Classical and Innovative Evidence for Therapeutic Strategies in Retinal Dysfunctions.

The human retina is a complex anatomical structure that has no regenerative capacity. The pathogenesis of most retinopathies can be attributed to inflammation, with the activation of the inflammasome protein platform, and to the impact of oxidative stress on the regulation of apoptosis and autophagy/mitophagy in retinal cells. In recent years, new therapeutic approaches to treat retinopathies have been investigated. Experimental data suggest that the secretome of mesenchymal cells could reduce oxidative stress, autophagy, and the apoptosis of retinal cells, and in turn, the secretome of the latter could induce changes in mesenchymal cells. Other studies have evidenced that noncoding (nc)RNAs might be new targets for retinopathy treatment and novel disease biomarkers since a correlation has been found between ncRNA levels and retinopathies. A new field to explore is the interaction observed between the ocular and intestinal microbiota; indeed, recent findings have shown that the alteration of gut microbiota seems to be linked to ocular diseases, suggesting a gut-eye axis. To explore new therapeutical strategies for retinopathies, it is important to use proper models that can mimic the complexity of the retina. In this context, retinal organoids represent a good model for the study of the pathophysiology of the retina.

Multimodal Intraoperative Neurophysiological Monitoring in Intramedullary Spinal Cord Tumors: A 10-Year Single Center Experience.

OBJECTIVE: The study aimed at evaluating the efficacy and the ability of D-wave monitoring combined with somatosensory evoked potentials (SSEPs) and motor evoked potentials (MEPs) to predict functional outcomes in intramedullary spinal cord tumor (IMSCT) surgery. METHODS: Between December 2011 and December 2020, all patients harboring IMSCT who underwent surgery at our institution were prospectively collected in a surgical spinal registry and retrospectively analyzed. Patient charts and surgical and histological reports were analyzed. The multimodal IONM included SSEPs, MEPs, and-whenever possible-D-waves. All patients were evaluated using the modified McCormick and Frankel grade at admission and 3, 6, and 12 months of follow-up. RESULTS: Sixty-four patients were enrolled in the study. SSEP and MEP monitoring was performed in all patients. The D-wave was not recordable in seven patients (11%). Significant IONM changes (at least one evoked potential modality) were registered in 26 (41%) of the 64 patients. In five cases (8%) where the SSEPs and MEPs lost and the D-wave permanently dropped by about 50%, patients experienced a permanent deterioration of their neurological status. Multimodal IONM (SSEP, MEP, and D-wave neuromonitoring) significantly predicted postoperative deficits (p = 0.0001), with a sensitivity of 100.00% and a specificity of 95.65%. However, D-waves demonstrated significantly higher sensitivity (100%) than MEPs (62.5%) and SSEPs (71.42%) alone. These tests' specificities were 85.10%, 13.89%, and 17.39%, respectively. Comparing the area under ROC curves (AUCs) of these evoked potentials in 53 patients (where all three modalities of IONM were registered) using the pairwise t-test, D-wave monitoring appeared to have higher accuracy and ability to predict postoperative deficits with strong statistical significance compared with MEP and SSEP alone (0.992 vs. 0.798 vs. 0.542; p = 0.018 and p < 0.001). CONCLUSION: The use of multimodal IONM showed a statistically significant greater ability to predict postoperative deficits compared with SSEP, MEP, and D-wave monitoring alone. D-wave recording significantly increased the accuracy and clinical value of neurophysiological monitoring in IMSCT tumor resection.

Validation of the Informal Caregiver Burden Assessment Questionnaire for Brazil - short version.

OBJECTIVES: to cross-culturally adapt the short version of the Informal Caregiver Burden Assessment Questionnaire to the Brazilian culture and test its psychometric properties. METHODS: the questionnaire was translated, adapted, and applied to a sample of 280 informal caregivers. The psychometric assessment was verified by estimating psychometric sensitivity and internal structure validity. RESULTS: inter-rater agreement was satisfactory among specialists. In the seven-factor model, item (Q9) of the domain "Perception of Efficacy and Control Mechanisms" showed a factor loading less than 0.40 (ʎ = 0.26), and an alternative six-factor model was evaluated. However, both models showed excellent fit indices, and it was decided to keep the seven-factor reference model. Reliability was satisfactory for the seven subscales (α > 0.70). CONCLUSIONS: the questionnaire was adapted and showed adequate psychometric indices in the Brazilian context in which it was evaluated, preserving its original essence.

p53/NF-kB Balance in SARS-CoV-2 Infection: From OMICs, Genomics and Pharmacogenomics Insights to Tailored Therapeutic Perspectives (COVIDomics).

