Predicting of novel homoserine dehydrogenase inhibitors against Paracoccidioides brasiliensis: integrating in silico and in vitro approaches.

Aim: To search for potential inhibitors to homoserine dehydrogenase (HSD) in Paracoccidioides brasiliensis the causative agent of paracoccidioidomycosis, an infection with a high mortality rate in Brazil.Materials & methods: The enzyme was modeled and used in the virtual screening of the compounds. The library was first screened by the Autodock, in which 66 molecules were better ranked than substrate, and then, also evaluated by the Molegro and Gold programs.Results: The HS23 and HS87 molecules were selected in common by the three programs, and ADME/Tox evaluation indicates they are not toxic. The molecular dynamics of PbHSD bonded to ligands showed stable complexes until 50 ns. To validate the results, compounds were purchased for assays of minimum inhibitory concentration (MIC), minimum fungicidal concentration (MFC), synergic profile with Amphotericin B (AmB) and cytotoxicity. The two molecules presented MIC of 32 µg/ml and MFC of 64 µg/ml against the P. brasiliensis (strain Pb18). They also showed synergistic activity with AmB and a lack of toxicity against Hela and Vero cell lines.Conclusion: These results suggest that the HS23 and HS87 are promising candidates as PbHSD inhibitors and may be used as hits for the development of new drugs against paracoccidioidomycosis.

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Expression levels of ACE and ACE2 in the placenta and white adipose tissue of lean and obese pregnant women.

BACKGROUND: This study evaluated the expression of ACE and ACE2 in the placenta and white adipose tissue in lean and obese women, and correlated their levels with anthropometric, clinical, and laboratory parameters, and tissue count of inflammatory cells. METHODS: A cross-sectional analytical study was performed with 49 pregnant women and their respective newborns. Samples of placenta and adipose tissue were used for measuring mRNA expression for ACE and ACE2 through qRT-PCR. Inflammatory cell counting was performed through conventional microscopy. RESULTS: An increase in ACE expression and a decrease in ACE2 were observed in the placenta and adipose tissue of women with obesity. ACE2 levels showed a negative correlation with pre-pregnancy BMI and total cholesterol. CONCLUSION: Maternal obesity can modulate the expression of RAS components in the placenta and white adipose tissue, with ACE2 correlated with pre-pregnancy BMI and total cholesterol.

Intracranial compliance in patients with COVID-19: a multicenter observational study.

BACKGROUND: Patients with severe coronavirus disease-19 (COVID-19) may require the use of invasive mechanical ventilation (MV) for prolonged periods. Aggressive MV parameters have been associated with changes in intracranial pressure (ICP) in patients with acute intracranial disorders. Significant ICP elevation could compromise intracranial compliance (ICC) and cerebrovascular hemodynamics (CVH). However, the effects of these parameters in individuals without neurological disorders have not yet been evaluated. OBJECTIVE: To evaluate ICC in patients on MV with COVID-19 infection compared to other diagnoses, to better characterize the effects of MV and COVID-19 upon ICC. We also compared between the ICC in patients with COVID-19 who did not require MV and healthy volunteers, to assess the isolated effect of COVID-19 upon ICC. METHODS: This was an exploratory, observational study with a convenience sample. The ICC was evaluated with a noninvasive ICP monitoring device. The P2/P1 ratio was calculated by dividing the amplitude of these two points, being defined as "abnormal" when P2 > P1. The statistical analysis was performed using a mixed linear model with random effects to compare the P2/P1 ratio in all four groups on the first monitoring day. RESULTS: A convenience sample of 78 subjects (15 MV-COVID-19, 15 MV non-COVID-19, 24 non-MV-COVID-19, and 24 healthy participants) was prospectively enrolled. There was no difference in P2/P1 ratios between MV patients with and without COVID-19, nor between non-MV patients with COVID-19 and healthy volunteers. However, the P2/P1 ratio was higher in COVID-19 patients with MV use than in those without it. CONCLUSION: This exploratory analysis suggests that COVID-19 does not impair ICC.

ANTECEDENTES: Pacientes com doença grave por coronavírus-19 (COVID-19) podem necessitar do uso de ventilação mecânica (VM) invasiva por um período prolongado. Parâmetros agressivos de VM têm sido associados a alterações na pressão intracraniana (PIC) em pacientes com doenças intracranianas agudas. Elevações significativas da PIC podem comprometer a complacência intracraniana (CIC) e a hemodinâmica cerebrovascular (HVC). No entanto, os efeitos desses parâmetros em indivíduos sem doenças neurológicas ainda não foram sistematicamente avaliados. OBJETIVO: Avaliar a CIC em pacientes em VM com COVID-19 comparados com outros diagnósticos, para melhor caracterizar os efeitos da VM e COVID-19 sobre a CIC. Também foi feita a comparação entre a CIC em pacientes com COVID-19 sem VM e voluntários saudáveis, para avaliar o efeito isolado da COVID-19 sobre a ICC. MéTODOS: Trata-se de um estudo exploratório, observacional com amostra por conveniência. A CIC foi avaliada com um dispositivo não invasivo de monitoramento da PIC. A relação P2/P1 foi calculada dividindo-se a amplitude desses dois pontos, sendo definida como "anormal" quando P2 > P1. A análise estatística foi realizada usando um modelo linear misto com efeitos aleatórios para comparar a relação P2/P1 nos quatro grupos no primeiro dia de monitoramento. RESULTADOS: Uma amostra de conveniência com 78 voluntários (15 COVID-19 em VM, 15 sem COVID-19 em VM, 24 com COVID em respiração espontânea e 24 saudáveis) foram prospectivamente incluídos. Não houve diferença nas razões P2/P1 entre pacientes em VM com e sem COVID-19, nem entre pacientes sem VM com COVID-19 ou saudáveis. No entanto, a relação P2/P1 foi maior em pacientes com COVID-19 com uso de VM do que naqueles sem. CONCLUSãO: Os dados dessa análise exploratória sugerem que a COVID-19 não prejudica a CIC.

