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1.
Int J Legal Med ; 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38689177

RESUMO

BACKGROUND: The increased use of virtual bone images in forensic anthropology requires a comprehensive study on the observational errors between dry bones and CT reconstructions. Here, we focus on the consistency of nonmetric sex estimation traits on the human skull. MATERIALS AND METHODS: We scored nine nonmetric traits on dry crania and mandibles (n = 223) of archaeological origin and their CT reconstructions. Additionally, we 3D surface scanned a subsample (n = 50) and repeated our observations. Due to the intricate anatomy of the mental eminence, we split it into two separate traits: the bilateral mental tubercles and the midsagittal mental protuberance. We provide illustrations and descriptions for both these traits. RESULTS: We obtained supreme consistency values between the CT and 3D surface modalities. The most consistent cranial traits were the glabella and the supraorbital margin, followed by the nuchal crest, zygomatic extension, mental tubercles, mental protuberance, mental eminence, mastoid process and ramus flexure, in descending order. The mental tubercles show higher consistency scores than the mental eminence and the mental protuberance. DISCUSSION: The increased interchangeability of the virtual modalities with each other as compared to the dry bone modality could be due to the lack of tactility on both the CT and surface scans. Moreover, tactility appears less essential with experience than a precise trait description. Future studies could revolve around the most consistent cranial traits, combining them with pelvic traits from a previous study, to test for accuracy.

2.
J Clin Periodontol ; 51(6): 680-690, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38385991

RESUMO

AIM: To evaluate site-related changes in periodontal pocket depth (PPD) after non-surgical periodontal therapy and to identify predictors for PPD changes in a retrospective patient data analysis. MATERIALS AND METHODS: PPD, clinical attachment level, bleeding on probing, tooth mobility (TM), furcation involvement (FI), abutment status, adherence to supportive periodontal care (SPC) and SPC follow-ups were obtained from fully documented patient data before periodontal therapy (baseline, T0), after active periodontal therapy (APT, T1) and during SPC (T2). PPD changes were classified into deteriorated or unchanged/improved at the site level. Multi-level logistic regression analysis was performed to identify factors influencing PPD changes during SPC. RESULTS: This retrospective study included 51 females and 65 males (mean T0 age: 54.8 ± 10.1 years, 25 smokers, 12 diabetics) suffering from Stage III/IV periodontitis. Evaluation outcome: T0/16,044 sampling sites/2674 teeth; T1/15,636/2606; T2/14,754/2459. During 9.0 ± 2.3 years SPC, PPD decreased (-1.33 ± 0.70 mm) by 21.8% of the sites, remained unchanged by 41.4% and increased (1.40 ± 0.78 mm) by 36.8%. Distopalatal FI (p < .001, odds ratio [OR]: 0.252, 95% confidence interval [CI] for OR: 0.118-0.540), residual pockets (p < .001, OR: 0.503, 95% CI: 0.429-0.590) and TM Degrees I-III (Degree I: p = .002, OR: 0.765, 95% CI: 0.646-0.905; Degree II: p = .006, OR: 0.658, 95% CI: 0.489-0.886; Degree III: p = .023, OR: 0.398, 95% CI: 0.180-0.879) correlated significantly with increasing PPD. CONCLUSIONS: Over 75% of PPD remained unchanged or increased during SPC. Distopalatal FI, TM Degrees I-III and residual pockets after APT lead to worsening of periodontal pockets.


Assuntos
Bolsa Periodontal , Humanos , Masculino , Feminino , Estudos Retrospectivos , Pessoa de Meia-Idade , Bolsa Periodontal/terapia , Idoso , Mobilidade Dentária , Adulto , Índice Periodontal , Perda da Inserção Periodontal/terapia , Defeitos da Furca/terapia , Progressão da Doença
3.
Cell Commun Signal ; 21(1): 136, 2023 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-37316874

RESUMO

The dimerization of RAF kinases represents a key event in their activation cycle and in RAS/ERK pathway activation. Genetic, biochemical and structural approaches provided key insights into this process defining RAF signaling output and the clinical efficacy of RAF inhibitors (RAFi). However, methods reporting the dynamics of RAF dimerization in living cells and in real time are still in their infancy. Recently, split luciferase systems have been developed for the detection of protein-protein-interactions (PPIs), incl. proof-of-concept studies demonstrating the heterodimerization of the BRAF and RAF1 isoforms. Due to their small size, the Nanoluc luciferase moieties LgBiT and SmBiT, which reconstitute a light emitting holoenzyme upon fusion partner promoted interaction, appear as well-suited to study RAF dimerization. Here, we provide an extensive analysis of the suitability of the Nanoluc system to study the homo- and heterodimerization of BRAF, RAF1 and the related KSR1 pseudokinase. We show that KRASG12V promotes the homo- and heterodimerization of BRAF, while considerable KSR1 homo- and KSR1/BRAF heterodimerization already occurs in the absence of this active GTPase and requires a salt bridge between the CC-SAM domain of KSR1 and the BRAF-specific region. We demonstrate that loss-of-function mutations impairing key steps of the RAF activation cycle can be used as calibrators to gauge the dynamics of heterodimerization. This approach identified the RAS-binding domains and the C-terminal 14-3-3 binding motifs as particularly critical for the reconstitution of RAF mediated LgBiT/SmBiT reconstitution, while the dimer interface was less important for dimerization but essential for downstream signaling. We show for the first time that BRAFV600E, the most common BRAF oncoprotein whose dimerization status is controversially portrayed in the literature, forms homodimers in living cells more efficiently than its wildtype counterpart. Of note, Nanoluc activity reconstituted by BRAFV600E homodimers is highly sensitive to the paradox-breaking RAFi PLX8394, indicating a dynamic and specific PPI. We report the effects of eleven ERK pathway inhibitors on RAF dimerization, incl. third-generation compounds that are less-defined in terms of their dimer promoting abilities. We identify Naporafenib as a potent and long-lasting dimerizer and show that the split Nanoluc approach discriminates between type I, I1/2 and II RAFi. Video Abstract.


