Parental and familial factors related to participation in a home-based physical activity intervention in children with obesity or Prader-Willi syndrome.

Background: Increasing physical activity (PA) participation is vital to promote the development of health behaviors in childhood. This study examined which parental and familial factors predicted completion of and compliance with a home-based family PA program in a cohort of families with a child with Prader-Willi syndrome (PWS; a rare disorder with obesity and developmental disability) or with obesity but with neurotypical development. Methods: Participants (n = 105) were parents of children with PWS (n = 41) and parents of children with obesity but without PWS (n = 64). Parents completed a series of questionnaires documenting their demographic characteristics, self-efficacy, social support, and family environment (active-recreational orientation and cohesion). Relationships between these factors and intervention completion and compliance were evaluated using bivariate correlations and logistic regression (compliance) and multiple regression (completion) analyses with groups together and then separately if the child group was a significant predictor. Results: None of the variables of interest (marital status, employment, employed hours per week, self-efficacy, social support, and family environment) were significant predictors of intervention completion. Intervention compliance was negatively associated with parents working part-time and working full-time and positively associated with family cohesion (Model R2 = 0.107, F(3,100) = 4.011, p = .010). Child group was not a factor. Conclusions: Compliance with a 24-week family home-based PA intervention was related to fewer employment hours of the primary caregiver and family environment factors. Future interventions should consider how to reduce the intervention's burden in working parents along with strategies to foster family cohesion.

Recomendaciones para la coordinación de los servicios de Neurología y Neurorradiología en la atención a pacientes con esclerosis múltiple / Recommendations for the coordination of Neurology and Neuroradiology Departments in the management of patients with multiple sclerosis

Introducción: El uso de la resonancia magnética (RM) está ampliamente extendido en el diagnóstico y el seguimiento de los pacientes con esclerosis múltiple (EM). La coordinación entre los servicios de Neurología y Neurorradiología es clave para la realización e interpretación de estudios radiológicos de la manera más eficaz posible. Sin embargo, esta coordinación es susceptible de mejoras en una gran parte de los hospitales nacionales. Métodos: Un panel de 17 neurólogos y neurorradiólogos de 8 hospitales españoles, presencialmente y a través de comunicación online, consensuaron una guía de buenas prácticas en la coordinación en EM. La guía se estableció en 4 fases: 1) definición del alcance de la guía y metodología del estudio; 2) revisión bibliográfica sobre buenas prácticas o recomendaciones en el uso de la RM en EM; 3) discusión y búsqueda de consenso entre los expertos; y 4) formalización y validación de los contenidos para elaborar el documento de consenso. Resultados: Se consensuaron un total de 9 recomendaciones dirigidas a la mejora de la coordinación entre los servicios de Neurología y Neurorradiología, que se pueden resumir en: 1) estandarizar las solicitudes de RM, informes y planificación; 2) crear protocolos compartidos para los estudios de RM; 3) establecer comités multidisciplinares y sesiones de coordinación, y 4) generar canales de comunicación formales entre los profesionales de ambos departamentos. Conclusiones: Se espera que las recomendaciones consensuadas sirvan de guía para optimizar la coordinación entre neurólogos y neurorradiólogos y que repercutan en la mejora del diagnóstico y seguimiento de los pacientes con EM.(AU)

Introduction: Magnetic resonance imaging (MRI) is widely used for the diagnosis and follow-up of patients with multiple sclerosis (MS). Coordination between Neurology and Neuroradiology departments is crucial for performing and interpreting radiological studies as efficiently and as accurately as possible. However, improvements can be made in the communication between these departments in many Spanish hospitals. Methods: A panel of 17 neurologists and neuroradiologists from 8 Spanish hospitals held in-person and online meetings to draft a series of good practice guidelines for the coordinated management of MS. The drafting process included 4 phases: 1) establishing the scope of the guidelines and the methodology of the study; 2) literature review on good practices or recommendations on the use of MRI in MS; 3) discussion and consensus between experts; and 4) validation of the contents. Results: The expert panel agreed a total of 9 recommendations for improving coordination between neurology and neuroradiology departments. The recommendations revolve around 4 main pillars: 1) standardising the process for requesting and scheduling MRI studies and reports; 2) designing common protocols for MRI studies; 3) establishing multidisciplinary committees and coordination meetings; and 4) creating formal communication channels between both departments. Conclusions: These consensus recommendations are intended to optimise coordination between neurologists and neuroradiologists, with the ultimate goal of improving the diagnosis and follow-up of patients with MS.(AU)

Assessing the quality of data for drivers of disease emergence.