SARS-CoV-2 infection affects different organs and tissues, including the upper and lower airways, the lung, the gut, the olfactory system and the eye, which may represent one of the gates to the central nervous system. Key transcriptional factors, such as p53 and NF-kB and their reciprocal balance, are altered upon SARS-CoV-2 infection, as well as other key molecules such as the virus host cell entry mediator ACE2, member of the RAS-pathway. These changes are thought to play a central role in the impaired immune response, as well as in the massive cytokine release, the so-called cytokine storm that represents a hallmark of the most severe form of SARS-CoV-2 infection. Host genetics susceptibility is an additional key side to consider in a complex disease as COVID-19 characterized by such a wide range of clinical phenotypes. In this review, we underline some molecular mechanisms by which SARS-CoV-2 modulates p53 and NF-kB expression and activity in order to maximize viral replication into the host cells. We also face the RAS-pathway unbalance triggered by virus-ACE2 interaction to discuss potential pharmacological and pharmacogenomics approaches aimed at restoring p53/NF-kB and ACE1/ACE2 balance to counteract the most severe forms of SARS-CoV-2 infection.

Intramedullary spinal cord tumors: the value of intraoperative neurophysiological monitoring in a series of 57 cases from two Italian centers.

BACKGROUND: Intramedullary spinal cord tumors are rare lesions of the central nervous system. Anatomical, molecular and radiological features are well defined, but correct management is still matter of debate. Pertinent literature has reported conflicting opinions regarding the use of intraoperative electrophysiological monitoring (IONM) in the surgical treatment of this kind of lesions, recently. We report a retrospective study from two Italian centers, in order to highlight the usefulness of IONM in the management of intramedullary lesions. METHODS: We performed a retrospective review of patients with intramedullary spinal tumor who underwent surgical resection from February 2011 to February 2018 in two different institutions. Clinical and radiological data, lesion features, timing of symptom onset and IONM findings were recorded. The IONM included somatosensory-evoked potentials (SSEP), motor-evoked potentials (MEP) and D-Wave whenever possible. We evaluated the outcome according to the Modified McCormick scale. We also evaluated the accuracy and relevance of surgical outcomes for each evoked potential (SSEP, MEP, D-Wave). RESULTS: A total of 57 patients were included. A gross total removal was achieved in 46 cases. Neurological follow-up was assessment at 3 days, and 3 and 6 months after surgery. Comparing the preoperative status and 6 months follow-up: the modified McCormick scale showed a neurological stability for 30 patients (52.63%), a worsening of neurological status for 7 patients (12.28%) and an improvement for 20 patients (35.08%). IONM presented high accuracy (sensibility of 100% and specificity of 95.65%) and significantly predicted postoperative permanent motor deficits (P<0.0001; AUC=0.978). D-Wave appeared to have significant greater predictive value than MEP and especially SSEP alone (0.967 vs 0.722 vs 0.542; P=0.044 and P<0.001 respectively). CONCLUSIONS: The gold standard in the intramedullary lesion treatment is maximal safe resection with good neurological outcome, as shown in our patients. The use of IONM is helpful in intramedullary tumors resection in order to minimize postoperative neurological deficits and our analysis suggests that the use of D-Wave presents a statistically significant higher accuracy for predicting postoperative deficits than SSEP and MEP alone.

