Emphatic accent used by individuals with and without voice and speech training

PURPOSE: To investigate how individuals with and without voice training use emphatic accent in two previously selected words during a reading. METHODS:Seventy seven individuals with ages between 19 and 57 years were distributed into two groups: 51 students from a radio training course - TG (trained group); and 26 subjects with no voice and speech training - UnTG (untrained group). Individuals read a radio report twice, emphasizing two different words in each reading: negotiates and reforms. The readings were recorded with an interval of two months between them, which corresponded to the beginning and end of the radio training course attended by the TG. Voice samples were submitted to: auditory-perceptual analysis of the occurrence, evaluation and use of emphasis; visual analysis of the spectrographic trace for delimitation of the pauses; acoustic analysis of the duration and fundamental frequency of the emphases. Results were submitted to statistical analysis. RESULTS: The TG had higher grades than the UnTG regarding the quality of emphasis use, and there was no difference in its occurrence and use. The word reforms had higher occurrence of emphasis and was better evaluated than the word negotiates. The TG used less pauses than the UnTG. Acoustic analysis showed that the word reforms was longer than negotiates in the UnTG. The mean fundamental frequency was higher for negotiates. CONCLUSION: Both groups demonstrated that the use of emphasis accompanies the individuality of speakers. The TG had better ability in the distribution of pauses. The words were distinctly emphasized due to syntactic and semantic aspects.OBJETIVO: Investigar como indivíduos com e sem treinamento vocal utilizam recursos de ênfase em duas palavras previamente selecionadas na leitura de texto. MÉTODOS: Setenta e sete indivíduos de 19 a 57 anos de idade formaram dois grupos: 51 alunos de curso de radialista denominados grupo treinado - GT e 26 indivíduos sem experiência em locução, denominados grupo não-treinado - GNT. Eles leram uma notícia duas vezes enfatizando, a cada leitura, uma palavra: negocia e reformas. As leituras foram gravadas em dois momentos com intervalo de dois meses entre elas, correspondentes ao início e ao final do curso de radialista do GT. O material foi submetido à avaliação perceptivo-auditiva da ocorrência, avaliação e forma de utilização da ênfase; identificação visual da espectrografia para delimitação das pausas junto às palavras estudadas; análise acústica da duração e frequência fundamental das ênfases. Testes estatísticos foram aplicados. RESULTADOS: GT foi melhor avaliado quanto à qualidade da utilização da ênfase que GNT, não havendo diferença na sua ocorrência e forma de utilização. Reformas teve maior ocorrência de ênfase e foi melhor avaliada que negocia. GT usou menos pausas que GNT. Na análise acústica, reformas durou mais que negocia no GNT. A média da frequência fundamental de negocia foi maior que reformas. CONCLUSÃO: Os grupos comportaram-se de forma semelhante, demonstrando que enfatizar obedece a individualidade dos falantes. GT apresentou mais habilidade na distribuição das pausas. As ênfases ocorreram diferentemente entre as palavras respeitando aspectos sintático-semânticos.Universidade Federal de São Paulo (UNIFESP)UNIFESPSciEL

A Unified Experimental/Theoretical Description of the Ultrafast Photophysics of Single and Double Thionated Uracils

Photoinduced processes in thiouracil derivatives have lately attracted considerable attention due to their suitability for innovative biological and pharmacological applications. Here, sub-20 fs broadband transient absorption spectroscopy in the near-UV are combined with CASPT2/MM decay path calculations to unravel the excited-state decay channels of water solvated 2-thio and 2,4-dithiouracil. These molecules feature linear absorption spectra with overlapping ππ* bands, leading to parallel decay routes which we systematically track for the first time. The results reveal that different processes lead to the triplet states population, both directly from the ππ* absorbing state and via the intermediate nπ* dark state. Moreover, the 2,4-dithiouracil decay pathways is shown to be strongly correlated either to those of 2- or 4-thiouracil, depending on the sulfur atom on which the electronic transition localizes

Chlamydia trachomatis: when the virulence-associated genome backbone imports a prevalence-associated major antigen signature

