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.

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.

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.

Optimizing ReBreed21 II: Fertility and reproductive efficiency in different parities during a shortened breeding season in beef cattle.

This study evaluated the efficiency of a rapid reinsemination program allowing timed AI (TAI) every 21d (ReBreed21) in a commercial beef cow-calf operation. Nelore females from different parities (n = 2085) were synchronized for first TAI (D0 = TAI) using an estradiol/progesterone (E2/P4) protocol and assigned to one of three reinsemination programs: Resynch33 (n = 753), traditional resynch program with second TAI at D42 after first TAI; ReBreed21 (n = 687); or ReBreed21+EC (n = 670). The ReBreed females (n = 1357) received intravaginal P4 insert on D12, on D19 P4 was removed, and a dose of equine chorionic gonadotropin (eCG) was administered, then, ReBreed21 females received 0.6 mg of EC (ReBreed21+EC) or nothing (ReBreed21) and on D21, nonpregnancy (NP) was determined using Doppler ultrasound to detect corpus luteum (CL) blood flow (BF) (NP: <25 % BF pixels of total CL area) and NP cows received immediate TAI and GnRH to induce ovulation. Pregnancy diagnosis was performed at D33 after TAI following all TAIs. Cows considered pregnant at D21, based on CL BF, but NP on D33 were designated False-Positives (FP) and false negatives (FN) were number of nonpregnant cows/heifers on d21 based on the CL BF found to subsequently be pregnant on D33 divided by the total number pregnant. Pregnancy/AI (P/AI) did not differ for the first TAI (55.1 %) among the treatments. Heifers had similar P/AI at the second AI in all groups and similar to the first AI. Primiparous had greater P/AI in ReBreed21+EC and Resynch33 at s TAI compared to ReBreed21, 51.7 %, 55.8 %, 34.2 %, respectively. Multiparous had greater P/AI at second TAI in Resynch33 (60.9 %) than ReBreed21 programs (34.7 %). The percentage FP and FN among ReBreed21 programs did not differ, 13.8 and 0.2 %, respectively. Overall accumulative pregnancies on D21 of the breeding season were greater for ReBreed21 and ReBreed21+EC than Resynch33 (69.7 %, 71.6 %, and 55.5 %, respectively). However, on D42 of the breeding season, only heifers had greater pregnancies in ReBreed21 programs than Resynch33 (73.3 %, 74.3.6 %, and 63.2 %, respectively). Average days to pregnancy were less (P = 0.01) for ReBreed21 and ReBreed21+EC than Resynch33. Thus, the ReBreed21 strategy can improve the efficiency of TAI programs in beef cattle. Of interest, ReBreed21 was particularly effective in nulliparous, somewhat effective in primiparous when EC was added to the program, but relatively ineffective in multiparous beef cattle.

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.

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.

An algorithm for the National Institute of Health Stroke Scale assessment: A multicenter, two-arm and cluster randomized study.

BACKGROUND: The NIH Stroke Scale (NIHSS) is a validated tool for assessing stroke severity, increasingly used by general practitioners in telemedicine services. Mobile apps may enhance its reliability. We aim to validate a digital platform (SPOKES) for NIHSS assessment in telemedicine and healthcare settings. METHODS: Hospitals using a telemedicine service were randomly allocated to control or SPOKES-user groups. The discrepancy between the NIHSS scores reported and those confirmed by experts was evaluated. Healthcare providers from comprehensive stroke centers were invited for interrater validation. Participants were randomized to assess the NIHSS using videos of real patients. Weighted Kappa (wk) statistics analyzed the agreement, and logistic regression determined the correlation with the congruency. RESULTS: A total of 299 telemedicine consultations from 12 hospitals were included. The difference between the NIHSS scores reported and double-checked was lower in the SPOKES group (p = 0.03), with a significantly higher level of complete agreement (72.5 % vs. 50.4 %, p = 0.005). Adoption of SPOKES was associated with complete congruency (OR 4.01, 95 %CI 1.42-11.35, p = 0.009). For interrater validation, 20 participants were considered. In the SPOKES group, almost-perfect and strong agreement occurred in 13.3 %(n = 6/45) and 84.4 %(n = 38/45) of ratings, respectively; in the control group, 6.7 %(n = 3/45) were almost-perfect, 28.9 %(n = 13/45) strong and 51 %(n = 23/45) were minimal. CONCLUSION: A free and reliable mobile application for NIHSS assessment can significantly improve interrater agreement between healthcare professionals, and between NIHSS-certified neurologists and general practitioners. Our results underscore the importance of ongoing training and education in enhancing the consistency and reliability of NIHSS scores.

Optimizing ReBreed21 I: Evaluation of endocrine and ovarian dynamics in non-bred Bos indicus heifers.