Validation of the Informal Caregiver Burden Assessment Questionnaire for Brazil - short version / Validación del Cuestionario de Evaluación de la Sobrecarga del Cuidador Informal de Brasil - versión corta / Validação do Questionário de Avaliação da Sobrecarga do Cuidador Informal para o Brasil - versão curta

ABSTRACT Objectives: to cross-culturally adapt the short version of the Informal Caregiver Burden Assessment Questionnaire to the Brazilian culture and test its psychometric properties. Methods: the questionnaire was translated, adapted, and applied to a sample of 280 informal caregivers. The psychometric assessment was verified by estimating psychometric sensitivity and internal structure validity. Results: inter-rater agreement was satisfactory among specialists. In the seven-factor model, item (Q9) of the domain "Perception of Efficacy and Control Mechanisms" showed a factor loading less than 0.40 (ʎ = 0.26), and an alternative six-factor model was evaluated. However, both models showed excellent fit indices, and it was decided to keep the seven-factor reference model. Reliability was satisfactory for the seven subscales (α > 0.70). Conclusions: the questionnaire was adapted and showed adequate psychometric indices in the Brazilian context in which it was evaluated, preserving its original essence.

RESUMEN Objetivos: adaptar transculturalmente la versión corta del Cuestionario de Evaluación de la Sobrecarga del Cuidador Informal para cultura brasileña y probar sus propriedades psicométricas. Métodos: cuestionario traducido, adaptado y aplicado para 280 cuidadores informales. Evaluación psicométrica verificada por la estimativa de la sensibilidad psicométrica y validez de la estructura interna. Resultados: la concordancia interevaluadores fue satisfactoria entre los especialistas. En el modelo de siete factores, el ítem (Q9) del dominio "Percepción de los mecanismos de eficacia y control" presentó carga factorial menor que 0,40 (ʎ = 0,26), y un modelo alternativo de seis factores fue evaluado. Sin embargo, los dos modelos evidenciaron óptimos índices de ajustamiento, y se optó por mantener el modelo-referencia de siete factores. La confiabilidad se mostró satisfactoria para las siete subescalas (α > 0,70). Conclusiones: el cuestionario fue adaptado y demostró indicadores psicométricos satisfactorios en el contexto brasileño en que fue evaluado, preservando su esencia original.

RESUMO Objetivos: adaptar transculturalmente a versão curta do Questionário de Avaliação da Sobrecarga do Cuidador Informal para cultura brasileira e testar suas propriedades psicométricas. Métodos: o questionário foi traduzido, adaptado e aplicado em uma amostra de 280 cuidadores informais. A avaliação psicométrica foi verificada pela estimativa da sensibilidade psicométrica e validade da estrutura interna. Resultados: a concordância interavaliadores foi satisfatória entre os especialistas. No modelo de sete fatores, o item (Q9) do domínio "Percepção dos Mecanismos de Eficácia e Controle" apresentou carga fatorial menor do que 0,40 (ʎ = 0,26), e um modelo alternativo de seis fatores foi avaliado. No entanto, os dois modelos evidenciaram ótimos índices de ajustamento, e optou-se por manter o modelo-referência de sete fatores. A confiabilidade mostrou-se satisfatória para as sete subescalas (α > 0,70). Conclusões: o questionário foi adaptado e demonstrou índices psicométricos satisfatórios no contexto brasileiro em que foi avaliado, preservando sua essência original.

Overcoming of Microenvironment Protection on Primary Chronic Lymphocytic Leukemia Cells after Treatment with BTK and MDM2 Pharmacological Inhibitors.

In B-chronic lymphocytic leukemia (B-CLL), the interaction between leukemic cells and the microenvironment promotes tumor cell survival. The Bruton's tyrosine kinase (BTK) inhibitor ibrutinib is one of the first-in-class molecules for the treatment of B-CLL patients; however, the emerging mechanisms of resistance to ibrutinib call for new therapeutic strategies. The purpose of the current study was to investigate the ability of ibrutinib plus the MDM2-inhibitor nutlin-3 to counteract the tumor microenvironment protective effect. We observed that primary B-CLL cells cultivated in microenvironment mimicking conditions were protected from apoptosis by the up-regulation of c-MYC and of p53. In the same setting, combined treatments with ibrutinib plus nutlin-3 led to significantly higher levels of apoptosis compared to the single treatments, counteracting the c-MYC up-regulation. Moreover, the combination induced high p53 levels and a significant dissipation of the mitochondrial membrane potential, together with BAX cleavage in the more active p18 form and phospho-BAD down-regulation, that are key components of the mitochondrial apoptotic pathway, enhancing the apoptosis level. Our findings propose a new therapeutic strategy to overcome the tumor microenvironment protection involved in B-CLL resistance to drugs, with possible clinical implications also for other hematologic and solid tumors for which ibrutinib is considered a therapeutic option.

