Short-term Covid-19 forecast for latecomers.

The number of new Covid-19 cases is still high in several countries, despite vaccination efforts. A number of countries are experiencing new and severe waves of infection. Therefore, the availability of reliable forecasts for the number of cases and deaths in the coming days is of fundamental importance. We propose a simple statistical method for short-term real-time forecasting of the number of Covid-19 cases and fatalities in countries that are latecomers-i.e., countries where cases of the disease started to appear some time after others. In particular, we propose a penalized LASSO regression model with an error correction mechanism to construct a model of a latecomer country in terms of other countries that were at a similar stage of the pandemic some days before. By tracking the number of cases in those countries, we use an adaptive rolling-window scheme to forecast the number of cases and deaths in the latecomer. We apply this methodology to 45 countries and we provide detailed results for four of them: Brazil, Chile, Mexico, and Portugal. We show that the methodology performs very well when compared to alternative methods. These forecasts aim to foster better short-run management of the healthcare system and can be applied not only to countries but also to different regions within a country. Finally, the modeling framework derived in the paper can be applied to other infectious diseases.

An eIF2α-binding motif in protein phosphatase 1 subunit GADD34 and its viral orthologs is required to promote dephosphorylation of eIF2α.

Transient protein synthesis inhibition, mediated by phosphorylation of the α subunit of eukaryotic translation initiation factor 2 (eIF2α), is an important protective mechanism cells use during stress conditions. Following relief of the stress, the growth arrest and DNA damage-inducible protein GADD34 associates with the broadly acting serine/threonine protein phosphatase 1 (PP1) to dephosphorylate eIF2α. Whereas the PP1-binding motif on GADD34 has been defined, it remains to be determined how GADD34 directs PP1 to specifically dephosphorylate eIF2α. In this report, we map a novel eIF2α-binding motif to the C terminus of GADD34 in a region distinct from where PP1 binds to GADD34. This motif is characterized by the consensus sequence Rx[Gnl]x(1-2)Wxxx[Arlv]x[Dn][Rg]xRFxx[Rlvk][Ivc], where capital letters are preferred and x is any residue. Point mutations altering the eIF2α-binding motif impair the ability of GADD34 to interact with eIF2α, promote eIF2α dephosphorylation, and suppress PKR toxicity in yeast. Interestingly, this eIF2α-docking motif is conserved among viral orthologs of GADD34, and is necessary for the proteins produced by African swine fever virus, Canarypox virus, and Herpes simplex virus to promote eIF2α dephosphorylation. Taken together, these data indicate that GADD34 and its viral orthologs direct specific dephosphorylation of eIF2α by interacting with both PP1 and eIF2α through independent binding motifs.

Heterogeneity in the Effects of Food Vouchers on Nutrition Among Low-Income Adults: A Quantile Regression Analysis.

PURPOSE: To determine whether baseline fruit and vegetable (FV) intake or other predictors are associated with response to food vouchers (change in FV intake) among low-income adults. DESIGN: Secondary analysis of a randomized, 2 x 2-factorial, community-based trial. SETTING: San Francisco, California. SUBJECTS: 359 low-income adults aged ≥21 years old. INTERVENTION: Participants were mailed $20 of food vouchers monthly for 6 months, and randomized to 1 of 4 arms according to: eligible foods (FV only or any foods) and redemption schedule (weekly or monthly). MEASURES: Change in FV intake measured in cup equivalents between baseline and month 6 of the trial, based on 24-hour dietary recalls. ANALYSIS: Quantile multivariate regressions were employed to measure associations between key predictors and change in FV intake across study arms. RESULTS: FV-only weekly vouchers were associated with increased FV intake at the 25th percentile (0.24 cups/day, p = 0.048) and 50th percentile (0.37 cups/day, p = 0.02) of the distribution, but not at lower and higher quantiles. Response to the vouchers diminished 0.10 cups/day for each additional household member (p = 0.02). CONCLUSION: Response to food vouchers varied along the FV intake distribution, pointing to some more responsive groups and others potentially needing additional support to increase FV intake. Larger households likely need vouchers of higher dollar value to result in similar changes in dietary intake as that observed in smaller households.

