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1.
EMBO Rep ; 23(12): e53552, 2022 12 06.
Artigo em Inglês | MEDLINE | ID: mdl-36250243

RESUMO

Parkinson's disease-related proteins, PINK1 and Parkin, act in a common pathway to maintain mitochondrial quality control. While the PINK1-Parkin pathway can promote autophagic mitochondrial turnover (mitophagy) following mitochondrial toxification in cell culture, alternative quality control pathways are suggested. To analyse the mechanisms by which the PINK1-Parkin pathway operates in vivo, we developed methods to detect Ser65-phosphorylated ubiquitin (pS65-Ub) in Drosophila. Exposure to the oxidant paraquat led to robust, Pink1-dependent pS65-Ub production, while pS65-Ub accumulates in unstimulated parkin-null flies, consistent with blocked degradation. Additionally, we show that pS65-Ub specifically accumulates on disrupted mitochondria in vivo. Depletion of the core autophagy proteins Atg1, Atg5 and Atg8a did not cause pS65-Ub accumulation to the same extent as loss of parkin, and overexpression of parkin promoted turnover of both basal and paraquat-induced pS65-Ub in an Atg5-null background. Thus, we have established that pS65-Ub immunodetection can be used to analyse Pink1-Parkin function in vivo as an alternative to reporter constructs. Moreover, our findings suggest that the Pink1-Parkin pathway can promote mitochondrial turnover independently of canonical autophagy in vivo.


Assuntos
Proteínas de Drosophila , Drosophila , Animais , Drosophila/genética , Autofagia/genética , Proteínas Serina-Treonina Quinases , Proteínas de Drosophila/genética
2.
MMWR Morb Mortal Wkly Rep ; 64(21): 565-9, 2015 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-26042646

RESUMO

Sexual violence against children erodes the strong foundation that children require for leading healthy and productive lives. Globally, studies show that exposure to violence during childhood can increase vulnerability to a broad range of mental and physical health problems, ranging from depression and unwanted pregnancy to cardiovascular disease, diabetes, and sexually transmitted diseases, including human immunodeficiency virus (HIV). Despite this, in many countries, the extent of sexual violence against children is unknown; estimates are needed to stimulate prevention and response efforts and to monitor progress. Consequently, CDC, as a member of the global public-private partnership known as Together for Girls, collaborated with Cambodia, Haiti, Kenya, Malawi, Swaziland, Tanzania, and Zimbabwe to conduct national household surveys of children and youth aged 13-24 years to measure the extent of violence against children. The lifetime prevalence of experiencing any form of sexual violence in childhood ranged from 4.4% among females in Cambodia to 37.6% among females in Swaziland, with prevalence in most countries greater than 25.0%. In most countries surveyed, the proportion of victims that received services, including health and child protective services, was ≤10.0%. Both prevention and response strategies for sexual violence are needed.


Assuntos
Abuso Sexual na Infância/estatística & dados numéricos , Serviço Social/estatística & dados numéricos , Adolescente , Camboja/epidemiologia , Criança , Essuatíni/epidemiologia , Feminino , Haiti/epidemiologia , Humanos , Quênia/epidemiologia , Malaui/epidemiologia , Masculino , Prevalência , Tanzânia/epidemiologia , Adulto Jovem , Zimbábue/epidemiologia
3.
Arch Dis Child Fetal Neonatal Ed ; 108(2): 194-199, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36261144

RESUMO

OBJECTIVE: To explore views of parents of preterm babies, adults born preterm and professionals, on the linkage of real-world health and education data for research on improving future outcomes of babies born preterm. DESIGN: Three-stage mixed-methods participatory design involving focus groups, a national survey and interviews. Survey participants who expressed uncertainty or negative views were sampled purposively for invitation to interview. Mixed methods were used for data analysis. SETTING AND PARTICIPANTS: All data collection was online. Participants were: focus groups-17 parents; survey-499 parents, 44 adults born preterm (total 543); interviews-6 parents, 1 adult born preterm, 3 clinicians, 2 teachers. RESULTS: Three key themes were identified: (1) Data linkage and opt-out consent make sense for improving future outcomes. We found clear demand for better information on long-term outcomes and strong support for data linkage with opt-out consent as a means of achieving this. (2) Information requirements-what, how and when. There was support for providing information in different formats and discussing linkage near to, or following discharge from, the neonatal unit, but not sooner. (3) Looking to the future; the rights of young people. We identified a desire for individuals born preterm to be consulted in the future on the use of their data. CONCLUSION: With appropriate information provision, at the right time, parents, adults born preterm and professionals are supportive of data linkage for research, including where temporary identifiers and opt-out consent are used. Resources are being co-produced to improve communication about routine data linkage.