Chlamydia trachomatis is the most prevalent sexually transmitted bacterium worldwide and the causative agent of trachoma. Its strains are classified according to their ompA genotypes, which are strongly linked to differential tissue tropism and disease outcomes [ocular disease, urogenital disease and lymphogranuloma venereum (LGV)]. While the genome-based species phylogenetic tree presents four main clades correlating with tropism/prevalence, namely ocular, LGV, urogenital T1 (more prevalent genotypes) and urogenital T2 (less prevalent genotypes), inter-clade exchange of ompA is considered a rare phenomenon probably mediating marked tropism alterations. An LGV epidemic, associated with the clonal expansion of the L2b genotype, has emerged in the last few decades, raising concerns particularly due to its atypical clinical presentation (ulcerative proctitis) and circulation among men who have sex with men (MSM). Here, we report an LGV outbreak, mostly affecting human immunodeficiency virus-positive MSM engaging in high-risk sexual practices, caused by an L2b strain with a rather unique non-LGV ompA signature that precluded the laboratory notification of this outbreak as LGV. C. trachomatis whole-genome capture and sequencing directly from clinical samples was applied to deeply characterize the genomic backbone of this novel LGV outbreak-causing clone. It revealed a chimeric genome structure due to the genetic transfer of ompA and four neighbouring genes from a serovar D/Da strain, likely possessing the genomic backbone associated with the more prevalent urogenital genotypes (T1 clade), to an LGV (L2b) strain. The hybrid L2b/D-Da strain presents the adhesin and immunodominant antigen MOMP (major outer membrane protein) (encoded by ompA) with an epitope repertoire typical of non-invasive genital strains, while keeping the genome-dispersed virulence fingerprint of a classical LGV strain. As previously reported for inter-clade ompA exchange among non-LGV clades, this novel C. trachomatis genomic mosaic involving a contemporary epidemiologically and clinically relevant LGV strain may have implications on its transmission, tissue tropism and pathogenic capabilities. The emergence of variants with epidemic and pathogenic potential highlights the need for more focused surveillance strategies to capture C. trachomatis evolution in action.info:eu-repo/semantics/publishedVersio

Multilayer OMIC data in medullary thyroid carcinoma identifies the STAT3 pathway as a potential therapeutic target in RETM918T tumors

Purpose: Medullary thyroid carcinoma (MTC) is a rare disease with few genetic drivers, and the etiology specific to each known susceptibility mutation remains unknown. Exploiting multilayer genomic data, we focused our interest on the role of aberrant DNA methylation in MTC development.Experimental Design: We performed genome-wide DNA methylation profiling assessing more than 27,000 CpGs in the largest MTC series reported to date, comprising 48 molecularly characterized tumors. mRNA and miRNA expression data were available for 33 and 31 tumors, respectively. Two human MTC cell lines and 101 paraffin-embedded MTCs were used for validation.Results: The most distinctive methylome was observed for RETM918T-related tumors. Integration of methylation data with mRNA and miRNA expression data identified genes negatively regulated by promoter methylation. These in silico findings were confirmed in vitro for PLCB2, DKK4, MMP20, and miR-10a, -30a, and -200c. The mutation-specific aberrant methylation of PLCB2, DKK4, and MMP20 was validated in 25 independent MTCs by bisulfite pyrosequencing. The methylome and transcriptome data underscored JAK/Stat pathway involvement in RETM918T MTCs. Immunostaining [immunohistochemistry (IHC)] for the active form of signaling effector STAT3 was performed in a series of 101 MTCs. As expected, positive IHC was associated with RETM918T-bearing tumors (P < 0.02). Pharmacologic inhibition of STAT3 activity increased the sensitivity to vandetanib of the RETM918T-positive MTC cell line, MZ-CRC-1.Conclusions: Multilayer OMIC data analysis uncovered methylation hallmarks in genetically defined MTCs and revealed JAK/Stat signaling effector STAT3 as a potential therapeutic target for the treatment of RETM918T MTCs.This work was supported by the Fondo de Investigaciones Sanitarias (FIS) project PI14/00240 and the Comunidad de Madrid (Grant S2011/BMD-2328 TIRONET) to MR. LI-P is supported by the Centro de Investigacion Biomédica en Red de Enfermedades Raras (CIBERER). VM was supported by a predoctoral fellowship from the "la Caixa"/CNIO international PhD programme. CM-C is supported by a postdoctoral fellowship from the Fundación AECC