Drivers are factors that have the potential to directly or indirectly influence the likelihood of infectious diseases emerging or re-emerging. It is likely that an emerging infectious disease (EID) rarely occurs as the result of only one driver; rather, a network of sub-drivers (factors that can influence a driver) are likely to provide conditions that allow a pathogen to (re-)emerge and become established. Data on sub-drivers have therefore been used by modellers to identify hotspots where EIDs may next occur, or to estimate which sub-drivers have the greatest influence on the likelihood of their occurrence. To minimise error and bias when modelling how sub-drivers interact, and thus aid in predicting the likelihood of infectious disease emergence, researchers need good-quality data to describe these sub-drivers. This study assesses the quality of the available data on sub-drivers of West Nile virus against various criteria as a case study. The data were found to be of varying quality with regard to fulfilling the criteria. The characteristic with the lowest score was completeness, i.e. where sufficient data are available to fulfil all the requirements for the model. This is an important characteristic as an incomplete data set could lead to erroneous conclusions being drawn from modelling studies. Thus, the availability of good-quality data is essential to reduce uncertainty when estimating the likelihood of where EID outbreaks may occur and identifying the points on the risk pathway where preventive measures may be taken.

Les facteurs d'émergence sont des éléments ayant le potentiel direct ou indirect d'influencer la probabilité d'émergence ou de réémergence d'une maladie infectieuse. Il est probablement rare qu'une maladie infectieuse émergente apparaisse en raison d'un seul facteur ; c'est plutôt un faisceau de sous-facteurs (éléments pouvant avoir une influence sur un même facteur) qui contribue à ce que les conditions soient réunies pour qu'un agent pathogène puisse (ré)émerger et s'établir. Les concepteurs de modèles ont donc utilisé les données relatives aux sous-facteurs pour identifier les zones sensibles où les prochaines maladies infectieuses émergentes pourraient survenir, ou pour faire une estimation des sous-facteurs ayant la plus grande influence sur la probabilité de leur occurrence. Les chercheurs ont besoin de données de qualité pour décrire ces sous-facteurs, afin de minimiser le risque d'erreur et de biais lors de la modélisation de l'interaction entre les différents sous-facteurs, et de contribuer ainsi à mieux prédire la probabilité d'apparition d'une maladie infectieuse émergente. Les auteurs présentent une étude de cas qui a consisté à évaluer la qualité des données disponibles relatives aux sous-facteurs d'émergence du virus de la fièvre de West Nile au regard de différents critères. Il est apparu que la qualité des données était variable au regard des critères examinés. Le paramètre dont le score était le plus bas est celui de la complétude - le fait que suffisamment de données soient disponibles pour répondre à toutes les exigences du modèle. Il s'agit pourtant d'un paramètre important car des données incomplètes peuvent inciter à tirer des conclusions erronées des études de modélisation. La disponibilité de données de bonne qualité est essentielle pour réduire l'incertitude lors de l'estimation de la probabilité d'apparition de maladies infectieuses émergentes dans des zones déterminées, ainsi que pour identifier les points critiques de concrétisation du risque où des mesures préventives pourraient être mises en place.

