Genetic and Molecular Characterization of Programmed Cell Death in the C.elegans Tail-Spike Cell

Work in Caenorhabditis elegans has been instrumental in deciphering the molecular basis of programmed cell death. However, despite extensive characterization of broadacting cell death genes, the molecular events triggering cell-specific activation of the cell death machinery remain, for the most part, unknown. In some C. elegans somatic cells, transcription of the egl-1 /BH3-only gene is believed to promoted cell-specific death. EGL-1 protein inhibits the CED-9/Bcl-2 protein, resulting in release of the caspase activator CED-4/Apaf-1. Subsequent activation of CED-3 caspase by CED-4 leads to cell death. But despite the important role of egl-1 transcription in promoting CED-3 activity in cells destined to die, it remains unclear whether temporal control of cell death is mediated by egl-1 expression. Here, we establish the C. elegans tail-spike cell as an attractive model for studying the initiation of programmed cell death. We show that, while death of the tail-spike cell is dependent upon the ced-3 and ced-4 genes, egl-1 and ced-9 play only a minor role in the death of this cell, demonstrating that temporal control of cell death can be achieved in the absence of egl-1. We go on to show that the timing of tail-spike cell death onset is controlled by transcriptional induction of the ced-3 caspase. In the tailspike cell, ced-3 expression is induced minutes before the cell dies, and this induction is sufficient to promote the cell’s demise. Both ced-3 expression and cell death are dependent upon the transcription factor-encoding gene pal-1, the C. elegans homolog of the mammalian tumor suppressor gene Cdx2. PAL-1 can bind to ced-3 promoter sites critical for tail-spike cell death, suggesting that it promotes cell death by directly activating ced-3 transcription. Our results highlight a previously undescribed role for transcriptional regulation of caspases in controlling the timing of cell death onset during animal development

Pseudobulbar Affect in Parkinsonian Disorders: A Review

Pseudobulbar affect (PBA) is a neurological symptom of inappropriate and uncontrollable laughter or crying that occurs secondary to a variety of neurological conditions, including parkinsonian disorders. PBA is a socially and emotionally debilitating symptom that has been estimated to affect 3.6% to 42.5% of the population with Parkinson’s disease. While indexing measures and treatment options for PBA have been extensively studied in neurological conditions such as amyotrophic lateral sclerosis and multiple sclerosis, there has been considerably less attention given in the literature to PBA in parkinsonian disorders. The purpose of this review is to discuss the pathophysiology of PBA, its prevalence and impact on quality of life in parkinsonian disorders, and the treatment options currently available. Areas requiring further study, including the development of standardized, cross-culturally validated methods of symptom assessment, and evidence-based studies exploring the efficacy of current treatment options in parkinsonian disorders, are also highlighted

CASOS DE LEPTOSPIROSE RELATADOS EM ARTIGOS CIENTÍFICOS: UMA ANÁLISE DOS DADOS CLÍNICOS

Tanto em países desenvolvidos quanto nos países em desenvolvimento, a Leptospirose é considerada um problema para a saúde pública (SILVA; MOREIRA, 2013). Inúmeros fatores contribuem para o acometimento do processo infeccioso, o qual é causado pela bactéria Leptospira interrogans, que se manifesta principalmente em locais com ausência ou deficiência de saneamento básico, acúmulo de lixo, entre outros fatores ambientais relacionáveis. Em virtude desses aspectos, é de grande valia compilar e comparar informações de relatos de casos de Leptospirose apresentados em artigos científicos. Os casos relatados a seguir foram retirados de quatro artigos científicos e trazem à luz a análise conjunta de dados clínico-laboratoriais dos quatro pacientes que tiveram o diagnóstico de Leptospirose. O primeiro deles refere-se a um paciente do sexo masculino, 24 anos, mulato, solteiro, desempregado, residente em São Miguel Paulista, SP, que apresentou, no dia 15 de abril de 1988, febre de 38,5 °C, calafrios, sudorese, cefaleia de pequena intensidade, dor epigástrica, dores no corpo, náuseas, vômitos, tosse com expectoração amarelada e urina de coloração avermelhada. No segundo caso, o paciente era do sexo masculino, 22 anos, branco, solteiro, servente, residente em Santo André, SP; no dia 31 de janeiro de 1989 apresentou quadro gripal, febre de 39 °C, dores nas pernas e icterícia. No terceiro caso, paciente masculino, 18 anos, pardo, estudante, residente na Asa Norte em Brasília, DF, apresentou, em 28 de janeiro de 1979, febre diária intermitente, cefaleia, mialgias predominantemente nos membros inferiores, polaciúria, disúria, febre de 40 °C, icterícia e dores no corpo. E, no último e quarto caso, paciente era também do sexo masculino, 15 anos, branco, estudante, residente na Asa Norte em Brasília, DF, e apresentou, em 31 de janeiro de 1979, febre alta contínua, cefaleia frontal intensa, dor de garganta e na região da nuca, náuseas, febre de 36,5 °C e dores no corpo. Os dois primeiros, procedentes de São Paulo, eram lavradores que viviam em zona rural, com precárias condições higiênicas e socioeconômicas, em contato diário com solo e água passíveis de contaminação por roedores ou animais domésticos. Ambos contraíram a infecção durante período chuvoso. Os dois últimos pacientes, estudantes de nível secundário, com bom padrão socioeconômico e de higiene, contaminaram-se, incidentalmente, durante pescaria no setor Norte do lago que circunda Brasília, também durante período chuvoso. Todos apresentaram início súbito de astenia e febre, sendo calafrios, cefaleia, dor abdominal, mialgias e náuseas referidos constantemente, além de icterícia e dores no corpo, principalmente na região das pernas. No Brasil pouco se sabe acerca da real distribuição da Leptospirose ou seu papel e efeitos no que se refere à saúde, ou mesmo seus reflexos nocivos na economia nacional. Assim, a doença deve ser encarada como um importante problema de saúde pública e precisa receber a necessária atenção por parte das autoridades responsáveis.   Palavras-chave: Leptospirose. Causas. Manifestação. Brasil. Ambiente

