in-heart-failure-management-and-treatment

Allogeneic mesenchymal stromal cells overexpressing mutant human Hypoxia-inducible factor 1-α (HIF1-α) in an ovine model of acute myocardial infarction

Background-Bone marrow mesenchymal stromal cells (BMMSCs) are cardioprotective in acute myocardial infarction (AMI) because of release of paracrine angiogenic and prosurvival factors. Hypoxia-inducible factor 1-α (HIF1-α), rapidly degraded during normoxia, is stabilized during ischemia and upregulates various cardioprotective genes. We hypothesized that BMMSCs engineered to overexpress mutant, oxygen-resistant HIF1-α would confer greater cardioprotection than nontransfected BMMSCs in sheep with AMI. Methods and Results-Allogeneic BMMSCs transfected with a minicircle vector encoding mutant HIF1-α (BMMSC-HIF) were injected in the peri-infarct of sheep (n=6) undergoing coronary occlusion. Over 2 months, infarct volume measured by cardiac magnetic resonance (CMR) imaging decreased by 71.7±1.3% (P < 0.001), and left ventricular (LV) percent ejection fraction (%EF) increased near 2-fold (P < 0.001) in the presence of markedly decreased end-systolic volume. Sheep receiving nontransfected BMMSCs (BMMSC; n=6) displayed less infarct size limitation and percent LVEF improvement, whereas in placebo-treated animals (n=6), neither parameters changed over time. HIF1-α-transfected BMMSCs (BMMSC-HIF) induced angio-/arteriogenesis and decreased apoptosis by HIF1-mediated overexpression of erythropoietin, inducible nitrous oxide synthase, vascular endothelial growth factor, and angiopoietin-1. Cell tracking using paramagnetic iron nanoparticles in 12 additional sheep revealed enhanced long-term retention of BMMSC-HIF. Conclusions-Intramyocardial delivery of BMMSC-HIF reduced infarct size and improved LV systolic performance compared to BMMSC, attributed to increased neovascularization and cardioprotective effects induced by HIF1-mediated overexpression of paracrine factors and enhanced retention of injected cells. Given the safety of the minicircle vector and the feasibility of BMMSCs for allogeneic application, this treatment may be potentially useful in the clinic.Fil: Hnatiuk, Anna. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Ong, Sang-Ging. Stanford University School of Medicine; Estados UnidosFil: Olea, Fernanda Daniela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Locatelli, Paola. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Riegler, Johannes. Stanford University School of Medicine; Estados UnidosFil: Lee, Won Hee. Stanford University School of Medicine; Estados UnidosFil: Jen, Cheng Hao. University of London; Reino UnidoFil: De Lorenzi, Andrea. Fundación Favaloro; ArgentinaFil: Giménez, Carlos Sebastián. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; ArgentinaFil: Laguens, Rubén. Universidad Favaloro; ArgentinaFil: Wu, Joseph C.. Stanford University School of Medicine; Estados UnidosFil: Crottogini, Alberto José. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Medicina Traslacional, Trasplante y Bioingeniería. Fundación Favaloro. Instituto de Medicina Traslacional, Trasplante y Bioingeniería; Argentin

Effect of vascular endothelial growth factor gene transfer on infarct size, left ventricular function and myocardial perfusion in sheep after 2months of coronary artery occlusion

