COVID-19 outcomes in people living with HIV: Peering through the waves

Objective: To evaluate clinical characteristics and outcomes of COVID-19 patients infected with HIV, and to compare with a paired sample without HIV infection. Methods: This is a substudy of a Brazilian multicentric cohort that comprised two periods (2020 and 2021). Data was obtained through the retrospective review of medical records. Primary outcomes were admission to the intensive care unit, invasive mechanical ventilation, and death. Patients with HIV and controls were matched for age, sex, number of comorbidities, and hospital of origin using the technique of propensity score matching (up to 4:1). They were compared using the Chi-Square or Fisher's Exact tests for categorical variables and the Wilcoxon for numerical variables. Results: Throughout the study, 17,101 COVID-19 patients were hospitalized, and 130 (0.76%) of those were infected with HIV. The median age was 54 (IQR: 43.0;64.0) years in 2020 and 53 (IQR: 46.0;63.5) years in 2021, with a predominance of females in both periods. People Living with HIV (PLHIV) and their controls showed similar prevalence for admission to the ICU and invasive mechanical ventilation requirement in the two periods, with no significant differences. In 2020, in-hospital mortality was higher in the PLHIV compared to the controls (27.9% vs. 17.7%; p = 0.049), but there was no difference in mortality between groups in 2021 (25.0% vs. 25.1%; p > 0.999). Conclusions: Our results reiterate that PLHIV were at higher risk of COVID-19 mortality in the early stages of the pandemic, however, this finding did not sustain in 2021, when the mortality rate is similar to the control group

Assessment of risk scores to predict mortality of COVID-19 patients admitted to the intensive care unit

ObjectivesTo assess the ABC2-SPH score in predicting COVID-19 in-hospital mortality, during intensive care unit (ICU) admission, and to compare its performance with other scores (SOFA, SAPS-3, NEWS2, 4C Mortality Score, SOARS, CURB-65, modified CHA2DS2-VASc, and a novel severity score).Materials and methodsConsecutive patients (≥ 18 years) with laboratory-confirmed COVID-19 admitted to ICUs of 25 hospitals, located in 17 Brazilian cities, from October 2020 to March 2022, were included. Overall performance of the scores was evaluated using the Brier score. ABC2-SPH was used as the reference score, and comparisons between ABC2-SPH and the other scores were performed by using the Bonferroni method of correction. The primary outcome was in-hospital mortality.ResultsABC2-SPH had an area under the curve of 0.716 (95% CI 0.693–0.738), significantly higher than CURB-65, SOFA, NEWS2, SOARS, and modified CHA2DS2-VASc scores. There was no statistically significant difference between ABC2-SPH and SAPS-3, 4C Mortality Score, and the novel severity score.ConclusionABC2-SPH was superior to other risk scores, but it still did not demonstrate an excellent predictive ability for mortality in critically ill COVID-19 patients. Our results indicate the need to develop a new score, for this subset of patients

The influence of olfactory stimulation in the development of limbic seizures in rats

