Most Promising Approaches to Improve Brain AVM Management: ARISE I Consensus Recommendations.

Brain arteriovenous malformations (bAVMs) are complex, and rare arteriovenous shunts that present with a wide range of signs and symptoms, with intracerebral hemorrhage being the most severe. Despite prior societal position statements, there is no consensus on the management of these lesions. ARISE (Aneurysm/bAVM/cSDH Roundtable Discussion With Industry and Stroke Experts) was convened to discuss evidence-based approaches and enhance our understanding of these complex lesions. ARISE identified the need to develop scales to predict the risk of rupture of bAVMs, and the use of common data elements to perform prospective registries and clinical studies. Additionally, the group underscored the need for comprehensive patient management with specialized centers with expertise in cranial and spinal microsurgery, neurological endovascular surgery, and stereotactic radiosurgery. The collection of prospective multicenter data and gross specimens was deemed essential for improving bAVM characterization, genetic evaluation, and phenotyping. Finally, bAVMs should be managed within a multidisciplinary framework, with clinical studies and research conducted collaboratively across multiple centers, harnessing the collective expertise and centralization of resources.

How P. aeruginosa cells with diverse stator composition collectively swarm.

Swarming is a macroscopic phenomenon in which surface bacteria organize into a motile population. The flagellar motor that drives swarming in Pseudomonas aeruginosa is powered by stators MotAB and MotCD. Deletion of the MotCD stator eliminates swarming, whereas deletion of the MotAB stator enhances swarming. Interestingly, we measured a strongly asymmetric stator availability in the wild-type (WT) strain, with MotAB stators produced at an approximately 40-fold higher level than MotCD stators. However, utilization of MotCD stators in free swimming cells requires higher liquid viscosities, while MotAB stators are readily utilized at low viscosities. Importantly, we find that cells with MotCD stators are ~10× more likely to have an active motor compared to cells uses the MotAB stators. The spectrum of motility intermittency can either cooperatively shut down or promote flagellum motility in WT populations. In P. aeruginosa, transition from a static solid-like biofilm to a dynamic liquid-like swarm is not achieved at a single critical value of flagellum torque or stator fraction but is collectively controlled by diverse combinations of flagellum activities and motor intermittencies via dynamic stator utilization. Experimental and computational results indicate that the initiation or arrest of flagellum-driven swarming motility does not occur from individual fitness or motility performance but rather related to concepts from the "jamming transition" in active granular matter.IMPORTANCEIt is now known that there exist multifactorial influences on swarming motility for P. aeruginosa, but it is not clear precisely why stator selection in the flagellum motor is so important. We show differential production and utilization of the stators. Moreover, we find the unanticipated result that the two motor configurations have significantly different motor intermittencies: the fraction of flagellum-active cells in a population on average with MotCD is active ~10× more often than with MotAB. What emerges from this complex landscape of stator utilization and resultant motor output is an intrinsically heterogeneous population of motile cells. We show how consequences of stator recruitment led to swarming motility and how the stators potentially relate to surface sensing circuitry.

Analgesic efficacy of erector spinae plane block versus paravertebral block in lung surgeries-A non-inferiority randomised controlled trial.

BACKGROUND: Pain management plays an essential role in postoperative recovery after lung surgeries. The Erector Spinae Plane Block (ESPB) is a widely used regional anaesthesia technique; however, few clinical trials have compared this block to active control in thoracic surgeries. This study evaluated the non-inferiority of the analgesia provided by ESPB when compared to paravertebral block (PVB) in lung surgeries. METHODS: Randomised, active-controlled, blinded for patients and assessors, non-inferiority trial. Patients who underwent unilateral lung surgeries were divided into two groups according to the regional anaesthesia technique-continuous ESPB or PVB at the T5 level. The primary outcome was to assess pain using a numerical rating scale (NRS) with a test of the interaction of three measures over 24 h postoperatively. An NRS score ≥ 7 was considered analgesia failure, and the prespecified non-inferiority margin was 10%. RESULTS: In the interim analysis that terminated this study, 120 participants were enrolled. ESPB patients reported higher mean NRS general values over 24 h, 4.6 ± 3.2 in the ESPB group versus 3.9 ± 2.9 in the PVB group, with a difference of -0.67 (-15.2%) and 95%CI: -1.29 to -0.05 (p = .02), demonstrating not non-inferiority. In addition, the ESPB group presented higher NRS failure of analgesia over 24 h (p < .01) and required more postoperative opioids (p = .01 over 24 h). There was no difference in patient satisfaction between groups. CONCLUSION: This trial demonstrated that a continuous erector spinae plane block was not non-inferior to a continuous paravertebral block for analgesia after lung surgery but resulted in higher levels of postoperative pain and opioid consumption.