Autoimmune Encephalitis in Latin America: A Critical Review.

Autoimmune encephalitis is an increasingly recognized cause of encephalitis. The majority of case series report patients residing in developed countries in the northern hemisphere. The epidemiologic features of autoimmune encephalitis in Latin America are still unclear. The aim of the study was to perform a review of the clinical presentation of autoimmune encephalitis in Latin America and compare to world literature. References were identified by an in-depth literature search and selected on the basis of relevance to the topic and authors' judgment. We selected clinical studies and case reports published from 2007 to July, 2020 including patients from Latin American countries. Of the 379 patients included, the majority were cases of anti-NMDA receptor encephalitis (93.14%), followed by anti-VGKC-complex encephalitis (N = 17; 4.48%), anti-GAD encephalitis (N = 9; 2.37%), anti-AMPA receptor encephalitis (N = 1; 0.26%), anti-GABA receptor encephalitis (N = 1; 0. 26%), anti-mGluR5 encephalitis (N = 1; 0. 26%), and anti-mGluR1 encephalitis (N = 1; 0. 26%). Reported cases of Anti-NMDA encephalitis in Latin-America had a very slight female predominance, lower prevalence of associated tumors and a lower incidence of extreme delta brush on electroencephalogram. Autoimmune encephalitis is possibly underdiagnosed in underdeveloped countries. Its outcome after treatment, however, appears to be similarly favorable in Latin American patients as has been reported in developed countries based on available case reports and case series. Regional specificities in the manifestation of autoimmune encephalitis could be related to epidemiologic factors, such as the presence of different triggers and different genetic and immunologic background, that need to be studied by future research.

Novel Targeting of Transcription and Metabolism in Glioblastoma.

Purpose: Glioblastoma (GBM) is highly resistant to treatment, largely due to disease heterogeneity and resistance mechanisms. We sought to investigate a promising drug that can inhibit multiple aspects of cancer cell survival mechanisms and become an effective therapeutic for GBM patients.Experimental Design: To investigate TG02, an agent with known penetration of the blood-brain barrier, we examined the effects as single agent and in combination with temozolomide, a commonly used chemotherapy in GBM. We used human GBM cells and a syngeneic mouse orthotopic GBM model, evaluating survival and the pharmacodynamics of TG02. Mechanistic studies included TG02-induced transcriptional regulation, apoptosis, and RNA sequencing in treated GBM cells as well as the investigation of mitochondrial and glycolytic function assays.Results: We demonstrated that TG02 inhibited cell proliferation, induced cell death, and synergized with temozolomide in GBM cells with different genetic background but not in astrocytes. TG02-induced cytotoxicity was blocked by the overexpression of phosphorylated CDK9, suggesting a CDK9-dependent cell killing. TG02 suppressed transcriptional progression of antiapoptotic proteins and induced apoptosis in GBM cells. We further demonstrated that TG02 caused mitochondrial dysfunction and glycolytic suppression and ultimately ATP depletion in GBM. A prolonged survival was observed in GBM mice receiving combined treatment of TG02 and temozolomide. The TG02-induced decrease of CDK9 phosphorylation was confirmed in the brain tumor tissue.Conclusions: TG02 inhibits multiple survival mechanisms and synergistically decreases energy production with temozolomide, representing a promising therapeutic strategy in GBM, currently under investigation in an ongoing clinical trial. Clin Cancer Res; 24(5); 1124-37. ©2017 AACR.

