1,4-Butanediol intoxication: a case report

Poster apresentado no 56th Annual Meeting of The International Association of Forensic Toxicologists, Ghent (Bélgica), 2018Gamma-hidroxibutyric acid (GHB) is an endogenous compound with known action at the neural level. Its psychoactive effects led to an illicit use context including recreational purposes, muscle building effects in bodybuilders and drugs-facilitated crimes, specifically, in sexual assaults. Besides the use of the main compound, there are precursors, like Gammabutyrolactone (GBL) and 1,4-butanediol (1,4-BD), usually non controlled substances, allowing a much easier way to obtain the target-compound. The authors present the first reported intoxication case in Portugal with 1,4-Butanediol, including the quantification of GHB and GHB-GLUC in serum, by GC-MS/MS TQD. A male, 25 years old, entered in coma at the hospital emergency room, with the suspicion of an intoxication due to an unknown liquid ingestion. The forensic toxicology lab was asked to collaborate in order to identify the possible substance(s) involved and provide adequate treatment to the patient. The suspicious liquid and a serum sample were sent by the hospital and analysed by GC-MS-single quadrupole and GC-MS/MS TQD, respectively. A methodology including protein precipitation and GC-MS/MS TQD analysis was used to detect and quantify GHB and GHB-GLUC in serum. Toxicological analysis revealed the presence of 1,4-Butanediol in the liquid and GHB [171 mg/L] and GHB-GLUC [13,7 mg/L] in serum.The victim reverted the coma state with no neurological sequelae. This was the first detected case in Portugal with 1,4-Butanediol, suggesting that it is important to be aware that consumers have different options to acess illicit compounds, such as GHB. On the other hand, GHB-GLUC was identified and quantified for the first time in a real case sample, due to intoxication. This case highlights the importance of analyzing all samples for active compounds, percursors and metabolites that can lead to the main intoxication origin.N/

Quantification of GHB and GHB-GLUC in an 1,4-butanediol intoxication: a case report

Gamma-hydroxybutyric acid (GHB) is an endogenous compound with known action at the neural level. Its psychoactive effects led to an illicit use context including recreational purposes, muscle building effects in bodybuilders and drug-facilitated crimes, specifically in sexual assaults. Besides the misuse of the main compound, there are precursors like Gammabutyrolactone (GBL) and 1,4-butanediol (1,4-BD), usually non controlled substances, becoming a much easier way to obtain the target-compound. The authors present the first reported intoxication case in Portugal with 1,4-Butanediol, including the quantification of GHB and GHB-GLUC in serum, by GC-MS/MS TQD. A suspicious liquid and a serum sample were sent by an hospital ER and analysed by GC-MS-single quadrupole and GC-MS/MS TQD, respectively. A methodology including protein precipitation and GC-MS/MS TQD analysis was used to detect and quantify GHB and GHB-GLUC in serum. Toxicological analysis revealed the presence of 1,4-Butanediol in the liquid and GHB [171 mg/L] and GHB-GLUC [13,7 mg/L] in serum. The victim reverted the coma with no neurological sequelae. This was the first detected case, in Portugal, with 1,4-Butanediol, suggesting that it is important to be aware that consumers have different options to obtain illicit compounds, such as GHB. On the other hand, GHB-GLUC was identified and quantified for the first time in a real case, due to intoxication. This case highlights the importance of analysing all samples for active compounds, precursors and metabolites that can lead to the main intoxication origin.publishe

