Physical Fitness, White Matter Volume and Academic Performance in Children: Findings From the ActiveBrains and FITKids2 Projects

The aims of this study were (i) to examine the association between cardiorespiratory fitness and white matter volume and test whether those associations differ between normal-weight and overweight/obese children (ii) to analyze the association between other physical fitness components (i.e., motor and muscular) and white matter volume, and (iii) to examine whether the fitness-related associations in white matter volume were related to academic performance. Data came from two independent projects: ActiveBrains project (n = 100; 10.0 1.1 years; 100% overweight/obese; Spain) and FITKids2 project (n = 242; 8.6 0.5 years; 36% overweight/obese, United States). Cardiorespiratory fitness was assessed in both projects, and motor and muscular fitness were assessed in the ActiveBrains project. T1-weighted images were acquired with a 3.0 T S Magnetom Tim Trio system. Academic performance was assessed by standardized tests. Cardiorespiratory fitness may positively relate to white matter volume in overweight/obese children, and in turn, academic performance. In addition, motor and muscular fitness may also influence white matter volume coupled with better academic performance. From a public health perspective, implementing exercise interventions that combine aerobic, motor and muscular training to enhance physical fitness may benefit brain development and academic successThe ActiveBrains study was supported by the Spanish Ministry of Economy and Competitiveness (DEP2013-47540, DEP2016- 79512-R, and PSI2012-3929). The FITKids2 study was supported by a grant from the National Institutes of Health (HD069381)

Deletion patterns, genetic variability and protein structure of pfhrp2 and pfhrp3: implications for malaria rapid diagnostic test in Amhara region, Ethiopia

Background: Although rapid diagnostic tests (RDTs) play a key role in malaria-control strategies, their efficacy has been threatened by deletion and genetic variability of the genes pfhrp2/3. This study aims to characterize the deletion, genetic patterns and diversity of these genes and their implication for malaria RDT effectiveness, as well as their genetic evolution in the Amhara region of Ethiopia. Methods: The study included 354 isolates from symptomatic patients from the Amhara region of Ethiopia who tested positive by microscopy. Exon 1-2 and exon 2 of genes pfhrp2 and -3 were amplified, and exon 2 was sequenced to analyse the genetic diversity, phylogenetic relationship and epitope availability. Results: The deletion frequency in exon 1-2 and exon 2 was 22 and 4.6% for pfhrp2, and 68 and 18% for pfhrp3, respectively. Double deletion frequency for pfhrp2 and pfhrp3 was 1.4%. High genetic diversity, lack of clustering by phylogenetic analysis and evidence of positive selection suggested a diversifying selection for both genes. The amino-acid sequences, classified into different haplotypes, varied widely in terms of frequency of repeats, with novel amino-acid changes. Aminoacidic repetition type 2 and type 7 were the most frequent in all the sequences. The most frequent epitopes among protein sequences were those recognized by MAbs 3A4 and C1-13. Conclusion: Deletions and high amino acidic variation in pfhrp2 and pfhrp3 suggest their possible impact on RDT use in the Amhara region, and the high genetic diversity of these genes could be associated with a diversifying selection in Ethiopia. Surveillance of these genes is, therefore, essential to ensure the effectiveness of public health interventions in this region.This work was supported by the project TRPY 111/18 funded by the Institute of Health Carlos III; and IMF received a research fellowship from the University of Alcalá that enables her to develop this study.S

The effects of physical activity on white matter microstructure in children with overweight or obesity: The ActiveBrains randomized clinical trial