Assuntos
Proteínas Proto-Oncogênicas B-raf , Dimerização , Luciferases
4.
Int J Legal Med ; 137(6): 1839-1852, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37336820

RESUMO

BACKGROUND: Computed tomography (CT) scans are a convenient means to study 3D reconstructions of bones. However, errors associated with the different nature of the observation, e.g. visual and tactile (on dry bone) versus visual only (on a screen) have not been thoroughly investigated. MATERIALS AND METHODS: We quantified the errors between modalities for sex estimation protocols of nonmetric (categorical and ordinal) and metric data, using 200 dry pelves of archaeological origin and the CT reconstructions of the same bones. In addition, we 3D surface scanned a subsample of 39 pelves to compare observations with dry bone and CT data. We did not focus on the sex estimation accuracy but solely on the consistency of the scoring, hence, the interchangeability of the modalities. RESULTS: Metric data yielded the most consistent results. Among the nonmetric protocols, ordinal data performed better than categorical data. We applied a slightly modified description for the trait with the highest errors and grouped the traits according to consistency and availability in good, intermediate, and poor. DISCUSSION: The investigated modalities were interchangeable as long as the trait definition was not arbitrary. Dry bone (gold standard) performed well, and CT and 3D surface scans performed better. We recommend researchers test their affinity for using virtual modalities. Future studies could use our consistency analysis and combine the best traits, validating their accuracy on various modalities.

5.
Neurosurg Rev ; 46(1): 16, 2022 12 14.
Artigo em Inglês | MEDLINE | ID: mdl-36513848
6.
Biology (Basel) ; 11(5)2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35625394

RESUMO

The increasing importance of trauma analysis by means of postmortem computed tomography (PMCT) is insufficiently reflected in forensic curricula, nor are best practice manuals available. We attempt to detect sharp force bone lesions on PMCT of closed forensic cases with the aims of assessing errors and pointing out patterns in anatomical location and manner of death (MOD). We investigated 41 closed sharp force fatality cases, with available PMCT and forensic reports. Two observers with different radiological training assessed the lesions on PMCT scans (2D and 3D) for comparison with the reports. Between 3% (suicides) and 15.3% (homicides) of sharp force injuries caused visible bone lesions. While our observations were repeatable, each forensic investigation left a similar number of bone lesions undetected. Injury patterns differed between MOD, with thoracic bone lesions being most frequent overall. Soft tissue injury location varied between the MOD. Associations between MOD and age as well as number of injuries were significant. The detection of bone lesions on PMCT for untrained forensic specialists is challenging, curricula and pertinent manuals are desirable. With the low frequency of bone lesions compared to soft tissue injuries, we should be aware when analyzing decomposed bodies.

7.
Medicina (B Aires) ; 81(4): 602-610, 2021.
Artigo em Espanhol | MEDLINE | ID: mdl-34453803

RESUMO

Self-efficacy is the confidence in one's own abilities to avoid smoking in situations that can trigger desire. It is considered an important predictor of relapses. In Argentina there is no valid instrument to evaluate it. The objective of this article was to adapt and validate a Spanish version (in local Argentinean language) of the Self-Efficacy/Temptation Scale. The transcultural adaptation of the scale was carried out: translation, review by a committee of experts, reverse translation, new review and test of the questionnaire. Reliability (reproducibility, stability and internal consistency) and validity were then evaluated. We performed a factor analysis of main components with Varimax rotation with data from a sample of 200 smokers. A culturally and linguistically adapted version of the instrument was obtained, with inter-observer reliability of Intraclass Correlation Coefficient (ICC) = 0.90 and stability of ICC = 0.77. The internal consistency analysis yielded a global Crombach a = 0.93 and 0.85 for versions of 20 and 9 items, respectively. In the domain of Positive Affections a = 0.82 and a = 0.89; Negative Affections a = 0.89 and a = 0.90 and for Craving a = 0.84 and a = 0.75, also respectively for the two versions. In the exploratory factor analysis, three factors were identified that explained 95% of the variance of the questionnaire in its extensive version and 69% in its short version. A reliable and valid Argentinean version of the Self-Efficacy/Temptation Scale was obtained, to be applied to smokers.


