Combining Cognitive Screening Tests for the Evaluation of Mild Cognitive Impairment in the Elderly

OBJECTIVE: To determine the accuracy of the Mini-Mental State Examination combined with the Verbal Fluency Test and Clock Drawing Test for the identification of patients with mild cognitive impairment and Alzheimer's disease (AD). METHOD: These tests were used to evaluate cognitive function in 247 older adults. Subjects were divided into three groups according to their cognitive state: mild cognitive impairment (n=83), AD (n=81), cognitively unimpaired controls (n=83), based on clinical and neuropsychological data. The diagnostic accuracy of each test for discriminating between these diagnostic groups (mild cognitive impairment or AD vs. controls) was examined with the aid of Receiver Operating Characteristic (ROC) curves. Additionally, we evaluated the benefit of the combination of tests on diagnostic accuracy. RESULTS: Although they were accurate enough for the identification of Alzheimer's disease, neither test alone proved adequate for the correct separation of patients with mild cognitive impairment from healthy subjects. Combining these tests did not improve diagnostic accuracy, as compared to the Mini-Mental State Examination alone, in the identification of patients with mild cognitive impairment or Alzheimer's disease. CONCLUSIONS: The present data do not warrant the combined use of the Mini-Mental State Examination, the Verbal Fluency Test and the Clock Drawing Test as a sufficient diagnostic schedule in screening for mild cognitive impairment. The present data do not support the notion that the combination of test scores is better that the use of Mini-Mental State Examination scores alone in the screening for Alzheimer's disease

GNAQ and BRAF mutations show differential activation of the mTOR pathway in human transformed cells

Somatic mutations in GNAQ gene were described as being the main oncogenic activation in uveal melanomas, whereas mutations in BRAF gene have been described as a key genetic alteration that contributes to skin melanoma development. We have previously reported differential activation of the MAPK and AKT/mTOR signalling pathways in uveal and skin melanomas harbouring, respectively, GNAQ and BRAF mutations. The aim of this work was to compare the functional effect of GNAQ and BRAF mutations in mTOR and MAPK pathway activation, cell proliferation and apoptosis. In this work, we performed transient transfection of HEK293 cells with BRAFWT, BRAFV 600E, GNAQWT, GNAQQ209P and GNAQQ209L vectors. We treated melanoma cell lines displaying different BRAF and GNAQ mutational status with the mTOR inhibitor RAD001 and with the MEK1/2 inhibitor U0126 and evaluated the effects in the growth of the cell lines and in mTOR and MAPK pathway effectors expression. At variance with the significant increase in the level of pmTOR Ser2448 and pS6 Ser235/236 proteins observed in cells transfected with BRAF vectors, no significant alteration in mTOR pathway effectors was observed in cells transfected with the three GNAQ expressing vectors. Also, GNAQ overexpression enhances Stat3 activation, which might mediate GNAQ oncogenic effects. None of the vectors led to significant differences in proliferation or apoptosis in the transfected cell lines. Cell lines harbouring a BRAF mutation were more sensitive to RAD001 treatment. U0126 leads to the reduction of MAPK and mTOR pathways activation in all cell lines tested. Our results indicate that GNAQ and BRAF activation drive distinct intracellular signalling pathways that may be useful for therapeutic decisions in human melanomas

DNA elimination in embryogenic development of Pennisetum glaucum x Pennisetum purpureum (Poaceae) hybrids.

Interspecific hybridization between Napier grass (Pennisetum purpureum), which is widely grown in Brazil for cattle forage, and pearl millet (Pennisetum glaucum) has been used as a breeding strategy for the development of improved cultivars. However, the hybrid between these two species is sterile due to its triploid condition (2n = 3x = 21 chromosomes), which hinders its use in crop breeding programs. It is known that genomic alterations result from the hybridization process. In order to measure the loss of DNA during embryo development, we used flow cytometry to estimate the nuclear DNA content of triploid and tetraploid embryos produced by interspecific hybridization between Napier grass and pearl millet. The triploid and tetraploid hybrids had a mean DNA content of 4.99-4.87 and 5.25-4.84 pg, at 10 and 30 days after pollination, respectively. The mean reduction in DNA content was higher in the tetraploid hybrids. The flow cytometry results revealed progressive genomic instability in these triploid and tetraploid hybrids, with this instability causing significant alterations in the DNA content of the hybrids

