Estimulação cerebral profunda na Doença de Parkinson: evidências de estudos de longa duração

A Doença de Parkinson (DP) é uma condição neurodegenerativa crônica que afeta principalmente idosos, mas pode ocorrer em adultos jovens. É a segunda doença neurodegenerativa mais comum, após o Alzheimer. A DP afeta 1% dos indivíduos acima de 60 anos em países industrializados. Sua causa envolve fatores genéticos e ambientais, como exposição a pesticidas e envelhecimento. A Estimulação Cerebral Profunda (DBS) é um tratamento que simula lesões cerebrais, melhorando sintomas motores e não motores. O presente estudo tem como objetivo analisar evidências de estudos sobre a eficácia da DBS no tratamento da DP. Trata-se de uma revisão sistemática de estudos quantitativos que utiliza as bases de dados PubMed (Medline), Cochrane Library e Scientific Electronic Library Online (SciELO) para selecionar artigos científicos. Os estudos incluídos abrangem o período de 2013 a 2023 e estão em inglês, abordando a DBS no tratamento da DP. A DBS melhora diversos sintomas motores e não motores, resultando em uma melhor qualidade de vida para os pacientes. Tais benefícios são sustentados mesmo em estágios avançados da Doença de Parkinson, a qual consiste em fornecer pulsos de corrente elétrica a áreas cerebrais profundas através de eletrodos implantados cirurgicamente, geralmente quando a terapia medicamentosa já não é eficaz. Em um estudo com 82 pacientes, a terapia com DBS resultou em uma redução de ± 52% nos sintomas motores do UPDRS sob medicação antes da cirurgia. A melhora nos sintomas motores com a estimulação, em comparação com a ausência de estimulação e medicação, foi de ± 61% no primeiro ano e ± 39% de 8 a 15 anos após a cirurgia (antes da reprogramação). A medicação foi reduzida em ± 55% após 1 ano e ± 44% após 8 a 15 anos, com a maioria dos pacientes mostrando melhorias após a reprogramação. De acordo com as literaturas analisadas, a DBS é uma terapia eficaz para a DP. Enfatiza-se a importância da inovação contínua e dos novos estudos para explorar as facetas não investigadas desse campo. Com a abordagem dos aspectos clínicos, cirúrgicos, tecnológicos e científicos, destacam-se os benefícios, limitações e desafios a serem superados. Ademais, inovações tecnológicas na DBS, como a estimulação direcional, adaptativa e a telemedicina estão sendo exploradas. Em suma, este artigo fornece evidências sobre os benefícios da DBS na DP, ressaltando a necessidade de pesquisas adicionais para otimizar tal intervenção terapêutica e melhorar a qualidade de vida dos pacientes

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

Funder: European Society of Intensive Care Medicine; doi: http://dx.doi.org/10.13039/501100013347Funder: Flemish Society for Critical Care NursesAbstract: Purpose: Intensive care unit (ICU) patients are particularly susceptible to developing pressure injuries. Epidemiologic data is however unavailable. We aimed to provide an international picture of the extent of pressure injuries and factors associated with ICU-acquired pressure injuries in adult ICU patients. Methods: International 1-day point-prevalence study; follow-up for outcome assessment until hospital discharge (maximum 12 weeks). Factors associated with ICU-acquired pressure injury and hospital mortality were assessed by generalised linear mixed-effects regression analysis. Results: Data from 13,254 patients in 1117 ICUs (90 countries) revealed 6747 pressure injuries; 3997 (59.2%) were ICU-acquired. Overall prevalence was 26.6% (95% confidence interval [CI] 25.9–27.3). ICU-acquired prevalence was 16.2% (95% CI 15.6–16.8). Sacrum (37%) and heels (19.5%) were most affected. Factors independently associated with ICU-acquired pressure injuries were older age, male sex, being underweight, emergency surgery, higher Simplified Acute Physiology Score II, Braden score 3 days, comorbidities (chronic obstructive pulmonary disease, immunodeficiency), organ support (renal replacement, mechanical ventilation on ICU admission), and being in a low or lower-middle income-economy. Gradually increasing associations with mortality were identified for increasing severity of pressure injury: stage I (odds ratio [OR] 1.5; 95% CI 1.2–1.8), stage II (OR 1.6; 95% CI 1.4–1.9), and stage III or worse (OR 2.8; 95% CI 2.3–3.3). Conclusion: Pressure injuries are common in adult ICU patients. ICU-acquired pressure injuries are associated with mainly intrinsic factors and mortality. Optimal care standards, increased awareness, appropriate resource allocation, and further research into optimal prevention are pivotal to tackle this important patient safety threat

Correction to: Prevalence, associated factors and outcomes of pressure injuries in adult intensive care unit patients: the DecubICUs study

