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1.
J Forensic Leg Med ; 105: 102716, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39002193

RESUMO

PURPOSE: To critically appraise and summarize the potential of linear and/or volumetric dimensions of the maxillary sinuses obtained with cone-beam and multi-slice computed tomography. METHODS: A bibliographic search was conducted in seven databases in August 2023. Cross-sectional retrospective studies using linear and volumetric measurements of the maxillary sinuses obtained with cone-beam and multi-slice computed tomography for sex estimation and presenting numerical estimation data were included. Narrative or systematic reviews, letters to the editor, case reports, laboratory studies in animals, and experimental studies were excluded. The critical appraisal and certainty of evidence were assessed using the guidelines described by Fowkes and Fulton and GRADE, respectively. RESULTS: A total of 656 studies were found, 32 of which were included. A total of 3631 individuals were analyzed and the overall sex estimation rate ranged from 54.9 % to 95 %. When compared with isolated measurements, combined linear measurements of the right and left maxillary sinuses, such as width, length, and height, provided a higher rate of sex estimation (54.9-95 %). In most of the studies (62.5 %), all measurements were higher in men than in women. Multiple methodological problems were found in the studies, especially distorting influences in 84.4 % of the answers. The certainty of evidence varied from very low to low. CONCLUSIONS: The combination of height, width, and length measurements of the right and left maxillary sinuses from cone-beam and multi-slice computed tomography can be useful in the estimation of sex of humans. Further primary studies are needed to increase the certainty of evidence. PROSPERO REGISTER: CRD42020161922.


Assuntos
Tomografia Computadorizada de Feixe Cônico , Seio Maxilar , Tomografia Computadorizada Multidetectores , Determinação do Sexo pelo Esqueleto , Humanos , Seio Maxilar/diagnóstico por imagem , Seio Maxilar/anatomia & histologia , Determinação do Sexo pelo Esqueleto/métodos , Antropologia Forense/métodos
2.
Nat Commun ; 15(1): 5620, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965208

RESUMO

Glutaminase (GLS) is directly related to cell growth and tumor progression, making it a target for cancer treatment. The RNA-binding protein HuR (encoded by the ELAVL1 gene) influences mRNA stability and alternative splicing. Overexpression of ELAVL1 is common in several cancers, including breast cancer. Here we show that HuR regulates GLS mRNA alternative splicing and isoform translation/stability in breast cancer. Elevated ELAVL1 expression correlates with high levels of the glutaminase isoforms C (GAC) and kidney-type (KGA), which are associated with poor patient prognosis. Knocking down ELAVL1 reduces KGA and increases GAC levels, enhances glutamine anaplerosis into the TCA cycle, and drives cells towards glutamine dependence. Furthermore, we show that combining chemical inhibition of GLS with ELAVL1 silencing synergistically decreases breast cancer cell growth and invasion. These findings suggest that dual inhibition of GLS and HuR offers a therapeutic strategy for breast cancer treatment.


Assuntos
Neoplasias da Mama , Proteína Semelhante a ELAV 1 , Glutaminase , Glutaminase/metabolismo , Glutaminase/genética , Glutaminase/antagonistas & inibidores , Proteína Semelhante a ELAV 1/metabolismo , Proteína Semelhante a ELAV 1/genética , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Feminino , RNA Mensageiro/metabolismo , RNA Mensageiro/genética , Regulação Neoplásica da Expressão Gênica , Processamento Alternativo , Proliferação de Células , Glutamina/metabolismo , Estabilidade de RNA
3.
Environ Toxicol Chem ; 43(8): 1855-1869, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38864594

RESUMO

It is crucial to investigate the effects of mixtures of contaminants on aquatic organisms, because they reflect what occurs in the environment. Cadmium (Cd) and nickel (Ni) are metals that co-occur in aquatic ecosystems, and information is scarce on their joint toxicity to Chlorophyceae using multiple endpoints. We evaluated the effects of isolated and combined Cd and Ni metals on multiple endpoints of the chlorophycean Raphidocelis subcapitata. The results showed that Cd inhibited cell density, increased reactive oxygen species (ROS) production (up to 308% at 0.075 mg L-1 of Cd), chlorophyll a (Chl a) fluorescence (0.050-0.100 mg L-1 of Cd), cell size (0.025-0.100 mg L-1 of Cd), and cell complexity in all concentrations evaluated. Nickel exposure decreased ROS production by up to 25% at 0.25 mg L-1 of Ni and Chl a fluorescence in all concentrations assessed. Cell density and oxygen-evolving complex (initial fluorescence/variable fluorescence [F0/Fv]) were only affected at 0.5 mg L-1 of Ni. In terms of algal growth, mixture toxicity showed antagonism at low doses and synergism at high doses, with a dose level change greater than the median inhibitory concentration. The independent action model and dose-level-dependent deviation best fit our data. Cadmium and Ni mixtures resulted in a significant increase in cell size and cell complexity, as well as changes in ROS production and Chl a fluorescence, and they did not affect the photosynthetic parameters. Environ Toxicol Chem 2024;43:1855-1869. © 2024 SETAC.