Background: Emerging research supports the idea that physical activity benefits brain development. However, the body of evidence focused on understanding the effects of physical activity on white matter microstructure during childhood is still in its infancy, and further well-designed randomized clinical trials are needed. Aim: This study aimed: (i) to investigate the effects of a 20-week physical activity intervention on global white matter microstructure in children with overweight or obesity, and (ii) to explore whether the effect of physical activity on white matter microstructure is global or restricted to a particular set of white matter bundles. Methods: In total, 109 children aged 8 to 11 years with overweight or obesity were randomized and allocated to either the physical activity program or the control group. Data were collected from November 2014 to June 2016, with diffusion tensor imaging (DTI) data processing and analyses conducted between June 2017 and November 2021. Images were pre-processed using the Functional Magnetic Resonance Imaging (MRI) of the Brain´s Software Library (FSL) and white matter properties were explored by probabilistic fiber tractography and tract-based spatial statistics (TBSS). Results: Intention-to-treat analyses were performed for all children who completed the pre-test and post-test DTI assessment, with good quality DTI data (N = 89). Of them, 83 children (10.06±1.11 years, 39 % girls, intervention group=44) met the per-protocol criteria (attended at least 70 % of the recommended sessions). Our probabilistic fiber tractography analysis did not show any effects in terms of global and tract-specific fractional anisotropy (FA) and mean diffusivity (MD) in the per-protocol or intention-to-treat analyses. Additionally, we did not observe any effects on the voxel-wise DTI parameters (i.e., FA and MD) using the most restricted TBSS approach (i.e., per protocol analyses and p-corrected image with a statistical threshold of p < 0.05). In the intention-to-treat analysis, we found that our physical activity program had a borderline effect (p-corrected image with a statistical threshold of p < 0.1) on 7 different clusters, including a cluster in the corpus callosum. Conclusion: We conclude that a 20-week physical activity intervention was not enough to induce changes in global and tract-specific white matter during childhood. The effects of physical activity on white matter microstructure could be restricted to local changes in several white matter tracts (e.g., the body of the corpus callosum). However, our results were not significant, and more interventions are needed to determine whether and how physical activity affects white matter microstructure during childhood.Spanish Ministry of Economy and Competitiveness and the Assessment and Promotion and the European Regional Development Fund (ERDF)” (DEP2013-47540, DEP2016- 79512-R, and DEP2017-91544-EXP)European Commission (No 667302)Alicia Koplowitz FoundationUniversity of Granada, Plan Propio de Investigación 2016, Excellence actions: Units of ExcellenceUnit of Excellence on Exercise and Health (UCEES)Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades and European Regional Development Fund (ERDF), ref. SOMM17/6107/ UGRSAMID III network, RETICS, funded by the PN I+D+I 2017-2021 (Spain)Spanish Ministry of Economy and Competitiveness (RTI2018-095284- 564J-100)Spanish Ministry of Science and Innovation (RYC2019-027287-I)Grant from ANID/BECAS Chile/72180543Margarita Salas grant from the Spanish Ministry UniversitiesSpanish Ministry of Science, Innovation and Universities (FJCI-2017-33396)Spanish Ministry of Science and Innovation (IJC2019-041916-I

Histiocytoid Sweet Syndrome associated with anorectal lymphogranuloma venereum in a patient with HIV infection

Sweet Syndrome belongs to a group of diseases known as neutrophilic dermatoses. An uncommon variant named Histiocytoid Sweet Syndrome (HSS) can be associated with a variety of conditions, including cancer, infections, drug toxicity and others. Here we present an instance of HSS in an HIV-positive patient in an infectious disease settin

Active Gains in brain Using Exercise During Aging (AGUEDA): protocol for a randomized controlled trial

Alzheimer’s disease is currently the leading cause of dementia and one of the most expensive, lethal and severe diseases worldwide. Age-related decline in executive function is widespread and plays a key role in subsequent dementia risk. Physical exercise has been proposed as one of the leading non-pharmaceutical approaches to improve executive function and ameliorate cognitive decline. This single-site, two-arm, single-blinded, randomized controlled trial (RCT) will include 90 cognitively normal older adults, aged 65–80 years old. Participants will be randomized to a 24-week resistance exercise program (3 sessions/week, 60 min/session, n = 45), or a wait-list control group (n = 45) which will be asked to maintain their usual lifestyle. All study outcomes will be assessed at baseline and at 24-weeks after the exercise program, with a subset of selected outcomes assessed at 12-weeks. The primary outcome will be indicated by the change in an executive function composite score assessed with a comprehensive neuropsychological battery and the National Institutes of Health Toolbox Cognition Battery. Secondary outcomes will include changes in brain structure and function and amyloid deposition, other cognitive outcomes, and changes in molecular biomarkers assessed in blood, saliva, and fecal samples, physical function, muscular strength, body composition, mental health, and psychosocial parameters. We expect that the resistance exercise program will have positive effects on executive function and related brain structure and function, and will help to understand the molecular, structural, functional, and psychosocial mechanisms involvedRTI2018-095284-J-100 funded by MCIN/AEI/10.13039/501100011033/ and “ERDF A way of making Europe”RYC2019-027287-I funded by MCIN/AEI/10.13039/501100011033/ and “ESF Investing in your future”“Margarita Salas” grant from the Spanish Ministry Universities. Plan Andaluz de Investigación (PAIDI) (Convocatoria 2020, Ref: P20_00124) 2021–2022.Ministerio de Economía y Competitividad–Proyectos I + D + I RETOS (Convocatoria 2020, Ref: PID2020-120249RB-I00).EXERNET Research Network on Exercise and Health (DEP2005- 00046/ACTI; 09/UPB/19; 45/UPB/20; 27/UPB/21).University of Granada “Proyectos de investigación precompetitivos para jóvenes investigadores” (Convocatoria 2021, Ref: PPJIA2021-39)

