Gene regulation by Epstein-Barr virus EBNA2 type 1 and type 2

Epstein-Barr virus, EBV, is a human herpes virus that establishes a life long, persistent, latent infection in B lymphocytes. In vitro, EBV readily transforms and immortalizes primary B cells. EBV exists in two types, named EBV type 1 and type 2. These are defined on the basis of polymorphism in the EBNA2 locus. The EBNA2 gene encodes a viral transcription factor that controls viral and cell genes and is absolutely required for B cell transformation. EBV type 1 strains are much more efficient than EBV type 2 at transforming B cells and the enhanced transformation efficiency was previously mapped to the EBNA2 gene. A transfection assay was devised to compare the ability of type 1 and type 2 EBNA2 to sustain cell proliferation in EREB2.5 lymphoblastoid cells, which contain a ΔEBNA2-Epstein-Barr virus and express a conditional EBNA2. The reduced proliferation in cells expressing type 2 EBNA2 correlated with loss of expression of some cell genes that are known to be targets of type 1 EBNA2. Microarray analysis of EBNA2 target genes in stably transfected Burkitt lymphoma cells identified a small number of genes that are more strongly induced by type 1 than type 2 EBNA2 and one of these genes (CXCR7) was shown to be required for proliferation of lymphoblastoid cell lines. The Epstein-Barr virus LMP1 gene is directly induced by EBNA2 and is critically involved in B cell transformation. In Daudi Burkitt lymphoma cells, EBNA2 type 1 induced LMP1 much more strongly than EBNA2 type 2, although both reached comparable levels after 48 hours. The results show that differential gene regulation by Epstein-Barr virus type 1 and type 2 EBNA2 is likely to be the basis for the much weaker B cell transformation activity of type 2 Epstein-Barr virus strains compared to type 1 strains

Sleep in psychiatric disorders

Altered sleep patterns are prominent in the majority of psychiatric disorders. This article examines the psychiatric disorders that are most often associated to sleep dysfunction as it is related in clinical practice and describes the polysomnographic findings. Patient's main complaints are related to difficulty in initiating and maintaining sleep (initial or middle insomnia, respectively) and poor quality of sleep. Early awakening or terminal insomnia is most described in the depressive conditions. Hypersomnia may be the main symptom in some depressive disorders, as seasonal depression, depression with atypical features or depressive episodes in bipolar disorder. Polysomnographic evaluation shows, in general, a significative reduction in the efficiency and total time of sleep, in detriment to the amount of slow wave sleep. The reduction of rapid eye movement (REM) sleep latency is mainly described for the depression, but has also been reported in other psychiatric disorders.O achado de padrões alterados de sono é notável na maioria dos transtornos psiquiátricos. Neste artigo são abordados os transtornos psiquiátricos que mais freqüentemente apresentam alterações de sono na prática clínica e a descrição dos achados polissonográficos. As queixas mais freqüentes dos pacientes são relacionadas à dificuldade para iniciar e manter o sono (insônia inicial e de manutenção, respectivamente) e sono não reparador, observadas na maioria dos transtornos. A insônia terminal ou despertar precoce é mais relacionada a quadros depressivos. A hipersonia pode aparecer em alguns quadros de depressão como sazonal, atípica ou em transtornos bipolares. Em relação aos achados polissonográficos, temos, em geral, redução significativa da eficiência e do tempo total do sono à custa da redução do sono de ondas lentas. A redução da latência para o sono de movimentos oculares rápidos (REM) é descrita principalmente para os quadros depressivos, mas pode aparecer em outras patologias.Universidade Federal de São Paulo (UNIFESP)Universidade de Medicina de Taubaté Faculdade de MedicinaUNIFESPSciEL

Measuring lactase enzymatic activity in the teaching lab

Understanding how enzymes work, and relating this to real life examples, is critical to a wide range of undergraduate degrees in the biological and biomedical sciences. This easy to follow protocol was developed for first year undergraduate pharmacy students and provides an entry-level introduction to enzyme reactions and analytical procedures for enzyme analysis. The enzyme of choice is lactase, as this represents an example of a commercially available enzyme relevant to human disease/pharmaceutical practice. Lactase is extracted from dietary supplement tablets, and assessed using a colorimetric assay based upon hydrolysis of an artificial substrate for lactase (ortho-nitrophenol-beta-D-galactopyranoside, ONPG). Release of ortho-nitrophenol following the hydrolytic cleavage of ONPG by lactase is measured by a change in absorbance at 420 nm, and the effect of the temperature on the enzymatic reaction is evaluated by carrying out the reaction on ice, at room temperature and at 37 °C. More advanced analysis can be implemented using this protocol by assessing the enzyme activity under different conditions and using different reagents

Properties of Contextual Memory Formed in the Absence of αCaMKII Autophosphorylation

