Brain-on-a-chip: an emerging platform for studying the nanotechnology-biology interface for neurodegenerative disorders.

Neurological disorders have for a long time been a global challenge dismissed by drug companies, especially due to the low efficiency of most therapeutic compounds to cross the brain capillary wall, that forms the blood-brain barrier (BBB) and reach the brain. This has boosted an incessant search for novel carriers and methodologies to drive these compounds throughout the BBB. However, it remains a challenge to artificially mimic the physiology and function of the human BBB, allowing a reliable, reproducible and throughput screening of these rapidly growing technologies and nanoformulations (NFs). To surpass these challenges, brain-on-a-chip (BoC) - advanced microphysiological platforms that emulate key features of the brain composition and functionality, with the potential to emulate pathophysiological signatures of neurological disorders, are emerging as a microfluidic tool to screen new brain-targeting drugs, investigate neuropathogenesis and reach personalized medicine. In this review, the advance of BoC as a bioengineered screening tool of new brain-targeting drugs and NFs, enabling to decipher the intricate nanotechnology-biology interface is discussed. Firstly, the main challenges to model the brain are outlined, then, examples of BoC platforms to recapitulate the neurodegenerative diseases and screen NFs are summarized, emphasizing the current most promising nanotechnological-based drug delivery strategies and lastly, the integration of high-throughput screening biosensing systems as possible cutting-edge technologies for an end-use perspective is discussed as future perspective.

Spain: health system review

This review of the Spanish health system analyses recent developments in health organization and governance, financing, health care provision, recent reforms and health system performance.Overall health status continues to improve in Spain, which presents the highest life expectancy in the European Union – although some socioeconomic inequalities in health persist and risk factors such as overweight, tobacco and alcohol consumption and illegal drug use remain a concern. Health system reforms since 2018 have focused on widening the population covered by the health system, reducing co-payments, improving the scope of coverage in terms of increasing provided services, and the reinforcement of primary care. Future challenges for the health system include addressing access gaps, such as the limited coverage of some services (such as dental and optical care), and large waiting lists for some services. Some gaps in efficiency remain, such as the low numbers of qualified personnel in some medical specialties, the shortage of mental health resources, the underuse of effective treatments, and the overuse of non-appropriate orineffective procedures.

Synergistic antifungal activity against Candida albicans between voriconazole and cyclosporine a loaded in polymeric nanoparticles.

The goal of this work is to investigate if the synergistic antifungal activity between cyclosporine A, CsA, and voriconazole, VRZ, increases when both drugs are encapsulated in a nanocarrier as compared when they are free. The preparation and characterization of blank and VRZ and CsA loaded polymeric based PLGA nanoparticles (PLGA, PLGA-PEG, and PLGA+PEG) was a necessary previous step. Using the more suitable NPs, those of PLGA, the antifungal susceptibility tests performed with VRZ-loaded PLGA NPs, show no significant increase of the antifungal activity in comparison to that of free VRZ. However, the synergistic behavior found for the (VRZ+CsA)-loaded PLGA NPs was fourfold stronger than that observed for the two free drugs together. On the other hand, the investigation into the suppression of C. albicans biofilm formation showed that blank PLGA NPs inhibit the biofilm formation at high NPs concentrations. However, a minor effect or even a slight biofilm increase formation was observed at low and moderate NPs concentrations. Therefore, the enhancement of the biofilm inhibition found for the three tested treatments (CsA alone, VRZ alone, and VRZ+CsA) when comparing free and encapsulated drugs, within the therapeutic window, can be attributed to the drug encapsulation approach. Indeed, polymeric PLGA NPs loaded with CsA, VRZ, or VRZ+CsA are more effective at inhibiting the C. albicans biofilm growth than their free counterparts.

Real-World Evaluation of Once-Weekly Subcutaneous Semaglutide in Patients with Type 2 Diabetes Mellitus in Spain (SEMA-RW Study).