Effects of an Exercise Program on Brain Health Outcomes for Children With Overweight or Obesity. The ActiveBrains Randomized Clinical Trial

IMPORTANCE Pediatric overweight and obesity are highly prevalent across the world, with implications for poorer cognitive and brain health. Exercise might potentially attenuate these adverse consequences. OBJECTIVES To investigate the effects of an exercise program on brain health indicators, including intelligence, executive function, academic performance, and brain outcomes, among children with overweight or obesity and to explore potential mediators and moderators of the main effects of exercise. DESIGN, SETTING, AND PARTICIPANTS All preexercise and postexercise data for this 20-week randomized clinical trial of 109 children aged 8 to 11 years with overweight or obesity were collected from November 21, 2014, to June 30, 2016, with neuroimaging data processing and analyses conducted between June 1, 2017, and December 20, 2021. All 109 children were included in the intention-to-treat analyses; 90 children (82.6%) completed the postexercise evaluation and attended 70%or more of the recommended exercise sessions and were included in per-protocol analyses. INTERVENTIONS All participants received lifestyle recommendations. The control group continued their usual routines, whereas the exercise group attended a minimum of 3 supervised 90-minute sessions per week in an out-of-school setting. MAIN OUTCOMES AND MEASURES Intelligence, executive function (cognitive flexibility, inhibition, andworking memory), and academic performancewere assessed with standardized tests, and hippocampal volume was measured with magnetic resonance imaging. RESULTS The 109 participants included 45 girls (41.3%); participants had a mean (SD) body mass index of 26.8 (3.6) and a mean (SD) age of 10.0 (1.1) years at baseline. In per-protocol analyses, the exercise intervention improved crystallized intelligence, with the exercise group improving from before exercise to after exercise (mean z score, 0.62 [95%CI, 0.44-0.80]) compared with the control group (mean z score, –0.10 [95%CI, –0.28 to 0.09]; difference between groups, 0.72 SDs [95%CI, 0.46-0.97]; P < .001). Total intelligence also improved significantly more in the exercise group (mean z score, 0.69 [95%CI, 0.48-0.89]) than in the control group (mean z score, 0.07 [95% CI, –0.14 to 0.28]; difference between groups, 0.62 SDs [95%CI, 0.31-0.91]; P < .001). Exercise also positively affected a composite score of cognitive flexibility (mean z score: exercise group, 0.25 [95% CI, 0.05-0.44]; control group, –0.17 [95%CI, –0.39 to 0.04]; difference between groups, 0.42 SDs [95%CI, 0.13-0.71]; P = .005). These main effects were consistent in intention-to-treat analyses and after multiple-testing correction. There was a positive, small-magnitude effect of exercise on total academic performance (mean z score: exercise group, 0.31 [95%CI, 0.18-0.44]; control group, 0.10 [95%CI, –0.04 to 0.24]; difference between groups, 0.21 SDs [95%CI, 0.01-0.40]; P = .03), which was partially mediated by cognitive flexibility. Inhibition, working memory, hippocampal volume, and other brain magnetic resonance imaging outcomes studied were not affected by the exercise program. The intervention increased cardiorespiratory fitness performance as indicated by longer treadmill time to exhaustion (mean z score: exercise group, 0.54 [95%CI, 0.27-0.82]; control group, 0.13 [95%CI, –0.16 to 0.41]; difference between groups, 0.42 SDs [95%CI, 0.01-0.82]; P = .04), and these changes in fitness mediated some of the effects (small percentage of mediation [approximately 10%-20%]). The effects of exercise were overall consistent across the moderators tested, except for larger improvements in intelligence among boys compared with girls. CONCLUSIONS AND RELEVANCE In this randomized clinical trial, exercise positively affected intelligence and cognitive flexibility during development among children with overweight or obesity. However, the structural and functional brain changes responsible for these improvementswere not identified.Spanish Government DEP2013-47540 DEP2016-79512-R DEP2017-91544-EXPEuropean Commission European Commission European Commission Joint Research Centre 667302Alicia Koplowitz FoundationERDF (FEDER in Spanish) B-CTS-355-UGR18University of Granada, Plan Propio de Investigacion, Visiting Scholar grantsJunta de AndaluciaUnit of Excellence on Exercise, Nutrition and Health (UCEENS)European Commission SOMM17/6107/UGREXERNET Research Network on Exercise and Health DEP2005-00046/ACTIHigh Council of Sports 09/UPB/19Spanish Government FPU 14/06837 FPI-BES-2014-068829 FJC2018-037925-I FJCI-2014-19563 IJCI-2017-33642 RYC2019-027287-I FPU15/02645 FJCI-2017-33396 IJC2019-041916-IJunta de AndaluciaNational Agency for Research and Development (ANID)/BECAS Chile 72180543Ramon Areces Foundatio

