High rate of cancer recurrence after DAA treatment in patients with prior hepatocellular carcinoma. Disruption of immune surveillance may facilitate the emergence of metastatic clones.

Health literacy, a more complex concept than knowledge, is a required capacity to obtain, understand, integrate and act on health information [1], in order to enhance individual and community health, which is defined by different levels, according to the autonomy and personal capacitation in decision making [2]. Medium levels of Health literacy in an adolescent population were found in a study conducted in 2013/2014, being higher in sexual and reproductive health and lower in substance use. It was also noticed that the higher levels of health literacy were in the area adolescents refer to have receipt more health information. The health literacy competence with higher scores was communication skills, and the lower scores were in the capacity to analyze factors that influence health. Higher levels were also found in younger teenagers, but in a higher school level, confirming the importance of health education in these age and development stage. Adolescents seek more information in health professionals and parents, being friends more valued as a source information in older adolescents, which enhance the importance of peer education mainly in older adolescents [3]. As a set of competences based on knowledge, health literacy should be developed through education interventions, encompassing the cultural and social context of individuals, since the society, culture and education system where the individual is inserted can define the way the development and enforcement of the health literacy competences [4]. The valued sources of information should be taken into account, as well as needs of information in some topics referred by adolescents in an efficient health education. Schizophrenia is a serious and chronic mental illness which has a profound effect on the health and well-being related with the well-known nature of psychotic symptoms. The exercise has the potential to improve the life of people with schizophrenia improving physical health and alleviating psychiatric symptoms. However, most people with schizophrenia remains sedentary and lack of access to exercise programs are barriers to achieve health benefits. The aim of this study is to evaluate the effect of exercise on I) the type of intervention in mental health, II) in salivary levels of alpha-amylase and cortisol and serum levels of S100B and BDNF, and on III) the quality of life and selfperception of the physical domain of people with schizophrenia. The sample consisted of 31 females in long-term institutions in the Casa de Saúde Rainha Santa Isabel, with age between 25 and 63, and with diagnosis of schizophrenia according to the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV-TR). Physical fitness was assessed by the six-minute walk distance test (6MWD). Biological variables were determined by ELISA (Enzyme-Linked Immunosorbent Assay). Psychological variables were assessed using SF-36, PSPP-SCV, RSES and SWLS tests. Walking exercise has a positive impact on physical fitness (6MWD -p = 0.001) and physical components of the psychological test...

IntroductionElevated serum levels of the proinflammatory cytokine tumor necrosis factor alpha (TNFα) correlate with an increased risk for atherothrombotic events and TNFα is known to induce prothrombotic molecules in endothelial cells. Based on the preexisting evidence for the impact of TNFα in the pathogenesis of autoimmune disorders and their known association with an acquired hypercoagulability, we investigated the effects of TNFα and the role of the TNF receptor subtypes TNFR1 and TNFR2 for arteriolar thrombosis in vivo.MethodsArteriolar thrombosis and platelet-rolling in vivo were investigated in wildtype, TNFR1-/-, TNFR2-/- and TNFR1-/R2-/- C57BL/6 mice using intravital microscopy in the dorsal skinfold chamber microcirculation model. In vitro, expression of prothrombotic molecules was assessed in human endothelial cells by real-time PCR and flow cytometry.ResultsIn wildtype mice, stimulation with TNFα significantly accelerated thrombotic vessel occlusion in vivo upon ferric chloride injury. Arteriolar thrombosis was much more pronounced in TNFR1-/- animals, where TNFα additionally led to increased platelet-endothelium-interaction. TNFα dependent prothrombotic effects were not observed in TNFR2-/- and TNFR1-/R2- mice. In vitro, stimulation of human platelet rich plasma with TNFα did not influence aggregation properties. In human endothelial cells, TNFα induced superoxide production, p-selectin, tissue factor and PAI-1, and suppressed thrombomodulin, resulting in an accelerated endothelial dependent blood clotting in vitro. Additionally, TNFα caused the release of soluble mediators by endothelial cells which induced prothrombotic and suppressed anticoagulant genes comparable to direct TNFα effects.ConclusionsTNFα accelerates thrombus formation in an in vivo model of arteriolar thrombosis. Its prothrombotic effects in vivo require TNFR2 and are partly compensated by TNFR1. In vitro studies indicate endothelial mechanisms to be responsible for prothrombotic TNFα effects. Our results support a more selective therapeutic approach in anticytokine therapy favouring TNFR2 specific antagonists.