Um dos modelos experimentais mais utilizados para estudar a epilepsia do lobo temporal (ELT) é o abrasamento (kindling) por estimulação elétrica diária da amígdala, o abrasamento elétrico convencional. Uma alternativa rápida e eficaz a esse modelo é o abrasamento elétrico rápido, também capaz de gerar crises límbicas, porém com 10 estímulos elétricos aplicados ao dia, por 2 dias. No 3º dia é aplicado um estímulo elétrico adicional, o 21º estímulo, quando podem ser testadas drogas antiepilépticas ou estudados mecanismos de plasticidade ou memória. Entre as principais áreas ativadas nas crises límbicas encontram-se o complexo amigdalóide, a formação hipocampal, o córtex piriforme e neocórtices adjacentes. O envolvimento de estruturas olfatórias na ELT é antigo e estudos indicam que a exposição a um estímulo olfatório é capaz de suprimir, inibir ou induzir a ocorrência de crises. Todas as evidências clínicas e experimentais dão suporte científico para a hipótese de que a estimulação olfatória com o 2,5-Dihydro-2,4,5-trimethylthiazoline (TMT), uma potente substância química, derivada das fezes de raposa e que biologicamente representa o cheiro de predador pode influenciar no processo de crises evocadas por estimulação elétrica da amígdala. O objetivo geral do presente estudo foi avaliar a influência da apresentação do estímulo olfatório com TMT nas crises epilépticas de ratos Wistar, submetidos ao abrasamento elétrico rápido da amígdala. Para tanto, os parâmetros químicos do TMT foram avaliados, bem como as respostas comportamentais de ratos Wistar machos naives submetidos ao estímulo olfatório com diferentes doses de TMT. Na sequência, um novo grupo de ratos Wistar machos naives foi submetido ao protocolo de abrasamento elétrico rápido da amígdala com a aquisição dos registros eletrencefalográficos (EEGráficos) do córtex piriforme, formação hipocampal além do complexo amigdalóide. Após abrasados os animais foram expostos ao TMT ou água destilada, previamente ao 21º estímulo elétrico. Posteriormente o tecido cerebral foi processado (perfundido, crioprotegido, congelado e cortado) e então foram feitas as técnicas histoquímicas de: Nissl e Fluoro-Jade C (FJC, marcador de neurodegeneração). As respostas comportamentais foram analisadas mediante o uso do Índice de Gravidade para Crises Límbicas e da neuroetologia. Adicionalmente foi avaliada a expressão EEGráfica do 1º, 20º e 21º estímulos e verificada a presença/ausência de neurodegeneração em regiões do sistema límbico. Os resultados da análise comportamental obtidos nesse estudo foram comparados com os obtidos no protocolo de estimulação olfatória com TMT nas crises audiogênicas agudas de ratos da cepa WAR. O TMT desencadeou reações de medo e modificou as sequências comportamentais, reduziu a atividade motora e os comportamentos de autolimpeza. Dados qualitativos da cromatografia gasosa e algoritmos matemáticos possibilitaram estabelecer as concentrações na câmara para as diferentes doses de TMT. Além disso, a cromatografia gasosa identificou que 30 minutos é o tempo necessário para saturação e dessaturação da câmara ao TMT, e indicou uma saturação homogênea do interior dessa câmara. O TMT puro no abrasamento elétrico rápido em ratos Wistar foi capaz de reduzir significativamente o Índice de Gravidade para Crises Límbicas comparado à água, corroborando os dados neuroetológicos que indicam o efeito supressor do TMT nas crises, tanto para o modelo de abrasamento elétrico rápido quanto para as crises audiogênicas agudas. Os resultados da duração da pós-descarga EEGráfica primária no 21º estímulo foram inconclusivos, sendo necessárias outras análises empregando diferentes métodos analíticos. Com a técnica de FJC não foi possível verificar morte celular por necrose em qualquer região cerebral avaliada.One of the most widely used experimental models to study temporal lobe epilepsy (TLE) is the kindling by electrical daily stimulation of the amygdala, the conventional kindling. A rapid and effective alternative to this model is rapid electrical kindling, also capable of generating limbic seizures, but with 10 electrical stimuli applied per day for 2 days. On the 3rd day an additional electrical stimulus is applied, the 21st stimulus, when antiepileptic drugs can be tested or mechanisms of plasticity and memory can be studied. Among the main areas activated in limbic seizures are the amygdaloid complex, the hippocampal formation, piriform cortex and adjacent neocortices. The involvement of the olfactory structures in TLE is old and studies indicate that exposure to an olfactory stimulus is capable to suppress or inhibit or induce the occurrence of seizures. All the clinical and experimental evidences provide scientific support for the hypothesis that the olfactory stimulation with 2,5-Dihydro-2,4,5-trimethylthiazoline (TMT), a powerful chemical substance derived from fox feces which biologically represents the \"predator smell can influence the seizures process evoked by electrical stimulation of the amygdala. The overall objective of this study was to evaluate the influence of olfactory stimulation with TMT in seizures of Wistar rats subjected to rapid electrical kindling of the amygdala. Therefore, the chemical parameters of TMT were evaluated, as well as behavioral responses of naive male Wistar rats exposed to the olfactory stimulus with different concentrations of TMT. Other group of rats was electrically stimulated in the amygdaloid complex, following the protocol of rapid electrical kindling and the electroencephalographic recordings (EEGraphic) obtained from the piriform cortex, hippocampal formation in addition to the amygdaloid complex. After scorched the animals were exposed to TMT or distilled water, prior to the 21st electrical stimulation. Subsequently the cerebral tissue was processed (perfused, cryoprotected, frozen and sliced) and then processed for Nissl and Fluoro-Jade C histochemistry (FJC, a marker of neurodegeneration). The behavioral responses were analyzed by using the Severity Index for Limbic Seizures and neuroethology. In addition to EEG, reviewed after the 1st, 20th and 21th stimuli we also examined the presence/absence of neurodegeneration in regions of the limbic system. The results obtained in this study were compared with those obtained in the protocol of olfactory stimulation with TMT on acute audiogenic seizures of rats from the WAR strain. The TMT triggered fear reactions and modified the behavioral sequences, reduced motor activity and grooming behavior. Qualitative data from gas chromatography and mathematical algorithms made possible to establish the concentrations in the camera for the different doses of TMT. In addition, the gas chromatography helped to identify that 30 minutes is the time required for saturation and desaturation of the camera to TMT and indicated a homogeneous saturation of the interior of such camera. The pure TMT in rapid electrical kindling in Wistar rats was able to significantly reduce the Severity Index for Limbic Seizures, compared to water, corroborating the data of the neuroethology method indicating the suppressive effect of TMT in seizures, in both, the model of rapid electrical kindling as well as the acute audiogenic seizures. However, the results of the duration of the EEGraphic primary after-discharge at the 21th stimulus were inconclusive, requiring further analysis using different analytical methods. With the technique of FJC it was not observed necrotic cell death in any studied brain region