Assuntos
Doenças do Recém-Nascido , Recém-Nascido Prematuro , Recém-Nascido , Lactente , Humanos , Adulto , Adolescente , Pais , Inquéritos e Questionários , Comunicação
4.
Nat Commun ; 14(1): 6774, 2023 10 27.
Artigo em Inglês | MEDLINE | ID: mdl-37891180

RESUMO

Most eukaryotic proteins are N-terminally acetylated, but the functional impact on a global scale has remained obscure. Using genome-wide CRISPR knockout screens in human cells, we reveal a strong genetic dependency between a major N-terminal acetyltransferase and specific ubiquitin ligases. Biochemical analyses uncover that both the ubiquitin ligase complex UBR4-KCMF1 and the acetyltransferase NatC recognize proteins bearing an unacetylated N-terminal methionine followed by a hydrophobic residue. NatC KO-induced protein degradation and phenotypes are reversed by UBR knockdown, demonstrating the central cellular role of this interplay. We reveal that loss of Drosophila NatC is associated with male sterility, reduced longevity, and age-dependent loss of motility due to developmental muscle defects. Remarkably, muscle-specific overexpression of UbcE2M, one of the proteins targeted for NatC KO-mediated degradation, suppresses defects of NatC deletion. In conclusion, NatC-mediated N-terminal acetylation acts as a protective mechanism against protein degradation, which is relevant for increased longevity and motility.


Assuntos
Longevidade , Processamento de Proteína Pós-Traducional , Masculino , Humanos , Sequência de Aminoácidos , Acetilação , Longevidade/genética , Ubiquitinas/metabolismo , Ubiquitina-Proteína Ligases/metabolismo
5.
Eur J Public Health ; 22(5): 712-6, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22467758

RESUMO

BACKGROUND: In 1996, Turkey made tobacco control a health priority. The tobacco control effort was extended in July 2009 with the expansion of the smoke-free law to include all enclosed workplaces and public places and, in January 2010, with a 20% increase in the Special Consumption Tax on Tobacco. METHODS: Sales data were averaged, by month, for the period January 2005 through June 2009 to establish an 'expected' monthly sales pattern. This was the period when no new tobacco control measures were implemented. The overall monthly average was then calculated for the same period. The expected monthly sales pattern was then graphed against the overall monthly sales average to delineate a seasonal sales pattern that was used to evaluate the divergence of actual monthly sales from the 'expected' pattern. RESULTS: A distinct seasonal pattern was found with sales above average from May through August. Comparison of actual cigarette sales to the 'expected' monthly sales pattern following the implementation of the expanded smoke-free law in July resulted in a 5.2% decrease. Cigarettes sales decreased by 13.6% following the January 2010 Special Consumption Tax. Since the implementation of the expanded smoke-free law in July 2009 and the tax increase in January 2010, cigarette sales in Turkey decreased by 10.7%. CONCLUSION: The effect of recent Turkish tobacco control policies could contribute to a reduction in the number of premature deaths related to tobacco use. Evidence has shown that periodic tax increases and strong enforcement of all tobacco control policies are essential to further decrease tobacco consumption.


Assuntos
Comércio , Política Pública , Impostos , Indústria do Tabaco/legislação & jurisprudência , Produtos do Tabaco/economia , Poluição por Fumaça de Tabaco/legislação & jurisprudência , Humanos , Saúde Pública , Fumar/legislação & jurisprudência , Poluição por Fumaça de Tabaco/prevenção & controle , Turquia , Local de Trabalho/legislação & jurisprudência
6.
Cent Eur J Public Health ; 20(1): 87-91, 2012 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-22571026