The alpha-isoform of calcium/calmodulin-dependent kinase II (αCaMKII) is a major synaptic kinase that undergoes autophosphorylation after NMDA receptor activation, switching the kinase into a calcium-independent activity state. This αCaMKII autophosphorylation is essential for NMDA receptor-dependent long-term potentiation (LTP), induced by a single tetanus, in hippocampal area CA1 and in neocortex. Furthermore, the αCaMKII autophosphorylation is essential for contextual long-term memory (LTM) formation after a single training trial but not after a massed training session. Here, we show that in the absence of αCaMKII autophosphorylation contextual fear conditioning is hippocampus dependent and that multi-tetanus-dependent late-LTP cannot be induced in hippocampal area CA1. Furthermore, we show that in the absence of αCaMKII autophosphorylation contextual LTM persists for 30 days, the latest time point tested. Additionally, contextual, but not cued, LTM formation in the absence of αCaMKII autophosphorylation appears to be impaired in 18 month-old mice. Taken together, our findings suggest that αCaMKII autophosphorylation-independent plasticity in the hippocampus is sufficient for contextual LTM formation and that αCaMKII autophosphorylation may be important for delaying age-related impairments in hippocampal memory formation. Furthermore, they propose that NMDA receptor-dependent LTP in hippocampal area CA1 is essential for contextual LTM formation after a single trial but not after massed training. Finally, our results challenge the proposal that NMDA receptor-dependent LTP in neocortex is required for remote contextual LTM

IMPACTO DAS DECISÕES DAS AUTORIDADES PÚBLICAS NA VIDA E NA MORTE DA POPULAÇÃO: COVID-19 NO BRASIL, MARÇO DE 2021

The Covid-19 pandemic has the entire world in agony, and Brazil is one of the countries being hit the hardest. This article analyzes a pandemic-related decision made by the Brazilian Ministry of Health in August 2020, when it rejected Pfizer’s proposal to acquire 70 million doses of the Pfizer/BioNTech vaccine. The question we ask is this: of the Brazilians aged 80 or older who died of Covid-19 in Brazil in March 2021, how many would still be alive if the Ministry of Health had acquired the 70 million doses of the Pfizer/BioNTech vaccine in August 2020?O mundo sofre com a pandemia da Covid-19. O Brasil é um dos países cuja população está sendo mais fortemente atingida. Este Artigo analisa uma decisão tomada pelo Ministério da Saúde do Brasil durante a pandemia da Covid-19, que, em agosto de 2020, recusou a proposta da farmacêutica Pfizer para aquisição de 70 milhões de doses da vacina Pfizer/BioNTech. Questiona-se: entre as pessoas com 80 anos ou mais de idade que faleceram de Covid-19 no Brasil, no mês de março de 2021, quantas delas poderiam estar vivas, caso o Ministério da Saúde do Brasil tivesse adquirido, em agosto de 2020, as 70 milhões de doses da vacina Pfizer/BioNTech

IMPACTO DAS DECISÕES DAS AUTORIDADES PÚBLICAS NA VIDA E NA MORTE DA POPULAÇÃO: COVID-19 NO BRASIL, JUNHO DE 2021

The Covid-19 pandemic has the entire world in agony, and Brazil is one of the countries being hit the hardest. This is the Fourth Article in the series that analyzes a pandemic-related decision made by the Brazilian Ministry of Health in August 2020, when it rejected Pfizer’s proposal to acquire 70 million doses of the Pfizer/BioNTech vaccine. The question we ask is this: of the Brazilians aged 60 or older who died of Covid-19 in Brazil in June 2021, how many would still be alive if the Ministry of Health had acquired the 70 million doses of the Pfizer/BioNTech vaccine in August 2020?El mundo sufre la pandemia de Covid-19. Brasil es uno de los países cuya población está siendo más afectada. Este es el cuarto artículo de la serie que analiza una decisión tomada por el Ministerio de Salud de Brasil durante la pandemia Covid-19, que en agosto de 2020 rechazó la propuesta de la farmacéutica Pfizer de adquirir 70 millones de dosis de la vacuna Pfizer / BioNTech. Se cuestiona: entre las personas de 60 años o más que murieron por Covid-19 en Brasil, en junio de 2021, cuántos de ellos podrían haber estado vivos, si el Ministerio de Salud de Brasil lo hubiera adquirido, en agosto de 2020, el 70 millones de dosis de la vacuna Pfizer / BioNTech?O mundo sofre com a pandemia da Covid-19. O Brasil é um dos países cuja população está sendo mais fortemente atingida. Este é o Quarto Artigo da série que analisa uma decisão tomada pelo Ministério da Saúde do Brasil durante a pandemia da Covid-19, que, em agosto de 2020, recusou a proposta da farmacêutica Pfizer para aquisição de 70 milhões de doses da vacina Pfizer/BioNTech. Questiona-se: entre as pessoas com 60 anos ou mais de idade que faleceram de Covid-19 no Brasil, no mês de junho de 2021, quantas delas poderiam estar vivas, caso o Ministério da Saúde do Brasil tivesse adquirido, em agosto de 2020, as 70 milhões de doses da vacina Pfizer/BioNTech

