Cardiorespiratory fitness is a strong and consistent predictor of morbidity and mortality among adults: an overview of meta-analyses representing over 20.9 million observations from 199 unique cohort studies.

OBJECTIVE: To examine and summarise evidence from meta-analyses of cohort studies that evaluated the predictive associations between baseline cardiorespiratory fitness (CRF) and health outcomes among adults. DESIGN: Overview of systematic reviews. DATA SOURCE: Five bibliographic databases were searched from January 2002 to March 2024. RESULTS: From the 9062 papers identified, we included 26 systematic reviews. We found eight meta-analyses that described five unique mortality outcomes among general populations. CRF had the largest risk reduction for all-cause mortality when comparing high versus low CRF (HR=0.47; 95% CI 0.39 to 0.56). A dose-response relationship for every 1-metabolic equivalent of task (MET) higher level of CRF was associated with a 11%-17% reduction in all-cause mortality (HR=0.89; 95% CI 0.86 to 0.92, and HR=0.83; 95% CI 0.78 to 0.88). For incident outcomes, nine meta-analyses described 12 unique outcomes. CRF was associated with the largest risk reduction in incident heart failure when comparing high versus low CRF (HR=0.31; 95% CI 0.19 to 0.49). A dose-response relationship for every 1-MET higher level of CRF was associated with a 18% reduction in heart failure (HR=0.82; 95% CI 0.79 to 0.84). Among those living with chronic conditions, nine meta-analyses described four unique outcomes in nine patient groups. CRF was associated with the largest risk reduction for cardiovascular mortality among those living with cardiovascular disease when comparing high versus low CRF (HR=0.27; 95% CI 0.16 to 0.48). The certainty of the evidence across all studies ranged from very low-to-moderate according to Grading of Recommendations, Assessment, Development and Evaluations. CONCLUSION: We found consistent evidence that high CRF is strongly associated with lower risk for a variety of mortality and incident chronic conditions in general and clinical populations.

Sleep Behaviors and the Shape of Subcortical Brain Structures in Children with Overweight/Obesity: A Cross-Sectional Study.

OBJECTIVES: To examine the relationship between sleep and subcortical brain structures using a shape analysis approach. METHODS: A total of 98 children with overweight/obesity (10.0 ± 1.1 y, 59 boys) were included in the cross-sectional analyses. Sleep behaviors (i.e., wake time, sleep onset time, total time in bed, total sleep time, sleep efficiency, and wakening after sleep onset) were estimated with wrist-worn accelerometers. The shape of the subcortical brain structures was acquired by magnetic resonance imaging. A partial correlation permutation approach was used to examine the relationship between sleep behaviors and brain shapes. RESULTS: Among all the sleep variables studied, only total time in bed was significantly related to pallidum and putamen structure, such that those children who spent more time in bed had greater expansions in the right and left pallidum (211-751 voxels, all p's <0.04) and right putamen (1783 voxels, p = 0.03). CONCLUSIONS: These findings suggest that more time in bed was related to expansions on two subcortical brain regions in children with overweight/obesity.

Mental Health Collaborative Care in Brazil and the Economy of Attention: Disclosing Barriers and Therapeutic Negotiations.

The introduction of mental health collaborative care (MHCC) is one of the strategies to scale up access to mental health care in primary health care in Brazil. This article investigates an experience of mental health collaborative care in the city of Rio de Janeiro, Brazil. It is a qualitative study involving interviews with physicians and mental health professionals working in primary health care units located in the northern part of the city of Rio de Janeiro, Brazil. The aim is to examine the various strategies and negotiations that primary health care professionals deploy to identify mental distress and plan health care interventions. We discuss the results within the economy of attention framework. We argue that divergences in diagnostic design and therapeutic planning carried out by professionals and users or observed in MHCC meetings illustrate the health-disease-care seeking phenomenon as a negotiated process, entangled in complex interactions. Our results evince that those interactions are not always evident and configure 'what is at stake' in mental suffering. The incorporation of cultural and structural determinants in collaborative care may enable the expansion of mental health initiatives sensitive to local needs and realities.

