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Item does not contain fulltext 01 juni 2023

Heme-oxygenase 1 (HO-1) is an enzyme with well-known anti-inflammatory and antioxidant properties, whose levels have been previously associated with disease severity in the context of sterile and infectious diseases. Moreover, the heme/HO-1 pathway has been associated with prothrombotic changes in other diseases. Accordingly, the potential of modulating HO-1 levels for the treatment of COVID-19 was extensively speculated during the COVID-19 pandemic, but very few actual data were generated. The aim of our study was to explore the association of HO-1, heme, and hemopexin (HPX) levels with COVID-19 severity and with markers of inflammation and coagulation activation. The study was conducted in 30 consecutive patients with COVID-19 admitted due to hypoxemia, and 30 healthy volunteers matched by sex, age, and geographic region. HO-1 and HPX levels were measured by enzyme immunoassay (ELISA) and heme levels were measured by a colorimetric method. A comprehensive panel of coagulation and fibrinolysis activation was also used. Patients with COVID-19 presented increased levels of HO-1 when compared to controls (5741 ± 2696 vs 1953 ± 612 pg/mL, respectively, P

Item does not contain fulltext Sporotrichosis is an implantation mycosis caused by the dimorphic fungus Sporothrix and mostly involves cutaneous and subcutaneous tissues and the lymphatic vessels. Among more than 50 different species, only Sporothrix schenckii, Sporothrix globosa and Sporothrix brasiliensis are frequently reported to cause infections in humans. Sporothrix brasiliensis is remarkably virulent and has been spreading rapidly in Brazil and other Latin American countries. In this study, we aimed to determine the genetic relatedness and antifungal susceptibility of Sporothrix strains by analysing 89 isolates from humans and cats in Curitiba, Southern Brazil. Calmodulin sequencing identified 81 S. brasiliensis and seven S. schenckii isolates. Amplified fragment length polymorphism genotyping analysis showed feline and human isolates clustering together. In vitro susceptibility testing with seven antifungals demonstrated a broad activity against all tested S. brasiliensis isolates, with no significant differences in minimal inhibitory concentration (MIC) values between feline and human isolates. Resistance was solely observed in one human isolate against itraconazole and posaconazole, with MICs of ≥16 μg/mL against both antifungals. Whole genome sequencing (WGS) analysis on this isolate and two related susceptible isolates did not reveal any unique substitutions in resistance-associated genes, including cyp51, hmg and erg6, when compared to two related susceptible isolates. The novel antifungal olorofim exhibited excellent activity against this large isolate collection, with all isolates considered as susceptible. Altogether, we indicate zoonotic transmission based on genotyping and revealed a broad activity of seven common antifungals, including olorofim, against a large S. brasiliensis isolate collection. 01 juli 2023

Objetivo: descrever a percepção do cliente de saúde sobre o atendimento humanizado realizado por uma professora e alunos do curso Técnico em Enfermagem durante a realização do estágio obrigatório supervisionado em um pronto-socorro que presta atendimento pelo Sistema Único de Saúde (SUS). Método: Trata-se de um estudo descritivo, do tipo relato de experiência realizado em junho de 2022. Resultados: os resultados demonstram que os professores e alunos do curso Técnico em Enfermagem realizam atendimento humanizado, com acolhimento e empatia, incluindo e percebendo as diferenças nos processos de gestão e cuidado. Conclusão: assim concluímos que estes aspectos são elementos importantes para a reabilitação física e emocional do paciente e de seus familiares.

Influenza-based virosome is an effective immunomodulating carrier that replicates the natural antigen presentation pathway and has tolerability profile due to their purity and biocompatibility. Based on that, this study aimed to develop a polyvalent virosome influenza vaccine containing the hemagglutinin and neuraminidase proteins derived from the swine influenza A viruses (IAVs) H1N1, H1N2 and H3N2 viruses, and to investigate its effectiveness in mice as a potential vaccine for swine. The humoral and cellular immune responses in mice vaccinated intranasally or intramuscularly with polyvalent influenza virosomal vaccine were investigated. Only intramuscular vaccination induced high hemagglutination inhibition (HI) titers. Seroconversion and seroprotection (> 4-fold rise in HI antibody titers, reaching a titer of ≥ 1:40) were achieved in 80% of mice (intramuscularly vaccinated group) at 21 days after booster immunization. Long-lasting immunity was observed 8 months after vaccination. Overall, mice immunized with the virosome displayed greater ability for B, effector-T and memory-T cells from the spleen to respond to H1N1, H1N2 and H3N2 antigens. All findings showed an efficient immune response against IAVs in mice vaccinated with a polyvalent virosome-based influenza vaccine.

Endothelial barrier (EB) disruption contributes to acute lung injury in COVID-19, and levels of both VEGF-A and Ang-2, which are mediators of EB integrity, have been associated with COVID-19 severity. Here we explored the participation of additional mediators of barrier integrity in this process, as well as the potential of serum from COVID-19 patients to induce EB disruption in cell monolayers. In a cohort from a clinical trial consisting of thirty patients with COVID-19 that required hospital admission due to hypoxia we demonstrate that i) levels of soluble Tie2 were increase, and of soluble VE-cadherin were decreased when compared to healthy individuals; ii) sera from these patients induce barrier disruption in monolayers of endothelial cells; and iii) that the magnitude of this effect is proportional to disease severity and to circulating levels of VEGF-A and Ang-2. Our study confirms and extends previous findings on the pathogenesis of acute lung injury in COVID-19, reinforcing the concept that EB is a relevant component of this disease. Our results pave the way for future studies that can refine our understanding of the pathogenesis of acute lung injury in viral respiratory disorders, and contribute to the identification of new biomarkers and therapeutic targets for these conditions.

Background. The role of liver function tests (LFT) as prognostic factors in patients admitted with COVID-19 has not been fully investigated, particularly outside resource-rich countries. We aimed at evaluating the prognostic value of abnormal LFT on admission and during hospitalization of patients with COVID-19. Methods. We performed a retrospective study that included 298 adult patients hospitalized for COVID-19, between 05/2020 and 02/2021, in 6 hospitals from 5 countries in South America. We analyzed demographic and comorbid variables and laboratory tests on admission and during hospitalization. LFT over twice the upper limit of normal (ALEx2) were also evaluated in relation to a variety of factors on admission and during hospitalization. De novo-ALEx2 was defined as the presence of ALEx2 at one week of hospitalization in patients without ALEx2 on admission. Patients were followed until hospital discharge or death. Multivariable analysis was used to evaluate the association between ALEx2 on admission and during hospitalization and mortality. Results. Of the total of 298 patients, 60% were male, with a mean age of 60 years, and 74% of patients had at least one comorbidity. Of those, 137 (46%) patients were transferred to the intensive care unit and 66 (22.1%) patients died during hospitalization. ALEx2 on admission was present in 87 (29.2%) patients and was found to be independently associated with 1-week mortality (odds ratio (OR) = 3.55; 95% confidence interval (95%CI) 1.05–12.05). Moreover, 84 (39.8%) out of 211 patients without ALEx2 at admission developed de novo-ALEx2, which was independently associated with mortality during second week of hospitalization (OR = 6.09; 95%CI 1.28–29) and overall mortality (OR = 2.93, 95%CI 1.05–8.19). Conclusions. A moderate elevation of LFT during admission was associated with a poor short-term prognosis in patients hospitalized with COVID-19. In addition, moderate elevation of LFT at one week of hospitalization was an independent risk factor for overall mortality in these patients.