Sepsis is a major determinant of outcome in critically ill HIV/AIDS patients

Submitted by Fábio Marques ([email protected]) on 2018-11-22T17:00:57Z No. of bitstreams: 1 Sepsis is a major determinant of outcome in HIV_Beatriz_Grinsztejn_INI_Lapclin-AIDS_2010.pdf: 326444 bytes, checksum: 176fa7e5a33453c31a87f95cfc16a782 (MD5)Approved for entry into archive by Regina Costa ([email protected]) on 2018-11-22T18:05:13Z (GMT) No. of bitstreams: 1 Sepsis is a major determinant of outcome in HIV_Beatriz_Grinsztejn_INI_Lapclin-AIDS_2010.pdf: 326444 bytes, checksum: 176fa7e5a33453c31a87f95cfc16a782 (MD5)Made available in DSpace on 2018-11-22T18:05:13Z (GMT). No. of bitstreams: 1 Sepsis is a major determinant of outcome in HIV_Beatriz_Grinsztejn_INI_Lapclin-AIDS_2010.pdf: 326444 bytes, checksum: 176fa7e5a33453c31a87f95cfc16a782 (MD5) Previous issue date: 2010Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Unidade de Tratamento Intensivo. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Unidade de Tratamento Intensivo. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Unidade de Tratamento Intensivo. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Unidade de Tratamento Intensivo. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em DST/AIDS. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Unidade de Tratamento Intensivo. Rio de Janeiro, RJ, Brasil.New challenges have arisen for the management of critically ill HIV/AIDS patients. Severe sepsis has emerged as a common cause of intensive care unit (ICU) admission for those living with HIV/AIDS. Contrastingly, HIV/AIDS patients have been systematically excluded from sepsis studies, limiting the understanding of the impact of sepsis in this population. We prospectively followed up critically ill HIV/AIDS patients to evaluate the main risk factors for hospital mortality and the impact of severe sepsis on the short- and long-term survival

Expression profiling in ovarian cancer reveals coordinated regulation of BRCA1/2 and homologous recombination genes

© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).Predictive biomarkers are crucial in clarifying the best strategy to use poly(ADP-ribose) polymerase inhibitors (PARPi) for the greatest benefit to ovarian cancer patients. PARPi are specifically lethal to cancer cells that cannot repair DNA damage by homologous recombination (HR), and HR deficiency is frequently associated with BRCA1/2 mutations. Genetic tests for BRCA1/2 mutations are currently used in the clinic, but results can be inconclusive due to the high prevalence of rare DNA sequence variants of unknown significance. Most tests also fail to detect epigenetic modifications and mutations located deep within introns that may alter the mRNA. The aim of this study was to investigate whether quantitation of BRCA1/2 mRNAs in ovarian cancer can provide information beyond the DNA tests. Using the nCounter assay from NanoString Technologies, we analyzed RNA isolated from 38 ovarian cancer specimens and 11 normal fallopian tube samples. We found that BRCA1/2 expression was highly variable among tumors. We further observed that tumors with lower levels of BRCA1/2 mRNA showed downregulated expression of 12 additional HR genes. Analysis of 299 ovarian cancer samples from The Cancer Genome Atlas (TCGA) confirmed the coordinated expression of BRCA1/2 and HR genes. To facilitate the routine analysis of BRCA1/2 mRNA in the clinical setting, we developed a targeted droplet digital PCR approach that can be used with FFPE samples. In conclusion, this study underscores the potential clinical benefit of measuring mRNA levels in tumors when BRCA1/2 DNA tests are negative or inconclusive.This research was funded by the Fundação para a Ciência e a Tecnologia, Portugal (PTDC/MED-ONC/29469/2017) and an unrestricted grant from AstraZeneca to M.C.-F. R.S. was a recipient of an EMBO Long-Term Fellowship (EMBO ALTF 101-2019). This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No. 842695.info:eu-repo/semantics/publishedVersio