Assuntos
Cádmio , Microalgas , Níquel , Espécies Reativas de Oxigênio , Poluentes Químicos da Água , Níquel/toxicidade , Cádmio/toxicidade , Poluentes Químicos da Água/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Microalgas/efeitos dos fármacos , Clorofíceas/efeitos dos fármacos , Clorofila A , Clorofila/metabolismo
4.
Am J Physiol Endocrinol Metab ; 326(5): E681-E695, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38597829

RESUMO

Hypothalamic proopiomelanocortin (POMC) neurons are sensors of signals that reflect the energy stored in the body. Inducing mild stress in proopiomelanocortin neurons protects them from the damage promoted by the consumption of a high-fat diet, mitigating the development of obesity; however, the cellular mechanisms behind these effects are unknown. Here, we induced mild stress in a proopiomelanocortin neuron cell line by inhibiting Crif1. In proopiomelanocortin neurons exposed to high levels of palmitate, the partial inhibition of Crif1 reverted the defects in mitochondrial respiration and ATP production; this was accompanied by improved mitochondrial fusion/fission cycling. Furthermore, the partial inhibition of Crif1 resulted in increased reactive oxygen species production, increased fatty acid oxidation, and reduced dependency on glucose for mitochondrial respiration. These changes were dependent on the activity of CPT-1. Thus, we identified a CPT-1-dependent metabolic shift toward greater utilization of fatty acids as substrates for respiration as the mechanism behind the protective effect of mild stress against palmitate-induced damage of proopiomelanocortin neurons.NEW & NOTEWORTHY Saturated fats can damage hypothalamic neurons resulting in positive energy balance, and this is mitigated by mild cellular stress; however, the mechanisms behind this protective effect are unknown. Using a proopiomelanocortin cell line, we show that under exposure to a high concentration of palmitate, the partial inhibition of the mitochondrial protein Crif1 results in protection due to a metabolic shift warranted by the increased expression and activity of the mitochondrial fatty acid transporter CPT-1.


Assuntos
Carnitina O-Palmitoiltransferase , Proteínas de Ciclo Celular , Ácidos Graxos , Mitocôndrias , Animais , Camundongos , Carnitina O-Palmitoiltransferase/metabolismo , Carnitina O-Palmitoiltransferase/genética , Linhagem Celular , Ácidos Graxos/metabolismo , Hipotálamo/metabolismo , Hipotálamo/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Pró-Opiomelanocortina/metabolismo , Pró-Opiomelanocortina/genética , Espécies Reativas de Oxigênio/metabolismo , Proteínas de Ciclo Celular/antagonistas & inibidores , Proteínas de Ciclo Celular/metabolismo
5.
Artigo em Português | PAHO-IRIS | ID: phr-59157

RESUMO

[RESUMO]. Objetivo. Realizar uma revisão sistemática de publicações científicas que abordaram experiências de aplicação de métodos de estratificação para definir áreas de risco de transmissão de sarampo. Método. Foram selecionados artigos publicados nos idiomas inglês, português e espanhol em periódicos indexados nas bases SciELO, PubMed e LILACS. A busca utilizou os descritores risk assessment AND measles, sem delimitação de período. Foram excluídos editoriais, artigos de opinião, estudos observacionais de nível individual e publicações que não tratavam da aplicação de métodos de estratificação de áreas de risco de transmissão de sarampo. As informações de ano de publicação, autoria, país de realização do estudo, objetivo, escala geográfica, método utilizado, indicadores e limitações foram extraídas por meio de formulário. Resultados. Foram selecionados 13 artigos publicados entre 2011 e 2022 em nove países das seis regiões da Organização Mundial da Saúde (OMS). Desses, 10 tiveram como referência a ferramenta Measles Risk Assessment Tool desenvolvida pela OMS/Centers for Disease Control and Prevention. Apenas um estudo adaptou a ferramenta ao contexto local. Os indicadores utilizados para a estratificação de risco enfocaram uma combinação das dimensões imunidade populacional, qualidade dos sistemas de vigilância e situação epidemiológica. Como dificuldades para a estratificação de risco, destaca-se a produção sistemática de dados com cobertura e qualidade adequadas. Conclusão. As estratégias de estratificação do risco de transmissão de sarampo parecem ser ainda pouco difundidas, especialmente na escala local. Reitera-se a necessidade de estímulo à capacitação de recursos humanos para processamento e interpretação das análises de risco nas rotinas dos serviços de vigilância.


[ABSTRACT]. Objective. To perform a systematic review of scientific publications addressing the use of stratification methods to define risk areas for measles transmission. Method. Articles published in English, Portuguese, and Spanish in journals indexed in the SciELO, PubMed, and LILACS databases were selected. The search terms risk assessment AND measles were used without date limits. Editorials, opinion articles, individual-level observational studies, and publications that did not focus on the application of methods to stratify measles transmission risk areas were excluded. Year of publication, authorship, country where the study was performed, objective, geographic level of analysis, method used, indicators, and limitations were recorded in a data form. Results. Thirteen articles published between 2011 and 2022 in nine countries from the six World Health Organization (WHO) regions were selected. Of these, 10 referred to the Measles Risk Assessment Tool developed by the WHO/Centers for Disease Control and Prevention. Only one study adapted the tool to the local context. The risk stratification indicators used in the selected studies focused on a combination of the following dimensions: population immunity, quality of surveillance systems, and epidemiologic status. The systematic output of data with adequate quality and coverage was a noteworthy aspect hindering risk stratification. Conclusion. There seems to be limited dissemination of measles risk stratification strategies, especially at local levels. The need to train human resources to process and interpret risk analyses as part of the routine of surveillance services is emphasized.