Behavioral, electrophysiological and cellular characterization of rapid amygdala burning and treatments with olfactory stimuli and with HUF-101, a potent analogue of cannabidiol

Cerca de 30% dos pacientes com Epilepsia do Lobo Temporal (ELT) não respondem aos atuais tratamentos e uma possível razão é a compreensão restrita dos mecanismos básicos envolvidos nas Epilepsias. Estudos indicam que a exposição a um estímulo olfatório é capaz de modular a ocorrência das crises epilépticas. Adicionalmente, cresce o uso do Canabidiol (CBD) como tratamento alternativo e complementar nas Epilepsias, entretanto, uma promissora opção é seu derivado sintético fluorado, o HUF-101. Assim, os objetivos deste estudo foram: (Capítulo I) Investigar em modelo animal as Epilepsias e sua repercussão na função cognitiva (aprendizado e memória), associada a potencial neurogênese hipocampal aberrante. (Capítulo II) Avaliar os efeitos do 2,5-Dihydro-2,4,5-trimethylthiazoline (TMT, incluindo nanoemulsão) e da estimulação elétrica hipotalâmica, nas respostas defensivas inatas ou condicionadas, sob uma variedade de condições. (Capítulo III) Verificar os efeitos eletrencefalográficos (EEGráficos) da exposição ao TMT, nas crises límbicas induzidas pelo Abrasamento Rápido da Amígdala (ARA). (Capítulo IV) Avaliar os efeitos da administração aguda de HUF-101, um potente derivado fluorado sintético do CBD, no ARA, um modelo experimental de ELT. Para tanto foram realizados diferentes protocolos: (Capítulo I) Ratos Wistar-Old machos (280-300 g) foram submetidos ao procedimento cirúrgico para implante de eletrodos, subsequentemente os animais foram expostos ao protocolo de ARA, que consistiu em 10 estimulações elétricas diárias, durante 2 dias consecutivos. Quarenta e oito horas após foram submetidos ao Labirinto Aquático de Morris (LAM) e seus cérebros foram processados para imunoistoquímica de Duplacortina, em adição foram realizadas análises comportamentais (Escala de Racine/Pinel & Rovner e para o LAM), EEGráfica e histologia para Nissl (CEUA: 133/2015). (Capítulo II) (Protocolo 1) Ratos Sprague Dawley machos adultos foram expostos à seguinte sequência de testes: Sobressalto Potencializado pelo Medo, Condicionamento Contextual com Estímulo Olfatório (Acetato de Amila ou TMT ou Veículo Nanoelmulsão ou TMT Nanoemulsão), Labirinto em Cruz Elevado, Campo Aberto, extração seriada e dosagem da Corticosterona e dissecção da Glândula Adrenal. (Protocolo 2) Ratos Wistar-Old machos adultos receberam 4 preparações (5 µL em cada narina) na seguinte sequência: sem odor (apenas estímulo mecânico), água, nanoemulsão contendo veículo e nanoemulsão contendo TMT, após foi realizado a neuroetologia. (Protocolo 3): Ratos Wistar-Old machos adultos após implante dos eletrodos foram submetidos a estimulação elétrica hipotalâmica (intensidade crescente da corrente: 100-1000 µA), ao final foi realizada a análise neuroetológica (CEUA: 20/2019). (Capítulo III) Ratos Wistar-Old machos (280-300 g) após estereotaxia, parte dos animais foi exposta a câmara saturada com Água ou TMT, enquanto a outra parte, após o ARA e previamente ao 21º estímulo, foi submetida a exposição olfatória, também com Água ou TMT. A atividade EEGráfica foi avaliada pela ocorrência da 1º e 2º pós descargas e pela Transformada Rápida de Fourier (CEUA: 200/2011). (Capítulo IV) Ratos Wistar-Old machos adultos após cirurgia estereotáxica foram submetidos ao ARA, no 3º dia foram injetados com veículo ou HUF-101 (10 mg/kg; i.p). Trinta minutos após o tratamento, os animais foram expostos ao estímulo teste. Respostas comportamentais foram classificadas de acordo com a Escala de Racine/Pinel & Rovner e sequências comportamentais (análise neuroetológica), além disso, foi realizada análise EEGráfica (CEUA: 27/2019). Os resultados indicaram: (Capítulo I) A Epilepsia induzida pelo ARA não interferiu na função cognitiva (aprendizado e memória espacial), associado à ausência da neurogênese hipocampal aberrante. (Capítulo II) O TMT líquido induziu respostas de medo inato, mas não medo condicionado ao contexto, além disso, desencadeou comportamentos tipo ansiosos, sem alterar a atividade locomotora. Adicionalmente, ratos expostos agudamente ao TMT apresentaram aumento da secreção de Corticosterona e do peso das Adrenais. Enquanto o TMT nanoemulsão não interferiu substancialmente nas respostas comportamentais de medo inato. E por último, a estimulação hipotalâmica induziu importantes comportamentos defensivos. (Capítulo III) Avaliações comportamentais e EEGráficas confirmaram que o TMT, um estímulo olfatório com forte relevância biológica (cheiro de predador), reduziu significativamente as crises epileptiformes límbicas. (Capítulo IV) A administração aguda do derivado fluorado sintético do CBD, o HUF-101 (10 mg/kg i.p.) apresentou efeito