The effects on the ontogeny of serum cytokines and immune cells caused by feeding suckling piglets with sow/gilt colostrum and milk replacer was assessed in the present study. After farrowing, the piglets born were randomized into six groups: GG and SS (n = 10/group): piglets were kept with their dam; GS (n = 10): piglets were changed from gilts to sows; SG (n = 10): piglets were changed from sows to gilts; GMR (n = 6) and SMR (n = 8): piglets from either gilts or sows were isolated from the dams and were bottle-fed ad libitum with commercial formula milk replacer. The piglets remained in the groups during the first 24 h of life and were later returned to their respective mothers. Serum immunoglobulin concentration and lymphocyte proliferation from the blood, spleen, thymus, and mesenteric lymph node of the piglets were assessed at 24 h and at 28 days of age. Serum cytokine concentrations were measured through a cytokine multiplex assay at 24 h. Overall, piglets suckling on sows (SS and GS) had a higher concentration of serum immunoglobulin at 24 h, which was also associated with a rise in plasma cytokine concentration and greater ability of B and T cells from lymphatic organs and blood mononuclear cells to respond to mitogens. We suggest a bias towards Th1-, Th2-, and Th17-cell polarizing and cytokines during the suckling period, which may be influenced by maternal immunological factors in the colostrum, such as dam parity. All findings suggest sow parity having a possible role, which may contribute to exerting a modulating action on immune response development.

GPR139 is an orphan G-protein-coupled receptor that is expressed in restricted areas of the nervous system, including the hypothalamus. In this study, we hypothesized that GPR139 could be involved in the regulation of energy balance and metabolism. In the first part of the study, we confirmed that GPR139 is expressed in the hypothalamus and particularly in proopiomelanocortin and agouti-related peptide neurons of the mediobasal hypothalamus. Using a lentivirus with a short-hairpin RNA, we inhibited the expression of GPR139 bilaterally in the mediobasal hypothalamus of mice. The intervention promoted a 40% reduction in the hypothalamic expression of GPR139, which was accompanied by an increase in body mass, a reduction in fasting blood glucose levels, and an increase in insulin levels. In the hypothalamus, inhibition of GPR139 was accompanied by a reduction in the expression of orexin. As previous studies using a pharmacological antagonist of orexin showed a beneficial impact on type 2 diabetes and glucose metabolism, we propose that the inhibition of hypothalamic GPR139 could be acting indirectly through the orexin system to control systemic glucose and insulin. In conclusion, this study advances the characterization of GPR139 in the hypothalamus, demonstrating its involvement in the regulation of body mass, blood insulin, and glycemia.

RESUMO: Este estudo apresenta análises sobre as relações de poder, estruturadas pelos sistemas simbólicos, reveladas nas interações dos personagens da obra literária Chove sobre minha infância, romance de Miguel Sanches Neto (2014). A leitura voltou-se às representações da mulher no contexto da narrativa, com destaque para as vivências familiares e as práticas socioculturais de reprodução da violência simbólica invisível e naturalizada pelo domínio masculino, relacionada às personagens Nelsa, Carmem e às mulheres pintadas. O estudo abordou nuances no campo do poder simbólico em meio aos sistemas estruturados, tais como a família e a religião. Ao analisarmos essas práticas e estruturas na ficção, o estudo visa ampliar o debate sobre a realidade empírica da condição de muitas mulheres no âmbito familiar e lançar luz para a consciência dessas formas simbólicas de opressão. As reflexões analisam os significados que direcionam a ordem familiar em seus aspectos culturais e ideológicos, no jogo que envolve o poder simbólico nas relações de ordem dominante, as quais são reveladas numa estrutura social impregnada de opressão à mulher e a supremacia do homem. Práticas conservadas e reproduzidas pela estrutura social, que precisam ser problematizadas e repensadas.

Advances in wound treatment depend on the availability of suitable animal models. All animal models try to reflect human wound healing problems. For acute wounds, it is easier to obtain adequate animal models, however, for chronic wounds such as those found in individuals with diabetic foot ulcer, approximations of the clinical picture become a challenge. Nowadays, the key points of wound healing processes are better understood, and therefore, therapeutic strategies can be developed to manipulate wound repair. Research efforts involves the development of therapies to aid in the treatment of impaired wound healing and, to improving normal wound healing to drive a process close to regenerative. To achieve a better animal model that is more appropriate for studying wound healing, six-week- old male C57BL/6 mice were separated into groups fed a Chow and High-Fat Diet for 0.5, 3, and 6 months, when part of the animals were induced to diabetes by streptozotocin. Then, mice were submitted to metabolic, molecular, and morphological analyses. We show that this model results in a severe metabolic phenotype with insulin resistance, reduced insulin expression, and glucose intolerance associated with obesity and, more importantly, skin changes. Furthermore, the skin phenotype, both structurally and transcriptionally, overlapped with conditions found in elderly patients with DM that reproduce the phenotype of most patients who develop diabetic foot ulcers.

Coronavirus disease 2019 (COVID-19) is caused by the SARS-CoV-2 virus, responsible for an atypical pneumonia that can progress to acute lung injury. MicroRNAs are small non-coding RNAs that control specific genes and pathways. This study evaluated the association between circulating miRNAs and lung injury associated with COVID-19. Methods: We evaluated lung injury by computed tomography at hospital admission and discharge and the serum expression of 754 miRNAs using the TaqMan OpenArray after hospital discharge in 27 patients with COVID-19. In addition, miR-150-3p was validated by qRT-PCR on serum samples collected at admission and after hospital discharge. Results: OpenArray analysis revealed that seven miRNAs were differentially expressed between groups of patients without radiological lung improvement compared to those with lung improvement at hospital discharge, with three miRNAs being upregulated (miR-548c-3p, miR-212-3p, and miR-548a-3p) and four downregulated (miR-191-5p, miR-151a-3p, miR-92a-3p, and miR-150-3p). Bioinformatics analysis revealed that five of these miRNAs had binding sites in the SARS-CoV-2 genome. Validation of miR-150-3p by qRT-PCR confirmed the OpenArray results. Conclusions: The present study shows the potential association between the serum expression of seven miRNAs and lung injury in patients with COVID-19. Furthermore, increased expression of miR-150 was associated with pulmonary improvement at hospital discharge.

Currently, up to 35% off all drugs approved for the treatment of human diseases belong to the G-protein-coupled receptor (GPCR) family. Out of the almost 800 existing GPCRs, 25% have no known endogenous ligands and are regarded as orphan receptors; many of these are currently under investigation as potential pharmacological targets. Here, we hypothesised that orphan GPCRs expressed in the hypothalamus could be targets for the treatment of obesity and other metabolic diseases. Using bioinformatic tools, we identified 78 class A orphan GPCRs that are expressed in the hypothalamus of mice. Initially, we selected two candidates and determined their responsivities to nutritional interventions: GPR162, the GPCR with highest expression in the hypothalamus, and GPR68, a GPCR with intermediate expression in the hypothalamus and that has never been explored for its potential involvement in metabolic regulation. GPR162 expression was not modified by fasting/feeding or by the consumption of a high-fat diet, and was therefore not subsequently evaluated. Conversely, GPR68 expression increased in response to the consumption of a high-fat diet and reduced under fasting conditions. Using immunofluorescence, GPR68 was identified in both proopiomelanocortin-expressing and agouti-related peptide-expressing neurons in the hypothalamic arcuate nucleus. Acute inhibition of GPR68 with an allosteric modulator promoted an increase in the expression of the orexigenic agouti-related peptide and neuropeptide Y, whereas 4- and 12-h inhibition of GPR68 resulted in increased caloric intake. Thus, GPR68 has emerged as an orphan GPCR that is expressed in the hypothalamus and is involved in the regulation of feeding.

Interleukin-17 (IL-17) is expressed in the intestine in response to changes in the gut microbiome landscape and plays an important role in intestinal and systemic inflammatory diseases. There is evidence that dietary factors can also modify the expression of intestinal IL-17. Here, we hypothesized that, similar to several other gut-produced factors, IL-17 may act in the hypothalamus to modulate food intake. We confirm that food intake increases IL-17 expression in the mouse ileum and human blood. There is no expression of IL-17 in the hypothalamus; however, IL-17 receptor A is expressed in both pro-opiomelanocortin (POMC) and agouti-related peptide (AgRP) neurons. Upon systemic injection, IL-17 promoted a rapid increase in hypothalamic POMC expression, which was followed by a late increase in the expression of AgRP. Both systemic and intracerebroventricular injections of IL-17 reduced calorie intake without affecting whole-body energy expenditure. Systemic but not intracerebroventricular injection of IL-17 increase brown adipose tissue temperature. Thus, IL-17 is a gut-produced factor that is controlled by diet and modulates food intake by acting in the hypothalamus. Our findings provide the first evidence of a cytokine that is acutely regulated by food intake and plays a role in the regulation of eating.

