O uso de formulário on-line como forma de organização do acesso aos serviços odontológicos de um centro de saúde de Florianópolis (SC): relato de experiência

Trabalho de Conclusão (Residência). Universidade Federal de Santa Catarina. Comissão de Residência Multiprofissional e Uniprofissional em Saúde. Residência Multiprofissional em Saúde da Família.O contexto de pandemia forçou uma alteração nos protocolos de biossegurança. As organizações de saúde tiveram de buscar alternativas para realizar o acompanhamento clínico não presencial dos pacientes. Os profissionais de saúde enfrentaram um duplo desafio: avançar nos conhecimentos sobre uma nova doença e adaptar-se a uma nova maneira de prestar cuidados. O avanço das tecnologias em saúde pode ser uma alternativa eficaz e segura para facilitar o contato entre profissionais da saúde e pacientes. Esse trabalho possui como finalidade relatar a experiência da prática profissional de uma residente cirurgiã-dentista na implementação e utilização de um formulário online, como ferramenta de acesso e instrumento de agendamento de consulta odontológica, no Centro de Saúde Jardim Atlântico, no município de Florianópolis (SC). Trata-se de uma pesquisa de caráter qualitativo, na modalidade relato de experiência, pois o estudo aborda questões subjetivas e reflexivas do processo de trabalho. O formulário online associado à demanda programada permite a ampliação do acesso, entretanto é necessário o aperfeiçoamento para a qualificação do acesso por meio deste modelo. Bem como, percebemos a necessidade de ouvir a população referente a sua satisfação com o formato de acesso atual

Revisiting theoretical description of the retrograde motion of cathode spots of vacuum arcs

A fresh attempt to develop a self-consistent descrip tion of the retrograde motion of cathode spots on volatile cathodes is undertaken. Three potential mechanisms of effect of transversal magnetic field on the distribution of parameters in the spot are studied: the effect of magnetic field on hydrodynamics processes in the spot, in particular, on the formation of liquid-metal jet and the droplet detachment, and the effect of transversal magnetic field over the motion of ions and emitted electrons in the near-cathode space-charge sheath. It is found that for typical conditions of cathode spots in vacuum arcs the effect of magnetic field over the formation of liquid-metal jet and the droplet detachment is negligible; the motion of the ions in the near-cathode space-charge sheath is not disturbed; and the motion of the emitted electrons is disturbed only marginally. Thus, the above-mentioned potential mechanisms are hardly relevant and the first-principle understanding is still missing. A phenomenological description of the retrograde motion is developed as an alternative. The description employs general considerations without relying on specific assumptions and the (only) unknown parameter can be determined from comparison with the experiment.info:eu-repo/semantics/publishedVersio

LiCl induces TNF-α and FasL production, thereby stimulating apoptosis in cancer cells

<p>Abstract</p> <p>Background</p> <p>The incidence of cancer in patients with neurological diseases, who have been treated with LiCl, is below average. LiCl is a well-established inhibitor of Glycogen synthase kinase-3, a kinase that controls several cellular processes, among which is the degradation of the tumour suppressor protein p53. We therefore wondered whether LiCl induces p53-dependent cell death in cancer cell lines and experimental tumours.</p> <p>Results</p> <p>Here we show that LiCl induces apoptosis of tumour cells both <it>in vitro </it>and <it>in vivo</it>. Cell death was accompanied by cleavage of PARP and Caspases-3, -8 and -10. LiCl-induced cell death was not dependent on p53, but was augmented by its presence. Treatment of tumour cells with LiCl strongly increased TNF-α and FasL expression. Inhibition of TNF-α induction using siRNA or inhibition of FasL binding to its receptor by the Nok-1 antibody potently reduced LiCl-dependent cleavage of Caspase-3 and increased cell survival. Treatment of xenografted rats with LiCl strongly reduced tumour growth.</p> <p>Conclusions</p> <p>Induction of cell death by LiCl supports the notion that GSK-3 may represent a promising target for cancer therapy. LiCl-induced cell death is largely independent of p53 and mediated by the release of TNF-α and FasL.</p> <p>Key words: LiCl, TNF-α, FasL, apoptosis, GSK-3, FasL</p

Seroprevalence of SARS-CoV-2 antibodies, associated factors, experiences and attitudes of nursing home and home healthcare employees in Switzerland

