Human Papillomavirus Modulates Matrix Metalloproteinases During Carcinogenesis: Clinical Significance and Role of Viral Oncoproteins.

Human papillomavirus (HPV) infections are associated with cervical cancer and other anogenital cancers. Despite progresses in HPV vaccination and screening, these cancers still show high incidence and mortality, requiring improved prognostic markers and tailored therapies. This review addresses the role of Matrix metalloproteinases (MMPs) in HPV-induced cancers and the modulation of MMP expression by HPV oncoproteins. Scientific literature indexed in PubMed and ScienceDirect about Human papillomavirus modulates matrix metalloproteinases was retrieved and critically analyzed, to obtain an overview of expression patterns and their implications for carcinogenesis and patient prognosis. Matrix metalloproteinases such as MMP1, MMP9 and MMP13 have been associated with patient prognosis in HPV-induced cancers and play a major role in the degradation of the extracellular matrix, tumor invasion and metastasis. The HPV E2 and E7 oncoproteins regulate MMP expression via AKT, MEK/ERK and AP-1 signaling among other mechanisms. Increased expression of MMPs is associated with cancer progression and poor prognosis in multiple HPV-induced cancers, suggesting their potential use as prognostic markers. The identification of specific signaling pathways that mediate MMP regulation by HPV is essential for developing efficient new cancer therapies.

Added Sugar and Oral Health: A Position Paper of the Brazilian Academy of Dentistry.

Excessive sugar consumption is the main cause of dental caries. Dental caries is highly prevalent and negatively impacts the quality of life at all stages. Furthermore, sugar consumption is associated with other noncommunicable conditions and diseases, such as obesity, diabetes, and cardiovascular diseases. The aim of this paper is to propose recommendations at the individual and population levels for health professionals, families, educators, stakeholders, and public officials to reduce the burden of dental caries and other noncommunicable diseases that are caused by the excessive sugar intake. A systematic search was performed in PubMed and Cochrane databases to investigate the effectiveness of strategies and policies aiming to reduce sugar consumption as well as the impact of different patterns of sugar consumption on the occurrence of dental caries. Reference list of the identified papers and practice guidelines were manually reviewed as well. Based on the best evidence available, the Brazilian Academy of Dentistry recommends not to offer sugars to children younger than 2 years of age, and to limit total sugar consumption to <25 g per day after 2 years of age. Furthermore, families should be informed to limit sugar exposure, sugar-free areas should be available, content of food labels and advertisement should be regulated, taxation of products with sugar should be introduced, and reformulation of foods and drinks to reduce concentrations of sugars should be considered.

Manual sobre biossegurança para reabertura de escolas no contexto da covid-19

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Performance and economic viability of tambaqui, Colossoma macropomum, selectively bred for weight gain

Tambaqui, Colossoma macropomum, is one of the most produced species in Brazilian fish farming, which has boosted the development of new technologies to increase its productivity. The aim of this study was to evaluate production performance in two second-generation tambaqui stocks selectively bred for weight gain in a semi-intensive rearing system and assess its influence on total production cost. We analyzed 300 fish (initial mean weight and standard length of 160 g and 17 cm, respectively) of two families (A and B, 150 fish each). The fish were individually marked with microchips and stocked in an 800-m2 excavated pond. For economic analysis, the obtained performance data were extrapolated for a fish farm with a 10-ha pond, adopting the Total Production Cost methodology. After 270 days of farming, the fish from family B were significantly superior (p < 0.05) for all analyzed performance parameters (final weight = 1965.0 g; weight gain = 1786.7 g; biomass gain = 255.2 kg) and morphometric growth in relation to the fish from family A (final weight = 1881.0 g; weight gain = 1737.5 g; biomass gain: 217.7 kg). The total production cost estimations indicated that fish from family B would allow for a 4% reduction in the average fixed cost and a 1% decrease in the total average production cost. (AU)