Postcranial anomalies of Eocene freshwater pleurodiran and cryptodiran turtles from the Spanish Duero Basin.

Testudines are one of the best-represented taxonomic groups among the Paleogene taxa of the Duero Basin (Castile and Leon Autonomous Community, central Spain). Among them, Neochelys (Podocnemidide) and Allaeochelys (Carettochelyidae) are most abundant, allowing the population to be assessed for osteological anomalies. The abundance of postcranial remains of both taxa allows us to identify several individuals with potential anomalies, mostly in their shells. Some of them have already been described in previous studies, but most of them are still unpublished. The objective of this study is to analyze in detail the anomalous Neochelys and Allaeochelys remains. As a result, different categories of causal agents (such as bacteria, fungi, parasites, or trauma) have been identified as potential producers of the anomalies in these freshwater turtles. Information regarding the pathogenesis and healing stages of some of these anomalies is provided.

Bright light therapy versus physical exercise to prevent co-occurring depression in adolescents and young adults with attention-deficit/hyperactivity disorder: a multicentre, three-arm, randomised controlled, pilot phase-IIa trial.

Depression is common in attention-deficit/hyperactivity disorder (ADHD), but preventive behavioural interventions are lacking. This randomised controlled, pilot phase-IIa trial aimed to study a physical exercise intervention (EI) and bright light therapy (BLT)-both implemented and monitored in an individual, naturalistic setting via a mobile health (m-health) system-for feasibility of trial design and interventions, and to estimate their effects on depressive symptoms in young people with ADHD. Two hundred seven participants aged 14-45 years were randomised to 10-week add-on intervention of either BLT (10,000 lx; daily 30-min sessions) (n = 70), EI (aerobic and muscle-strengthening activities 3 days/ week) (n = 69), or treatment-as-usual (TAU) (n = 68), of whom 165 (80%) were retained (BLT: n = 54; EI: n = 52; TAU: n = 59). Intervention adherence (i.e. ≥ 80% completed sessions) was very low for both BLT (n = 13, 22%) and EI (n = 4, 7%). Usability of the m-health system to conduct interventions was limited as indicated by objective and subjective data. Safety was high and comparable between groups. Changes in depressive symptoms (assessed via observer-blind ratings, Inventory of Depressive Symptomatology) between baseline and end of intervention were small (BLT: -0.124 [95% CI: -2.219, 1.971], EI: -2.646 [95% CI: -4.777, -0.515], TAU: -1.428 [95% CI: -3.381, 0.526]) with no group differences [F(2,153) = 1.45, p = 0.2384]. These findings suggest that the m-health approach did not achieve feasibility of EI and BLT in young people with ADHD. Prior to designing efficacy studies, strategies how to achieve high intervention adherence should be specifically investigated in this patient group. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03371810, 13 December 2017.

Associations between muscular strength and mental health in cognitively normal older adults: a cross-sectional study from the AGUEDA trial.