A predictive score for atrial fibrillation in poststroke patients.

BACKGROUND: Atrial fibrillation (AF) is a risk factor for cerebral ischemia. Identifying the presence of AF, especially in paroxysmal cases, may take time and lacks clear support in the literature regarding the optimal investigative approach; in resource-limited settings, identifying a higher-risk group for AF can assist in planning further investigation. OBJECTIVE: To develop a scoring tool to predict the risk of incident AF in the poststroke follow-up. METHODS: A retrospective longitudinal study with data collected from electronic medical records of patients hospitalized and followed up for cerebral ischemia from 2014 to 2021 at a tertiary stroke center. Demographic, clinical, laboratory, electrocardiogram, and echocardiogram data, as well as neuroimaging data, were collected. Stepwise logistic regression was employed to identify associated variables. A score with integer numbers was created based on beta coefficients. Calibration and validation were performed to evaluate accuracy. RESULTS: We included 872 patients in the final analysis. The score was created with left atrial diameter ≥ 42 mm (2 points), age ≥ 70 years (1 point), presence of septal aneurysm (2 points), and score ≥ 6 points at admission on the National Institutes of Health Stroke Scale (NIHSS; 1 point). The score ranges from 0 to 6. Patients with a score ≥ 2 points had a fivefold increased risk of having AF detected in the follow-up. The area under the curve (AUC) was of 0.77 (0.72-0.85). CONCLUSION: We were able structure an accurate risk score tool for incident AF, which could be validated in multicenter samples in future studies.

ANTECEDENTES: Fibrilação atrial (FA) é um fator de risco para isquemia cerebral. Identificar a presença de FA, especialmente em casos paroxísticos, pode demandar tempo, e não há fundamentos claros na literatura quanto ao melhor método de proceder à investigação; em locais de parcos recursos, identificar um grupo de mais alto risco de FA pode auxiliar no planejamento da investigação complementar. OBJETIVO: Desenvolver uma ferramenta de escore para prever o risco de FA no acompanhamento após acidente vascular cerebral (AVC). MéTODOS: Estudo longitudinal retrospectivo, com dados coletados dos prontuários eletrônicos de pacientes hospitalizados e acompanhados ambulatorialmente por isquemia cerebral, de 2014 a 2021, em um centro de AVC terciário. Foram coleados dados demográficos, clínicos, laboratoriais, de eletrocardiograma e ecocardiograma, além de dados de neuroimagem. Mediante uma regressão logística por stepwise, foram identificadas variáveis associadas. Um escore com números inteiros foi criado com base nos coeficientes beta. Calibração e validação foram realizadas para avaliar a precisão. RESULTADOS: Foram incluídos 872 pacientes na análise final. O escore foi criado com diâmetro de átrio esquerdo ≥ 42 mm (2 pontos), idade ≥ 70 anos (1 ponto), presença de aneurisma septal (2 pontos) e pontuação à admissão ≥ 6 na escala de AVC dos National Institutes of Health (National Institutes of Health Stroke Scale, NIHSS, em inglês; 1 ponto). O escore tem pontuação que varia de 0 a 6. Pacientes com escore ≥ 2 pontos tiveram cinco vezes mais risco de terem FA detectada no acompanhamento. A área sob a curva (area under curve, AUC, em inglês) foi de 0.77 (0.72­0.85). CONCLUSãO: Pudemos estruturar uma ferramenta precisa de escore de risco de FA, a qual poderá ser validada em amostras multicêntricas em estudos futuros.

Digital health in stroke: a narrative review.

Digital health is significantly transforming stroke care, particularly in remote and economically diverse regions, by harnessing mobile and wireless technologies, big data, and artificial intelligence (AI). Despite the promising advancements, a notable gap exists in the formal clinical validation of many digital health applications, raising concerns about their efficacy and safety in real-world clinical settings. Our review systematically explores the landscape of digital health in stroke care, assessing the development, validation, and implementation of various digital tools. We adopted a comprehensive search strategy, scrutinizing peer-reviewed articles published between January 2015 and January 2024, to gather evidence on the effectiveness of digital health interventions. A rigorous quality assessment was conducted to ensure the reliability of the included studies, with findings synthesized to underscore key technological innovations and their clinical outcomes. Ethical considerations were meticulously observed to maintain data confidentiality and integrity. Our findings highlight the transformative potential of mobile health technologies, AI, and telemedicine in improving diagnostic accuracy, treatment efficacy, and patient outcomes in stroke care. Our paper delves into the evolution and impact of digital health in cerebrovascular prevention, diagnosis, rehabilitation and stroke treatment, emphasizing the digital health's role in enhancing access to expert care, mitigating treatment delays and improving outcomes. However, the review also underscores the critical need for rigorous clinical validation and ethical considerations in the development and deployment of digital health technologies to ensure their safe and effective integration into stroke care practices.