Although, in randomized clinical trials, once-weekly subcutaneous semaglutide (OW s.c.) has demonstrated superior efficacy in comparison with placebo and active controls in terms of glycemic control and body weight reduction in patients with type 2 diabetes mellitus (T2DM), these results need to be confirmed in a real-world (RW) setting. An RW ambispective study (6 months retrospective and 6 months prospective) was conducted in 10 tertiary hospitals in Spain. We evaluated changes in HbA1c and body weight in patients with T2DM treated with semaglutide OW s.c. Additionally, we analyzed different subgroups of patients treated with semaglutide OW s.c. as an add-on to glucose-lowering therapy. A total of 752 patients with a mean age of 60.2 years, a mean HbA1c level of 8.5%, a mean body weight of 101.6 kg, and a mean T2DM duration of 10 years were included. At 12 months, compared with baseline, there was a mean difference of -2.1% in HbA1c levels (p < 0.001) and a mean difference of 9.2 kg in body weight (p < 0.001). Moreover, there were statistically significant differences (p < 0.001) between baseline and month 12 in both HbA1c and body weight in the four subgroups receiving semaglutide OW s.c. as an add-on to glucose-lowering therapy. Semaglutide OW s.c. was well tolerated, with gastrointestinal disorders being the most commonly reported side effects. In this RW study, 12 months of treatment with semaglutide OW s.c. in patients with T2DM was associated with significant and clinically relevant improvements in glycemic control and weight loss, regardless of the glucose-lowering therapy received, and the overall safety profile was positive.

A guide for the generation of repositories of clinical samples for research on Chagas disease.

Chagas disease, caused by the parasite Trypanosoma cruzi, affects over 6 million people, mainly in Latin America. Two different clinical phases, acute and chronic, are recognised. Currently, 2 anti-parasitic drugs are available to treat the disease (nifurtimox and benznidazole), but diagnostic methods require of a relatively complex infrastructure and trained personnel, limiting its widespread use in endemic areas, and the access of patients to treatment. New diagnostic methods, such as rapid tests (RDTs) to diagnose chronic Chagas disease, or loop-mediated isothermal amplification (LAMP), to detect acute infections, represent valuable alternatives, but the parasite's remarkable genetic diversity might make its implementation difficult. Furthermore, determining the efficacy of Chagas disease treatment is complicated, given the slow reversion of serological anti-T. cruzi antibody reactivity, which may even take decades to occur. New biomarkers to evaluate early therapeutic efficacy, as well as diagnostic tests able to detect the wide variety of circulating genotypes, are therefore, urgently required. To carry out studies that address these needs, high-quality and traceable samples from T. cruzi-infected individuals with different geographical backgrounds, along with associated clinical and epidemiological data, are necessary. This work describes the framework for the creation of such repositories, following standardised and uniform protocols, and considering the ethical, technical, and logistic aspects of the process. The manual can be adapted according to the resources of each laboratory, to guarantee that samples are obtained in a reproducible way, favouring the exchange of data among different work groups, and their generalizable evaluation and analysis. The main objective of this is to accelerate the development of new diagnostic methods and the identification of biomarkers for Chagas disease.

The expression of immune response genes in patients with chronic Chagas disease is shifted toward the levels observed in healthy subjects as a result of treatment with Benznidazole.

Introduction: Chagas disease, caused by the Trypanosoma cruzi parasite infection, is a potentially life-threatening neglected tropical disease with a worldwide distribution. During the chronic phase of the disease, there exists a fragile balance between the host immune response and parasite replication that keeps patients in a clinically-silent asymptomatic stage for years or even decades. However, in 40% of patients, the disease progresses to clinical manifestations mainly affecting and compromising the cardiac system. Treatment is recommended in the chronic phase, although there are no early markers of its effectiveness. The aim of this study is to identify differential expression changes in genes involved in the immune response in antigen-restimulated PBMC from chronic patients with Chagas disease due to benznidazole treatment. Methods: Thus, high-throughput real-time qPCR analysis has been performed to simultaneously determine global changes in the expression of 106 genes involved in the immune response in asymptomatic (IND) and early cardiac manifestations (CCC I) Chagas disease patients pre- and post-treatment with benznidazole. Results and discussion: The results revealed that 7 out of the 106 analyzed genes were differentially expressed (4 up- and 3 downregulated) after treatment in IND patients and 15 out of 106 (3 up- and 12 downregulated) after treatment of early cardiac Chagas disease patients. Particularly in CCC I patients, regulation of the expression level of some of these genes towards a level similar to that of healthy subjects suggests a beneficial effect of treatment and supports recommendation of benznidazole administration to early cardiac Chagas disease patients. The data obtained also demonstrated that both in asymptomatic patients and in early cardiac chronic patients, after treatment with benznidazole there is a negative regulation of the proinflammatory and cytotoxic responses triggered as a consequence of T. cruzi infection and the persistence of the parasite. This downregulation of the immune response likely prevents marked tissue damage and healing in early cardiac patients, suggesting its positive effect in controlling the pathology.

