Rotavirus Genotypes Circulating in Brazil Before and After the National Rotavirus Vaccine Program: A Review.

We describe the rotavirus genotypes before and after rotavirus vaccine introduction in Brazil. 86 studies reported 6,884 (15.2%) rotavirus-episodes among 45,305 children. Rotavirus caused 22.4% and 11.6% of cases before and after vaccine introduction. G1P[8] and G9P[8], and G2P[4] and heterotypic-strains were most common before and after vaccine introduction. The vaccines may have selected heterotypic strains in this highly-vaccinated population

Leptin modulates human Sertoli cells acetate production and glycolytic profile: a novel mechanism of obesity-induced male infertility?

AbstractHuman feeding behavior and lifestyle are gradually being altered, favoring the development of metabolic diseases, particularly type 2 diabetes and obesity. Leptin is produced by the adipose tissue acting as a satiety signal. Its levels have been positively correlated with fat mass and hyperleptinemia has been proposed to negatively affect male reproductive function. Nevertheless, the molecular mechanisms by which this hormone affects male fertility remain unknown. Herein, we hypothesize that leptin acts on human Sertoli cells (hSCs), the “nurse cells” of spermatogenesis, altering their metabolism. To test our hypothesis, hSCs were cultured without or with leptin (5, 25 and 50ng/mL). Leptin receptor was identified by qPCR and Western blot. Protein levels of glucose transporters (GLUT1, GLUT2 and GLUT3), phosphofructokinase, lactate dehydrogenase (LDH) and monocarboxylate transporter 4 (MCT4) were determined by Western Blot. LDH activity was assessed and metabolite production/consumption determined by proton nuclear magnetic resonance. Oxidative damage was evaluated by assessing lipid peroxidation, protein carbonilation and nitration. Our data shows that leptin receptor is expressed in hSCs. The concentration of leptin found in lean, healthy patients, upregulated GLUT2 protein levels and concentrations of leptin found in lean and obese patients increased LDH activity. Of note, all leptin concentrations decreased hSCs acetate production illustrating a novel mechanism for this hormone action. Moreover, our data shows that leptin does not induce or protect hSCs from oxidative damage. We report that this hormone modulates the nutritional support of spermatogenesis, illustrating a novel mechanism that may be linked to obesity-induced male infertility

Hypopigmented macules associated to seizures must raise avareness for the possibility of the diagnosis of tuberous sclerosis

A esclerose tuberosa (ET) é uma doença multissistêmica de herança autossômica dominante caracterizada pelo desenvolvimento de hamartomas em diversos órgãos, com incidência estimada em 1:10.000 a 1:6.000 nascidos vivos. Sua ocorrência relaciona-se a mutações com perda de função nos genes TSC1 e TSC2, cujos produtos proteicos (respectivamente hamartina e tuberina) formam um heterodímero com importante função na supressão tumoral e no controle do ciclo celular [...

Preclinical validation of a new hybrid molecule loaded in liposomes for melanoma management

The aggressiveness of melanoma and lack of effective therapies incite the discovery of novel strategies. Recently, a new dual acting hybrid molecule (HM), combining a triazene and a ʟ-tyrosine analogue, was synthesized. HM was designed to specifically be activated by tyrosinase, the enzyme involved in melanin biosynthesis and overexpressed in melanoma. HM displayed remarkable superior antiproliferative activity towards various cancer cell lines compared with temozolomide (TMZ), a triazene drug in clinical use, that acts through DNA alkylation. In B16-F10 cells, HM induced a cell cycle arrest at phase G0/G1 with a 2.8-fold decrease in cell proliferation index. Also, compared to control cells, HM led to a concentration-dependent reduction in tyrosinase activity and increase in caspase 3/7 activity. To maximize the therapeutic performance of HM in vivo, its incorporation in long blood circulating liposomes, containing poly(ethylene glycol) (PEG) at their surface, was performed for passively targeting tumour sites. HM liposomes (LIP HM) exhibited high stability in biological fluids. Preclinical studies demonstrated its safety for systemic administration and in a subcutaneous murine melanoma model, significantly reduced tumour progression. In a metastatic murine melanoma model, a superior antitumour effect was also observed for mice receiving LIP HM, with markedly reduction of lung metastases compared to positive control group (TMZ). Biodistribution studies using 111In-labelled LIP HM demonstrated its ability for passively targeting tumour sites, thus correlating with the high therapeutic effect observed in the two experimental murine melanoma models. Overall, our proposed nanotherapeutic strategy was validated as an effective and safe alternative against melanoma.</p