anticonvulsivante no ARA. Dados adicionais e complementares indicaram efeito neuroprotetor do HUF-101 somente após indução do Status Epilepticus, mas não no ARA.About 30% of patients with Temporal Lobe Epilepsy (TLE) do not respond to current treatments and a possible reason is the restricted understanding of the basic mechanisms involved in Epilepsies. Studies indicate that exposure to an olfactory stimulus is capable of modulating the occurrence of epileptic seizures. Additionally, the use of Canabidiol (CBD) as an alternative and complementary treatment in Epilepsies has grown, however, a promising option is its fluorinated synthetic derivative, HUF-101. Thus, the objectives of this study were: (Chapter I) To investigate in an animal model to Epilepsies its repercussion on cognitive function (learning and memory) potentially associated with aberrant hippocampal neurogenesis. (Chapter II) To evaluate the effects of 2,5-Dihydro-2,4,5-trimethylthiazoline (TMT, including nanoemulsion) and hypothalamic electrical stimulation, on innate or conditional defensive responses, under a variety of conditions. (Chapter III) To verify the behavioral and electrencephalographic (EEGraphic) effects of TMT in the limbic seizures induced by Amygdala Rapid Kindling (ARK). (Chapter IV) To evaluate the effects of acute administration of HUF-101, a potent synthetic fluorinated derivative of CBD, in ARK, an experimental model of ELT. For this purpose, different protocols were performed: (Chapter I) Male Wistar-Old rats (280-300 g) were submitted to the surgical procedure for electrode implantation, subsequently the animals were exposed to the ARK protocol, which consisted in 10 daily electrical stimuli, during 2 consecutive days. Forty-eight hours later, they were submitted to the Morris Water Maze (MWM) and their brains were processed for immunohistochemistry of Doublecortin, in addition behavioral (Racine/Pinel & Rovner Scale and for MWM), EEGraphic and histology for Nissl analyzes were performed (CEUA: 133/2015). (Chapter II) (Protocol 1) Adult male Sprague Dawley rats were exposed to the following sequence of tests: Fear Potentiated Startle, Contextual Conditioning with Olfactory Stimulation (Amyl Acetate or TMT or Vehicle Nanoelmulsion or TMT Nanoemulsion), Elevated Plus Maze, Open Field, serial extraction and Corticosterone dosing and Adrenal Gland dissection. (Protocol 2) Adult male Wistar-Old rats received 4 preparations (5 µl in each nostril) in the following sequence: no odor (only mechanical stimulus), water, vehicle-containing nanoemulsion and TMT-containing nanoemulsion after it was realized neuroethology. (Protocol 3): Adult male Wistar-Old rats, after electrode implantation, were submitted to hypothalamic electrical stimulation (increasing intensity of the current: 100-1000 µA) and at the end the neuroethological analysis was performed (CEUA: 20/2019). (Chapter III) Male Wistar-Old rats (280-300 g) after stereotactic surgery, part of the animals was exposed to a chamber saturated with water or TMT, while the other part, after ARK and prior to the 21st stimulus, underwent olfactory exposure, also with water or TMT. The EEG activity was evaluated by the occurrence of the 1st and 2nd afterdischarges and by the Fast Fourier Transform (CEUA: 200/2011). (Chapter IV) Adult male Wistar-Old rats after stereotactic surgery were submitted to ARK, on the 3rd day they were injected with vehicle or HUF-101 (10 mg/kg; i.p). Thirty minutes after the treatment, animals were exposed to the test stimulus. Behavioral responses were classified according to the Racine/Pinel & Rovner Scale and behavioral sequences (neuroethological analysis), in addition, the EEG analysis was performed (CEUA: 27/2019). The results indicated: (Chapter I) ARK-induced epilepsy did not interfere with cognitive function (learning and spatial memory), associated with the absence of aberrant hippocampal neurogenesis. (Chapter II) TMT induced responses of innate fear but not conditioned fear to the context, in addition, triggered anxious-like behaviors, without altering the locomotor activity. Additionally, rats exposed acutely to TMT had increased Corticosterone secretion and Adrenal weight. TMT nanoemulsion did not interfer substantially in the behavioral responses of innate fear. And finally, hypothalamic stimulation induced important defensive behaviors. (Chapter III) EEG assessments confirmed that TMT, an olfactory stimulus with strong biological relevance, significantly reduced limbic epileptiform seizures. (Chapter IV) Acute administration of the synthetic fluorinated derivative of CBD, HUF-101 (10 mg/kg, i.p.) showed anticonvulsant effect. Additional and complementary data indicated neuroprotective effect of the HUF-101 only after induction of Status Epilepticus, but not in ARK