A saúde digital está transformando significativamente o cuidado com o acidente vascular cerebral (AVC), especialmente em regiões remotas e economicamente diversas, ao aproveitar tecnologias móveis e sem fio, big data e inteligência artificial (IA). Apesar dos avanços promissores, existe uma lacuna notável na validação clínica formal de muitas aplicações de saúde digital, levantando preocupações sobre sua eficácia e segurança em ambientes clínicos do mundo real. Nossa revisão explora sistematicamente a paisagem da saúde digital no cuidado do AVC, avaliando o desenvolvimento, validação e implementação de várias ferramentas digitais. Adotamos uma estratégia de busca abrangente, examinando artigos revisados por pares publicados entre janeiro de 2015 e janeiro de 2024, para reunir evidências sobre a eficácia das intervenções de saúde digital. Uma avaliação de qualidade rigorosa foi conduzida para garantir a confiabilidade dos estudos incluídos, com os achados sintetizados para destacar as principais inovações tecnológicas e seus resultados clínicos. Considerações éticas foram meticulosamente observadas para manter a confidencialidade e integridade dos dados. Nossas descobertas destacam o potencial transformador das tecnologias de saúde móvel, IA e telemedicina em melhorar a precisão diagnóstica, a eficácia do tratamento e os resultados dos pacientes no cuidado do AVC. Nosso artigo aprofunda-se na evolução e impacto da saúde digital na prevenção, diagnóstico, reabilitação e tratamento do AVC, enfatizando seu papel em melhorar o acesso ao cuidado especializado, mitigar atrasos no tratamento e melhorar os desfechos. No entanto, a revisão também sublinha a necessidade crítica de validação clínica rigorosa e considerações éticas no desenvolvimento e implantação de tecnologias de saúde digital para garantir sua integração segura e eficaz nas práticas de cuidado do AVC.

Use of Machine Perfusion to Increase the Number of Expanded Criteria Deceased Donor Kidney Transplants: A Pharmacoeconomic Analysis.

Background: The discard of expanded criteria donor (ECD) kidneys is unacceptably high, considering the growing demand for transplantation. Using machine perfusion may reduce the discard rate, increase the number of transplants, and reduce mortality on the waiting list. Methods: We developed a 5-y Markov model to simulate incorporating the pulsatile perfusion machine into the current government-funded healthcare system. The model compared the universal use of static cold storage for all kidneys with the selective use of machine perfusion for ECD kidneys. Real-life data were used to compose the cohort characteristics in this model. This pharmacoeconomic analysis aimed to determine the cost-effectiveness and budgetary impact of using machine perfusion to preserve ECD kidneys. Results: Compared with the universal use of static cold storage, the use of machine perfusion for ECD kidneys was associated with an increase in the number of kidney transplants (n = 1123), a decrease in the number of patients on the waiting list (n = 815), and decrease in mortality (n = 120), with a cost difference of US dollar 4 486 009 in the period. The budget impact analysis revealed an additional cost of US dollar 4 453 749 >5 y. The budget impact analysis demonstrated a progressive reduction in costs, becoming cost-saving during the last year of the analysis. Conclusions: This stochastic model showed that incorporating machine perfusion for ECD kidneys is most often a dominant or cost-effective technology associated with an increase in the number of transplants and a reduction in the number of patients on the waiting list, reducing mortality on the waiting list.

High triglyceride-glucose index and HOMA-IR are associated with different cardiometabolic profile in adults from the ELSA-Brasil study.

BACKGROUND AND AIMS: Insulin resistance (IR) is a risk factor for several cardiometabolic disorders; however, there is conflicting evidence about the reliability of certain IR markers. In this context, the triglyceride-glucose index (TyG) has been proposed as a surrogate marker for IR. This study aimed to compare the TyG index and homeostasis model assessment of insulin resistance (HOMA-IR). METHODS AND RESULTS: A cross-sectional analysis was conducted using baseline data from 11,314 adults (aged 35-74 years) from the ELSA-Brasil study. The correlation between TyG and HOMA-IR, their interrater reliability, and their predictive value in identifying metabolic syndrome (MetS) were assessed. The mean TyG and HOMA-IR in our sample were 8.81 ± 0.52 and 2.78 ± 1.58 for men, and 8.53 ± 0.48 and 2.49 ± 1.38 for women, respectively. TyG and HOMA-IR showed a weak to moderate correlation with each other (Pearson's r for men: 0.395 and 0.409 for women, p-value <0.05) and other markers of glycemic metabolism. Additionally, the area under the curve for the prediction of MetS was greater for TyG than HOMA-IR, regardless of sex (TyG: 0.836 for men and 0.826 for women; HOMA-IR: 0.775 for men and 0.787 for women). The concordance between these markers was low (Cohens kappa coefficient: 0.307 for men and 0.306 for women). Individuals with increased TyG exhibited mainly anthropometrical and glycemic metabolic alterations, whereas those with elevated HOMA-IR displayed mostly lipid-associated metabolic alterations. CONCLUSION: TyG and HOMA-IR might indicate different profiles of cardiometabolic disorders, showing poor agreement in classifying individuals (normal vs. altered) and a weak correlation. Therefore, further studies are needed to investigate the role of TyG as a surrogate marker of IR.

Diet Based on Pereskia aculeata Miller Flour Increases Muscle Volume and Modulates the Expression of Myokines in Mice Subjected to Resistance Training.

The study aimed to evaluate the effects of Pereskia aculeata Miller (ora-pro-nobis [OPN]) flour on body and biochemical parameters, thermogenic activity, and molecular expression of markers in the muscle tissue of mice subjected to resistance training (RT). Twelve mice were randomly assigned to two groups (n=6 animals/group): G1: control (Control) fed a standard diet + RT and G2: experimental (OPN) fed a diet based on OPN flour + RT. The RT consisted of a 6-week program using a vertical ladder combined with a fixed weight attached to the animal. Several parameters were measured, including assessment of body composition, biochemical markers, thermogenic activity, and molecular (mRNA expression of interleukin (IL)-6, fibronectin type III domain-containing protein 5 (FNDC5), peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM). The OPN group exhibited a decrease in body weight and visceral adiposity, higher energy expenditure, and lipid oxidation rate. In addition, it was observed an increase in muscle volume and in mRNA expression levels of IL-6, FNDC5, PGC-1α, and TFAM. These findings suggest that OPN flour could be a nutritional option to enhance performance in RT.