Validation of a rapid, saliva-based, and ultra-sensitive SARS-CoV-2 screening system for pandemic-scale infection surveillance

Without any realistic prospect of comprehensive global vaccine coverage and lasting immunity, control of pandemics such as COVID-19 will require implementation of large-scale, rapid identification and isolation of infectious individuals to limit further transmission. Here, we describe an automated, high-throughput integrated screening platform, incorporating saliva-based loop-mediated isothermal amplification (LAMP) technology, that is designed for population-scale sensitive detection of infectious carriers of SARS-CoV-2 RNA. Central to this surveillance system is the "Sentinel" testing instrument, which is capable of reporting results within 25 min of saliva sample collection with a throughput of up to 3840 results per hour. It incorporates continuous flow loading of samples at random intervals to cost-effectively adjust for fluctuations in testing demand. Independent validation of our saliva-based RT-LAMP technology on an automated LAMP instrument coined the "Sentinel", found 98.7% sensitivity, 97.6% specificity, and 98% accuracy against a RT-PCR comparator assay, confirming its suitability for surveillance screening. This Sentinel surveillance system offers a feasible and scalable approach to complement vaccination, to curb the spread of COVID-19 variants, and control future pandemics to save lives

Risk of chronic arthralgia and impact of pain on daily activities in a cohort of patients with chikungunya virus infection from Brazil

Objectives: To investigate risk factors for persistent arthralgia in patients with chikungunya, and describe its impact on daily activities. Methods: From September 2014 to July 2016, a surveillance study enrolled patients with acute febrile illness in Salvador, Brazil, and detected those with chikungunya virus infection using IgM enzyme-linked immunosorbent assay or reverse transcriptase polymerase chain reaction. Telephone follow-ups were performed to ascertain the progression of disease. Results: Of 153 followed cases, 65 (42.5%) reported chronic arthralgia that lasted >3 months, and 47 (30.7%) were still symptomatic at the time of the interview (approximately 1.5 years after symptom onset). Limitations in daily activities and mental distress were reported by 93.8% and 61.5% of those with chronic arthralgia, respectively. Female sex [risk ratio (RR) 1.79, 95% confidence interval (CI) 1.95–2.69] and age (RR 1.02 for each 1-year increase, 95% CI 1.01–1.03) were independent risk factors for chronic arthralgia. Chronic arthralgia was not associated with co-infection with dengue virus (RR 0.97, 95% CI 0.48–1.94) or chikungunya viral load at diagnosis (median chikungunya virus RNA of 5.60 and 5.52 log10 copies/μL for those with and without chronic arthralgia, respectively; P = 0.75). Conclusions: These findings reinforce the high frequency of chronic chikungunya arthralgia, and highlight the substantial disability associated with the persistence of pain. Development of novel strategies to mitigate the transmission of chikungunya virus and to provide long-term medical assistance for patients with chikungunya are needed urgently.Fil: Silva, Monaíse M. O.. Fundación Oswaldo Cruz; BrasilFil: Kikuti, Mariana. Universidade Federal da Bahia; Brasil. Fundación Oswaldo Cruz; BrasilFil: Anjos, Rosângela O.. Fundación Oswaldo Cruz; BrasilFil: Portilho, Moyra M.. Fundación Oswaldo Cruz; BrasilFil: Santos, Viviane C.. Fundación Oswaldo Cruz; BrasilFil: Gonçalves, Thaiza S.F.. Fundación Oswaldo Cruz; BrasilFil: Tauro, Laura Beatriz. Fundación Oswaldo Cruz; Brasil. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Nordeste. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Puerto Iguazú | Universidad Nacional de Misiones. Instituto de Biología Subtropical. Instituto de Biología Subtropical - Nodo Puerto Iguazú; ArgentinaFil: Moreira, Patrícia S. S.. Fundación Oswaldo Cruz; BrasilFil: Jacob Nascimento, Leile C.. Fundación Oswaldo Cruz; BrasilFil: Santana, Perla M.. Fundación Oswaldo Cruz; BrasilFil: Campos, Gúbio S.. Universidade Federal da Bahia; BrasilFil: Siqueira, André M.. Fundación Oswaldo Cruz; BrasilFil: Kitron, Uriel D.. University of Emory; Estados Unidos. Fundación Oswaldo Cruz; BrasilFil: Reis, Mitermayer G.. University of Yale; Estados Unidos. Fundación Oswaldo Cruz; Brasil. Universidade Federal da Bahia; BrasilFil: Ribeiro, Guilherme S.. Fundación Oswaldo Cruz; Brasil. Universidade Federal da Bahia; Brasi