Made available in DSpace on 2020-12-12T01:57:45Z (GMT). No. of bitstreams: 0 Previous issue date: 2020-03-01 National Council for Scientific Research Federal Agency for Scientific Organizations Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) Chromoblastomycosis is a neglected disease characterized by cutaneous, subcutaneous or disseminated lesions. It is considered an occupational infectious disease that affects mostly rural workers exposed to contaminated soil and vegetal matter. Lesions mostly arise after a traumatic inoculation of herpotrichiellaceous fungi from the Chaetothyriales order. However, the environmental niche of the agents of the disease remains obscure. Its association with insects has been predicted in a few studies. Therefore, the present work aimed to analyze if social insects, specifically ants, bees, and termites, provide a suitable habitat for the fungi concerned. The mineral oil flotation method was used to isolate the microorganisms. Nine isolates were recovered and phylogenetic analysis identified two strains as potential agents of chromoblastomycosis, i.e., Fonsecaea pedrosoi CMRP 3076, obtained from a termite nest (n = 1) and Rhinocladiella similis CMRP 3079 from an ant exoskeleton (n = 1). In addition, we also identified Fonsecaea brasiliensis CMRP 3445 from termites (n = 1), Exophiala xenobiotica CMRP 3077 from ant exoskeleton (n = 1), Cyphellophoraceae CMRP 3103 from bees (n = 1), Cladosporium sp. CMRP 3119 from bees (n = 1), Hawksworthiomyces sp. CMRP 3102 from termites (n = 1), and Cryptendoxyla sp. from termites (n = 2). The environmental isolate of F. pedrosoi CMRP 3076 was tested in two animal models, Tenebrio molitor and Wistar rat, for its pathogenic potential with fungal retention in T. molitor tissue. In the Wistar rat, the cells resembling muriform cells were observed 30 d after inoculation. Graduate Program in Microbiology Parasitology and Pathology Federal University of Paraná University Center Campo Real Federal University of Paraná Graduate Program in Pharmacology UFPR Medical Department Federal University of Maranhão Embrapa Amazônia Oriental CPATU Westerdijk Fungal Biodiversity Institute Department of Biochemistry and Microbiology Institute of Biological Sciences UNESP-São Paulo State University Division of Microbial Resources CPQBA University of Campinas Center of Expertise in Mycology of Radboud University Medical Center Canisius Wilhelmina Hospital Department of Biochemistry and Microbiology Institute of Biological Sciences UNESP-São Paulo State University CNPq: 312811/2018–7 CAPES: Brazil CAPES: Finance Code 001, Brasilia

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) employs angiotensin-converting enzyme 2 (ACE2) as its receptor for cell entrance, and studies have suggested that upon viral binding, ACE2 catalytic activity could be inhibited; therefore, impacting the regulation of the renin-angiotensin-aldosterone system (RAAS). To date, only few studies have evaluated the impact of SARS-CoV-2 infection on the blood levels of the components of the RAAS. The objective of this study was to determine the blood levels of ACE, ACE2, angiotensin-II, angiotensin (1–7), and angiotensin (1–9) at hospital admission and discharge in a group of patients presenting with severe or critical evolution of coronavirus disease 2019 (COVID-19). We showed that ACE, ACE2, angiotensin (1–7), and angiotensin (1–9) were similar in patients with critical and severe COVID-19. However, at admission, angiotensin-II levels were significantly higher in patients presenting as critical, compared to patients presenting with severe COVID-19. We conclude that blood levels of angiotensin-II are increased in hospitalized patients with COVID-19 presenting the critical outcome of the disease. We propose that early measurement of Ang-II could be a useful biomarker for identifying patients at higher risk for extremely severe progression of the disease.

Coagulation activation is a prominent feature of severe acute respiratory syndrome coronavirus 2 (COVID-19) infection. Activation of the contact system and intrinsic pathway has increasingly been implicated in the prothrombotic state observed in both sterile and infectious inflammatory conditions. We therefore sought to assess activation of the contact system and intrinsic pathway in individuals with COVID-19 infection. Baseline plasma levels of protease:serpin complexes indicative of activation of the contact and intrinsic pathways were measured in samples from inpatients with COVID-19 and healthy individuals. Cleaved kininogen, a surrogate for bradykinin release, was measured by enzyme-linked immunosorbent assay, and extrinsic pathway activation was assessed by microvesicle tissue factor–mediated factor Xa (FXa; MVTF) generation. Samples were collected within 24 hours of COVID-19 diagnosis. Thirty patients with COVID-19 and 30 age- and sex-matched controls were enrolled. Contact system and intrinsic pathway activation in COVID-19 was demonstrated by increased plasma levels of FXIIa:C1 esterase inhibitor (C1), kallikrein:C1, FXIa:C1, FXIa:α1-antitrypsin, and FIXa:antithrombin (AT). MVTF levels were also increased in patients with COVID-19. Because FIXa:AT levels were associated with both contact/intrinsic pathway complexes and MVTF, activation of FIX likely occurs through both contact/intrinsic and extrinsic pathways. Among the protease:serpin complexes measured, FIXa:AT complexes were uniquely associated with clinical indices of disease severity, specifically total length of hospitalization, length of intensive care unit stay, and extent of lung computed tomography changes. We conclude that the contact/intrinsic pathway may contribute to the pathogenesis of the prothrombotic state in COVID-19. Larger prospective studies are required to confirm whether FIXa:AT complexes are a clinically useful biomarker of adverse clinical outcomes.

Orientador: Licio Augusto Velloso Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas Resumo: A proteína PGC1? é um co-ativador de transcrição gênica que desempenha papel importante na regulação de uma série de fenômenos metabólicos que compreendem desde o controle da termogênese e mitocondriogênese até a regulação da secreção de insulina e a produção hepática de glicose. Como vários dos fenômenos biológicos controlados direta ou indiretamente pela PGC1? tem importância vital, a regulação dos níveis de PGC1? nos tecidos deve ser finamente ajustada. Nos últimos anos, inúmeros estudos exploraram os mecanismos envolvidos com o controle da expressão gênica e tradução da PGC1?. Entretanto, apenas alguns poucos estudos avaliaram a degradação da mesma. Um dos mais importantes mecanismos envolvidos com a regulação funcional e da meia-vida de proteínas é a ubiquitinação, que pode direcionar proteínas alvo ao proteassoma para degradação ou a outras modificações pós-traducionais. O objetivo do presente estudo foi avaliar a participação de uma proteína com atividade deubiquitinase e ubiquitina ligase, a A20, na manutenção da homeostase do tecido adiposo de animais submetidos à dieta rica em gordura e voluntários humanos magros e obesos antes e após cirurgia de redução de peso. Foram utilizados o tecido adiposo branco visceral e subcutâneo e o tecido adiposo marrom de camundongos Swiss machos submetidos a 16 semanas de dieta hiperlipídica e o tecido adiposo subcutâneo de voluntários magros e obesos antes e após a cirurgia bariátrica. Esses tecidos foram avaliados quanto ao conteúdo protéico e expressão gênica da proteína A20, e sua associação com a PGC1? por imunoprecipitação e imunofluorescência, bem como a ubiquitinação desta última. Os resultados obtidos a partir do tecido adiposo de humanos mostram uma diminuição na expressão da proteína A20 nos pacientes antes e após a cirurgia bariátrica com relação aos voluntários magros. A PGC1? aparece mais ubiquitinada nos pacientes obesos em relação e a associação entre A20 e PGC1? parece aumentar com o ganho de peso na mesma proporção que o conteúdo protéico de PGC1? parece diminuir. No tecido adiposo subcutâneo de camundongos obesos, observamos uma diminuição de PGC1? bem como redução da marcação por cadeias de poliubiquitina desta proteína, associado a um aumento de A20 e aumento da associação de A20 com PGC1?. Camundongos obesos foram também tratados com um oligonucleotídeo antisense (ASO) para A20, resultando na redução de sua expressão gênica. Os animais tratados apresentaram uma piora na tolerância à glicose no teste de GTT o que ocorreu concomitantemente a redução de PGC1?. Nossos resultados indicam que, no tecido adiposo, a A20 se associa a PGC1? e a redução da sua expressão resulta em redução da expressão da PGC1? o que é acompanhando de uma piora no controle homeostático da glicose Abstract: Peroxisome proliferator-activated receptor ? coactivator 1 alpha (PGC-1?) plays an important role in whole body metabolism and, particularly in glucose homeostasis. Its expression is tightly regulated and, small variations in tissue levels can have a major impact in a number of physiological and pathological conditions. Recent studies have shown that the ubiquitin/proteasome system plays a role in the control of PGC-1? degradation. Here we evaluated the interaction of PGC-1? with the protein A20, which plays a dual-role in the control of the ubiquitin/proteasome system acting as a deubiquitinase and as an E3 ligase. We employed immunoprecipitation, quantitative real-time PCR and immunofluorescence staining to evaluate PGC-1?, A20, PPAR? and ubiquitin in the adipose tissue of humans and mice. Our results show that, in distinct sites of the adipose tissue A20 binds to PGC-1?. At least in the subcutaneous fat of humans and mice the levels of PGC-1? decrease during obesity, while its physical association with A20 increases. The inhibition of A20 leads to a reduction of PGC-1? and PPAR? expression, suggesting that A20 acts as a protective factor against PGC-1? disposal. Thus, we provide evidence that mechanisms regulating PGC-1? ubiquitination are potentially involved in the control of the function of this transcriptional co-activator Mestrado Fisiopatologia Médica Mestra em Ciências