Asociación entre Glucemia inestable, tiempo de estancia y mortalidad de pacientes en estado críticos: Estudio de cohorte / Associação Entre Glicemia Instável, Tempo de Permanência e Mortalidade de Pacientes Críticos: Estudo de Coorte / Relationships between unstable Glycemia, Hospital Length Of Stay, and mortality In Critically Ill patients: A cohort study

Resumen Introducción: El control y la evaluación de los niveles glucémicos de pacientes en estado críticos es un desafío y una competencia del equipo de enfermería. Por lo que, determinar las consecuencias de esta durante la hospitalización es clave para evidenciar la importancia del oportuno manejo. Objetivo: Determinar la asociación entre la glucemia inestable (hiperglucemia e hipoglucemia), el resultado de la hospitalización y la duración de la estancia de los pacientes en una unidad de cuidados intensivos. Metodología: Estudio de cohorte prospectivo realizado con 62 pacientes a conveniencia en estado crítico entre marzo y julio de 2017. Se recogieron muestras diarias de sangre para medir la glucemia. Se evaluó la asociación de la glucemia inestable con la duración de la estancia y el resultado de la hospitalización mediante ji al cuadrado de Pearson. El valor de p<0.05 fue considerado significativo. Resultados: De las 62 personas participantes, 50 % eran hombres y 50 % mujeres. La edad media fue de 63.3 años (±21.4 años). La incidencia de glucemia inestable fue del 45.2 % y se asoció con una mayor duración de la estancia en la UCI (p<0.001) y una progresión a la muerte como resultado de la hospitalización (p=0.03). Conclusión: Entre quienes participaron, la glucemia inestable se asoció con una mayor duración de la estancia más prolongada y con progresión hacia la muerte, lo que refuerza la importancia de la actuación de enfermería para prevenir su aparición.

Resumo Introdução: O controle e avaliação dos níveis glicêmicos em pacientes críticos é um desafio e uma competência da equipe de enfermagem. Portanto, determinar as consequências da glicemia instável durante a hospitalização é chave para evidenciar a importância da gestão oportuna. Objetivo: Determinar a associação entre glicemia instável (hiperglicemia e hipoglicemia), os desfechos hospitalares e o tempo de permanência dos pacientes em uma unidade de terapia intensiva. Métodos: Um estudo de coorte prospectivo realizado com 62 pacientes a conveniência em estado crítico entre março e julho de 2017. Foram coletadas amostras diariamente de sangue para medir a glicemia. A associação entre a glicemia instável com o tempo de permanência e o desfecho da hospitalização foi avaliada pelo teste qui-quadrado de Pearson. O valor de p <0,05 foi considerado significativo. Resultados: Das 62 pessoas participantes, 50% eram homens e 50% mulheres. A idade média foi de 63,3 anos (±21,4 anos). A incidência de glicemia instável foi de 45,2% e se associou a um tempo de permanência mais prolongado na UTI (p <0,001) e uma progressão para óbito como desfecho da hospitalização (p = 0,03). Conclusão: Entre os participantes, a glicemia instável se associou a um tempo mais longo de permanência e com progressão para óbito, enfatizando a importância da actuação da equipe de enfermagem para prevenir sua ocorrência.

Abstract Introduction: The control and evaluation of glycemic levels in critically ill patients is a challenge and a responsibility of the nursing team; therefore, determining the consequences of this during hospitalization is key to demonstrate the importance of timely management. Objective: To determine the relationship between unstable glycemia (hyperglycemia and hypoglycemia), hospital length of stay, and the hospitalization outcome of patients in an Intensive Care Unit (ICU). Methods: A prospective cohort study conducted with 62 critically ill patients by convenience sampling between March and July 2017. Daily blood samples were collected to measure glycemia. The correlation of unstable glycemia with the hospital length of stay and the hospitalization outcome was assessed using Pearson's chi-square. A p-value <0.05 was considered significant. Results: Among the 62 patients, 50% were male and 50% were female. The mean age was 63.3 years (±21.4 years). The incidence of unstable glycemia was 45.2% and was associated with a longer ICU stay (p<0.001) and a progression to death as a hospitalization outcome (p=0.03). Conclusion: Among critically ill patients, unstable glycemia was associated with an extended hospital length of stay and a progression to death, emphasizing the importance of nursing intervention to prevent its occurrence.

Oral supplementation with resveratrol improves hormonal profile and increases expression of genes associated with thermogenesis in oophorectomy mice.

Menopause causes important bodily and metabolic changes, which favor the increased occurrence of cardiovascular diseases, obesity, diabetes, and osteoporosis. Resveratrol exerts proven effects on body metabolism, improving glucose and lipid homeostasis and reducing inflammation and oxidative stress in various organs and tissues. Accordingly, this study evaluates the effects of resveratrol supplementation on the expression of markers associated with thermogenesis in brown adipose tissue, and on the body, metabolic and hormonal parameters of female mice submitted to bilateral oophorectomy. Eighteen female mice were randomized into three groups: G1: control (CONTROL), G2: oophorectomy (OOF), and G3: oophorectomy + resveratrol (OOF + RSV); the animals were kept under treatment for twelve weeks, being fed a standard diet and treated with resveratrol via gavage. Body, biochemical, hormonal, and histological parameters were measured; in addition to the expression of markers associated with thermogenesis in brown adipose tissue. The results showed that animals supplemented with resveratrol showed reduced body weight and visceral adiposity, in addition to glucose, total cholesterol, and triglyceride levels; decreased serum FSH levels and increased estrogen levels were observed compared to the OOF group and mRNA expression of PRDM16, UCP1, and SIRT3 in brown adipose tissue. The findings of this study suggest the important role of resveratrol in terms of improving body, metabolic, and hormonal parameters, as well as modulating markers associated with thermogenesis in brown adipose tissue of female mice submitted to oophorectomy.

Miller Fisher's Rules and Digital Health: The Best of Both Worlds.

