•COVID-19 lockdown led to a significant increase in residential electricity usage.•Shift in energy usage from morning peak to central hours registered during lockdown.•The study provides a set of ...daily load profiles for residential buildings.•Remote working can have a significant impact on energy use in residential buildings.•Findings can assist cities analysts, regulators and businesses in weighing effects of remote working.
The COVID-19 pandemic had a profound impact on society, causing changes in various aspects of people's lives, including their energy use habits. This has prompted a need for checking and updating standard energy use profiles, particularly for residential electricity use. To address this topic, a study was conducted on 24 multifamily buildings in Milan, using clustering to extract patterns from a database of quarter-hourly electricity use data from 2019 to 2020. This study found an increase in electricity usage during the COVID-19 lockdown period for residential buildings, likely associated with the imposed restrictions. The research also highlighted a shift in energy usage from the morning peak to the central hours of the day during the working days of the lockdown period, while a gradual increase in electricity usage throughout the day and no morning peak was observed during the Autumn (post-COVID) period. The findings can assist regulators and businesses in weighing the benefits and drawbacks of remote working and provide modellers with a complete set of daily load profiles for an Italian residential case study.
Different variables concur to the outdoor comfort assessment and, among them, the Mean Radiant Temperature (Tmr) represents the most challenging one to experimentally evaluate. According to the ...scientific literature, the most accurate method for in-field Tmr calculation is integral radiation measurements with three net radiometers. Nevertheless, net radiometers are expensive sensors and their implementation on large scale may be hindered by their price. To provide a cost-effective alternative some researchers proposed the use of globe thermometers. Globe thermometers are affordable sensors but typically exploited indoors, and their accuracy in urban settings is still under investigation.
The scope of this work is to provide information regarding the extent to which globe thermometers can substitute net radiometers in the evaluation of the Tmr in outdoor urban settings. To this purpose, an experimental comparison has been performed between the Tmr calculated using net radiometers, assumed as a reference, and using two different globe thermometers: a standard 150 mm black globe and a grey 50 mm globe.
The results revealed that the black globe tends to overestimate the Tmr while the grey globe mainly underestimates it. Moreover, the analyses evidenced a wide fluctuation in the profile of the Tmr calculated using globe thermometers, due to the rapid variation of meteorological parameters and the globes' long response time. To improve the fit between globe thermometers and net radiometers' response, regressive functions have been proposed, resulting in a significant enhancement of the adherence between Tmr calculated using the standard black globe's measurements and the reference Tmr.
•Tmr is key parameter for outdoor thermal comfort assessment in urban settings.•Globe thermometers cannot directly substitute net radiometers to assess the Tmr.•A regression equation is used to assess the Tmr from the standard globe thermometer.•In 90.4% of cases, the equation results in a negligible error for Tmr.•This result decreases greatly the cost and number of required sensors.
MicroRNAs (miRNAs) are small noncoding RNAs playing a fundamental role in the regulation of gene expression. Evidence accumulating in the past decades indicate that they are capable of simultaneously ...modulating diverse signaling pathways involved in a variety of pathophysiological processes. In the present review, we provide a comprehensive overview of the function of a highly conserved group of miRNAs, the miR-181 family, both in physiological as well as in pathological conditions. We summarize a large body of studies highlighting a role for this miRNA family in the regulation of key biological processes such as embryonic development, cell proliferation, apoptosis, autophagy, mitochondrial function, and immune response. Importantly, members of this family have been involved in many pathological processes underlying the most common neurodegenerative disorders as well as different solid tumors and hematological malignancies. The relevance of this miRNA family in the pathogenesis of these disorders and their possible influence on the severity of their manifestations will be discussed. A better understanding of the miR-181 family in pathological conditions may open new therapeutic avenues for devasting disorders such as neurodegenerative diseases and cancer.