La autoeficacia es la confianza en las propias habilidades para evitar fumar en situaciones quepuedan desencadenar el deseo. Se la considera un importante predictor de recaídas. En Argentina no existe un instrumento válido que permita evaluarla. El objetivo del presente trabajo fue adaptar y validar una versión en español (Argentina) de la Escala de Autoeficacia/Tentaciones. Se llevó a cabo la adaptación transcultural de la escala: traducción, revisión por un comité de expertos, traducción inversa, nueva revisión y prueba del cuestionario. Luego se evaluaron la confiabilidad (reproducibilidad, estabilidad y consistencia interna) y la validez. Se realizó un análisis factorial de componentes principales con rotación Varimax con datos de una muestra de 200 pacientes fumadores. Se obtuvo una versión cultural y lingüísticamente adaptada del instrumento, con una confiabilidad interobservador evaluada con el Coeficiente de Correlación Intraclase (ICC) = 0.90 y estabilidad de ICC = 0.77. En el análisis de la consistencia interna se obtuvo un a de Crombach global de 0.93 y de 0.85 para las versiones de 20 y 9 ítems, respectivamente. En el dominio de afectos positivos a = 0.82 y a = 0.89; afectos negativos a = 0.89 y a = 0.90 y para deseo intenso de fumar (craving) a = 0.84 y a = 0.75, también respectivamente para las dos versiones. En el análisis factorial exploratorio se identificaron tres factores que explicaron el 95% de la varianza del cuestionario en su versión extensa y 69% en su versión corta. Se obtuvo una versión argentina de la Escala de Autoeficacia/Tentaciones confiable y válida para ser aplicada a fumadores.


Assuntos
Autoeficácia , Traduções , Argentina , Humanos , Reprodutibilidade dos Testes , Inquéritos e Questionários
8.
Medicina (B.Aires) ; 81(4): 602-610, ago. 2021. graf
Artigo em Espanhol | LILACS | ID: biblio-1346513

RESUMO

Resumen La autoeficacia es la confianza en las propias habilidades para evitar fumar en situaciones que puedan desencadenar el deseo. Se la considera un importante predictor de recaídas. En Argentina no existe un instrumento válido que permita evaluarla. El objetivo del presente trabajo fue adaptar y validar una versión en español (Argentina) de la Escala de Autoeficacia/Tentaciones. Se llevó a cabo la adaptación transcul tural de la escala: traducción, revisión por un comité de expertos, traducción inversa, nueva revisión y prueba del cuestionario. Luego se evaluaron la confiabilidad (reproducibilidad, estabilidad y consistencia interna) y la validez. Se realizó un análisis factorial de componentes principales con rotación Varimax con datos de una muestra de 200 pacientes fumadores. Se obtuvo una versión cultural y lingüísticamente adaptada del instrumento, con una confiabilidad interobservador evaluada con el Coeficiente de Correlación Intraclase (ICC) = 0.90 y estabilidad de ICC = 0.77. En el análisis de la consistencia interna se obtuvo un α de Crombach global de 0.93 y de 0.85 para las versiones de 20 y 9 ítems, respectivamente. En el dominio de afectos positivos α = 0.82 y α = 0.89; afectos negativos α = 0.89 y α = 0.90 y para deseo intenso de fumar (craving) α = 0.84 y α = 0.75, también respectivamente para las dos versiones. En el análisis factorial exploratorio se identificaron tres factores que explicaron el 95% de la varianza del cuestionario en su versión extensa y 69% en su versión corta. Se obtuvo una versión argentina de la Escala de Autoeficacia/Tentaciones confiable y válida para ser aplicada a fumadores.


Abstract Self-efficacy is the confidence in one's own abilities to avoid smoking in situations that can trigger desire. It is considered an important predictor of relapses. In Argentina there is no valid instrument to evaluate it. The objective of this article was to adapt and validate a Spanish version (in local Argentinean language) of the Self-Efficacy/Temptation Scale. The transcultural adaptation of the scale was carried out: translation, review by a committee of experts, reverse translation, new review and test of the questionnaire. Reliability (reproduc ibility, stability and internal consistency) and validity were then evaluated. We performed a factor analysis of main components with Varimax rotation with data from a sample of 200 smokers. A culturally and linguistically adapted version of the instrument was obtained, with inter-observer reliability of Intraclass Correlation Coefficient (ICC) = 0.90 and stability of ICC = 0.77. The internal consistency analysis yielded a global Crombach α = 0.93 and 0.85 for versions of 20 and 9 items, respectively. In the domain of Positive Affections α = 0.82 and α = 0.89; Negative Affections α = 0.89 and α = 0.90 and for Craving α = 0.84 and α = 0.75, also respectively for the two versions. In the exploratory factor analysis, three factors were identified that explained 95% of the variance of the questionnaire in its extensive version and 69% in its short version. A reliable and valid Argentinean version of the Self-Efficacy/Temptation Scale was obtained, to be applied to smokers.