Los inductores o factores de inducción [drivers] son aquellos que, directa o indirectamente, pueden influir en la probabilidad de que surjan o resurjan enfermedades infecciosas. Todo indica que rara vez una enfermedad infecciosa emergente aparece por efecto de un solo factor de inducción, sino que es probable que haya más bien una combinación de "subfactores de influencia" [sub-drivers] (factores que pueden influir en un inductor) que cree condiciones propicias para que un patógeno (re)surja y logre asentarse. Los creadores de modelos, por consiguiente, se han servido de datos sobre estos subfactores de influencia para localizar aquellas zonas donde con mayor probabilidad puedan aparecer próximamente enfermedades infecciosas emergentes o para determinar cuáles son los subfactores que más influyen en la probabilidad de que ello ocurra. Para reducir al mínimo los errores y sesgos al modelizar la interacción entre los subfactores y ayudar así a calcular la probabilidad de que surja una enfermedad infecciosa emergente, los investigadores necesitan datos de buena calidad para caracterizar estos subfactores. En el análisis expuesto por los autores se utilizó el virus del Nilo Occidental como ejemplo de estudio para evaluar, con arreglo a diversos criterios, la calidad de los datos existentes sobre los subfactores que inciden en la aparición de este virus. Lo que se constató, en relación con el grado de cumplimiento de los criterios, es que esos datos eran de calidad variable. La característica o parámetro que deparó la puntuación más baja fue la completud, es decir, la existencia de datos suficientes para aportar al modelo toda la información requerida para que este funcione bien. Se trata de una característica importante, pues un conjunto incompleto de datos podría llevar a extraer conclusiones erróneas de los estudios de modelización. Por ello, para reducir la incertidumbre a la hora de calcular la probabilidad de que en cierto lugar surjan brotes de enfermedades infecciosas emergentes y de determinar, dentro de la cadena de materialización del riesgo, aquellos eslabones en los que cabe adoptar medidas preventivas, es indispensable disponer de datos de buena calidad.

Recommendations for the coordination of Neurology and Neuroradiology Departments in the management of patients with multiple sclerosis.

INTRODUCTION: Magnetic resonance imaging (MRI) is widely used for the diagnosis and follow-up of patients with multiple sclerosis (MS). Coordination between neurology and neuroradiology departments is crucial for performing and interpreting radiological studies as efficiently and as accurately as possible. However, improvements can be made in the communication between these departments in many Spanish hospitals. METHODS: A panel of 17 neurologists and neuroradiologists from 8 Spanish hospitals held in-person and online meetings to draft a series of good practice guidelines for the coordinated management of MS. The drafting process included 4 phases: 1) establishing the scope of the guidelines and the methodology of the study; 2) literature review on good practices or recommendations on the use of MRI in MS; 3) discussion and consensus between experts; and 4) validation of the contents. RESULTS: The expert panel agreed a total of 9 recommendations for improving coordination between neurology and neuroradiology departments. The recommendations revolve around 4 main pillars: 1) standardising the process for requesting and scheduling MRI studies and reports; 2) designing common protocols for MRI studies; 3) establishing multidisciplinary committees and coordination meetings; and 4) creating formal communication channels between both departments. CONCLUSIONS: These consensus recommendations are intended to optimise coordination between neurologists and neuroradiologists, with the ultimate goal of improving the diagnosis and follow-up of patients with MS.

Recommendations for the coordination of Neurology and Neuroradiology Departments in the management of patients with multiple sclerosis. / Recomendaciones para la coordinación de los servicios de Neurología y Neurorradiología en la atención a pacientes con esclerosis múltiple.

INTRODUCTION: Magnetic resonance imaging (MRI) is widely used for the diagnosis and follow-up of patients with multiple sclerosis (MS). Coordination between Neurology and Neuroradiology departments is crucial for performing and interpreting radiological studies as efficiently and as accurately as possible. However, improvements can be made in the communication between these departments in many Spanish hospitals. METHODS: A panel of 17 neurologists and neuroradiologists from 8 Spanish hospitals held in-person and online meetings to draft a series of good practice guidelines for the coordinated management of MS. The drafting process included 4 phases: 1) establishing the scope of the guidelines and the methodology of the study; 2) literature review on good practices or recommendations on the use of MRI in MS; 3) discussion and consensus between experts; and 4) validation of the contents. RESULTS: The expert panel agreed a total of 9 recommendations for improving coordination between neurology and neuroradiology departments. The recommendations revolve around 4 main pillars: 1) standardising the process for requesting and scheduling MRI studies and reports; 2) designing common protocols for MRI studies; 3) establishing multidisciplinary committees and coordination meetings; and 4) creating formal communication channels between both departments. CONCLUSIONS: These consensus recommendations are intended to optimise coordination between neurologists and neuroradiologists, with the ultimate goal of improving the diagnosis and follow-up of patients with MS.

Brain and Lung Imaging Correlation in Patients with COVID-19: Could the Severity of Lung Disease Reflect the Prevalence of Acute Abnormalities on Neuroimaging? A Global Multicenter Observational Study.