Nomophobia among medical students and its association with depression, anxiety, stress and academic performance / Nomofobia entre discentes de medicina e sua associação com depressão, ansiedade, estresse e rendimento acadêmico

Abstract: Introduction: As the world becomes increasingly interconnected, the adoption of technology remains one of the defining factors of human progress. Nomophobia (NO MObile PHOne PhoBIA) represents a mental condition caused by the fear of being detached from mobile phone connectivity. Such condition is directly associated with depression, anxiety, and stress. Moreover, nomophobia can lead to structural brain damage. Objective: The present study aims to assess the effect of nomophobia on medical students at a private institution and its association with depression, anxiety, stress and academic performance. Method: This is a cross-sectional observational study carried out in medical students at Centro Universitário Christus. Nomophobia was measured using the Nomophobia Questionnaire (NMP-Q). The NMP-Q has 20 questions, which are asked on a 7-point Likert scale. This scale has been validated for the Brazilian Portuguese language. Depression, anxiety and stress were measured by the DASS-21, a simplified version of the DASS instrument. The DASS-21 questionnaire was also validated for the Brazilian Portuguese language. Academic performance was measured through API, the product of a complex mathematical operation that results in the student's average grade in the semester and functions as a reference index for pedagogical follow-up in the assessed institution. In addition, the device use habits were assessed. Descriptive results were presented, and bivariate analyses of association and correlation were performed. This study was approved by the research ethics committee. Result: A sample of 292 students was assessed. Virtually all students (99.7%) had some degree of nomophobia, and 64.5% had a moderate or severe level of nomophobia. More than 50% of the students had higher than mild degrees of stress, and 19.5% and 11.2% of the students had severe or very severe levels of anxiety and depression, respectively. When analyzing the correlation of NMP-Q with DASS-21 scores, it was observed that increases in NMP-Q lead to increases in the overall DASS score (p < 0.001), and that worse results in DASS-21 are associated with worse API. Conclusion: Our study suggests that nomophobia is likely to increase anxiety, stress and depression and, as a result, leads to a decrease in academic performance.

Resumo: Introdução: À medida que o mundo se torna cada vez mais interconectado, a adoção de tecnologia continua sendo um dos fatores definidores do progresso humano. A nomofobia representa uma condição mental causada pelo medo de ficar sem celular. Tal condição está diretamente associada à depressão, à ansiedade e ao estresse. Ainda, a nomofobia pode levar a danos cerebrais estruturais. Objetivo: O presente estudo visa conhecer o efeito da nomofobia nos estudantes de Medicina de uma faculdade privada e sua associação com depressão, ansiedade, estresse e rendimento acadêmico. Método: Trata-se de um estudo observacional de corte transversal, do qual participaram estudantes do curso de Medicina do Centro Universitário Christus. O distúrbio foi mensurado por meio do Questionário sobre Nomofobia (NMP-Q). Esse instrumento tem 20 questões, todas baseadas na escala do tipo Likert de 7 pontos, a qual foi validada para o português brasileiro. A depressão, a ansiedade e o estresse foram mensurados pelo instrumento DASS-21, uma versão simplificada da DASS. Validou-se também o questionário DASS-21 para o português brasileiro. O rendimento acadêmico foi mensurado por meio do IRA, fruto de uma complexa operação matemática que resulta em uma nota média do aluno no semestre e funciona como um índice de referência para o acompanhamento pedagógico na faculdade estudada. Além disso, estudaram-se os hábitos de uso do dispositivo. Apresentaram-se os resultados descritivos, e realizaram-se análises bivariadas de associação e correlação. Esse estudo foi aprovado pelo Comitê de Ética em Pesquisa. Resultado: Obteve-se uma amostra de 292 estudantes. Praticamente todos os alunos (99,7%) apresentaram algum grau de nomofobia, e 64,5% demonstraram nível moderado ou grave de nomofobia. Mais de 50% dos estudantes apresentaram graus superiores ao nível leve de estresse, e 19,5% e 11,2% dos estudantes manifestaram ansiedade e depressão graves ou muito graves, respectivamente. Quando se analisou a correlação dos escores no NMP-Q com os escores da DASS-21, observou-se que aumentos nessa pontuação levam à elevação do escore geral da DASS (p < 0,001) e que piores resultados na DASS-21 estão associados ao pior IRA. Conclusão: Nosso estudo sugere que a nomofobia pode provavelmente aumentar a ansiedade, o estresse e a depressão, e, como consequência, levar uma baixa do rendimento acadêmico.