Região Norte do Brasil e a pandemia de COVID-19: análise socioeconômica e epidemiológica / North region of Brazil and the COVID-19 pandemic: socioeconomic and epidemiologic analysis / Región Norte de Brasil y la pandemia de COVID-19: análisis socioeconómico y epidemiológico

Objetivo: analisar o perfil epidemiológico das doenças respiratórias e os indicadores socioeconômicos e de assistência em saúde da região Norte do Brasil durante a pandemia de COVID-19. Método: estudo epidemiológico, de caráter descritivo e quantitativo, em relação ao período de janeiro de 2010 a fevereiro de 2020. Os dados foram coletados no DATASUS e no boletim epidemiológico sobre a COVID-19 do Ministério da Saúde. Os resultados foram dispostos em números absolutos, frequência relativa e medidas de tendência central. Resultados: no período houve 1.163.303 internações, consumindo 891.494.215,40 reais. Pará e Amazonas somam 66% desses gastos. Os meses de abril, maio e junho apresentaram médias maiores de hospitalizações durante todos os anos. A faixa etária mais onerosa foi entre 60 e 69 anos. A região Norte é menos provida de médicos, leitos de UTI e respiradores. Amazonas, Amapá e Roraima têm os maiores coeficientes de incidência de COVID-19 por 1.000.000 de habitantes. Conclusão: a pandemia aumenta a vulnerabilidade socioeconômica e assistencial do sistema de saúde do Norte brasileiro, com sobrecarga e número de óbitos crescente. Portanto, há necessidade urgente de realocar recursos e reorganizar a rede de atenção à saúde.

Objective: to analyze the epidemiological profile of respiratory diseases and the socioeconomic and health care indicators of northern Brazil during the COVID-19 pandemic. Methods: epidemiological study, of a descriptive and quantitative character, in relation to the period from January 2010 to February 2020. Data were collected in DATASUS and in the epidemiological bulletin on COVID-19 of the Ministry of Health. The results were displayed in absolute numbers, relative frequency and measures of central tendency. Results: in the period there were 1,163,303 hospitalizations, consuming 891,494,215.40 reais. Pará and Amazonas account for 66% of these expenses. The months of April, May and June showed higher averages of hospitalizations during all years. The most expensive age group was between 60 and 69 years. The northern region is less equipped with doctors, ICU beds and respirators. Amazonas, Amapá and Roraima have the highest incidence coefficients of COVID-19 per 1,000,000 inhabitants. Conclusion: the pandemic increases the socioeconomic and assistance vulnerability of the health system in northern Brazil, with an overload and an increasing number of deaths. Therefore, there is an urgent need to reallocate resources and reorganize the health care network.

Objetivo: analizar el perfil epidemiológi co de las enfermedades respiratorias y los indicadores socioeconómicos y de salud del Norte de Brasil durante la pandemia COVID- 19. Método: estudio epidemiológico, de carácter descriptivo y cuantitativo, en relación con el período comprendido entre enero de 2010 y febrero de 2020. Los datos se recopilaron en DATASUS y en el boletín epidemiológico sobre COVID-19 del Ministerio de Salud. Los resultados se mostraron en números absolutos. frecuencia relativa y medidas de tendencia central. Resultados: en el período hubo 1.163.303 hospitalizaciones, que consumieron 891.494.215,40 reales. Pará y Amazonas representan el 66% de estos gastos. Los meses de abril, mayo y junio mostraron promedios más altos de hospitalizaciones durante todos los años. El grupo de edad más caro fue entre 60 y 69 años. La región Norte está menos equipada con médicos, camas de UCI y respiradores. Amazonas, Amapá y Roraima tienen las tasas más altas de incidencia de COVID-19 por cada 1,000,000 de habitantes. Conclusión: la pandemia aumenta la vulnerabilidad socioeconómica y asistencial del sistema de salud en el Norte de Brasil, con una sobrecarga y un número creciente de muertes. Por lo tanto, existe una necesidad urgente de reasignar recursos y reorganizar la red de atención médica.

