Mechanisms of Human Mitochondrial DNA Maintenance: The Determining Role of Primary Sequence and Length over Function

Although the regulation of mitochondrial DNA (mtDNA) copy number is performed by nuclear-coded factors, very little is known about the mechanisms controlling this process. We attempted to introduce nonhuman ape mtDNA into human cells harboring either no mtDNA or mutated mtDNAs (partial deletion and tRNA gene point mutation). Unexpectedly, only cells containing no mtDNA could be repopulated with nonhuman ape mtDNA. Cells containing a defective human mtDNA did not incorporate or maintain ape mtDNA and therefore died under selection for oxidative phosphorylation function. On the other hand, foreign human mtDNA was readily incorporated and maintained in these cells. The suicidal preference for self-mtDNA showed that functional parameters associated with oxidative phosphorylation are less relevant to mtDNA maintenance and copy number control than recognition of mtDNA self-determinants. Non–self-mtDNA could not be maintained into cells with mtDNA even if no selection for oxidative phosphorylation was applied. The repopulation kinetics of several mtDNA forms after severe depletion by ethidium bromide treatment showed that replication and maintenance of mtDNA in human cells are highly dependent on molecular features, because partially deleted mtDNA molecules repopulated cells significantly faster than full-length mtDNA. Taken together, our results suggest that mtDNA copy number may be controlled by competition for limiting levels of trans-acting factors that recognize primarily mtDNA molecular features. In agreement with this hypothesis, marked variations in mtDNA levels did not affect the transcription of nuclear-coded factors involved in mtDNA replication.

Restriction-modification gene complexes as selfish gene entities: Roles of a regulatory system in their establishment, maintenance, and apoptotic mutual exclusion

We have reported some type II restriction-modification (RM) gene complexes on plasmids resist displacement by an incompatible plasmid through postsegregational host killing. Such selfish behavior may have contributed to the spread and maintenance of RM systems. Here we analyze the role of regulatory genes (C), often found linked to RM gene complexes, in their interaction with the host and the other RM gene complexes. We identified the C gene of EcoRV as a positive regulator of restriction. A C mutation eliminated postsegregational killing by EcoRV. The C system has been proposed to allow establishment of RM systems in new hosts by delaying the appearance of restriction activity. Consistent with this proposal, bacteria preexpressing ecoRVC were transformed at a reduced efficiency by plasmids carrying the EcoRV RM gene complex. Cells carrying the BamHI RM gene complex were transformed at a reduced efficiency by a plasmid carrying a PvuII RM gene complex, which shares the same C specificity. The reduction most likely was caused by chromosome cleavage at unmodified PvuII sites by prematurely expressed PvuII restriction enzyme. Therefore, association of the C genes of the same specificity with RM gene complexes of different sequence specificities can confer on a resident RM gene complex the capacity to abort establishment of a second, incoming RM gene complex. This phenomenon, termed “apoptotic mutual exclusion,” is reminiscent of suicidal defense against virus infection programmed by other selfish elements. pvuIIC and bamHIC genes define one incompatibility group of exclusion whereas ecoRVC gene defines another.

Suicídio : uma análise epidemiológica : estudo retrospetivo da casuística da Delegação do Sul do Instituto Nacional de Medicina Legal e Ciências Forenses, I.P. (2007-2012)

Trabalho Final do Curso de Mestrado Integrado em Medicina, Faculdade de Medicina, Universidade de Lisboa, 2014

Perfil sociodemográfico dos sujeitos que tentaram o suicídio no município de Arapiraca, Alagoas

