Towards environmental sustainability of non-residential buildings: An integrated approach to combine thermal comfort of people with energy saving strategies for heating system management

Buildings are constructed and operated to satisfy human needs and improve quality of life. Good indoor air quality and thermal comfort are prerequisites for human health and well-being. At the same time, these aspects are strictly linked to the buildings’ energy consumption, with a direct impact on energy efficiency global goals and climate changes. Global technical regulations and guidelines aim at increasing the energy performance of buildings, with targets of NZEB and ZEB, both for new and existing buildings. In this context the research was carried out in order to investigate energy saving strategies related to heating systems, combining with indoor comfort analyses. The case study is an existing building, located in Perugia (Italy), which is the main seat of Arpa Umbria. The recent energy crisis has imposed strict measures to contain energy consumption, especially for heating; for this reason, the study aims to identify optimal management of the heating, based on a thermal calibrated model of the building and thermo-hygrometric monitoring. With the model, different management strategies were defined and simulated in order to develop schedules to set switch-on/off systems based on indoor and outdoor weather conditions. The results are presented in an integrated approach, combining the estimated reduction of energy consumption with human well-being

On the Possible Wind Energy Contribution for Feeding a High Altitude Smart Mini Grid

The use of renewable energy sources to increase electricity access, especially in remote areas as high mountains, is a possible contribution to poverty reduction, climate change mitigation and improved resilience. In this paper an evaluation of the wind potential of a remote area in Nepal is performed, using CFD methods and the simulation of a micro wind turbine projected by Perugia University. With an accurate analysis of wind data and air density effects it is possible to test energy production potential in areas with high average wind speed. The overall estimated production for each turbine is an interesting result and an easily exportable contribution to the perspective of sustainable development at very high altitudes and remote areas

Preventing Persistence of HPV Infection with Natural Molecules

Human papillomavirus (HPV) infection is one the most common sexually transmitted infections worldwide. In most cases, the infection is temporary and asymptomatic; however, when persistent, it may lead to lesions that can evolve into cancer in both women and men. Nowadays, prophylactic vaccination is the primary preventive strategy for HPV infections, but vaccines do not cover all types of HPV strains. Scientific research has uncovered the beneficial role of some natural supplements in preventing persistent HPV infections or treating HPV-related lesions. We review the current insight into the roles of natural molecules in HPV infection with a special focus on epigallocatechin gallate (EGCG), folic acid, vitamin B12, and hyaluronic acid (HA). Specifically, EGCG from green tea extracts plays a critical role in suppressing HPV oncogenes and oncoproteins (E6/E7), which are responsible for HPV oncogenic activity and cancer development. Folic acid and vitamin B12 are essential vitamins for multiple functions in the body, and accumulating evidence suggests their importance in maintaining a high degree of methylation of the HPV genome, thus decreasing the likelihood of causing malignant lesions. HA, due to its re-epithelizing property, may prevent HPV virus entry in damaged mucosa and epithelia. Thereby, based on these premises, the combination of EGCG, folic acid, vitamin B12, and HA may be a very promising therapeutic approach to prevent HPV persistence

Oxidative Stress Biomarkers: Establishment of Reference Values for Isoprostanes, AOPP, and NPBI in Cord Blood

Oxidative stress (OS) is a common pathogenic factor involved in the onset of several diseases in humans, from immunologic disorders to malignancy, being a serious public health problem. In perinatal period, OS has been associated with adverse outcome of pregnancy and neonatal diseases. Dangerous effects of OS are mediated by increased production of free radicals (FRs) following various mechanisms, such as hypoxia, ischemia reperfusion, hyperoxia, inflammation, mitochondrial dysfunction, Fenton chemistry, and prostaglandin metabolism. FRs have short half-life, and their measurement in vivo is faced with many challenges. However, oxyradical derivatives are stable and thus may be measured and monitored repeatedly. The quantification of OS is based on the measurement of specific biomarkers in biologic fluids and tissues, which reflect induced oxidative damage to lipids, proteins, and DNA. Prostanoids, non-protein-bound iron (NPBI), and advanced oxidation protein products (AOPP) are actually considered truly specific and reliable for neonatal injury. Defining reference values for these biomarkers is necessary to investigate their role in neonatal diseases or also to evaluate the success of treatments. In this work, we wanted to define laboratory reference values for biomarkers of OS in a healthy population of term newborns