[RESUMEN]. Objetivo. Realizar una revisión sistemática de las publicaciones científicas en las que se han abordado experiencias de aplicación de métodos de estratificación para definir las zonas de riesgo de transmisión del sarampión. Método. Se seleccionaron artículos publicados en español, inglés o portugués en revistas indizadas en las bases de datos SciELO, PubMed y LILACS. En la búsqueda se utilizaron los descriptores "risk assessment" y "measles", sin limitaciones en la fecha de publicación. Se excluyeron editoriales, artículos de opinión, estudios de observación de pacientes individuales y publicaciones que no tratasen de la aplicación de métodos de estratificación de zonas de riesgo de transmisión del sarampión. Se empleó un formulario para extraer la información sobre año de publicación, autoría, país de realización del estudio, objetivo, escala geográfica, método utilizado, indicadores y limitaciones. Resultados. Se seleccionaron 13 artículos publicados entre el 2011 y el 2022 en nueve países de las seis regiones de la Organización Mundial de la Salud (OMS). En 10 de ellos se utilizó como referencia la herramienta de evaluación del riesgo de sarampión creada por la OMS y los Centros para el Control y la Prevención de Enfermedades de Estados Unidos. Solamente en un estudio se adaptó la herramienta al contexto local. Los indicadores utilizados para la estratificación del riesgo se basaron en una combinación de las dimensiones de inmunidad poblacional, calidad de los sistemas de vigilancia y situación epidemiológica. Entre las dificultades de la estratificación del riesgo se destaca la de generación sistemática de datos con una cobertura y calidad adecuadas. Conclusiones. Las estrategias de estratificación del riesgo de transmisión del sarampión siguen sin estar, al parecer, muy extendidas, en especial a nivel local. Cabe reiterar la necesidad de fomentar la capacitación de recursos humanos para procesar e interpretar los análisis de riesgo en las operaciones habituales de los servicios de vigilancia.


Assuntos
Sarampo , Medição de Risco , Estudos Ecológicos , Vigilância em Saúde Pública , Sarampo , Medição de Risco , Estudos Ecológicos , Vigilância em Saúde Pública , Sarampo , Medição de Risco , Estudos Ecológicos , Vigilância em Saúde Pública
6.
Ecotoxicology ; 33(1): 104-118, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38236330

RESUMO

Aquatic organisms are exposed to several compounds that occur in mixtures in the environment. Thus, it is important to investigate their impacts on organisms because these combined effects can be potentiated. Cobalt (Co) and nickel (Ni) are metals that occur in the environment and are used in human activities. To the best of our knowledge, there are no studies that investigated the combined effects of these metals on a freshwater Chlorophyceae. Therefore, this study analyzed the isolated and combined effects of Co and Ni in cell density, physiological and morphological parameters, reactive oxygen species (ROS), carbohydrates and photosynthetic parameters of the microalga Raphidocelis subcapitata. Data showed that Co affected the cell density from 0.25 mg Co L-1; the fluorescence of chlorophyll a (Chl a) (0.10 mg Co L-1); ROS production (0.50 mg Co L-1), total carbohydrates and efficiency of the oxygen evolving complex (OEC) at all tested concentrations; and the maximum quantum yield (ΦM) from 0.50 mg Co L-1. Ni exposure decreased ROS and cell density (0.35 mg Ni L-1); altered Chl a fluorescence and carbohydrates at all tested concentrations; and did not alter photosynthetic parameters. Regarding the Co-Ni mixtures, our data best fitted the concentration addition (CA) model and dose-ratio dependent (DR) deviation in which synergism was observed at low doses of Co and high doses of Ni and antagonism occurred at high doses of Co and low doses of Ni. The combined metals affected ROS production, carbohydrates, ΦM, OEC and morphological and physiological parameters.


Assuntos
Clorofíceas , Microalgas , Poluentes Químicos da Água , Humanos , Níquel/toxicidade , Clorofila A/farmacologia , Cobalto/toxicidade , Espécies Reativas de Oxigênio , Metais , Carboidratos/farmacologia , Poluentes Químicos da Água/toxicidade , Poluentes Químicos da Água/análise
7.
Artigo em Português | MEDLINE | ID: mdl-38226153

RESUMO

Objective: To perform a systematic review of scientific publications addressing the use of stratification methods to define risk areas for measles transmission. Method: Articles published in English, Portuguese, and Spanish in journals indexed in the SciELO, PubMed, and LILACS databases were selected. The search terms risk assessment AND measles were used without date limits. Editorials, opinion articles, individual-level observational studies, and publications that did not focus on the application of methods to stratify measles transmission risk areas were excluded. Year of publication, authorship, country where the study was performed, objective, geographic level of analysis, method used, indicators, and limitations were recorded in a data form. Results: Thirteen articles published between 2011 and 2022 in nine countries from the six World Health Organization (WHO) regions were selected. Of these, 10 referred to the Measles Risk Assessment Tool developed by the WHO/Centers for Disease Control and Prevention. Only one study adapted the tool to the local context. The risk stratification indicators used in the selected studies focused on a combination of the following dimensions: population immunity, quality of surveillance systems, and epidemiologic status. The systematic output of data with adequate quality and coverage was a noteworthy aspect hindering risk stratification. Conclusion: There seems to be limited dissemination of measles risk stratification strategies, especially at local levels. The need to train human resources to process and interpret risk analyses as part of the routine of surveillance services is emphasized.