Novel Directed Enzyme Prodrug Therapy for Cancer Treatment Based on 2'-Deoxyribosyltransferase-Conjugated Magnetic Nanoparticles.

Directed enzyme prodrug therapy (DEPT) strategies show promise in mitigating chemotherapy side effects during cancer treatment. Among these, the use of immobilized enzymes on solid matrices as prodrug activating agents (IDEPT) presents a compelling delivery strategy, offering enhanced tumor targeting and reduced toxicity. Herein, we report a novel IDEPT strategy by employing a His-tagged Leishmania mexicana type I 2'-deoxyribosyltransferase (His-LmPDT) covalently attached to glutaraldehyde-activated magnetic iron oxide nanoparticles (MIONPs). Among the resulting derivatives, PDT-MIONP3 displayed the most favorable catalyst load/retained activity ratio, prompting its selection for further investigation. Substrate specificity studies demonstrated that PDT-MIONP3 effectively hydrolyzed a diverse array of 6-oxo and/or 6-amino purine 2'-deoxynucleosides, including 2-fluoro-2'-deoxyadenosine (dFAdo) and 6-methylpurine-2'-deoxyribose (d6MetPRib), both well-known prodrugs commonly used in DEPT. The biophysical characterization of both MIONPs and PDT-MIONPs was conducted by TEM, DLS, and single particle ICPMS techniques, showing an ideal nanosized range and a zeta potential value of -47.9 mV and -78.2 mV for MIONPs and PDT-MIONPs, respectively. The intracellular uptake of MIONPs and PDT-MIONPs was also determined by TEM and single particle ICPMS on HeLa cancer cell lines and NIH3T3 normal cell lines, showing a higher intracellular uptake in tumor cells. Finally, the selectivity of the PDT-MIONP/dFAdo IDEPT system was tested on HeLa cells (24 h, 10 µM dFAdo), resulting in a significant reduction in tumoral cell survival (11% of viability). Based on the experimental results, PDT-MIONP/dFAdo presents a novel and alternative IDEPT strategy, providing a promising avenue for cancer treatment.

One- versus Two-Minute Intercostal Nerve Cryoanalgesia in Children Undergoing Surgery for Funnel Chest Deformity.

An inherent defect of the sternum and ribs results in the formation of a funnel-shaped anterior chest wall. The gold standard of surgical correction is the minimally invasive Nuss procedure, which might cause severe pain and carries the risk of sensory disturbances and chronic discomfort. Integrating cryoanalgesia with standard multimodal analgesia improves the outcomes of this procedure. Based on histological results, it was hypothesised that the time of cryo-application can be reduced from the current standard period of two minutes. The goal of this study was to evaluate the efficacy of a one-minute application compared with the routine two-minute method in the same patient, considering the subjective perception of pain and sensory disturbances. A total of 33 patients were included in this prospective study. The results show that the assessment of pain severity and sensory disturbances did not differ significantly in terms of the time of cryo-application during first 14 days after the surgical procedure. The one-minute cryo-application time for intraoperative intercostal nerve cryoablation prior to the Nuss procedure seems to be as safe and effective as the routinely used two-minute application time in regards to pain severity, sensory disturbances, and the risk of chronic pain development. Intercostal nerve cryoanalgesia is an essential element of multimodal analgesia.

Basic Psychological Needs in the Face of Achievement Vulnerability: A Study in Young Team Athletes.

The susceptibility of athletes to experience of emotional and psychological difficulties arising from the pressure and expectations associated with achieving and maintaining high performance can become a vulnerability in the desire to achieve success in sport. This study aims to investigate the protective value in the perception of satisfaction in basic psychological needs against the vulnerability that perfectionism generates in the appearance of reactivity linked to fear of failure. A cross-sectional, relational, and semi-randomized research design was used, applying perfectionism, fear of failure, and basic psychological needs measures adapted to both the competitive sports context and the Spanish language in a sample of 372 young Spanish athletes, under descriptive analyses and predictive models. The results showed that as the age of the participants increased, the indicators of perfectionism and fear of failure decreased, with no gender differences. The results offer and confirm the positive relationships between the dimensions of perfectionism and fear of making mistakes (where processes such as self-devaluation and fear of failing the people that participants deemed as important to them are intertwined). The perception of satisfaction of the basic psychological needs of autonomy, social relationships, and competence emerges as protective factors that mediate the perfectionism-fear of failure relationship. On the other hand, discrepancies are shown between the perfectionist dimensions concerning the relationships with the BPNs, describing certain sources of vulnerability, although there are adjustments of mental effort and discomfort in the young athletes. The conclusions offer the opportunity to investigate the aspects that facilitate the emergence of fear of failure in young athletes, mainly the performance of coaches connected to the emergence of patterns in pursuit of perfection.