Intoxicação por 1,4-Butanediol: descrição de um caso

Apresentação oral no 16ª congresso Nacional de Medicina Legal e Ciências Forenses, Coimbra, 2017Introdução: O Ácido gamahidroxibutírico (GHB) é um composto endógeno, com ação conhecida em diversas áreas cerebrais. O seu uso ilícito inclui objetivos recreativos, o incremento da massa muscular, e como substância facilitadora de abuso sexual. A disponibilidade de dois percursores, nomeadamente a Gamabutirolactona (GBL) e o 1,4-butanediol (1,4-BD), os quais não se encontram alocados à lista de substâncias controladas, contrariamente ao próprio GHB, torna ainda mais fácil a sua obtenção e consumo. Material e Métodos: Um indivíduo do sexo masculino, com 25 anos, deu entrada no Serviço de Urgência de um Hospital Central, em estado de coma (CGS 7), com suspeita de intoxicação por ingestão de líquido, o qual o acompanhava. O SQTF recebeu uma amostra de soro e o referido líquido para análise. O procedimento analítico incluiu a análise direta do líquido por GC-MS, para identificação do mesmo, e a análise da amostra de soro através de extração líquido-líquido das substâncias de interesse, seguida da utilização de técnica de análise instrumental hifenada, nomeadamente um cromatógrafo de gases GC-450 acoplado a um espectrómetro de massa do tipo triplo quadrupolo MS-300 (Bruker). Resultados e Discussão: A análise do líquido permitiu a identificação da substância 1,4-Butanediol. A análise da amostra de soro permitiu a determinação de GHB numa concentração de 171 mg/L. Paralelamente, foi detetada, pela primeira vez, a presença do metabolito GHB-Glucuronizado (GHB-GLUC), metabolito este recentemente descrito. Conclusão: A informação hospitalar recebida indica que o indivíduo reverteu o estado comatoso, sem sugestão de sequelas neurológicas. Os dados clínicos e os resultados laboratoriais confirmam o diagnóstico de intoxicação por 1,4-Butanediol, detetado pela primeira vez no nosso país.N/

Methodological Quality of Systematic Reviews Addressing Orthodontic Interventions: Methodological Study

Objective: To assess the methodological quality and characteristics of systematic reviews (SRs) of interventional studies in orthodontics and assess how the certainty of the evidence is reported using the GRADE approach. Material and Methods: Six electronic databases were searched, followed by a hand search of the reference lists of eligible studies (PROSPERO #CRD42020180852). The required study design was randomized and nonrandomized studies of interventions published between January 2019 and May 2020. The Assessing the Methodological Quality of Systematic Reviews (AMSTAR 2) tool was used for the quality appraisal of the included SRs. Paired reviewers independently screened the studies, extracted data, and appraised the methodological quality. Results: The study included 46 SRs; 19.5% had moderate to high methodological quality, and the remaining had low to critically low methodological quality. Fifty-four percent of the reviews assessed the certainty of evidence using the GRADE approach, and 34.8% followed all GRADE criteria. Conclusion: Most reviews had a good judgment of the AMSTAR2 items, although some critical items contributed to decreased overall quality. Half of the reviews used the GRADE approach to assess the certainty of the evidence, and this approach should be included in future systematic reviews of interventions

Promoção à saúde da mulher: desmistificando o climatério / Women's health promotion: demystifying the climacteric

O climatério é definido pela Organização Mundial da Saúde como uma fase de transição entre o período reprodutivo e o não reprodutivo da vida da mulher, que compreende a faixa etária de 35 a 65 anos. Esta pesquisa objetivou analisar a vivência das mulheres que fazem parte da nossa microárea em relação ao entendimento e exercício da sexualidade durante o período do climatério. Foi realizada uma pesquisa de campo descritiva exploratória de abordagem quantitativa e de intervenção na população feminina de 35 a 65 anos adscrita da Unidade de Atenção Primária à Saúde (UAPS) Jardim Paraíso, no ano de 2018. Participaram 34 mulheres e foi utilizado o Índice Menopausal de Blatt & Kupperman (IMBK); e o Quociente Sexual - versão feminina (QS-F) com posterior avaliação dos resultados e orientação das pacientes. A média de idade da amostra foi 54 anos; as manifestações de intensidade moderada foram as mais prevalentes e no desempenho sexual prevaleceu o padrão “Regular”. A intensidade dos sintomas no climatério pode afetar o desempenho sexual da mulher nesse período e o planejamento de ações promovidas pelos serviços de saúde deve estar voltado à educação e incentivo à mudanças no estilo de vida. 