RESUMO

OBJECTIVE: The purpose of this paper is to use data from the Global Youth Tobacco Survey (GYTS) conducted in Turkey in 2003 and 2009 to examine changes in tobacco use and important tobacco control measures. METHODS: The GYTS were conducted in grades 7-9 in 2003 and 7-10 in 2009 in Turkey. Data in this paper are limited to 13 to 15 year old students. A total of 15,957 students from 202 schools participated in 2003 and 5,054 students from 69 schools participated in 2009. The overall response rate was 92.1% in 2003 and 87.5% in 2009. RESULTS: Between 2003 and 2009 current cigarette smoking did not change significantly for either boys (9.4% to 10.2%) or girls (3.5% to 5.3%). Current cigarette smoking was higher among boys than girls in 2003 and in 2009. In 2009, half of students reported they had been exposed to second hand smoking (SHS) at home and 80% reported they had been exposed to SHS in public places. Three in ten students reported they had been exposed to pro-tobacco advertising in newspapers or magazines; one in ten had an object with a cigarette brand logo on it; and 7% had been offered free cigarettes by a cigarette company representative. Two-thirds of current cigarette smokers reported that they wanted to stop smoking; and almost two-thirds had been taught in school in the past year about the dangers of smoking. CONCLUSION: Passing and implementing the Law No. 4207 on Prevention of Hazards of Tobacco Products, ratifying the World Health Organization Framework Convention on Tobacco Control (WHO FCTC), raising tax on tobacco, and requiring pictorial warning labels were important steps forward for tobacco control in Turkey. However, as to the tobacco control much work yet to be accomplished including developing an effective enforcement plan for all tobacco control efforts.


Assuntos
Conhecimentos, Atitudes e Prática em Saúde , Política de Saúde , Nicotiana , Prevenção do Hábito de Fumar , Fumar/legislação & jurisprudência , Adolescente , Comportamento do Adolescente , Publicidade , Feminino , Humanos , Masculino , Meios de Comunicação de Massa , Prevalência , Fatores Sexuais , Fumar/psicologia , Abandono do Hábito de Fumar/métodos , Poluição por Fumaça de Tabaco/legislação & jurisprudência , Poluição por Fumaça de Tabaco/prevenção & controle , Turquia/epidemiologia
7.
BMC Public Health ; 11: 72, 2011 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-21284864

RESUMO

BACKGROUND: GHPSS is a school-based survey that collects self-administered data from students in regular classroom settings. GHPSS produces representative data at the national or city level in each country. This study aims to investigate the prevalence of tobacco use, exposure to secondhand smoke, and cessation counseling among medical students using the GHPSS data. METHODS: The Global Health Professions Student Survey (GHPSS) was conducted among 3rd year medical students in 47 countries and the Gaza Strip/West Bank from 2005-2008 to determine the prevalence of tobacco use and amount of formal training in cessation counseling. RESULTS: In 26 of the 48 sites, over 20% of the students currently smoked cigarettes, with males having higher rates than females in 37 sites. Over 70% of students reported having been exposed to secondhand smoke in public places in 29 of 48 sites. The majority of students recognized that they are role models in society (over 80% in 42 of 48 sites), believed they should receive training on counseling patients to quit using tobacco (over 80% in 41 of 48 sites), but few reported receiving formal training (less than 40% in 46 of 48 sites). CONCLUSION: Tobacco control efforts must discourage tobacco use among health professionals, promote smoke free workplaces, and implement programs that train medical students in effective cessation-counseling techniques.


Assuntos
Aconselhamento/estatística & dados numéricos , Abandono do Hábito de Fumar/estatística & dados numéricos , Fumar/epidemiologia , Estudantes de Medicina , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Feminino , Inquéritos Epidemiológicos , Humanos , Internacionalidade , Masculino
8.
PLoS One ; 16(4): e0250171, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33857226

RESUMO

Effective and rapid decision making during a pandemic requires data not only about infections, but also about human behavior. Mobile phone surveys (MPS) offer the opportunity to collect real-time data on behavior, exposure, knowledge, and perception, as well as care and treatment to inform decision making. The surveys aimed to collect coronavirus disease 2019 (COVID-19) related information in Ecuador and Sri Lanka using mobile phones. In Ecuador, a Knowledge, Attitudes and Practices (KAP) survey was conducted. In Sri Lanka, an evaluation of a novel medicine delivery system was conducted. Using the established mobile network operator channels and technical assistance provided through The Bloomberg Philanthropies Data for Health Initiative (D4H), Ministries of Health fielded a population-based COVID-19-specific MPS using Surveda, the open source data collection tool developed as part of the initiative. A total of 1,185 adults in Ecuador completed the MPS in 14 days. A total of 5,001 adults over the age of 35 in Sri Lanka completed the MPS in 44 days. Both samples were adjusted to the 2019 United Nations Population Estimates to produce population-based estimates by age and sex. The Ecuador COVID-19 MPS found that there was compliance with the mitigation strategies implemented in that country. Overall, 96.5% of Ecuadorians reported wearing a face mask or face covering when leaving home. Overall, 3.8% of Sri Lankans used the service to receive medicines from a government clinic. Among those who used the medicine delivery service in Sri Lanka, 95.8% of those who used a private pharmacy received their medications within one week, and 69.9% of those using a government clinic reported the same. These studies demonstrate that MPS can be conducted quickly and gather essential data. MPS can help monitor the impact of interventions and programs, and rapidly identify what works in mitigating the impact of COVID-19.