Pd loading threshold for an efficient noble metal use in Pd/CeO2 methane oxidation catalysts

The influence of the noble metal-support interaction on the performance, activation behavior and stability of Pd/CeO$_2$ catalysts for total methane oxidation was systematically investigated. A series of samples with 1–3 wt% Pd loading supported on CeO2 with surface areas varying between 30 and 120 m2/g were tested as-prepared and after different reductive treatments. Distinct Pd structural states were identified, which influence the catalytic performance depending on the pre-treatment and the theoretical monolayer Pd coverage of CeO$_2$. Although reductive treatments improved the catalytic activity, the stability strongly depended on the Pd coverage on ceria and the type of reducing agent. A threshold of Pd concentration on the ceria surface was identified that ensures optimal noble metal efficiency, activity and long-term durability. Below this threshold, rapid catalyst deactivation occurs due to redispersion on the strongly interacting support whereas above this threshold Pd is prone to sintering irrespective of the atmosphere

Outcome measurement in functional neurological disorder: a systematic review and recommendations.

OBJECTIVES We aimed to identify existing outcome measures for functional neurological disorder (FND), to inform the development of recommendations and to guide future research on FND outcomes. METHODS A systematic review was conducted to identify existing FND-specific outcome measures and the most common measurement domains and measures in previous treatment studies. Searches of Embase, MEDLINE and PsycINFO were conducted between January 1965 and June 2019. The findings were discussed during two international meetings of the FND-Core Outcome Measures group. RESULTS Five FND-specific measures were identified-three clinician-rated and two patient-rated-but their measurement properties have not been rigorously evaluated. No single measure was identified for use across the range of FND symptoms in adults. Across randomised controlled trials (k=40) and observational treatment studies (k=40), outcome measures most often assessed core FND symptom change. Other domains measured commonly were additional physical and psychological symptoms, life impact (ie, quality of life, disability and general functioning) and health economics/cost-utility (eg, healthcare resource use and quality-adjusted life years). CONCLUSIONS There are few well-validated FND-specific outcome measures. Thus, at present, we recommend that existing outcome measures, known to be reliable, valid and responsive in FND or closely related populations, are used to capture key outcome domains. Increased consistency in outcome measurement will facilitate comparison of treatment effects across FND symptom types and treatment modalities. Future work needs to more rigorously validate outcome measures used in this population

EuReCa ONE—27 Nations, ONE Europe, ONE Registry A prospective one month analysis of out-of-hospital cardiac arrest outcomes in 27 countries in Europe

AbstractIntroductionThe aim of the EuReCa ONE study was to determine the incidence, process, and outcome for out of hospital cardiac arrest (OHCA) throughout Europe.MethodsThis was an international, prospective, multi-centre one-month study. Patients who suffered an OHCA during October 2014 who were attended and/or treated by an Emergency Medical Service (EMS) were eligible for inclusion in the study. Data were extracted from national, regional or local registries.ResultsData on 10,682 confirmed OHCAs from 248 regions in 27 countries, covering an estimated population of 174 million. In 7146 (66%) cases, CPR was started by a bystander or by the EMS. The incidence of CPR attempts ranged from 19.0 to 104.0 per 100,000 population per year. 1735 had ROSC on arrival at hospital (25.2%), Overall, 662/6414 (10.3%) in all cases with CPR attempted survived for at least 30 days or to hospital discharge.ConclusionThe results of EuReCa ONE highlight that OHCA is still a major public health problem accounting for a substantial number of deaths in Europe.EuReCa ONE very clearly demonstrates marked differences in the processes for data collection and reported outcomes following OHCA all over Europe. Using these data and analyses, different countries, regions, systems, and concepts can benchmark themselves and may learn from each other to further improve survival following one of our major health care events

Impaired sense of agency in functional movement disorders: An fMRI study.