Background: In large mammalian models of acute myocardial infarction (AMI), plasmid-mediated vascular endothelial growth factor (pVEGF) gene transfer has been shown to induce angio-arteriogenesis, proliferation of myocyte precursors and adult cardiomyocyte mitosis, reducing infarct size at 15days after coronary artery occlusion. However, it is unknown whether these effects persist at longer follow-up times, nor how they affect cardiac performance. We thus assessed infarct size, left ventricular (LV) function and perfusion in 2-month-old ovine AMI. Methods: Adult sheep with coronary artery occlusion were randomized to blindly receive ten intramyocardial injections of 3.8mg of pVEGF or empty plasmid distributed at the infarct border. Three and 60days later, LV perfusion (single-photon emission computed tomography) and function (stress echocardiography) were assessed. Finally, hemodynamics (LV catheterization), scar size and peri-infarct histology were studied. Results: Infarct size was 30% smaller in pVEGF-treated sheep (23.6±1.9% versus 32.7±2.7% of the LV; p<0.02). Percentage fractional shortening and wall thickening at the infarct border improved after pVEGF, as did myocardial perfusion and LV wall motion under pharmacological stress. Global LV function did not differ between groups, although the force-frequency response was preserved in pVEGF group and lost in placebo animals. These effects were associated with angio-arteriogenesis and proliferation of cardiomyocyte precursors. Conclusions: In sheep with AMI, pVEGF gene transfer affords long-term infarct size reduction, yielding regional LV function and perfusion improvement and reducing remodeling progression. These results suggest the potential usefulness of this approach in the clinical setting.Fil: Vera Janavel, Gustavo L.. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: De Lorenzi, Andrea. Fundación Favaloro; ArgentinaFil: Cortés, Claudia. Fundación Favaloro; ArgentinaFil: Olea, Fernanda Daniela. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Cabeza Meckert, Patricia. Fundación Favaloro; ArgentinaFil: Bercovich, Andrés. Biosidus S. A.; ArgentinaFil: Criscuolo, Marcelo. Biosidus S. A.; ArgentinaFil: Laguens, Rubén. Universidad Favaloro. Área de Investigación y Desarrollo; ArgentinaFil: Crottogini, Alberto Jose. Universidad Favaloro. Área de Investigación y Desarrollo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentin

Neuroticism and Conscientiousness Moderate the Effect of Oral Medication Beliefs on Adherence of People with Mental Illness during the Pandemic

Background. After the declaration of the pandemic status in several countries, the continuity of face-to-face visits in psychiatric facilities has been delayed or even interrupted to reduce viral spread. Little is known about the personality factors associated with medication beliefs and adherence amongst individuals with mental illness during the COVID-19 pandemic. This brief report describes a preliminary naturalistic longitudinal study that explored whether the Big Five personality traits prospectively moderate the effects of medication beliefs on changes in adherence during the pandemic for a group of outpatients with psychosis or bipolar disorder. Methods. Thirteen outpatients undergoing routine face-to-face follow-up assessments during the pandemic were included (41 observations overall) and completed the Revised Italian Version of the Ten-Item Personality Inventory, the Beliefs about Medicines Questionnaire, the Morisky Medication Adherence Scale-8-item and the Beck Depression Inventory-II. Results. Participants had stronger concerns about their psychiatric medications rather than beliefs about their necessity, and adherence to medications was generally low. Participants who had more necessity beliefs than concerns had better adherence to medications. People scoring higher in Conscientiousness and Neuroticism traits and more concerned about the medication side effects had poorer adherence. Conclusions. These preliminary data suggest the importance of a careful assessment of the adherence to medications amongst people with psychosis/bipolar disorder during the pandemic. Interventions aimed to improve adherence might focus on patients' medication beliefs and their Conscientiousness and Neuroticism personality traits

HtrA1 in differentiation and growth of human placental tissues

HtrA1 is a secreted multidomain protein with serine protease activity. We used immunohistochemistry, western blotting, real time PCR and ELISA techniques to analyse the role of HtrA1 in normal and pathological development of human placental villous trees. In addition, we evaluated the alterations of maternal plasma HtrA1 level in preeclampsia (PE) complicated by intrauterine growth restriction (IUGR). HtrA1 is expressed in the mesenchymal villi which are considered the basis of growth and differentiation of the villous trees and in the villous stroma directly opposed to cell islands and cell columns in first trimester placentas. In addition, the villous trophoblast, the syncytial knots and the foetal vessels are stained for HtrA1 in first as well as third trimester placentas [1]. When the placenta escapes the normal differentiation and growth control mechanisms, which are present during normal pregnancy, it may develop gestational diseases, such as trophoblastic disease as well as PE and IUGR [1,2]. The most striking finding of our investigation is the decrease of this protease in placental tissues with increasing severity of gestational diseases and the increase of HtrA1 in maternal plasma of PE complicated by IUGR [3]. Based on these data HtrA1 could be considered as a possible marker of an occurring IUGR in preeclamptic women

Closed doors: predictors of stress, anxiety, depression, and PTSD during the onset of COVID-19 pandemic in Brazil