IMPACTO DAS DECISÕES DAS AUTORIDADES PÚBLICAS NA VIDA E NA MORTE DA POPULAÇÃO: COVID-19 NO BRASIL, ABRIL DE 2021

The Covid-19 pandemic has the entire world in agony, and Brazil is one of the countries being hit the hardest. This is the S econd Article in the series that analyzes a pandemic-related decision made by the Brazilian Ministry of Health in August 2020, when it rejected Pfizer’s proposal to acquire 70 million doses of the Pfizer/BioNTech vaccine. The question we ask is this: of the Brazilians aged 70 or older who die d of Covid-19 in Brazil in April 2021, how many would still be alive if the Ministry of Health had acquired the 70 million doses of the Pfizer/BioNTech vaccine in August 2020?O mundo sofre com a pandemia da Covid-19. O Brasil é um dos países cuja população está sendo mais fortemente atingida. Este é o Segundo Artigo da série que analisa uma decisão tomada pelo Ministério da Saúde do Brasil durante uma pandemia da Covid-19, que, em agosto de 2020, recusou a proposta farmacêutica Pfizer para aquisição de 70 milhões de doses da vacina Pfizer / BioNTech . Questiona-se: entre as pessoas com 70 anos ou mais de idade que faleceram de Covid-19 no Brasil, no mês de abril de 2021, quantas delas puderam estar vivas, caso o Ministério da Saúde do Brasil adquiriu adquirido, em agosto de 2020 , como 70 milhões de doses da vacina Pfizer / BioNTech

IMPACTO DAS DECISÕES DAS AUTORIDADES PÚBLICAS NA VIDA E NA MORTE DA POPULAÇÃO: COVID-19 NO BRASIL, JULHO DE 2021. RESULTADO CONCLUSIVO DO ESTUDO

The Covid-19 pandemic has the entire world in agony, and Brazil is one of the countries being hit the hardest. This is the Fifth and final Article in the series that analyzes a pandemic-related decision made by the Brazilian Ministry of Health in August 2020, when it rejected Pfizer’s proposal to acquire 70 million doses of the Pfizer/BioNTech vaccine. The question we ask is this: 1) Of the Brazilians aged 50 or older who died of Covid-19 in Brazil in July 2021, how many would still be alive if the Ministry of Health had acquired the 70 million doses of the Pfizer/BioNTech vaccine in August 2020? 2) Among people who died of Covid-19 in Brazil, analyzing the conclusive results, these may be alive, if the Ministry of Health of Brazil will have acquired, in August 2020, as 70 million doses of the Pfizer / BioNTech vaccine? This series of studies is mentioned in the Final Report of the Parliamentary Inquiry Commission (CPI) of the Covid-19 Pandemic of the Federal Senate, in Chapter 13, which deals with indictments, specifically in item 13.1, on preventable deaths, and in the Conclusions.La pandemia de Covid-19 tiene al mundo entero en agonía, y Brasil es uno de los países más afectados. Este es el quinto y último artículo de la serie que analiza una decisión relacionada con una pandemia tomada por el Ministerio de Salud de Brasil en agosto de 2020, cuando rechazó la propuesta de Pfizer de adquirir 70 millones de dosis de la vacuna Pfizer / BioNTech. La pregunta que nos hacemos es la siguiente: 1) De los brasileños de 50 años o más que murieron de Covid-19 en Brasil en julio de 2021, ¿cuántos seguirían con vida si el Ministerio de Salud hubiera adquirido los 70 millones de dosis de Pfizer / BioNTech? vacuna en agosto de 2020? 2) Entre las personas que murieron por Covid-19 en Brasil, analizando los resultados concluyentes, ¿estos pueden estar vivos, si el Ministerio de Salud de Brasil habrá adquirido, en agosto de 2020, como 70 millones de dosis de la vacuna Pfizer / BioNTech? Esta serie de estudios se menciona en el Informe Final de la Comisión de Investigación Parlamentaria (CPI) de la Pandemia Covid-19 del Senado Federal, en el Capítulo 13, que trata de las acusaciones, específicamente en el ítem 13.1, sobre muertes evitables, y en el Conclusiones.O mundo sofre com a pandemia da Covid-19. O Brasil é um dos países cuja população está sendo mais fortemente atingida. Este é o Quinto e último Artigo da série que analisa uma decisão tomada pelo Ministério da Saúde do Brasil durante a pandemia da Covid-19, que, em agosto de 2020, recusou a proposta da farmacêutica Pfizer para aquisição de 70 milhões de doses da vacina Pfizer/BioNTech. Questiona-se: 1) Entre as pessoas com 50 anos ou mais de idade que faleceram de Covid-19 no Brasil, no mês de julho de 2021, quantas delas poderiam estar vivas, caso o Ministério da Saúde do Brasil tivesse adquirido, em agosto de 2020, as 70 milhões de doses da vacina Pfizer/BioNTech? 2) Entre as pessoas que faleceram de Covid-19 no Brasil, quantas delas poderiam estar vivas, caso o Ministério da Saúde do Brasil tivesse adquirido, em agosto de 2020, as 70 milhões de doses da vacina Pfizer/BioNTech? Essa série de estudos está citada no Relatório Final da Comissão Parlamentar de Inquérito (CPI) da Pandemia da Covid-19 do Senado Federal, no Capítulo 13, que trata dos indiciamentos, especificamente no item 13.1, sobre as mortes evitáveis, e nas Conclusões