Excesso ponderal e pressão arterial em crianças do 1º Ciclo

Introdução: Portugal é o 6.° país da União Europeia cuja prevalência de excesso de peso e obesidade ultrapassa os 30%. As crianças obesas apresentam risco mais elevado para hipertensão arterial do que crianças não obesas, risco que aumenta com o aumento do IMC e não apenas na classificação de obesidade. A hipertensão arterial é um dos principais factores de risco modificável de doenças cardiovasculares. A sua incidência e prevalência em crianças tem aumentado nas últimas décadas, principalmente, nos países desenvolvidos. Crianças com hipertensão arterial tendem a ser adultos hipertensos com elevado número de morbilidades associadas. Como tal, a sua prevenção deve iniciar-se o mais precocemente possível. Métodos: Estudo transversal em crianças do 1º ciclo, com avaliação nutricional por parâmetros antropométricos e de pressão arterial. A avaliação nutricional incluiu peso e altura para cálculo do índice de massa corporal (IMC), prega cutânea tricipital e prega subescapular para cálculo da percentagem de massa gorda (%MG) através da equação de Slaughter, e o perímetro da cintura para a razão cintura/altura. Para a medição da pressão arterial foi utilizado um tensiómetro de braço, OMRON® M6, realizadas duas medições da pressão arterial sistólica e a pressão arterial diastólica com um intervalo de alguns minutos e classificada de acordo com o percentil de altura (National High Blood Pressure Education Program, 2004). A análise estatística foi efectuada com programa IBM SPSS (Statistical Package for the Social Sciences). Resultados: Foram incluídos 181 crianças, 90 (49,7%) do sexo masculino, entre os 5 e os 10 anos com idade, média 7,4n1,2 anos. De acordo com o IMC, a maioria (61,9%) apresentava eutrofia, 38 (21%) excesso ponderal e 29 (16%) obesidade. A razão perímetro da cintura/altura foi superior ao percentil 90, em 62 (32,4%) crianças. A classificação da %MG foi superior ao percentil 91 em 47 (26,3%) e destes, 21 (11,6%) foram classificados com percentil superior a 98. A pressão arterial sistólica estava elevada (>Percentil 90) em 6 (3,3%) crianças, enquanto a diastólica estava elevada em 44 (24,3%) crianças, das quais 25 (13,8%) acima do Percentil 95. Verificou-se uma correlação positiva entre a pressão arterial sistólica e diastólica e o Z-Score de IMC (r=0,328; p<0,000) e (r=0,263; p<0,000) ; e entre a %MG (r=0,271; p<0,000) e (r=0,187; p<0,000), enquanto apenas a sistólica mostrou correlação fraca com a razão cintura/altura (r=0,181; p=0,015). As crianças eutróficas apresentavam valores de pressão arterial inferiores aos das crianças com excesso ponderal e obesidade (sistólica: 88,5n10,0 vs 93,6n9,7; p=0,050) (diastólica: 61,7n9,3 vs 64,7n7,4; P=0,024). Conclusão: Estes dados confirmam a elevada prevalência de excesso de peso e pressão arterial elevada em crianças no 1º ciclo, bem como a sua associação. Cerca de 1/3 das crianças apresentava excesso ponderal e ¼ tinha valores de pressão arterial elevados. Apesar de num estudo transversal não serem avaliados factores de causalidade, a correlação observada entre a pressão arterial e excesso de peso, indica que futuras intervenções devem focar não apenas a obesidade, mas igualmente a pressão arterial, especialmente em crianças com excesso de peso.info:eu-repo/semantics/draf

La formación en competencia matemática aplicada a la Farmacia Galénica: Comparación de tres cursos consecutivos