As hortas comunitárias são espaços para reflexão sobre a produção e consumo de alimentos, atuam como um meio de promover a integração dos alunos com a comunidade, enfatizando a conscientização ambiental e a educação alimentar. Com a intenção de atingir tais objetivos, em 2018 foi criado o programa de extensão Ervaterapia, que visa criar canteiros de ervas medicinais e promover a integração entre alunos e comunidade externa. O trabalho foi realizado através da distribuição de mudas para a comunidade, palestras, oficinas, e criação de canteiros em escolas municipais de Brusque. Além disso, os alunos do IFC Brusque criaram uma história em quadrinhos chamada “Super Ervas”, que posteriormente foi utilizada em aulas de leitura. Pôde-se observar a conscientização da comunidade quanto a importância das ervas medicinais, pois houve uma crescente procura pelos produtos naturais, com a finalidade de amenizar sintomas como gripe, cólicas menstruais, dores de cabeça, ansiedade, entre outros, diminuindo o consumo de remédios alopáticos que apresentam diversos efeitos colaterais. Observou-se também a compreensão das crianças em relação aos cuidados com as plantas por meio da criação de canteiros de ervas medicinais nas escolas e da leitura das histórias em quadrinhos. Além disso, foram distribuídas aproximadamente 300 mudas para toda a comunidade, dentre elas: camomila, poejo, estévia, funcho, tomilho, hortelã, erva cidreira, manjericão, orégano e lavanda. Conclui-se que o projeto promoveu conscientização sobre uma maneira alternativa de tratar males cotidianos através das ervas medicinais, instruindo como usá-las, formas de plantio e os benefícios que elas trazem para a saúde humana.

The characterization of the hypothalamic neuronal network, that controls food intake and energy expenditure, has provided great advances in the understanding of the pathophysiology of obesity. Most of the advances in this field were obtained thanks to the development of a number of genetic and nongenetic animal models that, at least in part, overtook the anatomical constraints that impair the study of the human hypothalamus. Despite the undisputed differences between human and rodent physiology, most seminal studies undertaken in rodents that have unveiled details of the neural regulation of energy homeostasis were eventually confirmed in humans; thus, placing experimental studies in the forefront of obesity research. During the last 15 years, researchers have provided extensive experimental proof that supports the existence of hypothalamic dysfunction, which leads to a progressive whole-body positive energy balance, and thus, to obesity. Here, we review the experimental work that unveiled the mechanisms behind hypothalamic dysfunction in obesity.

Therapeutic drug monitoring (TDM) of vancomycin is commonly performed using immunoassays. This case describes falsely elevated vancomycin serum concentrations, possibly secondary to endogenous protein interference. Vancomycin was prescribed for a patient with a suspected septic knee. A blood sample for TDM was inadvertently collected before the first dose. The reported concentration was 36.1 mg/L using the Roche Modular P analyzer and remained high over the next 48 hours and 8 months later in the absence of vancomycin therapy. Vancomycin was undetectable in the patient sample by liquid chromatography-tandem mass spectrometry. The sample was subsequently investigated for endogenous protein interference. The responsible interference was removed by polyethylene glycol precipitation and heat inactivation. Four alternative immunoassays with varying test principles measured vancomycin concentrations ranging from undetectable to 108 mg/L. A glucose-6-phosphate dehydrogenase detection method was common to the two immunoassays exhibiting the greatest interference. To our knowledge, this is the first report of falsely elevated vancomycin concentrations on the Roche Modular P analyzer. Immunoassays are generally robust in facilitating TDM but are susceptible to cross-reactivity. Assay interference should be considered and laboratory professionals contacted when vancomycin levels do not correlate with clinical expectations.

In experimental obesity, the hypothalamus is affected by an inflammatory response activated by dietary saturated fats. This inflammation is triggered as early as one day after exposure to a high-fat diet, and during its progression, there is recruitment of inflammatory cells from the systemic circulation. The objective of the present study was identifying chemokines potentially involved in the development of hypothalamic diet-induced inflammation. In order to identify chemokines potentially involved in this process, we performed a real-time PCR array that determined Ackr2 as one of the transcripts undergoing differential regulation in obese-prone as compared to obese-resistant mice fed a high-fat diet for three days. ACKR2 is a decoy receptor that acts as an inhibitor of the signals generated by several CC inflammatory chemokines. Our results show that Ackr2 expression is rapidly induced after exposure to dietary fats both in obese-prone and obese-resistant mice. In immunofluorescence studies, ACKR2 was detected in hypothalamic neurons expressing POMC and NPY and also in microglia and astrocytes. The lentiviral overexpression of ACKR2 in the hypothalamus reduced diet-induced hypothalamic inflammation; however, there was no change in spontaneous caloric intake and body mass. Nevertheless, the overexpression of ACKR2 resulted in improvement of glucose tolerance, which was accompanied by reduced insulin secretion and increased whole body insulin sensitivity. Thus, ACKR2 is a decoy chemokine receptor expressed in most hypothalamic cells that is modulated by dietary intervention and acts to reduce diet-induced inflammation, leading to improved glucose tolerance due to improved insulin action.

The species belonging to the genus Fonsecaea are the main causative agents of chromoblastomycosis. The invasive potential of Fonsecaea differs significantly among its various sibling species. Moreover, the lack of clarity on the virulence and availability of precise markers to distinguish and detect Fonsecaea species is attributed to the different ways of dissemination and pathogenicity. Therefore, the present study aimed to propose new molecular tools to differentiate between sibling species causing chromoblastomycosis. We used an infection model of chromoblastomycosis in BALB/c to study species-specific molecular markers for the in vivo detection of Fonsecaea species in biological samples. Specific primers based on the CBF5 gene were developed for Fonsecaea pedrosoi, Fonsecaea monophora, Fonsecaea nubica, and Fonsecaea pugnacius. In addition, a padlock probe was designed for F. pugnacius based on ITS sequences. We also assessed the specificity of Fonsecaea species using in silico, in vitro, and in vivo assays. The results showed that markers and probes could effectively discriminate the species in both clinical and environmental samples, enabling bioprospecting of agents of chromoblastomycosis, thereby elucidating the infection route of the disease.

