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The smart tourism ecosystem concept, in addition to integrating various components, processes, and actions in the design of a place, advocates certain results through the convergence of technological resources, business environments, and valueinducing experiences. This conceptual paper should result in theoretical contributions regarding the specificity of the tourist experience within the framework of a smart tourism ecosystem, with a view to the competitiveness and sustainability of accommodation and destinations. From the perspective of a smart tourism ecosystem, the production and consumption of tourist value -- which, hopefully, should be socially, culturally, environmentally, and economically sustainable --, is shared, and generate distinctive experiences, and the corresponding interactions are promoted by technology, through the collection, processing, and communication of data. The suggested approach has relevant implications at the management level, given the need to obtain differentiating factors, mediated by technology, with the incorporation of added value for the stakeholders. [ABSTRACT FROM AUTHOR]

Introdução: A detecção precoce do câncer de mama (CM) é importante para reduzir as taxas de mortalidade. Para preveni-lo, a mulher deve adotar comportamentos de autocuidado em saúde. Esse estudo objetiva examinar a percepção de risco, a percepção da doença e o autocuidado de mulheres saudáveis com relação ao CM. Método: Participaram 211 mulheres (M=59,11 anos; DP=8,54) sem histórico de CM selecionados por conveniência. Os instrumentos foram questionário de dados sociodemográficos, clínicos e de comportamento em saúde, questionários de percepção da doença e percepção de risco. Estatística não paramétrica (Spearman) foi utilizada para analisar a relação entre percepção da doença, percepção de risco e variáveis sociodemográficas. As respostas abertas sobre as causas da doença foram classificadas segundo análise de conteúdo. Resultados: Observou-se que existe relação entre a percepção de risco e da doença, e autocuidado em mulheres saudáveis. Identificou-se que as mulheres têm razoável percepção de entendimento da doença (M=3. 18), a consideravam mais crônica que aguda (M=3. 22), razoavelmente cíclica (M=3,56), com consequências graves à saúde (M=4,22), e relativamente ameaçadora (M=3,15). Conclusões: A percepção do CM, a percepção de risco e o autocuidado são variáveis inter-relacionadas em mulheres saudáveis

Purpose: This study aimed to assess the quality of the lucite cone applicator (LCA), the standard applicator for superficial hyperthermia at the Erasmus MC Cancer Institute, using the most recent quality assurance guidelines, thus verifying their feasibility., Materials and Methods: The assessment was conducted on each of the six LCAs available for clinical treatments. The temperature distribution was evaluated using an infrared camera across different layers of a fat-muscle mimicking phantom. The maximum temperature increase, thermal effective penetration depth (TEPD), and thermal effective field size (TEFS) were used as quality metrics. The experimental results were validated through comparison with simulated results, using a canonical phantom model and a realistic phantom model segmented from CT imaging., Results: A maximum temperature increase above 6 °C at 2 cm depth in the fat-muscle phantom for all the experiments was found. A mean negative difference between simulated and experimental data was of 1.3 °C when using the canonical phantom model. This value decreased to a mean negative difference of 0.4 °C when using the realistic model. Simulated and measured TEPD showed good agreement for both in silico scenarios, while discrepancies were present for TEFS., Conclusions: The LCAs passed all QA guidelines requirements for superficial hyperthermia delivery when used singularly or in an array configuration. A further characterization of parameters such as antenna efficiency and heat transfer coefficients would be beneficial for translating experimental results to simulated values. Implementing the QA guidelines was time-consuming and demanding, requiring careful preparation and correct setup of antenna elements.

The challenge to explain the diffuse and unconclusive message reported by hyperthermia studies investigating the thermal dose parameter is still to be unravelled. In the present review, we investigated a wide range of technical and clinical parameters characterising hyperthermia treatment to better understand and improve the probability of detecting a thermal dose effect relationship in clinical studies. We performed a systematic literature review to obtain hyperthermia clinical studies investigating the associations of temperature and thermal dose parameters with treatment outcome or acute toxicity. Different hyperthermia characteristics were retrieved, and their influence on temperature and thermal dose parameters was assessed. In the literature, we found forty-eight articles investigating thermal dose effect relationships. These comprised a total of 4107 patients with different tumour pathologies. The association between thermal dose and treatment outcome was the investigated endpoint in 90% of the articles, while the correlation between thermal dose and toxicity was investigated in 50% of the articles. Significant associations between temperature-related parameters and treatment outcome were reported in 63% of the studies, while those between temperature-related parameters and toxicity were reported in 15% of the studies. One clear difficulty for advancement is that studies often omitted fundamental information regarding the clinical treatment, and among the different characteristics investigated, thermometry details were seldom and divergently reported. To overcome this, we propose a clear definition of the terms and characteristics that should be reported in clinical hyperthermia treatments. A consistent report of data will allow their use to further continue the quest for thermal dose effect relationships.

