Gene expression modulation by paraquat-induced oxidative stress conditions in Paracoccidioides brasiliensis

Paracoccidioides brasiliensis is a thermodimorphic fungus associated with paracoccidioidomycosis (PCM), the most common systemic mycosis in Latin America. the infection is initiated by inhalation of environmentally dispersed conidia produced by the saprophytic phase of the fungus. in the lungs, P. brasiliensis assumes the parasitic yeast form and must cope with the adverse conditions imposed by cells of the host immune system, which includes a harsh environment, highly concentrated in reactive oxygen species (ROS). in this work, we used the ROS-generating agent paraquat to experimentally simulate oxidative stress conditions in order to evaluate the stress-induced modulation of gene expression in cultured P. brasiliensis yeast cells, using a microarray hybridization approach. the large-scale evaluation inherent to microarray-based analyses identified 2070 genes differentially transcribed in response to paraquat exposure, allowing an integrated visualization of the major metabolic changes that constitute the systemic defense mechanism used by the fungus to overcome the deleterious effects of ROS. These include overexpression of detoxifying agents, as well as of molecular scavengers and genes involved in maintenance of the intracellular redox potential. Particularly noteworthy was to verify that the oxidative stress resistance mechanism of P. brasiliensis also involves coordinated overexpression of a series of genes responsible for chitin-biosynthesis, suggesting that this pathway may constitute a specific regulon. Further analyses aiming at confirming and understanding the mechanisms that control such regulon may provide interesting new targets for chemotherapeutic approaches against P. brasiliensis and other pathogenic fungi. (C) 2013 Elsevier Inc. All rights reserved.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Univ Mogi das Cruzes, Nucleo Integrado Biotecnol, BR-08780911 Mogi Das Cruzes, SP, BrazilUniversidade Federal de São Paulo, Inst Ciencia & Tecnol, BR-12231280 Sao Jose Dos Campos, SP, BrazilUniv Fed ABC, Ctr Ciencias Nat & Humanidades, BR-09210170 Santo Andre, SP, BrazilUniversidade Federal de São Paulo, Inst Ciencia & Tecnol, BR-12231280 Sao Jose Dos Campos, SP, BrazilWeb of Scienc

Fibrosing Alopecia in a Pattern Distribution: Pathogenesis, Diagnosis and Treatment

Fibrosing alopecia in a pattern distribution is a recently recognized type of scarring alopecia, with hair loss in androgens- dependent area. Loss of follicular openings, perifollicular erythema, perifollicular hyperkeratosis and anisotriquia are the trichoscopic clues and follicular lichenoid inflammatory infiltrate the important finding in histopathology. It shares features of androgenetic alopecia and lichen planopilaris. Dermatologists should be familiarized with this entity in order to optimize the diagnosis and provide early treatment to prevent irreversible follicular damage.Alopecia fibrosante em padrão de distribuição androgenética é uma forma clínica de alopecia cicatricial recentemente reconhecida, manifestando-se por rarefacção de cabelo na área dependente de androgénios. Ausência de orifícios foliculares, eritema e hiperqueratose peri-pilar, e anisotriquia são as pistas em tricoscopia e o infiltrado inflamatório liquenóide folicular achado importante em histopatologia. Partilha características de alopecia androgenética e líquen plano pilar. Os dermatologistas devem estar familiarizados com esta entidade, a fim de otimizar o diagnóstico e tratar precocemente, evitando dano folicular irreversível

Sex workers' narratives about clients with disabilities: can training improve sexual health in Portugal? = Narrativas de trabalhadores(as) do sexo sobre clientes com diversidade funcional: poderá a formação melhorar a saúde sexual em Portugal?

People with disabilities face barriers that limit their sexual lives. In Portugal, some individuals with physical impairments have shown interest in resorting to sexual assistance provided by trained professionals, according to the client’s preferences and needs. However, in Portugal, sex workers lacking any formal training represent the only way to access commercial sex services. Thus, this study analyzes the experiences of sex workers that provide services for disabled clients. The interviews of thirteen sex workers were analyzed using the thematic analysis method proposed by Braun and Clarke. The key findings show that men seek out sexual and emotional satisfaction from sex work. Additionally, specificities inherent to the lack of training and the relationships established tend to embarrass professionals. Finally, we conclude that training coupled with sexual education and popular awareness about gender differences in the pursuit of sex is fundamental to improve the sexual health of those who choose sex services as a way of sexual expression.info:eu-repo/semantics/publishedVersio

Anti-EGFR therapy: strategies in head and neck squamous cell carcinoma.

Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor that activates downstream signaling pathways, including the Ras-MEK-Erk and PI3K-AKT pathways, leading to cell proliferation, resistance to apoptosis, angiogenesis and the ability to metastasize. EGFR overexpression is a significant finding in cancer, particularly in head and neck cancer, where it is also associated with a poor prognosis. In recent years, several molecules have been designed to inhibit EGFR activation. Among the many available anti-EGFR drugs, only cetuximab was approved for the treatment of head and neck cancers. However, no predictive biomarkers of cetuximab response are currently known. In the present review, we provide an updated assessment of EGFR biology and its clinical impact in head and neck cancers. A special emphasis is placed on novel patents of EGFR-inhibitors that are anticipated to diversify the anti-EGFR therapies available to treat head and neck cancers. In particular, we outline a new class of irreversible multi-target inhibitors (e.g. afatinib, icotinib, CUDC-101), which may significantly contribute to new head and neck cancer therapies.The authors would like to acknowledge Dr. Laura Mussel white for critical revision of the manuscript. André L. Carvalho and Rui M. Reis have a National Counsel of Technological and Scientific Development (CNPq) scholarship. A.C.C, has a FAPESP (2013/13834-7) scholarship.info:eu-repo/semantics/publishedVersio

Violence against aged people: a new issue?

O envelhecimento da população mundial é um fato concreto e de conhecimento público. O Brasil inicia seu processo de transição demográfica seguindo o padrão mundial: o aumento do número de idosos com possibilidade de atingir elevadas faixas etárias, o que traz a necessidade de pesquisas nesse campo, devido à demanda apresentada por essa nova parcela da população. A questão da violência doméstica contra idosos tem se ampliado e sugere necessidade de maior campo de investigação nessa área, dado o risco suposto ao qual essa população mais idosa está submetida. O objetivo deste artigo é verificar os estudos relacionados ao tema já realizados no Brasil e em diferentes países, com enfoque epidemiológico. O trabalho apresenta diversos pontos de abordagem da violência contra idosos, considerando questões relacionadas à cultura do envelhecimento, ações de políticas públicas, atuação de equipes de saúde, definição do termo abordado, aspectos legais e éticos da violência contra o idoso. Tal estudo permite ao pesquisador analisar os diferentes aspectos que envolvem a temática, demonstrando a necessidade de pesquisas específicas direcionadas ao tema.The world population is getting older and this is a very well known fact. The demographic transition of the Brazilian population is just beginning, and follows the world pattern: an increase in the number of older persons with an actual chance of reaching higher ages. As a consequence, there is the need of new studies to supply data about this new aspect of the population demands. Household violence against old persons has been growing and this strongly recommends that special research studies should be conducted, in view of the risk to which these individuals are exposed. The objective of this study is to list and analyze Brazilian and international studies related to aged persons, in light of an epidemiological point of view. The article presents many ways of approaching violence against old people, considering the culture of aging, actions of public policies, the practice of health teams, and legal and ethical aspects of violence against aged people. Such a study allows the researcher to analyze different aspects of the theme, showing the need of specific research on the elderly

Perfil dos pacientes com síndrome de Down atendidos na UFRGS: uma avaliação descritiva documental de 18 anos