Years of accumulating research show high schizophrenia comorbidity with panic anxiety. Recent research has shown that auditory hallucinations have paroxysmal onset, concurrent with abrupt onset panic anxiety in patients with schizophrenia who hear voices. Fixed-dose adjunctive alprazolam or clonazepam (antipanic benzodiazepines) can substantially relieve positive and negative symptoms and panic in some schizophrenia cases. Clinical experience and limited research suggest a more uniform and pronounces benefit in patients with schizophrenia who also have panic premorbidly, concurrently, and/or with voices. Although more research is needed, there could be a distinct panic psychosis diagnosis. This is consistent with an evolutionary theory postulating five core psychoses. With appropriate medication and skilled psychotherapy, many can improve to their premorbid baseline and remain there for extended periods. Perhaps the major impediments to clinical improvement are the difficulty of diagnosing panic in psychosis, failure to use fixed dose and sufficient clonazepam, and limited use of skilled psychotherapy. [ Psychiatr Ann . 2018;48(12):561–565.]

Orientador: Antonieta Keiko Kakuda Shimo Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas Resumo: A gestação é um período de rápidas mudanças e adaptações, tanto corporais quanto emocionais. Ganho de peso, aumento das mamas, quadris e abdômen são algumas das mudanças corporais que acompanharão a mulher durante a gestação. Esse corpo em adaptação encontra na sociedade a cobrança da "perfeição", do ideal de beleza e boa forma. A imagem corporal é a representação mental do nosso corpo. Ela está em constante mutação, podendo ser alterada por informações, experiências sociais, emocionais e fisiológicas que o indivíduo recolhe no decorrer da vida. É por meio do corpo que interagimos com o mundo, é a partir dele que desenvolvemos a nossa identidade. A gestante vê o seu corpo mudando rapidamente e fugindo do que ela estabeleceu como sua identidade. O objetivo dessa pesquisa é avaliar a imagem corporal e a satisfação corporal de gestantes por meio da Escala de Medida em Imagem Corporal e um questionário sócio- demográfico e saber como esta escala se comporta na população gestante. O estudo se caracteriza como descritivo-exploratório. A amostra é composta por 93 gestantes do município de Vinhedo - SP que realizaram seus pré-natais das Unidades Básicas de Saúde e responderam aos questionários. Os escores totais e dos componentes da imagem corporal e a satisfação corporal (que é o equilíbrio entre os componentes da imagem corporal) foram analisados e relacionados aos dados sócio-demográficos como idade, IMC, entre outros. Tendo a escala se comportado de forma adequada para a população deste estudo, mostrando consistência interna muito boa (alfa de Cronbach = 0,912), obteve-se como resultado que a maioria das gestantes apresenta imagem corporal boa, sem alteração. Quando esta informação é relacionada aos dados sócio-demográficos, percebe-se relação significativa entre o peso corporal e a imagem corporal. Na avaliação da satisfação corporal, por sua vez, a maioria das gestantes (60,22%) estava insatisfeita. Esse resultado permite pensar que, quando se avalia os componentes da imagem corporal, eles podem se apresentar com escore elevado, mas não necessariamente em equilíbrio. Na associação com os dados sócio- demográficos, o peso corporal é, novamente, um fator de alteração na satisfação corporal das gestantes. Considerando os resultados obtidos, conclui-se que a avaliação da imagem corporal e da satisfação corporal, por meio de escalas como a deste estudo, devem ser de conhecimento dos profissionais que trabalham com gestantes e aplicadas nos programas de pré-natal para identificar, tratar e/ou prevenir alterações que possam comprometer o bem estar e a auto-estima das gestantes. Programas de apoio a gestante com atendimento psicológico e atividades físicas que permitam às mulheres conhecerem e identificarem seus corpos são úteis para manter a imagem corporal boa neste período Abstract: Pregnancy is a short period of body and emotional changes and adaptations. Weight gain, increases in breast size, widening of hips and belly are some of the body changes that will happen to the woman during pregnancy. This body in change finds in society a call for "perfection", body ideals and good shape. Body image is the mental representation of our body. It is constantly changing, and might be modified by informations and social, emotional and physiological experiences that the individual collects during life. By the body we experience the world and based on it we develop our identity. The pregnant woman sees her body changing and becoming different from what she had established as her identity. The aim of this research is to evaluate pregnant women's body image and body satisfaction using the Body Image Rating Scale (Escala de Medida em Imagem Corporal) and a social-demographic questionnaire, and to know how this scale behaves in a pregnant woman group. This is a descriptive-exploratory research. The sample is composed of 93 pregnant women from Vinhedo - SP that made their prenatal appointments at the Basic Health Units in this city and answered the questionnaires. The body image total and components scores and the scores of body satisfaction (the balance of body image components) were analyzed and related to the social-demographic data such as age, BMI, and others. Since the scale behaved properly to the sample of this study, in which internal consistency was good (Cronbach's alpha = 0,912), the results showed that the majority of the pregnant women presents positive body image, without disturbances. When this information is related to social-demographic data, significant relation between body weight and body image is noticed. In the evaluation of body satisfaction, however, the majority of the pregnant women (60.22%) was dissatisfied. This result shows that, when the components of body image are assessed, they can have high scores, but not necessarily in balance. In association with social-demographic data, body weight is, again, a factor of disturbance in pregnant women's body satisfaction. In conclusion, considering the achieved results, body image and body satisfaction assessment, using scales like the one this research did, must be known by professionals who work with pregnancy and must be applied in prenatal programs to identify, treat and/or prevent disturbances that can compromise welfare and self-esteem of pregnant women. Supporting programs to pregnant women with psychological therapy and physical activities that allow women to know and to identify their bodies are useful to keep the positive body image during this period Mestrado Enfermagem e Trabalho Mestre em Enfermagem

AIM To assess the impact of the different stages of acute kidney injury (AKI) on the prognosis of patients hospitalized with decompensated cirrhosis. METHODS This was a prospective cohort study of consecutive patients admitted in two tertiary hospitals in southern Brazil. Participants were considered eligible if they were admitted for acute decompensation of cirrhosis. The main exposure factor was the onset of AKI. AKI stages were defined according the European recommendations. The outcomes evaluated were survival time and death rates at 28 and 90 days from hospital admission. A χ2 test was used to compare mortality between groups. Kaplan-Meier survival analyses were undertaken assessing time to event as days from AKI diagnosis to death or liver transplant. RESULTS Two hundred and five patients were included in the study, and 121 met the criteria for AKI. Patients with AKI 1b, AKI 2 and AKI 3 had higher 90-day mortality than patients without AKI (P = 0.008, P < 0.001 and P < 0.001, respectively). However, there was no difference in 90-day mortality when patients with AKI 1a were compared with those without AKI (P = 0.742). The mean survival of patients without AKI was higher than that of patients with AKI 1b (591.4 and 305.4 days, respectively, P = 0.015), while there was no significant difference between the mean survival of patients without AKI and that of patients with AKI 1a (591.4 and 373.6 days, respectively, P = 0.198). CONCLUSION Only AKI ≥1b seems to substantially impact mortality of patients hospitalized for acute decompensation of cirrhosis.

A horta comunitária com ervas medicinais é uma ótima ferramenta de estudo econscientização ambiental, tanto para os discentes envolvidos no projeto e outros domeio acadêmico, quanto para as comunidades interna e externa que usufruem daservas disponíveis em canteiros de fácil acesso. Neste projeto, foram elaborados emantidos canteiros com diferentes ervas medicinais, dentre elas, ora-pro-nóbis,menta, manjericão, cavalinha, boldo, alfavaca, babosa, erva-cidreira, capim-limão,entre outras. O projeto não envolve apenas o fornecimento de tratamento naturalpara a comunidade, mas, principalmente, busca a conscientização quanto aosmalefícios que o uso excessivo de remédios alopáticos pode acarretar aometabolismo.

O reaproveitamento da água, seja ele da chuva ou oriundo de outro lugar, é muitoimportante, pois é dada uma nova finalidade para algo que já foi utilizado e quepossui aplicação para outro objetivo prático. Isto ajuda em medidas para diminuir osgastos e na preservação da água. Diante disto, pretendemos fazer a captação deágua da chuva, para utilizar na limpeza e nos canteiros de ervas medicinais do IFCcampus Brusque. Tornando-se um meio de conscientização para a economia deágua, que é algo extremamente importante nos dias atuais, em vista da situação emque nos encontramos.