Objetivo: Realizar una revisión sistemática de las publicaciones científicas en las que se han abordado experiencias de aplicación de métodos de estratificación para definir las zonas de riesgo de transmisión del sarampión. Métodos: Se seleccionaron artículos publicados en español, inglés o portugués en revistas indizadas en las bases de datos SciELO, PubMed y LILACS. En la búsqueda se utilizaron los descriptores "risk assessment" y "measles", sin limitaciones en la fecha de publicación. Se excluyeron editoriales, artículos de opinión, estudios de observación de pacientes individuales y publicaciones que no tratasen de la aplicación de métodos de estratificación de zonas de riesgo de transmisión del sarampión. Se empleó un formulario para extraer la información sobre año de publicación, autoría, país de realización del estudio, objetivo, escala geográfica, método utilizado, indicadores y limitaciones. Resultados: Se seleccionaron 13 artículos publicados entre el 2011 y el 2022 en nueve países de las seis regiones de la Organización Mundial de la Salud (OMS). En 10 de ellos se utilizó como referencia la herramienta de evaluación del riesgo de sarampión creada por la OMS y los Centros para el Control y la Prevención de Enfermedades de Estados Unidos. Solamente en un estudio se adaptó la herramienta al contexto local. Los indicadores utilizados para la estratificación del riesgo se basaron en una combinación de las dimensiones de inmunidad poblacional, calidad de los sistemas de vigilancia y situación epidemiológica. Entre las dificultades de la estratificación del riesgo se destaca la de generación sistemática de datos con una cobertura y calidad adecuadas. Conclusión: Las estrategias de estratificación del riesgo de transmisión del sarampión siguen sin estar, al parecer, muy extendidas, en especial a nivel local. Cabe reiterar la necesidad de fomentar la capacitación de recursos humanos para procesar e interpretar los análisis de riesgo en las operaciones habituales de los servicios de vigilancia.

8.
Artigo em Inglês | MEDLINE | ID: mdl-37940483

RESUMO

OBJECTIVE: We evaluated the influence of an adjacent zirconium implant, tube current (mA), and a metal artifact reduction algorithm (MARA) on horizontal root fracture (HRF) diagnosis in cone beam computed tomography (CBCT). STUDY DESIGN: Nineteen teeth (9 with HRF, 10 without) were individually placed in a human maxilla. Scan volumes were acquired without and with a zirconium implant adjacent to the tooth at settings of 4, 8, and 10 mA, with MARA disabled and enabled, using a 5×5 cm field of view, 0.085-mm voxel size, and 90 kV. Four maxillofacial radiologists individually assessed the scans. Diagnostic metrics were compared by multiway analysis of variance (α=5%). Inter- and intraexaminer agreements for HRF diagnosis were evaluated with the weighted kappa test. RESULTS: Area under the receiver operating characteristic curve (AUC), sensitivity, and specificity were significantly lower in the presence of the implant (P≤.005). AUC values were higher in scans obtained with 8 and 10 mA compared with 4 mA (P=0.010), but 10 mA without MARA was better with the implant present. MARA did not significantly influence outcomes (P≥0.240). Inter- and intraexaminer agreements ranged from moderate to almost perfect. CONCLUSIONS: The presence of the zirconium implant impairs HRF detection. Settings of 8 or 10 mA improve HRF detection regardless MARA condition without the implant. With an adjacent implant, 10 mA without MARA is recommended to improve diagnostic performance.


Assuntos
Fraturas dos Dentes , Raiz Dentária , Humanos , Raiz Dentária/diagnóstico por imagem , Zircônio , Fraturas dos Dentes/diagnóstico por imagem , Artefatos , Tomografia Computadorizada de Feixe Cônico/métodos , Algoritmos
9.
J Oral Rehabil ; 51(3): 517-525, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37941125

RESUMO

BACKGROUND: There is no established protocol for the low doses of cone-beam computed tomography (CBCT) acquisition and filter application on the diagnosis of condylar morphological alterations. OBJECTIVES: The objective of the study was to evaluate the influence of voxel size and filter application on the diagnosis of condylar morphological alterations in CBCT using an ex vivo model. METHODS: CBCT scans of 36 temporomandibular joints were acquired using OP300 Maxio with voxel sizes of 0.085, 0.125 and 0.280 mm. Three radiologists evaluated the condyles in the CBCT volumes under three filter modes: no filter, '1x' sharpen filter and '2x' sharpen filter. The area under the ROC curve, sensitivity and specificity were calculated by comparing the evaluators' responses with the reference standard and compared among experimental groups using analysis of variance (ANOVA) (α = 5%). RESULTS: The area under the ROC curve, sensitivity and specificity were not affected by voxel size and filter application (p > .05). For osteophyte and flattening, there were more true-positive responses in smaller voxel size. For erosion, the increase of true- and false-positive responses occurred with a larger voxel size. Overall, there was a tendency to decrease true positives for osteophyte and erosion and increase false positives for flattening with the '2x' sharpen filter. CONCLUSIONS: The diagnosis of condylar morphological alterations assessed in this ex vivo analysis is not influenced by the voxel size and the application of the filters. However, attention is needed with the occurrence of false-positive diagnosis with a larger voxel size for erosion and '2x' sharpen filter for flattening.


