Adaptive “Velari”

As it is known, the global phenomenon of rising temperatures causes uncomfortable and often harmful conditions for human beings living in moderate-climate zones, such as the Mediterranean area, especially in the hottest periods. Examinations of metropolitan cities can witness that high temperatures generate Urban Heat Island (UHI), due to population, buildings, vehicles and human activi-ties in general. With the increase of rising temperatures in the latest decades, people living in big cities have gotten used to tackling heat discomfort with electricity charged cooling systems. As a result, the energy consumption for air-conditioning causes UHIs’ effects to further grow. It is scientifically confirmed that the behavioral habit of relying on artificially generated cold whenever temperatures rise will even-tually make the climate crisis more problematic in the near future. Energy commu-nities are used to producing, storing and consuming energy on site; therefore, power sources must be in close proximity to users. Albeit neglected in the Modern Era, the most proximate and sustainable energy supply is directly available to us: sunlight. The origin of hot temperatures, discomfort and energy waste is, indeed, the most exploitable power generator men can access to. In Southern Europe or Middle East cities, the use of veils as urban-scale shading devices is part of the consolidated tradition; a well-known example can be found in the Spanish city of Sevilla, where textile curtains named “Sevillans” are stretched between buildings. At the present time, we’re witnessing that the climate mitigation action of shading systems can be pursued in combination with energy production, with the development of membrane integrated flexible photovoltaic cells (PV). Masdar City in the United Arab Emirates, designed by the Foster Studio, or the Solar trees of the German pavilion at EXPO 2015 in Milan and the Promenade of the EXPO 2021 in Dubai are some innova-tive yet relevant cases. The use of PV cells for sun-shielding purposes is optimal to respond to a double-sided problem with a single object. Manufacturing an adaptive velario using composite fibers (i-Mesh), could both allow us to design the shape and modulate the density of integrated PV cells as needed. Method: To identify the best position for the adaptive tensile canopies, it is necessary to superimpose different site-specific data: temperatures in the urban area, in particular close to buildings; surfaces that receive most of the daytime radiation; sunlight and ventilation. To develop the most suitable solutions to many environmental scenarios, three-dimensional simu-lations performed with virtual models must be used both at urban (Envimet) and at building scale (in-Sight). Expected results: An algorithm capable of determining the “Velari” best position and the proper shading/density factor. A model, applied to a case study in Rome, to serve an evaluation of the benefits of this technology in terms of decreasing surface temperatures of external horizontal and vertical surfaces of buildings and streets