Experimental Hyperthyroidism Decreases Gene Expression and Serum Levels of Adipokines in Obesity

Aims. To analyze the influence of hyperthyroidism on the gene expression and serum concentration of leptin, resistin, and adiponectin in obese animals. Main Methods. Male Wistar rats were randomly divided into two groups: control (C)—fed with commercial chow ad libitum—and obese (OB)—fed with a hypercaloric diet. After group characterization, the OB rats continued receiving a hypercaloric diet and were randomized into two groups: obese animals (OB) and obese with 25 μg triiodothyronine (T3)/100 BW (OT). The T3 dose was administered every day for the last 2 weeks of the study. After 30 weeks the animals were euthanized. Samples of blood and adipose tissue were collected for biochemical and hormonal analyses as well as gene expression of leptin, resistin, and adiponectin. Results. T3 treatment was effective, increasing fT3 levels and decreasing fT4 and TSH serum concentration. Administration of T3 promotes weight loss, decreases all fat deposits, and diminishes serum levels of leptin, resistin, and adiponectin by reducing their gene expression. Conclusions. Our results suggest that T3 modulate serum and gene expression levels of leptin, resistin, and adiponectin in experimental model of obesity, providing new insights regarding the relationship between T3 and adipokines in obesity

Frequency of TERT promoter mutations in human cancers

Reactivation of telomerase has been implicated in human tumorigenesis, but the underlying mechanisms remain poorly understood. Here we report the presence of recurrent somatic mutations in the TERT promoter in cancers of the central nervous system (43%), bladder (59%), thyroid (follicular cell-derived, 10%) and skin (melanoma, 29%). In thyroid cancers, the presence of TERT promoter mutations (when occurring together with BRAF mutations) is significantly associated with higher TERT mRNA expression, and in glioblastoma we find a trend for increased telomerase expression in cases harbouring TERT promoter mutations. Both in thyroid cancers and glioblastoma, TERT promoter mutations are significantly associated with older age of the patients. Our results show that TERT promoter mutations are relatively frequent in specific types of human cancers, where they lead to enhanced expression of telomerase.We thank to Mrs Mafalda Rocha for the excellent technical support in the sequencing work. This work was partially supported by the Portuguese Science and Technology Foundation (FCT) through BPD (SFRH/BPD/85249/2012 to H. P.), PhD (SFRH/BD/81940/2011 to J.V. and SFRH/BD/79135/2011 to A. A.) and BI grants, and the grant through the Program Ciencia 2008 (J.L.) and the project (PIC/IC/83037/2007). Further funding was obtained from the project 'Microenvironment, metabolism and cancer' partially supported by Programa Operacional Regional do Norte (ON.2-O Novo Norte), under the Quadro de Referencia Estrategico Nacional (QREN), and through the Fundo Europeu de Desenvolvimento Regional (FEDER). IPATIMUP is an associate laboratory of the Portuguese Ministry of Science, Technology and Higher Education and is partially supported by the FCT

IMPACTOS DA EXPLORAÇÃO FLORESTAL NA ESTRUTURA E NA COMPOSIÇÃO FLORÍSTICA DA VEGETAÇÃO REMANESCENTE EM ÁREA MANEJADA NA FLORESTA NACIONAL DO TAPAJÓS, BELTERRA, PARÁ