Assuntos
Humanos , Traduções , Autoeficácia , Argentina , Inquéritos e Questionários , Reprodutibilidade dos Testes
9.
Oncogene ; 39(4): 814-832, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31558800

RESUMO

Fusion proteins involving the BRAF serine/threonine kinase occur in many cancers. The oncogenic potential of BRAF fusions has been attributed to the loss of critical N-terminal domains that mediate BRAF autoinhibition. We used whole-exome and RNA sequencing in a patient with glioblastoma multiforme to identify a rearrangement between TTYH3, encoding a membrane-resident, calcium-activated chloride channel, and BRAF intron 1, resulting in a TTYH3-BRAF fusion protein that retained all features essential for BRAF autoinhibition. Accordingly, the BRAF moiety of the fusion protein alone, which represents full-length BRAF without the amino acids encoded by exon 1 (BRAFΔE1), did not induce MEK/ERK phosphorylation or transformation. Likewise, neither the TTYH3 moiety of the fusion protein nor full-length TTYH3 provoked ERK pathway activity or transformation. In contrast, TTYH3-BRAF displayed increased MEK phosphorylation potential and transforming activity, which were caused by TTYH3-mediated tethering of near-full-length BRAF to the (endo)membrane system. Consistent with this mechanism, a synthetic approach, in which BRAFΔE1 was tethered to the membrane by fusing it to the cytoplasmic tail of CD8 also induced transformation. Furthermore, we demonstrate that TTYH3-BRAF signals largely independent of a functional RAS binding domain, but requires an intact BRAF dimer interface and activation loop phosphorylation sites. Cells expressing TTYH3-BRAF exhibited increased MEK/ERK signaling, which was blocked by clinically achievable concentrations of sorafenib, trametinib, and the paradox breaker PLX8394. These data provide the first example of a fully autoinhibited BRAF protein whose oncogenic potential is dictated by a distinct fusion partner and not by a structural change in BRAF itself.


Assuntos
Glioblastoma/genética , Glioblastoma/patologia , Compostos Heterocíclicos com 2 Anéis/farmacologia , Proteínas de Fusão Oncogênica , Proteínas Proto-Oncogênicas B-raf/genética , Piridonas/farmacologia , Pirimidinonas/farmacologia , Sulfonamidas/farmacologia , Idoso , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Canais de Cloreto/genética , Canais de Cloreto/metabolismo , Feminino , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Fosforilação , Domínios Proteicos , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Proteínas Proto-Oncogênicas B-raf/metabolismo , Transdução de Sinais
10.
Rev. argent. salud publica ; 10(40): 32-38, 30 de septiembre 2019.
Artigo em Espanhol | BINACIS, ARGMSAL, LILACS | ID: biblio-1024651

RESUMO

El consumo de tabaco, alcohol y otras drogas comienza generalmente en la adolescencia. En Argentina, sucede a edades cada vez más tempranas. El objetivo de este estudio fue explorar factores sociales y personales predictores del inicio del consumo en adolescentes del país. MÉTODOS: En 2014 se realizó una encuesta anónima autoadministrada en estudiantes de primer año del secundario en 33 escuelas públicas y privadas de Buenos Aires, Córdoba y Tucumán, que se repitió en los mismos alumnos en 2015. Incluyó aspectos sociodemográficos, personales, consumo de tabaco en familiares y amigos, y consumo personal de tabaco, alcohol, marihuana y paco o cocaína. Mediante regresión logística multinivel con intercepto aleatorio según escuela, se determinó la asociación entre las variables independientes y el inicio del consumo de cada sustancia durante el seguimiento. RESULTADOS: En 2014 respondieron 3172 alumnos, de los cuales 2018 (64%) completaron la segunda encuesta. En 2015 hubo 16,4% de incidencia de consumo de tabaco, 49,8% de consumo de alcohol y 10,8% de drogas ilícitas. Ser mujer y tener un índice de búsqueda de sensaciones alto fueron predictores del consumo de tabaco y alcohol, y haber fumado, bebido, tener amigos que consumen y mayor edad fueron predictores del consumo de drogas ilícitas. CONCLUSIONES: Es importante identificar a los alumnos con un índice de búsqueda de sensaciones alto, que es el factor de riesgo común al inicio del consumo de todas las sustancias


Assuntos
Nicotiana , Adolescente , Bebidas Alcoólicas
11.
J Med Chem ; 62(8): 3886-3897, 2019 04 25.
Artigo em Inglês | MEDLINE | ID: mdl-30977659

RESUMO

Despite the clinical success of BRAF inhibitors like vemurafenib in treating metastatic melanoma, resistance has emerged through "paradoxical MEK/ERK signaling" where transactivation of one protomer occurs as a result of drug inhibition of the other partner in the activated dimer. The importance of the dimerization interface in the signaling potential of wild-type BRAF in cells expressing oncogenic Ras has recently been demonstrated and proposed as a site of therapeutic intervention in targeting cancers resistant to adenosine triphosphate competitive drugs. The proof of concept for a structure-guided approach targeting the dimerization interface is described through the design and synthesis of macrocyclic peptides that bind with high affinity to BRAF and that block paradoxical signaling in malignant melanoma cells occurring through this drug target. The lead compounds identified are type-IV kinase inhibitors and represent an ideal framework for conversion into next-generation BRAF inhibitors through macrocyclic drug discovery.