The influence of olfactory stimulation in the development of limbic seizures in rats

Um dos modelos experimentais mais utilizados para estudar a epilepsia do lobo temporal (ELT) é o abrasamento (kindling) por estimulação elétrica diária da amígdala, o abrasamento elétrico convencional. Uma alternativa rápida e eficaz a esse modelo é o abrasamento elétrico rápido, também capaz de gerar crises límbicas, porém com 10 estímulos elétricos aplicados ao dia, por 2 dias. No 3º dia é aplicado um estímulo elétrico adicional, o 21º estímulo, quando podem ser testadas drogas antiepilépticas ou estudados mecanismos de plasticidade ou memória. Entre as principais áreas ativadas nas crises límbicas encontram-se o complexo amigdalóide, a formação hipocampal, o córtex piriforme e neocórtices adjacentes. O envolvimento de estruturas olfatórias na ELT é antigo e estudos indicam que a exposição a um estímulo olfatório é capaz de suprimir, inibir ou induzir a ocorrência de crises. Todas as evidências clínicas e experimentais dão suporte científico para a hipótese de que a estimulação olfatória com o 2,5-Dihydro-2,4,5-trimethylthiazoline (TMT), uma potente substância química, derivada das fezes de raposa e que biologicamente representa o cheiro de predador pode influenciar no processo de crises evocadas por estimulação elétrica da amígdala. O objetivo geral do presente estudo foi avaliar a influência da apresentação do estímulo olfatório com TMT nas crises epilépticas de ratos Wistar, submetidos ao abrasamento elétrico rápido da amígdala. Para tanto, os parâmetros químicos do TMT foram avaliados, bem como as respostas comportamentais de ratos Wistar machos naives submetidos ao estímulo olfatório com diferentes doses de TMT. Na sequência, um novo grupo de ratos Wistar machos naives foi submetido ao protocolo de abrasamento elétrico rápido da amígdala com a aquisição dos registros eletrencefalográficos (EEGráficos) do córtex piriforme, formação hipocampal além do complexo amigdalóide. Após abrasados os animais foram expostos ao TMT ou água destilada, previamente ao 21º estímulo elétrico. Posteriormente o tecido cerebral foi processado (perfundido, crioprotegido, congelado e cortado) e então foram feitas as técnicas histoquímicas de: Nissl e Fluoro-Jade C (FJC, marcador de neurodegeneração). As respostas comportamentais foram analisadas mediante o uso do Índice de Gravidade para Crises Límbicas e da neuroetologia. Adicionalmente foi avaliada a expressão EEGráfica do 1º, 20º e 21º estímulos e verificada a presença/ausência de neurodegeneração em regiões do sistema límbico. Os resultados da análise comportamental obtidos nesse estudo foram comparados com os obtidos no protocolo de estimulação olfatória com TMT nas crises audiogênicas agudas de ratos da cepa WAR. O TMT desencadeou reações de medo e modificou as sequências comportamentais, reduziu a atividade motora e os comportamentos de autolimpeza. Dados qualitativos da cromatografia gasosa e algoritmos matemáticos possibilitaram estabelecer as concentrações na câmara para as diferentes doses de TMT. Além disso, a cromatografia gasosa identificou que 30 minutos é o tempo necessário para saturação e dessaturação da câmara ao TMT, e indicou uma saturação homogênea do interior dessa câmara. O TMT puro no abrasamento elétrico rápido em ratos Wistar foi capaz de reduzir significativamente o Índice de Gravidade para Crises Límbicas comparado à água, corroborando os dados neuroetológicos que indicam o efeito supressor do TMT nas crises, tanto para o modelo de abrasamento elétrico rápido quanto para as crises audiogênicas agudas. Os resultados da duração da pós-descarga EEGráfica primária no 21º estímulo foram inconclusivos, sendo necessárias outras análises empregando diferentes métodos analíticos. Com a técnica de FJC não foi