Objective: To examine the associations between muscular strength and mental health. Design: We used baseline data of 91 cognitively healthy older adults (71.69 ± 3.91 years old, 57 % women) participating in the AGUEDA randomized controlled trial. Methods: Muscular strength was assessed using both objective (i.e., handgrip strength, biceps curl, squats, and isokinetic test) and perceived (i.e., International Fitness Scale) indicators. Psychological ill-being indicators: anxiety, depression, stress, and loneliness; and psychological well-being indicators: satisfaction with life, self-esteem, and emotional well-being) were assessed using a set of valid and reliable self-reported questionnaires. Linear regression analyses were performed adjusting for sex, age, years of education, body mass index , alcohol, diet, and smoking (model 1), and additionally by cardiorespiratory fitness (model 2). Results: Elbow extension was positively associated with stress in model 1 (ß = 0.252, 95 % Confidence Interval [95 % CI] = 0.007 to 0.497, p = 0.044), and even after further adjustment for cardiorespiratory fitness (ß = 0.282, 95 % CI = 0.032 to 0.532, p = 0.028). Perceived strength was negatively associated with depressive symptoms in model 1 (ß = -0.271, 95 % CI = -0.491 to -0.049, p = 0.017) and model 2 reported associations tending towards significant (ß = -0.220, 95 % CI = -0.445 to 0.005, p = 0.055). Handgrip strength was positively associated with self-esteem in model 1 (ß = 0.558, 95 % CI = 0.168 to 0.949, p = 0.006) and model 2 (ß = 0.546, 95 % CI = 0.135 to 0.956, p = 0.010). No further associations were found among other muscular strength and mental health variables. Conclusion: Handgrip had a moderate association with self-esteem and there was a small association between perceived strength with depressive symptoms and elbow extension with stress. No other associations were observed between muscular strength and mental health outcomes in cognitively normal older adults.

Beyond skeletal studies: A computational analysis of nasal airway function in climate adaptation.

OBJECTIVES: Ecogeographic variation in human nasal anatomy has historically been analyzed on skeletal morphology and interpreted in the context of climatic adaptations to respiratory air-conditioning. Only a few studies have analyzed nasal soft tissue morphology, actively involved in air-conditioning physiology. MATERIALS AND METHODS: We used in vivo computer tomographic scans of (N = 146) adult individuals from Cambodia, Chile, Russia, and Spain. We conducted (N = 438) airflow simulations during inspiration using computational fluid dynamics to analyze the air-conditioning capacities of the nasal soft tissue in the inflow, functional, and outflow tract, under three different environmental conditions: cold-dry; hot-dry; and hot-humid. We performed statistical comparisons between populations and sexes. RESULTS: Subjects from hot-humid regions showed significantly lower air-conditioning capacities than subjects from colder regions in all the three conditions, specifically within the isthmus region in the inflow tract, and the anterior part of the internal functional tract. Posterior to the functional tract, no differences were detected. No differences between sexes were found in any of the tracts and under any of the conditions. DISCUSSION: Our statistical analyses support models of climatic adaptations of anterior nasal soft tissue morphology that fit with, and complement, previous research on dry skulls. However, our results challenge a morpho-functional model that attributes air-conditioning capacities exclusively to the functional tract located within the nasal cavity. Instead, our findings support studies that have suggested that both, the external nose and the intra-facial soft tissue airways contribute to efficiently warming and humidifying air during inspiration. This supports functional interpretations in modern midfacial variation and evolution.

Adolescent Cardiorespiratory Fitness and Future Work Ability.

