Early‐onset coenzyme Q10 deficiency associated with ataxia and respiratory chain dysfunction due to novel pathogenic COQ8A variants, including a large intragenic deletion

Coenzyme Q10 (CoQ10) deficiency is a clinically and genetically heterogeneous subtype of mitochondrial disease. We report two girls with ataxia and mitochondrial respiratory chain deficiency who were shown to have primary CoQ10 deficiency. Muscle histochemistry displayed signs of mitochondrial dysfunction—ragged red fibers, mitochondrial paracrystalline inclusions, and lipid deposits while biochemical analyses revealed complex II+III respiratory chain deficiencies. MRI brain demonstrated cerebral and cerebellar atrophy. Targeted molecular analysis identified a homozygous c.1015G>A, p.(Ala339Thr) COQ8A variant in subject 1, while subject 2 was found to harbor a single heterozygous c.1029_1030delinsCA variant predicting a p.Gln343_Val344delinsHisMet amino acid substitution. Subsequent investigations identified a large‐scale COQ8A deletion in trans to the c.1029_1030delinsCA allele. A skin biopsy facilitated cDNA studies that confirmed exon skipping in the fibroblast derived COQ8A mRNA transcript. This report expands the molecular genetic spectrum associated with COQ8A ‐related mitochondrial disease and highlights the importance of thorough investigation of candidate pathogenic variants to establish phase. Rapid diagnosis is of the utmost importance as patients may benefit from therapeutic CoQ10 supplementation

Linking Hydrogen (δ2H) Isotopes in Feathers and Precipitation: Sources of Variance and Consequences for Assignment to Isoscapes

Background: Tracking small migrant organisms worldwide has been hampered by technological and recovery limitations and sampling bias inherent in exogenous markers. Naturally occurring stable isotopes of H (d 2 H) in feathers provide an alternative intrinsic marker of animal origin due to the predictable spatial linkage to underlying hydrologically driven flow of H isotopes into foodwebs. This approach can assess the likelihood that a migrant animal originated from a given location(s) within a continent but requires a robust algorithm linking H isotopes in tissues of interest to an appropriate hydrological isotopic spatio-temporal pattern, such as weighted-annual rainfall. However, a number of factors contribute to or alter expected isotopic patterns in animals. We present results of an extensive investigation into taxonomic and environmental factors influencing feather d 2 H patterns across North America. Principal Findings: Stable isotope data were measured from 544 feathers from 40 species and 140 known locations. For d 2 H, the most parsimonious model explaining 83 % of the isotopic variance was found with amount-weighted growingseason precipitation d 2 H, foraging substrate and migratory strategy. Conclusions/Significance: This extensive H isotopic analysis of known-origin feathers of songbirds in North America and elsewhere reconfirmed the strong coupling between tissue d 2 H and global hydrologic d 2 H patterns, and accounting for variance associated with foraging substrate and migratory strategy, can be used in conservation and research for th

Geographic Variation of Strontium and Hydrogen Isotopes in Avian Tissue: Implications for Tracking Migration and Dispersal

Background: Isotopes can provide unique solutions to fundamental problems related to the ecology and evolution of migration and dispersal because prior movements of individuals can theoretically be tracked from tissues collected from a single capture. However, there is still remarkably little information available about how and why isotopes vary in wild animal tissues, especially over large spatial scales. Methodology/Principal Findings: Here, we describe variation in both stable-hydrogen (dDF) and strontium ( 87Sr/86SrF) isotopic compositions in the feathers of a migratory songbird, the Tree Swallow (Tachycineta bicolor), across 18 sampling sites in North America and then examine potential mechanisms driving this variation. We found that dDF was correlated with latitude of the sampling site, whereas 87Sr/86SrF was correlated with longitude. dDF was related to dD of meteoric waters where molting occurred and 87Sr/86SrF was influenced primarily by the geology in the area where feathers were grown. Using simulation models, we then assessed the utility of combining both markers to estimate the origin of individuals. Using 13 geographic regions, we found that the number of individuals correctly assigned to their site of origin increased from less than 40 % using either dD or 87Sr/86Sr alone to 74 % using both isotopes. Conclusions/Significance: Our results suggest that these isotopes have the potential to provide predictable an