Effect of the COVID-19 Pandemic on the Epidemiology of Pediatric Traumatic Brain Injury in Brazil.

Aim In response to the coronavirus 2019 disease (COVID-19) pandemic, governments worldwide implemented measures to prevent infection, resulting in restricted school activities, restricted children's freedom of movement, and increased risk of violence and injuries at home, including traumatic brain injury (TBI), among children. In Brazil, the consequences of the COVID-19 pandemic on the causes, severity, and mortality of pediatric TBI have not yet been investigated. Thus, our study aimed to determine whether the COVID-19 pandemic has affected the epidemiology of pediatric TBI among Brazilian children. Materials and methods We investigated the patients with TBI aged <18 years who visited a tertiary trauma center in Brazil in 2019 and 2020. TBI-related variables, such as classification, mechanism, clinical manifestations, need for intervention, morbidity, and mortality, were recorded. Furthermore, we used a nationwide databank to collect information on mortality from external causes of trauma and violence in the pediatric population in 2019 and 2020. The Mann-Whitney test was used to compare quantitative variables related to the mechanisms and severity of TBI in both periods in order to determine the impact of the COVID-19 pandemic. Results Of the patients with traumatic brain injury, 1371 visited the trauma center in 2019 and 1052 in 2020. No difference was noted in the incidence rate of abusive head trauma between these periods (p=0.142) or in mortality from violence in Brazil. Recreational causes of pediatric TBI increased during the first year of the COVID-19 pandemic in Brazil and falls from bicycles significantly increased during the pandemic (p<0.001). Conclusion A global reduction in pediatric admissions to emergency rooms as well as no impact on mortality and severity of pediatric TBI were observed during the COVID-19 pandemic in Brazil. Additionally, a public education program regarding child safety during recreational activities, particularly how to avoid falls from bicycles was recommended.

How individual P. aeruginosa cells with diverse stator distributions collectively form a heterogeneous macroscopic swarming population.

Swarming is a macroscopic phenomenon in which surface bacteria organize into a motile population. The flagellar motor that drives swarming in Pseudomonas aeruginosa is powered by stators MotAB and MotCD. Deletion of the MotCD stator eliminates swarming, whereas deletion of the MotAB stator enhances swarming. Interestingly, we measured a strongly asymmetric stator availability in the WT strain, with MotAB stators produced ∼40-fold more than MotCD stators. However, recruitment of MotCD stators in free swimming cells requires higher liquid viscosities, while MotAB stators are readily recruited at low viscosities. Importantly, we find that cells with MotCD stators are ∼10x more likely to have an active motor compared to cells without, so wild-type, WT, populations are intrinsically heterogeneous and not reducible to MotAB-dominant or MotCD-dominant behavior. The spectrum of motility intermittency can either cooperatively shut down or promote flagellum motility in WT populations. In P. aeruginosa , transition from a static solid-like biofilm to a dynamic liquid-like swarm is not achieved at a single critical value of flagellum torque or stator fraction but is collectively controlled by diverse combinations of flagellum activities and motor intermittencies via dynamic stator recruitment. Experimental and computational results indicate that the initiation or arrest of flagellum-driven swarming motility does not occur from individual fitness or motility performance but rather related to concepts from the 'jamming transition' in active granular matter. Importance: After extensive study, it is now known that there exist multifactorial influences on swarming motility in P. aeruginosa , but it is not clear precisely why stator selection in the flagellum motor is so important or how this process is collectively initiated or arrested. Here, we show that for P. aeruginosa PA14, MotAB stators are produced ∼40-fold more than MotCD stators, but recruitment of MotCD over MotAB stators requires higher liquid viscosities. Moreover, we find the unanticipated result that the two motor configurations have significantly different motor intermittencies, the fraction of flagellum-active cells in a population on average, with MotCD active ∼10x more often than MotAB. What emerges from this complex landscape of stator recruitment and resultant motor output is an intrinsically heterogeneous population of motile cells. We show how consequences of stator recruitment led to swarming motility, and how they potentially relate to surface sensing circuitry.

Time from biopsy to radical prostatectomy by race in an equal-access healthcare system: Results from the SEARCH cohort.