Importance: Although research indicates that low fitness in youth is associated with a higher risk of chronic disability in men, the association of fitness in adolescence with work ability in working men and women remains unknown. Objective: To examine the associations of adolescent health-related physical fitness with future work ability. Design, Setting, and Participants: This 45-year observational cohort study, conducted in Finland, examined the direct and indirect longitudinal associations of objectively measured health-related fitness in adolescence (in 1976) with self-reported work ability and sickness absence in early middle age (in 2001) and the Work Ability Index in late middle age (in 2021). A countrywide stratified random baseline sample included fitness measurements for cardiorespiratory fitness (CRF) (running 1.5 km for girls and 2 km for boys), musculoskeletal fitness (MF; standing broad jump and sit-ups for both sexes, pull-ups for boys, and flexed-arm hang for girls), and height and weight, from which body mass index (BMI) was calculated. Structural equation modeling-based path analysis, adjusted for age and sex at baseline and for educational level, work-related physical strain, and leisure-time physical activity in late middle age, was conducted. Data analysis was performed from January to July 2023. Main Outcomes and Measures: Self-reported work ability was measured with structured questions in early middle age and with the validated Work Ability Index in late middle age. Results: The final sample from longitudinal analyses (1207 individuals; 579 [48%] male individuals) consisted of participants with fitness measurement from age 12 to 19 years, and work ability assessment from age 37 to 44 years and/or age 57 to 64 years. Higher adolescent CRF was associated with higher work ability (839 participants; ß = 0.12; 95% CI, 0.01 to 0.22; P = .03) and lower sickness absence (834 participants; ß = -0.07; 95% CI, -0.12 to -0.02; P = .004) in early middle age and, indirectly, mediated by work ability in early middle age, with a higher work ability at the end of working age (603 participants; ß = 0.04; 95% CI, 0.001 to 0.08; P = .04). The results remained consistent in both sexes and after adjustment for the confounders. Neither MF nor BMI was associated with work ability (MF, 1192 participants; ß = -0.07; 95% CI, -0.17 to 0.03; BMI, 1207 participants, ß = 0.09; 95% CI, -0.004 to 0.19) or sickness absence (MF, 1185 participants, ß = 0.02; 95% CI, -0.03 to 0.06; BMI, 1202 participants, ß = -0.03; 95% CI, -0.09 to 0.03) in early middle age or with late middle age work ability, mediated by work ability in early middle age (MF, 603 participants, ß = -0.02; 95% CI, -0.06 to 0.01; BMI, 603 participants, ß = 0.03; 95% CI, -0.004 to 0.07). Conclusions and Relevance: These findings suggest that low CRF in youth is associated with poor work ability at the middle and end of working life, which highlights the informative and prognostic value of CRF assessment early in youth. Enhancing CRF in the first decades of life might contribute to better work capacity and productivity in the labor force, which would have implications for health, quality of life, society, and the economy.

How to design and establish a national school-based physical fitness monitoring and surveillance system for children and adolescents: A 10-step approach recommended by the FitBack network.

BACKGROUND: Providing individual- and population-level data on children's physical fitness (PF) is a crucial public health and education priority. However, few national fitness monitoring or surveillance systems are currently in practice internationally. We aim to summarize the current European PF monitoring and surveillance systems for school-aged children and to provide experience-based guidelines on how to design such systems. METHODS: The FitBack network consists of experts from diverse backgrounds with the common interest to improve the accessibility of PF monitoring for young people globally. Through FitBack network, we identified and compared the national or regional PF monitoring and surveillance systems currently in operation across Europe. We formulated a 10-step approach for designing and establishing one's own system, based on analysis of experienced strengths, weaknesses, opportunities, and threats to monitoring childhood fitness. RESULTS: We identified a total of eight PF monitoring systems in Finland, France, Galicia of Spain, Hungary, Lithuania, Portugal, Serbia, and Slovenia. The FitBack network recommends the following steps for designing and establishing one's own system: (1) set up mission statements and aims, (2) involve stakeholders, (3) utilize scientific background, (4) governance structure, (5) ensure sufficient funding, (6) data management planning, (7) provide meaningful feedback, (8) conduct pilot testing, (9) plan implementation process, and (10) invest in communication with stakeholders. CONCLUSIONS: This study provides an updated overview of the best practices for school-aged children's fitness monitoring and surveillance in Europe. Additionally, it offers a 10-step approach to assist in the creation of similar systems in Europe or globally.

Beyond the Wizard of Oz: Negative Effects of Imperfect Machine Learning to Examine the Impact of Reliability of Augmented Reality Cues on Visual Search Performance.