The original version of this article unfortunately contained a mistake

Respostas moleculares e metabólicas associadas a ausência do processo autofágico durante limitação energética em Arabidopsis thaliana

The oxidation of carbohydrate in mitochondria is the primary energy source for cellular metabolism. However, during energy-limited conditions alternative substrates are required to support respiration. The oxidation of amino acids plays a key role in this process by generating electrons that can be transferred to mitochondrial electron transport chain via the electron transfer flavoprotein/ ubiquinone oxireductase (ETF/ETFQO) system. Compelling evidence has demonstrated the close association of autophagy in providing alternative substrates for power generation under carbohydrate-limited conditions; however, how and to which extent autophagy and primary metabolism interact to support respiration remains unclear. To obtain a comprehensive picture of the metabolic importance of autophagy during development and extended darkness Arabidopsis thaliana mutants with impairments in autophagy were used. atg mutants showed reduction of growth and seed production. Following extended darkness atg mutants were characterized by early signs of senescence as well as decreased chlorophyll content and maximum photochemical efficiency of PSII (Fv/Fm). Metabolite profile of dark-treated leaves revealed an extensive metabolic reprogramming in which increases in amino acids contents were partially compromised and thus limiting their utilization as substrate to sustain respiration in atg mutants. Additionally, transcript levels of genes involved in alternative pathways of respiration, amino acid catabolism, and chloroplast vesiculation (CV) were up-regulated in atg mutants. Our results thus suggest that autophagy contributes to energy availability by supplying amino acids for alternative pathways of respiration. Furthermore, our finding demonstrated the potential role of CV as a compensatory protein degradation pathway under C-limiting conditions when autophagy is impaired .A oxidação de carboidratos na mitocôndria é a principal fonte de energia para metabolismo celular. Contudo, em condições de limitação energética, substratos alternativos são necessários para a manutenção da respiração. A oxidação de aminoácidos tem papel fundamental nesse processo gerando elétrons que podem ser transferidos para cadeia de transporte de elétrons mitocondrial através do sistema flavoproteína de transferência de elétrons/ flavoproteína de transferência de elétrons oxidoredutase da ubiquinona (ETF/ETFQO). A associação entre autofagia e o fornecimento de substratos alternativos para geração de energia tem sido relatada, porém pouco se sabe acerca do papel da autofagia no metabolismo primário para a manutenção do processo respiratório. Com intuito de se investigar a importância metabólica da autofagia durante o desenvolvimento e em condições de senescência induzida pela escuro, plantas mutantes de Arabidopsis thaliana com comprometimento do processo autofágico foram utilizadas. Mutantes atg apresentaram redução no crescimento e na produção de sementes. Sob escuro prolongado, fenótipos de senescência antecipada assim como redução no conteúdo de clorofila e na eficiência fotoquímica máxima do FSII (Fv/Fm) foram observados nos mutantes atg. A análise do perfil metabólico revelou uma extensa reprogramação metabólica em que o aumento do conteúdo de aminoácidos foi parcialmente comprometido, limitando seu uso como substrato para suprir a respiração nos mutantes atg. Adicionalmente, níveis de transcritos de genes envolvidos em vias de catabolismo de aminoácidos e degradação do cloroplasto (CV) foram induzidos nesses genótipos. Em conjunto, os resultados obtidos demonstram uma potencial função compensatória de CV como processo de degradação de proteínas em condições de limitação de carbono, particularmente quando o processo autofágico é comprometido.Coordenação de Aperfeiçoamento de Pessoal de Nível Superio

Decifrando a resposta à limitação de carbono em Arabidopsis thaliana: autofagia, respiração alternativa e além