Clinical Consensus Statement on the Use of Indocyanine Green Fluorescence-guided Surgery in Pediatric Patients.

BACKGROUND AND AIMS: Indocyanine Green Fluorescence (ICG-F)- guided surgery is becoming an increasingly helpful tool in pediatric surgical care. This consensus statement investigates the utility of ICG-F in various pediatric surgical applications, primarily focusing on its evidence base, safety, indications, use across different surgical specialties and dosing strategies. The aim is to establish an international consensus for ICG-F use in pediatric surgery. METHODS: An international panel of 15 pediatric surgeons from 9 countries was assembled. The structured process consisted of a rapid scoping review, iterative discussion sessions, mixed-methods studies with key stakeholders, and voting rounds on individual statements to create draft consensus statements. RESULTS: 100 articles were identified during the review and summarized by application. Based on this condensed evidence, consensus statements were generated after 3 iterative rounds of anonymous voting. Key areas of agreement were quality of evidence, the safety of ICG, pediatric surgical indications, utilization per surgical specialty, and dosing of ICG. CONCLUSION: This consensus statement aims to guide healthcare professionals in managing ICG-F use in pediatric surgical cases based on the best available evidence, key stakeholder consultation, and expert opinions. Despite ICG-F's promising potential, the need for higher-quality evidence, prospective trials, and safety studies is underscored. The consensus also provides a framework for pediatric surgeons to utilize ICG-F effectively. LEVEL OF EVIDENCE: III.

Barriers and Strategies to Optimize the Use of Glucagon-Like Peptide 1 Receptor Agonists in People with Type 2 Diabetes and High Cardiovascular Risk or Established Cardiovascular Disease: A Delphi Consensus in Spain.

INTRODUCTION: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are effective for glycemic control, with many also demonstrating cardiovascular (CV) benefit, in people with type 2 diabetes (T2D). This study aimed to find a consensus on the barriers and strategies for the optimal use of GLP-1 RAs in people with T2D and high CV risk or established cardiovascular disease (CVD) in Spain. METHODS: A two-round Delphi survey (53 questions) was conducted among members of four national scientific societies in Spain, including physicians experienced in the management of people with T2D. The degree of consensus was evaluated with a 7-point Likert scale, establishing consensus when ≥ 70% of the panelists agreed (6-7) or disagreed (1-2). RESULTS: A total of 97 physicians participated in the first round (endocrinology: 34%, family and community medicine: 21%, internal medicine: 23%, and cardiology: 23%), and 96 in the second round. The main barriers identified were: therapeutic inertia and late use of GLP-1 RAs; lack of a comprehensive approach to CV risk; lack of knowledge on the usefulness of GLP-1 RAs in CVD prevention and treatment; and economic/administrative barriers. Strategies with a highest consensus included: the need to establish simple protocols that integrate awareness of CV risk monitoring; training professionals and patients; and the use of new technologies. CONCLUSION: Physicians identified clinical, healthcare, and economic/administrative barriers that limit the use of GLP-1 RAs in people with T2D and high CV risk or established CVD in Spain, highlighting the importance of integrating these therapies according to clinical practice guidelines.

Genomic Characterization of Piscicolin CM22 Produced by Carnobacterium maltaromaticum CM22 Strain Isolated from Salmon (Salmo salar).

Carnobacterium maltaromaticum is a species of lactic acid bacteria (LAB) that has been isolated from various natural environments. It is well-known for producing a diverse spectrum of bacteriocins with potential biotechnological applications. In the present study, a new psychrotolerant strain of C. maltaromaticum CM22 is reported, isolated from a salmon gut sample and producing a variant of the bacteriocin piscicolin 126 that has been named piscicolin CM22. After identification by 16S rRNA gene, this strain has been genomically characterized by sequencing and assembling its complete genome. Moreover, its bacteriocin was purified and characterized. In vitro tests demonstrated that both the strain and its bacteriocin possess antimicrobial activity against several Gram-positive bacteria of interest in human and animal health, such as Listeria monocytogenes, Clostridium perfringens, or Enterococcus faecalis. However, this bacteriocin did not produce any antimicrobial effect on Gram-negative species. The study of its genome showed the genetic structure of the gene cluster that encodes the bacteriocin, showing a high degree of homology to the gene cluster of piscicolin 126 described in other C. maltaromaticum. Although more studies are necessary concerning its functional properties, this new psychrotolerant strain C. maltaromaticum CM22 and its bacteriocin could be considered an interesting candidate with potential application in agri-food industry.