Introdução: as tentativas de suicídio são uma das causas mais frequentes de atendimento nos serviços de urgência no Brasil. Poucos estudos abordam as características epidemiológicas das tentativas de suicídio, principalmente na região nordeste. Diante da importância de se conhecer as características das tentativas de suicídio e propor estratégias de minimização é que o presente estudo caracterizou o perfil sociodemográfico das pessoas que tentaram suicídio em Arapiraca – AL, no período de 2009 a 2013. Metodologia: Trata-se de um estudo descritivo de série histórica, com dados obtidos através da ficha de notificação/ investigação individual de Intoxicação Exógena do SINAN, de pacientes que foram atendidos no serviço de urgência e emergência da Unidade de Emergência Doutor Daniel Houly em Arapiraca. Foram analisadas as seguintes variáveis das tentativas de suicídios: faixa etária, sexo, raça, idade gestacional, zona de residência, vínculo empregatício, agente tóxico, hospitalização e evolução. Resultados: Do ano de 2009 a 2013 o total de atendidos por tentativas de suicídios na referida unidade foi de 1.184 indivíduos, sendo 71,54% do sexo feminino e 28,46% do sexo masculino. A faixa etária de maior frequência foi à de 20-29 anos, correspondendo a 33 % e a raça parda foi a que apresentou maior número de casos, 21% (n= 239). Em relação à residência 77% (n = 922) dos casos residiam em zona urbana, e o principal agente tóxico utilizado nas tentativas de suicídio, foi a ingestão medicamentosa (n = 822, 72%). Cerca de 73% (n=865) tiveram que ser hospitalizados e 95% tiveram tratamento adequado, evoluindo para cura. Conclusão: A partir dos dados foi possível traçar o perfil sociodemográfico das tentativas de suicídio, alcançando os objetivos propostos. A discussão do tema bem como a implementação da educação em saúde se constituem em elementos primordiais para a identificação dos sujeitos com ideação suicida e a busca da evitabilidade de novos casos. Ações de vigilância são necessárias para minimizar as taxas de suicídio, bem como a formação e articulação de rede de assistência no agreste alagoano. Ainda ressalta-se a necessidade de mais estudos com a população que apresenta comportamento suicida no município. Palavras-chave: Tentativa de Suicídio. Saúde Pública. Saúde Mental.

2005 - 2007 suicide prevention report : Illinois Suicide Prevention Strategic Planning Committee.

"December 2007"

2007 Illinois suicide prevention strategic plan.

In 2007, an alliance was formed between the Illinois Suicide Prevention Strategic Planning Committee and the Illinois Suicide Prevention Coalition, unifying the strengths of the groups to continue to advance the plan. The joint mission of this alliance is "to reduce suicide and its stigma throughout Illinois by collaboratively working with concerned stakeholders from the public and private sectors to increase awareness and education, provide opportunities to develop individual and organizational capacity in addressing suicide prevention, and advocate for access to treatment."

State agency review and initial recommendations report : recommendations of policy and program changes to support suicide prevention.

In addition to the development and implementation of an Illinois Suicide Prevention Strategic Plan, the alliance was charged with reviewing the statutorily prescribed missions, policies and procedures of the Illinois departments of Public Health, Human Services and Aging and the State Board of Education. This report is a compilation of that review and includes recommendations to incorporate suicide prevention in the missions, policies and procedures of these state agencies.

A qualitative analysis of health care provider perceptions of depression and suicidality in Mozambique

Thesis (Master's)--University of Washington, 2016-06

New Thinking for Intervention: Towards a Culturally Responsive Model of Understanding Indigenous Suicide

Thesis (Ed.D.)--University of Washington, 2016-06

Telephone counselling for adolescent suicide prevention: Changes in suicidality and mental state from beginning to end of a counselling session

Telephone counselling is an accessible and confidential means by which distressed young people can seek help. Telephone counselling services were funded under Australia's National Youth Suicide Prevention Strategy between 1997 and 2000. In this study, the effectiveness of telephone counselling for young people seeking help in the context of suicidal ideation or intent was evaluated in an investigation of calls made by suicidal young people to a telephone counselling service. Independent raters measured callers' suicidality and mental state at the beginning and, end of 100 taped counselling sessions. Changes in suicidality and mental state were measured using a reliable rating scale developed for the study. Significant decreases in suicidality and significant improvement in mental state were found to occur during the course of counselling sessions, suggesting positive immediate impact.-Limitations of the study with respect to longer-term outcomes and the relevance of the results for suicide prevention are discussed. Notwithstanding the study limitations, the results lend support for continuing development of hotline services.

Sexual abuse, antisocial behaviour and substance use: gender differences in young community adolescents

Objective: To investigate gender-specific relationships between self-reported sexual abuse, antisocial behaviour and substance use in a large community sample of adolescents. Method: A cross-sectional study of students aged, on average, 13 (n = 2596), 14 (n = 2475) and 15 years (n = 2290), from 27 schools in South Australia with a questionnaire including sexual abuse, frequency and severity of substance use, depressive symptomatology (CES-D), family functioning (McMaster Family Assessment Device), and antisocial behaviour (an adapted 22-item Self-Report Delinquency Scale). Logistic regression analyses using HLM V5.05 with a population-average model were conducted. Results: In the model considered, reported sexual abuse is significantly independently associated with antisocial behaviour, controlling for confounding factors of depressive symptomatology and family dysfunction, with increased risks of three- to eightfold for sexually abused boys, and two- to threefold for sexually abused girls, compared to nonabused. Increased risks of extreme substance use in sexually abused girls (age 13) and boys (ages 13-15) are more than fourfold, compared to nonabused. Age differences were not statistically significant. Conclusion: Childhood sexual abuse is a risk factor for the development of antisocial behaviour and substance use in young adolescents. Clinicians should be aware of gender differences.