Assuntos
COVID-19/epidemiologia , Conhecimentos, Atitudes e Prática em Saúde , Adolescente , Adulto , Telefone Celular , Equador/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , SARS-CoV-2/isolamento & purificação , Sri Lanka/epidemiologia , Inquéritos e Questionários , Adulto Jovem
9.
Sci Rep ; 10(1): 2693, 2020 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-32060339

RESUMO

Mutations in PINK1 and Parkin/PRKN cause the degeneration of dopaminergic neurons in familial forms of Parkinson's disease but the precise pathogenic mechanisms are unknown. The PINK1/Parkin pathway has been described to play a central role in mitochondrial homeostasis by signalling the targeted destruction of damaged mitochondria, however, how disrupting this process leads to neuronal death was unclear until recently. An elegant study in mice revealed that the loss of Pink1 or Prkn coupled with an additional mitochondrial stress resulted in the aberrant activation of the innate immune signalling, mediated via the cGAS/STING pathway, causing degeneration of dopaminergic neurons and motor impairment. Genetic knockout of Sting was sufficient to completely prevent neurodegeneration and accompanying motor deficits. To determine whether Sting plays a conserved role in Pink1/parkin related pathology, we tested for genetic interactions between Sting and Pink1/parkin in Drosophila. Surprisingly, we found that loss of Sting, or its downstream effector Relish, was insufficient to suppress the behavioural deficits or mitochondria disruption in the Pink1/parkin mutants. Thus, we conclude that phenotypes associated with loss of Pink1/parkin are not universally due to aberrant activation of the STING pathway.


Assuntos
Proteínas de Drosophila/genética , Proteínas de Membrana/genética , Doença de Parkinson/genética , Proteínas Serina-Treonina Quinases/genética , Ubiquitina-Proteína Ligases/genética , Animais , Comportamento Animal/fisiologia , DNA Mitocondrial/genética , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Neurônios Dopaminérgicos/patologia , Drosophila melanogaster/genética , Humanos , Camundongos , Mitocôndrias/genética , Doença de Parkinson/patologia , Fenótipo , Transdução de Sinais/genética
10.
Mol Cell Endocrinol ; 518: 110991, 2020 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-32841709

RESUMO

The function of the gonadotropin-releasing hormone (GnRH) neuron is critical to maintain reproductive function and a significant decrease in GnRH can lead to disorders affecting fertility, including hypogonadotropic hypogonadism. Spexin (SPX) is a novel hypothalamic neuropeptide that exerts inhibitory effects on reproduction and feeding by acting through galanin receptor 2 (GALR2) and galanin receptor 3 (GALR3). Fatty acids can act as nutritional signals that regulate the hypothalamic-pituitary-gonadal (HPG) axis, and elevated levels of circulating saturated fatty acids associated with high fat diet (HFD)-feeding have been shown to induce neuroinflammation, endoplasmic reticulum stress and hormonal resistance in the hypothalamus, as well as alter neuropeptide expression. We previously demonstrated that palmitate, the most common saturated fatty acid in a HFD, elevates the expression of Spx, Galr2 and Galr3 mRNA in a model of appetite-regulating neuropeptide Y hypothalamic neurons. Here, we found that Spx, Galr2 and Galr3 mRNA were also significantly induced by palmitate in a model of reproductive GnRH neurons, mHypoA-GnRH/GFP. As a follow-up to our previous report, we examined the molecular pathways by which Spx and galanin receptor mRNA was regulated in this cell line. Furthermore, we performed inhibitor studies, which revealed that the effect of palmitate on Spx and Galr3 mRNA involved activation of the innate immune receptor TLR4, and we detected differential regulation of the three genes by the protein kinases PKC, JNK, ERK, and p38. However, the intracellular metabolism of palmitate to ceramide did not appear to be involved in the palmitate-mediated gene regulation. Overall, this suggests that SPX may play a role in reproduction at the level of the hypothalamus and the pathways by which Spx, Galr2 and Galr3 are altered by fatty acids could provide insight into the mechanisms underlying reproductive dysfunction in obesity.