Commentary: Euthyroid Sick Syndrome in Patients With COVID-19

Recent data from case reports and small clinical studies indicates thyroid disorders characterized by reduction of T3 levels are found associated with adverse events and all causes of mortality in Covid-19 patients (1–7). In this scenario the paper from Zuo et al. (4) consistently describes the presence of the euthyroid sick syndrome (EES) correlating with Covid-19 disease severity but not with non-invasive or invasive ventilation. None of these reports clarify the clinical meaning of these endocrine disturbances, and their pathogenesis remains elusive. In this respect, hypotheses include they represent a stress-evoked response or are generated by a direct attack of the virus to the gland. This latter hypothesis is sustained by findings demonstrating gland cell types can be target of viruses from bat origin. Consistently, it has been reported that i) human thyrocytes express the mRNA for ACE2 (8), the host receptor of the virus Spike protein, ii) viral particles were detected in the follicular epithelium of patients who died of SARS and also of Covid-19 presenting subacute thyroiditis (9) iii) Covid-19 patients may present, where measured, high levels of pro-calcitonin (PCT). Overall, these intriguing data would need to be confirmed by larger clinical studies to establish conclusively the causal relationship, if any, among thyroid diseases and virus infection, and, more importantly, their clinical relevance as possible prognostic indicators of mortality and of severe cardiovascular events (10). However, in the light of the present data, we like to share some considerations on the possibility that reduced serum T3 levels, as observed in EES, because they are not representative of its tissue-specific levels, coincide with accumulation of T3 metabolites, i.e. thyromimetics. The accumulation of such compounds in the olfactory epithelium and skeletal muscle could offer a pathogenic hypothesis for the onset of anosmia and sarcopenia, two fingerprint manifestations of Covid-19 infection. In extra thyroid tissues, T3 levels are controlled by type 1, 2, and 3 deiodinases (DIO1, DIO2, and DIO3 respectively), enzymes removing iodide ions with respect to their position on the aromatic rings and that have a high specific tissue expression. In particular, DIO2 and DIO3 are the main isoforms expressed in neurons and skeletal muscle, and they are rapidly modulated at inflammatory conditions, including ESS (4) and, in general, infective agent attacks (11, 12). At conditions of reduced DIO2 activity, T4 metabolism is mainly driven towards revT3, the alternative metabolite with a very low intrinsic activity at thyroid hormone receptors and considered among the source of other iodinated metabolites belonging to three different chemical classes including thyronamines and thyroacetic acids. These metabolites are indicated as endogenous thyromimetics accumulating in thyroid hormone target tissues and sharing the same but not all the biological effects of T3 (13). Among these compounds, the 3-iodothyronamine (T1AM) is the more characterized in term of pharmacokinetic and pharmacodynamics features (13). Pharmacologically administered T1AM elicited neurological and metabolic effects with high potency. The mechanism of several of these effects remains to be clarified, and possible targets have been described including the trace amine associated receptors (TAAR1-5), while its affinity at thyroid hormone receptors is negligible. TAARs are evolutionarily conserved in vertebrates including humans, exerting an indispensable role in olfaction (14). T1AM, and possibly other thyronamines by the means of their nature as “amines in trace”, is a high affinity ligand for TAAR1 and is described as an inverse agonist at the TAAR5 (15). The olfactory epithelium expresses several TAAR isoforms including TAAR5 but also ACE2 and TMPRSS2, the host virus receptors. According to its pharmacodynamics, T1AM is expected to reduce the basal activity of TAAR5. Down-regulation of TAARs (and anosmia) is reported as a secondary event to immune innate signaling activation induced by virus infection (16). It is then possible to postulate accumulation of T1AM, as result of an increase of revT3 concentration, might have a role in increasing the threshold of olfactory receptor activation thus participating to Covid-19 induced anosmia. The fast recovery from this adverse event experienced by some Covid-19 patients would be consistent with the short half-life of T1AM. In those where anosmia persists even after infection resolution, desensitization effects could add to more complex damages at neurological circuits. Sarcopenia associated with Covid-19 is likely secondary to the cytokine storm and of a long bed rest even if a direct attack of the virus to the skeletal myocytes cannot be excluded since satellite cells and adult myofibers express ACE2 (17). Sarcopenia has a negative impact on patient recovery (18), and it represents a negative prognostic factor for cardiovascular complications (19). Since T3 strongly controls skeletal muscle regenerative capacity and metabolic functions (20), reduced levels of T3 together with vascular inflammation and cachexia, might trigger skeletal muscle catabolism and an incorrect myogenic program of satellite cells. In addition, a role for calcitonin in controlling satellite cell quiescence and their escape from fiber niche, a condition exposing satellite cells to aging and a fibrotic fate, has been described recently (21). In the skeletal muscle, Ju et al. (2017) reported T1AM activated catabolic pathways involved in sarcopenia including AMPK activation (22). Overall, anosmia and sarcopenia have an inflammatory ground which includes a crucial balance between DIO2/DIO3, thus controlling T3 local production (23, 24). Accumulation of revT3 and of T1AM may act in concert as pathogenic events in these Covid-19 clinical manifestations. The role of thyromimetics in Covid-19 related anosmia and sarcopenia is a hypothesis which needs to be confirmed by clinical data. In this respect we launched the opportunity to include the evaluation of thyromimetics among the biomarkers of the thyroid function. Covid-19 pandemic might offer an extraordinary opportunity for investigating the role of the thyroid and to assign a physiopathological role to endogenous thyromimetics

3-iodothyronamine (T1AM), a novel antagonist of muscarinic receptors.

3-iodothyronamine (T1AM) is a trace amine suspected to derive from thyroid hormone metabolism. T1AM was described as a ligand of G-protein coupled monoaminergic receptors, including trace amine associated receptors, suggesting the amine may exert a modulatory role on the monoaminergic transmission. Nothing is known on the possibility that T1AM could also modulate the cholinergic transmission interacting with muscarinic receptors. We evaluated whether T1AM (10 nM\u2013100 \u3bcM) was able to i) displace [3H]-NMS (0.20 nM) binding to membrane preparations from CHO cells stably transfected with human muscarinic receptor subtypes (M1-M5); ii) modify basal or acetylcholine induced pERK1/2 levels in CHO expressing the human muscarinic type 3 receptor subtype by Western blot iii) modify basal and carbachol-induced contraction of isolated rat urinary bladder. T1AM fitting within rat muscarinic type 3 receptor was simulated by Docking studies. T1AM recognized all muscarinic receptor subtypes (pKi values in the micromolar range). Interacting at type 3, T1AM reduced acetylcholine-increased pERK1/2 levels. T1AM reduced carbachol-induced contraction of the rat urinary bladder. The fenoxyl residue and the iodide ion were found essential for establishing contacts with the active site of the rat muscarinic type 3 receptor subtype. Our results indicate that T1AM binds at muscarinic receptors behaving as a weak, not selective, antagonist. This finding adds knowledge on the pharmacodynamics features of T1AM and it may prompt investigation on novel pharmacological effects of T1AM at conditions of hyper-activation of the muscarinic tone including the overactive urinary bladder