possível verificar morte celular por necrose em qualquer região cerebral avaliada.One of the most widely used experimental models to study temporal lobe epilepsy (TLE) is the kindling by electrical daily stimulation of the amygdala, the conventional kindling. A rapid and effective alternative to this model is rapid electrical kindling, also capable of generating limbic seizures, but with 10 electrical stimuli applied per day for 2 days. On the 3rd day an additional electrical stimulus is applied, the 21st stimulus, when antiepileptic drugs can be tested or mechanisms of plasticity and memory can be studied. Among the main areas activated in limbic seizures are the amygdaloid complex, the hippocampal formation, piriform cortex and adjacent neocortices. The involvement of the olfactory structures in TLE is old and studies indicate that exposure to an olfactory stimulus is capable to suppress or inhibit or induce the occurrence of seizures. All the clinical and experimental evidences provide scientific support for the hypothesis that the olfactory stimulation with 2,5-Dihydro-2,4,5-trimethylthiazoline (TMT), a powerful chemical substance derived from fox feces which biologically represents the \"predator smell can influence the seizures process evoked by electrical stimulation of the amygdala. The overall objective of this study was to evaluate the influence of olfactory stimulation with TMT in seizures of Wistar rats subjected to rapid electrical kindling of the amygdala. Therefore, the chemical parameters of TMT were evaluated, as well as behavioral responses of naive male Wistar rats exposed to the olfactory stimulus with different concentrations of TMT. Other group of rats was electrically stimulated in the amygdaloid complex, following the protocol of rapid electrical kindling and the electroencephalographic recordings (EEGraphic) obtained from the piriform cortex, hippocampal formation in addition to the amygdaloid complex. After scorched the animals were exposed to TMT or distilled water, prior to the 21st electrical stimulation. Subsequently the cerebral tissue was processed (perfused, cryoprotected, frozen and sliced) and then processed for Nissl and Fluoro-Jade C histochemistry (FJC, a marker of neurodegeneration). The behavioral responses were analyzed by using the Severity Index for Limbic Seizures and neuroethology. In addition to EEG, reviewed after the 1st, 20th and 21th stimuli we also examined the presence/absence of neurodegeneration in regions of the limbic system. The results obtained in this study were compared with those obtained in the protocol of olfactory stimulation with TMT on acute audiogenic seizures of rats from the WAR strain. The TMT triggered fear reactions and modified the behavioral sequences, reduced motor activity and grooming behavior. Qualitative data from gas chromatography and mathematical algorithms made possible to establish the concentrations in the camera for the different doses of TMT. In addition, the gas chromatography helped to identify that 30 minutes is the time required for saturation and desaturation of the camera to TMT and indicated a homogeneous saturation of the interior of such camera. The pure TMT in rapid electrical kindling in Wistar rats was able to significantly reduce the Severity Index for Limbic Seizures, compared to water, corroborating the data of the neuroethology method indicating the suppressive effect of TMT in seizures, in both, the model of rapid electrical kindling as well as the acute audiogenic seizures. However, the results of the duration of the EEGraphic primary after-discharge at the 21th stimulus were inconclusive, requiring further analysis using different analytical methods. With the technique of FJC it was not observed necrotic cell death in any studied brain region