Despite knowing exactly what an object looks like, searching for it in a person's visual field is a time-consuming and error-prone experience. In Augmented Reality systems, new algorithms are proposed to speed up search time and reduce human errors. However, these algorithms might not always provide 100% accurate visual cues, which might affect users' perceived reliability of the algorithm and, thus, search performance. Here, we examined the detrimental effects of automation bias caused by imperfect cues presented in the Augmented Reality head-mounted display using the YOLOv5 machine learning model. 53 participants in the two groups received either 100% accurate visual cues or 88.9% accurate visual cues. Their performance was compared with the control condition, which did not include any additional cues. The results show how cueing may increase performance and shorten search times. The results also showed that performance with imperfect automation was much worse than perfect automation and that, consistent with automation bias, participants were frequently enticed by incorrect cues.

The effects of physical activity on white matter microstructure in children with overweight or obesity: The ActiveBrains randomized clinical trial / Los efectos de la actividad física sobre la microestructura de la sustancia blanca en niños con sobrepeso u obesidad: el ensayo clínico aleatorizado ActiveBrains

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...(AU)

A new Crocodyloidea from the middle Eocene of Zamora (Duero Basin, Spain).

The eusuchian crocodyliforms recorded in the Eocene levels of the Spanish Duero Basin belong to three lineages: Planocraniidae, with the species Duerosuchus piscator; Alligatoroidea, represented by several specimens of the genus Diplocynodon; and Crocodyloidea, which includes several specimens traditionally attributed to Asiatosuchus. The genus Asiatosuchus, established in 1940 based on a middle Eocene species from Mongolia, has subsequently served as a wastebasket taxon for Paleogene remains belonging to several species, not only from Asia but also belonging to the European and North American records. Many of these species are known by highly fragmentary remains, sharing the presence of characters such as a flat and triangular skull, and long symphyses in the lower jaw, recognized as characteristic for the crocodyloids. In addition to isolated cranial remains, among the material traditionally attributed to Asiatosuchus at the Duero Basin stands out a nearly complete skull and a left mandible, from the middle Eocene area of Casaseca de Campeán (Zamora Province). The present study analyses in detail these specimens, previously reported during the 1980s, but analyzed in a very preliminary way. They are included for the first time in a phylogenetic analysis to establish the systematic position of this Spanish form. The results confirm that it corresponds to a new species of basal crocodyloid, defined here as Asiatosuchus oenotriensis sp. nov.

Assessing cardiorespiratory fitness in clinical and community settings: Lessons and advancements in the 100th year anniversary of VO2max.

Cardiorespiratory fitness (CRF) is a well-established biomarker that has applications to all adults across the health and disease spectrum. Despite overwhelming evidence supporting the prognostic utility of CRF, it remains vastly underutilized. CRF is optimally measured via cardiopulmonary exercise testing which may not be feasible to implement on a large scale. Therefore, it is prudent to develop ways to accurately estimate CRF that can be applied in clinical and community settings. As such, several prediction equations incorporating non-exercise information that is readily available from routine clinical encounters have been developed that provide an adequate reflection of CRF that could be implemented to raise awareness of the importance of CRF. Further, technological advances in smartphone apps and consumer-grade wearables have demonstrated promise to provide reasonable estimates of CRF that are widely available, which could enhance the utilization of CRF in both clinical and community settings.

Trajectories of osteogenic physical activity in children and adolescents: A 3-year cohort study.

OBJECTIVES: We explored the latent profiles based on locomotor skills and cardiorespiratory fitness in Finnish schoolchildren and examined their associations with latent growth curves of osteogenic physical activity (PA) over three years. DESIGN: Prospective cohort study. METHODS: Altogether 1147 Finnish adolescents aged 11-13 years participated in the study. Osteogenic PA in terms of osteogenic index (OI) was calculated based on acceleration peak histograms using all of the peaks with acceleration >1.3 g. Locomotor skills were assessed using the five-leap and side-to-side jumping tests and cardiorespiratory fitness (CRF) using 20-metre shuttle run test. The latent growth curve models for the locomotor skills and cardiorespiratory fitness profiles were tested to examine the longitudinal development of OI scores over time three years (from T0 to T3). RESULTS: OI scores were lower amongst children in the "Low locomotor profile" compared with "Moderate" and "High locomotor" profiles. The OI scores linearly decreased from T0 to T3 in each locomotor profile and the decrease was similar in all the profiles. Moreover, OI scores were lower in the "Low CRF profile" compared with "Moderate" and "High CRF" profiles. The OI scores decreased in each profile over time, but the decrease was steepest in the "Low CRF profile", whereas "Moderate" and "High CRF profiles" had similar developmental trajectories. CONCLUSIONS: Children with the highest locomotor skills and higher CRF accumulate more osteogenic PA than their least skilful and fit peers, which can have important implications on bone health in this critical period for bone growth.