Cultura de segurança do paciente na ótica de trabalhadores e equipes da atenção primária

OBJETIVO: Analisar se a cultura de segurança do paciente entre os profissionais da atenção primária à saúde difere entre as equipes de saúde. MÉTODOS: Estudo transversal, quantitativo, realizado nos meses de abril e maio de 2017, em um município da região Sul do Brasil. Participaram 144 profissionais que responderam ao questionário “Pesquisa sobre Cultura de Segurança do Paciente para Atenção Primária”. Os dados foram analisados no programa Statistical Analysis Software e expressos em porcentagens de respostas positivas. Os preceitos éticos estabelecidos para pesquisas com seres humanos foram cumpridos. RESULTADOS: A cultura de segurança do paciente é positiva entre 50,81% dos profissionais e as dimensões “seu serviço de saúde” (63,39%) e “segurança do paciente e qualidade” (61,22%) obtiveram as maiores médias de respostas positivas. Identificou-se diferenças significativas entre as equipes de saúde da família e de saúde bucal (α = 0,05 e p < 0,05), nas dimensões “segurança do paciente” (p = 0,0274) e “trabalho no serviço de saúde” (p = 0,0058). CONCLUSÕES: Concluiu-se que, apesar de próxima da média, a cultura de segurança do paciente entre os profissionais da Atenção Primária à Saúde é positiva e existem diferenças na cultura de segurança entre as equipes de saúde da família e saúde bucal em relação às equipes de atenção básica.OBJECTIVE: Analyze if the patient safety culture among professionals in the primary health care differs among health care teams. METHODS: Cross-sectional and quantitative study conducted in April and May 2017, in a city in Southern Brazil. A total of 144 professionals who responded to the questionnaire “Survey on Patient Safety Culture in Primary Health Care” participated in the study. Data were analyzed in the Statistical Analysis Software program and expressed in percentage of positive responses. The ethical principles established for research with human beings were applied. RESULTS: Patient safety culture is positive among 50.81% of the professionals, and the dimensions “your health service” (63.39%) and “patient safety and quality” (61.22%) obtained the highest average of positive responses. Significant differences were found between the family health and oral health teams (α = 0.05 and p < 0.05), in the dimensions “patient safety” (p = 0.0274) and “work at the health service” (p = 0.0058). CONCLUSIONS: We concluded that, although close to the average, patient safety culture among professionals in the Primary Health Care is positive and that there are differences in safety culture between family health and oral health teams in comparison with the primary health care teams

Pharmacological perspectives in sarcopenia: A potential role for renin-angiotensin system blockers?

Sarcopenia represents a major health problem highly prevalent in elderly and age-related chronic diseases. Current pharmacological strategies available to prevent and reverse sarcopenia are largely unsatisfactory thus raising the need to identify novel targets for pharmacological intervention and possibly more effective and safe drugs. This review highlights the current knowledge of the potential benefits of renin-angiotensin system blockade in sarcopenia and discuss the main mechanisms underlying the effects

A stereoselective, catalytic strategy for the in-flow synthesis of advanced precursors of rasagiline and tamsulosin

The diastereoselective, trichlorosilane-mediate reduction of imines, bearing different and removable chiral auxiliaries, in combination either with achiral bases or catalytic amounts of chiral Lewis bases, was investigated to afford immediate precursors of chiral APIs (Active Pharmaceutical Ingredients). The carbon-nitrogen double bond reduction was successfully performed in batch and in flow mode, in high yields and almost complete stereocontrol. By this metal-free approach, the formal synthesis of rasagiline and tamsulosin was successfully accomplished in micro(meso) flow reactors, under continuous flow conditions. The results of these explorative studies represent a new, important step towards the development of automated processes for the preparation of enantiopure biologically active compound