Esquizofrenia e cannabis: Qual a relação?

RESUMO: A droga ilícita mais consumida no mundo, entre pessoas de 15 a 64 anos, é a maconha. Estudos epidemiológicos apontam uma possível associação causal entre esse ativo, oriundo do gênero cannabis, e a esquizofrenia. Há muita especulação quanto aos impactos dessa droga sobre a psicose esquizofrênica. Posto a relevância do assunto, o objetivo dessa revisão foi integrar as informações presentes na literatura, visando investigar possíveis associações entre o uso de cannabis e esquizofrenia. O uso de cannabis foi analisado quanto a possibilidade de favorecer o desenvolvimento de esquizofrenia em pacientes previamente hígidos, e, quanto a possibilidade de atenuar ou agravar a sintomatologia apresentada por pacientes com o transtorno psicótico. Como metodologia, foi realizada pesquisa de livros e artigos internacionais entre fevereiro e março de 2020, realizada nos documentos indexados encontrados nas bases de dados National Library of Medicine and National Institutes of Health (PUBMED), Literatura Latino- Americana e do Caribe em Ciências da Saúde (LILACS). A combinação dos descritores em inglês: “schizophrenia” e “cannabis” identificaram 44 artigos, e dentre esses, 15 foram incluídos nessa revisão. Conclui-se que, as referências utilizadas demonstraram evidências de que a maconha é um dos fatores que aumentam o risco de desenvolvimento de esquizofrenia. Diante disso, quanto aos resultados, eles demonstraram evidências que corroboram que a maconha é um dos fatores que aumentam o risco de desenvolvimento de esquizofrenia. Quanto à exposição da Cannabis em indivíduos que são portadores do transtorno esquizofrênico, os resultados dividem-se em duas frentes: os possíveis efeitos nocivos e os possíveis efeitos terapêuticos (farmacológicos)

Neuroplasticidade e estilo de vida: qual a relação?