A Comparison between LMS tools to support e-health educational activities.

The objective of this study is to understand how a Learning Management System (LMS) plataform is used in a telehealth center to support two virtual learning enviroments focused on the education of the healthcare professionals and the students of a medical schoool. The study outcome is expected to provide indications towards choosing a better LSM for the telehelath center to support their educacional activities.

Adaptação transcultural e validação do Nomophobia Questionnaire (NMP-Q) para a língua portuguesa (NMP-Q-BR) / Transcultural adaptation and validation of the Nomophobia Questionnaire (NMP-Q) for the portuguese language (NMP-Q-BR)

Objetivo: Adaptar transculturalmente o Nomophobia Questionnaire (NMP-Q) e validá-lo em português. Métodos: Foi realizado estudo transversal quantitativo de validação de instrumento. A pesquisa foi desenvolvida no Centro Universitário Christus - Unichristus, com acadêmicos do primeiro semestre do curso de Medicina. As etapas de tradução e de adaptação cultural do instrumento foram realizadas de acordo com o modelo de Beaton. A confiabilidade e a precisão do instrumento foram avaliadas com 40 estudantes. No que se refere à análise da estrutura fatorial do NMP-Q, foi testado um modelo de quatro fatores, de acordo com o indicado na versão original. Resultados: A validação foi constatada com base na equivalência semântica, idiomática, cultural e conceitual após o parecer final de duas especialistas na área. Na matriz de componente rotativa do tipo Varimax com Normalização de Kaiser, os quatro fatores esperados apresentaram cargas mínimas de 0,4. O Alfa de Cronbach para o questionário geral foi de 0,952 (IC 95% 0,923-0,972), e, para os fatores individuais, foi maior que 0,7 (exceto um). Conclusões: Verificamos que a versão brasileira do instrumento (NMP-Q-BR) apresenta excelente validação. A validação do NMP-Q-BR em português proporciona a possibilidade de ampliação dos estudos sobre Nomofobia no país, justificada pela necessidade de aprofundamento das pesquisas na área.

Objective: To cross-culturally adapt the Nomophobia Questionnaire (NMP-Q) and validate it in Portuguese. Methods: A cross-sectional quantitative study of instrument validation was performed. The research was developed at the Centro Universitário Christus - Unichristus, with academics from the first semester of the medical course. The stages of translation and cultural adaptation of the instrument were performed according to the Beaton model. The instrument's reliability and accuracy were assessed with forty students. Regarding the analysis of the factorial structure of the NMP-Q, a 4-factor model was tested, according to what was indicated in the original version. Results: The validation was found based on semantic, idiomatic, cultural and conceptual equivalence after the final opinion of two experts in the field. In the rotary component matrix of the Varimax type with Kaiser Normalization, the four expected factors presented minimum loads of 0.4. The Cronbach Alpha for the general questionnaire was 0.952 (95% CI 0.923-0.972), and for the individual factors it was greater than 0.7 (except one). Conclusions: We found that the Brazilian version of the instrument (NMP-Q-BR) has excellent validation. The validation of the NMP-Q-BR in Portuguese provides the possibility of expanding the studies on Nomophobia in the country, justified by the need for further research in the area.

Atividade antifúngica dos lacatobacillus presentes no iogurte sobre a candida albicans in vitro / Antifungal activity of lactobacillus present in the yogurt on candida albicans in vitro