Evaluation of Strength and Irradiated Movement Pattern Resulting from Trunk Motions of the Proprioceptive Neuromuscular Facilitation

Introduction. The proprioceptive neuromuscular facilitation (PNF) is a physiotherapeutic concept based on muscle and joint proprioceptive stimulation. Among its principles, the irradiation is the reaction of the distinct regional muscle contractions to the position of the application of the motions. Objective. To investigate the presence of irradiated dorsiflexion and plantar flexion and the existing strength generated by them during application of PNF trunk motions. Methods. The study was conducted with 30 sedentary and female volunteers, the PNF motions of trunk flexion, and extension with the foot (right and left) positioned in a developed equipment coupled to the load cell, which measured the strength irradiated in Newton. Results. Most of the volunteers irradiated dorsal flexion in the performance of the flexion and plantar flexion during the extension motion, both presenting an average force of 8.942 N and 10.193 N, respectively. Conclusion. The distal irradiation in lower limbs became evident, reinforcing the therapeutic actions to the PNF indirect muscular activation

Scale up of implementation of a multidimensional intervention to enhance hypertension and diabetes care at the primary care setting: A protocol for a cluster-randomized study in Brazil

Background: Hypertension and diabetes mellitus (DM) are highly prevalent in low and middle-income countries (LMICs), and the proportion of patients with uncontrolled diseases is higher than in high-income countries. Innovative strategies are required to surpass barriers of low sources, distance and quality of health care. Our aim is to assess the uptake and effectiveness of the implementation of an integrated multidimensional strategy in the primary care setting, for the management of people with hypertension and diabetes mellitus in Brazil.Methods: This scale up implementation study called Control of Hypertension and diAbetes in MINas Gerais (CHArMING) Project has mixed-methods, and comprehends 4 steps: (1) needs assessment, including a standardized structured questionnaire and focus groups with health care practitioners; (2) baseline period, 3 months before the implementation of the intervention; (3) cluster randomized controlled trial (RCT) with a 12-months follow-up period; and (4) a qualitative study after the end of follow-up. The cluster RCT will randomize 35 centers to intervention (n = 18) or usual care (n = 17). Patients ≥18 years old, with diagnosis of hypertension and/or DM, of 5 Brazilian cities in a resource-constrained area will be enrolled. The intervention consists of a multifaceted strategy, with a multidisciplinary approach, including telehealth tools (decision support systems, short message service, telediagnosis), continued education with an approach to issues related to the care of people with hypertension and diabetes in primary care, including pharmacological and non-pharmacological treatment and behavioral change. The project has actions focused on professionals and patients.Conclusions: This study consists of a multidimensional strategy with multidisciplinary approach using digital health to improve the control of hypertension and/or DM in the primary health care setting. We expect to provide the basis for implementing an innovative management program for hypertension and DM in Brazil, aiming to reduce the present and future burden of these diseases in Brazil and other LMICs.Clinical Trial Identifier: This study was registered in ClinicalTrials.gov. (NCT05660928).</p

ESCORE MMCD PARA PREDIÇÃO DE TERAPIA RENAL SUBSTITUTIVA E MORTALIDADE INTRA-HOSPITALAR EM PACIENTES HOSPITALIZADOS COM COVID-19 DE 2020 A 2022