Assuntos
Hormônio Liberador de Gonadotropina/metabolismo , Neurônios/citologia , Palmitatos/farmacologia , Hormônios Peptídicos/genética , Receptor Tipo 2 de Galanina/genética , Receptor Tipo 3 de Galanina/genética , Animais , Linhagem Celular , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Hipotálamo/metabolismo , Camundongos , Proteínas Quinases Ativadas por Mitógeno/genética , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Hormônios Peptídicos/metabolismo , Proteína Quinase C/genética , Proteína Quinase C/metabolismo , Receptor Tipo 2 de Galanina/metabolismo , Receptor Tipo 3 de Galanina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Regulação para Cima
11.
Artigo em Inglês | MEDLINE | ID: mdl-33381279

RESUMO

OBJECTIVES: The Noncommunicable Disease (NCD) Mobile Phone Survey, a component of the Bloomberg Philanthropies Data for Health Initiative, determines the prevalence of NCDs and their associated risk factors and demonstrates the use of mobile phone administered surveys to supplement periodic national household surveys. The NCD Mobile Phone Survey uses Surveda to administer the survey; Surveda is an open-source, multi-modal software specifically developed for the project. The objective of the paper is to describe Surveda, review data collection methods used in participating countries and discuss how Surveda and similar approaches can improve public health surveillance. METHODS: Surveda features full-service survey design and implementation through a web application and collects data via Short Messaging Service (SMS), Interactive Voice Response (IVR) and/or mobile web. Surveda's survey design process employs five steps: creating a project, creating questionnaires, designing and starting a survey, monitoring survey progress, and exporting survey results. RESULTS: The NCD Mobile Phone Survey has been successfully conducted in five countries, Zambia (2017), Philippines (2018), Morocco (2019), Malawi (2019), and Sri Lanka (2019), with a total of 23,682 interviews completed. DISCUSSION: This approach to data collection demonstrates that mobile phone surveys can supplement face-to-face data collection methods. Furthermore, Surveda offers major advantages including automated mode-switch, question randomization and comparison features. CONCLUSION: Accurate and timely survey data informs a country's abilities to make targeted policy decisions while prioritizing limited resources. The high acceptance of Surveda demonstrates that the use of mobile phones for surveillance can deliver accurate and timely data collection.

12.
Prev Med ; 49(2-3): 224-8, 2009.
Artigo em Inglês | MEDLINE | ID: mdl-19520108

RESUMO

OBJECTIVE: The United Nations Relief and Works Agency for Palestine Refugees in the Near East (UNRWA) has made tobacco use prevention a primary health issue. UNRWA provides education, health, relief and social services in five fields of operation: Jordan, Lebanon, Syria, Gaza Strip and the West Bank. The purpose of this paper is to compare tobacco use among Palestine refugee students and students in the general population of the five fields of operation. METHODS: Global Youth Tobacco Survey (GYTS) data were collected from representative samples of students in UNRWA schools in each of the five fields of operation in 2008. For comparison, previous data are included from GYTS conducted in Gaza Strip, Lebanon, and the West Bank (2005) and in Jordan and Syria (2007). Data are presented for three groups of students: refugees attending schools within and outside the camps and non-refugee students in the general population. RESULTS: In each of the five fields of operation, there was no difference in current cigarette smoking, current use of shisha, or susceptibility to initiate smoking among the three groups of students. Cigarette smoking and susceptibility was lowest in the Gaza Strip and highest in the West Bank; shisha use was lowest in the Gaza Strip but over 30% in Lebanon, Syria, and the West Bank. Exposure to secondhand smoke in public places was greater than 60% in almost all sites. Exposure to indirect advertising was almost 10%. CONCLUSIONS: The similarity in tobacco use among the three groups of students suggests that a coordinated plan between the UNRWA and the governmental authority could be most beneficial in reducing the burden of tobacco-related morbidity and mortality.


Assuntos
Árabes/psicologia , Refugiados/psicologia , Fumar/etnologia , Estudantes/psicologia , Tabagismo/etnologia , Adolescente , Estudos Transversais , Feminino , Inquéritos Epidemiológicos , Humanos , Masculino , Oriente Médio/epidemiologia , Fatores de Risco
13.
Asia Pac J Public Health ; 21(3): 259-67, 2009 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-19443882

RESUMO

The 2003 School Health Act of Taiwan stipulated that school campuses of senior high and below should be smoke free, but data from the Global Youth Tobacco Survey show that the majority of students are exposed to smoke in public and at home. More than 50% of nonsmokers indicated that they had been exposed to secondhand smoke (SHS) in public places, with the exposure rate as high as 90% among smokers. More than 40% of junior and senior high school students were exposed to SHS at home. Support for banning smoking in public places ranged from almost 60% to almost 80%. More than 60% of current smokers and almost 90% of never smokers think that smoke from others is harmful to them. With a clear body of evidence detailing the harmful effects, reduction and eventual elimination of exposure to SHS should be the goal of the tobacco control community.