The sense of agency (SA) is an established framework that refers to our ability to exert and perceive control over our own actions. Having an intact SA provides the basis for the human perception of voluntariness, while impairments in SA are hypothesized to lead to the perception of movements being involuntary that may be seen many neurological or psychiatric disorders. Individuals with functional movement disorders (FMD) experience a lack of control over their movements, yet these movements appear voluntary by physiology. We used fMRI to explore whether alterations in SA in an FMD population could explain why these patients feel their movements are involuntary. We compared the FMD group to a control group that was previously collected using an ecologically valid, virtual-reality movement paradigm that could modulate SA. We found selective dysfunction of the SA neural network, whereby the dorsolateral prefrontal cortex and pre-supplementary motor area on the right did not respond differentially to the loss of movement control. These findings provide some of the strongest evidence to date for a physiological basis underlying these disabling disorders

Impaired sense of agency in functional movement disorders: An fMRI study.

The sense of agency (SA) is an established framework that refers to our ability to exert and perceive control over our own actions. Having an intact SA provides the basis for the human perception of voluntariness, while impairments in SA are hypothesized to lead to the perception of movements being involuntary that may be seen many neurological or psychiatric disorders. Individuals with functional movement disorders (FMD) experience a lack of control over their movements, yet these movements appear voluntary by physiology. We used fMRI to explore whether alterations in SA in an FMD population could explain why these patients feel their movements are involuntary. We compared the FMD group to a control group that was previously collected using an ecologically valid, virtual-reality movement paradigm that could modulate SA. We found selective dysfunction of the SA neural network, whereby the dorsolateral prefrontal cortex and pre-supplementary motor area on the right did not respond differentially to the loss of movement control. These findings provide some of the strongest evidence to date for a physiological basis underlying these disabling disorders

CASOS DE LEPTOSPIROSE RELATADOS EM ARTIGOS CIENTÍFICOS: UMA ANÁLISE DOS DADOS CLÍNICOS

Tanto em países desenvolvidos quanto nos países em desenvolvimento, a Leptospirose é considerada um problema para a saúde pública (SILVA; MOREIRA, 2013). Inúmeros fatores contribuem para o acometimento do processo infeccioso, o qual é causado pela bactéria Leptospira interrogans, que se manifesta principalmente em locais com ausência ou deficiência de saneamento básico, acúmulo de lixo, entre outros fatores ambientais relacionáveis. Em virtude desses aspectos, é de grande valia compilar e comparar informações de relatos de casos de Leptospirose apresentados em artigos científicos. Os casos relatados a seguir foram retirados de quatro artigos científicos e trazem à luz a análise conjunta de dados clínico-laboratoriais dos quatro pacientes que tiveram o diagnóstico de Leptospirose. O primeiro deles refere-se a um paciente do sexo masculino, 24 anos, mulato, solteiro, desempregado, residente em São Miguel Paulista, SP, que apresentou, no dia 15 de abril de 1988, febre de 38,5 °C, calafrios, sudorese, cefaleia de pequena intensidade, dor epigástrica, dores no corpo, náuseas, vômitos, tosse com expectoração amarelada e urina de coloração avermelhada. No segundo caso, o paciente era do sexo masculino, 22 anos, branco, solteiro, servente, residente em Santo André, SP; no dia 31 de janeiro de 1989 apresentou quadro gripal, febre de 39 °C, dores nas pernas e icterícia. No terceiro caso, paciente masculino, 18 anos, pardo, estudante, residente na Asa Norte em Brasília, DF, apresentou, em 28 de janeiro de 1979, febre diária intermitente, cefaleia, mialgias predominantemente nos membros inferiores, polaciúria, disúria, febre de 40 °C, icterícia e dores no corpo. E, no último e quarto caso, paciente era também do sexo masculino, 15 anos, branco, estudante, residente na Asa Norte em Brasília, DF, e apresentou, em 31 de janeiro de 1979, febre alta contínua, cefaleia frontal intensa, dor de garganta e na região da nuca, náuseas, febre de 36,5 °C e dores no corpo. Os dois primeiros, procedentes de São Paulo, eram lavradores que viviam em zona rural, com precárias condições higiênicas e socioeconômicas, em contato diário com solo e água passíveis de contaminação por roedores ou animais domésticos. Ambos contraíram a infecção durante período chuvoso. Os dois últimos pacientes, estudantes de nível secundário, com bom padrão socioeconômico e de higiene, contaminaram-se, incidentalmente, durante pescaria no setor Norte do lago que circunda Brasília, também durante período chuvoso. Todos apresentaram início súbito de astenia e febre, sendo calafrios, cefaleia, dor abdominal, mialgias e náuseas referidos constantemente, além de icterícia e dores no corpo, principalmente na região das pernas. No Brasil pouco se sabe acerca da real distribuição da Leptospirose ou seu papel e efeitos no que se refere à saúde, ou mesmo seus reflexos nocivos na economia nacional. Assim, a doença deve ser encarada como um importante problema de saúde pública e precisa receber a necessária atenção por parte das autoridades responsáveis.   Palavras-chave: Leptospirose. Causas. Manifestação. Brasil. Ambiente