The present study evaluated follicular and endocrine dynamics during ReBreed21, a reproductive strategy that allows resynchronization of ovulation every 21 days in Bos indicus (Nelore) heifers. A synchronized estrous cycle was induced using a standard timed ovulation protocol (d -10: P4 implant inserted + 2 mg estradiol benzoate; d -2: P4 removed+ 0.5 mg cloprostenol + 0.6 mg estradiol cypionate + 200 IU equine chorionic gonadotropin (eCG); d0: 8.4 µg buserelin) without AI to ensure nonpregnancy in heifers. Day of GnRH was designated d0 of estrous cycle. On d12, heifers (n = 80) were randomized into three experimental groups: (1) ReBreed21 (n = 28) d12 P4 device inserted, d19 P4 device withdrawal plus 200 IU eCG, and d21 8.4 µg buserelin (GnRH); (2) ReBreed21+G (n = 26) same as ReBreed21 plus GnRH (16.8 µg) treatment on d12; and (3) Control (n = 26) no treatment. ReBreed21+G increased two-fold (62.9%; 18/26) percentage of heifers with synchronized follicular wave emergence compared to Control (34.6%; 9/26) whereas ReBreed21 (53.6%; 15/28) was intermediate. The ReBreeed21 groups (eCG on d19) increased (P < 0.01) follicular growth between d19 and d21 in ReBreed21 (2.3 ± 0.2 mm) and ReBreed21+G (3.4 ± 0.2 mm) compared with Control (1.2 ± 0.3 mm), resulting in greater (P < 0.01) follicle diameter on d21 for ReBreed21 (10.7 ± 0.4 mm) and ReBreed21+G (10.8 ± 0.4 mm) compared with Control (9.1 ± 0.5 mm). Structural luteolysis was similar among groups (P = 0.51), although the average day when P4 was <1 ng/mL was later (P < 0.01) for ReBreed21 (20.5 ± 0.2) and ReBreed21+G (20.7 ± 0.2) compared to Control (19.2 ± 0.4). Overall ovulation at the end of the estrous cycle was increased (P = 0.03) for ReBreed21 groups (83.3%; 45/54) compared with Control (57.7%; 15/26). Synchronized ovulation on day 22-23 was greater (P < 0.01) for ReBreed21 (78.6%; 22/28) and ReBreed21+G (76.9%; 20/26) compared with Control (30.8%; 8/26). Thus, the ReBreed21 resynchronization program produced acceptable endocrine and follicular dynamics, including synchronized ovulation at the end of the protocol in nonpregnant heifers providing good rationale for testing the fertility and practical implementation of this protocol under field conditions.

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/.

Association of musculoskeletal involvement with lung function and mortality in patients with idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a progressive disease associated with high mortality. Low muscle mass, frailty and sarcopenia lead to functional impairment that negatively impact quality of life and survival but are not used in clinical practice. We aimed to determine the association of Fat-free mass index (FFMI) and frailty with lung function, exercise tolerance and survival in patients with IPF. In this study, 70 patients with IPF underwent assessment of body composition, lung function, 6-min walk distance (6MWD) testing, hand grip strength, quality of life (QoL) assessment by St. George's Respiratory questionnaire (SGRQ) and frailty assessment using the SHARE-FI tool. FFMI was calculated using pectoralis muscle cross-sectional area (PM-CSA) on CT chest images and the lowest quartile defined reduced muscle mass. Sarcopenia was defined as low FFMI and handgrip strength. Regression analyses were conducted to determine predictive value of frailty, low FFMI and sarcopenia on clinical outcomes. The Cox proportional hazards model was used to analyze the impact of FFMI and frailty score on survival. The mean age was 70 years with moderate impairment in lung function (mean ppFVC 68.5%, ppDLCO 45.6%). Baseline forced vital capacity (p < 0.001), diffusion capacity of lung for carbon monoxide (p = < 0.01), 6WMD (p < 0.05) were significantly lower in frail patients compared to non-frail patients. BMI was found to closely correlate with FFMI (r = 0.79, p < 0.001), but not with frailty score (r = - 0.2, p = 0.07). Frailty was a significant predictor of FVC, DLCO, 6MWD, SGRQ scores when adjusted for age and gender. Muscle mass and sarcopenia were significant predictors of FVC, DLCO, but not 6MWD or QoL scores. Multivariate cox-proportional hazards ratio model adjusting for age and gender showed that frailty was significantly associated with increased mortality (HR = 2.6, 95% CI 1.1-6.1). Low FFMI (HR = 1.3, 95% CI 0.6-2.8), and sarcopenia (HR = 2.1, 95% CI 0.8-5.3), though associated with a trend to increased mortality, were not statistically significant. Frailty is associated with lower lung function and higher mortality in patients with IPF. Longitudinal evaluations are necessary to further determine the associations between low FFMI, sarcopenia and frailty with outcomes in IPF.

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.

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.

Profiles of interferon-stimulated genes in multiple tissues and circulating pregnancy-associated glycoproteins and their association with pregnancy loss in dairy cows†.

Pregnancy loss (PL) in lactating dairy cows disrupts reproductive and productive efficiency. We evaluated the expression of interferon-stimulated genes (ISG) in blood leukocytes, vaginal and cervical epithelial cells, luteolysis-related genes, progesterone, and pregnancy-associated glycoprotein (PAG) profiles in lactating dairy cows (n = 86) to gain insight about PL. Expression of ISG on d17, d19, and d21 was greater in cows that maintained the pregnancy (P33) compared to nonpregnant with no PL (NP). Greater ISG differences between groups were observed in the cervix (96.7-fold) than vagina (31.0-fold), and least in blood leukocytes (5.6-fold). Based on individual profiles of ISG and PAG, PL was determined to occur either before (~13%) or after (~25%) d22. For cows with PL before d22, ISG expression was similar on d17 but by d21 was lower and OXTR was greater than P33 cows and similar to NP; timing of luteolysis was similar compared to NP cows suggesting embryonic failure to promote luteal maintenance and to attach to the endometrium (no increase in PAG). For cows with PL after d22, ISG expression was similar to P33 cows on d17, d19, and d21 and luteolysis, when it occurred, was later than NP cows; delayed increase in PAG suggested later or inadequate embryonic attachment. In conclusion, PL before d22 occurred due to embryonic demise/failure to signal for luteal maintenance, as reflected in reduced ISG expression by d21. Alternatively, embryos with PL between d22 and 33 adequately signaled for luteal maintenance (ISG) but had delayed/inadequate embryonic attachment and/or inappropriate luteolysis causing PL.

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.

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.