PURPOSE: Our aim was to study the association between abnormal findings on chest and brain imaging in patients with coronavirus disease 2019 (COVID-19) and neurologic symptoms. MATERIALS AND METHODS: In this retrospective, international multicenter study, we reviewed the electronic medical records and imaging of hospitalized patients with COVID-19 from March 3, 2020, to June 25, 2020. Our inclusion criteria were patients diagnosed with Severe Acute Respiratory Syndrome coronavirus 2 (SARS-CoV-2) infection with acute neurologic manifestations and available chest CT and brain imaging. The 5 lobes of the lungs were individually scored on a scale of 0-5 (0 corresponded to no involvement and 5 corresponded to >75% involvement). A CT lung severity score was determined as the sum of lung involvement, ranging from 0 (no involvement) to 25 (maximum involvement). RESULTS: A total of 135 patients met the inclusion criteria with 132 brain CT, 36 brain MR imaging, 7 MRA of the head and neck, and 135 chest CT studies. Compared with 86 (64%) patients without acute abnormal findings on neuroimaging, 49 (36%) patients with these findings had a significantly higher mean CT lung severity score (9.9 versus 5.8, P < .001). These patients were more likely to present with ischemic stroke (40 [82%] versus 11 [13%], P < .0001) and were more likely to have either ground-glass opacities or consolidation (46 [94%] versus 73 [84%], P = .01) in the lungs. A threshold of the CT lung severity score of >8 was found to be 74% sensitive and 65% specific for acute abnormal findings on neuroimaging. The neuroimaging hallmarks of these patients were acute ischemic infarct (28%), intracranial hemorrhage (10%) including microhemorrhages (19%), and leukoencephalopathy with and/or without restricted diffusion (11%). The predominant CT chest findings were peripheral ground-glass opacities with or without consolidation. CONCLUSIONS: The CT lung disease severity score may be predictive of acute abnormalities on neuroimaging in patients with COVID-19 with neurologic manifestations. This can be used as a predictive tool in patient management to improve clinical outcome.

A Cross-Sectional Examination of Patterns of Sedentary Behavior and Cardiometabolic Risk in Community-Dwelling Adults Aged 55 Years and Older.

INTRODUCTION: Sedentary behavior (SB) is highly prevalent among older adults, with more than 25% engaging in 6 hours or more of SB daily. SB has been associated with several cardiometabolic biomarkers in younger adults; however, there is a paucity of research in older populations. This study examined associations between patterns of SB and cardiometabolic biomarkers in community-dwelling adults aged 55 years and older. METHODS: Data were drawn from a convenience sample of 54 community-dwelling individuals (12 males, 42 females; mean age = 72.6 ± 6.8 years, range = 56-89 years). Cardiometabolic biomarkers assessed included systolic (SBP) and diastolic blood pressure (DBP), body mass index, waist circumference, and fasting blood glucose and cholesterol parameters. SB was assessed via accelerometry over a 7-day period, and measures included daily time in SB, number and length of sedentary bouts, the number and length of breaks between sedentary bouts, moderate-to-vigorous physical activity (MVPA), and light physical activity (LPA). Associations between the SB measures and each cardiometabolic risk factor were examined using separate stepwise multiple regression models, controlling for sex, MVPA, and accelerometer wear time. Isotemporal substitution models were used to examine the change in cardiometabolic outcomes when SB is replaced by an equal duration of either LPA or MVPA. RESULTS: Adjusted regression analyses showed that daily sedentary time was positively associated with DBP (ß = 0.052, ∆R 2 = 0.112, p = 0.022) and inversely associated with HDL cholesterol (ß = -0.111, ∆R 2 = 0.121, p = 0.039). Sedentary bout length was also associated with DBP and HDL cholesterol (ß = 0.575, ∆R 2 = 0.152, p = 0.007; ß = -1.529, ∆R 2 = 0.196, p = 0.007, respectively). Replacement of 10 minutes of SB a day with LPA was associated with improved DBP and HDL cholesterol (p ≤ 0.05). No other significant associations (p ≤ 0.05) were found. CONCLUSION: Sitting for prolonged periods of time without interruption is unfavorably associated with DBP and HDL cholesterol. Prospective studies should identify causal relationships and observe specific changes in cardiometabolic profiles in older populations.

Quadriceps Impairment Is Associated with Gait Mechanics in Young Adults with Obesity.