Throughout their life, plants are constantly challenged with environmental changes that compromises carbohydrate production. Energy deprivation triggers massive reprogramming of transcription, which further supports cellular energetic homeostasis. Therefore, catabolic pathways are generally activated leading to the catabolism of protein, lipid, and chlorophyll. Although our current understanding of plant mechanisms to overcome low energy conditions has significantly enhanced, there are still many open questions to be addressed. This thesis is therefore largely focused on understanding (i) the importance of autophagy as a mechanism of lipids and chloroplast recycling; and (ii) the transcriptional regulation of respiratory alternative pathways during low energy stress. Compelling evidence demonstrated that autophagy and amino acid catabolism are important factors of plant response to energy deprivation. This fact aside, the importance of autophagy on the remobilization of lipid substrates to sustain energy production remains unclear. Thus, we first summarized and discussed novel findings demonstrating the multifaceted roles of autophagy in lipid metabolism. Next, we provided experimental evidence of autophagy requirement to ensure lipid homeostasis during energy starvation conditions. Our findings revealed that autophagy disruption affects proper membrane mobilization and activates a general chloroplast lipid degradation program while failing to produce cytosolic lipid droplets. The degradation of chloroplasts is a hallmark of natural and stress-induced senescence, and a key role of autophagy in this process has been demonstrated elsewhere. Notably, the marked degradation of chloroplast components in mutants with disruption of autophagy (atg mutants) reported by several previous studies, raised the question whether other pathways of chloroplast degradation may also have a role in the remobilization of chloroplast components. It has been previously reported that the chloroplast vesiculation (CV) pathway is highly induced in atg mutants contributing with their early senescence phenotype during energy starvation. Thus, in the second part of this thesis the importance of CV and its coordination with autophagy under extended darkness was investigated. By using CV RNAi lines it was demonstrated that CV pathway plays a relatively minor role on Arabidopsis starvation response. However, further characterization of double mutants for CV and autophagy pathways highlighted the requirement of CV for chloroplast remodeling of atg mutants under darkness. Within the last chapter novel insights concerning the regulatory components that modulates plant survival under low energetic conditions are shown. To this end, the WRKY45 transcription factor was identified as a potential regulator of metabolic reprogramming, by precisely adjusting amino acid and organic acid response via a possible regulation of mitochondrial stress signaling components. Collectively, the results obtained here describe novel mechanisms underlying plant responses to low energy conditions. These findings are discussed in the context of our current knowledge concerning energetic metabolism, autophagy, and senescence in plants. Keywords: Autophagy. Energetic stress. Lipids. Metabolism. Senescence.Durante seu ciclo de vida, plantas são constantemente expostas a mudanças ambientais que comprometem a produção de carboidratos. A depleção de energia resulta em acentuada reprogramação transcricional que sustenta a manutenção da homeostase energética. Dessa forma, vias catabólicas são geralmente ativadas levando a degradação de proteínas, lipideos e clorofila. Embora nossa compreensão atual acerca dos mecanismos que compõem a resposta de plantas ao déficit de energia tenha melhorado significativamente, ainda há muitas questões a serem abordadas. Portanto, essa tese é amplamente focada na compreensão (i) da autofagia como mecanismo de reciclagem de lipídeos e cloroplastos, (ii) da regulação transcricional das vias respiratórias alternativas durante condições de déficit de energia. Evidências tem demonstrado que a autofagia e o catabolismo de aminoácidos são peças- chaves na resposta de plantas à privação de energia. Apesar disso, pouco se sabe acerca do papel da autofagia na remobilização de substratos lipídicos para sustentar a produção de energia. Assim, primeiramente, sumarizamos estudos recentes que demonstram as múltiplas funções da autofagia no metabolismo lipídico. Em seguida, fornecemos evidências experimentais da importância da autofagia para a homeostase lipídica durante condições de déficit de energia. Nossos resultados demonstram que a ausência da autofagia afeta a mobilização de lipídeos de membrana e ativa degradação de lipídeos do cloroplasto, ao mesmo tempo que a produção de corpos lipídicos no citosol é comprometida. A degradação de cloroplastos é uma característica marcante da senescência natural e induzida por estresse, e o papel central da autofagia nesse processo foi amplamente caracterizado. Notavelmente, a degradação acentuada de componentes do cloroplasto em mutantes da autofagia (mutantes atg) reportada em vários estudos anteriores, sugere que outras vias de degradação do cloroplasto também atuem na remobilização dos componentes do cloroplasto. Dessa forma, foi observado anteriormente que a via de vesiculação do cloroplasto (CV) é altamente induzida em mutantes atg, contribuindo para seu fenótipo de senescência precoce durante condições de déficit de energia. Portanto, na segunda parte desta tese investigou-se a importância da via CV e sua coordenação com a autofagia durante condições de escuro prolongado. Assim, usando linhas mutantes RNAi para o gene CV, foi demonstrado que essa via desempenha um papel minoritário na resposta ao déficit de energia em Arabidopsis. A caracterização adicional de duplos mutantes para as vias CV e autofagia revelou a importância de CV na remodelação estrutural do cloroplasto de mutantes atg no escuro prolongado. No último capítulo, novas informações sobre componentes regulatórios que modulam a sobrevivência das plantas em condições de baixa energia foram revelados. Nesse contexto, o fator de transcrição WRKY45 foi identificado como um potencial componente da reprogramação metabólica sob escuro prolongado, atuando nos níveis de aminoácidos e ácidos orgânicos por meio de vias relacionadas ao estresse mitocondrial. Coletivamente, os dados obtidos descrevem novos mecanismos inerentes às respostas de plantas a condições de baixa energia. Os resultados são discutidos no contexto do conhecimento atual acerca metabolismo energético, autofagia e senescência em plantas. Palavras-chave: Autofagia. Estresse energético. Lipídeos. Metabolismo. Senescência.Conselho Nacional de Desenvolvimento Científico e Tecnológic