[Trauma and literality: psychodynamic reason in the spirit of neuroscientific traumatization]. / Trauma e literalidade: a razão psicodinâmica no espírito da traumatização neurocientífica.

Since its origin in the surgical medicine of the 17th century, trauma research has had multiple interpretations and has been associated either with visible injuries to organs and tissues, or with the influence of pathogenic psychic agents on memory, consciousness and personality. With the intensification of the role of classification systems since DSM-III, the phenomenon of trauma came to be incorporated into the psychiatric realm through Post-Traumatic Stress Disorder and destined finally to the constraints of neuroscientific research. Based on a narrative review, this article will address one of the fundamental epistemological premises for this transition, which informs how psychological trauma gained autonomy over anatomical descriptions to be reclassified, around a century later, as an essentially bodily phenomenon and incorporated into the jargon of neurosciences.

Desde o seu nascimento na medicina cirúrgica do século XVII, a pesquisa do trauma admitiu interpretações múltiplas e associadas ora às lesões visíveis de órgãos e tecidos, ora à influência de agentes psíquicos patogênicos sobre a memória, a consciência e a personalidade. Com o aprofundamento do papel dos sistemas classificatórios desde DSM-III, o fenômeno do trauma será incorporado ao prisma psiquiátrico através do Transtorno de Estresse Pós-Traumático e destinado, finalmente, à circunscrição da pesquisa neurocientífica. A partir de revisão narrativa, este artigo abordará uma das premissas epistemológicas fundamentais para essa transição, que informa como o trauma psicológico ganhou autonomia sobre as descrições anatômicas para ser, cerca de um século depois, por ela reanexado enquanto fenômeno essencialmente corporal e aderido à gramática das neurociências.

Physical fitness in male adolescents and atherosclerosis in middle age: a population-based cohort study.

OBJECTIVES: To examine the associations between physical fitness in male adolescents and coronary and carotid atherosclerosis in middle age. METHODS: This population-based cohort study linked physical fitness data from the Swedish Military Conscription Register during adolescence to atherosclerosis data from the Swedish CArdioPulmonary bioImage Study in middle age. Cardiorespiratory fitness was assessed using a maximal cycle-ergometer test, and knee extension muscular strength was evaluated through an isometric dynamometer. Coronary atherosclerosis was evaluated via Coronary Computed Tomography Angiography (CCTA) stenosis and Coronary Artery Calcium (CAC) scores, while carotid plaques were evaluated by ultrasound. The associations were analysed using multinomial logistic regression, adjusted (marginal) prevalences and restricted cubic splines. RESULTS: The analysis included 8986 male adolescents (mean age 18.3 years) with a mean follow-up of 38.2 years. Physical fitness showed a reversed J-shaped association with CCTA stenosis and CAC, but no consistent association was observed for carotid plaques. After adjustments, compared with adolescents in the lowest tertile of cardiorespiratory fitness and muscular strength, those in the highest tertile had 22% (OR 0.78; 95% CI 0.61 to 0.99) and 26% (OR 0.74; 95% CI 0.58 to 0.93) lower ORs for severe (≥50%) coronary stenosis, respectively. The highest physical fitness group (high cardiorespiratory fitness and muscular strength) had 33% (OR 0.67; 95% CI 0.52 to 0.87) lower OR for severe coronary stenosis compared with those with the lowest physical fitness. CONCLUSION: This study supports that a combination of high cardiorespiratory fitness and high muscular strength in adolescence is associated with lower coronary atherosclerosis, particularly severe coronary stenosis, almost 40 years later.