PURPOSE: Obesity influences gait and muscle function, which may contribute to knee osteoarthritis. This study aimed 1) to compare gait biomechanics and quadriceps function between individuals with and without obesity and 2) to examine the association between quadriceps function and gait biomechanics. METHODS: Forty-eight individuals with and 48 without obesity participated and were matched on age and sex. Gait biomechanics at standardized and self-selected speeds were used to assess peak vertical ground reaction force (vGRF), vertical loading rate (vLR), internal knee extension moment (KEM), peak knee flexion angle (KFA), knee flexion excursion (KFE), and knee joint stiffness. Quadriceps function was assessed using peak isometric strength (peak torque), early (RTD100) and late (RTD200) rate of torque development (RTD), and vastus lateralis cross-sectional area (CSA) and echo intensity (EI). RESULTS: When normalized to fat-free mass, individuals with obesity had lower RTD100 (P = 0.04) and RTD200 (P = 0.02) but higher vastus lateralis CSA (P < 0.01) and EI (P < 0.01) compared with normal weight controls. The group-speed interaction was significant for normalized vGRF (P < 0.01), normalized vLR (P = 0.02), normalized KEM (P = 0.03), and normalized knee joint stiffness (P = 0.02). Post hoc analyses indicate a smaller normalized vGRF and normalized KEM, and lower knee joint stiffness in individuals with obesity compared with normal weight controls at self-selected speed. There were main effects of speed for all kinematic and kinetic variables, and body mass index group for all absolute kinetic variables as well as normalized vGRF (all P < 0.001). A lower vastus lateralis EI (P = 0.04) and greater RTD100 (P < 0.01) were associated with a larger KEM in individuals with obesity. CONCLUSION: Individuals with obesity have quadriceps dysfunction that is weakly associated with KEM during walking. Exercise interventions that improve quadriceps function may improve walking mechanics.

The relationship between metabolic syndrome, cytokines and physical activity in obese youth with and without Prader-Willi syndrome.

BACKGROUND: The objective of this study was to examine the associations between adiposity, metabolic syndrome (MetS), cytokines and moderate-to-vigorous physical activity (MVPA) in youth with Prader-Willi syndrome (PWS) and non-syndromic obesity (OB). METHODS: Twenty-one youth with PWS and 34 with OB aged 8-15 years participated. Measurements included body composition, blood pressure, fasting blood markers for glucose control, lipids and inflammation and MVPA. Group differences for adiposity, MetS, blood parameters and MVPA were determined using independent t-tests and chi-square (χ2) analyses. Bivariate correlations and analysis of variance (ANOVA) examined the associations between adiposity, MetS severity, cytokines and MVPA. RESULTS: PWS presented similar percentage of body fat (%), lower body mass index (BMI) z-scores, insulin resistance, triglycerides, MetS severity, C-reactive protein (CRP), tumor necrosis factor-α (TNF-α) and MVPA and higher high-density lipoprotein (HDL) and adiponectin (ADP) than OB. Fewer PWS presented MetS based on BMI z-score (61.9% vs. 91.2%) and glucose (14.3% vs. 44.1%) compared to OB. In all youth, MetS severity was significantly associated with body fat %, ADP, interleukin-6 (IL-6) and TNF-α and also with CRP in PWS, but associations became non-significant for CRP and IL-6 when controlling for body fat %. In PWS, those with low MVPA had significantly higher TNF-α than those with high MVPA (1.80±0.45 vs. 1.39±0.26 pg/mL). CONCLUSIONS: Although PWS presented better cardiometabolic profiles than OB and lower MetS risk, associations between body fat, MetS and cytokines were somewhat similar for both groups, with the exception of CRP. Results suggest a potential role for MVPA related to MetS and inflammation and extend associations shown in OB to PWS.

Cortisol advantage of neighbouring the opposite sex in utero.