BACKGROUND Many studies in hospital settings exist and have shown healthcare employees to be particularly exposed to SARS-CoV-2. While research focused on hospital staff, little evidence exists for employees in nursing homes and home care. The aims of this study were to assess the seroprevalence in nursing homes and home care employees in the Canton of Zurich, compare it to the general population, assess factors associated with seropositivity and explore the perspective of the employees regarding how the pandemic changed their daily work. METHODS This cross-sectional study is part of the national Corona Immunitas research program of coordinated, seroprevalence studies in Switzerland. Six nursing homes and six home healthcare organizations providing at home care services in Zurich were selected and 296 and 131 employees were recruited, respectively. Assessments included standardized questionnaires, blood sampling for antibodies, and additional work-specific questions. All participants were recruited between 21st September and 23rd October 2020, before the second wave of the pandemic hit Switzerland, and were possibly exposed to SARS-CoV-2 at their work during the first wave in spring 2020. RESULTS Seroprevalence of SARS-CoV-2 was 14.9% (95% CI 11.1%-19.6%; range 3.8% to 24.4%) for nursing home employees and 3.8% (95% CI 1.4-9.1%; range 0% to 10%) for home healthcare employees, compared to the general population of Zurich at 3.5% in September 2020 for those aged 20-64. Nurses were 2.6 times more likely to have SARS-CoV-2 antibodies than those employees who were not nurses (95% CI 1.1-6.2). The employees (nursing homes vs. home healthcare) perceived the implementation of general safety measures (44.9% vs. 57.3%) and wearing masks during work (36.8% vs. 43.5%), especially due to the limited communication with residents/clients, as the most crucial changes. CONCLUSIONS Nursing home employees who worked through SARS-CoV-2 outbreaks at their work were substantially more affected by SARS-CoV-2 infection compared to the general population and to home healthcare employees who similarly worked through outbreaks in their communities. Employees reported that important resources to cope with the burdensome changes they perceived in their daily work were personal resources and team support. TRIAL REGISTRATION Current Controlled Trials ISRCTN18181860 dated 09/07/2020. Retrospectively registered

Adjuvant formulated virus-like particles expressing native-like forms of the Lassa virus envelope surface glycoprotein are immunogenic and induce antibodies with broadly neutralizing activity

Lassa mammarenavirus (LASV) is a rodent-borne arenavirus endemic to several West African countries. It is the causative agent of human Lassa fever, an acute viral hemorrhagic fever disease. To date, no therapeutics or vaccines against LASV have obtained regulatory approval. Polyclonal neutralizing antibodies derived from hyperimmunized animals may offer a useful strategy for prophylactic and therapeutic intervention to combat human LASV infections. The LASV envelope surface glycoprotein complex (GP) is the major target for neutralizing antibodies, and it is the main viral antigen used for the design of an LASV vaccine. Here, we assessed the immunogenic potential of mammalian cell-derived virus-like particles (VLPs) expressing GP from the prototypic LASV strain Josiah in a native-like conformation as the sole viral antigen. We demonstrate that an adjuvanted prime-boost immunization regimen with GP-derived VLPs elicited neutralizing antibody responses in rabbits, suggesting that effective antigenic epitopes of GP were displayed. Notably, these antibodies exhibited broad reactivity across five genetic lineages of LASV. VLP-based immunization strategies may represent a powerful approach for generating polyclonal sera containing cross-reactive neutralizing antibodies against LASV

Autonomic modulation and antiarrhythmic therapy in a model of long QT syndrome type 3