Assuntos
Osteófito , Tomografia Computadorizada de Feixe Cônico Espiral , Humanos , Sensibilidade e Especificidade , Tomografia Computadorizada de Feixe Cônico/métodos , Osso e Ossos
10.
Int J Pharm ; 650: 123694, 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38081562

RESUMO

A swirling airflow is incorporated in several dry powder inhalers (DPIs) for effective powder de-agglomeration. This commonly requires the use of a flow-straightening grid in the DPI to reduce drug deposition loss caused by large lateral spreading of the emerging aerosol. Here, we propose a novel grid-free DPI design concept that improves the aerosol flow characteristics and reduces the aforementioned drug loss. The basis of this design is the implementation of a secondary airflow that swirls in the opposite direction (counter-swirl) to that of a primary swirling airflow. In-vitro deposition, computational fluid dynamics simulations and particle image velocimetry measurements are used to evaluate the counter-swirl DPI aerosol performance and flow characteristics. In comparison with a baseline-DPI that has only a primary swirling airflow, the counter-swirl DPI has 20% less deposition of the emitted drug dose in the induction port and pre-separator of a next generation impactor (NGI). This occurs as a result of the lower flow-swirl generated from the counter-swirl DPI which eliminates the axial reverse flow outside of the mouthpiece and substantially reduces lateral spreading in the exiting aerosol. Modifications to the counter-swirl DPI design were made to prevent drug loss from the secondary airflow tangential inlets, which involved the addition of wall perforations in the tangential inlets and the separation of the primary and secondary swirling airflows by an annular channel. These modified DPI devices were successful in that aspect but had higher flow-swirl than that in the counter-swirl DPI and thus had higher drug mass retained in the device and deposited in the induction port and pre-separator of the NGI. The fine particle fraction in the aerosols generated from all the counter-swirl-based DPIs and the baseline-DPI are found to be statistically similar to each other.


Assuntos
Inaladores de Pó Seco , Pulmão , Inaladores de Pó Seco/métodos , Tamanho da Partícula , Aerossóis , Administração por Inalação , Desenho de Equipamento , Pós
11.
Gene ; 898: 148069, 2024 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-38070788

RESUMO

PURPOSE: Li-Fraumeni Syndrome (LFS) is a rare cancer predisposing condition caused by germline pathogenic TP53 variants, in which core tumors comprise sarcomas, breast, brain and adrenocortical neoplasms. Clinical manifestations are highly variable in carriers of the Brazilian germline founder variant TP53 p.R337H, possibly due to the influence of modifier genes such as miRNA genes involved in the regulation of the p53 pathway. Herein, we investigated the potential phenotypic effects of two miRNA-related functional SNPs, pri-miR-34b/c rs4938723 and 3'UTR KRAS rs61764370, in a cohort of 273 LFS patients from Southern and Southeastern Brazil. METHODS: The genotyping of selected SNPs was performed by TaqMan® allelic discrimination and subsequently custom TaqMan® genotyping results were confirmed by Sanger sequencing in all SNP-positive LFS patients. RESULTS: Although the KRAS SNP showed no effect as a phenotype modulator, the rs4938723 CC genotype was significantly associated with development of LFS non-core tumors (first tumor diagnosis) in p.R337H carriers (p = 0.039). Non-core tumors were also more frequently diagnosed in carriers of germline TP53 DNA binding domain variants harboring the rs4938723 C variant allele. Previous studies described pri-miR-34b/c rs4938723 C as a risk allele for sporadic occurrence of thyroid and prostate cancers (non-core tumors of the LFS spectrum). CONCLUSION: With this study, we presented additional evidence about the importance of analyzing miRNA genes that could indirectly regulate p53 expression, and, therefore, may modulate the LFS phenotype, such as those of the miR-34 family.


Assuntos
Síndrome de Li-Fraumeni , MicroRNAs , Masculino , Humanos , Síndrome de Li-Fraumeni/genética , Síndrome de Li-Fraumeni/epidemiologia , Proteína Supressora de Tumor p53/genética , Regiões 3' não Traduzidas/genética , Proteínas Proto-Oncogênicas p21(ras)/genética , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença , MicroRNAs/genética , Mutação em Linhagem Germinativa , Fenótipo
12.
Rev. panam. salud pública ; 48: e1, 2024. tab, graf
Artigo em Português | LILACS-Express | LILACS | ID: biblio-1536669