A utilização de ilustrações dentro de materiais de estudo sempre ajudaram apromover o aprendizado de maneira lúdica. Sendo assim, nosso projeto visapromover a educação da população quanto ao consumo desenfreado de remédiosalopáticos, enfatizando soluções naturais, como um simples chá, que é menosprejudicial, podendo ser eficaz e saudável, tanto para o homem quanto para o meioambiente. Nosso enfoque maior são as crianças pelo fato de termos a convicção deque elas poderão mudar nosso futuro ao conscientizar-se sobre valores e princípiosque permeiam o respeito à natureza e ao corpo humano.

Background: Coronavirus disease 19 (COVID-19) can develop into a severe respiratory syndrome that results in up to 40% mortality. Acute lung inflammatory edema is a major pathological finding in autopsies explaining O2 diffusion failure and hypoxemia. Only dexamethasone has been shown to reduce mortality in severe cases, further supporting a role for inflammation in disease severity. SARS-CoV-2 enters cells employing angiotensin-converting enzyme 2 (ACE2) as a receptor, which is highly expressed in lung alveolar cells. ACE2 is one of the components of the cellular machinery that inactivates the potent inflammatory agent bradykinin, and SARS-CoV-2 infection could interfere with the catalytic activity of ACE2, leading to the accumulation of bradykinin. Methods: In this case control study, we tested two pharmacological inhibitors of the kinin–kallikrein system that are currently approved for the treatment of hereditary angioedema, icatibant, and inhibitor of C1 esterase/kallikrein, in a group of 30 patients with severe COVID-19. Results: Neither icatibant nor inhibitor of C1 esterase/kallikrein resulted in changes in time to clinical improvement. However, both compounds were safe and promoted the significant improvement of lung computed tomography scores and increased blood eosinophils, which are indicators of disease recovery. Conclusions: In this small cohort, we found evidence for safety and a beneficial role of pharmacological inhibition of the kinin–kallikrein system in two markers that indicate improved disease recovery.

Chromoblastomycosis is a chronic, cutaneous or subcutaneous mycosis characterized by the presence of muriform cells in host tissue. Implantation disease is caused by melanized fungi related to black yeasts, which, in humid tropical climates, are mainly members of the genus Fonsecaea. In endemic areas of Brazil, F. pedrosoi and F. monophora are the prevalent species. The current hypothesis of infection is traumatic introduction via plant materials, especially by plant thorns. However, isolation studies have demonstrated a low frequency of the agents in environmental substrates. The present study aimed to detect F. pedrosoi and F. monophora in shells of babassu coconuts, soil, plant debris, and thorns from endemic areas of chromoblastomycosis in Maranhão state, northern Brazil, using Rolling Circle Amplification (RCA) with padlock probes as a new environmental screening tool for agents of chromoblastomycosis. In addition to molecular screening, the environmental samples were analyzed by fungal isolation using mineral oil flotation. The limit of detection of the RCA method was 2.88 × 107 copies of DNA per sample for the used padlock probes, indicating that this represents an efficient and sensitive molecular tool for the environmental screening of Fonsecaea agents. In contrast, with isolation from the same samples using several selective methods, no agents of chromoblastomycosis were recovered.

The fungal genus Fonsecaea contains etiological agents of human chromoblastomycosis, a (sub)tropical, (sub)cutaneous implantation disease caused by plant contact. The invasive potential differs significantly between species. Infections by Fonsecaea monophora are believed to originate from the environment and the species has been reported as one of the main causative agents of the disease, but also of cases of primary brain infection. The epidemiology of the disease has not been fully elucidated and questions related to its infection route and virulence are still to be clarified. The environmental species Fonsecaea erecta was isolated from organic material and living plants in endemic areas for chromoblastomycosis in Brazil. The present paper describes Agrobacteriumtumefaciens-mediated transformation (AMT) of the environmental species F. erecta and the pathogenic species F. monophora. We propose the use of Agrobacterium transformation for future gene function studies related to Fonsecaea virulence and pathogenicity. We evaluated the co-cultivation ratios 1:1, 10:1 and 100:1 (Agrobacterium:conidia) at 28 °C during 72 h. pAD1625 and pCAMDsRed plasmids were inserted into both species. Confirmation of transformation was realized by hph gene amplification and Southern blot determined the amount of foreign DNA integrated into the genome. In order to evaluate a potential link between environmental and clinical strains, we obtained red fluorescent transformants after pCAMDsRed insertion. We observed by confocal fluorescence microscopy that both F. monophora and F. erecta were able to colonize the palm Bactris gasipaes, penetrating the epidermis. These results contribute to understanding the ability of Fonsecaea species to adapt to different environmental and host conditions.

Chromoblastomycosis is a chronic, cutaneous or subcutaneous mycosis characterized by the presence of muriform cells in host tissue. Implantation disease is caused by melanized fungi related to black yeasts, which, in humid tropical climates, are mainly members of the genus Fonsecaea. In endemic areas of Brazil, F. pedrosoi and F. monophora are the prevalent species. The current hypothesis of infection is traumatic introduction via plant materials, especially by plant thorns. However, isolation studies have demonstrated a low frequency of the agents in environmental substrates. The present study aimed to detect F. pedrosoi and F. monophora in shells of babassu coconuts, soil, plant debris, and thorns from endemic areas of chromoblastomycosis in Maranhão state, northern Brazil, using Rolling Circle Amplification (RCA) with padlock probes as a new environmental screening tool for agents of chromoblastomycosis. In addition to molecular screening, the environmental samples were analyzed by fungal isolation using mineral oil flotation. The limit of detection of the RCA method was 2.88 × 107 copies of DNA per sample for the used padlock probes, indicating that this represents an efficient and sensitive molecular tool for the environmental screening of Fonsecaea agents. In contrast, with isolation from the same samples using several selective methods, no agents of chromoblastomycosis were recovered.