BACKGROUND: Professor Fisher's legacy, defined by meticulous observation, curiosity, and profound knowledge, has established a foundational cornerstone in medical practice. However, the advent of automated algorithms and artificial intelligence (AI) in medicine raises questions about the applicability of Fisher's principles in this era. Our objective was to propose adaptations to these enduring rules, addressing the challenges and leveraging the opportunities presented by digital health. SUMMARY: The adapted rules we propose advocate for the harmonious integration of traditional bedside manners with contemporary technological advancements. The judicious use of advanced devices for patient examination, recording, and sharing, while upholding patient confidentiality, is pivotal in modern practice and academic research. Additionally, the strategic employment of AI tools at the bedside, to aid in diagnosis and hypothesis generation, underscores their role as valued complements to clinical reasoning. These adapted rules emphasize the importance of continual learning from experience, literature, and colleagues, and stress the necessity for a critical approach toward AI-derived information, which further consolidates clinical skills. These aspects underscore the perpetual relevance of Professor Fisher's rules, advocating not for their replacement but for their evolution. Thus, a balanced methodology that adeptly utilizes the strengths of AI and digital tools, while steadfastly maintaining the core humanistic values, arises as essential in the modern practice of medicine. KEY MESSAGES: A commitment between traditional medical wisdom and modern technological capabilities may enhance medical practice and patient care. This represents the future of medicine - a resolute commitment to progress and technology, while preserving the essence of medical humanities.

An automated flowchart for the Modified Rankin Scale assessment: A multicenter inter-rater agreement analysis.

BACKGROUND AND OBJECTIVE: The Modified Rankin Scale (mRS) is a widely adopted scale for assessing stroke recovery. Despite limitations, the mRS has been adopted as primary outcome in most recent clinical acute stroke trials. Designed to be used by multidisciplinary clinical staff, the congruency of this scale is not consistent, which may lead to mistakes in clinical or research application. We aimed to develop and validate an interactive and automated digital tool for assessing the mRS-the iRankin. METHODS: A panel of five board-certified and mRS-trained vascular neurologists developed an automated flowchart based on current mRS literature. Two international experts were consulted on content and provided feedback on the prototype platform. The platform contained five vignettes and five real video cases, representing mRS grades 0-5. For validation, we invited neurological staff from six comprehensive stroke centers to complete an online assessment. Participants were randomized into two equal groups usual practice versus iRankin. The participants were randomly allocated in pairs for the congruency analysis. Weighted kappa (kw) and proportions were used to describe agreement. RESULTS: A total of 59 professionals completed the assessment. The kw was dramatically improved among nurses, 0.76 (95% confidence interval (CI) = 0.55-0.97) × 0.30 (0.07-0.67), and among vascular neurologists, 0.87 (0.72-1) × 0.82 (0.66-0.98). In the accuracy analysis, after the standard mRS values for the vignettes and videos were determined by a panel of experts, and considering each correct answer as equivalent to 1 point on a scale of 0-15, it revealed a higher mean of 10.6 (±2.2) in the iRankin group and 8.2 (±2.3) points in the control group (p = 0.02). In an adjusted analysis, the iRankin adoption was independently associated with the score of congruencies between reported and standard scores (beta coefficient = 2.22, 95% CI = 0.64-3.81, p = 0.007). CONCLUSION: The iRankin adoption led to a substantial or near-perfect agreement in all analyzed professional categories. More trials are needed to generalize our findings. Our user-friendly and free platform is available at https://www.irankinscale.com/.

A Brazilian series utilizing the SMASH-U system for etiologic classification of intracerebral hemorrhage.

BACKGROUND: Understanding the causes of intracerebral hemorrhage (ICH) is crucial for effective treatment and preventing recurrences. The SMASH-U scale is a suggested method for classifying and predicting the outcomes of ICH. OBJECTIVE: To describe the SMASH-U classification and outcomes by etiology in patients admitted to a comprehensive stroke center in São Paulo, Brazil. METHODS: A retrospective analysis was conducted on patients admitted to the hospital or outpatient clinic between April 2015 and January 2018. Two stroke neurologists evaluated the SMASH-U classification, and patients with incomplete medical records were excluded. RESULTS: Out of the 2000 patients with a stroke diagnosis evaluated, 140 were included in the final analysis. The mean age was 57.9 (± 15.5) years, and 54.3% were male. Hypertension was the most frequent etiology, accounting for 41.4% of cases, followed by amyloid angiopathy (18.5%) and structural lesions (14.1%). Structural lesions were more common among women and patients under 45 years old. Favorable outcomes were observed in 61% of patients with structural lesions, compared to 10% of patients with medication-related etiologies. CONCLUSION: This study provides important evidence regarding the etiological classification of Brazilian patients with ICH. Hypertension and amyloid angiopathy were the most frequent causes, while structural lesions and systemic diseases were more common in younger patients.

ANTECEDENTES: Compreender as causas da hemorragia intracerebral (HIC) é crucial para o tratamento eficaz e prevenção de recorrências. A escala SMASH-U é um método sugerido para classificar e prever os resultados da HIC. OBJETIVO: Descrever a classificação SMASH-U e os resultados por etiologia em pacientes admitidos em um centro de acidente vascular cerebral (AVC) em São Paulo, Brasil. MéTODOS: Foi realizada uma análise retrospectiva de pacientes admitidos no hospital ou ambulatório entre abril de 2015 e janeiro de 2018. Dois neurologistas especializados em doenças cerebrovasculares avaliaram a classificação SMASH-U e pacientes com prontuários incompletos foram excluídos. RESULTADOS: Dos 2000 pacientes com diagnóstico de AVC avaliados, 140 foram incluídos na análise final. A idade média foi de 57,9 (±15,5) anos e 54,3% eram do sexo masculino. A hipertensão foi a etiologia mais frequente, correspondendo a 41,4% dos casos, seguida pela angiopatia amiloide (18,5%) e lesões estruturais (14,1%). As lesões estruturais foram mais comuns em mulheres e pacientes com menos de 45 anos. Resultados favoráveis foram observados em 61% dos pacientes com lesões estruturais, em comparação com 10% dos pacientes com etiologias relacionadas a medicamentos. CONCLUSãO: Este estudo fornece evidências importantes sobre a classificação etiológica de pacientes brasileiros com HIC. A hipertensão e a angiopatia amiloide foram as causas mais frequentes, enquanto lesões estruturais e doenças sistêmicas foram mais comuns em pacientes mais jovens.