Introduction: Evaluate the profile of patients with Down Syndrome (DS) assisted in the Discipline of Dental Care of Patients with Specials Needs in the School of Dentistry, at Federal University of Rio Grande do Sul (UFRGS). Method: Based on the dental records of patients treated at an outpatient level between 2001 and 2019, information was obtained regarding the patient's age in the first care, sex, form of access, systemic condition of DS, medication used, and treatment received on his last visit to the clinic. Result: DS represented 9% of patients, the prevalence of which was male (61%) and median age of 24 years. Regarding the conditions associated with DS, 2.8% presented autism and 15.9% had chronic diseases, with cardiopathy and hypothyroidism as the most prevalent. Related to the medicines of continuous use, 21.4% used medication, being the most frequent: antiepileptics, antipsychotics, anticonvulsants, antithyroid agents. Conclusion: The relevance of this article is made in view of the extreme importance of knowing, in depth, the condition of patients with Down Syndrome, because only in this way can be offered an adequate treatment, restoring and developing the health and life quality of themselves.Objetivo: Avaliar o perfil dos pacientes com Síndrome de Down (SD) atendidos na Disciplina de Atendimento Odontológico do Paciente com Necessidades Especiais (PNE) da Faculdade de Odontologia da Universidade Federal do Rio Grande do Sul (UFRGS). Método: A partir dos prontuários odontológicos dos pacientes atendidos em nível ambulatorial entre os anos de 2001 e 2019 foram obtidas informações em relação a idade do paciente no primeiro atendimento, sexo, forma de acesso, condição sistêmica do paciente com SD, medicamento de uso contínuo utilizado e, tratamento recebido em sua última visita a clínica. Resultado: Verificou-se que a SD representou 9% dos PNEs atendidos na disciplina, sendo 61% do sexo masculino com uma mediana de idade de 24 anos (pacientes sem doença crônica) e, de 13,5 anos (pacientes com doença crônica), advindos de Porto Alegre. Destes pacientes, 5% apresentavam condições sistêmicas associadas e, 16% doenças crônicas. 21,4% faziam uso de medicação sendo os mais frequentes: antiepilépticos, antipsicóticos, anticonvulsivantes, antitireoidianos. O tratamento mais realizado em sua última visita clínica foi a cirurgia (30,4%) para os pacientes com doenças crônica e, a prevenção (31,0%) para aqueles sem doença crônica. Conclusão: Destaca-se assim, a importância do cirurgião-dentista estar atendo às condições sistêmicas e às associadas, as quais estão ligadas também ao uso de medicamentos e, ter o conhecimento farmacológico, para saber manejar os pacientes com SD em clínica, tendo em vista que há probabilidade de manifestações bucais e sistêmicas com o uso destes medicamentos, além de suas reações adversas.Objetivo: Avaliar o perfil dos pacientes com Síndrome de Down (SD) atendidos na Disciplina de Atendimento Odontológico do Paciente com Necessidades Especiais (PNE) da Faculdade de Odontologia da Universidade Federal do Rio Grande do Sul (UFRGS). Método: A partir dos prontuários odontológicos dos pacientes atendidos em nível ambulatorial entre os anos de 2001 e 2019 foram obtidas informações em relação a idade do paciente no primeiro atendimento, sexo, forma de acesso, condição sistêmica do paciente com SD, medicamento de uso contínuo utilizado e, tratamento recebido em sua última visita a clínica. Resultado: Verificou-se que a SD representou 9% dos PNEs atendidos na disciplina, sendo 61% do sexo masculino com uma mediana de idade de 24 anos (pacientes sem doença crônica) e, de 13,5 anos (pacientes com doença crônica), advindos de Porto Alegre. Destes pacientes, 5% apresentavam condições sistêmicas associadas e, 16% doenças crônicas. 21,4% faziam uso de medicação sendo os mais frequentes: antiepilépticos, antipsicóticos, anticonvulsivantes, antitireoidianos. O tratamento mais realizado em sua última visita clínica foi a cirurgia (30,4%) para os pacientes com doenças crônica e, a prevenção (31,0%) para aqueles sem doença crônica. Conclusão: Destaca-se assim, a importância do cirurgião-dentista estar atendo às condições sistêmicas e às associadas, as quais estão ligadas também ao uso de medicamentos e, ter o conhecimento farmacológico, para saber manejar os pacientes com SD em clínica, tendo em vista que há probabilidade de manifestações bucais e sistêmicas com o uso destes medicamentos, além de suas reações adversas

Atrial fibrosis and decreased connexin 43 in rat hearts after exposure to high-intensity infrasound

Background: Noise is an important environmental risk factor. Industrial environments are rich in high-intensity infrasound (hi-IFS), which we have found to induce myocardial and coronary perivascular fibrosis in rats. The effects of exposure to IFS on the ventricles have been studied, but not on the atria. We hypothesized that rats exposed to hi-IFS develop atrial remodeling involving fibrosis and connexin 43, which we sought to evaluate. Material and methods: Seventy-two Wistar rats, half exposed to hi-IFS (120 dB, < 20 Hz) during a maximum period of 12 weeks and half age-matched controls, were studied. Atrial fibrosis was analyzed by Chromotropeaniline blue staining. The immunohistochemical evaluation of Cx43 was performed using the polyclonal antibody connexin-43 m diluted 1:1000 at 4 degrees C overnight. Digitized images were obtained with an optical microscope using 400 x magnifications. The measurements were performed using image J software. A two-way ANOVA model was used to compare the groups. Results: The mean values of the ratio "atrial fibrosis / cardiomyocytes" increased to a maximum of 0.1095 +/- 0,04 and 0.5408 +/- 0,01, and of the ratio "CX43 / cardiomyocytes" decreased to 0.0834 +/- 0,03 and 0.0966 +/- 0,03, respectively in IFS-exposed rats and controls. IFS-exposed rats exhibited a significantly higher ratio of fibrosis (p < .001) and lower ratio of Cx43 (p = .009). Conclusion: High-intensity infrasound exposure leads to an increase in atrial interstitial fibrosis and a decrease in connexin 43 in rat hearts. This finding reinforces the need for further experimental and clinical studies concerning the effects of exposure to infrasound