Assuntos
Desenho de Fármacos , Inibidores de Proteínas Quinases/síntese química , Proteínas Proto-Oncogênicas B-raf/antagonistas & inibidores , Linhagem Celular , Dimerização , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , MAP Quinase Quinase Quinases/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Simulação de Dinâmica Molecular , Peptídeos/química , Peptídeos/metabolismo , Peptídeos/farmacologia , Ligação Proteica , Inibidores de Proteínas Quinases/metabolismo , Inibidores de Proteínas Quinases/farmacologia , Proteínas Proto-Oncogênicas B-raf/metabolismo , Relação Estrutura-Atividade
12.
J Stud Alcohol Drugs ; 80(1): 69-76, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30807277

RESUMO

OBJECTIVE: This study assesses the association between exposure to alcohol in movies and alcohol use transitions among Latin American adolescents. METHOD: A school-based longitudinal study involving 33 secondary schools in Argentina and 57 in Mexico was performed. The baseline sample included 1,504 never drinker adolescents in Argentina and 5,264 in Mexico (mean age = 12.5 years), of whom 1,055 and 3,540, respectively, completed a follow-up survey a year and a half later. Exposure to the 500 popular contemporary films was assessed by querying adolescents on 50 randomly selected titles. Films were content-coded for alcohol and exposure estimated from films seen. Logistic regression models estimated adjusted relative risk (aRR) for the following outcomes, net covariates, at follow-up: use of alcohol (having ever drank), current drinking (drinking in the past 30 days), ever binge drinking (≥ 4 drinks [females] or 5 for males). RESULTS: At follow-up, respective adolescent drinking rates for Mexico and Argentina were 31% and 36% for use of alcohol, 18% and 27% for current drinking, and 8% and 19% for ever binge drinking. Greater exposure to alcohol in movies was independently associated with trying alcohol (aRR = 1.30, 95% CI [1.17, 1.43]), current drinking (aRR = 1.22, 95% CI [1.03, 1.44]), and binge drinking (aRR = 1.71, 95% CI [1.30, 2.25]) in Mexican adolescents, whereas in Argentina, movie alcohol exposure was associated only with trying alcohol (aRR = 1.25, 95% CI [1.02, 1.53]). CONCLUSIONS: Exposure to alcohol in movies predicted underage drinking transitions in these Latin American adolescents, replicating prior results for U.S. and European cohorts.


Assuntos
Comportamento do Adolescente , Consumo de Bebidas Alcoólicas/epidemiologia , Filmes Cinematográficos/estatística & dados numéricos , Consumo de Álcool por Menores/estatística & dados numéricos , Adolescente , Criança , Feminino , Humanos , América Latina/epidemiologia , Estudos Longitudinais , Masculino , Inquéritos e Questionários
13.
Oncogene ; 38(8): 1324-1339, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30659267

RESUMO

Copy number gains, point mutations and epigenetic silencing events are increasingly observed in genes encoding elements of the Ras/Raf/MEK/ERK signaling axis in human breast cancer. The three Raf kinases A-Raf, B-Raf, and Raf-1 have an important role as gatekeepers in ERK pathway activation and are often dysregulated by somatic alterations of their genes or by the aberrant activity of receptor tyrosine kinases (RTKs) and Ras-GTPases. B-Raf represents the most potent Raf isoform and a critical effector downstream of RTKs and RAS proteins. Aberrant RTK signaling is mimicked by the polyoma middle T antigen (PyMT), which activates various oncogenic signaling pathways, incl. the RAS/ERK axis, in a similar manner as RTKs in human breast cancer. Mammary epithelial cell directed expression of PyMT in mice by the MMTV-PyMT transgene induces mammary hyperplasia progressing over adenoma to metastatic breast cancer with an almost complete penetrance. To understand the functional role of B-Raf in this model for luminal type B breast cancer, we crossed MMTV-PyMT mice with animals that either lack B-Raf expression in the mammary gland or express the signaling impaired B-RafAVKA mutant. The AVKA mutation prevents phosphorylation of T599 and S602 in the B-Raf activation loop and thereby activation of the kinase by upstream signals. We demonstrate for the first time that B-Raf expression and activation is important for tumor initiation in vivo as well as for lung metastasis. Isogenic tumor cell lines generated from conditional Braf knock-out or knock-in mice displayed a reduction in EGF-induced ERK pathway activity as well as in proliferation and invasive growth in three-dimensional matrigel cultures. Our results suggest that B-Raf, which has been hardly studied in the context of breast cancer, represents a critical effector of the PyMT oncoprotein and invite for an assessment of its functional role in human breast cancer.