BACKGROUND: We previously showed that within an equal-access health system, race was not associated with the time between prostate cancer (PC) diagnosis and radical prostatectomy (RP). However, in the more recent time-period of the study (2003-2007), Black men had significantly longer times to RP. We sought to revisit the question in a larger study population with more contemporary patients. We hypothesized that time from diagnosis to treatment would not differ by race, even after accounting for active surveillance (AS) and the exclusion of men at very low to low risk of PC progression. METHODS: We analyzed data from 5885 men undergoing RP from 1988 to 2017 at eight Veterans Affairs Hospitals from SEARCH. Multiple linear regression was used to compare time from biopsy to RP and to examine the risk of delays (>90 and >180 days) between races. In sensitivity analyses we excluded men deemed to have initially chosen AS based on having >365 days from biopsy to RP and men at very low to low PC risk for progression according to National Comprehensive Cancer Network Clinical Practice Guidelines. RESULTS: At biopsy, Black men (n = 1959) were younger, had lower body mass index, and higher prostate specific antigen levels, (all p < 0.02), compared to White men (n = 3926). Time from biopsy to RP was longer in Black men (mean days: 98 vs. 92; adjusted ratio of mean number of days, 1.07 [95% confidence interval: 1.03-1.11], p < 0.001); however, there were no differences in delays >90 or >180 days after adjusting for confounders (all p ≥ 0.286). Results were similar following the exclusion of men potentially under on AS and at very low and low risk. CONCLUSIONS: In an equal-access healthcare system, we did not find evidence of clinically relevant differences in time from biopsy to RP in Black versus White men.

Prolotherapy in the treatment of chronic migraine ­ Case report / Proloterapia no tratamento da enxaqueca crônica ­ Relato de caso

Introduction:Chronic migraine is a socioeconomic and individual burden since it is the largest cause of disability in people under 50 years of age. Although there are several prophylactic drug alternatives, some patients are vulnerable to refractoriness with significant damage to their quality of life. Prolotherapy, a subcutaneous injection of dextrose in peripheral nerves, advocates as a promising tool in the management of this pathology. Case report:A patient with refractory chronic migraine to drug therapy who was submitted to neurofascial prolotherapy. Weekly administration of a 2 ml solution of 1% ropivacaine and 10% glucose in the head peripheral nerves for 6 weeks. Reduced disability and frequency of migraine attacks for a period of 8 weeks after interventions. Conclusion: Prolotherapy proved itself to be a notable technique for reducing the number of days in a month that a patient with refractory chronic migraine to standardized therapy has had headaches. However, placebo group studies are needed to determine the efficacy of the procedure.

Introdução: A enxaqueca crônica representa um fardo socioeconômico e individual, pois é a maior causa de incapacidade em pessoas com menos de 50 anos de idade. Embora existam diversas alternativas de medicamentos profiláticos, alguns pacientes são vulneráveis ​​à refratariedade com prejuízos significativos à sua qualidade de vida. A proloterapia, uma injeção subcutânea de dextrose nos nervos periféricos, é defendida como uma ferramenta promissora no manejo desta patologia. Relato de caso: Paciente com enxaqueca crônica refratária à terapia medicamentosa que foi submetido à proloterapia neurofascial. Administração semanal de 2 ml de solução de ropivacaína a 1% e glicose a 10% nos nervos periféricos da cabeça durante 6 semanas. Redução da incapacidade e frequência de ataques de enxaqueca por um período de 8 semanas após as intervenções. Conclusão: A proloterapia provou ser uma técnica notável para reduzir o número de dias em um mês que um paciente com enxaqueca crônica refratária à terapia padronizada teve dores de cabeça. No entanto, são necessários estudos em grupo placebo para determinar a eficácia do procedimento.

Fatores associados ao controle da hipertensão arterial entre usuários atendidos na estratégia saúde da família / Factors associated with the control of arterial hypertension among users assisted in the family health strategy / Factores asociados al control de la hipertensión arterial entre los usuarios asistidos en la estrategia de salud de la família

Objetivo: analisar o percentual de pacientes sob tratamento anti-hipertensivo que apresentam níveis de pressão arterial controlados e fatores associados. Método: estudo transversal e analítico. A seleção de pacientes ocorreu por amostragem probabilística, por conglomerados tratados de forma descritiva e analítica. Participaram do estudo 720 indivíduos. Resultados: após regressão logística, permaneceram associadas ao não controle da pressão arterial as variáveis sexo, adesão à terapia medicamentosa, história pregressa de doença cardíaca e automedicar-se. Conclusão: a prevalência de controle da pressão arterial foi de 54,3 %, as dificuldades no tratamento anti-hipertensivo relacionam-se a fatores como aspectos pessoais, ao ambiente de vida, ao acesso aos cuidados de saúde, destacando-se como variável modificável a não adesão medicamentosa. Reforça-se a necessidade de incentivo das políticas públicas para o estabelecimento de novas estratégias para abordagem dos fatores modificáveis no manejo da hipertensão