Insuficiência renal aguda

A Insuficiência Renal Aguda (IRA) pode estar associada a várias etiologias no organismo humano, sendo este um dos motivos da importância dispensada àa esta doença. A prevenção é a principal ferramenta do médico e quando esta não foi possível, o tratamento visa afastar as principais causas, com investigação das demais e medidas de suporte para manter a viabilidade renal, muitas das vezes com êxito. A taxa de mortalidade em pacientes com IRA não se alterou muito nos últimos 30 anos. Os óbitos podem ocorrer em consequência da doença de base e não da própria IRA, pois o rim é um dos poucos órgãos cuja função pode ser substituída em parte por longos períodos (ex. diálise).The Acute Renal Failure (ARF) can be related to several etiologies in the human organism, being one of the reasons of the importance given to this disease. The prevention is the doctor's main tool and, when it is not possible, the treatment looks forward repelling the main causes, also investigating the others and keeping supportive care to maintain the renal viability, most of the times, successfully. The mortality rate in patients with ARF did not change much in the last 30 years. The deaths can occur as a result of the underlying disease and not of ARF, because the kidney is one of the few organs which function can be substituted, in part, for long periods (ex. dialysis)

Conversando sobre Património Industrial e outras Histórias: palavras, espaços e imagens

O conjunto de entrevistas apresentadas neste livro procura dar uma nova visão acerca do património industrial. Com uma abordagem aos estudos e às trajectórias de diversos estudiosos do Brasil e de Portugal, aos percursos de formação de cada autor (a), às suas várias temporalidades e vinculações institucionais distintas, a obra valoriza as narrativas orais de quem viveu o processo de construção e consolidação dessa área de pesquisa nos dois países. O objectivo é contribuir para o debate complexo e contínuo sobre o património e possibilita uma ampliação do nosso entendimento dos modos como esta área se firmou e se vem afirmando em diversos espaços, dentro e fora das universidades

Valores hematológicos de bovinos sadios da raça Curraleiro Pé Duro (Bos taurus): efeito da idade, sexo e gestação.

Para a determinação dos valores dos constituintes sangüíneos do hemograma de bovinos sadios da raça Curraleiro Pé Duro, foram examinadas 300 amostras, colhidas em quatro propriedades nos estados de Goiás, Tocantins e Bahia. Avaliou-se a influência da idade, sexo e gestaçãoe para tanto os animais foram distribuídos conforme a faixa etária (0 a 3, 4 a 6, 7 a 12, 13 a 24, 25 a 36, > 36 meses). Os parâmetros estudados foram eritrograma, e leucograma. Realizou-se a estatística descritiva dos dados, obtendo-se as médias, desvio padrão e coeficiente de variação para todos os parâmetros avaliados. As comparações entre médias foram feitas por meio de testes não-paramétricos. A contagem de hemácias (9,99 ± 2,46 x 106/?L), teor de hemoglobina (12,80 ± 2,16 g/dL), volume globular (38,0 ± 4,73%) nos animais mais jovens foram maiores em relação aos animais adultos, diminuindo com o desenvolvimento etário. Os índices hematimétricos (VCM e HCM) foram menores nos animais mais jovens (39,28 ± 6,63 ?3 e 13,17 ± 2,38 pg, respectivamente), aumentando com evoluir da idade. A contagem dos leucócitos (12.728,13 ? 3.854,09/?L), linfócitos (8.494,38 ± 3.078,82/?L), segmentados (3.834,50 ? 2.645,01/?L) e monócitos (276,13 ± 306/?L) diminuíram e os eosinófilos (110,94 ± 136,73/?L) aumentaram com o avançar da idade, enquanto os valores absolutos dos bastonetes e basófilos não sofreram variações significativas em função da idade. Os resultados obtidos demonstraram valores absolutos de leucócitos e linfócitos superiores nos machos em relação às fêmeas e de eosinófilos maior nas fêmeas em relação aos machos. A gestação influenciou significativamente apenas o leucograma, no qual os valores absolutos de segmentados e eosinófilos foram superiores nas fêmeas em gestação