AIMS: Clinical observations in patients with long QT syndrome carrying sodium channel mutations (LQT3) suggest that bradycardia caused by parasympathetic stimulation may provoke torsades de pointes (TdP). beta-Adrenoceptor blockers appear less effective in LQT3 than in other forms of the disease. METHODS AND RESULTS: We studied effects of autonomic modulation on arrhythmias in vivo and in vitro and quantified sympathetic innervation by autoradiography in heterozygous mice with a knock-in deletion (DeltaKPQ) in the Scn5a gene coding for the cardiac sodium channel and increased late sodium current (LQT3 mice). Cholinergic stimulation by carbachol provoked bigemini and TdP in freely roaming LQT3 mice. No arrhythmias were provoked by physical stress, mental stress, isoproterenol, or atropine. In isolated, beating hearts, carbachol did not prolong action potentials per se, but caused bradycardia and rate-dependent action potential prolongation. The muscarinic inhibitor AFDX116 prevented effects of carbachol on heart rate and arrhythmias. beta-Adrenoceptor stimulation suppressed arrhythmias, shortened rate-corrected action potential duration, increased rate, and minimized difference in late sodium current between genotypes. beta-Adrenoceptor density was reduced in LQT3 hearts. Acute beta-adrenoceptor blockade by esmolol, propranolol or chronic propranolol in vivo did not suppress arrhythmias. Chronic flecainide pre-treatment prevented arrhythmias (all P < 0.05). CONCLUSION: Cholinergic stimulation provokes arrhythmias in this model of LQT3 by triggering bradycardia. beta-Adrenoceptor density is reduced, and beta-adrenoceptor blockade does not prevent arrhythmias. Sodium channel blockade and beta-adrenoceptor stimulation suppress arrhythmias by shortening repolarization and minimizing difference in late sodium current.status: publishe

X-ray Structure of 4,4′-Dihydroxybenzophenone Mimicking Sterol Substrate in the Active Site of Sterol 14α-Demethylase (CYP51)

A universal step in the biosynthesis of membrane sterols and steroid hormones is the oxidative removal of the 14α-methyl group from sterol precursors by sterol 14α-demethylase (CYP51). This enzyme is a primary target in treatment of fungal infections in organisms ranging from humans to plants, and development of more potent and selective CYP51 inhibitors is an important biological objective. Our continuing interest in structural aspects of substrate and inhibitor recognition in CYP51 led us to determine (to a resolution of 1.95Å) the structure of CYP51 from Mycobacterium tuberculosis (CYP51Mt) co-crystallized with 4,4′-dihydroxybenzophenone (DHBP), a small organic molecule previously identified among top type I binding hits in a library screened against CYP51Mt. The newly determined CYP51Mt-DHBP structure is the most complete to date and is an improved template for three-dimensional modeling of CYP51 enzymes from fungal and prokaryotic pathogens. The structure demonstrates the induction of conformational fit of the flexible protein regions and the interactions of conserved Phe-89 essential for both fungal drug resistance and catalytic function, which were obscure in the previously characterized CYP51Mt-estriol complex. DHBP represents a benzophenone scaffold binding in the CYP51 active site via a type I mechanism, suggesting (i) a possible new class of CYP51 inhibitors targeting flexible regions, (ii) an alternative catalytic function for bacterial CYP51 enzymes, and (iii) a potential for hydroxybenzophenones, widely distributed in the environment, to interfere with sterol biosynthesis. Finally, we show the inhibition of M. tuberculosis growth by DHBP in a mouse macrophage model

Graphene oxide and reduced graphene oxide: From preparation to verification of safety and therapeutic efficacy in Silico and in Vitro

To present a possible new alternative for wound treatment, this work evaluated the biological safety and therapeutic efficacy of graphene oxide (GO) and reduced graphene oxide (rGO) nanoparticles (NPs). First, the nanostructures were studied in silico and showed to be able to inhibit the production of some pro-inflammatory cytokines and stimulate the production of the anti-inflammatory cytokine IL-10, especially rGO. The results of the morphological and structural characterization of GO NPs synthesized from the Hummers method and reduced by ascorbic acid, were consistent with the literature, confirming their achievement. In the broth microdilution assay, GO and rGO showed antimicrobial activity against the clinical isolate of Streptococcus agalactiae (S. agalactiae) at a minimum inhibitory concentration (MIC) of 625 µg/mL for GO and 312.5 µg/mL for rGO. In addition, the nanostructure of rGO was able to inhibit, in subinhibitory concentration, the formation of S. agalactiae biofilm by up to 77% when compared to the positive control. Both NPs, in all tested concentrations, did not cause hemolysis, and alterations in coagulation in vitro assays. However, in the safety tests, it was evidenced that only the MIC of 312, µg/mL for rGO was biologically safe and presented anti-inflammatory and healing behavior in vitro. In general, the present work confirmed rGO\u27s potential in the treatment of chronic wounds, since in silico showed anti-inflammatory behavior and in vitro showed therapeutic efficacy at low concentrations, prevented biofilm formation, and showed no significant toxic effects