Genetics and Epigenetics of One-Carbon Metabolism Pathway in Autism Spectrum Disorder: A Sex-Specific Brain Epigenome?

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition affecting behavior and communication, presenting with extremely different clinical phenotypes and features. ASD etiology is composite and multifaceted with several causes and risk factors responsible for different individual disease pathophysiological processes and clinical phenotypes. From a genetic and epigenetic side, several candidate genes have been reported as potentially linked to ASD, which can be detected in about 10-25% of patients. Folate gene polymorphisms have been previously associated with other psychiatric and neurodegenerative diseases, mainly focused on gene variants in the DHFR gene (5q14.1; rs70991108, 19bp ins/del), MTHFR gene (1p36.22; rs1801133, C677T and rs1801131, A1298C), and CBS gene (21q22.3; rs876657421, 844ins68). Of note, their roles have been scarcely investigated from a sex/gender viewpoint, though ASD is characterized by a strong sex gap in onset-risk and progression. The aim of the present review is to point out the molecular mechanisms related to intracellular folate recycling affecting in turn remethylation and transsulfuration pathways having potential effects on ASD. Brain epigenome during fetal life necessarily reflects the sex-dependent different imprint of the genome-environment interactions which effects are difficult to decrypt. We here will focus on the DHFR, MTHFR and CBS gene-triad by dissecting their roles in a sex-oriented view, primarily to bring new perspectives in ASD epigenetics.

Sex/Gender-Specific Imbalance in CVD: Could Physical Activity Help to Improve Clinical Outcome Targeting CVD Molecular Mechanisms in Women?

In the last two decades, new insights have been gained regarding sex/gender-related differences in cardiovascular disease (CVD). CVD represents the leading cause of death worldwide in both men and women, accounting for at least one-third of all deaths in women and half of deaths in women over 50 years in developing countries. Important sex-related differences in prevalence, presentation, management, and outcomes of different CVDs have been recently discovered, demonstrating sex/gender-specific pathophysiologic features in the presentation and prognosis of CVD in men and women. A large amount of evidence has highlighted the role of sex hormones in protecting women from CVDs, providing an advantage over men that is lost when women reach the menopause stage. This hormonal-dependent shift of sex-related CVD risk consequently affects the overall CVD epidemiology, particularly in light of the increasing trend of population aging. The benefits of physical activity have been recognized for a long time as a powerful preventive approach for both CVD prevention and aging-related morbidity control. Exercise training is indeed a potent physiological stimulus, which reduces primary and secondary cardiovascular events. However, the underlying mechanisms of these positive effects, including from a sex/gender perspective, still need to be fully elucidated. The aim of this work is to provide a review of the evidence linking sex/gender-related differences in CVD, including sex/gender-specific molecular mediators, to explore whether sex- and gender-tailored physical activity may be used as an effective tool to prevent CVD and improve clinical outcomes in women.

miRNAs as Influencers of Cell-Cell Communication in Tumor Microenvironment.

microRNAs (miRNAs) are small noncoding RNAs that regulate gene expression at the posttranscriptional level, inducing the degradation of the target mRNA or translational repression. MiRNAs are involved in the control of a multiplicity of biological processes, and their absence or altered expression has been associated with a variety of human diseases, including cancer. Recently, extracellular miRNAs (ECmiRNAs) have been described as mediators of intercellular communication in multiple contexts, including tumor microenvironment. Cancer cells cooperate with stromal cells and elements of the extracellular matrix (ECM) to establish a comfortable niche to grow, to evade the immune system, and to expand. Within the tumor microenvironment, cells release ECmiRNAs and other factors in order to influence and hijack the physiological processes of surrounding cells, fostering tumor progression. Here, we discuss the role of miRNAs in the pathogenesis of multicomplex diseases, such as Alzheimer's disease, obesity, and cancer, focusing on the contribution of both intracellular miRNAs, and of released ECmiRNAs in the establishment and development of cancer niche. We also review growing evidence suggesting the use of miRNAs as novel targets or potential tools for therapeutic applications.

Purinergic Signaling in Controlling Macrophage and T Cell Functions During Atherosclerosis Development.