Doenças respiratórias no Triângulo Mineiro: Análise epidemiológica e projetiva com a pandemia de COVID-19 / Respiratory diseases in the Triângulo Mineiro: Epidemiological analysis and projective with the COVID-19 pandemic

Objetivos: investigar as internações por doenças respiratórias no Triângulo Mineiro (Minas Gerais, Brasil), discutindo-as no contexto da atenção em saúde, e a pandemia de COVID-19. Métodos: estudo epidemiológico, descritivo e quantitativo sobre as doenças do aparelho respiratório nas macrorregiões de saúde Triângulo do Norte e Triângulo do Sul, de janeiro de 2014 a dezembro de 2019. Foram utilizados dados provenientes do Sistema de Informação Hospitalar do Sistema Único de Saúde (SIH/SUS), disponíveis no endereço eletrônico do Departamento de Informática do SUS (DATASUS). Os dados foram apresentados por números absolutos, frequência relativa e medidas de tendência central. Resultados: nesse período, houve 76.745 internações por doenças do aparelho respiratório no Sistema Único de Saúde (SUS), com aspecto crescente desde 2018. As cidades de Uberlândia e Uberaba somam juntas quase metade desse total. Com os serviços hospitalares e profissionais foram gastos, aproximadamente, 90 milhões de reais. As faixas etárias cuja internação foi mais frequente foram a de 1 a 4 anos e a de 80 anos ou mais. As maiores frequências de óbitos concentraram-se no segundo e terceiro trimestre do ano e entre os indivíduos acima de 60 anos. Conclusões: O contexto caótico e oneroso ao SUS, decorrente das internações por doenças respiratórias, agravar-se-á ao se somar ao cenário de pandemia por COVID-19. Por isso, é imperiosa a prevenção dos fatores de risco e a promoção de saúde por meio da melhora na atenção primária em saúde, bem como a ampliação e a reorganização da rede hospitalar.(AU)

Objective: to investigate the hospitalizations for respiratory diseases in the Triângulo Mineiro (Minas Gerais, Brazil), and discuss them in the context of health care and the COVID-19 pandemic. Methods: epidemiologic, descriptive, and quantitative study on Respiratory Tract Diseases in Triângulo do Norte and Triângulo do Sul health macroregions, from January 2014 to December 2019. It was used data from the Informational Hospital System of the Unified Health System (SIH/SUS), available at the electronic address of the Information Technology Department of Unified Health System (DATASUS). Data were presented by absolute numbers, relative frequency, and central tendency measures. Results: in this period, there were 76.745 hospitalizations for Respiratory Tract Diseases at SUS, with a growing aspect since 2018. Uberlandia and Uberaba cities together add up to half of that amount. It was spent approximately 90 million of Brazilian Reals currency on hospital and professional services. The age groups whose hospitalization was more frequent were from 1 to 4 years and 80 years or more. Most deaths were concentrated in the second and third trimesters of the year and among individuals over 60 years of age. Conclusions: the chaotic and onerous context to SUS resulting from hospitalizations for respiratory tract diseases will become more severe by adding the COVID-19 pandemic scenario. Therefore, it is imperative to prevent risk factors and promote health by improving primary health care, as well as the hospital network ampliation and reorganization.(AU)

Parasitological evaluation of lettuce served in school meals at a Federal State School in Rio de Janeiro, Brazil

The Brazilian "National School Lunch Program" (PNAE) must provide healthy food for students in public primary education. Thus, it is necessary to ensure both nutritional and parasitological quality, reducing health risks. Vegetables must be clean, presenting no parasites and larvae, according to Brazilian legislation. Lettuce (Lactuca sativa L.) is one of the favorite vegetables among students, and is eaten raw in salads. This paper aims to evaluate the parasitological quality of lettuce served in school lunches. 72 samples of leaf lettuce, 36 from conventional agriculture (CA) and 36 from family agriculture (FA), were analyzed. Half the samples in each group were sanitized by immersion in a sodium hypochlorite solution, with 2% active stabilized chlorine for 10 minutes (n=18/each) and half were not sanitized (n=18/each). Parasite load evaluation was performed by two methods in each subgroup: spontaneous sedimentation (SS) and sedimentation by centrifugation (SC). The parasite frequencies found were evaluated by the chi-squared test. Medically relevant parasites identified were helminths (Strongyloides stercoralis, Ascaris lumbricoides and Hookworms) as well as protozoa (Balantidium coli and Entamoeba coli). 44.6% of the FA samples presented some form of parasite by SS evaluation and 33.4% by SC evaluation; 66.7% of the CA samples presented parasites by SS evaluation, and 44.5% by SC evaluation. No significant differences were noted between the FA and CA groups in either technique. No parasites were found in any of the sanitized lettuces, regardless of the subgroup or technique applied. These results evidence the importance of adequate training and guidance for vegetable growers, food handlers as well as the general population regarding proper hygiene of lettuce leaves prior to consumption.