Assuntos
Atitude Frente a Saúde , Exposição Ambiental , Estudantes/psicologia , Poluição por Fumaça de Tabaco , Adolescente , Feminino , Humanos , Masculino , Inquéritos e Questionários , Taiwan
14.
Cell Rep ; 27(5): 1541-1550.e5, 2019 04 30.
Artigo em Inglês | MEDLINE | ID: mdl-31042479

RESUMO

Mitochondrial Ca2+ uptake is an important mediator of metabolism and cell death. Identification of components of the highly conserved mitochondrial Ca2+ uniporter has opened it up to genetic analysis in model organisms. Here, we report a comprehensive genetic characterization of all known uniporter components conserved in Drosophila. While loss of pore-forming MCU or EMRE abolishes fast mitochondrial Ca2+ uptake, this results in only mild phenotypes when young, despite shortened lifespans. In contrast, loss of the MICU1 gatekeeper is developmentally lethal, consistent with unregulated Ca2+ uptake. Mutants for the neuronally restricted regulator MICU3 are viable with mild neurological impairment. Genetic interaction analyses reveal that MICU1 and MICU3 are not functionally interchangeable. More surprisingly, loss of MCU or EMRE does not suppress MICU1 mutant lethality, suggesting that this results from uniporter-independent functions. Our data reveal the interplay among components of the mitochondrial Ca2+ uniporter and shed light on their physiological requirements in vivo.


Assuntos
Proteínas de Ligação ao Cálcio/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Proteínas de Drosophila/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/metabolismo , Mutação , Animais , Cálcio/metabolismo , Proteínas de Ligação ao Cálcio/genética , Proteínas de Transporte de Cátions/genética , Proteínas de Drosophila/genética , Drosophila melanogaster , Mitocôndrias/metabolismo , Proteínas de Transporte da Membrana Mitocondrial/genética , Fenótipo
15.
Nat Commun ; 10(1): 3280, 2019 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-31337756

RESUMO

Somatic mutations in the mitochondrial genome (mtDNA) have been linked to multiple disease conditions and to ageing itself. In Drosophila, knock-in of a proofreading deficient mtDNA polymerase (POLG) generates high levels of somatic point mutations and also small indels, but surprisingly limited impact on organismal longevity or fitness. Here we describe a new mtDNA mutator model based on a mitochondrially-targeted cytidine deaminase, APOBEC1. mito-APOBEC1 acts as a potent mutagen which exclusively induces C:G>T:A transitions with no indels or mtDNA depletion. In these flies, the presence of multiple non-synonymous substitutions, even at modest heteroplasmy, disrupts mitochondrial function and dramatically impacts organismal fitness. A detailed analysis of the mutation profile in the POLG and mito-APOBEC1 models reveals that mutation type (quality) rather than quantity is a critical factor in impacting organismal fitness. The specificity for transition mutations and the severe phenotypes make mito-APOBEC1 an excellent mtDNA mutator model for ageing research.


Assuntos
Desaminase APOBEC-1/fisiologia , DNA Mitocondrial/química , Drosophila/genética , Desaminase APOBEC-1/genética , Desaminase APOBEC-1/metabolismo , Animais , Drosophila/fisiologia , Mitocôndrias/metabolismo , Mitocôndrias/fisiologia , Modelos Genéticos , Mutação , Organismos Geneticamente Modificados
16.
Prev Med ; 47 Suppl 1: S11-4, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18585772