Assuntos
Neoplasias da Mama/genética , Transformação Celular Neoplásica/genética , Neoplasias Mamárias Animais/genética , Proteínas Proto-Oncogênicas B-raf/genética , Animais , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Modelos Animais de Doenças , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Sistema de Sinalização das MAP Quinases , Neoplasias Mamárias Animais/patologia , Camundongos , Camundongos Knockout , Mutação , Proteínas Proto-Oncogênicas A-raf/genética , Proteínas Proto-Oncogênicas B-raf/deficiência , Proteínas Proto-Oncogênicas c-raf/genética
14.
Rev Asoc Med Argent ; 131(1): 24-31, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30294003

RESUMO

Tobacco use is the primary preventable cause of death and disability in the world. To combat the tobacco epidemic, most countries have signed and ratified the World Health Organzation's Framework Convention on Tobacco Control (WHO FCTC). Article 13 of this treaty requires implementation of a comprehensive ban on tobacco advertising, promotion and sponsorship. Implementation guidelines for Article 13 recognize that the depiction of tobacco use in commercially-produced films promotes tobacco use amongst young people. In this article we review the relationship between the tobacco industry and the movie industry over the past 100 years; the cross sectional and longitudinal studies that demonstrate a causal relationship between exposure to movie smoking depictions and youth smoking initiation; and the policy interventions recommended by the WHO to limit youth exposure to tobacco in movies.


El consumo de Tabaco es la primera causa de mortalidad prevenible en el mundo. Para combatir esta epidemia, los países miembros de la Organización Mundial de la Salud han firmado, y la mayoría de ellos ratificado, el Convenio Marco para el Control del Tabaco. El articulo 13 de este tratado toda forma de publicidad, promoción y patrocinio del tabaco. Las guías para la implementación de este artículo reconocen que la presencia de tabaco en el cine es una forma de promoción de los productos del tabaco dirigida principalmente a los jóvenes.En esta revisión describimos la relación entre la industria del cine y la del tabaco en los últimos 100 año, los estudios de corte transveral y longitudinales que demiuestran como la exposición a tabaco en el cine induce a los jóvenes a iniciarse en el tabaquismo, y las políticas públicas recomendadas para evitar la presencia de tabaco en el cine, al menos en las películas para niños y adolescentes.

15.
Salud Publica Mex ; 60(4): 423-431, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30137944

RESUMO

OBJECTIVE: To assess the validity of a standard measure of smoking susceptibility for predicting cigarette and e-cigarette use in a sample of early adolescents in Argentina and Mexico. MATERIALS AND METHODS: A school-based longitudinal survey was conducted in 2014-16 among secondary students. We analyzed students who were never smokers of regular cigarettes or e-cigarettes at baseline and who completed both surveys. The main independent variable was smoking susceptibility. Multilevel logistic regression models were used, adjusting for sociodemographic and personal variables, social network use of cigarettes and exposure to advertising. RESULTS: In the adjusted analysis, smoking susceptibility independently predicted cigarette initiation (Argentina: AOR 2.28; 95%CI 1.66-3.14; Mexico: AOR 2.07; 95%CI 1.74-2.45) and current smoking (Argentina: AOR 3.61; 95%CI 2.48-5.24; Mexico: AOR 1.69; 95%CI 1.29-2.22); however, it only predicted e-cigarette initiation in Mexico (Mexico: AOR 1.29; 95%CI 1.02-1.63). CONCLUSIONS: Smoking susceptibility was a valid measure to predict future cigarette smoking in this sample.


Assuntos
Comportamento do Adolescente , Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Psicologia do Adolescente , Fumar/epidemiologia , Produtos do Tabaco/estatística & dados numéricos , Adolescente , Publicidade , Argentina/epidemiologia , Previsões , Humanos , Intenção , Modelos Logísticos , México/epidemiologia , Influência dos Pares , Utilização de Procedimentos e Técnicas , Fatores de Risco , Fumar/psicologia , Rede Social
16.
Salud pública Méx ; 60(4): 423-431, Jul.-Aug. 2018. tab, graf
Artigo em Inglês | LILACS | ID: biblio-979158

RESUMO

Abstract Objective To assess the validity of a standard measure of smoking susceptibility for predicting cigarette and e-cigarette use in a sample of early adolescents in Argentina and Mexico. Materials and methods A school-based longitudinal survey was conducted in 2014-16 among secondary students. We analyzed students who were never smokers of regular cigarettes or e-cigarettes at baseline and who completed both surveys. The main independent variable was smoking susceptibility. Multilevel logistic regression models were used, adjusting for sociodemographic and personal variables, social network use of cigarettes and exposure to advertising. Results In the adjusted analysis, smoking susceptibility independently predicted cigarette initiation (Argentina: AOR 2.28; 95%CI 1.66-3.14; Mexico: AOR 2.07; 95%CI 1.74-2.45) and current smoking (Argentina: AOR 3.61; 95%CI 2.48-5.24; Mexico: AOR 1.69; 95%CI 1.29-2.22); however, it only predicted e-cigarette initiation in Mexico (Mexico: AOR 1.29; 95%CI 1.02-1.63). Conclusion Smoking susceptibility was a valid measure to predict future cigarette smoking in this sample.