Sexual abuse and suicidality: gender differences in a large community sample of adolescents

Objective: A cross-sectional study of gender specific relationships between self-reported child sexual abuse and suicidality in a community sample of adolescents. Method: Students aged 14 years on average (N = 2,485) from 27 schools in South Australia completed a questionnaire including items on sexual abuse and suicidality, and measures of depression (Centre for Epidemiological Studies Depression Scale), hopelessness (Beck Hopelessness Scale), and family functioning (McMaster Family Assessment Device General Functioning Subscale). Data analysis included logistic regression. Results: In boys, self-report sexual abuse is strongly and independently associated with suicidal thoughts, plans, threats, deliberate self-injury, and suicide attempts, after controlling for current levels of depression, hopelessness, and family dysfunction. In girls, the relationship between sexual abuse and suicidality is mediated fully by depression, hopelessness, and family dysfunction. Girls who report current high distress about sexual abuse, however, have a threefold increased risk of suicidal thoughts and plans, compared to non-abused girls. Boys who report current high distress about sexual abuse have 10-fold increased risk for suicidal plans and threats, and 15-fold increased risk for suicide attempts, compared to non-abused boys. Fifty-five percent (n = 15) of sexually abused boys attempted suicide versus 29% (n = 17) girls. Conclusions: A history of sexual abuse should alert clinicians, professionals and caters in contact with adolescents, to greatly increased risks of suicidal behavior and attempts in boys, even in the absence of depression and hopelessness. Distress following sexual abuse, along with depression and hopelessness indicate increased risk of suicidal behavior in girls, as well as boys. (C) 2004 Published by Elsevier Ltd.

Suicide in developing countries (3) Prevention efforts

Until now, suicide prevention efforts have been limited in developing countries, although there are pockets of excellent achievement. Various universal, selective, and indicated interventions have been implemented, many of which target a different pattern of risk factors to those in developed countries. In the absence of sufficient mental health services, developing countries rely heavily on nongovemment organizations (NGOs) to provide crisis interventions for suicidal individuals, as well as proactive interventions aimed at raising community awareness and building resilience. Often these NGOs work within a social and public health framework, collaborating with others to provide nested suicide prevention programs that are responsive to local community needs. There is a clear need to develop appropriate, relevant and effective national suicide prevention plans in developing countries, since, to date, only Sri Lanka has done so. These plans should focus on a range of priority areas, specify the actions necessary to achieve positive change in these priority areas, consider the range of collaborators required to implement these actions, and structure their efforts at national, regional, and local levels. The plans should also promote the collection of accurate data on completed and attempted suicide, and should foster evaluation efforts.

A genetically informed study of the processes underlying the association between parental marital instability and offspring adjustment

Parental divorce is associated with problematic offspring adjustment, but the relation may be due to shared genetic or environmental factors. One way to test for these confounds is to study offspring of twins discordant for divorce. The current analyses used this design to separate the mechanisms responsible for the association between parental divorce, experienced either before or after the age of 16, and offspring well-being. The results were consistent with a causal role of divorce in earlier initiation of sexual intercourse and emotional difficulties, in addition to a greater probability of educational problems, depressed mood, and suicidal ideation. In contrast, the increased risk for cohabitation and earlier initiation of drug use was explained by selection factors, including genetic confounds.

Media guidelines on the reporting of suicide

There is strong evidence for the existence of the Werther effect, or the phenomenon of an observer copying suicidal behavior he or she has seen modelled in the media. As a consequence, a number of countries have developed guidelines that promote responsible reporting of suicide. Using nine such guidelines as examples, this paper demonstrates that they tend to have similar content (emphasizing, for example, that suicide should not be,glamorized or sensationalized and that explicit descriptions should be avoided, and stressing the importance of providing information about help services), but differ in the way in which they have been developed (e.g., the extent to which media professionals have been involved) and implemented (e.g., whether their roll-out has involved a considered dissemination strategy). The paper also reviews the evidence from evaluations of media guidelines, and concludes that it is too limited to determine whether the guidelines have had an impact on the behavior of media professionals or on completed and attempted suicide rates. It makes recommendations for further evaluative work, and suggests that the lessons from well-designed evaluations should be shared.