Population sex ratios naturally fluctuate around equality. It is argued that the production of an equal number of male and female offspring by individual parents should be favoured by selection, if all costs and benefits are equal. Theoretically, an even sex ratio should yield the highest probability for a fetus to be adjacent to a fetus of the opposite sex in utero. This may cause developmental costs or benefits that have been overlooked. We examined the physiological and developmental parameters associated with in utero sex ratios in the nutria (Myocastor coypus), an invasive wildlife species with a strong reproductive output. Using hair testing, we found that litters with even sex ratios had the highest average cortisol levels. Fetuses neighbouring the opposite sex exhibited longer trunks than those neighbouring the same sex, which might imply better lung development. Our results are the first, to our knowledge, to link intra-utero sex ratios and fetal cortisol and suggest that fetal cortisol might be a mechanism by which even sex ratios are maintained via developmental advantages.

Comparing Class-Based and Home-Based Exercise for Older Adults With Chronic Health Conditions: 12-Month Follow-Up of a Randomized Clinical Trial.

OBJECTIVE: To assess the maintenance of physical activity (PA) and health gains among participants in a class-based (CB) or home-based (HB) PA intervention over a 12-month study period. METHODS: A total of 172 adults aged 50 years and older were randomly allocated to either a CB or an HB intervention, each involving an intensive 3-month phase with a 9-month follow-up period. Measures at baseline, 3, 6, and 12 months included self-reported PA and health, body mass index, waist circumference (WC), blood pressure, cardiovascular endurance (6-min walk test), physical function, and functional fitness (senior fitness test). Outcomes were analyzed using generalized estimating equations. RESULTS: Maximum improvement was typically observed at 3 or 6 months followed by a modest diminution, with no differences between groups. For body mass index, waist circumference, 6-min walk test, and senior fitness test, there was progressive improvement through the study period. Greater improvement was seen in the CB group compared with the HB group on three items on the senior fitness test (lower body strength and endurance [29% vs. 21%, p < .01], lower body flexibility [2.8 cm vs. 0.4 cm, p < .05], and dynamic agility [14% vs. 7%, p < .05]). CONCLUSION: The interventions were largely comparable; thus, availability, preferences, and cost may better guide program choice.

Predictors of Physical Activity Levels in Community-Dwelling Older Adults: A Multivariate Approach Based on a Socio-Ecological Framework.

The purpose of this study was to explore cross-sectional relationships between self-reported physical activity (PA) and personal, social, and environmental factors in community-dwelling adults aged 50 years and older. Accounting for clustering by neighborhood, generalized estimating equations were used to examine associations between selected correlates and the Physical Activity Scale for the Elderly (PASE) score while adjusting for confounders. Data for 601 participants were analyzed: 79% female, 37% married, mean age 76.8 (± 8.7) years, mean PASE score 112.6 (± 64.8). Age, living in seniors' housing, using nursing/home care services, receiving encouragement to be active, and having benches available in the neighborhood were inversely associated with PASE. Self-efficacy, SF-12 score, PA barriers, social support, and the presence of trails showed positive associations. Several personal, social, and environmental factors associated with PA were identified. The inverse association between PA and living in seniors' housing units should be considered when developing PA programs for older adults.

Leakage decrease detected by dynamic susceptibility-weighted contrast-enhanced perfusion MRI predicts survival in recurrent glioblastoma treated with bevacizumab

Background and purpose. In glioblastoma, tumor progression appears to be triggered by expression of VEGF, a regulator of blood vessel permeability. Bevacizumab is a monoclonal antibody that inhibits angiogenesis by clearing circulating VEGF, resulting in a decline in the contrast-enhancing tumor, which does not always correlate with treatment response. Our objectives were: (1) to evaluate whether changes in DSC perfusion MRI-derived leakage could predict survival in recurrent glioblastoma, and (2) to estimate whether leakage at baseline was related to treatment outcome. Materials and methods. We retrospectively analyzed DSC perfusion MRI in 24 recurrent glioblastomas treated with bevacizumab as second line chemotherapy. Leakage at baseline and changes in maximum leakage between baseline and the first follow-up after treatment were selected for quantitative analysis. Survival univariate analysis was made constructing survival curves using Kaplan-Meier method and comparing subgroups by log rank probability test. Results. Leakage reduction at 8 weeks after initiation of bevacizumab treatment had a significant influence on overall survival (OS) and progression-free survival (PFS). Median OS and PFS were 2.4 and 2.8 months longer for patients with leakage reduction at the first follow-up. Higher leakage at baseline was associated with leakage reduction after treatment. Odds ratio of treatment response was 9 for patients with maximum leakage at baseline >5. Conclusions. Leakage decrease may predict OS and PFS in recurrent glioblastomas treated with bevacizumab. Leakage reduction postulates as a potential biomarker for treatment response evaluation. Leakage at baseline seems to predict response to treatment, but was not independently associated with survival (AU)

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Leakage decrease detected by dynamic susceptibility-weighted contrast-enhanced perfusion MRI predicts survival in recurrent glioblastoma treated with bevacizumab.