Resumen Objetivo Evaluar la validez de una medida estándar de susceptibilidad para predecir el consumo de cigarros convencionales y electrónicos en una muestra de adolescentes de Argentina y México. Material y métodos Entre 2014 y 2016 se realizó una encuesta longitudinal en alumnos de secundarias. Se analizaron los alumnos no fumadores y que no habían probado cigarrillos electrónicos en la encuesta basal y que completaron ambas encuestas. La variable independiente principal era la susceptibilidad al consumo de cigarros. Se efectuó una regresión logística multinivel, ajustando por variables sociodemográficas y personales, consumo en el círculo social íntimo y exposición a la publicidad. Resultados En el análisis ajustado, la susceptibilidad al consumo predijo de manera independiente el inicio del consumo de cigarros convencionales (Argentina: RMA2.28; IC95%1.66-3.14; México: RMA2.07; IC95%1.74-2.45) y su consumo actual (Argentina: RMA3.61; IC95%2.48-5.24; México: RMA1.69; IC95%1.29-2.22). Sin embargo, sólo predijo el inicio del consumo de cigarros electrónicos en México (México: ORA 1.29; IC95%1.02-1.63). Conclusión Esta medida es válida para predecir el futuro consumo de cigarros en esta muestra.


Assuntos
Humanos , Adolescente , Fumar/epidemiologia , Comportamento do Adolescente , Psicologia do Adolescente , Produtos do Tabaco/estatística & dados numéricos , Sistemas Eletrônicos de Liberação de Nicotina/estatística & dados numéricos , Argentina/epidemiologia , Modelos Logísticos , Publicidade , Intenção , Rede Social , Influência dos Pares , Previsões , Utilização de Procedimentos e Técnicas , México/epidemiologia
17.
Rev. Asoc. Méd. Argent ; 131(1): 24-31, mar. 2018. ilus
Artigo em Espanhol | LILACS | ID: biblio-973095

RESUMO

El consumo de tabaco es la primera causa de mortalidad prevenible en el mundo. Para combatir esta epidemia, los países miembros de la Organización Mundial de la Salud han firmado, y la mayoría de ellos ratificado, el Convenio Marco para el Control del Tabaco. El artículo 13 de este tratado regula toda forma de publicidad, promoción y patrocinio del tabaco. Las guías para la implementación de este artículo reconocen que la presencia de tabaco en el cine es una forma de promoción de los productos del tabaco dirigida principalmente a los jóvenes. En esta revisión describimos la relación entre la industria del cine y la del tabaco en los últimos 100 años, los estudios de corte transversal y longitudinales que demuestran cómo la exposición a tabaco en el cine induce a los jóvenes a iniciarse en el tabaquismo, y las políticas públicas recomendadas para evitar la presencia de tabaco en el cine, al menos en las películas para niños y adolescentes.


Tobacco use is the primary preventable cause of death and disability in the world. To combat the tobacco epidemic, most countries have signed and ratified the World Health Organzation’s Framework Convention on Tobacco Control (WHO FCTC). Article 13 of this treaty requires implementation of a comprehensive ban on tobacco advertising, promotion and sponsorship. Implementation guidelines for Article 13 recognize that the depiction of tobacco use in commercially-produced films promotes tobacco use amongst young people. In this article we review the relationship between the tobacco industry and the movie industry over the past 100 years; the cross sectional and longitudinal studies that demonstrate a causal relationship between exposure to movie smoking depictions and youth smoking initiation; and the policy interventions recommended by the WHO to limit youth exposure to tobacco in movies.


Assuntos
Humanos , Adolescente , Filmes Cinematográficos , Uso de Tabaco/legislação & jurisprudência , Fumar/psicologia , Uso de Tabaco/prevenção & controle , Uso de Tabaco/psicologia , Organização Mundial da Saúde , Argentina
18.
Addict Behav ; 80: 150-153, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29407686

RESUMO

INTRODUCTION: In a previous cross-sectional study of early adolescents, we developed a marketing receptivity index (MRI) that integrates point-of-sale (PoS) marketing exposures, brand recall, and ownership of branded merchandise. The MRI had independent, positive associations with smoking susceptibility among never smokers and with current smoking behavior. The current longitudinal study assessed the MRI's predictive validity among adolescents who have never smoked cigarettes METHODS: Data come from a longitudinal, school-based survey of 33 secondary schools in Argentina. Students who had never smoked at baseline were followed up approximately 17months later (n=1700). Questions assessed: PoS marketing exposure by querying frequency of going to stores where tobacco is commonly sold; cued recall of brand names for 3 cigarette packages from dominant brands but with the brand name removed; and ownership of branded merchandise. A four-level MRI was derived: 1.low PoS marketing exposure only; 2. high PoS exposure or recall of 1 brand; 3. recall of 2 or more brands; and 4. ownership of branded merchandise. Logistic regression models regressed smoking initiation by follow up survey on the MRI, each of its components, and students' willingness to try a brand, adjusting for sociodemographics, social network smoking, and sensation seeking. RESULTS: The MRI had an independent positive association with smoking initiation. When analyzed separately, each MRI component was associated with outcomes except branded merchandise ownership. CONCLUSIONS: The MRI and its components were associated with smoking initiation, except for branded merchandise ownership, which may better predict smoking progression than initiation. The MRI appears valid and useful for future studies.