BACKGROUND: The rise in mental health problems in the population directly or indirectly because of the coronavirus disease 2019 (COVID-19) pandemic is a major concern. The aim of this study was to investigate and compare independent predictors of symptoms of stress, anxiety, depression, and posttraumatic stress disorder (PTSD) in Brazilians one month after the implementation of measures of social distancing. METHODS: This cross-sectional study was performed using a web-based survey. The Depression, Anxiety, and Stress Scale (DASS-21) and PTSD Checklist for DSM-5 (PCL-5) were the outcomes. Data were gathered regarding demographics, social distancing, economic problems, exposure to the news of the pandemic, psychiatric history, sleep disturbances, traumatic situations, and substance use. The Alcohol Use Disorders Identification Test - Consumption (AUDIT-C) was also administered. The predictors of the symptoms were investigated using hierarchical multiple linear regression. RESULTS: Of a sample of 3587 participants, approximately two-thirds considered that their mental health worsened after the beginning of the social restriction measures. The most important predictors of the symptoms investigated were the intensity of the distress related to the news of the pandemic, younger age, current psychiatric diagnosis, trouble sleeping, emotional abuse or violence, and economic problems. CONCLUSIONS: These results confirmed the hypothesis that the pandemic impacted the mental health of the population and indicated that the level of distress related to the news was the most important predictor of psychological suffering

The effect of continuous positive airway pressure on blood pressure in patients with obstructive sleep apnea and uncontrolled hypertension : study design and challenges during the COVID-19 pandemic

OBJECTIVES: To describe the MORPHEOS (Morbidity in patients with uncontrolled HTN and OSA) trial, and describe the challenges imposed by the COVID-19 pandemic. METHODS: MORPHEOS is a multicenter (n=6) randomized controlled trial designed to evaluate the blood pressure (BP) lowering effects of treatment with continuous positive airway pressure (CPAP) or placebo (nasal strips) for 6 months in adult patients with uncontrolled hypertension (HTN) and moderate-to-severe obstructive sleep apnea (OSA). Patients using at least one antihypertensive medication were included. Uncontrolled HTN was confirmed by at least one abnormal parameter in the 24-hour ABPM and >= 80% medication adherence evaluated by pill counting after the run-in period. OSA was defined by an apnea-hypopnea index >= 15 events/ hours. The co-primary endpoints are brachial BP (office and ambulatory BP monitoring, ABPM) and central BP. Secondary outcomes include hypertension-mediated organ damage (HMOD) to heart, aorta, eye, and kidney. We pre-specified several sub-studies from this investigation. Visits occur once a week in the first month and once a month thereafter. The programmed sample size was 176 patients but the pandemic prevented this final target. A post-hoc power analysis will be calculated from the final sample. ClinicalTrials.gov: NCT02270658. RESULTS: The first 100 patients are predominantly males (n=69), age: 52±10 years, body mass index: 32.7±3.9 kg/m2 with frequent co-morbidities. CONCLUSIONS: The MORPHEOS trial has a unique study design including a run-in period; pill counting, and detailed analysis of hypertension-mediated organ damage in patients with uncontrolled HTN that will allow clarification of the impact of OSA treatment with CPAP

Comparison of HIV-1 Genotypic Resistance Test Interpretation Systems in Predicting Virological Outcomes Over Time

Background: Several decision support systems have been developed to interpret HIV-1 drug resistance genotyping results. This study compares the ability of the most commonly used systems (ANRS, Rega, and Stanford's HIVdb) to predict virological outcome at 12, 24, and 48 weeks. Methodology/Principal Findings: Included were 3763 treatment-change episodes (TCEs) for which a HIV-1 genotype was available at the time of changing treatment with at least one follow-up viral load measurement. Genotypic susceptibility scores for the active regimens were calculated using scores defined by each interpretation system. Using logistic regression, we determined the association between the genotypic susceptibility score and proportion of TCEs having an undetectable viral load (<50 copies/ml) at 12 (8-16) weeks (2152 TCEs), 24 (16-32) weeks (2570 TCEs), and 48 (44-52) weeks (1083 TCEs). The Area under the ROC curve was calculated using a 10-fold cross-validation to compare the different interpretation systems regarding the sensitivity and specificity for predicting undetectable viral load. The mean genotypic susceptibility score of the systems was slightly smaller for HIVdb, with 1.92±1.17, compared to Rega and ANRS, with 2.22±1.09 and 2.23±1.05, respectively. However, similar odds ratio's were found for the association between each-unit increase in genotypic susceptibility score and undetectable viral load at week 12; 1.6 [95% confidence interval 1.5-1.7] for HIVdb, 1.7 [1.5-1.8] for ANRS, and 1.7 [1.9-1.6] for Rega. Odds ratio's increased over time, but remained comparable (odds ratio's ranging between 1.9-2.1 at 24 weeks and 1.9-2.