BACKGROUND AND PURPOSE: In glioblastoma, tumor progression appears to be triggered by expression of VEGF, a regulator of blood vessel permeability. Bevacizumab is a monoclonal antibody that inhibits angiogenesis by clearing circulating VEGF, resulting in a decline in the contrast-enhancing tumor, which does not always correlate with treatment response. Our objectives were: (1) to evaluate whether changes in DSC perfusion MRI-derived leakage could predict survival in recurrent glioblastoma, and (2) to estimate whether leakage at baseline was related to treatment outcome. MATERIALS AND METHODS: We retrospectively analyzed DSC perfusion MRI in 24 recurrent glioblastomas treated with bevacizumab as second line chemotherapy. Leakage at baseline and changes in maximum leakage between baseline and the first follow-up after treatment were selected for quantitative analysis. Survival univariate analysis was made constructing survival curves using Kaplan-Meier method and comparing subgroups by log rank probability test. RESULTS: Leakage reduction at 8 weeks after initiation of bevacizumab treatment had a significant influence on overall survival (OS) and progression-free survival (PFS). Median OS and PFS were 2.4 and 2.8 months longer for patients with leakage reduction at the first follow-up. Higher leakage at baseline was associated with leakage reduction after treatment. Odds ratio of treatment response was 9 for patients with maximum leakage at baseline >5. CONCLUSIONS: Leakage decrease may predict OS and PFS in recurrent glioblastomas treated with bevacizumab. Leakage reduction postulates as a potential biomarker for treatment response evaluation. Leakage at baseline seems to predict response to treatment, but was not independently associated with survival.

The cardiac maladaptive ATF3-dependent cross-talk between cardiomyocytes and macrophages is mediated by the IFNγ-CXCL10-CXCR3 axis.

RATIONAL: Pressure overload induces adaptive and maladaptive cardiac remodeling processes in the heart. Part of the maladaptive process is the cross-talk between cardiomyocytes and macrophages which is dependent on the function of the Activating Transcription Factor 3, ATF3. Yet, the molecular mechanism involved in cardiomyocytes-macrophages communication leading to macrophages recruitment to the heart and cardiac maladaptive remodeling is currently unknown. METHODS AND RESULTS: Isolated peritoneal macrophages from either wild type or ATF3-KO mice were cultured in serum free medium to collect conditioned medium (CM). CM was used to probe an antibody cytokine/chemokine array. The interferon γ induced protein 10kDa, CXCL10, was found to be enriched in wild type macrophages CM. Wild type cardiomyocytes treated with CXCL10 in vitro, resulted in significant increase in cell volume as compared to ATF3-KO cardiomyocytes. In vivo, pressure overload was induced by phenylephrine (PE) infusion using micro-osmotic pumps. Consistently, CXCL11 (CXCL10 competitive agonist) and CXCL10 receptor antagonist (AMG487) attenuated PE-dependent maladaptive cardiac remodeling. Significantly, we show that the expression of the CXCL10 receptor, CXCR3, is suppressed in cardiomyocytes and macrophages derived from ATF3-KO mice. CXCR3 is positively regulated by ATF3 through an ATF3 transcription response element found in its proximal promoter. Finally, mice lacking CXCR3 display a significant reduction of cardiac remodeling processes following PE infusion. CONCLUSIONS: Chronic PE infusion results in a unique cardiomyocytes-macrophages cross-talk that is mediated by IFNγ. Subsequently, macrophages that are recruited to the heart secrete CXCL10 resulting in maladaptive cardiac remodeling mediated by the CXCR3 receptor. ATF3-KO mice escape from PE-dependent maladaptive cardiac remodeling by suppressing the IFNγ-CXCL10-CXCR3 axis at multiple levels.

Is Self-Reported Physical Activity Participation Associated with Lower Health Services Utilization among Older Adults? Cross-Sectional Evidence from the Canadian Community Health Survey.