El papel mediador de la disregulación emocional en la adherencia al tratamiento en adolescentes con diabetes mellitus tipo 1.

ntroducción: La Diabetes Mellitus tipo 1 (DM1) es una enfermedad crónica que requiere de un estrecho seguimiento y control terapéutico para la prevención de complicaciones. Un peor funcionamiento ejecutivo contribuye a un peor cumplimiento terapéutico y a un peor manejo de la diabetes. El fenotipo de disregulación emocional se ha señalado como un indicador de autorregulación deficiente, psicopatología general, gravedad de los síntomas, exposición a la adversidad psicosocial y deterioro funcional. Se desconoce el papel de la disregulación emocional en la adherencia al tratamiento de la DM1. Hipótesis y objetivos: El objetivo del presente estudio es determinar el papel de l fenotipo de disregulación emocional en la adherencia al tratamiento de la DM1. Se hipotetiza que el fenotipo de disregulación emocional mediará la relación entre las funciones ejecutivas y la adherencia al tratamiento de la DM1. Población y método: Se reclutaron 55 pacientes entre 10 y 18 años con un diagnóstico de DM1 de al menos 3 años de evolución atendidos en el Servicio de endocrinología infantil de los Hospitales Universitarios Gregorio Marañón y Fundación Jiménez Díaz. Se evaluó la adherencia al tratamiento a la DM1 con la escala de vida relacionada con la DM1 (PedsQL- heteroinformada), las funciones ejecutivas con un cuestionario heteroaplicado (BRIEF-2) y la disregulación emocional con la subescala del Cuestionario de Capacidades y Dificultades (SDQ-Dysregulation Profile). Se desarrollaron modelos de mediación para evaluar el papel de la disregulación emocional como variable de mediación en la relación entre las funciones ejecutivas y la adherencia al tratamiento de la DM1. Los modelos de mediación se analizaron mediante métodos de muestreo Bootstrap. Resultados: Se halló una correlación estadísticamente significativa entre la variable Independiente (BRIEF-2) y el mediador propuesto (SDQ-DP). Los resultados apoyan el modelo de mediación total de la disregulación emocional en la relación entre las funciones ejecutivas y la adherencia al tratamiento de la DM1. El efecto indirecto mediante bootstrapping apoya el modelo de mediación ya que el efecto indirecto es significativamente diferente de cero en p<.05 (0.098). Discusión: Este estudio es pionero en presentar la disregulación emocional como un potencial factor de riesgo en la adherencia al tratamiento de la DM1. El fenotipo de disregulación emocional medido por el SDQ-DP parece mediar de forma completa la asociación establecida entre alteraciones en la función ejecutiva y la adherencia al tratamiento en la DM1 Conclusiones: El objetivo principal del tratamiento en la DM1 es proporcionar al paciente las herramientas necesarias para lograr el mejor control de su enfermedad a fin de evitar, retardar o detener las complicaciones agudas y a largo plazo. El perfil de disregulación emocional podría ser un factor de riesgo en la adherencia al tratamiento de la DM1. Se requieren más estudios y diseños prospectivos para confirmar el papel mediador de la disregulación emocional de las funciones ejecutivas y la adherencia al tratamiento en la DM1. Bibliografía: Hilliard ME, Harris MA, Weissberg-Benchell J. Diabetes resilience: a model of risk and protection in type 1 diabetes. Curr Diab Rep. 2012 Dec;12(6):739-48. Sildorf SM, Breinegaard N, Lindkvist EB, Tolstrup JS, Boisen KA, Teilmann GK, Skovgaard AM, Svensson J. Poor Metabolic Control in Children and Adolescents With Type 1 Diabetes and Psychiatric Comorbidity. Diabetes Care. 2018 Nov;41(11):2289-2296 Carballo JJ, Serrano-Drozdowskyj E, García Nieto R, Díaz de Neira-Hernando M, Pérez-Fominaya M, Molina-Pizarro CA, De León-Martínez V, Baca-García E. Prevalence and correlates of psychopathology in children and adolescents evaluated with the strengths and difficulties questionnaire dysregulation profile in a clinical setting. Psychopathology. 2014;47(5):303-11.2022-2