Assessment of female sexual function in remote postpatum period: a cross-sectional study / Avaliação da função sexual feminina no puerpério remoto: um estudo transversal

Abstract Objectives: (i) to evaluate female sexual function in remote postpartum period within Brazilian women and (ii) to compare female sexual dysfunction in relation to the mode of delivery. Methods: in this cross-sectional study, two groups of remote postpartum women, who underwent vaginal delivery (n=30) and cesarean (n=48), were studied. The sexual function of participants was assessed through an online Brazilian version of FSFI between 45 and 180 days after delivery. Data were analyzed by descriptive and inferential statistics using Fisher exact test, and Student t test. Results: based on the data of 78 women who completed the online questionnaire, 78% (n=61) showed sexual dysfunction on remote postpartum period being that the FSFI mean score for vaginal postpartum was 22.17 and for cesarean postpartum, 21.12 (p=0.443). Conclusions: the majority of remote postpartum women showed sexual dysfunction. There was no significant difference found on female sexual function between modes of delivery.

Resumo Objetivos: (i) avaliar a função sexual feminina no puerpério remoto em mulheres brasileiras e (ii) comparar a disfunção sexual feminina em relação a via de parto. Métodos: neste estudo transversal, dois grupos de mulheres no puerpério remoto, que passaram por parto vaginal (n=30) e cesárea (n=48), foram estudados. A função sexual das participantes foi avaliada via online através da versão brasileira do FSFI entre 45 e 180 dias após o parto. Os dados foram analisados pela estatística descritiva e inferencial, utilizando o teste exato de Fisher e o teste t de Student. Resultados: com base nos dados de 78 mulheres que completaram o questionário online, 78% (n=61) apresentaram disfunção sexual no pós-parto remoto, sendo que o escore médio do FSFI foi de 22,17 para o pós-parto vaginal e 21,12 para o puerpério de cesárea, (p=0,443). Conclusões: a maior parte das mulheres no puerpério remoto apresentou disfunção sexual. Não foi encontrada diferença significativa na função sexual feminina entre os tipos de parto.

Mecanismos de resistência antimicrobiana em pseudomonasaeruginosa / Mechanisms responsible for antimicrobial resistance in pseudomonas aeruginosa

Pseudomonas aeruginosa é uma bactéria de grande importância para indivíduos imunocomprometidos. No Brasil, ela é um dos principais agentes em infecções hospitalares e pode provocar diversos tipos de processos clínicos. Atualmente, um dos maiores desafios em infecções provocadas por P. aeruginosa é a resistência apresentada diante de inúmeros antimicrobianos. Além da resistência intrínseca de P.aeruginosa, essa bactéria facilmente desenvolve mecanismos de resistência adicionais, através de mutações e da aquisição de elementos genéticos móveis, por exemplo. Dessa forma, P. aeruginosa é considerada um patógeno multirresistente, o que limita as alternativas terapêuticas capazes de combatê-lo. Portanto, compreender osmecanismos que levam a essa resistência é de extrema importância para enfrentar as infecções por P. aeruginosa.