Atherosclerosis is a hardening and narrowing of arteries causing a reduction of blood flow. It is a leading cause of death in industrialized countries as it causes heart attacks, strokes, and peripheral vascular disease. Pathogenesis of the atherosclerotic lesion (atheroma) relies on the accumulation of cholesterol-containing low-density lipoproteins (LDL) and on changes of artery endothelium that becomes adhesive for monocytes and lymphocytes. Immunomediated inflammatory response stimulated by lipoprotein oxidation, cytokine secretion and release of pro-inflammatory mediators, worsens the pathological context by amplifying tissue damage to the arterial lining and increasing flow-limiting stenosis. Formation of thrombi upon rupture of the endothelium and the fibrous cup may also occur, triggering thrombosis often threatening the patient's life. Purinergic signaling, i.e., cell responses induced by stimulation of P2 and P1 membrane receptors for the extracellular nucleotides (ATP, ADP, UTP, and UDP) and nucleosides (adenosine), has been implicated in modulating the immunological response in atherosclerotic cardiovascular disease. In this review we will describe advancements in the understanding of purinergic modulation of the two main immune cells involved in atherogenesis, i.e., monocytes/macrophages and T lymphocytes, highlighting modulation of pro- and anti-atherosclerotic mediated responses of purinergic signaling in these cells and providing new insights to point out their potential clinical significance.

Crosstalk Between Adipokines and Paraoxonase 1: A New Potential Axis Linking Oxidative Stress and Inflammation.

Paraoxonase 1 (PON1) is a high-density lipoprotein (HDL)-associated protein that endows its carrier with (lipo-)lactonase-dependent antioxidative features. Low levels of PON1 activity have been observed in association with obesity, a major risk factor for cardiovascular disease (CVD). Considering the well-recognized atheroprotective role of PON1, exogenous/endogenous factors that might modulate its levels/activity are raising great interest. Since adipokines represent a molecular link between obesity and CVD, we here explored the possible impact of these substances on PON1 activity/expression. The levels of interleukin (IL)-6, IL-8, tumor necrosis factor alpha, monocyte chemoattractant protein-1, hepatocyte growth factor, resistin, leptin, and adiponectin were measured along with arylesterase, paraoxonase, and lactonase activities of PON1 in 107 postmenopausal women. Moreover, the direct effect of resistin on PON1 expression was evaluated in vitro. Multivariate analysis revealed that only resistin was significantly and inversely correlated with PON1-lactonase activities (r = -0.346, p < 0.001) regardless of confounding factors such as age or HDL-cholesterol. It is worth noting that no statistical link was found between adipokine and arylesterase or paraoxonase, the two promiscuous activities of PON1. Notably, resistin down-regulated PON1 expression occurred in hepatocellular carcinoma cultures. Our study suggests that resistin might be a negative modulator of PON1 expression and anti-oxidative activity.

TRAIL, OPG, and TWEAK in kidney disease: biomarkers or therapeutic targets?

Ligands and receptors of the tumor necrosis factor (TNF) superfamily regulate immune responses and homeostatic functions with potential diagnostic and therapeutic implications. Kidney disease represents a global public health problem, whose prevalence is rising worldwide, due to the aging of the population and the increasing prevalence of diabetes, hypertension, obesity, and immune disorders. In addition, chronic kidney disease is an independent risk factor for the development of cardiovascular disease, which further increases kidney-related morbidity and mortality. Recently, it has been shown that some TNF superfamily members are actively implicated in renal pathophysiology. These members include TNF-related apoptosis-inducing ligand (TRAIL), its decoy receptor osteoprotegerin (OPG), and TNF-like weaker inducer of apoptosis (TWEAK). All of them have shown the ability to activate crucial pathways involved in kidney disease development and progression (e.g. canonical and non-canonical pathways of the transcription factor nuclear factor-kappa B), as well as the ability to regulate cell proliferation, differentiation, apoptosis, necrosis, inflammation, angiogenesis, and fibrosis with double-edged effects depending on the type and stage of kidney injury. Here we will review the actions of TRAIL, OPG, and TWEAK on diabetic and non-diabetic kidney disease, in order to provide insights into their full clinical potential as biomarkers and/or therapeutic options against kidney disease.