Endothelial cell (EC) activity is essential for tissue regeneration in several (patho)physiological contexts. However, our capacity to deliver in vivo biomolecules capable of controlling EC fate is relatively limited. Here, we screened a library of microRNA (miR) mimics and identified 25 miRs capable of enhancing the survival of ECs exposed to ischemia-mimicking conditions. In vitro , we showed that miR-425-5p, one of the hits, was able to enhance EC survival and migration. In vivo , using a mouse Matrigel plug assay, we showed that ECs transfected with miR-425-5p displayed enhanced survival compared with scramble-transfected ECs. Mechanistically, we showed that miR-425-5p modulated the PTEN/PI3K/AKT pathway and inhibition of miR-425-5p target genes ( DACH1 , PTEN , RGS5 , and VASH1 ) phenocopied the pro-survival. For the in vivo delivery of miR-425-5p, we modulated small extracellular vesicles (sEVs) with miR-425-5p and showed, in vitro , that miR-425-5p-modulated sEVs were (1) capable of enhancing the survival of ECs exposed to ischemia-mimic conditions, and (2) efficiently internalized by skin cells. Finally, using a streptozotocin-induced diabetic wound healing mouse model, we showed that, compared with miR-scrambled-modulated sEVs, topical administration of miR-425-5p-modulated sEVs significantly enhanced wound healing, a process mediated by enhanced vascularization and skin re-epithelialization., Competing Interests: P.d.C.M. collaborates with Mirabilis Therapeutics. The other authors declare no competing interests., (© 2022 The Authors.)

Introduction: A condition called multisystem inflammatory syndrome in children (MIS-C), related to past SARS-CoV-2 infection, has been described in a series of cases. There is a growing body of evidence suggesting a similar entity in adults (MIS-A). We report a case of a young adult with a hyperinflammatory systemic syndrome with end-organ lesions and a recent SARS-CoV-2 infection., Methods and Procedures: The patient developed end-organ lesions in the respiratory, cardiovascular, digestive, haematological and mucocutaneous systems. A wide diagnostic work-up did not find any specific aetiology (autoimmunity, neoplastic or infectious). There was evidence of past SARS-CoV-2 infection with positive autoimmune titres (positive IgG). A presumptive diagnosis of MIS-A was made and treatment with corticosteroids was introduced with improvement., Discussion: COVID-19-related multisystem inflammatory syndrome in adults is still an unknown entity with no diagnostic criteria or treatment guidelines. Much of what is known is inferred from what we already know about MIS-C. There have been several reported cases with severity ranging from mild to severe. The mechanisms behind this condition are still largely unknown. More evidence is needed to establish diagnosis and treatment., Learning Points: COVID-19-related multisystem inflammatory syndrome in adults is a new entity with few case reports.Awareness is important for early diagnosis and treatment., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2021.)

Introduction: A strong association between stroke and atrial fibrillation (AF) has been demonstrated. Anticoagulation for the prevention of stroke in high-risk patients has the benefit of improving the life expectancy, quality of life, autonomy and social functioning of the patient. The COVID-19 pandemic poses challenges for stroke patients because of the association between SARS-CoV-2 infection and thromboembolic risk., Case Description: We describe the case of an 84-year-old female patient admitted due to an embolic stroke and non-anticoagulated AF. Her admission symptoms were sensory-motor aphasia and severe right limb paresis with an NIHSS score of 24. The diagnosis of embolic stroke (namely, total anterior circulation infarct; TACI) was made. Her stroke was extensive so she was not started on anticoagulation. During hospitalization, new embolic events occurred and a concomitant diagnosis of COVID-19 was made with progressive respiratory dysfunction followed by multiorgan failure. The patient died despite appropriate treatment., Discussion: The prognosis of elderly patients with cardioembolic stroke depends on anticoagulation administration. The NIHSS score on admission of our patient meant anticoagulation therapy was not appropriate. The diagnosis of COVID-19 contributed to the patient's death., Learning Points: Anticoagulation should be considered in stroke patients with total infarction and atrial fibrillation.There is an association between COVID-19 and thromboembolic stroke.Elderly patients with stroke and COVID-19 are at higher risk of death., Competing Interests: Conflicts of Interests: The Authors declare that there are no competing interests., (© EFIM 2020.)