Orientadora: Vania Aparecida Vicente PhD Coorientadores: Sybren de Hoog PhD, Renata Rodrigues Gomes PhD, Mauro Antônio Alves Castro PhD Tese (doutorado) - Universidade Federal do Paraná, Setor de Ciências Biológicas, Programa de Pós-Graduação em Microbiologia, Parasitologia e Patologia. Defesa : Curitiba, 10/03/2020 Inclui referências Área de concentração: Microbiologia Resumo: Fungos melanizados são caracterizados por pigmentação escura na parede celular. Estima-se que mais de cem espécies de fungos pretos possam causar doenças, que podem ocorrer por via de inoculação traumática desses agentes nos tecidos. Este grupo de fungos são membros da ordem Chaetothyriales e são relatados como agentes de cromoblastomicose e feo-hifomicose. A cromoblastomicose é descrita como uma infecção subcutânea que apresenta lenta evolução de lesões verrucosas nos tecidos, que formam células septadas nos tecidos, denominadas células muriformes. Enquanto, a feo-hifomicose é definida pela presença de hifas nos tecidos de vários órgãos, como fígado, coração, rim, cérebro e outros. Mas o neurotropismo ocorre com frequência notável por esse grupo de fungos, possivelmente devido à capacidade de algumas espécies de metabolizar hidrocarbonetos aromáticos. As leveduras negras Fonsecaea monophora e Fonsecaea pugnacius compartilharam o mesmo perfil de patogenicidade, sendo relatadas como agente de cromoblastomicose e agente causador de infecção cerebral primária em humanos. Este trabalho teve como objetivo gerar dados de seqüenciamento de genoma e analisar comparativamente os genomas das espécies de F. monophora e F. pugnacius para entender os mecanismos de biologia e virulência desses agentes. Foi realizada uma análise genômica comparativa das linhagens de irmãos: F. monophora e F. pugnacius, incluindo a montagem do genoma de F. pugnacius. O tamanho dos genomas são 34,21 e 34,8 Mb respectivamente, e o core do genoma dessas espécies compreende quase 70% dos genes. A similaridade do repertório de enzimas associada à ocorrência de fatores de virulência sugeriu uma tolerância geral a condições extremas, o que pode explicar a tendência oportunista dessa espécie como as demais espécies do gênero Fonsecaea. A virulência foi testada nos modelos: Tenebrio molitor e Balb/C para apoiar essa hipótese. A capacidade de sobrevivência de ambos os fungos no interior do Tenebrio molitor foi confirmada por análise histopatológica e pela presença de melanina no tecido hospedeiro. Embora F. pugnacius tenha sido isolado do cérebro de BALB/C após infecção intraperitoneal, os níveis de citocinas não foram estatisticamente significativos, corroborando com a hipótese de ser agente oportunista. Uma dupla capacidade ecológica pode ser concluída a partir da presença de vias metabólicas para eliminação de nutrientes e extremotolerância, combinadas com a capacidade de infectar hospedeiros humanos. Abstract: Black yeasts-like are fungi characterized by dark pigmentation in the cell wall. It has been estimated that more than a hundred species of black fungi can cause disease, which can occur in the injured tissues by fungi. This group of fungi are members of Chaetothyriales order and are related like as agents of chromoblastomycosis and phaeohyphomycosis. Chromoblastomycosis is characterized as a subcutaneous infection present slow evolution of verrucous lesions in the tissues, which form septate cells in the tissues, called muriforms cells. While, phaeohyphomycosis is defined by the presence of hyphae in the tissues of several organs such as liver, heart, kidney, brain and others. But the neurotropism occurs with remarkable frequency in the fungal group, possibly due to the ability of some species to metabolize aromatic hydrocarbons. The black yeasts Fonsecaea monophora and Fonsecaea pugnacius shared the same pathogenicity profile, being reported as a chromoblastomycosis agent and causal agent of primary brain infection in humans. This work aimed generate genome sequencing data and comparative analyze the genomes of F. monophora and F. pugnacius species to understand the biology and virulence mechanisms these agents. A comparative genomic analysis of sibling strains: F. monophora and F. pugnacius was undertaken, including the genome assembly of F. pugnacius. The genome size of strains are 34,21 and 34,8 Mb and the core genomes of those species comprises almost 70% of the genes. The similarity of enzymes repertory associated with the occurrence of virulence factors suggested a general tolerance to extreme conditions, which might explain the opportunistic tendency of this species like the others Fonsecaea sibling species. Virulence was tested in the Tenebrio molitor model and Balb/C were performed in order to supportthis hypothesis. The capacity of both fungi to survive inside Tenebrio molitor was confirmed by histopathological analysis and by presence of melanin in host tissue. Although F. pugnacius was isolated from brain in a murine model following intraperitoneal infection, cytokine levels were not statistically significant, indicating a profile of an opportunistic agent. A dual ecological ability can be concluded from presence of metabolic pathways for nutrient scavenging and extremotolerance, combined with a capacity to infect human hosts.

A twice-weekly galactomannan (gm) screening protocol was implemented in high-risk hematology inpatients. Study objectives were to determine adherence to the protocol, use of selected resources, and patient outcomes. This retrospective cohort study compared outcomes of interest before and after implementation of gm screening. Adults undergoing matched related allogeneic hematopoietic stem-cell transplantation or induction chemotherapy for acute leukemia were eligible. Patients could be enrolled more than once and were evaluated as episodes. Adherence to the gm protocol was assessed in post-implementation episodes. Use of broad-spectrum antifungals (bsafs), consultations (infectious diseases, respirology), and diagnostic procedures (computed tomography imaging, bronchoalveolar lavage) were compared between phases, as were the patient outcomes of all-cause mortality and clinical success (alive and not taking a bsaf). Of 182 episodes consecutively screened, 70 per phase were enrolled. Clinical characteristics and duration of assessment were similar for the phases. Full or partial adherence to the protocol was observed in 61 post-implementation episodes (87%), with full adherence in 40 episodes (57%). More episodes in the pre-implementation phase than in the post-implementation phase involved receipt of bsafs, consultations, and diagnostics (27% vs. 7%, p = 0.02, 46% vs. 26%, p = 0.014, and 46% vs. 31%, p = 0.083 respectively). Although mortality was similar in the two phases, clinical success at the final assessment was observed in fewer pre-implementation than post-implementation episodes (79% vs. 98%, p < 0.001). Implementation of a gm screening protocol was feasible and associated with significantly fewer episodes involving receipt of bsafs and consultations, and with significantly more episodes showing clinical success.

Objetivo: Analisar qual é o entendimento dos familiares de idosos sobre os Cuidados Paliativos (CP) em uma Instituição de Longa Permanência para Idosos (ILPI). Métodos: Pesquisa exploratória, transversal e qualitativa. Informações coletadas por meio de entrevistas semiestruturadas e analisadas usando a técnica de Bardin. Seis entrevistados eram familiares de idosos em CP e oito eram familiares de idosos que não estavam em CP. Resultados: Entre os familiares de idosos que estão em CP, a maioria tem conhecimento sobre CP. Quando questionados acerca do entendimento dos CP, a maioria citou qualidade de vida (QV), cuidado multidisciplinar e identificou que o familiar está em CP. Sobre os cuidados que gostariam de receber, foram o tratamento não invasivo, alívio da dor, estar com a família e ter QV. Dentre familiares de idosos que não estavam em CP, foram esclarecidos termos relacionados à QV e diminuição de tratamentos invasivos. Quanto ao conhecimento, parte demonstrou conhecimento vago e outros não o tinham. Sobre o entendimento dos CP, abordou-se a QV. Conclusão: A maioria dos familiares possuem um bom entendimento dos CP com dificuldades na definição do conceito. Familiares dos idosos que estão em CP possuem entendimento melhor sobre o tipo de atenção recebida por eles.

Este artigo tem como objetivo relacionar a qualificação acadêmica com a experiência prática dos profissionais da educação. Discute questões relacionadas à interdisciplinaridade, destacando sua fundamentação filosófica, a prática educativa e os princípios éticos. A metodologia baseia-se na pesquisa qualitativa, que utilizou a abordagem da pesquisa documental, aprofundada com depoimentos de alguns dos participantes da formação docente analisada nesta pesquisa. Os dados são analisados com autores e leituras de outras pesquisas que tratam da mesma temática. A pesquisa evidencia o propósito de superar, nos espaços acadêmicos analisados, a lógica disciplinar e fragmentadora do conhecimento, indicando desafios para repensar a formação de professores numa perspectiva interdisciplinar, com a atitude e a sabedoria do diálogo, da troca de saberes e experiências, buscando o entendimento. Dessa forma, sugere-se passar do paradigma disciplinar para o interdisciplinar, tendo a intersubjetividade como fundamento ético-antropológico para a efetivação de uma proposta interdisciplinar, tanto de investigação quanto de formação.

Este artigo tem como objetivo discutir e contextualizar os resultados obtidos na Avaliacao Nacional da Alfabetizacao (ANA) de 2016. A ANA e uma avaliacao de larga escala que mensura os niveis de alfabetizacao e letramento em Lingua Portuguesa e alfabetizacao em Matematica das criancas matriculadas no 3o ano do ensino fundamental. Inicialmente, sao apresentados e discutidos os conceitos de alfabetizacao para as escalas de Leitura e de Matematica. Com base nessas definicoes, e tracado um panorama geral sobre a alfabetizacao em Lingua Portuguesa e em Matematica no Pais e sao apresentados resultados agregados por grandes regioes, unidades da Federacao, rede e localizacao, alem de exploradas algumas relacoes entre os indices de alfabetizacao e os indicadores contextuais das escolas e dos municipios. Os resultados mostram que aproximadamente 22% dos estudantes do 3o ano nao eram alfabetizados em Lingua Portuguesa e 54% nao cumpriram as expectativas de aprendizagem esperadas em Matematica. Nas regioes Norte e Nordeste e nas areas rurais, o resultado apresenta um quadro ainda mais preocupante. Ha fortes indicios de uma associacao positiva entre o indice de alfabetizacao da escola e o nivel socioeconomico dos estudantes atendidos por ela. Tambem se observa uma relacao direta entre o nivel de alfabetizacao da instituicao e o seu indice de adequacao da formacao do corpo docente. Por fim, nota-se que os municipios com maior Indice de Desenvolvimento Humano Municipal (IDHM) e maior produto interno bruto per capita tendem a apresentar melhores indices de alfabetizacao, enquanto aqueles com maior desigualdade na distribuicao da renda tendem a apresentar resultados piores.