Role of physical exercise in the regulation of epigenetic mechanisms in inflammation, cancer, neurodegenerative diseases, and aging process.

The genetic heritage for decades has been considered to respond only to gene promoters or suppressors, with specific roles for oncogenes or tumor-suppressor genes. Epigenetics is progressively attracting increasing interest because it has demonstrated the capacity of these regulatory processes to regulate the gene expression without modifying gene sequence. Several factors may influence epigenetics, such as lifestyles including food selection. A role for physical exercise is emerging in the epigenetic regulation of gene expression. In this review, we resume physiological and pathological implications of epigenetic modification induced by the physical activity (PA). Inflammation and cancer mechanisms, immune system, central nervous system, and the aging process receive benefits due to PA through epigenetic mechanisms. Thus, the modulation of epigenetic processes by physical exercise positively influences prevention, development, and the course of inflammatory and cancer diseases, as well as neurodegenerative illnesses. This growing field of studies gives rise to a new role for PA as an option in prevention strategies and to integrate pharmacological therapeutic treatments.

Psychometric properties evaluation of the Psychological Empowerment Instrument in a Brazilian context.

AIM: To evaluate the psychometric properties of the Psychological Empowerment Instrument among Brazilian nurses. BACKGROUND: The Psychological Empowerment Instrument-Brazil is a structured questionnaire that aims to measure the psychological empowerment in the work environment. METHOD: A methodological study involving 219 nurses. Confirmatory factor analysis was conducted to evaluate the factor structure validity of the Psychological Empowerment Instrument-Brazil. Model fit indices and saliences of factor loadings were assessed. The convergent validity was estimated using the average variance extracted and composite reliability. The correlational analysis was verified using the Spearman Correlation between the Psychological Empowerment Instrument-Brazil and other specific tools. Discriminant validity, internal consistency, test-retest and floor/ceiling effects were also assessed. RESULTS: Factor structure indices of the second-order hierarchical model were [λ = 0.47-0.84; χ2 /df = 1.84, GFI = 0.93, CFI = 0.96, TLI = 0.94, RMSEA = 0.06 (90% CI = 0.04-0.08)]. Model refinement was not required. All subscales presented suitable average variance extracted, composite reliability and Cronbach's alpha, except the Impact subscale (0.39; composite reliability = 0.65, α = 0.63). All correlations between Psychological Empowerment Instrument-Brazil and the other questionnaires were significant. CONCLUSION: Psychometric properties of the Psychological Empowerment Instrument-Brazil were suitable when applied to Brazilian nurses. IMPLICATIONS FOR NURSING MANAGEMENT: Psychological Empowerment Instrument-Brazil supports the evaluation of the empowerment level, as well as the applicability of the psychological empowerment in the work environment of Brazilian nurses.

F13A1 Gene Variant (V34L) and Residual Circulating FXIIIA Levels Predict Short- and Long-Term Mortality in Acute Myocardial Infarction after Coronary Angioplasty.

Factor XIIIA (FXIIIA) levels are independent predictors of early prognosis after acute myocardial infarction (AMI) and the Valine-to-Leucine (V34L) single nucleotide polymorphism (SNP) seems associated with lower AMI risk. Since the long-term AMI prognosis merits deeper investigation, we performed an observational study evaluating relationships between FXIIIA residual levels, cardiovascular risk-factors, and inherited genetic predispositions. FXIIIA V34L was genotyped in 333 AMI patients and a five-year follow-up was performed. FXIIIA levels assessed at day-zero (d0) and four days after AMI (d4), and conventional risk factors were analyzed, focusing on the development of major adverse cardiovascular events (MACE). FXIIIA assessed at d0 and d4 was also an independent MACE predictor in the long-term follow-up (FXIIIAd0, Odds Ratio (OR) = 3.02, 1.79⁻5.1, p = 0.013; FXIIIAd4, OR = 4.46, 2.33⁻8.55, p = 0.0001). FXIIIAd4 showed the strongest MACE association, suggesting that the FXIIIA protective role is maximized when high levels are maintained for longer time. Conversely, FXIIIA levels stratified by V34L predicted MACE at a lesser extent among L34-carriers (Hazard Risk (HR)VV34 = 3.89, 2.19⁻6.87, p = 0.000003; HRL34-carriers = 2.78, 1.39⁻5.57, p = 0.0039), and V34L did not predict all MACE, only multiple-MACE occurrence (p = 0.0087). Finally, in survival analysis, heart failure and death differed significantly from stroke and recurrent ischemia (p = 0.0013), with FXIIIA levels appreciably lower in the former (p = 0.05). Overall, genetically-determined FXIIIA levels have a significant long-term prognostic role, suggesting that a pharmacogenetics approach might help to select those AMI patients at risk of poor prognosis in the need of dedicated treatments.