BackgroundBehavioral risks such as age at first sexual intercourse, number of sexual partners and partner’s sexual behavior are associated with an increased risk of HPV infection, persistence of the infection and the development of neoplastic precursor lesions. The objective of this study was to evaluate the risk factors associated with HPV positivity and with a diagnosis of cervical neoplasia in women referred with an abnormal cervical smear.MethodsThis study evaluated a series of 198 women referred with an abnormal cervical smear. Risk factors for HPV infection were investigated using a questionnaire. All cervical specimens were tested for 27 HPV genotypes using the Roche polymerase chain reaction reverse line blot assay.ResultsThe overall prevalence of HPV was 87 %. First sexual intercourse before 16 years of age was significantly associated with a positive HPV test (OR 4.41; 95 %CI: 1.20 − 19.33; p = 0.01). A significant association was also found between this risk factor and CIN 1 lesions or worse (OR 2.2; 95 %CI 0.94 − 5.08; p = 0.03).ConclusionsThe age at which a woman begins to be sexually active is associated with HPV infection and with a diagnosis of cervical neoplasia.

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We need to effectively combine the knowledge from surging literature with complex datasets to propose mechanistic models of SARS-CoV-2 infection, improving data interpretation and predicting key targets of intervention. Here, we describe a large-scale community effort to build an open access, interoperable and computable repository of COVID-19 molecular mechanisms. The COVID-19 Disease Map (C19DMap) is a graphical, interactive representation of disease-relevant molecular mechanisms linking many knowledge sources. Notably, it is a computational resource for graph-based analyses and disease modelling. To this end, we established a framework of tools, platforms and guidelines necessary for a multifaceted community of biocurators, domain experts, bioinformaticians and computational biologists. The diagrams of the C19DMap, curated from the literature, are integrated with relevant interaction and text mining databases. We demonstrate the application of network analysis and modelling approaches by concrete examples to highlight new testable hypotheses. This framework helps to find signatures of SARS-CoV-2 predisposition, treatment response or prioritisation of drug candidates. Such an approach may help deal with new waves of COVID-19 or similar pandemics in the long-term perspective.

Phospholipases D (PLDs) are principally responsible for the local and systemic effects of Loxosceles envenomation including dermonecrosis and hemolysis. Despite their clinical relevance in loxoscelism, to date, only the SMase I from Loxosceles laeta, a class I member, has been structurally characterized. The crystal structure of a class II member from Loxosceles intermedia venom has been determined at 1.7Å resolution. Structural comparison to the class I member showed that the presence of an additional disulphide bridge which links the catalytic loop to the flexible loop significantly changes the volume and shape of the catalytic cleft. An examination of the crystal structures of PLD homologues in the presence of low molecular weight compounds at their active sites suggests the existence of a ligand-dependent rotamer conformation of the highly conserved residue Trp230 (equivalent to Trp192 in the glycerophosphodiester phosphodiesterase from Thermus thermophofilus, PDB code: 1VD6) indicating its role in substrate binding in both enzymes. Sequence and structural analyses suggest that the reduced sphingomyelinase activity observed in some class IIb PLDs is probably due to point mutations which lead to a different substrate preference.

Hypoxia promotes vascularization by stabilization and activation of the hypoxia inducible factor 1α (HIF-1α), which constitutes a target for angiogenic gene therapy. However, gene therapy is hampered by low gene delivery efficiency and non-specific side effects. Here, we developed a gene transfer technique based on magnetic targeting of magnetic nanoparticle-lentivirus (MNP-LV) complexes allowing site-directed gene delivery to individual wounds in the dorsal skin of mice. Using this technique, we were able to control HIF-1α dependent wound healing angiogenesis in vivo via site-specific modulation of the tyrosine phosphatase activity of SHP-2. We thus uncover a novel physiological role of SHP-2 in protecting HIF-1α from proteasomal degradation via a Src kinase dependent mechanism, resulting in HIF-1α DNA-binding and transcriptional activity in vitro and in vivo. Excitingly, using targeting of MNP-LV complexes, we achieved simultaneous expression of constitutively active as well as inactive SHP-2 mutant proteins in separate wounds in vivo and hereby specifically and locally controlled HIF-1α activity as well as the angiogenic wound healing response in vivo. Therefore, magnetically targeted lentiviral induced modulation of SHP-2 activity may be an attractive approach for controlling patho-physiological conditions relying on hypoxic vessel growth at specific sites.