Introdução: A lesão renal aguda (LRA) com necessidade de terapia renal substitutiva (TRS) em suas formas mais graves é uma complicação importante de pacientes com covid-19. O desenvolvimento de um escore de risco para predizer a necessidade de TRS pode ser muito útil, para melhor alocação de recursos de saúde. Assim, este estudo teve como objetivo desenvolver e validar um escore para predição de necessidade de TRS, em pacientes hospitalizados com covid-19, entre 2020 e 2022. Métodos: Trata-se de uma coorte retrospectiva multicêntrica de pacientes consecutivos internados por covid-19, confirmada laboratorialmente, em 40 hospitais brasileiros, entre março de 2020 e julho de 2022. Foram excluídos do estudo pacientes menores de 18 anos, grávidas, em cuidados paliativos ou terapia dialítica à admissão. A seleção de variáveis preditoras foi realizada utilizando modelos aditivos generalizados (GAM). Enquanto, a regressão do operador de seleção e contração mínima absoluta (LASSO) foi usada para derivação de pontuação. O escore foi desenvolvido no período de março a julho de 2020, com validação temporal e geográfica de julho a setembro de 2020 e nova validação temporal no período de março de 2021 a julho de 2022. O desempenho do MMCD foi avaliado pela área sob a curva da característica de operação do receptor (AUROC, com intervalo de confiança de 95%), análise gráfica com teste de intercepto e inclinação e escore de Brier. Resultados: Foram incluídos 3.680 pacientes na amostra de desenvolvimento, 1.532 na validação temporal 2020, 1.378 na validação geográfica e 9.473 na validação temporal 2021-2022. Quatro preditores da necessidade de TRS foram identificados: ventilação mecânica a qualquer momento da internação, sexo masculino, creatinina à admissão e diabetes mellitus. O escore nomeado como MMCD apresentou excelente discriminação, calibração e desempenho geral nas coortes de derivação e validações (desenvolvimento: AUROC: 0.929; IC95%: 0.918–0.939, escore de Brier: 0.057; validação temporal 2020: AUROC 0.927, IC95% 0.911–0.941, escore de Brier 0.056; validação geográfica 2020: AUROC: 0.819, IC95% 0.792–0.845, escore de Brier 0.122; validação temporal 2021/2022: AUROC 0.916, IC95% 0.909-0.924, escore de Brier 0.057). Conclusão: O MMCD apresentou excelente capacidade preditiva para TRS nas diferentes fases da pandemia, o que pode contribuir para subsidiar decisões mais assertivas na alocação de recursos assistenciais

Mechanical ventilation and death in pregnant patients admitted for COVID-19: a prognostic analysis from the Brazilian COVID-19 registry score

Abstract Background The assessment of clinical prognosis of pregnant COVID-19 patients at hospital presentation is challenging, due to physiological adaptations during pregnancy. Our aim was to assess the performance of the ABC2-SPH score to predict in-hospital mortality and mechanical ventilation support in pregnant patients with COVID-19, to assess the frequency of adverse pregnancy outcomes, and characteristics of pregnant women who died. Methods This multicenter cohort included consecutive pregnant patients with COVID-19 admitted to the participating hospitals, from April/2020 to March/2022. Primary outcomes were in-hospital mortality and the composite outcome of mechanical ventilation support and in-hospital mortality. Secondary endpoints were pregnancy outcomes. The overall discrimination of the model was presented as the area under the receiver operating characteristic curve (AUROC). Overall performance was assessed using the Brier score. Results From 350 pregnant patients (median age 30 [interquartile range (25.2, 35.0)] years-old]), 11.1% had hypertensive disorders, 19.7% required mechanical ventilation support and 6.0% died. The AUROC for in-hospital mortality and for the composite outcome were 0.809 (95% IC: 0.641–0.944) and 0.704 (95% IC: 0.617–0.792), respectively, with good overall performance (Brier = 0.0384 and 0.1610, respectively). Calibration was good for the prediction of in-hospital mortality, but poor for the composite outcome. Women who died had a median age 4 years-old higher, higher frequency of hypertensive disorders (38.1% vs. 9.4%, p < 0.001) and obesity (28.6% vs. 10.6%, p = 0.025) than those who were discharged alive, and their newborns had lower birth weight (2000 vs. 2813, p = 0.001) and five-minute Apgar score (3.0 vs. 8.0, p < 0.001). Conclusions The ABC2-SPH score had good overall performance for in-hospital mortality and the composite outcome mechanical ventilation and in-hospital mortality. Calibration was good for the prediction of in-hospital mortality, but it was poor for the composite outcome. Therefore, the score may be useful to predict in-hospital mortality in pregnant patients with COVID-19, in addition to clinical judgment. Newborns from women who died had lower birth weight and Apgar score than those who were discharged alive