Modulation of Indoleamine 2,3-Dioxygenase 1 During Inflammatory Bowel Disease Activity in Humans and Mice

Background and Aims: Indoleamine 2,3 dioxygenase-1 (IDO1), a key enzyme in tryptophan metabolism, is strongly up-regulated both in human inflammatory bowel disease (IBD) and animal models of colitis, however its role in the pathogenesis is still controversial. In this study, we investigated IDO1 expression and activity in a mouse model of DSS-induced chronic colitis as well as in colon biopsies and sera from IBD patients. Methods: Chronic colitis was induced in mice through the oral administration of dextran sodium sulfate (DSS), and IDO1 activity was induced by i.p. treatment with N-acetyl serotonin (NAS). IDO1 expression and catalytic activity (measured as Kyn/Trp ratio) was evaluated in sera and tissue samples collected from mice and 93 IBD patients under immunotherapy with Vedolizumab (VDZ) or Ustekinumab (UST). Results: Strong up-regulation of IDO1 was found in colons of mice with acute colitis, which follows disease activity. Enhanced IDO1 activity by NAS treatment protects the intestinal mucosa during the recovery phase of chronic colitis. In IBD patients, IDO1 expression and activity correlate with the severity of mucosal inflammation with inflamed regions showing higher IDO1 expression compared to non-inflamed regions within the same patient. Endoscopic response to VDZ/UST treatment is associated with decreased expression of IDO1. Conclusions: This is the first study demonstrating immunomodulatory activity of IDO1 in a chronic mouse model of DSS-induced colitis. As its expression and catalytic activity correlate with the grade of mucosal inflammation and treatment response, IDO1 could represent a promising biomarker for disease severity and treatment monitoring in IBD.</p

ALK rearrangement in a large series of consecutive non-small cell lung cancers: Comparison between a new immunohistochemical approach and fluorescence in situ hybridization for the screening of patients eligible for crizotinib treatment

Context. - Echinoderm microtubule associated protein-like 4-anaplastic lymphoma receptor tyrosine kinase (EML4-ALK) translocation has been described in a subset of patients with non-small cell lung cancer (NSCLC) and has been shown to have oncogenic activity. Fluorescence in situ hybridization (FISH) is used to detect ALK-positive NSCLC, but it is expensive, time-consuming, and difficult for routine application. Objective. - To evaluate the potential role of immunohistochemistry (IHC) as a screening tool to identify candidate cases for FISH analysis and for ALK inhibitor therapy in NSCLC. Design. - We performed FISH and IHC for ALK and mutational analysis for epidermal growth factor receptor (EGFR) and KRAS in 523 NSCLC specimens. We conducted IHC analysis with the monoclonal antibody D5F3 (Ventana Medical Systems, Tucson, Arizona) and a highly sensitive detection system. We also performed a MassARRAY-based analysis (Sequenom, San Diego, California) in a small subset of 11 samples to detect EML4-ALK rearrangement. Results. - Of the 523 NSCLC specimens, 20 (3.8%) were positive for ALK rearrangement by FISH analysis. EGFR and KRAS mutations were identified in 70 (13.4%) and 124 (23.7%) of the 523 tumor samples, respectively. ALK rearrangement and EGFR and KRAS mutations were mutually exclusive. Of 523 tumor samples analyzed, 18 (3.4%) were ALK+ by IHC, 18 samples (3.4%) had concordant IHC and FISH results, and 2 ALK+ cases (0.3%) by FISH failed to show ALK protein expression. In the 2 discrepant cases, we did not detect any mass peaks for the EML4-ALK variants by MassARRAY. Conclusions. - Our results show that IHC may be a useful technique for selecting NSCLC cases to undergo ALK FISH analysis