RESUMO

RESUMO Objetivo. Realizar uma revisão sistemática de publicações científicas que abordaram experiências de aplicação de métodos de estratificação para definir áreas de risco de transmissão de sarampo. Métodos. Foram selecionados artigos publicados nos idiomas inglês, português e espanhol em periódicos indexados nas bases SciELO, PubMed e LILACS. A busca utilizou os descritores risk assessment AND measles, sem delimitação de período. Foram excluídos editoriais, artigos de opinião, estudos observacionais de nível individual e publicações que não tratavam da aplicação de métodos de estratificação de áreas de risco de transmissão de sarampo. As informações de ano de publicação, autoria, país de realização do estudo, objetivo, escala geográfica, método utilizado, indicadores e limitações foram extraídas por meio de formulário. Resultados. Foram selecionados 13 artigos publicados entre 2011 e 2022 em nove países das seis regiões da Organização Mundial da Saúde (OMS). Desses, 10 tiveram como referência a ferramenta Measles Risk Assessment Tool desenvolvida pela OMS/Centers for Disease Control and Prevention. Apenas um estudo adaptou a ferramenta ao contexto local. Os indicadores utilizados para a estratificação de risco enfocaram uma combinação das dimensões imunidade populacional, qualidade dos sistemas de vigilância e situação epidemiológica. Como dificuldades para a estratificação de risco, destaca-se a produção sistemática de dados com cobertura e qualidade adequadas. Conclusão. As estratégias de estratificação do risco de transmissão de sarampo parecem ser ainda pouco difundidas, especialmente na escala local. Reitera-se a necessidade de estímulo à capacitação de recursos humanos para processamento e interpretação das análises de risco nas rotinas dos serviços de vigilância.


ABSTRACT Objective. To perform a systematic review of scientific publications addressing the use of stratification methods to define risk areas for measles transmission. Method. Articles published in English, Portuguese, and Spanish in journals indexed in the SciELO, PubMed, and LILACS databases were selected. The search terms risk assessment AND measles were used without date limits. Editorials, opinion articles, individual-level observational studies, and publications that did not focus on the application of methods to stratify measles transmission risk areas were excluded. Year of publication, authorship, country where the study was performed, objective, geographic level of analysis, method used, indicators, and limitations were recorded in a data form. Results. Thirteen articles published between 2011 and 2022 in nine countries from the six World Health Organization (WHO) regions were selected. Of these, 10 referred to the Measles Risk Assessment Tool developed by the WHO/Centers for Disease Control and Prevention. Only one study adapted the tool to the local context. The risk stratification indicators used in the selected studies focused on a combination of the following dimensions: population immunity, quality of surveillance systems, and epidemiologic status. The systematic output of data with adequate quality and coverage was a noteworthy aspect hindering risk stratification. Conclusion. There seems to be limited dissemination of measles risk stratification strategies, especially at local levels. The need to train human resources to process and interpret risk analyses as part of the routine of surveillance services is emphasized.


RESUMEN Objetivo. Realizar una revisión sistemática de las publicaciones científicas en las que se han abordado experiencias de aplicación de métodos de estratificación para definir las zonas de riesgo de transmisión del sarampión. Métodos. Se seleccionaron artículos publicados en español, inglés o portugués en revistas indizadas en las bases de datos SciELO, PubMed y LILACS. En la búsqueda se utilizaron los descriptores "risk assessment" y "measles", sin limitaciones en la fecha de publicación. Se excluyeron editoriales, artículos de opinión, estudios de observación de pacientes individuales y publicaciones que no tratasen de la aplicación de métodos de estratificación de zonas de riesgo de transmisión del sarampión. Se empleó un formulario para extraer la información sobre año de publicación, autoría, país de realización del estudio, objetivo, escala geográfica, método utilizado, indicadores y limitaciones. Resultados. Se seleccionaron 13 artículos publicados entre el 2011 y el 2022 en nueve países de las seis regiones de la Organización Mundial de la Salud (OMS). En 10 de ellos se utilizó como referencia la herramienta de evaluación del riesgo de sarampión creada por la OMS y los Centros para el Control y la Prevención de Enfermedades de Estados Unidos. Solamente en un estudio se adaptó la herramienta al contexto local. Los indicadores utilizados para la estratificación del riesgo se basaron en una combinación de las dimensiones de inmunidad poblacional, calidad de los sistemas de vigilancia y situación epidemiológica. Entre las dificultades de la estratificación del riesgo se destaca la de generación sistemática de datos con una cobertura y calidad adecuadas. Conclusión. Las estrategias de estratificación del riesgo de transmisión del sarampión siguen sin estar, al parecer, muy extendidas, en especial a nivel local. Cabe reiterar la necesidad de fomentar la capacitación de recursos humanos para procesar e interpretar los análisis de riesgo en las operaciones habituales de los servicios de vigilancia.

13.
Res Sq ; 2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37502859

RESUMO

Obesity-related type II diabetes (diabesity) has increased global morbidity and mortality dramatically. Previously, the ancient drug salicylate demonstrated promise for the treatment of type II diabetes, but its clinical use was precluded due to high dose requirements. In this study, we present a nitroalkene derivative of salicylate, 5-(2-nitroethenyl)salicylic acid (SANA), a molecule with unprecedented beneficial effects in diet-induced obesity (DIO). SANA reduces DIO, liver steatosis and insulin resistance at doses up to 40 times lower than salicylate. Mechanistically, SANA stimulated mitochondrial respiration and increased creatine-dependent energy expenditure in adipose tissue. Indeed, depletion of creatine resulted in the loss of SANA action. Moreover, we found that SANA binds to creatine kinases CKMT1/2, and downregulation CKMT1 interferes with the effect of SANA in vivo. Together, these data demonstrate that SANA is a first-in-class activator of creatine-dependent energy expenditure and thermogenesis in adipose tissue and emerges as a candidate for the treatment of diabesity.