[Obstacles to return to work: Translation and cross-cultural adaptation of the questionnaire to the Brazilian context]. / Obstáculos para retorno ao trabalho: tradução e adaptação cultural do questionário para o contexto brasileiro.

The few existing questionnaires addressing return to work in Brazil are medical and/or psychological and do not examine work environment-related issues. The Obstacles to Return-to-Work Questionnaire (ORTWQ) is multidimensional, including biopsychosocial and environmental factors, and has proven useful in the return to work issue. The scope of this study is to describe the translation and cultural adaptation process of ORTWQ for use in the Brazilian context. It also discusses aspects related to work and the importance for health professionals to identify obstacles to return to work for occupational health vigilance. For the cultural adaptation process, there were five steps: translation, synthesis, back translation, evaluation by an expert committee and the pre-test process. Before the pre-test phase, the Content Validity Index was checked and was considered adequate when it was ≥ 0.8. The expression "increase working hours" was withdrawn from the questionnaire, since the partial returnto-work regime is rare in Brazil. The sample for the pre-test involved 40 individuals. The average time for completing ORTWQ was 14 minutes and the Brazilian version of ORTWQ proved to be adequate. Further studies should assess psychometric qualities of the questionnaire.

Os raros questionários existentes no Brasil que abordam retorno ao trabalho são físicos e/ou psicológicos e não abrangem questões relativas ao ambiente de trabalho. O Obstacles to Return-to-Work Questionnaire (ORTWQ) é multidimensional, inclui fatores biopsicossociais, ambientais e tem se mostrado útil como preditor de retorno ao trabalho. Este estudo tem como objetivo discutir a importância, para a Vigilância em Saúde do Trabalhador, de questionários que identificam os obstáculos para retorno ao trabalho, bem como traduzir e adaptar culturalmente o ORTWQ para uso no contexto brasileiro. Cinco etapas foram seguidas para a adaptação cultural: tradução, síntese, retrotradução, avaliação por comitê de especialistas e pré-teste. Antes do pré-teste, o Índice de Validade de Conteúdo foi verificado e considerado adequado quando ≥ 0,8. Foi retirado do questionário, o termo "aumentar as horas de trabalho", uma vez que o regime de retorno parcial ao trabalho é raro no Brasil. Participaram do pré-teste 40 sujeitos. A versão brasileira do ORTWQ mostrou-se adequada e o tempo médio para preenchimento foi de 14 minutos. Outros estudos devem avaliar as qualidades psicométricas desse questionário.

Obstáculos para retorno ao trabalho: tradução e adaptação cultural do questionário para o contexto brasileiro / Obstacles to return to work: Translation and cross-cultural adaptation of the questionnaire to the Brazilian context

Resumo Os raros questionários existentes no Brasil que abordam retorno ao trabalho são físicos e/ou psicológicos e não abrangem questões relativas ao ambiente de trabalho. O Obstacles to Return-to-Work Questionnaire (ORTWQ) é multidimensional, inclui fatores biopsicossociais, ambientais e tem se mostrado útil como preditor de retorno ao trabalho. Este estudo tem como objetivo discutir a importância, para a Vigilância em Saúde do Trabalhador, de questionários que identificam os obstáculos para retorno ao trabalho, bem como traduzir e adaptar culturalmente o ORTWQ para uso no contexto brasileiro. Cinco etapas foram seguidas para a adaptação cultural: tradução, síntese, retrotradução, avaliação por comitê de especialistas e pré-teste. Antes do pré-teste, o Índice de Validade de Conteúdo foi verificado e considerado adequado quando ≥ 0,8. Foi retirado do questionário, o termo "aumentar as horas de trabalho", uma vez que o regime de retorno parcial ao trabalho é raro no Brasil. Participaram do pré-teste 40 sujeitos. A versão brasileira do ORTWQ mostrou-se adequada e o tempo médio para preenchimento foi de 14 minutos. Outros estudos devem avaliar as qualidades psicométricas desse questionário.