Nefazodone (NEF) is an antidepressive agent that was widely used in the treatment of depression until its withdrawal from the market, due to reports of liver injury and failure. NEF hepatotoxicity has been associated with mitochondrial impairment due to interference with the OXPHOS enzymatic activities, increased ROS generation and decreased antioxidant defenses. However, the mechanisms by which NEF induces mitochondrial dysfunction in hepatocytes are not completely understood. Here, we investigated the mitochondrial mechanisms affected upon NEF exposure and whether these might be linked to drug hepatotoxicity, in order to infer liabilities of future drug candidates. Two moderately hepatotoxic NEF concentrations (20 and 50 μM) were selected from dose-response growth curves performed in HepG2 cells. Cell viability, caspase activity, nuclear morphology, mitochondrial transmembrane potential, mitochondrial superoxide levels, and the expression of genes associated with different cellular pathways were evaluated at different time points. NEF treatment led to an increase in the expression of genes associated with DNA-damage response, antioxidant defense and apoptosis and a decreased expression of genes encoding proteins involved in oxidative phosphorylation, DNA repair, cell proliferation and cell cycle progression, which seem to constitute mechanisms underlying the observed mitochondrial and cell function impairment., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Red cell distribution width (RDW), a classical parameter used in the differential diagnosis of anemia, has recently been recognized as a marker of chronic inflammation and high levels of oxidative stress (OS). Fanconi anemia (FA) is a genetic disorder associated to redox imbalance and dysfunctional response to OS. Clinically, it is characterized by progressive bone marrow failure, which remains the primary cause of morbidity and mortality. Macrocytosis and increased fetal hemoglobin, two indicators of bone marrow stress erythropoiesis, are generally the first hematological manifestations to appear in FA. However, the significance of RDW and its possible relation to stress erythropoiesis have never been explored in FA. In the present study we analyzed routine complete blood counts from 34 FA patients and evaluated RDW, correlating with the hematological parameters most consistently associated with the FA phenotype., Results: We showed, for the first time, that RDW is significantly increased in FA. We also showed that increased RDW is correlated with thrombocytopenia, neutropenia and, most importantly, highly correlated with anemia. Analyzing sequential hemograms from 3 FA patients with different clinical outcomes, during 10 years follow-up, we confirmed a consistent association between increased RDW and decreased hemoglobin, which supports the postulated importance of RDW in the evaluation of hematological disease progression., Conclusions: This study shows, for the first time, that RDW is significantly increased in FA, and this increment is correlated with neutropenia, thrombocytopenia, and highly correlated with anemia. According to the present results, it is suggested that increased RDW can be a novel marker of stress erythropoiesis in FA.

Gonadal failure, along with early pregnancy loss and perinatal death, may be an important filter that limits the propagation of harmful mutations in the human population. We hypothesized that men with spermatogenic impairment, a disease with unknown genetic architecture and a common cause of male infertility, are enriched for rare deleterious mutations compared to men with normal spermatogenesis. After assaying genomewide SNPs and CNVs in 323 Caucasian men with idiopathic spermatogenic impairment and more than 1,100 controls, we estimate that each rare autosomal deletion detected in our study multiplicatively changes a man's risk of disease by 10% (OR 1.10 [1.04-1.16], p<2 × 10(-3)), rare X-linked CNVs by 29%, (OR 1.29 [1.11-1.50], p<1 × 10(-3)), and rare Y-linked duplications by 88% (OR 1.88 [1.13-3.13], p<0.03). By contrasting the properties of our case-specific CNVs with those of CNV callsets from cases of autism, schizophrenia, bipolar disorder, and intellectual disability, we propose that the CNV burden in spermatogenic impairment is distinct from the burden of large, dominant mutations described for neurodevelopmental disorders. We identified two patients with deletions of DMRT1, a gene on chromosome 9p24.3 orthologous to the putative sex determination locus of the avian ZW chromosome system. In an independent sample of Han Chinese men, we identified 3 more DMRT1 deletions in 979 cases of idiopathic azoospermia and none in 1,734 controls, and found none in an additional 4,519 controls from public databases. The combined results indicate that DMRT1 loss-of-function mutations are a risk factor and potential genetic cause of human spermatogenic failure (frequency of 0.38% in 1306 cases and 0% in 7,754 controls, p = 6.2 × 10(-5)). Our study identifies other recurrent CNVs as potential causes of idiopathic azoospermia and generates hypotheses for directing future studies on the genetic basis of male infertility and IVF outcomes., Competing Interests: The authors have declared that no competing interests exist.

The Glutatione-S-transferases (GSTs) comprise a family of enzymes closely associated with the cell detoxification of xenobiotics. GSTs exist as homo- or heterodimers and have been grouped into at least seven distinct classes. The main function of GSTs is to catalyze the conjugation of reduced glutathione (GSH) to an electrophilic site of a broad range of potentially toxic and carcinogenic compounds, thereby making such compounds less dangerous and enabling their ready-excretion. Placental GST, known as GST-P 7-7, is the main isoform found in normal placental tissue and comprises 67% of the total GST concentration in this tissue. During development, GST-P 7-7 decreases in concentration and is absent in adult tissues. Interestingly, GST-P 7-7 expression has been detected in adult tissues after exposure to carcinogenic agents in several experimental test systems, being considered a reliable biomarker of exposure and susceptibility in early phases of carcinogenesis. In this article, we review a series of studies involving GST-P 7-7 expression as a suitable tool for understanding cancer pathogenesis, especially cancer risk.