14.
Artigo em Inglês | MEDLINE | ID: mdl-36966237

RESUMO

This systematic review provides a comprehensive assessment of risk factors related to early sexual intercourse (ESI) among adolescents. We used PRISMA guidelines to identify eligible cohort studies published between January 1999 and December 2020. We searched on three databases: PubMed, Embase and LILACS. Studies were screened for quality and eligibility. Of 2787 identified studies, seven met our inclusion criteria. The studies examined a range of factors, which were organized into four dimensions - individual, family, social and environmental, and sociodemographic. Risk factors with strong associations for ESI were: adolescent and parental substance use, aggression and conduct disorders, family attachment, school achievement, family living situation, and maternal education. Three studies were birth cohorts. This review demonstrates the important roles of substance use, family attachment and academic factors in shaping adolescents' sexual behavior. A strength of this review is its focus on longitudinal studies, enabling exploration of exposures collected before initiation of sexual intercourse.

15.
Pharmaceuticals (Basel) ; 16(3)2023 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-36986530

RESUMO

Hyaluronic acid (HA) is a polymer with unique biological properties that has gained in interest over the years, with applications in pharmaceutical, cosmetic, and biomedical fields; however, its widespread use has been limited by its short half-life. Therefore, a new cross-linked hyaluronic acid was designed and characterized using a natural and safe cross-linking agent, such as arginine methyl ester, which provided improved resistance to enzymatic action, as compared to the corresponding linear polymer. The antibacterial profile of the new derivative was shown to be effective against S. aureus and P. acnes, making it a promising candidate for use in cosmetic formulations and skin applications. Its effect on S. pneumoniae, combined with its excellent tolerability profile on lung cells, also makes this new product suitable for applications involving the respiratory tract.

16.
J Environ Manage ; 335: 117539, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36841003

RESUMO

The achievement of the Sustainable Development Goals is being pursued worldwide. While energy production and consumption are to be oriented towards renewable energies, ecologically and socially sustainable agriculture is also a target for science and society. Due to the expansion of renewable energies, agricultural land in particular is the focus of various interest groups, from food production to energy production. In this interdisciplinary study, we show the opportunities and limits of joint synergies from the nexus of food production, energy production, energy consumption, biodiversity protection and social acceptance of renewable energies in a scenario. Biodiversity agriphotovoltaics, i.e. agriphotovoltaics in combination with biodiversity protection measures, such as flower strips, can make a valuable contribution to promoting biotope connectivity in addition to significant energy production. We show this in a GIS-based regional assessment for Lower Saxony in northern Germany. This rough spatial assessment is followed by a modelling of energy production and consumption during the cultivation of a characteristic agricultural field in the loess region of Lower Saxony. Our focus here is on the possibilities of using cable electricity or battery storage for carrying out the cultivation. In an accompanying survey of farmers regarding the use of agriphotovoltaics, we collected and evaluated their prior knowledge, experiences, and attitudes towards this technology. Finally, we show which advantages agriphotovoltaics and electrified agricultural machinery can also have for the sustainable transformation of agriculture and which challenges exist for a truly sustainable use of these technologies.


Assuntos
Agricultura , Conservação dos Recursos Naturais , Biodiversidade , Desenvolvimento Sustentável , Tecnologia
17.
Viruses ; 15(2)2023 02 13.
Artigo em Inglês | MEDLINE | ID: mdl-36851739

RESUMO

RNA viruses are known to induce a wide variety of respiratory tract illnesses, from simple colds to the latest coronavirus pandemic, causing effects on public health and the economy worldwide. Influenza virus (IV), parainfluenza virus (PIV), metapneumovirus (MPV), respiratory syncytial virus (RSV), rhinovirus (RhV), and coronavirus (CoV) are some of the most notable RNA viruses. Despite efforts, due to the high mutation rate, there are still no effective and scalable treatments that accompany the rapid emergence of new diseases associated with respiratory RNA viruses. Host-directed therapies have been applied to combat RNA virus infections by interfering with host cell factors that enhance the ability of immune cells to respond against those pathogens. The reprogramming of immune cell metabolism has recently emerged as a central mechanism in orchestrated immunity against respiratory viruses. Therefore, understanding the metabolic signature of immune cells during virus infection may be a promising tool for developing host-directed therapies. In this review, we revisit recent findings on the immunometabolic modulation in response to infection and discuss how these metabolic pathways may be used as targets for new therapies to combat illnesses caused by respiratory RNA viruses.


Assuntos
Infecções por Coronavirus , Coronavirus , Infecções por Enterovirus , Metapneumovirus , Vírus Sincicial Respiratório Humano , Humanos , RNA
18.
J Oral Rehabil ; 50(1): 1-11, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36271700