T follicular helper cells promote a beneficial gut ecosystem for host metabolic homeostasis by sensing microbiota-derived extracellular ATP

The ATP-gated ionotropic P2X7 receptor regulates T follicular helper (Tfh) cell abundance in the Peyer’s patches (PPs) of the small intestine; deletion of P2rx7, encoding for P2X7, in Tfh cells results in enhanced IgA secretion and binding to commensal bacteria. Here, we show that Tfh cell activity is important for generating a diverse bacterial community in the gut and that sensing of microbiota-derived extracellular ATP via P2X7 promotes the generation of a proficient gut ecosystem for metabolic homeostasis. The results of this study indicate that Tfh cells play a role in host-microbiota mutualism beyond protecting the intestinal mucosa by induction of affinity-matured IgA and suggest that extracellular ATP constitutes an inter-kingdom signaling molecule important for selecting a beneficial microbial community for the host via P2X7-mediated regulation of B cell help

Dependence of immunoglobulin class switch recombination in B Cells on vesicular release of ATP and CD73 ectonucleotidase activity

Immunoglobulin (Ig) isotype diversification by class switch recombination (CSR) is an essential process for mounting a protective humoral immune response. Ig CSR deficiencies in humans can result from an intrinsic B cell defect; however, most of these deficiencies are still molecularly undefined and diagnosed as common variable immunodeficiency (CVID). Here, we show that extracellular adenosine critically contributes to CSR in human naive and IgM memory B cells. In these cells, coordinate stimulation of B cell receptor and toll-like receptors results in the release of ATP stored in Ca2+-sensitive secretory vesicles. Plasma membrane ectonucleoside triphosphate diphosphohydrolase 1 CD39 and ecto-5′-nucleotidase CD73 hydrolyze ATP to adenosine, which induces CSR in B cells in an autonomous fashion. Notably, CVID patients with impaired class-switched antibody responses are selectively deficient in CD73 expression in B cells, suggesting that CD73-dependent adenosine generation contributes to the pathogenesis of this disease

A machine-learning based bio-psycho-social model for the prediction of non-obstructive and obstructive coronary artery disease

Background: Mechanisms of myocardial ischemia in obstructive and non-obstructive coronary artery disease (CAD), and the interplay between clinical, functional, biological and psycho-social features, are still far to be fully elucidated. Objectives: To develop a machine-learning (ML) model for the supervised prediction of obstructive versus non-obstructive CAD. Methods: From the EVA study, we analysed adults hospitalized for IHD undergoing conventional coronary angiography (CCA). Non-obstructive CAD was defined by a stenosis &lt; 50% in one or more vessels. Baseline clinical and psycho-socio-cultural characteristics were used for computing a Rockwood and Mitnitski frailty index, and a gender score according to GENESIS-PRAXY methodology. Serum concentration of inflammatory cytokines was measured with a multiplex flow cytometry assay. Through an XGBoost classifier combined with an explainable artificial intelligence tool (SHAP), we identified the most influential features in discriminating obstructive versus non-obstructive CAD. Results: Among the overall EVA cohort (n = 509), 311 individuals (mean age 67 ± 11&nbsp;years, 38% females; 67% obstructive CAD) with complete data were analysed. The ML-based model (83% accuracy and 87% precision) showed that while obstructive CAD was associated with higher frailty index, older age and a cytokine signature characterized by IL-1β, IL-12p70 and IL-33, non-obstructive CAD was associated with a higher gender score (i.e., social characteristics traditionally ascribed to women) and with a cytokine signature characterized by IL-18, IL-8, IL-23. Conclusions: Integrating clinical, biological, and psycho-social features, we have optimized a sex- and gender-unbiased model that discriminates obstructive and non-obstructive CAD. Further mechanistic studies will shed light on the biological plausibility of these associations. Clinical trial registration: NCT02737982