Pseudomonas aeruginosa is a bacterium of great importance forimmunocompromised individuals. In Brazil, it is one of the leadingcauses of hospital infections and can cause many types of infections.Currently, one of the biggest challenges in infections caused by P.aeruginosa is the resistance presented against numerousantimicrobials. In addition to the intrinsic resistance of P. aeruginosa,inherent in the species, this bacterium easily acquire additionalmechanisms of resistance via mutation and acquisition of mobilegenetic elements, for example. Accordingly, P. aeruginosa isconsidered a multidrug-resistant pathogen, which limits thetherapeutic alternatives able to fight it. Therefore, understanding themechanisms that lead to this resistance is of utmost importance totackle infections by P. aeruginosa.

Therapeutic administration of recombinant Paracoccin confers protection against paracoccidioides brasiliensis infection: involvement of TLRs.

BACKGROUND: Paracoccin (PCN) is an N-acetylglucosamine-binding lectin from the human pathogenic fungus Paracoccidioides brasiliensis. Recombinant PCN (rPCN) induces a T helper (Th) 1 immune response when prophylactically administered to BALB/c mice, protecting them against subsequent challenge with P. brasiliensis. In this study, we investigated the therapeutic effect of rPCN in experimental paracoccidioidomycosis (PCM) and the mechanism accounting for its beneficial action. METHODOLOGY/PRINCIPAL FINDINGS: Four distinct regimens of rPCN administration were assayed to identify which was the most protective, relative to vehicle administration. In all rPCN-treated mice, pulmonary granulomas were less numerous and more compact. Moreover, fewer colony-forming units were recovered from the lungs of rPCN-treated mice. Although all therapeutic regimens of rPCN were protective, maximal efficacy was obtained with two subcutaneous injections of 0.5 µg rPCN at 3 and 10 days after infection. The rPCN treatment was also associated with higher pulmonary levels of IL-12, IFN-γ, TNF-α, nitric oxide (NO), and IL-10, without IL-4 augmentation. Encouraged by the pulmonary cytokine profile of treated mice and by the fact that in vitro rPCN-stimulated macrophages released high levels of IL-12, we investigated the interaction of rPCN with Toll-like receptors (TLRs). Using a reporter assay in transfected HEK293T cells, we verified that rPCN activated TLR2 and TLR4. The activation occurred independently of TLR2 heterodimerization with TLR1 or TLR6 and did not require the presence of the CD14 or CD36 co-receptors. The interaction between rPCN and TLR2 depended on carbohydrate recognition because it was affected by mutation of the receptor's N-glycosylation sites. The fourth TLR2 N-glycan was especially critical for the rPCN-TLR2 interaction. CONCLUSIONS/SIGNIFICANCE: Based on our results, we propose that PCN acts as a TLR agonist. PCN binds to N-glycans on TLRs, triggers regulated Th1 immunity, and exerts a therapeutic effect against P. brasiliensis infection.

Identification of a vaccine against schistosomiasis using bioinformatics and molecular modeling tools.

Schistosomiasis is a serious public health problem in Brazil and worldwide. Although the drugs used to treatment schistosomiasis are effective, the disease continues to expand in all endemic countries due to constant reinfection, poor sanitation, and the lack of effective programs for disease control. However, advances generated through genome projects have provided important information that has improved the understanding of the biology of this parasite. These advances, associated with the advent of bioinformatic analysis, are becoming an important tool in reverse vaccinology. Through database access to the DNA and protein sequences of Schistosoma mansoni and the use of bioinformatics programs, fourteen epitopes were identified. Five epitopes were obtained from proteins whose immunogenic potential had already been assessed in other studies (KP), and nine whose immunogenic potential is unknown (UP). To improve stimulation of the host immune system, the selected epitopes were modeled with a sugar moiety. After this addition, all of the epitopes showed structures similar to those observed in the native proteins, but only eleven of the peptides presented thermodynamically stable structures. Prediction analysis and molecular modeling showed that the glycopeptides presented here are important targets in the search for a vaccine against schistosomiasis. Additionally, they suggest that these molecules may be used in immunological assays to evaluate the level of protection, the effect on pathology reduction and the profile of cytokines and antibodies induced by them.