Assuntos
Fumar Cigarros/epidemiologia , Marketing , Produtos do Tabaco , Adolescente , Argentina/epidemiologia , Criança , Emblemas e Insígnias , Feminino , Humanos , Modelos Logísticos , Estudos Longitudinais , Masculino , Rememoração Mental , Embalagem de Produtos , Reprodutibilidade dos Testes
19.
Salud Publica Mex ; 59(1): 76-83, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28423113

RESUMO

OBJECTIVE:: To examine and compare overall prevalence and time trends in tobacco and alcohol portrayals and brand appearances in youth-rated US and nationally-produced films that were the most successful in Argentina and Mexico from 2004-2012. MATERIALS AND METHODS:: Top-grossing nationally produced films from Argentina (n=73), Mexico (n=85) and the US (n=643) were content analyzed. Logistic regression was used to determine differences between Mexican, Argentine and US produced films. Linear regression models assessed significant cross-country differences in the mean number of tobacco and alcohol seconds. RESULTS:: Films from Mexico and Argentina were more likely than US films to contain tobacco, (OR=4.2; p<0.001) and (OR=7.2; p<0.001). Alcohol was present in 93% of Argentine, 83% in Mexican and 83% US films. CONCLUSIONS:: Smoking and alcohol were highly prevalent in nationally produced films. They may have a significant impact and should be targeted by policies to reduce youth exposure to portrayals of risk behaviors.


Assuntos
Consumo de Bebidas Alcoólicas , Filmes Cinematográficos/tendências , Fumar , Adolescente , Argentina , Humanos , México , Filmes Cinematográficos/estatística & dados numéricos , Fatores de Tempo
20.
Arch. argent. pediatr ; 115(2): 155-159, abr. 2017. graf, tab
Artigo em Inglês, Espanhol | LILACS, BINACIS | ID: biblio-1038361

RESUMO

El consumo de tabaco, alcohol y otras drogas comienza a temprana edad. Es importante identificar los factores de riesgo asociados al inicio. En 2014, se encuestaron estudiantes de primer año del secundario en Buenos Aires, Córdoba y Tucumán. Respondieron 3172 alumnos (42% de mujeres); edad media de 12,8 años. El 10% había fumado; el 32% había consumido alcohol; el 17% había tenido consumo excesivo durante el último mes, y 8% había consumido, al menos, una droga ilícita en su vida. El índice de búsqueda de emociones alto se asoció al consumo de tabaco (OR 4,25; IC 95%: 2,2-8,1), alcohol (OR 5,56; IC 95%: 3,73-8,31) y marihuana / paco / cocaína (OR 11,73; IC 95%: 5,81-23,69). Tener amigos que consumían tabaco / alcohol se asoció al consumo de tabaco (OR 12,6; IC 95%: 7,8-20,5) y alcohol (OR 5,17; IC 95%: 4,15-6,40). Tener padres que imponían pocas restricciones en el uso de medios se asoció al consumo de tabaco (OR 3,7; IC 95%: 2,1-6,5) y percibir un bajo control y soporte parental (OR 3,02; IC 95%: 1,40-6,52) se asoció al consumo de marihuana/paco/cocaína.


Tobacco, alcohol and drug use starts at an early age. It is important to identify risk factors associated with initiation. In 2014, a survey was conducted among students attending first year of secondary schools in Buenos Aires, Córdoba, and Tucumán. A total of 3172 students completed the survey (42% were girls); their mean age was 12.8 years old. Findings showed that 10% had smoked; 32% had consumed alcohol; 17% had a heavy drinking episode in the past month; and 8% had used at least one illegal drug once in their lifetime. A high sensation seeking index was associated with the use of tobacco (odds ratio [OR]: 4.25, 95% confidence interval [CI]: 2.2-8.1), alcohol (OR: 5.56, 95% CI: 3.73-8.31), and marijuana, coca paste or cocaine, (OR: 11.73, 95% CI: 5.81-23.69). Having friends who smoke or drink was associated with tobacco (OR: 12.6, 95% CI: 7.8-20.5) and alcohol use (OR: 5.17, 95% CI: 4.15-6.40). Having permissive parents in terms of media use was associated with tobacco use (OR: 3.7, 95% CI: 2.1-6.5), and perceiving a low parental support and control (OR: 3.02, 95% CI: 1.40-6.52) was associated with marijuana, coca paste and cocaine use


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Consumo de Bebidas Alcoólicas/epidemiologia , Fumar/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Instituições Acadêmicas , Saúde da População Urbana , Fatores de Risco , Autorrelato
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