Gene therapy is proving to be an effective approach to treat or prevent ocular diseases ensuring a targeted, stable, and regulated introduction of exogenous genetic material with therapeutic action. ...Retinal diseases can be broadly categorized into two groups, namely monogenic and complex (multifactorial) forms. The high genetic heterogeneity of monogenic forms represents a significant limitation to the application of gene-specific therapeutic strategies for a significant fraction of patients. Therefore, mutation-independent therapeutic strategies, acting on common pathways that underly retinal damage, are gaining interest as complementary/alternative approaches for retinal diseases. This review will provide an overview of mutation-independent strategies that rely on the modulation in the retina of key genes regulating such crucial degenerative pathways. In particular, we will describe how gene-based approaches explore the use of neurotrophic factors, microRNAs, genome editing and optogenetics in order to restore/prolong visual function in both outer and inner retinal diseases. We predict that the exploitation of gene delivery procedures applied to mutation/gene independent approaches may provide the answer to the unmet therapeutic need of a large fraction of patients with genetically heterogeneous and complex retinal diseases.
Herbs have been used for voice care since ancient times and many herbal remedies are still in use in every geographical areas and cultures, both as traditional medicine and as sources of botanicals ...used in commercial products. Many of these plants are used as extracts and other phytopreparates, and a full phytochemical analysis is sometimes incomplete or lacking. The mechanisms of action of these botanicals include antibacterial, anti-inflammatory, mucolytic, and other general activities; nevertheless, mechanisms that could be specifically referred to voice are often unknown, as well as the corresponding molecular targets and therefore a rational approach in the use of these remedies is hard to be applied by phoniatricians. To address this problem, we collected information on plants used for voice care from several different geographical areas, using both literature data and a pool of contributors from an international network of artistic phoniatrics and vocologists. The plants have been organized in a database (Herbs for Voice Database) and classified according to the natural compounds contained in them, their molecular targets and the pathologies they are recommended for. This first database contains 44 plants, 101 phytocompounds, and 32 recognized molecular targets. The distribution of herbs and phytocompounds according to the botanical families, their known biological activity, traditional uses, and molecular targets were analyzed. In particular, data analysis shows that the somatosensory and pain receptor Transient Receptor Potential Ankyrin 1 ion channel is targeted by a large number of different phytochemicals contained in the herbs for voice, and could therefore be involved in a mechanism of action common to many plants.
Melanoma has the highest mortality rate among skin cancers, and early-diagnosis is essential to maximize survival rate. The current procedure for melanoma diagnosis is based on dermoscopy, i.e., a ...qualitative visual inspection of lesions with intrinsic limited diagnostic reliability and reproducibility. Other non-invasive diagnostic techniques may represent valuable solutions to retrieve additional objective information of a lesion. This review aims to compare the diagnostic performance of non-invasive techniques, alternative to dermoscopy, for melanoma detection in clinical settings. A systematic review of the available literature was performed using PubMed, Scopus and Google scholar databases (2010-September 2020). All human,
, non-invasive studies using techniques, alternative to dermoscopy, for melanoma diagnosis were included with no restriction on the recruited population. The reference standard was histology but dermoscopy was accepted only in case of benign lesions. Attributes of the analyzed studies were compared, and the quality was evaluated using CASP Checklist. For studies in which the investigated technique was implemented as a diagnostic tool (DTA studies), the QUADAS-2 tool was applied. For DTA studies that implemented a melanoma vs. other skin lesions classification task, a meta-analysis was performed reporting the SROC curves. Sixty-two references were included in the review, of which thirty-eight were analyzed using QUADAS-2. Study designs were: clinical trials (13), retrospective studies (10), prospective studies (8), pilot studies (10), multitiered study (1); the remain studies were proof of concept or had undefined study type. Studies were divided in categories based on the physical principle employed by each diagnostic technique. Twenty-nine out of thirty-eight DTA studies were included in the meta-analysis. Heterogeneity of studies' types, testing strategy, and diagnostic task limited the systematic comparison of the techniques. Based on the SROC curves, spectroscopy achieved the best performance in terms of sensitivity (93%, 95% CI 92.8-93.2%) and specificity (85.2%, 95%CI 84.9-85.5%), even though there was high concern regarding robustness of metrics. Reflectance-confocal-microscopy, instead, demonstrated higher robustness and a good diagnostic performance (sensitivity 88.2%, 80.3-93.1%; specificity 65.2%, 55-74.2%). Best practice recommendations were proposed to reduce bias in future DTA studies. Particular attention should be dedicated to widen the use of alternative techniques to conventional dermoscopy.