In silico and in vitro elastase inhibition assessment assays of rosmarinic acid natural product from Rosmarinus officinalis Linn.

The use of various herbs and their compounds has been a strategy widely used in the fight against various human diseases. For example, rosmarinic acid, a bioactive phenolic compound commonly found in Rosemary plants (Rosmarinus officinalis Labiatae), has multiple therapeutic benefits in different diseases, such as cancer. Therefore, the study aimed to evaluate in silico and in vitro the inhibition potential of the enzyme Elastase from the porcine pancreas by rosmarinic acid isolated from the plant species R. officinalis Linn. Through Molecular Docking, the mechanism of action was investigated. In addition, rosmarinic acid presented a range of 5-60 µg/mL and significantly inhibited Elastase. At 60 µg/mL, there was an inhibition of 55% on the enzymatic activity. The results demonstrate the inhibition of Elastase by rosmarinic acid, which can lead to the development of new enzyme inhibitors that can be an inspiration for developing various drugs, including anticancer drugs.

Optic Disc and Retinal Architecture Changes in Patients with Spinocerebellar Ataxia Type 2.

BACKGROUND: ATXN2 is the causative gene of spinocerebellar ataxia type 2 (SCA2) and has been implicated in glaucoma pathogenesis. Therefore, studying ocular changes in SCA2 could uncover clinically relevant changes. OBJECTIVE: The aim was to investigate optic disc and retinal architecture in SCA2. METHODS: We evaluated 14 patients with SCA2 and 26 controls who underwent intraocular pressure measurement, fundoscopy, and macular and peripapillary spectral domain optical coherence tomography (SD-OCT). We compared SD-OCT measurements in SCA2 and controls, and the frequency of glaucomatous changes among SCA2, controls, and 76 patients with other SCAs (types 1, 3, 6, and 7). RESULTS: The macula, peripapillary retinal nerve fiber and inner plexiform layers were thinner in SCA2 than in controls. Increased cup-to-disc ratio was more frequent in SCA2 than in controls and other SCAs. CONCLUSIONS: Ocular changes are part of SCA2 phenotype. Future studies should further investigate retinal and optic nerve architecture in this disorder.

A predictive score for atrial fibrillation in poststroke patients / Escore preditivo de fibrilação atrial em pacientes pós-AVC

Abstract Background Atrial fibrillation (AF) is a risk factor for cerebral ischemia. Identifying the presence of AF, especially in paroxysmal cases, may take time and lacks clear support in the literature regarding the optimal investigative approach; in resource-limited settings, identifying a higher-risk group for AF can assist in planning further investigation. Objective To develop a scoring tool to predict the risk of incident AF in the poststroke follow-up. Methods A retrospective longitudinal study with data collected from electronic medical records of patients hospitalized and followed up for cerebral ischemia from 2014 to 2021 at a tertiary stroke center. Demographic, clinical, laboratory, electrocardiogram, and echocardiogram data, as well as neuroimaging data, were collected. Stepwise logistic regression was employed to identify associated variables. A score with integer numbers was created based on beta coefficients. Calibration and validation were performed to evaluate accuracy. Results We included 872 patients in the final analysis. The score was created with left atrial diameter ≥ 42 mm (2 points), age ≥ 70 years (1 point), presence of septal aneurysm (2 points), and score ≥ 6 points at admission on the National Institutes of Health Stroke Scale (NIHSS; 1 point). The score ranges from 0 to 6. Patients with a score ≥ 2 points had a fivefold increased risk of having AF detected in the follow-up. The area under the curve (AUC) was of 0.77 (0.72-0.85). Conclusion We were able structure an accurate risk score tool for incident AF, which could be validated in multicenter samples in future studies.

Resumo Antecedentes Fibrilação atrial (FA) é um fator de risco para isquemia cerebral. Identificar a presença de FA, especialmente em casos paroxísticos, pode demandar tempo, e não há fundamentos claros na literatura quanto ao melhor método de proceder à investigação; em locais de parcos recursos, identificar um grupo de mais alto risco de FA pode auxiliar no planejamento da investigação complementar. Objetivo Desenvolver uma ferramenta de escore para prever o risco de FA no acompanhamento após acidente vascular cerebral (AVC). Métodos Estudo longitudinal retrospectivo, com dados coletados dos prontuários eletrônicos de pacientes hospitalizados e acompanhados ambulatorialmente por isquemia cerebral, de 2014 a 2021, em um centro de AVC terciário. Foram coleados dados demográficos, clínicos, laboratoriais, de eletrocardiograma e ecocardiograma, além de dados de neuroimagem. Mediante uma regressão logística por stepwise, foram identificadas variáveis associadas. Um escore com números inteiros foi criado com base nos coeficientes beta. Calibração e validação foram realizadas para avaliar a precisão. Resultados Foram incluídos 872 pacientes na análise final. O escore foi criado com diâmetro de átrio esquerdo ≥ 42 mm (2 pontos), idade ≥ 70 anos (1 ponto), presença de aneurisma septal (2 pontos) e pontuação à admissão ≥ 6 na escala de AVC dos National Institutes of Health (National Institutes of Health Stroke Scale, NIHSS, em inglês; 1 ponto). O escore tem pontuação que varia de 0 a 6. Pacientes com escore ≥ 2 pontos tiveram cinco vezes mais risco de terem FA detectada no acompanhamento. A área sob a curva (area under curve, AUC, em inglês) foi de 0.77 (0.72-0.85). Conclusão Pudemos estruturar uma ferramenta precisa de escore de risco de FA, a qual poderá ser validada em amostras multicêntricas em estudos futuros.