A revista Estudos Educacionais, publicada entre 1941 e 1946, por alunos do Curso Normal do Instituto de Educação de Florianópolis, foi analisada considerando a configuração no interior da qual a escola catarinense se colocava na primeira metade do século 20: inserção escolanovista e correspondente criação de um sistema de ensino que respondesse ao impulso modernizador. Deste fazia parte a sujeição do corpo ao desenvolvimento de um aparato psíquico forte e regulado. O objetivo de intervir nos corpos infantis aparece no periódico em três eixos: a) as ciências auxiliares (Psicologia, Sociologia e Biologia); b) o valor moral do esporte; e c) a nacionalização do ensino. Tais eixos foram analisados como resultantes do processo de constituição do Estado moderno que imputou à intervenção nos corpos importante papel no controle das paixões e na edificação de um sujeito adequado à vida industrial.

Aim: The following work aims to investigate the putative correlation between early trauma and cognitive functions, as well as psychotic symptoms and cognitive functions, in individuals diagnosed with schizophrenia. Methods: A quantitative assessment was performed with 20 individuals diagnosed with schizophrenia according to the 5th edition of the Diagnostic and Statistical Manual (DSM-5) criteria and who were in ongoing outpatient treatment in Psychosocial Care Centres in Brazil. Clinical measurements comprised a semistructured clinical interview, a screening questionnaire for common mental disorders, the Positive and Negative Syndrome Scale (PANSS), and the Early Trauma Inventory Self-Report-Short Form (ETISR-SF). Cognitive assessment included Beta III test, Concentrated Attention (CA) test, Color Trails Test (CTT), and Visual Face Memory (VFM) test. Results: Age-adjusted analysis showed a negative correlation between early trauma and visual memory performance (r = -0.585, p = 0.007) and negative symptoms and attention performance (r = -0.715, p = 0.000). Conclusion: Although a cause-effect relationship cannot be firmly stated, an association between early trauma experience and cognitive impairment such as visual memory, as well as a relationship between negative symptoms and attention domains, is suggested by our preliminary findings. Future studies with larger sample sizes and prospective design will clarify the long-term effects of early exposure to trauma and its clinical meaning in terms of developing psychotic-related illness.

Agradecimentos: The Laboratory of Cell Signaling is supported by funding provided by the Fundação de Amparo a Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Cientifico e Tecnologico. The Laboratories of Cell Signaling belongs to the Obesity and Comorbidities Research Center and the National Institute of Science and Technology - Neuroimmunomodulation Abstract: The characterization of the hypothalamic neuronal network, that controls food intake and energy expenditure, has provided great advances in the understanding of the pathophysiology of obesity. Most of the advances in this field were obtained thanks to the development of a number of genetic and nongenetic animal models that, at least in part, overtook the anatomical constraints that impair the study of the human hypothalamus. Despite the undisputed differences between human and rodent physiology, most seminal studies undertaken in rodents that have unveiled details of the neural regulation of energy homeostasis were eventually confirmed in humans; thus, placing experimental studies in the forefront of obesity research. During the last 15 years, researchers have provided extensive experimental proof that supports the existence of hypothalamic dysfunction, which leads to a progressive whole-body positive energy balance, and thus, to obesity. Here, we review the experimental work that unveiled the mechanisms behind hypothalamic dysfunction in obesity FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQ Fechado

O artigo tem como objetivo identificar as repercussões da Pedagogia do Oprimido para a academia e para os movimentos sociais, contribuindo com a formação humana e social numa perspectiva crítica. Discute a atualidade do pensamento freiriano buscando compreender a sua força para mobilizar a esperança e organizar projetos e práticas que concretizam o ideário da Pedagogia do Oprimido nas lutas da emancipação de grupos e pessoas. Trata-se de uma pesquisa qualitativa, que utilizou a abordagem da pesquisa documental e bibliográfica tendo por base o contexto da produção da obra freireana. Além disso, analisa as repercussões da Pedagogia do Oprimido para o contexto sociocultural contemporâneo. Os resultados apontam para a atualidade da obra, constituindo-se em base importante para os estudos universitários e para os movimentos sociais, contribuindo para a formação política e as lutas de libertação. Por isso, é uma das principais obras que vem sendo indicada como referência mundial na área da educação e das ciências humanas.

Aim: To evaluate and characterize the etiopathogenesis of the fusarial onychomycosis in an ex vivo study through fragments of sterile human nail, without the addition of any nutritional source. Materials & methods: The infection and invasion of Fusarium oxysporum in the nail were evaluated by scanning electron microscopy (SEM), CFU, matrix, histopathology and Fourier Transform Infrared Spectrometer coupled to an equipment with diamond accessory (FTIR-ATR). Results: F. oxysporum infected and invaded across the nail, regardless of application face. However, the dorsal nail surface was the strongest barrier, while the ventral was more vulnerable to infection and invasion process. The fungal–nail interaction resulted in the formation of a dense biofilm. Conclusion: F. oxysporum infect and invade the healthy human nail, resulting in biofilm formation. Therefore, F. oxysporum is likely a primary onychomycosis agent.

This essay has as its theme the challenge of education as a conversation in the time of the forgetfulness of the truth. Among the philosophical issues with a strong presence in education, the one that deals with truth is perhaps the most thought-provoking and challenging. Especially today, when the entry into the post-truth and post-phatic era is being announced, this question is indispensable for the comprehension and for the realization of the formative processes. The essay is organized in three moments: Initially, we will make some considerations about the problem of education in the post-truth and post-phatic era; then, we will deal with conversation from the Rorty’s philosophical perspective; Finally, we will address the possible relationship between education and conversation as a way of addressing the problem of truth and the notion of “redescription” as a broad way of understanding the truth.

Obesity-associated hypothalamic inflammation plays an important role in the development of defective neuronal control of whole body energy balance. Because dietary fats are the main triggers of hypothalamic inflammation, we hypothesized that CD1, a lipid-presenting protein, may be involved in the hypothalamic inflammatory response in obesity. Here, we show that early after the introduction of a high-fat diet, CD1 expressing cells gradually appear in the mediobasal hypothalamus. The inhibition of hypothalamic CD1 reduces diet-induced hypothalamic inflammation and rescues the obese and glucose-intolerance phenotype of mice fed a high-fat diet. Conversely, the chemical activation of hypothalamic CD1 further increases diet-induced obesity and hypothalamic inflammation. A bioinformatics analysis revealed that hypothalamic CD1 correlates with transcripts encoding for proteins known to be involved in diet-induced hypothalamic abnormalities in obesity. Thus, CD1 is involved in at least part of the hypothalamic inflammatory response in diet-induced obesity and its modulation affects the body mass phenotype of mice.

Background Peroxisome proliferator-activated receptor γ coactivator- 1alpha (PGC-1α) plays an important role in whole body metabolism and, particularly in glucose homeostasis. Its expression is highly regulated and, small variations in tissue levels can have a major impact in a number of physiological and pathological conditions. Recent studies have shown that the ubiquitin/proteasome system plays a role in the control of PGC-1α degradation. Methods Here we evaluated the interaction of PGC-1α with the protein A20, which plays a dual-role in the control of the ubiquitin/proteasome system acting as a deubiquitinase and as an E3 ligase. We employed immunoprecipitation, quantitative real-time PCR and immunofluorescence staining to evaluate PGC-1α, A20, PPARγ and ubiquitin in the adipose tissue of humans and mice. Results In distinct sites of the adipose tissue, A20 binds to PGC-1α. At least in the subcutaneous fat of humans and mice the levels of PGC-1α decrease during obesity, while its physical association with A20 increases. The inhibition of A20 leads to a reduction of PGC-1α and PPARγ expression, suggesting that A20 acts as a protective factor against PGC-1α disposal. Conclusion We provide evidence that mechanisms regulating PGC-1α ubiquitination are potentially involved in the control of the function of this transcriptional co-activator.