Synthetic modified vaccinia Ankara vaccines confer cross-reactive and protective immunity against mpox virus.

BACKGROUND: Although the mpox global health emergency caused by mpox virus (MPXV) clade IIb.1 has ended, mpox cases are still reported due to low vaccination coverage and waning immunity. COH04S1 is a clinically evaluated, multiantigen COVID-19 vaccine candidate built on a fully synthetic platform of the highly attenuated modified vaccinia Ankara (MVA) vector, representing the only FDA-approved smallpox/mpox vaccine JYNNEOS. Given the potential threat of MPXV resurgence and need for vaccine alternatives, we aimed to assess the capacity COH04S1 and its synthetic MVA (sMVA) backbone to confer MPXV-specific immunity. METHODS: We evaluated orthopoxvirus-specific and MPXV cross-reactive immune responses in samples collected during a Phase 1 clinical trial of COH04S1 and in non-human primates (NHP) vaccinated with COH04S1 or its sMVA backbone. MPXV cross-reactive immune responses in COH04S1-vaccinated healthy adults were compared to responses measured in healthy subjects vaccinated with JYNNEOS. Additionally, we evaluated the protective efficacy of COH04S1 and sMVA against mpox in mpox-susceptible CAST/EiJ mice. RESULTS: COH04S1-vaccinated individuals develop robust orthopoxvirus-specific humoral and cellular responses, including cross-reactive antibodies to MPXV-specific virion proteins as well as MPXV cross-neutralizing antibodies in 45% of the subjects. In addition, NHP vaccinated with COH04S1 or sMVA show similar MPXV cross-reactive antibody responses. Moreover, MPXV cross-reactive humoral responses elicited by COH04S1 are comparable to those measured in JYNNEOS-vaccinated subjects. Finally, we show that mice vaccinated with COH04S1 or sMVA are protected from lung infection following challenge with MPXV clade IIb.1. CONCLUSIONS: These results demonstrate the capacity of sMVA vaccines to elicit cross-reactive and protective orthopox-specific immunity against MPXV, suggesting that COH04S1 and sMVA could be developed as bivalent or monovalent mpox vaccine alternatives against MPXV.

Mpox is an ilness caused by the mpox virus (MPXV) that belongs to the poxvirus family. The 2022-2023 mpox outbreak highlights the need to develop effective vaccines against MPXV. We have developed a COVID-19 vaccine using as scaffold chemically synthesized genetic material of a highly attenuated and safe poxvirus vector. This scaffold is the same present in a vaccine that has been approved and is given to prevent mpox. Here, we show that healthy human volunteers or monkeys vaccinated with this COVID-19 vaccine generated a robust immune response against MPXV, similar to that generated by the mpox vaccine with the same scaffold. This COVID-19 vaccine is also able to protect mice from infection caused by the MPXV strain isolated from the recent mpox outbreak. This COVID-19 vaccine in a poxvirus scaffold might be an additional tool to curtail mpox outbreaks.

Every Move Counts to Improve Bone Health at Clinical Sites in Young Pediatric Cancer Survivors: The iBoneFIT Project.