Pleural mesothelioma (PM) is an aggressive cancer with poor prognosis and no effective therapies, mainly caused by exposure to asbestos. Antagonists of growth hormone-releasing hormone (GHRH) display ...strong antitumor effects in many experimental cancers, including lung cancer and mesothelioma. Here, we aimed to determine whether GHRH antagonist MIA-690 potentiates the antitumor effect of cisplatin and pemetrexed in PM. In vitro, MIA-690, in combination with cisplatin and pemetrexed, synergistically reduced cell viability, restrained cell proliferation and enhanced apoptosis, compared with drugs alone. In vivo, the same combination resulted in a strong growth inhibition of MSTO-211H xenografts, decreased tumor cell proliferation and increased apoptosis. Mechanistically, MIA-690, particularly with chemotherapeutic drugs, inhibited proliferative and oncogenic pathways, such as MAPK ERK1/2 and cMyc, and downregulated cyclin D1 and B1 mRNAs. Inflammatory pathways such as NF-kB and STAT3 were also reduced, as well as oxidative, angiogenic and tumorigenic markers (iNOS, COX-2, MMP2, MMP9 and HMGB1) and growth factors (VEGF and IGF-1). Overall, these findings strongly suggest that GHRH antagonists of MIA class, such as MIA-690, could increase the efficacy of standard therapy in PM.
Mitochondrial diseases (MDs) are a heterogeneous group of devastating and often fatal disorders due to defective oxidative phosphorylation. Despite the recent advances in mitochondrial medicine, ...effective therapies are still not available for these conditions. Here, we demonstrate that the microRNAs miR‐181a and miR‐181b (miR‐181a/b) regulate key genes involved in mitochondrial biogenesis and function and that downregulation of these miRNAs enhances mitochondrial turnover in the retina through the coordinated activation of mitochondrial biogenesis and mitophagy. We thus tested the effect of miR‐181a/b inactivation in different animal models of MDs, such as microphthalmia with linear skin lesions and Leber's hereditary optic neuropathy. We found that miR‐181a/b downregulation strongly protects retinal neurons from cell death and significantly ameliorates the disease phenotype in all tested models. Altogether, our results demonstrate that miR‐181a/b regulate mitochondrial homeostasis and that these miRNAs may be effective gene‐independent therapeutic targets for MDs characterized by neuronal degeneration.
Synopsis
MicroRNAs 181a/b is important for mitochondria homeostasis in the retina. miR‐181a/b inactivation in different animal models of mitochondrial diseases protects neuronal degeneration and ameliorates the disease phenotype in tested models.
miR‐181a/b control mitochondrial biogenesis in the retina and their downregulation enhances mitochondrial turnover through the coordinated activation of mitochondrial biogenesis and mitophagy.
miR‐181a/b inhibition protects neurons from cell death and ameliorates the phenotype of different in vivo models of mitochondrial disease, i.e. such as Microphthalmia with Linear Skin Lesions (MLS) and Leber Hereditary Optic Neuropathy (LHON).
miR‐181a/b may represent effective gene‐independent therapeutic targets for genetically heterogeneous mitochondrial diseases characterized by neuronal degeneration.
MicroRNAs 181a/b is important for mitochondria homeostasis in the retina. miR‐181a/b inactivation in different animal models of mitochondrial diseases protects neuronal degeneration and ameliorates the disease phenotype in tested models.
A thorough study on the (E) to (Z) photoisomerization of ferulic acid derivatives (esters, amides of all types, and ketones) was carried out. At the photostationary state, only aliphatic or benzylic ...tertiary amides reach a nearly complete conversion of (E) isomers into the (Z) ones, whereas for esters, primary and secondary amides or aromatic tertiary amides mixtures of (Z)/(E) ranging from 7 : 93 to 72 : 28 are observed. Ketones show rather limited photoisomerization. However, (Z) ketones may be obtained by the reaction of organometal compounds with an isomerized (Z) Weinreb amide.
A comprehensive study of photoisomerzation of ferulic acid derived esters, amides, and ketones was carried out. Only in the case of aliphatic tertiary amides, a nearly complete E→Z conversion was achieved.
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