Purpose. To examine relationships between leisure time physical activity (LTPA) and health services utilization (H) in a nationally representative sample of community-dwelling older adults. Methods. Cross-sectional data from 56,652 Canadian Community Health Survey respondents aged ≥ 50 years (48% M; 52% F; mean age 63.5 ± 10.2 years) were stratified into three age groups and analysed using multivariate generalized linear modeling techniques. Participants were classified according to PA level based on self-reported daily energy expenditure. Nonleisure PA (NLPA) was categorized into four levels ranging from mostly sitting to mostly lifting objects. Results. Active 50-65-year-old individuals were 27% less likely to report any GP consultations (ORadj = 0.73; P < 0.001) and had 8% fewer GP consultations annually (IRRadj = 0.92; P < 0.01) than their inactive peers. Active persons aged 65-79 years were 18% less likely than inactive respondents to have been hospitalized overnight in the previous year (ORadj = 0.82, P < 0.05). Higher levels of NLPA were significantly associated with lower levels of HSU, across all age groups. Conclusion. Nonleisure PA appeared to be a stronger predictor of all types of HSU, particularly in the two oldest age groups. Considering strategies that focus on reducing time spent in sedentary activities may have a positive impact on reducing the demand for health services.

ATF3-dependent cross-talk between cardiomyocytes and macrophages promotes cardiac maladaptive remodeling.

RATIONALE: Pressure overload induces adaptive remodeling processes in the heart. However, when pressure overload persists, adaptive changes turn into maladaptive alterations leading to cardiac hypertrophy and heart failure. ATF3 is a stress inducible transcription factor that is transiently expressed following neuroendocrine stimulation. However, its role in chronic pressure overload dependent cardiac hypertrophy is currently unknown. OBJECTIVE: The objective of the study was to study the role of ATF3 in chronic pressure overload dependent cardiac remodeling processes. METHODS AND RESULTS: Pressure overload was induced by phenylephrine (PE) mini-osmotic pumps in various mice models of whole body, cardiac specific, bone marrow (BM) specific and macrophage specific ATF3 ablations. We show that ATF3-KO mice exhibit a significantly reduced expression of cardiac remodeling markers following chronic pressure overload. Consistently, the lack of ATF3 specifically in either cardiomyocytes or BM derived cells blunts the hypertrophic response to PE infusion. A unique cross-talk between cardiomyocytes and macrophages was identified. Cardiomyocytes induce an ATF3 dependent induction of an inflammatory response leading to macrophage recruitment to the heart. Adoptive transfer of wild type macrophages, but not ATF3-KO derived macrophages, into wild type mice potentiates maladaptive response to PE infusion. CONCLUSIONS: Collectively, this study places ATF3 as a key regulator in promoting pressure overload induced cardiac hypertrophy through a cross-talk between cardiomyocytes and macrophages. Inhibiting this cross-talk may serve as a useful approach to blunt maladaptive remodeling processes in the heart.

Gender, age and ethnicity influence on pain levels and analgesic use in the acute whiplash injury.

PURPOSE: Initial pain level in the acute whiplash injury is the most consistent predictor of transformation to a chronic pain syndrome. The risk factors for those early pain levels were, to our knowledge, scarcely evaluate to this date. We set to evaluate whether gender, age or ethnicity comprise a risk factor for those initial pain levels. Further, gender, age and ethnicity have been shown to be bias factors in pain management. We investigated if gender, age or ethnicity are bias factor in pain management in the face of a standardized pain treatment protocol in the acute whiplash injury. METHODS: We reviewed 2,538 patients with acute whiplash injury that were treated at our emergency department (ED). Gender, age and ethnicity were investigated as risk factors for elevated visual analog scale (VAS) scores. Those factors were also investigated as bias in pain medication administration in the face of a standardized analgesic protocol. RESULTS: Women had significantly higher VAS scores (p = 0.009). Age and ethnicity did not influence pain levels. There was no influence of gender or age on pain medication administration. The Jewish patients (the majority in Israel) were administered fewer pain medication (p < 0.0001). CONCLUSION: Women have higher initial pain levels in the acute whiplash injury. Age and ethnicity have less impact on those pain levels. A pain management protocol might reduce bias in pain management in the acute whiplash injury in the ED. The Jewish population tends to be less receptive to pain medication administration.