Se analizan los resultados de test y problemas numéricos de Farmacia Galénica realizados por estudiantes de 1º del Grado en Farmacia de 3 cursos consecutivos para valorar el impacto de las acciones de mejora en la estrategia de enseñanza-aprendizaje. Los errores más frecuentes conciernen a la aplicación del concepto de porcentaje. Las actividades para diagnosticar la capacidad de resolución de problemas son motivadoras para trabajar las carencias detectadas y mejorar el rendimient

SARS-CoV-2 introductions and early dynamics of the epidemic in Portugal

Genomic surveillance of SARS-CoV-2 in Portugal was rapidly implemented by the National Institute of Health in the early stages of the COVID-19 epidemic, in collaboration with more than 50 laboratories distributed nationwide. Methods By applying recent phylodynamic models that allow integration of individual-based travel history, we reconstructed and characterized the spatio-temporal dynamics of SARSCoV-2 introductions and early dissemination in Portugal. Results We detected at least 277 independent SARS-CoV-2 introductions, mostly from European countries (namely the United Kingdom, Spain, France, Italy, and Switzerland), which were consistent with the countries with the highest connectivity with Portugal. Although most introductions were estimated to have occurred during early March 2020, it is likely that SARS-CoV-2 was silently circulating in Portugal throughout February, before the first cases were confirmed. Conclusions Here we conclude that the earlier implementation of measures could have minimized the number of introductions and subsequent virus expansion in Portugal. This study lays the foundation for genomic epidemiology of SARS-CoV-2 in Portugal, and highlights the need for systematic and geographically-representative genomic surveillance.We gratefully acknowledge to Sara Hill and Nuno Faria (University of Oxford) and Joshua Quick and Nick Loman (University of Birmingham) for kindly providing us with the initial sets of Artic Network primers for NGS; Rafael Mamede (MRamirez team, IMM, Lisbon) for developing and sharing a bioinformatics script for sequence curation (https://github.com/rfm-targa/BioinfUtils); Philippe Lemey (KU Leuven) for providing guidance on the implementation of the phylodynamic models; Joshua L. Cherry (National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health) for providing guidance with the subsampling strategies; and all authors, originating and submitting laboratories who have contributed genome data on GISAID (https://www.gisaid.org/) on which part of this research is based. The opinions expressed in this article are those of the authors and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. This study is co-funded by Fundação para a Ciência e Tecnologia and Agência de Investigação Clínica e Inovação Biomédica (234_596874175) on behalf of the Research 4 COVID-19 call. Some infrastructural resources used in this study come from the GenomePT project (POCI-01-0145-FEDER-022184), supported by COMPETE 2020 - Operational Programme for Competitiveness and Internationalisation (POCI), Lisboa Portugal Regional Operational Programme (Lisboa2020), Algarve Portugal Regional Operational Programme (CRESC Algarve2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and by Fundação para a Ciência e a Tecnologia (FCT).info:eu-repo/semantics/publishedVersio

Extending the phenotypic spectrum assessed by the CDR plus NACC FTLD in genetic frontotemporal dementia

INTRODUCTION: We aimed to expand the range of the frontotemporal dementia (FTD) phenotypes assessed by the Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains (CDR plus NACC FTLD). METHODS: Neuropsychiatric and motor domains were added to the standard CDR plus NACC FTLD generating a new CDR plus NACC FTLD-NM scale. This was assessed in 522 mutation carriers and 310 mutation-negative controls from the Genetic Frontotemporal dementia Initiative (GENFI). RESULTS: The new scale led to higher global severity scores than the CDR plus NACC FTLD: 1.4% of participants were now considered prodromal rather than asymptomatic, while 1.3% were now considered symptomatic rather than asymptomatic or prodromal. No participants with a clinical diagnosis of an FTD spectrum disorder were classified as asymptomatic using the new scales. DISCUSSION: Adding new domains to the CDR plus NACC FTLD leads to a scale that encompasses the wider phenotypic spectrum of FTD with further work needed to validate its use more widely. Highlights: The new Clinical Dementia Rating Dementia Staging Instrument plus National Alzheimer's Coordinating Center Behavior and Language Domains neuropsychiatric and motor (CDR plus NACC FTLD-NM) rating scale was significantly positively correlated with the original CDR plus NACC FTLD and negatively correlated with the FTD Rating Scale (FRS). No participants with a clinical diagnosis in the frontotemporal dementia spectrum were classified as asymptomatic with the new CDR plus NACC FTLD-NM rating scale. Individuals had higher global severity scores with the addition of the neuropsychiatric and motor domains. A receiver operating characteristic analysis of symptomatic diagnosis showed nominally higher areas under the curve for the new scales.</p