Digital health in stroke: a narrative review / Saúde digital em acidente vascular cerebral: uma revisão narrativa

Abstract Digital health is significantly transforming stroke care, particularly in remote and economically diverse regions, by harnessing mobile and wireless technologies, big data, and artificial intelligence (AI). Despite the promising advancements, a notable gap exists in the formal clinical validation of many digital health applications, raising concerns about their efficacy and safety in real-world clinical settings. Our review systematically explores the landscape of digital health in stroke care, assessing the development, validation, and implementation of various digital tools. We adopted a comprehensive search strategy, scrutinizing peer-reviewed articles published between January 2015 and January 2024, to gather evidence on the effectiveness of digital health interventions. A rigorous quality assessment was conducted to ensure the reliability of the included studies, with findings synthesized to underscore key technological innovations and their clinical outcomes. Ethical considerations were meticulously observed to maintain data confidentiality and integrity. Our findings highlight the transformative potential of mobile health technologies, AI, and telemedicine in improving diagnostic accuracy, treatment efficacy, and patient outcomes in stroke care. Our paper delves into the evolution and impact of digital health in cerebrovascular prevention, diagnosis, rehabilitation and stroke treatment, emphasizing the digital health's role in enhancing access to expert care, mitigating treatment delays and improving outcomes. However, the review also underscores the critical need for rigorous clinical validation and ethical considerations in the development and deployment of digital health technologies to ensure their safe and effective integration into stroke care practices.

Resumo A saúde digital está transformando significativamente o cuidado com o acidente vascular cerebral (AVC), especialmente em regiões remotas e economicamente diversas, ao aproveitar tecnologias móveis e sem fio, big data e inteligência artificial (IA). Apesar dos avanços promissores, existe uma lacuna notável na validação clínica formal de muitas aplicações de saúde digital, levantando preocupações sobre sua eficácia e segurança em ambientes clínicos do mundo real. Nossa revisão explora sistematicamente a paisagem da saúde digital no cuidado do AVC, avaliando o desenvolvimento, validação e implementação de várias ferramentas digitais. Adotamos uma estratégia de busca abrangente, examinando artigos revisados por pares publicados entre janeiro de 2015 e janeiro de 2024, para reunir evidências sobre a eficácia das intervenções de saúde digital. Uma avaliação de qualidade rigorosa foi conduzida para garantir a confiabilidade dos estudos incluídos, com os achados sintetizados para destacar as principais inovações tecnológicas e seus resultados clínicos. Considerações éticas foram meticulosamente observadas para manter a confidencialidade e integridade dos dados. Nossas descobertas destacam o potencial transformador das tecnologias de saúde móvel, IA e telemedicina em melhorar a precisão diagnóstica, a eficácia do tratamento e os resultados dos pacientes no cuidado do AVC. Nosso artigo aprofunda-se na evolução e impacto da saúde digital na prevenção, diagnóstico, reabilitação e tratamento do AVC, enfatizando seu papel em melhorar o acesso ao cuidado especializado, mitigar atrasos no tratamento e melhorar os desfechos. No entanto, a revisão também sublinha a necessidade crítica de validação clínica rigorosa e considerações éticas no desenvolvimento e implantação de tecnologias de saúde digital para garantir sua integração segura e eficaz nas práticas de cuidado do AVC.

Intracranial compliance in patients with COVID-19: a multicenter observational study / Complacência intracraniana em pacientes com COVID-19: um estudo observacional multicêntrico

Abstract Background Patients with severe coronavirus disease-19 (COVID-19) may require the use of invasive mechanical ventilation (MV) for prolonged periods. Aggressive MV parameters have been associated with changes in intracranial pressure (ICP) in patients with acute intracranial disorders. Significant ICP elevation could compromise intracranial compliance (ICC) and cerebrovascular hemodynamics (CVH). However, the effects of these parameters in individuals without neurological disorders have not yet been evaluated. Objective To evaluate ICC in patients on MV with COVID-19 infection compared to other diagnoses, to better characterize the effects of MV and COVID-19 upon ICC. We also compared between the ICC in patients with COVID-19 who did not require MV and healthy volunteers, to assess the isolated effect of COVID-19 upon ICC. Methods This was an exploratory, observational study with a convenience sample. The ICC was evaluated with a noninvasive ICP monitoring device. The P2/P1 ratio was calculated by dividing the amplitude of these two points, being defined as "abnormal" when P2 > P1. The statistical analysis was performed using a mixed linear model with random effects to compare the P2/P1 ratio in all four groups on the first monitoring day. Results A convenience sample of 78 subjects (15 MV-COVID-19, 15 MV non-COVID-19, 24 non-MV-COVID-19, and 24 healthy participants) was prospectively enrolled. There was no difference in P2/P1 ratios between MV patients with and without COVID-19, nor between non-MV patients with COVID-19 and healthy volunteers. However, the P2/P1 ratio was higher in COVID-19 patients with MV use than in those without it. Conclusion This exploratory analysis suggests that COVID-19 does not impair ICC.