Objetivo: Este artigo tem como objetivo avaliar a atividade antifúngica in vitro dos Lactobacillus bulgaricus e Streptococcus thermophilus que estão presentes no iogurte sobre o crescimento da Candida albicans. Método: Foi realizado o repique da Candida albicans, fornecido em um tubo, na placa de petri contendo o ágar sabouraud dextrose para formação de colônias e aumento da população de Candida albicans. As amostras foram diluídas em soro fisiológico e semeada na placa de petri e incubou-se por duas horas. Após as duas horas, realizou-se a semeadura do iogurte, contendo os Lactobacillus bulgaricus e Streptococcus thermophilus, sobre a placa de petri contendo a Candida albicans e incubou-se na estufa a 37º C por 48 horas. Resultado: Após o período de incubação, verificamos que houve a inibição do crescimento da Candida albicans, reduzindo a quantidade de colônias das placas onde foi semeado o iogurte. Conclusão: Os Lactobacillus presentes no iogurte foram eficazes na atividade antifúngica contra a Candida albicans in vitro. Atualmente, poucos estudos foram realizados in vitro, sendo necessário realizar novos experimentos isolando os Lactobacillus bulgaricus e Streptococcus thermophilus presentes no iogurte, para maior certeza da eficácia da atividade antifúngica de cada Lactobacillus.

Objective: this paper aims to assess the antifungal activity in vitro of Lactobacillus bulgaricus and Streptococcus thermophilus that exist in yogurts on the Candida albicans growing. Method: we ringed the Candida albicans, that was provided in a tube and in a Petri´s plate, containing agar Sabouraud dextrose to compose the colonies and increase the Candida albicans population. Samples were diluted in physiological solution and seeded in the Petri´s plate, being incubated for two hours. After this time, we put the yogurt- containing the Lactobacillus bulgaricus and the Streptococcus thermophilus on the Petri´s plate. It was incubated in the heating chamber under 37oC for 48 hours. Results: After the incubation period, we verified that Candida albicans growing was inhibited, reducing the number of colonies in plates where the yogurt was seeded in. Conclusion: the Lactobacillus existent in the yogurt has an effective antifungal activity in vitro. Nowadays, few investigations were conducted in vitro, being necessary another studies to ensure the antifungal activity effectiveness of Lactobacillus present in yogurts

[Blood feeding preference of Lutzomyia whitmani (Diptera, Psychodidae) in a transmission area for American cutaneous leishmaniasis in the State of Maranhão, Brazil]. / Preferência alimentar sanguínea de Lutzomyia whitmani (Diptera, Psychodidae) em área de transmissão de leishmaniose cutânea americana, no Estado do Maranhão, Brasil.

The aim of this study was to determine the sources of blood meals for females of Lutzomyia whitmani, a phlebotomine species incriminated as the main vector for American cutaneous leishmaniasis in Maranhão. For this, 70 Lutzomyia whitmani females were collected in the municipality of Axixá, an area with one of the greatest numbers of cases of American cutaneous leishmaniasis in humans in Maranhão. They were analyzed using the precipitin technique. Ninety percent of the specimens showed a reaction to some type of antiserum positive immune reaction, among which 73% presented single reactions, with predominance for chicken blood (22%), rodent blood (14.3%) and human blood (12.7%). Among the double reactions, the predominant combinations were chicken/human (6.3%), chicken/opossum (4.8%), ox/human (3.2%) and opossum/human (3.2%). Thus, we conclude that humans and domestic and synanthropic animals are blood meal sources for Lutzomyia whitmani and may play an important role in the transmission cycle for American cutaneous leishmaniasis, thus explaining the cases of this disease in Axixá.

Preferência alimentar sanguínea de Lutzomyia whitmani (Diptera, Psychodidae) em área de transmissão de leishmaniose cutânea americana, no Estado do Maranhão, Brasil / Blood feeding preference of Lutzomyia whitmani (Diptera, Psychodidae) in a transmission area for American cutaneous leishmaniasis in the State of Maranhão, Brazil

O objetivo deste estudo foi determinar as fontes de alimento sanguíneo de fêmeas de Lutzomyia whitmani, espécie de flebotomíneo incriminada no Maranhão como principal vetor da leishmaniose cutânea americana. Para isso, 70 fêmeas desta espécie coletadas no município de Axixá, área com um dos maiores números de casos de leishmaniose cutânea americana em humanos no Maranhão, foram analisadas utilizando a técnica da precipitina. Dos indivíduos analisados, 90 por cento apresentaram reação a algum tipo de antissoro e dentre estes, 73 por cento apresentaram reações do tipo simples com predominância para sangue de galinha (22,2 por cento), roedor (14,3) e humano (12,7 por cento). Nas reações duplas predominaram as combinações galinha/humano (6,3 por cento), galinha/gambá (4,8 por cento), boi/humano e gambá/humano (3,2 por cento). Assim, concluímos que seres humanos, animais domésticos e sinantrópicos constituem fonte alimentar sanguínea para Lutzomyia whitmani podendo desempenhar um papel importante no ciclo de transmissão da leishmaniose cutânea americana explicando os casos da doença em Axixá.