PURPOSE: We aimed to examine the associations of 24-hour movement behaviors (moderate-to-vigorous physical activity [MVPA], light physical activity [LPA], sedentary behavior [SB] and sleep) with age-, sex- and race-specific areal bone mineral density (aBMD) Z-score parameters at clinical sites in young pediatric cancer survivors. METHODS: This cross-sectional multicenter study was carried out within the iBoneFIT framework in which 116 young pediatric cancer survivors (12.1 ± 3.3 years old; 42% female) were recruited. We obtained anthropometric and body composition data (i.e., body mass, stature, body mass index and region-specific lean mass), time spent in movement behaviors over at least seven consecutive 24-hour periods (wGT3x-BT accelerometer, ActiGraph) and aBMD Z-score parameters (age-, sex- and race-specific total at the body, total hip, femoral neck and lumbar spine). Survivors were classified according to somatic maturity (pre or peri/post-pubertal depending on the estimated years from peak height velocity). The adjusted models' coefficients were used to predict the effect of reallocating time proportionally across behaviors on the outcomes. RESULTS: In pre-pubertal young pediatric cancer survivors, reallocating time to MVPA from LPA, SB and sleep was significantly associated with higher aBMD at total body (B = 1.765, P = .005), total hip (B = 1.709, P = .003) and lumbar spine (B = 2.093, P = .001). In peri/post-pubertal survivors, reallocating time to LPA from MVPA, SB and sleep was significantly associated with higher aBMD at all sites (B = 2.090 to 2.609, P = .003 to .038). Reallocating time to SB from MVPA or LPA was significantly associated with lower aBMD at most sites in pre-pubertal and peri/post-pubertal survivors, respectively. Finally, reallocating time to sleep from MVPA, LPA and SB was significantly associated with lower aBMD at total body (B = -2.572, P = .036) and total hip (B = -3.371, P = .015). CONCLUSIONS: These findings suggest that every move counts and underline the benefits of increasing MVPA or LPA, when low MVPA levels are present, for bone regeneration following pediatric cancer treatment completion.

Adults with metabolically healthy overweight or obesity present more brown adipose tissue and higher thermogenesis than their metabolically unhealthy counterparts.

BACKGROUND: There is a subset of individuals with overweight/obesity characterized by a lower risk of cardiometabolic complications, the so-called metabolically healthy overweight/obesity (MHOO) phenotype. Despite the relatively higher levels of subcutaneous adipose tissue and lower visceral adipose tissue observed in individuals with MHOO than individuals with metabolically unhealthy overweight/obesity (MUOO), little is known about the differences in brown adipose tissue (BAT). METHODS: This study included 53 young adults (28 women) with a body mass index (BMI) ≥25 kg/m2 which were classified as MHOO (n = 34) or MUOO (n = 19). BAT was assessed through a static 18F-FDG positron emission tomography/computed tomography scan after a 2-h personalized cooling protocol. Energy expenditure, skin temperature, and thermal perception were assessed during a standardized mixed meal test (3.5 h) and a 1-h personalized cold exposure. Body composition was assessed by dual-energy x-ray absorptiometry, energy intake was determined during an ad libitum meal test and dietary recalls, and physical activity levels were determined by a wrist-worn accelerometer. FINDINGS: Participants with MHOO presented higher BAT volume (+124%, P = 0.008), SUVmean (+63%, P = 0.001), and SUVpeak (+133%, P = 0.003) than MUOO, despite having similar BAT mean radiodensity (P = 0.354). In addition, individuals with MHOO exhibited marginally higher meal-induced thermogenesis (P = 0.096) and cold-induced thermogenesis (+158%, P = 0.050). Moreover, MHOO participants showed higher supraclavicular skin temperature than MUOO during the first hour of the postprandial period and during the cold exposure, while no statistically significant differences were observed in other skin temperature parameters. We observed no statistically significant differences between MHOO and MUOO in thermal perception, body composition, outdoor ambient temperature exposure, resting metabolic rate, energy intake, or physical activity levels. INTERPRETATION: Adults with MHOO present higher BAT volume and activity than MUOO. The higher meal- and cold-induced thermogenesis and cold-induced supraclavicular skin temperature are compatible with a higher BAT activity. Overall, these results suggest that BAT presence and activity might be linked to a healthier phenotype in young adults with overweight or obesity. FUNDING: See acknowledgments section.