Objectives: to analyze the percentage of patients under antihypertensive treatment who have controlled blood pressure levels and associated factors. Method: cross-sectional and analytical study. The selection of patients occurred by probabilistic sampling, by clusters treated descriptively and analytically. A total of 720 individuals participated in the studys. Results: after logistic regression, the variables gender, adherence to drug therapy, previous history of heart disease and self-medicating remained associated with non-control of blood pressure. Conclusion: the prevalence of blood pressure control was 54.3%, the difficulties in antihypertensive treatment are related to factors such as personal aspects, the living environment, access to health care, highlighting as a modifiable variable non-medication adherence. The need to encourage public policies to establish new strategies to address modifiable factors in the management of hypertension is reinforced

Objetivos: analizar el porcentaje de pacientes en tratamiento antihipertensivo que tienen niveles controlados de presión arterial y factores asociados. Método: estudio transversal y analítico. La selección de los pacientes ocurrió por muestreo probabilístico, por conglomerados tratados descriptiva y analíticamente. Un total de 720 individuos participaron en el estudio. Resultados: después de la regresión logística, las variables sexo, adhesión a la terapia medicamentosa, historia previa de cardiopatía y automedicación permanecieron asociadas al no control de la presión arterial. Conclusión: la prevalencia de control de la presión arterial fue de 54,3%, las dificultades en el tratamiento antihipertensivo se relacionan con factores como aspectos personales, el ambiente de vida, el acceso a la atención de salud, destacando como variable modificable la adhesión a la medicación. Se refuerza la necesidad de impulsar políticas públicas para establecer nuevas estrategias para abordar factores modificables en el manejo de la hipertensión

Associação entre determinantes em saúde e ocorrência de casos humanos de leptospirose em Minas Gerais: um estudo ecológico 2010-2019 / Association between health determinants and the occurrence of human cases of leptospirosis in Minas Gerais: an ecological study 2010-2019

Introdução: A leptospirose é considerada um problema de saúde pública com grande impacto social e econômico. A doença foi citada como duplamente omissa, uma vez já classificada na literatura internacional como doença tropical negligenciada (DTN), ainda conta com a baixa atenção governamental. Tal fato, pode estar associado ao adoecimento por essa enfermidade atingir majoritariamente a porção pobre e marginalizada da sociedade. Objetivos: O presente estudo objetiva avaliar a associação entre determinantes em saúde e adoecimento por leptospirose nos municípios do estado de Minas Gerais no período de 2010 a 2019. Metodologia: Trata-se de um estudo ecológico, no qual as unidades de análise foram os 853 municípios do estado de Minas Gerais. Foram utilizados dados secundários agregados não nominais entre os anos de 2010 e 2019. Foi utilizado o Modelo Binomial Negativo com Inflação de Zeros como técnica de análise multivariada, considerando a incidência por leptospirose em 2016 como desfecho e os indicadores do Índice Mineiro de Responsabilidade Social de 2016 ou em data mais próxima disponível como variáveis explicativas Resultados: Os resultados do modelo múltiplo demonstraram que os fatores que permaneceram associados à incidência de leptospirose foram os índices de Saúde, Educação, Renda e Emprego e a variável Infraestrutura Urbana. Segundo os coeficientes estimados, o índice de saúde do IMRS foi associado a um aumento da incidência de leptospirose. Por outro lado, os demais fatores ­ índice de educação, renda e emprego e a variável infraestrutura urbana ­ estiveram associados a menores taxas da doença, agindo assim, como fatores de proteção ao adoecimento. Conclusão: Há uma forte associação da leptospirose com a pobreza no estado de Minas Gerais. O investimento em infraestrutura urbana e garantia de condições sanitárias favoráveis para a população, bem como melhora da propagação de informação e educação reduziria o impacto da doença na população pobre e desassistida.

Introduction: Leptospirosis is considered a public health problem with great social and economic impact. The disease was cited as doubly omitted, since it is already classified in the international literature as a neglected tropical disease (NTD), it still has low government attention. This fact may be associated with the illness caused by this disease, which mostly affects the poor and marginalized portion of society. Objectives: This study aims to evaluate the association between health determinants and the illness from leptospirosis in the municipalities of the state of Minas Gerais from 2010 to 2019. Methodology: This is an ecological study and the units of analysis were the 853 municipalities in the state of Minas Gerais. Non-nominal aggregated secondary data between the years 2010 and 2019 were used. The Negative Binomial Model with Zero Inflation was used as a multivariate analysis technique, considering the incidence of leptospirosis in 2016 as the outcome and the IMRS indicators of 2016 or on a date closest available as explanatory variables Results: The results of the multiple model showed that the factors that remained associated with the incidence of leptospirosis were the Health, Education, Income and Employment indexes and the Urban Infrastructure variable. According to the estimated coefficients, the IMRS health index was associated with an increased incidence of leptospirosis. On the other hand, the other factors ­ education, income and employment index and the urban infrastructure variable ­ were associated with lower rates of the disease, thus acting as protective factors against illness. Conclusion: There is a strong association between leptospirosis and poverty in the state of Minas Gerais. Investment in urban infrastructure and guaranteeing favorable sanitary conditions for the population, as well as improving the dissemination of information and education would reduce the impact of the disease on the poor and underserved population. Descriptors: Social Determinants of Health; Zoonosis Surveillance; Leptospirosis, Social Vulnerability, Ecological Studies.