The present work was developed in an area of 1600 ha located in the Floresta Nacional do Tapajós, Belterra- Pará. Its objective is to analyze the impacts such as damage to remaining trees caused by logging from community management in the area caused by logging from community management in the area. The sample consisted of 8 permanent plots (PP) of 0.25 hectares (50m x 50m), divided into 25 sub plots of 10m x 10m. In this work, measurements of the permanent plots were carried out at two different times, the first before any intervention in the forest in the year 2016 and the second one year after the intervention to follow its effect, in the year 2017. The floristic diversity maintained without significant difference between the evaluated years ranging from 153 to 150 species before and after the exploitation respectively. It should be noted that the mild damages affected few individuals when compared to those that did not suffer any damage and as regards the structure of the forest, this was little affected according to the diversity indices of Shannon- Wiener (H') and the equability index (E).KEYWORDS: Amazon rainforest, Disturbance, Growth dynamics.El presente trabajo fue desarrollado en un área de 1600 ha situada en el Floresta Nacional do Tapajós, Belterra- Pará. Tiene por objetivo, analizar los impactos causados por la explotación maderera como, daños a los árboles remanentes, causados por la explotación maderera proveniente del manejo comunitario en el área proveniente del manejo comunitario en el área. Entre las clases de tamaño, sólo se observó la clase de árbol. La muestra consistía en 8 parcelas permanentes (PP) de 0,25 hectáreas (50m x 50m), divididas en 25 subparcelas de 10m x 10 m. En este trabajo se realizaron mediciones de las parcelas permanentes en dos momentos distintos, el primero antes de cualquier intervención en el bosque en el año 2016 y, la segunda un año después de la intervención para acompañar su efecto, en el año 2017. La diversidad florística mantuvo sin diferencia significativa entre los años evaluados que varían de 153 a 150 especies antes y después de la explotación respectivamente. Destaca-se que los daños leves y severos acometieron a pocos individuos cuando comparados con los que no sufrieron daño alguno y en lo que concierne a la estructura del bosque, ésta fue poco afectada conforme a las indigencias de diversidad de Shannon- Wiener (H ') y el índice de equidad (E).PALABRAS CLAVE: Dinámica de crecimiento, Perturbación, Selva amazónica.O presente trabalho foi desenvolvido em uma área de 1.600 ha situada na Floresta Nacional do Tapajós localizada em Belterra- Pará. Tem por objetivo, analisar os impactos, bem como, danos às árvores remanescentes, causados pela exploração madeireira proveniente do manejo comunitário na área. A amostra consistia em 8 parcelas permanentes (PP) de 0,25 hectares (50m x 50m), divididas em 25 sub parcelas de 10 m x 10 m. Neste trabalho, foram realizadas mensurações das parcelas permanentes em dois momentos distintos, o primeiro antes de qualquer intervenção na floresta no ano de 2016 e, a segunda um ano após a intervenção para acompanhar o seu efeito, no ano de 2017. A diversidade florística manteve-se sem diferença significativa entre os anos avaliados variando de 153 para 150 espécies antes e após a exploração respectivamente. Destaca-se que os danos leves acometeram poucos indivíduos quando comparados com os que não sofreram dano algum e no que concerne à estrutura da floresta, esta foi pouco afetada conforme os índices de diversidade de Shannon-Wiener (H') e o índice de equabilidade (E).PALAVRAS CHAVE: Dinâmica de crescimento, Floresta Amazônica, Perturbação.

BANDA ORTODÔNTICA COMO POSSIBILIDADE RESTAURADORA PARA GRANDES DESTRUIÇÕES CORONÁRIAS EM ODONTOPEDIATRIA: RELATO DE CASO

The aim of this report was to describe a clinical case involving the cementation of an orthodontic band as a restorative option for significant coronal destruction in primary molars. Data were collected from the patient'smedical records and photographic records taken during thethree sessions: consultation, treatment, and follow-up. A 4-year-old female patient presented with extensive coronal destruction caused by a deep carious lesion. It wasdetermined that the best course of action for this case would be to cement an orthodontic band to preserve theremaining teeth. Thus, this study confirms that thecementation of an orthodontic band on crowns ofdeciduous teeth that are highly demineralized is analternative for rehabilitative treatment in early childhoodEl objetivo de este estudio es reportar un caso clínico de cementación con banda ortodóncica como opción restauradora para la destrucción coronaria mayor en molares primarios. Los datos se obtuvieron de las historias clínicas de los pacientes y de los registros fotográficos tomados durante las tres sesiones, incluyendo: consulta, tratamiento y seguimiento.  La paciente de 4 años de edad tenía una extensa destrucción coronaria causada por una lesión de caries profunda. Se consideró que la mejor opción para el caso sería la cementación de la banda de ortodoncia con el fin de preservar el resto dental. Así, se pudo confirmar en la descripción de este estudio que la cementación de la banda ortodóncica en coronas de dientes deciduos que se encuentran bastante desmineralizados es una alternativa para el tratamiento rehabilitador en la primera infancia. O objetivo deste trabalho é relatar um caso clínico de cimentação de banda ortodôntica como opção restauradora para grandes destruições coronárias em molares decíduos. Os dados foram obtidos por meio do prontuário da paciente e dos registros fotográficos realizados durante as  três sessões, incluindo: consulta, tratamento e acompanhamento.  A paciente do sexo feminino de 04 anos, apresentava extensa destruição coronária causada por lesão cariosa profunda. Foi ponderado que a melhor opção para o caso seria a cimentação da banda ortodôntica de modo a preservar o remanescente dentário. Dessa forma, pôde ser confirmado na descrição desse estudo que a  cimentação da banda ortodôntica em coroas de dentes decíduos bastante desmineralizadas é uma alternativa de tratamento reabilitador na primeira infância.O objetivo deste trabalho é relatar um caso clínico de cimentação de banda ortodôntica como opção restauradora para grandes destruições coronárias em molares decíduos. Os dados foram obtidos por meio do prontuário da paciente e dos registros fotográficos realizados durante as  três sessões, incluindo: consulta, tratamento e acompanhamento.  A paciente do sexo feminino de 04 anos, apresentava extensa destruição coronária causada por lesão cariosa profunda. Foi ponderado que a melhor opção para o caso seria a cimentação da banda ortodôntica de modo a preservar o remanescente dentário. Dessa forma, pôde ser confirmado na descrição desse estudo que a  cimentação da banda ortodôntica em coroas de dentes decíduos bastante desmineralizadas é uma alternativa de tratamento reabilitador na primeira infância

TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas

Context: Telomerase promoter mutations (TERT) were recently described in follicular cell-derived thyroid carcinomas (FCDTC) and seem to be more prevalent in aggressive cancers. Objectives: We aimed to evaluate the frequency of TERT promoter mutations in thyroid lesions and to investigate the prognostic significance of such mutations in a large cohort of patients with differentiated thyroid carcinomas (DTCs). Design: This was a retrospective observational study. Setting and Patients: We studied 647 tumors and tumor-like lesions. A total of 469 patients with FCDTC treated and followed in five university hospitals were included. Mean follow-up (±SD) was 7.8 ± 5.8 years. Main Outcome Measures: Predictive value of TERT promoter mutations for distant metastasization, disease persistence at the end of follow-up, and disease-specific mortality. Results: TERT promoter mutations were found in 7.5% of papillary carcinomas (PTCs), 17.1% of follicular carcinomas, 29.0% of poorly differentiated carcinomas, and 33.3% of anaplastic thyroid carcinomas. Patients with TERT-mutated tumors were older (P < .001) and had larger tumors (P = .002). In DTCs, TERT promoter mutations were significantly associated with distant metastases (P < .001) and higher stage (P < .001). Patients with DTC harboring TERT promoter mutations were submitted to more radioiodine treatments (P = .009) with higher cumulative dose (P = .004) and to more treatment modalities (P = .001). At the end of follow-up, patients with TERT-mutated DTCs were more prone to have persistent disease (P = .001). TERT promoter mutations were significantly associated with disease-specific mortality [in the whole FCDTC (P < .001)] in DTCs (P < .001), PTCs (P = .001), and follicular carcinomas (P < .001). After adjusting for age at diagnosis and gender, the hazard ratio was 10.35 (95% confidence interval 2.01–53.24; P = .005) in DTC and 23.81 (95% confidence interval 1.36–415.76; P = .03) in PTCs. Conclusions: TERT promoter mutations are an indicator of clinically aggressive tumors, being correlated with worse outcome and disease-specific mortality in DTC. TERT promoter mutations have an independent prognostic value in DTC and, notably, in PTC.We acknowledge GENZYME for funding our work through a research project. This study was supported by the Portuguese Foundation for Science and Technology through PhD Grant SFRH/BD/81940/2011 (to J.V.); PhD Grant SFRH/BD/87887/2012 (to C.T.); PhD Grant SFRH/BD/79135/2011 (to A.A.); and the Scientific Investigation Project PIC/IC/83037/2007. Further funding was obtained from the project “Microenvironment, Metabolism and Cancer,” partially supported by Programa Operacional Regional do Norte (ON.2-O Novo Norte), under the Quadro de Referência Estratégico Nacional, and through the European Regional Development Fund. The work of J.M.C.-T. was supported by Grant PI12/00749-FEDER from the Instituto de Salud Carlos III, the Ministry of Economy and Competitiveness (Madrid, Spain). The Institute of Molecular Pathology and Immunology of the University of Porto (IPATIMUP) is an associate laboratory of the Portuguese Ministry of Science, Technology, and Higher Education, which is partially supported by the Foundation for Science and Technology