The wake- and sleep-modulating neurons of the lateral hypothalamic area demonstrate a differential pattern of degeneration in Alzheimers disease.

BACKGROUND: Sleep-wake dysfunction is an early and common event in Alzheimer's disease (AD). The lateral hypothalamic area (LHA) regulates the sleep and wake cycle through wake-promoting orexinergic neurons (OrxN) and sleep-promoting melanin-concentrating hormone or MCHergic neurons (MCHN). These neurons share close anatomical proximity with functional reciprocity. This study investigated LHA OrxN and MCHN loss patterns in AD individuals. Understanding the degeneration pattern of these neurons will be instrumental in designing potential therapeutics to slow down the disease progression and remediate the sleep-wake dysfunction in AD. METHODS: Postmortem human brain tissue from donors with AD (across progressive stages) and controls were examined using unbiased stereology. Formalin-fixed, celloidin-embedded hypothalamic sections were stained with Orx-A/MCH, p-tau (CP13), and counterstained with gallocyanin. Orx or MCH-positive neurons with or without CP13 inclusions and gallocyanin-stained neurons were considered for stereology counting. Additionally, we extracted RNA from the LHA using conventional techniques. We used customized Neuropathology and Glia nCounter (Nanostring) panels to study gene expression. Wald statistical test was used to compare the groups, and the genes were considered differentially expressed when the p-value was <.05. RESULTS: We observed a progressive decline in OrxN alongside a relative preservation of MCHN. OrxN decreased by 58% (p=0.03) by Braak stages (BB) 1-2 and further declined to 81% (p=0.03) by BB 5-6. Conversely, MCHN demonstrated a non-statistical significant decline (27%, p=0.1088) by BB 6. We observed a progressive increase in differentially expressed genes (DEGs), starting with glial profile changes in BB2. While OrxN loss was observed, Orx-related genes showed upregulation in BB 3-4 compared to BB 0-1. GO and KEGG terms related to neuroinflammatory pathways were mainly enriched. CONCLUSIONS: To date, OrxN loss in the LHA represents the first neuronal population to die preceding the loss of LC neurons. Conversely, MCHN shows resilience to AD p-tau accumulation across Braak stages. The initial loss of OrxN correlates with specific neuroinflammation, glial profile changes, and an overexpression of HCRT, possibly due to hyperexcitation following compensation mechanisms. Interventions preventing OrxN loss and inhibiting p-tau accumulation in the LHA could prevent neuronal loss in AD and, perhaps, the progression of the disease.

Basic Life Support: an accessible tool in layperson training.

OBJECTIVES: 1) To evaluate the efficiency of a new method of training laypeople on cardiopulmonary resuscitation (CPR). 2) To assess previous knowledge of the participants. METHODS: Instructors were trained according to the 2015 American Heart Association Guidelines, with emphasis on CPR. Dummies made with PET bottles were used, and a questionnaire was applied to the participants before and after training. Statistical analysis was performed in the R commander program. Participants with incomplete documents were excluded from the study. RESULTS: Out of 101 participants, 96 were included: 69 lay people, 17 health professionals, and ten health students. There was an improvement in the overall performance after training (mean pre: 62.7%, mean post: 75.8%, p <0.01), also present in the following main concepts: "mouth-to-mouth breathing is not necessary" (p <0.01), "risk of contamination" (p <0.01), "compression technique" (p <0.01). The concepts "recognition of severity" and "what is chest compression" did not improve, but had good pre-test means, 96.8% and 81.2%. There was no statistical difference in the knowledge between the groups (laypeople vs. health professionals and students, pre=0,06 e post=0,33). CONCLUSION: The tools used in training were efficient. However, further studies are necessary to assess the long-term impact of this intervention.

Basic Life Support: an accessible tool in layperson training

SUMMARY OBJECTIVES 1) To evaluate the efficiency of a new method of training laypeople on cardiopulmonary resuscitation (CPR). 2) To assess previous knowledge of the participants. METHODS Instructors were trained according to the 2015 American Heart Association Guidelines, with emphasis on CPR. Dummies made with PET bottles were used, and a questionnaire was applied to the participants before and after training. Statistical analysis was performed in the R commander program. Participants with incomplete documents were excluded from the study. RESULTS Out of 101 participants, 96 were included: 69 lay people, 17 health professionals, and ten health students. There was an improvement in the overall performance after training (mean pre: 62.7%, mean post: 75.8%, p <0.01), also present in the following main concepts: "mouth-to-mouth breathing is not necessary" (p <0.01), "risk of contamination" (p <0.01), "compression technique" (p <0.01). The concepts "recognition of severity" and "what is chest compression" did not improve, but had good pre-test means, 96.8% and 81.2%. There was no statistical difference in the knowledge between the groups (laypeople vs. health professionals and students, pre=0,06 e post=0,33). CONCLUSION The tools used in training were efficient. However, further studies are necessary to assess the long-term impact of this intervention.

RESUMO OBJETIVOS 1) Avaliar a eficiência da nova proposta de ensino de ressuscitação cardiopulmonar (RCP) à população leiga. 2) Avaliar o conhecimento prévio dos participantes da oficina. MÉTODOS Instrutores foram treinados de acordo com as diretrizes de 2015 da American Heart Association com enfoque na RCP. Utilizaram-se manequins confeccionados com garrafas PET, além de aplicação de questionário aos participantes antes e depois do treinamento. A análise estatística foi realizada no programa R commander. Foram excluídos do estudo participantes com documentos incompletos. RESULTADOS Dos 101 participantes, 96 foram incluídos: 69 leigos, 17 profissionais da saúde e dez estudantes da área da saúde. Houve melhora do desempenho geral após o treinamento (média pré: 62,7%; média pós: 75,8%; p<0,01), presente também nos seguintes conceitos principais: "respiração boca a boca não é necessária" (p<0,01), "risco de contaminação" (p<0,01), "técnica de compressão" (p<0,01). Os conceitos "reconhecimento de gravidade" e "o que é massagem cardíaca" não apresentaram melhora, mas tiveram boas médias pré-teste: 96,8% e 81,2%. Não se verificou diferença estatística no conhecimento entre grupos (leigos vs profissionais e estudantes da saúde, ppre=0,06 e ppos=0,33). CONCLUSÃO As ferramentas utilizadas no treinamento se mostraram eficientes. No entanto, novos estudos são necessários para avaliar o impacto no longo prazo.