Atenção domiciliar na saúde pública: perspectiva macro, meso e microrregional em Minas Gerais, Brasil / Home care in public health: macro, meso and microrregional perspectives in Minas Gerais, Brazil / Atención domiciliaria en salud pública: perspectivas macro, meso y microrregionales en Minas Gerais, Brasil

Objetivo: Investigardados de atenção domiciliar na saúde pública, a partir da perspectiva macro, meso e microrregional no âmbito de Minas Gerais (MG), Brasil. Método: Estudo com delineamento ecológico. Os dados foram extraídos do Sistema de Informação em Saúde para a Atenção Básica (SISAB) do Ministério da Saúdebrasileiroe se referem aosatendimentosdomiciliaresefetuados no período de2016 a 2018. Exploraram-se as variáveis estratificadas por:sexo, modalidade de atenção domiciliar 1, 2 ou 3, atendimento programado ou não, visita pós-óbito e desfecho. Considerou-se a perspectiva macro o estado de Minas Gerais, mesoa região do norte do estadoe microrregional omunicípio de Montes Claros (MG).Resultados:Em Minas Geraisforam efetuados 665.395atendimentos domiciliares, com maior frequência para assistência às mulheres (51,72%).Observou-se que osatendimentos programados apresentaram frequênciasacima de 95%. No período avaliado, houve aumentodevisitas domiciliaresapós o óbito do paciente. A modalidade de atendimento domiciliar2 foi a mais prevalente nas regiões investigadas e, além disso, registra-se preponderância para a permanência de pacientesna atenção domiciliar. Em Montes Claros, os atendimentos com desfecho urgência/emergência (0,05%), internação hospitalar (0,09%), alta administrativa/clínica (0,26%) eóbito (0,45%) foram baixos. Conclusão:De modo significativo, os atendimentos forammajoritariamente programados, sugerindo planejamento de ações em saúdeem Minas Gerais. A necessidade de permanecerna AD implica em baixos índicespara alta clínica/administrativa, o que pode impactar na resolubilidade do sistema de saúde.

Objective:To investigatedata on home care in public health, from a macro, meso and micro regional perspective in Minas Gerais (MG), Brazil. Method:Study with ecological design. Data were extracted from the Health Information System for Primary Care (SISAB) of the Brazilian Ministry of Health and refer to home care provided from 2016 to 2018. Variables stratified by: gender, type of home care were explored. 1, 2or 3, scheduled or unscheduled care, post-death visit and outcome. The macro perspective was the state of Minas Gerais, the meso the northern region of the state and the micro-region the municipality of Montes Claros (MG). Results:In Minas Gerais, 665,395 home visits were carried out, most frequently for women (51.72%). It was observed that scheduled appointments had frequencies above 95%. In the evaluated period, there was an increase in home visits after the patient's death. Home care modality 2 was themost prevalent in the investigated regions and, in addition, there is a preponderance for the permanence of patients in home care. In Montes Claros, attendances with urgency/emergency outcome (0.05%), hospitalization (0.09%), administrative/clinical discharge (0.26%) and death (0.45%) were low. Conclusion:Significantly, the appointments were mostly scheduled, suggesting planning of health actions in Minas Gerais. The need to remain in the HC implies low rates for clinical/administrative discharge, which may impact the resolution of the health system.