The Great American Crime Decline : Possible Explanations

This chapter examines the most important features of the crime decline in the United States during the 1990s-2010s but also takes a broader look at the violence declines of the last three centuries. The author argues that violent and property crime trends might have diverged in the 1990s, with property crimes increasingly happening in the online sphere and thus traditional property crime statistics not being reflective of the full picture. An important distinction is made between ‘contact crimes’ and crimes that do not require a victim and offender to be present in the same physical space. Contrary to the uncertainties engendered by property crime, the declines in violent (‘contact’) crime are rather general, and have been happening not only across all demographic and geographic categories within the United States but also throughout the developed world. An analysis of research literature on crime trends has identified twenty-four different explanations for the crime drop. Each one of them is briefly outlined and examined in terms of conceptual clarity and empirical support. Nine crime decline explanations are highlighted as the most promising ones. The majority of these promising explanations, being relative newcomers in the crime trends literature, have not been subjected to sufficient empirical scrutiny yet, and thus require further research. One potentially fruitful avenue for future studies is to examine the association of the most promising crime decline explanations with improvements in self-control

Promoting adherence to Tuberculosis (TB) treatment: experience of evaluation and production of educational material on TB.

Submitted by Sandra Infurna ([email protected]) on 2019-02-12T09:59:45Z No. of bitstreams: 1 ValeriaS_trajano_etal_IOC_2018.pdf: 890812 bytes, checksum: b78b923e11a362385056710e33505f4a (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-02-12T10:08:37Z (GMT) No. of bitstreams: 1 ValeriaS_trajano_etal_IOC_2018.pdf: 890812 bytes, checksum: b78b923e11a362385056710e33505f4a (MD5)Made available in DSpace on 2019-02-12T10:08:37Z (GMT). No. of bitstreams: 1 ValeriaS_trajano_etal_IOC_2018.pdf: 890812 bytes, checksum: b78b923e11a362385056710e33505f4a (MD5) Previous issue date: 2018Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto de Comunicação e Informação Científica e Tecnologia em Saúde. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ. Brasil.Secretaria Estadual de Saúde. Programa Estadual de Tuberculose. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inovações em Terapias, Ensino e Bioprodutos. Rio de Janeiro, RJ. Brasil.A tuberculose (TB) é hoje a principal causa de morte por doença infecciosa no mundo. No Brasil, o abandono do tratamento da TB representa o maior desafio a ser superado no controle da doença. No presente estudo, profissionais da área da saúde, educação e comunicação avaliaram e produziram material educativo sobre TB tendo como tema principal o tratamento da doença. A primeira fase do projeto consistiu na avaliação do material educativo sobre TB já existente, feita por meio da ficha para avaliação de material impresso em saúde da Organização Panamericana de Saúde (OPAS). Em seguida, foram realizados outros quatro encontros para discussão e definição do texto, das imagens e do design gráfico do novo material a ser produzido. Foram elaborados um calendário e um folder, utilizando fotografias de acesso livre na internet. Procurou-se transmitir mensagens positivas como “Tuberculose tem cura” e de encorajamento para a realização da terapia, ressaltando a necessidade do acompanhamento clínico durante o tratamento pelos profissionais de saúde. A possibilidade da ocorrência de efeitos colaterais ao tratamento anti-TB também foi abordada, sendo inseridas mensagens relativas à transmissibilidade do bacilo, fator que ainda gera muitas dúvidas entre pacientes e familiares e é causa de isolamento dos pacientes do convívio social. O teste de legibilidade escolhido avaliou o texto final do folder e do calendário, respectivamente, como história em quadrinhos e excepcional. O calendário “Tuberculose tem cura” foi distribuído em janeiro de 2016 na Clínica da Família Rinaldo De Lamare, que assiste à população da Rocinha, no Rio de Janeiro.Tuberculosis (TB) is today the leading cause of death from infectious disease in the world. In Brazil, default of TB treatment represents the greatest challenge to be overcome in controlling the disease. In the present study, health, education and communication professionals evaluated and produced educational material on TB, the treatment of the disease being the main theme addressed. The first phase of the project consisted in the evaluation of the existing educational material on TB, made through the evaluation form of the Pan American Health Organization (PAHO) printed material in health. Then, four other meetings were held to discuss and define the text, images and graphic design of the new material to be produced. A calendar and a folder were developed using free access photos on the internet. We sought to transmit positive messages such as "Tuberculosis is curable", encouraging the completion of treatment and emphasizing the need for clinical follow-up by health professionals. The possibility of side effects to anti-TB treatment was also considered, as well as messages related to the transmissibility of the bacillus, a factor that still generates many doubts among patients and their families and is a cause of patients´ isolation from social life. The readability test chosen evaluated the final text of the folder and calendar, respectively, as comics and exceptional. The calendar "Tuberculosis is curable" was distributed in January 2016 at the Family’s Clinic Rinaldo de Lamare, that assists Rocinha’s population, in Rio de Janeiro