RESUMO

OBJECTIVES: Indonesia has the fifth highest rate of annual cigarette consumption per person of all countries worldwide. The Global Youth Tobacco Survey (GYTS) was developed to provide data on youth tobacco use to countries for their development of youth-based tobacco control programs. Data in this report can be used as baseline measures for future evaluation of the tobacco control program implemented by Indonesia's Ministry of Health. METHODS: The 2006 Indonesia GYTS is a school-based survey that included separate samples for Java and Sumatera, representing more than 84% of the population of Indonesia. Each sample used a two-stage cluster sample design that produced representative samples of students in secondary grades 1-3, which are associated with ages 13-15 years. RESULTS: This report shows that more than 1 in 10 students (12.6%) currently smoked cigarettes, with the prevalence among boys (24.5%) significantly higher than among girls (2.3%). Of the students who currently smoked, more than 7 in 10 (75.9%) reported that they desired to stop smoking now. Regarding secondhand smoke exposure, more than 6 in 10 students (64.2%) reported that they were exposed to smoke from other people in their home during the week before the survey. More than 9 in 10 students (92.9%) had seen a lot of advertisements for cigarettes on billboards during the past month and more than 8 in 10 (82.8%) had seen a lot of advertisements for cigarettes in newspapers or in magazines. CONCLUSIONS: Tobacco control in Indonesia will likely not move forward until the government evaluates and strengthens existing laws, considers passing new strong laws, and develops protocols for enforcing all laws. The Indonesian government also should strongly consider accession to the World Health Organization Framework Convention on Tobacco Control.


Assuntos
Comportamento do Adolescente , Abandono do Hábito de Fumar/estatística & dados numéricos , Fumar/epidemiologia , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Adolescente , Comportamento do Adolescente/psicologia , Exposição Ambiental , Feminino , Humanos , Indonésia/epidemiologia , Masculino , Vigilância da População/métodos , Prevalência , Fatores Sexuais , Fumar/psicologia , Abandono do Hábito de Fumar/psicologia , Prevenção do Hábito de Fumar , Poluição por Fumaça de Tabaco/prevenção & controle , Organização Mundial da Saúde
17.
Prev Med ; 47 Suppl 1: S4-10, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18206221

RESUMO

OBJECTIVE: The Global Youth Tobacco Survey (GYTS) in Brazil was developed to provide data on youth tobacco use to the National Tobacco Control Program. METHOD: The GYTS uses a standardized methodology for constructing sampling frames, selecting schools and classes, preparing questionnaires, carrying out field procedures, and processing data. The GYTS questionnaire is self-administered and includes questions about: initiation; prevalence; susceptibility; knowledge and attitudes; environmental tobacco smoke; cessation; media and advertising. SUDDAN and Epi-Info Software were used for analysis. Weighted analysis was used in order to obtain percentages and 95% confidence intervals. RESULTS: Twenty-three studies were carried out between 2002 and 2005 in Brazilian capitals: 2002 (9); 2003 (4); 2004 (2) and 2005 (9). The total number of students was 22832. The prevalence rate among the cities varied from 6.2% (João Pessoa, 2002) to 17.7% (Porto Alegre, 2002). CONCLUSION: The tobacco use prevalence rates in 18 Brazilian cities show significant heterogeneity among the macro regions. Data in this report can be used to evaluate the efforts already done and also as baseline for evaluation of new steps for tobacco control in Brazil regarding the goals of the WHO FCTC.


Assuntos
Comportamento do Adolescente , Fumar/epidemiologia , Tabagismo/epidemiologia , Adolescente , Idade de Início , Brasil/epidemiologia , Criança , Saúde Global , Humanos , Vigilância da População/métodos , Prevalência , Fumar/psicologia , Abandono do Hábito de Fumar/estatística & dados numéricos , Prevenção do Hábito de Fumar , Tabagismo/prevenção & controle , Tabagismo/psicologia , Organização Mundial da Saúde
18.
Prev Med ; 47 Suppl 1: S20-6, 2008 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-18406456

RESUMO

BACKGROUND: The adoption of the World Health Organization Framework Convention on Tobacco Control (WHO FCTC) in 2004 marked a critical achievement in efforts to stem the tobacco epidemic in Mexico. The Global Youth Tobacco Survey (GYTS) findings are useful for evaluating achievement of FCTC articles and designing tobacco control programs. OBJECTIVE: To use data from the GYTS conducted in 21 Mexican cities between 2000 and 2005 to monitor Articles in the WHO FCTC. METHODS: The GYTS uses a two-stage cluster sample survey design that produces representative samples of students aged 13-15 years enrolled in public, private and technical schools. The survey was undertaken at 542 schools in 21 cities. The GYTS surveyed 43,950 students during 2000-2005. RESULTS: The current smoking rate ranged from 10.7% to 29.4%. Among never smokers, susceptibility to initiate smoking ranged from 20.2% to 34.4%. Among current smokers, the percentage who bought their cigarettes in a store was above 40% in 6 cities, but significantly declined over five years in the only city with two assessments (Monterrey). Exposure to secondhand smoke in public places was greater than 50% in 15 of the 21 cities. Over 80% of students in all 21 cities reported that they saw of advertisements for cigarettes on billboards. CONCLUSION: Using determinants measured by GYTS in Mexico, the government can monitor the impact of enforcing various provisions of the National Health Law and the progress made in achieving the goals of the WHO FCTC and the Regional strategy. When these goals are met, tobacco consumption and exposure in Mexico will have declined substantially.