IMPACTO DAS DECISÕES DAS AUTORIDADES PÚBLICAS NA VIDA E NA MORTE DA POPULAÇÃO: COVID-19 NO BRASIL, MAIO DE 2021

The Covid-19 pandemic has the entire world in agony, and Brazil is one of the countries being hit the hardest. This is the Third Article in the series that analyzes a pandemic-related decision made by the Brazilian Ministry of Health in August 2020, when it rejected Pfizer’s proposal to acquire 70 million doses of the Pfizer/BioNTech vaccine. The question we ask is this: of the Brazilians aged 60 or older who died of Covid-19 in Brazil in May 2021, how many would still be alive if the Ministry of Health had acquired the 70 million doses of the Pfizer/BioNTech vaccine in August 2020?El mundo sufre la pandemia de Covid-19. Brasil es uno de los países cuya población está siendo más afectada. Este es el tercer artículo de la serie que analiza una decisión tomada por el Ministerio de Salud de Brasil durante la pandemia Covid-19, que en agosto de 2020 rechazó la propuesta de la farmacéutica Pfizer de adquirir 70 millones de dosis de la vacuna Pfizer / BioNTech. La pregunta es: entre las personas de 60 años o más que murieron por Covid-19 en Brasil, en mayo de 2021, cuántos de ellos podrían haber estado vivos, si el Ministerio de Salud de Brasil lo hubiera adquirido, en agosto de 2020, el 70 millones de dosis de la vacuna Pfizer / BioNTech?O mundo sofre com a pandemia da Covid-19. O Brasil é um dos países cuja população está sendo mais fortemente atingida. Este é o Terceiro Artigo da série que analisa uma decisão tomada pelo Ministério da Saúde do Brasil durante a pandemia da Covid-19, que, em agosto de 2020, recusou a proposta da farmacêutica Pfizer para aquisição de 70 milhões de doses da vacina Pfizer/BioNTech. Questiona-se: entre as pessoas com 60 anos ou mais de idade que faleceram de Covid-19 no Brasil, no mês de maio de 2021, quantas delas poderiam estar vivas, caso o Ministério da Saúde do Brasil tivesse adquirido, em agosto de 2020, as 70 milhões de doses da vacina Pfizer/BioNTech

Brazilian consensus on guidelines for diagnosis and treatment for restless legs syndrome

The Consensus on restless legs syndrome is an effort of neurologists from several Brazilian states, which tirelessly reviewed the literature of recent years in search of evidence, both in regard to diagnosis and treatment, according to the Oxford Centre for Evidence-based Medicine.Serv Neurol & Neurocirurgia, Passo Fundo, RS, BrazilUniv São Paulo, Fac Med Ribeirao Preto, BR-14049 Ribeirao Preto, SP, BrazilClin Carlos Bacelar, Rio de Janeiro, RJ, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, São Paulo, BrazilHosp Moinhos Vento, BR-90560030 Porto Alegre, RS, BrazilUniversidade Federal de São Paulo, Dept Neurol, São Paulo, BrazilHosp Israelita Albert Einstein, São Paulo, BrazilUniv Fed Alagoas, Fac Med, Maceio, AL, BrazilUniv Fed Pernambuco, Recife, PE, BrazilClin Rio Sono, Rio de Janeiro, RJ, BrazilUniv São Paulo, Fac Med, Hosp Clin, São Paulo, BrazilPontificia Univ Catolica Rio Grande do Sul, Porto Alegre, RS, BrazilUniv Brasilia, Fac Med, Brasilia, DF, BrazilHosp Clin Porto Alegre, Porto Alegre, RS, BrazilProSSono Ctr Med Sono, Ribeirao Preto, BrazilUniversidade Federal de São Paulo, Dept Psicobiol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Neurol, São Paulo, BrazilWeb of Scienc