RESUMO

BACKGROUND: There is no established acquisition protocol based on scientific evidence for the acquisition of cone-beam computed tomography (CBCT) exams to evaluate the temporomandibular joint (TMJ). OBJECTIVES: To evaluate the influence of acquisition protocols and jaw positioning on the diagnostic accuracy of TMJ condylar morphological alterations (CMA), dimension, position and excursion. METHODS: Thirty-six TMJs on 18 dry skulls were imaged using a CBCT unit (OP300 Maxio, Instrumentarium, Tuusula, Finland) at two exposure settings (4.5 and 6.3 mA), three voxel resolutions (0.085, 0.125 and 0.280 mm), three jaw positions (concentric, anteriorised and posteriorised) and three jaw excursions (normoexcursion, hyperexcursion and hypoexcursion). The macroscopic anatomy examination and high-resolution CBCT images were used as ground truth for CMA. Twenty-five TMJs had at least one CMA with 11 healthy TMJs serving as controls. Three experienced oral and maxillofacial radiologists evaluated the parasagittal images for the presence of CMA, position and excursion and measured dimensions. The area under the ROC curve, sensitivity and specificity were calculated. Weighted Kappa (α = 0.05) was used to determine intra- and interexaminer reliability and comparisons between dependent variables analysed by Analysis of Variance at an a prior level of significance of 0.05. RESULTS: The agreement of the evaluation of the position and excursion with the reference standard was high, independent of the protocol (range, 0.75-0.91). Various combinations of acquisition protocols and jaw position did not influence the CMA evaluation. Erosion was overdiagnosed in protocols with larger voxel sizes and the detection of osteophytes greater in images with smaller voxel sizes. The anteroposterior dimension was greater in the open jaw position (p < .05). CONCLUSION: CBCT protocols using reduced radiation exposure from the CBCT machine evaluated in this study can be used to assess condylar morphology, dimension, position and excursion, without compromising diagnostic performances for these parameters.


Assuntos
Transtornos da Articulação Temporomandibular , Humanos , Transtornos da Articulação Temporomandibular/diagnóstico por imagem , Reprodutibilidade dos Testes , Articulação Temporomandibular/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico/métodos , Sensibilidade e Especificidade
19.
Oral Radiol ; 39(1): 53-58, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-35218461

RESUMO

OBJECTIVE: To evaluate whether the automatic exposure compensation in the presence of high-density materials can affect the measurement of alveolar bone level. METHODS: Thirty regions of seven dry skulls and six mandibles were radiographed with and without a high-density material, using two digital radiographic technologies: photostimulable phosphor plate (PSP, Digora Optime) and sensor (CMOS, Digora Toto), totaling 120 images. The distances from the cement-enamel junction to the alveolar bone crest were measured using cone-beam computed tomography (CBCT) images to represent the reference standard. The same measurements of alveolar bone level and the average of the pixel values of the image were evaluated on the radiographs. Paired t test compared the average pixel values and alveolar bone-level measurements between images with and without high-density material. One-way analysis of variance compared the difference between radiographic and CBCT measurements (α = 0.05). RESULTS: The high-density material reduced the pixel values in PSP (p = 0.002) and CMOS (p < 0.001) technologies, demonstrating the AEC functioning in both technologies. There was no difference in bone-level measurements between the images without and with the high-density material for both technologies (p ≥ 0.091), or between the tomographic and radiographic measurements (p ≥ 0.319). CONCLUSION: In the presence of high-density material, the automatic exposure compensation reduces the average pixel values of the images (i.e., images get darker), but does not influence the radiographic measurements of alveolar bone level.


Assuntos
Processo Alveolar , Radiografia Dentária Digital , Radiografia Dentária Digital/métodos , Processo Alveolar/diagnóstico por imagem , Tomografia Computadorizada de Feixe Cônico , Mandíbula/diagnóstico por imagem
20.
Minerva Obstet Gynecol ; 75(2): 109-116, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34825789

RESUMO

BACKGROUND: The aim of this study was to assess whether the presence of grade 3 placenta <36 weeks of pregnancy is associated with adverse perinatal outcomes. METHODS: Retrospective cohort study in which patients were separated into the following three groups: 1) grade 3 placenta <36 weeks, 2) grade 3 placenta >36 weeks, 3) no occurrence of grade 3 placenta throughout pregnancy. The χ2 and general linear model tests were used to compare adverse perinatal outcomes. Binary logistic regression model was used to estimate the odds ratio (OR) for adverse perinatal outcomes. Receiver operating characteristic (ROC) curve was used to determine the cut-off of the middle cerebral artery Pulsatility Index (MCA PI) in the detection of births <37 weeks in grade 3 placentas <36 weeks. RESULTS: Significant association was observed between grade 3 placenta <36 weeks and birth <37 weeks (P<0.001), birth weight <10th percentile (P=0.001), 5-min Apgar Score <7 (P=0.014), admission to neonatal intensive care unit (P<0.001), and fetal death (P=0.002). Grade 3 placenta <36 weeks was significant predictor for birth <37 weeks (OR: 2.6; 95% CI: 1.74-3.92), pre-eclampsia (OR: 1.8; 95% CI: 1.02-3.27), birth weight <10th percentile (OR: 2.1; 95% CI: 1.39-3.10), fetal death (OR: 5.6; 95% CI: 1.65-18.78), and composite perinatal outcomes (OR: 2.2; 95% CI: 1.51-3.17). The MCA PI showed an area under ROC curve of 0.641 (95% CI: 0.546-0.728) in the detection of births <37 weeks. CONCLUSIONS: Grade 3 placenta <36 weeks was associated with a higher prevalence of adverse perinatal outcomes.


Assuntos
Resultado da Gravidez , Ultrassonografia Pré-Natal , Gravidez , Recém-Nascido , Feminino , Humanos , Resultado da Gravidez/epidemiologia , Peso ao Nascer , Terceiro Trimestre da Gravidez , Estudos Retrospectivos , Idade Gestacional , Placenta , Morte Fetal
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