Resumo Antecedentes Pacientes com doença grave por coronavírus-19 (COVID-19) podem necessitar do uso de ventilação mecânica (VM) invasiva por um período prolongado. Parâmetros agressivos de VM têm sido associados a alterações na pressão intracraniana (PIC) em pacientes com doenças intracranianas agudas. Elevações significativas da PIC podem comprometer a complacência intracraniana (CIC) e a hemodinâmica cerebrovascular (HVC). No entanto, os efeitos desses parâmetros em indivíduos sem doenças neurológicas ainda não foram sistematicamente avaliados. Objetivo Avaliar a CIC em pacientes em VM com COVID-19 comparados com outros diagnósticos, para melhor caracterizar os efeitos da VM e COVID-19 sobre a CIC. Também foi feita a comparação entre a CIC em pacientes com COVID-19 sem VM e voluntários saudáveis, para avaliar o efeito isolado da COVID-19 sobre a ICC. Métodos Trata-se de um estudo exploratório, observacional com amostra por conveniência. A CIC foi avaliada com um dispositivo não invasivo de monitoramento da PIC. A relação P2/P1 foi calculada dividindo-se a amplitude desses dois pontos, sendo definida como "anormal" quando P2 > P1. A análise estatística foi realizada usando um modelo linear misto com efeitos aleatórios para comparar a relação P2/P1 nos quatro grupos no primeiro dia de monitoramento. Resultados Uma amostra de conveniência com 78 voluntários (15 COVID-19 em VM, 15 sem COVID-19 em VM, 24 com COVID em respiração espontânea e 24 saudáveis) foram prospectivamente incluídos. Não houve diferença nas razões P2/P1 entre pacientes em VM com e sem COVID-19, nem entre pacientes sem VM com COVID-19 ou saudáveis. No entanto, a relação P2/P1 foi maior em pacientes com COVID-19 com uso de VM do que naqueles sem. Conclusão Os dados dessa análise exploratória sugerem que a COVID-19 não prejudica a CIC.

A Brazilian series utilizing the SMASH-U system for etiologic classification of intracerebral hemorrhage / Classificação etiológica de pacientes admitidos com hemorragia intracerebral utilizando a escala SMASH-U: uma série brasileira

Abstract Background Understanding the causes of intracerebral hemorrhage (ICH) is crucial for effective treatment and preventing recurrences. The SMASH-U scale is a suggested method for classifying and predicting the outcomes of ICH. Objective To describe the SMASH-U classification and outcomes by etiology in patients admitted to a comprehensive stroke center in São Paulo, Brazil. Methods A retrospective analysis was conducted on patients admitted to the hospital or outpatient clinic between April 2015 and January 2018. Two stroke neurologists evaluated the SMASH-U classification, and patients with incomplete medical records were excluded. Results Out of the 2000 patients with a stroke diagnosis evaluated, 140 were included in the final analysis. The mean age was 57.9 (± 15.5) years, and 54.3% were male. Hypertension was the most frequent etiology, accounting for 41.4% of cases, followed by amyloid angiopathy (18.5%) and structural lesions (14.1%). Structural lesions were more common among women and patients under 45 years old. Favorable outcomes were observed in 61% of patients with structural lesions, compared to 10% of patients with medication-related etiologies. Conclusion This study provides important evidence regarding the etiological classification of Brazilian patients with ICH. Hypertension and amyloid angiopathy were the most frequent causes, while structural lesions and systemic diseases were more common in younger patients.

Resumo Antecedentes Compreender as causas da hemorragia intracerebral (HIC) é crucial para o tratamento eficaz e prevenção de recorrências. A escala SMASH-U é um método sugerido para classificar e prever os resultados da HIC. Objetivo Descrever a classificação SMASH-U e os resultados por etiologia em pacientes admitidos em um centro de acidente vascular cerebral (AVC) em São Paulo, Brasil. Métodos Foi realizada uma análise retrospectiva de pacientes admitidos no hospital ou ambulatório entre abril de 2015 e janeiro de 2018. Dois neurologistas especializados em doenças cerebrovasculares avaliaram a classificação SMASH-U e pacientes com prontuários incompletos foram excluídos. Resultados Dos 2000 pacientes com diagnóstico de AVC avaliados, 140 foram incluídos na análise final. A idade média foi de 57,9 (±15,5) anos e 54,3% eram do sexo masculino. A hipertensão foi a etiologia mais frequente, correspondendo a 41,4% dos casos, seguida pela angiopatia amiloide (18,5%) e lesões estruturais (14,1%). As lesões estruturais foram mais comuns em mulheres e pacientes com menos de 45 anos. Resultados favoráveis foram observados em 61% dos pacientes com lesões estruturais, em comparação com 10% dos pacientes com etiologias relacionadas a medicamentos. Conclusão Este estudo fornece evidências importantes sobre a classificação etiológica de pacientes brasileiros com HIC. A hipertensão e a angiopatia amiloide foram as causas mais frequentes, enquanto lesões estruturais e doenças sistêmicas foram mais comuns em pacientes mais jovens.

Synthesis of (-) - 6, 6'-dinitrohinokinin from hinokinin natural product and in silico and in vitro trypanocidal activity assessment

Chagas disease is a public health problem affecting approximately seven million people worldwide. Thus, there is a need to discover drugs for the adequate treatment of this disease because currently available drugs have serious side effects. Therefore, this study aimed to evaluate the in vitro trypanocidal activity of (-)-6,6'-dinitrohinokinin, obtained from the partial synthesis of (-)-hinokinin, on the trypomastigotes and amastigotes forms. For the trypomastigote assay, blood was collected from mice infected with Trypanosoma cruzi through cardiac puncture at the parasitemic peak. The results show that (-)-6,6'-dinitrohinokinin was effective against the trypomastigote forms, presenting an IC50 of 19.83 µM and lysis percentage values ​​of 78.4% and 69.4% at concentrations of 200 and 100 µM, respectively. Molecular docking calculations indicate that (-)-6,6'-dinitrohinokinin favorably interacts with the amino acids present in the active site of the protein trypanothione reductase, a typical target for anti-trypanosomal drug development. According to the results, the (-)-6,6'-dinitrohinokinin showed more significant trypanocidal activity with IC50 of 1.83 µM than benzonidazole positive control with IC50 of 53.2 µM, showing to be a prototype molecule promising for the development of a new antiparasitic drug.