RESUMO: Essa revisão teve como fundamento o gradativo rompimento do pensamento de que o cérebro é um conjunto de multiestruturas isoladas permitiu a estruturação de um novo conceito: o cérebro é um órgão dinâmico e adaptável frente às exigências impostas ao mesmo. Diante desse cenário, a neuroplasticidade ganha relevância, posto que, de acordo com C. H. Phelp (1990), trata-se de uma mudança adaptativa estrutural e funcional do sistema nervoso, que “ocorre em qualquer estágio da ontogenia, como função de interações com o ambiente interno ou externo ou, ainda, como resultado de injúrias, de traumatismos ou de lesões que afetam o ambiente neural”. Teve como objetivo revisar possíveis associações entre neuroplasticidade e estilo de vida. Apresntou como metodologia a busca de livros e artigos, nacionais e internacionais, utilizando a Biblioteca Virtual em Saúde – BVS MS e o PubMed. Ultilizou-se como descritores: plasticidade neuronal, exercícios aeróbicos, yoga, e estilo de vida. 12 artigos foram selecionados e revisados, mas apenas 7 foram incluídos. Teve como resultados mais significativos encontradas referentes à estilo de vida, yoga e exercícios aeróbicos, ao lado da demonstração da relação entre neuroplasticidade e patologia de Alzheimer. Conclui-se que há relação entre neuroplasticidade e estilo de vida, porém, há diminuta amostragem de estudos sobre a temática. Ainda, os mecanismos que demonstram o vínculo descrito são pouco compreendidos, inferindo e demandando maior volume de estudos esclarecedores sobre a temática. &nbsp

The Enhanced Efficacy of Intracellular Delivery of Doxorubicin/C6-Ceramide Combination Mediated by the F3 Peptide/Nucleolin System Is Supported by the Downregulation of the PI3K/Akt Pathway

Targeting multiple cellular populations is of high therapeutic relevance for the tackling of solid tumors heterogeneity. Herein, the ability of pegylated and pH-sensitive liposomes, functionalized with the nucleolin-binding F3 peptide and containing doxorubicin (DXR)/C6-ceramide synergistic combination, to target, in vitro, ovarian cancer, including ovarian cancer stem cells (CSC), was assessed. The underlying molecular mechanism of action of the nucleolin-mediated intracellular delivery of C6-ceramide to cancer cells was also explored. The assessment of overexpression of surface nucleolin expression by flow cytometry was critical to dissipate differences identified by Western blot in membrane/cytoplasm of SKOV-3, OVCAR-3 and TOV-112D ovarian cancer cell lines. The former was in line with the significant extent of uptake into (bulk) ovarian cancer cells, relative to non-targeted and non-specific counterparts. This pattern of uptake was recapitulated with putative CSC-enriched ovarian SKOV-3 and OVCAR-3 sub-population (EpCAMhigh/CD44high). Co-encapsulation of DXR:C6-ceramide into F3 peptide-targeted liposomes improved cytotoxic activity relative to liposomes containing DXR alone, in an extent that depended on the intrinsic resistance to DXR and on the incubation time. The enhanced cytotoxicity of the targeted combination was mechanistically supported by the downregulation of PI3K/Akt pathway by C6-ceramide, only among the nucleolin-overexpressing cancer cells presenting a basal p-Akt/total Akt ratio lower than 1

Observation of Live Ticks (Haemaphysalis flava) by Scanning Electron Microscopy under High Vacuum Pressure

Scanning electron microscopes (SEM), which image sample surfaces by scanning with an electron beam, are widely used for steric observations of resting samples in basic and applied biology. Various conventional methods exist for SEM sample preparation. However, conventional SEM is not a good tool to observe living organisms because of the associated exposure to high vacuum pressure and electron beam radiation. Here we attempted SEM observations of live ticks. During 1.5×10−3 Pa vacuum pressure and electron beam irradiation with accelerated voltages (2–5 kV), many ticks remained alive and moved their legs. After 30-min observation, we removed the ticks from the SEM stage; they could walk actively under atmospheric pressure. When we tested 20 ticks (8 female adults and 12 nymphs), they survived for two days after SEM observation. These results indicate the resistance of ticks against SEM observation. Our second survival test showed that the electron beam, not vacuum conditions, results in tick death. Moreover, we describe the reaction of their legs to electron beam exposure. These findings open the new possibility of SEM observation of living organisms and showed the resistance of living ticks to vacuum condition in SEM. These data also indicate, for the first time, the usefulness of tick as a model system for biology under extreme condition