Objetivo:Investigardatos sobre la atención domiciliaria en salud pública, desde una perspectiva macro, mesoy micro regional en Minas Gerais (MG), Brasil. Método:Estudio con diseño ecológico. Los datos fueron extraídos del Sistema de Información en Salud para la Atención Primaria (SISAB) del Ministerio de Salud de Brasil y se refieren a la atención domiciliaria brindada entre 2016 y 2018. Se exploraron variables estratificadas por: género, tipo de atención domiciliaria 1, 2 o 3, atención programada o no programada, visita posterior a la muerte y resultado. La perspectiva macro fue el estado de Minas Gerais, la meso la región norte del estado y la microrregión el municipio de Montes Claros (MG). Resultados: En Minas Gerais se realizaron 665.395 visitas domiciliarias, con mayor frecuencia a mujeres (51,72%). Se observó que las citas programadas tenían frecuencias superiores al 95%. En el período evaluado, hubo un aumento de las visitas domiciliarias después de la muerte del paciente. La modalidad de atención domiciliaria 2 fue la más prevalente en las regiones investigadas y, además, hay preponderancia para la permanencia de los pacientes en la atención domiciliaria. En Montes Claros, las atenciones con resultado de urgencia/emergencia (0,05%), hospitalización (0,09%), alta administrativa/clínica (0,26%) y muerte (0,45%) fueron bajas. Conclusión:Significativamente,las citas fueron en su mayoría programadas, lo que sugiere la planificación de acciones de salud en Minas Gerais. La necesidad de permanencia en el HC implica bajas tasas de alta clínico/administrativa, lo que puede impactar en la resolución del sistema de salud.

Intradermal Immunization of SARS-CoV-2 Original Strain Trimeric Spike Protein Associated to CpG and AddaS03 Adjuvants, but Not MPL, Provide Strong Humoral and Cellular Response in Mice.

Despite the intramuscular route being the most used vaccination strategy against SARS-CoV-2, the intradermal route has been studied around the globe as a strong candidate for immunization against SARS-CoV-2. Adjuvants have shown to be essential vaccine components that are capable of driving robust immune responses and increasing the vaccination efficacy. In this work, our group aimed to develop a vaccination strategy for SARS-CoV-2 using a trimeric spike protein, by testing the best route with formulations containing the adjuvants AddaS03, CpG, MPL, Alum, or a combination of two of them. Our results showed that formulations that were made with AddaS03 or CpG alone or AddaS03 combined with CpG were able to induce high levels of IgG, IgG1, and IgG2a; high titers of neutralizing antibodies against SARS-CoV-2 original strain; and also induced high hypersensitivity during the challenge with Spike protein and a high level of IFN-γ producing CD4+ T-cells in mice. Altogether, those data indicate that AddaS03, CpG, or both combined may be used as adjuvants in vaccines for COVID-19.

Measuring haemolysis in cattle serum by direct UV-VIS and RGB digital image-based methods.

A simple, rapid procedure is required for the routine detection and quantification of haemolysis, one of the main sources of unreliable results in serum analysis. In this study, we compared two different approaches for the rapid determination of haemolysis in cattle serum. The first consisted of estimating haemolysis via a simple direct ultraviolet-visible (UV-VIS) spectrophotometric measurement of serum samples. The second involved analysis of red, green, blue (RGB) colour data extracted from digital images of serum samples and relating the haemoglobin (Hb) content by means of both univariate (R, G, B and intensity separately) and multivariate calibrations (R, G, B and intensity jointly) using partial least squares regression and artificial neural networks. The direct UV-VIS analysis and RGB-multivariate analysis using neural network methods were both appropriate for evaluating haemolysis in serum cattle samples. The procedures displayed good accuracy (mean recoveries of 100.7 and 102.1%, respectively), adequate precision (with coefficients of variation from 0.21 to 2.68%), limit of detection (0.14 and 0.21 g L-1, respectively), and linearity of up to 10 g L-1.

Immunogenicity of SARS-CoV-2 Trimeric Spike Protein Associated to Poly(I:C) Plus Alum.

The SARS-CoV-2 pandemic has had a social and economic impact worldwide, and vaccination is an efficient strategy for diminishing those damages. New adjuvant formulations are required for the high vaccine demands, especially adjuvant formulations that induce a Th1 phenotype. Herein we assess a vaccination strategy using a combination of Alum and polyinosinic:polycytidylic acid [Poly(I:C)] adjuvants plus the SARS-CoV-2 spike protein in a prefusion trimeric conformation by an intradermal (ID) route. We found high levels of IgG anti-spike antibodies in the serum by enzyme linked immunosorbent assay (ELISA) and high neutralizing titers against SARS-CoV-2 in vitro by neutralization assay, after two or three immunizations. By evaluating the production of IgG subtypes, as expected, we found that formulations containing Poly(I:C) induced IgG2a whereas Alum did not. The combination of these two adjuvants induced high levels of both IgG1 and IgG2a. In addition, cellular immune responses of CD4+ and CD8+ T cells producing interferon-gamma were equivalent, demonstrating that the Alum + Poly(I:C) combination supported a Th1 profile. Based on the high neutralizing titers, we evaluated B cells in the germinal centers, which are specific for receptor-binding domain (RBD) and spike, and observed that more positive B cells were induced upon the Alum + Poly(I:C) combination. Moreover, these B cells produced antibodies against both RBD and non-RBD sites. We also studied the impact of this vaccination preparation [spike protein with Alum + Poly(I:C)] in the lungs of mice challenged with inactivated SARS-CoV-2 virus. We found a production of IgG, but not IgA, and a reduction in neutrophil recruitment in the bronchoalveolar lavage fluid (BALF) of mice, suggesting that our immunization scheme reduced lung inflammation. Altogether, our data suggest that Alum and Poly(I:C) together is a possible adjuvant combination for vaccines against SARS-CoV-2 by the intradermal route.