Assuntos
Comportamento do Adolescente , Fumar/epidemiologia , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Tabagismo/epidemiologia , Adolescente , Publicidade , Idade de Início , Criança , Exposição Ambiental , Humanos , México/epidemiologia , Vigilância da População , Prevalência , Abandono do Hábito de Fumar , Prevenção do Hábito de Fumar , Estudantes , Poluição por Fumaça de Tabaco/prevenção & controle , Tabagismo/prevenção & controle , Organização Mundial da Saúde
19.
J Am Acad Dermatol ; 59(4): 706-12, 2008 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-18550209

RESUMO

Woringer-Kolopp disease, also known as pagetoid reticulosis, is an exceedingly rare variant of mycosis fungoides. Accurate diagnosis and effective treatment is essential to prevent progression to debilitating disease. We identified 7 patients with Woringer-Kolopp disease treated at our institution. We review the major clinical and pathologic characteristics of this disease, focusing on treatment strategies and patient outcomes. All of our patients were successfully treated with skin-directed therapies including topical steroids, topical nitrogen mustard, psoralen plus ultraviolet A, narrow-band ultraviolet B, and radiation therapy. Our observations confirm that Woringer-Kolopp disease carries an excellent prognosis, and support that the most effective and appropriate treatment for recalcitrant or severe Woringer-Kolopp disease is localized radiation therapy.


Assuntos
Micose Fungoide/diagnóstico , Micose Fungoide/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/patologia , Adolescente , Adulto , Idoso , Biópsia , Criança , Diagnóstico Diferencial , Feminino , Dermatoses da Mão/diagnóstico , Humanos , Lactente , Masculino , Mecloretamina/administração & dosagem , Micose Fungoide/tratamento farmacológico , Micose Fungoide/radioterapia , Recidiva Local de Neoplasia/patologia , Terapia PUVA , Fótons/uso terapêutico , Doses de Radiação , Terapia de Salvação , Pele/patologia , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/radioterapia , Resultado do Tratamento
20.
BMC Public Health ; 8 Suppl 1: S3, 2008 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-19091046

RESUMO

INTRODUCTION: Thailand ratified the World Health Organization (WHO) Framework Convention on Tobacco Control (FCTC) on November 8, 2004. The WHO FCTC requires all parties to inform all persons of the health consequences of tobacco consumption and exposure to tobacco smoke. Each party has agreed to develop, implement and evaluate effective tobacco control programs to measure progress in reaching the goals of the WHO FCTC. METHODS: The Global Youth Tobacco Survey (GYTS) was developed to provide data on youth tobacco use to countries for their development of youth-based tobacco control programs. Data in this report can be used as baseline measures for future evaluation of the tobacco control programs implemented by the Ministry of Public Health. RESULTS: Overall, about 1 in 10 Thai students are current smokers, this number including 4 times more boys than girls (17% versus 3.9%). Almost 2 in 10 Thai students start smoking before the age of 10, and almost 7 in 10 students are reported to have been exposed to smoke from others in public places. About 4 in 10 students are reported to have an object with a cigarette brand logo on it. CONCLUSION: The key for Thailand is to implement and enforce the provisions on indirect tobacco advertising, smoking in public places, selling tobacco to youths under 18 years of age, and to use the data from the GYTS to monitor progress toward achieving the goals of the WHO FCTC. When these goals are met, tobacco consumption and exposure in Thailand will have declined substantially.


Assuntos
Comportamento do Adolescente , Vigilância da População , Política Pública , Fumar/epidemiologia , Tabagismo/epidemiologia , Adolescente , Comportamento do Adolescente/psicologia , Feminino , Humanos , Masculino , Programas Nacionais de Saúde , Prevalência , Administração em Saúde Pública , Informática em Saúde Pública , Assunção de Riscos , Serviços de Saúde Escolar/estatística & dados numéricos , Abandono do Hábito de Fumar , Prevenção do Hábito de Fumar , Tailândia/epidemiologia , Indústria do Tabaco , Poluição por Fumaça de Tabaco/estatística & dados numéricos , Tabagismo/prevenção & controle
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