Abstract The few existing questionnaires addressing return to work in Brazil are medical and/or psychological and do not examine work environment-related issues. The Obstacles to Return-to-Work Questionnaire (ORTWQ) is multidimensional, including biopsychosocial and environmental factors, and has proven useful in the return to work issue. The scope of this study is to describe the translation and cultural adaptation process of ORTWQ for use in the Brazilian context. It also discusses aspects related to work and the importance for health professionals to identify obstacles to return to work for occupational health vigilance. For the cultural adaptation process, there were five steps: translation, synthesis, back translation, evaluation by an expert committee and the pre-test process. Before the pre-test phase, the Content Validity Index was checked and was considered adequate when it was ≥ 0.8. The expression "increase working hours" was withdrawn from the questionnaire, since the partial returnto-work regime is rare in Brazil. The sample for the pre-test involved 40 individuals. The average time for completing ORTWQ was 14 minutes and the Brazilian version of ORTWQ proved to be adequate. Further studies should assess psychometric qualities of the questionnaire.

Physical training interventions for children and teenagers affected by acute lymphoblastic leukemia and related treatment impairments.

A decreased physical fitness has been reported in patients and survivors of acute lymphoblastic leukemia (ALL). This is influenced by the negative effects of the disease and by the treatments of childhood cancer. In the past, children were advised to recover in bed, and to take as much relax as possible. Nowadays, it is considered that too much immobility may result in a further decrease of physical fitness and functioning. Exercise training for ALL children has frequently been reported to improve physical fitness and the well-being of the children, since it prevents the negative effects of a sedentary life-style, such as obesity and a poor skeletal health. In recent years, different studies and protocols on this subject has become available for children and young adults with cancer, both during and after treatment. The efficacy of recent physical exercise training interventions, that act on several ALL impairments in children such as skeletal, musculoskeletal, neuromuscular, cardiopulmonary and cardiovascular systems, fatigue, body balance disorders and metabolism alterations have been examined. These side effects might be prevented or significantly reduced by introducing a physical exercise program during or shortly after cancer treatment. Several interventions are discussed and presented for each impairment, reducing their level caused by the disease and thus suggesting the importance of physical training activity in ameliorating the children quality of life.

Assessment of the praxis circuit in glioma surgery to reduce the incidence of postoperative and long-term apraxia: a new intraoperative test.

OBJECTIVEApraxia is a cognitive-motor deficit affecting the execution of skilled movements, termed praxis gestures, in the absence of primary sensory or motor disorders. In patients affected by stroke, apraxia is associated with lesions of the lateral parietofrontal stream, connecting the posterior parietal areas with the ventrolateral premotor area and subserving sensory-motor integration for the hand movements. In the neurosurgical literature to date, there are few reports regarding the incidence of apraxia after glioma surgery. A retrospective analysis of patients who harbored a glioma around the central sulcus and close to the parietofrontal circuits in depth showed a high incidence of long-term postoperative hand apraxia, impairing the patients' quality of life. To avoid the occurrence of postoperative apraxia, the authors sought to develop an innovative intraoperative hand manipulation task (HMt) that can be used in association with the brain mapping technique to identify and preserve the cortical and subcortical structures belonging to the praxis network.METHODSThe intraoperative efficacy of the HMt was investigated by comparing the incidence of postoperative ideomotor apraxia between patients undergoing mapping with (n = 79) and without (n = 41) the HMt. Patient groups were balanced for all demographic and clinical features.RESULTSIn patients with lesions in the dominant hemisphere, the HMt dramatically reduced the incidence of apraxia, with a higher sensitivity for the ideomotor than for the constructional abilities; patients with lesions in the nondominant hemisphere benefitted from the HMt for both ideomotor and constructional abilities. The administration of the test did not reduce the extent of resection.CONCLUSIONSThe HMt is a safe and feasible intraoperative tool that allowed surgeons to prevent the occurrence of long-term hand apraxia while attaining resection goals for the surgical treatment of glioma.