Quantifying how step-wise fluorination tunes local solute hydrophobicity, hydration shell thermodynamics and the quantum mechanical contributions of solute-water interactions

The ability to locally tune solute-water interactions and thus control the hydrophilic/hydrophobic character of a solute is key to control molecular self-assembly and to develop new drugs and biocatalysts; it has been a holy grail in synthetic chemistry and biology. To date, the connection between (i) the hydrophobicity of a functional group; (ii) the local structure and thermodynamics of its hydration shell; and (iii) the relative influence of van der Waals (dispersion) and electrostatic interactions on hydration remains unclear. We investigate this connection using spectroscopic, classical simulation and ab initio methods by following the transition from hydrophile to hydrophobe induced by the step-wise fluorination of methyl groups. Along the transition, we find that water-solute hydrogen bonds are progressively transformed into dangling hydroxy groups. Each structure has a distinct thermodynamic, spectroscopic and quantum-mechanical signature connected to the associated local solute hydrophobicity and correlating with the relative contribution of electrostatics and dispersion to the solute-water interactions

Assessment of data on vector and host competence for Japanese encephalitis virus: A systematic review update of Oliveira et al. 2018

Japanese Encephalitis (JE) is an emerging, zoonotic disease transmitted primarily by Culex species mosquitoes (particularly Culex tritaeniorhynchus) carrying the flavivirus Japanese encephalitis virus (JEV). Japanese encephalitis virus maintains its life cycle between mosquitoes and vertebrate hosts, primarily pigs and wading birds (Le Flohic et al., 2013). JE is an untreatable and incurable disease that, in humans, can result in inflammation of the brain (encephalitis) causing fever, headache, respiratory signs, gastrointestinal signs, confusion, seizures, coma, and, in some cases, death (Fischer et al., 2012; Kliegman et al., 2015). The United States (US) is considered a susceptible region with great potential for JEV introduction, given the availability of competent insect vectors, susceptible maintenance (avian) hosts, large populations of susceptible, amplifying hosts (domestic and feral pigs), intensive travel and trade activities to and from JEV-affected countries, and areas with similar climatic and environmental conditions to countries where the virus is epidemic. To investigate the risk of JEV introduction and establishment, Oliveira and colleagues performed a risk assessment (Oliveira et al., 2019) supported by a systematic review of vector and host competency for JEV (Oliveira et al., 2018). 3Although Oliveira et al. (2019) found the risk of introduction of JEV in the US through entry of infected mosquitoes via airplanes to be very high, the risk of establishment was considered negligible; yet, increases in international trade and globalization, as well as changes in climate and land use, and the recent incursion of a new JEV genotype into areas previously free from disease, as observed in Australia with the invasion and expansion of JEV (Genotype IV) in the eastern and southeastern states, warrants the need for an update of the review and risk assessment. The objective of this review is to update the systematic review (Oliveira et al., 2018) on host and vector competence of transmission of the Japanese encephalitis virus

Hydrophobic but water-friendly: favorable water–perfluoromethyl interactions promote hydration shell defects

Although perfluorination is known to enhance hydrophobicity and change protein activity, its influence on hydration-shell structure and thermodynamics remains an open question. Here we address that question by combining experimental Raman multivariate curve resolution spectroscopy with theoretical classical simulations and quantum mechanical calculations. Perfluorination of the terminal methyl group of ethanol is found to enhance the disruption of its hydration-shell hydrogen bond network. Our results reveal that this disruption is not due to the associated volume change but rather to the electrostatic stabilization of the water dangling OH···F interaction. Thus, the hydration shell structure of fluorinated methyl groups results from a delicate balance of solute–water interactions that is intrinsically different from that associated with a methyl group