The Mediating Role of Cardiorespiratory Fitness in the Association between a Negative Lifestyle and Poor Mental Health in Chilean Schoolchildren.

BACKGROUND: A negative lifestyle has a reported relationship with psychological problems and deteriorated well-being. However, there is little information regarding the mediating role of cardiorespiratory fitness (CRF) in this relationship. OBJECTIVES: The objectives of the present study are twofold: first, to investigate the association between negative lifestyle, physical self-concept (PSC), and depression, and second, to assess the potential mediating role of CRF in this complex relationship. METHODS: This cross-sectional study included 612 schoolchildren aged between 9 and 14 years from the Araucanía region (southern Chile). CRF was measured using the Leger test, and lifestyle, depression, and PSC were measured using validated questionnaires. RESULTS: A negative lifestyle reported an inverse association with PSC (p < 0.001) and a positive association with depression levels (p < 0.001). The mediation analysis showed that CRF was positively related to PSC (p < 0.001) and inversely related to depression (p = 0.001); besides, the indirect effect CRF acted as a partial mediator in the association between a negative lifestyle and PSC (indirect effect = -1.15; SE = 0.01; 95% CI, -1.87, -0.55) and depression levels (indirect effect = 0.22; SE = 0.08; 95% CI, 0.08, 0.38). CONCLUSION: In conclusion, CRF in schoolchildren played a potential mediating role in the association between a negative lifestyle and depression and PSC.

Galactokinase 1 is the source of elevated galactose-1-phosphate and cerebrosides are modestly reduced in a mouse model of classic galactosemia.

Classic galactosemia (CG) arises from loss-of-function mutations in the Galt gene, which codes for the enzyme galactose-1-phosphate uridylyltransferase (GALT), a central component in galactose metabolism. The neonatal fatality associated with CG can be prevented by galactose dietary restriction, but for decades it has been known that limiting galactose intake is not a cure and patients often have lasting complications. Even on a low-galactose diet, GALT's substrate galactose-1-phosphate (Gal1P) is elevated and one hypothesis is that elevated Gal1P is a driver of pathology. Here we show that Gal1P levels were elevated above wildtype (WT) in Galt mutant mice, while mice doubly mutant for Galt and the gene encoding galactokinase 1 (Galk1) had normal Gal1P levels. This indicates that GALK1 is necessary for the elevated Gal1P in CG. Another hypothesis to explain the pathology is that an inability to metabolize galactose leads to diminished or disrupted galactosylation of proteins or lipids. Our studies reveal that levels of a subset of cerebrosides-galactosylceramide 24:1, sulfatide 24:1, and glucosylceramide 24:1-were modestly decreased compared to WT. In contrast, gangliosides were unaltered. The observed reduction in these 24:1 cerebrosides may be relevant to the clinical pathology of CG, since the cerebroside galactosylceramide is an important structural component of myelin, the 24:1 species is the most abundant in myelin, and irregularities in white matter, of which myelin is a constituent, have been observed in patients with CG. Therefore, impaired cerebroside production may be a contributing factor to the brain damage that is a common clinical feature of the human disease.

External Validation of the Machine Learning-Based Thermographic Indices for Rheumatoid Arthritis: A Prospective Longitudinal Study.

External validation is crucial in developing reliable machine learning models. This study aimed to validate three novel indices-Thermographic Joint Inflammation Score (ThermoJIS), Thermographic Disease Activity Index (ThermoDAI), and Thermographic Disease Activity Index-C-reactive protein (ThermoDAI-CRP)-based on hand thermography and machine learning to assess joint inflammation and disease activity in rheumatoid arthritis (RA) patients. A 12-week prospective observational study was conducted with 77 RA patients recruited from rheumatology departments of three hospitals. During routine care visits, indices were obtained at baseline and week 12 visits using a pre-trained machine learning model. The performance of these indices was assessed cross-sectionally and longitudinally using correlation coefficients, the area under the receiver operating curve (AUROC), sensitivity, specificity, and positive and negative predictive values. ThermoDAI and ThermoDAI-CRP correlated with CDAI, SDAI, and DAS28-CRP cross-sectionally (ρ = 0.81; ρ = 0.83; ρ = 0.78) and longitudinally (ρ = 0.55; ρ = 0.61; ρ = 0.60), all p < 0.001. ThermoDAI and ThermoDAI-CRP also outperformed Patient Global Assessment (PGA) and PGA + C-reactive protein (CRP) in detecting changes in 28-swollen joint counts (SJC28). ThermoJIS had an AUROC of 0.67 (95% CI, 0.58 to 0.76) for detecting patients with swollen joints and effectively identified patients transitioning from SJC28 > 1 at baseline visit to SJC28 ≤ 1 at week 12 visit. These results support the effectiveness of ThermoJIS in assessing joint inflammation, as well as ThermoDAI and ThermoDAI-CRP in evaluating disease activity in RA patients.