"This Is about My Health": Partnering with Patients and Families to Share Knowledge and Tools about Healthcare Communication for Adults with Intellectual and Developmental Disabilities.

This project involved patients with intellectual and developmental disabilities and a family caregiver as advisors on a knowledge translation (KT) effort on healthcare communication. The project demonstrated that with the right supports, patient and family advisors can effectively share their experiences and add a powerful voice to KT activities. Lessons learned included the importance of being creative, responsive and flexible to support the advisors, of recognizing their expertise and of building capacity in multiple advisors to allow for diverse voices and greater flexibility. This work requires adequate time and funding, which needs to be factored into planning.

Olfactory nerve: from ugly duckling to swan.

BACKGROUND: The olfactory nerve has never been the shining star of neurological examination. Quite the contrary, examining the first cranial nerve is often an overlooked step. As cases of anosmia secondary to COVID-19 infection continue to rise, the 2020 pandemic has shed new light on this much-forgotten nerve, its value as an aid to diagnosis of several diseases and its central role in our daily lives. OBJECTIVE: We aimed to emphasize how essential and simple clinical examination of the olfactory system can be by highlighting practical techniques and clinical tips for its assessment. We also share pearls and pitfalls in localization and differential diagnosis, which may prove valuable to busy clinicians. METHODS: A broad review of the literature was conducted by searching PubMed, Cochrane and Google Scholar for articles and books containing topics regarding examination of the olfactory nerve and its anatomy, physiology and pathology. No particular inclusion or exclusion criteria were used. RESULTS: Forty different works were found, between books and articles, from which 20 were selected after careful analysis. CONCLUSIONS: Despite the tragedy and adversity that followed the COVID-19 pandemic, its legacy has taught us a crystal-clear lesson: olfaction should no longer be neglected in clinical practice.

Current Approaches for Dissolution Similarity Assessment, Requirements, and Global Expectations.

This report summarizes podium presentations and breakout sessions from the second day of the 2019 M-CERSI workshop on In Vitro Dissolution Similarity Assessment in Support of Drug Product Quality: What, How, and When? Presenters from the U.S. Food and Drug Administration (FDA), Health Canada (HC), European Medicines Agency (EMA), Brazilian Health Surveillance Agency (ANVISA), and the pharmaceutical industry shared experiences/concerns with dissolution profile similarity assessment supporting minor/moderate Chemistry, Manufacturing and Control (CMC) changes. Members from regulatory agencies explained that dissolution profile similarity testing is only part of the overall assessment of the acceptability of the proposed changes; decisions are usually made based on aggregate weight of evidence. Scientific shortcomings of f2 were highlighted but no proposal on how to replace it was made. Controlling dissolution timepoint variability and application of pairwise batch-to-batch comparisons (PBC) of dissolution profiles caused considerable debate. Several industry participants suggested increased sample sizes to raise confidence in decision-making and to avoid PBC. They proposed identification of a single mathematical method with predefined acceptance criteria and suggested that dissolution timepoint selection should follow EMA and HC guidance. A majority of meeting attendees favored applying clinically relevant dissolution specifications (CRDS) and dissolution safe space to determine the impact of minor/moderate CMC changes as opposed to dissolution profile similarity assessment via statistical methods. Day 2 of the workshop highlighted the need and opportunities for global harmonization including variability, timepoint selection, role of CRDS, and statistical methods to address the ambiguity globally operating pharmaceutical companies are currently facing.

Epstein-Barr Virus in Childhood and Adolescent Classic Hodgkin Lymphoma in a French Cohort of 301 Patients.