Brain functional network integrity sustains cognitive function despite atrophy in presymptomatic genetic frontotemporal dementia

© 2020 The Authors. Alzheimer's & Dementia published by Wiley Periodicals, Inc. on behalf of Alzheimer's Association. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Introduction: The presymptomatic phase of neurodegenerative disease can last many years, with sustained cognitive function despite progressive atrophy. We investigate this phenomenon in familial frontotemporal dementia (FTD). Methods: We studied 121 presymptomatic FTD mutation carriers and 134 family members without mutations, using multivariate data-driven approach to link cognitive performance with both structural and functional magnetic resonance imaging. Atrophy and brain network connectivity were compared between groups, in relation to the time from expected symptom onset. Results: There were group differences in brain structure and function, in the absence of differences in cognitive performance. Specifically, we identified behaviorally relevant structural and functional network differences. Structure-function relationships were similar in both groups, but coupling between functional connectivity and cognition was stronger for carriers than for non-carriers, and increased with proximity to the expected onset of disease. Discussion: Our findings suggest that the maintenance of functional network connectivity enables carriers to maintain cognitive performance.K.A.T. is supported by the British Academy Postdoctoral Fellowship (PF160048) and the Guarantors of Brain (101149). J.B.R. is supported by the Wellcome Trust (103838), the Medical Research Council (SUAG/051 G101400), and the Cambridge NIHR Biomedical Research Centre. R. S.‐V. is supported by the Instituto de Salud Carlos III and the JPND network PreFrontAls (01ED1512/AC14/0013) and the Fundació Marató de TV3 (20143810). M.M and E.F are supported by the UK Medical Research Council, the Italian Ministry of Health, and the Canadian Institutes of Health Research as part of a Centres of Excellence in Neurodegeneration grant, and also a Canadian Institutes of Health Research operating grant (MOP 327387) and funding from the Weston Brain Institute. J.D.R., D.C., and K.M.M. are supported by the NIHR Queen Square Dementia Biomedical Research Unit, the NIHR UCL/H Biomedical Research Centre, and the Leonard Wolfson Experimental Neurology Centre (LWENC) Clinical Research Facility. J.D.R. is supported by an MRC Clinician Scientist Fellowship (MR/M008525/1) and has received funding from the NIHR Rare Disease Translational Research Collaboration (BRC149/NS/MH), the MRC UK GENFI grant (MR/ M023664/1), and The Bluefield Project. F.T. is supported by the Italian Ministry of Health (Grant NET‐2011‐02346784). L.C.J. and J.V.S. are supported by the Association for Frontotemporal Dementias Research Grant 2009, ZonMw Memorabel project number 733050103 and 733050813, and the Bluefield project. R.G. is supported by Italian Ministry of Health, Ricerca Corrente. J.L. was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany's Excellence Strategy within the framework of the Munich Cluster for Systems Neurology (EXC 2145; SyNergy ‐ ID 390857198). The Swedish contributors C.G., L.O., and C.A. were supported by grants from JPND Prefrontals Swedish Research Council (VR) 529‐2014‐7504, JPND GENFI‐PROX Swedish Research Council (VR) 2019‐02248, Swedish Research Council (VR) 2015‐ 02926, Swedish Research Council (VR) 2018‐02754, Swedish FTD Initiative‐Schorling Foundation, Swedish Brain Foundation, Swedish Alzheimer Foundation, Stockholm County Council ALF, Karolinska Institutet Doctoral Funding, and StratNeuro, Swedish Demensfonden, during the conduct of the study.info:eu-repo/semantics/publishedVersio