Comparative study of senescent Th biomarkers in healthy donors and early arthritis patients. Analysis of VPAC receptors and their influence

Pro-inflammatory CD4+CD28− T cells are characteristic of immunosenescence, but also of several autoimmune/inflammatory diseases. Vasoactive intestinal peptide (VIP) acts as an anti-inflammatory and immunomodulatory mediator on these cells. Our objective was to study the mutual influence between senescent Th cells and VIP axis in early arthritis (EA), comparing with non-EA donors. We characterized the correlation between senescent Th cells and clinic parameters of EA as well as the behavior of senescent Th biomarkers by real-time PCR. Clinical data were systematically recorded at baseline and after 6 months of follow-up. The number of CD4+CD28− T cells measured by sorting is higher in patients who initially meet ACR classification criteria for rheumatoid arthritis (RA) compared to those who were classified as undifferentiated arthritis (UA). A slight positive correlation between EA CD4+CD28− T cells and CRP or ESR and a negative correlation with bone mineral density were found. Th senescent biomarkers in EA CD4+CD28− T cells were similar to donors, however some of them increased after 6 months of follow-up. VPAC receptors were analyzed by real-time PCR and immunofluorescence, and CD4+CD28− T cells showed higher expression of VPAC2 and lower of VPAC1, VPAC2 showing a significant increased expression in EA cells. Sorted CD4+CD28− T cells were in vitro expanded in presence of VIP, wherein VIP increased senescent biomarker CD27, while it diminished CD57 or NKG2 senescent biomarkers. Our study demonstrates for the first time the existence of a link between senescent Th cells and the VIP axis

The Neuropeptide VIP Limits Human Osteoclastogenesis: Clinical Associations with Bone Metabolism Markers in Patients with Early Arthritis

We aimed to evaluate the direct action of VIP on crucial molecules involved in human osteoclast differentiation and function. We also investigated the relationship between VIP serum levels and bone remodeling mediators in early arthritis patients. The expression of VIP receptors and osteoclast gene markers in monocytes and in vitro differentiated osteoclasts was studied by real-time PCR. NFATc1 activity was measured using a TransAM® kit. Osteoclastogenesis was confirmed by quantification of tartrate-resistant acid phosphatase positive multinucleated cells. OsteoAssay® Surface Multiple Well Plate was used to evaluate bone-resorbing activity. The ring-shaped actin cytoskeleton and the VPAC1 and VPAC2 expression were analyzed by immunofluorescence. We described the presence of VIP receptors in monocytes and mature osteoclasts. Osteoclasts that formed in the presence of VIP showed a decreased expression of osteoclast differentiation gene markers and proteolytic enzymes involved in bone resorption. VIP reduced the resorption activity and decreased both β3 integrin expression and actin ring formation. Elevated serum VIP levels in early arthritis patients were associated with lower BMD loss and higher serum OPG concentration. These results demonstrate that VIP exerts an anti-osteoclastogenic action impairing both differentiation and resorption activity mainly through the negative regulation of NFATc1, evidencing its bone-protective effects in humans