OBJECTIVE: The aim was to analyze the role of Epstein-Barr virus (EBV) in the bioclinical characteristics of patients treated for classic Hodgkin lymphoma (cHL) in France. METHODS: Biopathologic data of 301 patients treated for a cHL in/or according to the EuroNet PHL-C1 trial between November 2008 and February 2013 were centrally reviewed. RESULTS: Median age at diagnosis was 14 (3 to 18) years and the F/M ratio 0.86, 0.47 before 10 years and 0.9 from 11 to 18. CHL subtypes were nodular sclerosis for 266/301 (88%) patients, mixed cellularity for 22/301 (7%), lymphocyte rich for 2/301 (1%), and 11/301 were unclassified. EBV positivity by in situ hybridization was observed for 68/301 (23%) patients, significantly associated with mixed cellularity subtype and male sex, particularly overrepresented in boys below 10 years: 15/23 (65%) versus 28/139 among other male patients (20%). EBV viral load was detectable in 22 of 108 (22%) tested cases and was overrepresented in EBV cHL (13/28) versus non-EBV cHL (9/80) patients. Detailed semiquantitative histologic analysis showed a high number of B-cell residual follicles in EBV cHL relative to EBV-negative HL. CONCLUSION: Distribution of EBV cHL in children and adolescents is associated with young age and male sex, suggesting a specific physiopathology and may require a differential therapeutic approach.

Olfactory nerve: from ugly duckling to swan / Nervo olfatório: de patinho feio a cisne

ABSTRACT Background: The olfactory nerve has never been the shining star of neurological examination. Quite the contrary, examining the first cranial nerve is often an overlooked step. As cases of anosmia secondary to COVID-19 infection continue to rise, the 2020 pandemic has shed new light on this much-forgotten nerve, its value as an aid to diagnosis of several diseases and its central role in our daily lives. Objective: We aimed to emphasize how essential and simple clinical examination of the olfactory system can be by highlighting practical techniques and clinical tips for its assessment. We also share pearls and pitfalls in localization and differential diagnosis, which may prove valuable to busy clinicians. Methods: A broad review of the literature was conducted by searching PubMed, Cochrane and Google Scholar for articles and books containing topics regarding examination of the olfactory nerve and its anatomy, physiology and pathology. No particular inclusion or exclusion criteria were used. Results: Forty different works were found, between books and articles, from which 20 were selected after careful analysis. Conclusions: Despite the tragedy and adversity that followed the COVID-19 pandemic, its legacy has taught us a crystal-clear lesson: olfaction should no longer be neglected in clinical practice.

RESUMO Antecedentes: O nervo olfatório nunca foi a estrela do exame neurológico. Pelo contrário, o exame desse nervo craniano é um passo frequentemente ignorado. No entanto, o aumento exponencial de casos de anosmia secundária a COVID-19 o colocou sob os holofotes, tanto em relação á sua função para o ser humano em sociedade, como seu papel no auxílio do diagnóstico de diversas patologias. Objetivos: Enfatizar quão importante é examinar o nervo olfatório e compreender as desordens do seu sistema. Ressaltamos pérolas clínicas e erros comuns no exame deste nervo, além dicas que possam auxiliar no diagnóstico de uma série de doenças neurológicas e sistêmicas. Métodos: Uma ampla revisão da literatura foi conduzida por meio de busca no PubMed, Cochrane e Google Acadêmico por artigos e livros relacionados aos tópicos do exame físico, fisiologia, anatomia e patologia do nervo olfatório. Não foram utilizados critérios específicos de inclusão ou exclusão. Resultados: Foram encontrados 40 artigos itens relacionados na língua inglesa, dentre os quais livros e artigos, tendo sido analisados e selecionados um a um até o total de 20 referências. Conclusões: Apesar da tragédia e adversidade trazidas pela pandemia de COVID-19, uma lição clara permanece: o olfato não deve mais ser negligenciado na prática clínica.

Influence of Haemolysis on the Mineral Profile of Cattle Serum.

Haemolysis of serum samples is the leading cause of preanalytical errors in clinical laboratories. Little is known about the potential alterations in the concentrations of mineral elements in haemolyzed serum and the phenomenon has not been specifically studied in bovine serum samples. We investigate how haemolysis affects the mineral content of bovine samples. We used ICP-MS to measure the concentrations of 12 mineral elements (Ca, Co, Cr, Cu, Fe, Mg, Mn, Mo, Ni, P, Se and Zn) in bovine whole blood, serum and gradually haemolyzed samples and observed significant differences between the different types of samples, particularly in the Fe and Zn concentrations. However, in practice, the high interindividual variability makes it difficult to establish whether a given value corresponds to normal or haemolyzed samples. In response to this problem, we propose to consider that a result is significantly biased when the haemolysis threshold (the degree of haemolysis above which the concentration of an element in serum is significantly altered) of a given element is surpassed. The haemolysis threshold values for the different elements considered were found as follows: 0.015 g Hb L-1 for Fe, 2 g for Zn, 4 g for Cr and 8 g for Ca, Se and Mo.