The aim of this study was to determine the sources of blood meals for females of Lutzomyia whitmani, a phlebotomine species incriminated as the main vector for American cutaneous leishmaniasis in Maranhão. For this, 70 Lutzomyia whitmani females were collected in the municipality of Axixá, an area with one of the greatest numbers of cases of American cutaneous leishmaniasis in humans in Maranhão. They were analyzed using the precipitin technique. Ninety percent of the specimens showed a reaction to some type of antiserum positive immune reaction, among which 73 percent presented single reactions, with predominance for chicken blood (22 percent), rodent blood (14.3 percent) and human blood (12.7 percent). Among the double reactions, the predominant combinations were chicken/human (6.3 percent), chicken/opossum (4.8 percent), ox/human (3.2 percent) and opossum/human (3.2 percent). Thus, we conclude that humans and domestic and synanthropic animals are blood meal sources for Lutzomyia whitmani and may play an important role in the transmission cycle for American cutaneous leishmaniasis, thus explaining the cases of this disease in Axixá.

Fatores epidemiológicos, relacionados à progressão lenta da síndrome da imunodeficiência adquirida (AIDS) / Epidemiological factors related to slow progression of the acquired immune deficiency syndrome (AIDS)

Com o objetivo de identificação de fatores envolvidos na progressão lenta para aids, realizou-se estudo transversal para avaliação de dados epidemiológicos de indivíduos infectados pelo Vírus da Imunodeficiência Humana tipo 1 (HIV-1), atendidos no Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto-USP. Foram selecionados pacientes, conforme critérios definidos, constituíndo duas populações: população 1, composta por lentos progressores (P1), que possuía anticorpos anti-HIV há mais de oito anos e com ocorrência de menos de duas doenças oportunistas no último ano, e a população 2 (P2), pacientes rápidos progressores, com diagnóstico de infecção pelo HIV e doença manifesta a menos de dois anos e com mais de duas doenças oportunistas, diagnosticadas no último ano. Todos os indivíduos foram submetidos a questionário, contendo dados demográficos, profissão, ocorrência de outras doenças sexualmente transmissíveis, forma de contágio, data de diagnóstico e hábitos. O período do estudo foi de março de 1998 a outubro de 1999. Obtivemos na P1: doze homens e quatro mulheres, idade média 30,7 anos, forma de contágio predominantemente sangüínea, tempo de progressão da doença 10,5 anos; P2: 12 homens e 4 mulheres; idade média 34,8 anos, forma de contágio predominantemente sexual, tempo de progressão da doença de 1,5 anos. Tabagismo foi o principal vício em ambas as populações. Quando interrogados sobre a causa do bom estado de saúde, os indivíduos da P1 responderam estar ela relacionada à fé e ao uso adequado das medicações. Os pacientes da P2 não foram interrogados sobre a causa de seu estado de saúde. Quanto à prática sexual, nove pacientes da P1 mantinham relações, sendo cinco sem uso regular do preservativo. Na P2, apenas um paciente utilizava preservativo. Dois pacientes da P1 e um da P2 revelaram ter apresentado DST, Sífilis e Papiloma Vírus Humano. Em vista do reduzido número de pacientes, não foi possível estabelecer associação entre as variáveis estudadas e os padrões de progressão da doença. Os dados sobre hábitos não parecem contribuir para o padrão de desenvolvimento da doença. O estudo oferece um perfil epidemiológico dessas populações de pacientes