DNA G-quadruplexes in the genome of Trypanosoma cruzi as potential therapeutic targets for Chagas disease: Dithienylethene ligands as effective antiparasitic agents.

Chagas disease is caused by the parasite Trypanosoma cruzi and affects over 7 million people worldwide. The two actual treatments, Benznidazole (Bzn) and Nifurtimox, cause serious side effects due to their high toxicity leading to treatment abandonment by the patients. In this work, we propose DNA G-quadruplexes (G4) as potential therapeutic targets for this infectious disease. We have found 174 PQS per 100,000 nucleotides in the genome of T. cruzi and confirmed G4 formation of three frequent motifs. We synthesized a family of 14 quadruplex ligands based in the dithienylethene (DTE) scaffold and demonstrated their binding to these identified G4 sequences. Several DTE derivatives exhibited micromolar activity against epimastigotes of four different strains of T. cruzi, in the same concentration range as Bzn. Compounds L3 and L4 presented remarkable activity against trypomastigotes, the active form in blood, of T. cruzi SOL strain (IC50 = 1.5-3.3 µM, SI = 25-40.9), being around 40 times more active than Bzn and displaying much better selectivity indexes.

Stability of Cesium-Based Lead Halide Perovskites under UV Radiation.

Lead halide perovskites have been extensively studied for their potential applications, including photodetectors, solar cells, and high-energy radiation detection. These applications are possible because of their unique optoelectronic properties, such as tunable band gap, high optical absorption coefficient, and unique defect self-healing properties, which result in high defect tolerance. Despite these advantages, the long-term stability remains a critical issue that could hinder commercial applications of these materials. Reports on the stability of lead halide perovskites for optoelectronic applications have normally focused on methylammonium (MA)/formamidinium (FA), with very limited information for other systems, in particular, Cs-containing perovskites. In this paper, we report the stability of thick CsPbBr3-x Cl x polycrystalline thin films (∼8 µm) with several halide Br-Cl ratios after exposure to deep UV radiation. The chemical, crystal structure, optical, and electrical properties are analyzed, and the results are used to propose a degradation mechanism. The chemical analysis on the surface and bulk of the films indicates the formation of cesium oxide after UV exposure, with no significant change in the crystalline structure. The proposed mechanism explains the formation of cesium oxides during UV exposure. The I-V characteristics of diode structures also showed significant degradation after UV exposure, primarily at lower diode rectification ratios. The mechanism proposed in this paper can contribute to developing strategies to enhance the long-term stability of inorganic lead halide perovskites under UV exposure.

Exploring the mediating role of promoting school physical activity on the relationship between low socioeconomic status and academic achievement and school climate: evidence from 4,990 Chilean schools.

There is evidence that promoting school physical activity (PSPA) benefits children and adolescents, but little is understood about how this promotion may relate to academic achievement and school climate across varying levels of socioeconomic status (SES). Hence, the study aimed to address this knowledge gap by examining two main objectives: (1) determining the association between PSPA and academic achievement and school climate according to schools' SES and (2) exploring the potential mediating role of PSPA in the relationship between schools' SES and academic achievement and school climate. This cross-sectional study at the school level focused on 4,990 schools (including public, subsidized, and private schools) that participated in the National Educational Study 2018 (Chile), which was applied to primary schoolchildren (4th grade, aged 8-10 years). Schools were divided into non-PSPA (n = 4,280) and PSPA (n = 710) during the year 2018. Changes in academic achievement from 2017 to 2018 and school climate were considered. PSPA was associated with improvements in maths (low-SES OR: 1.80, p < 0.001) and reading (middle-SES OR: 1.45, p = 0.029; low-SES OR: 1.47, p < 0.001). The indirect effect (IE) showed that PSPA partially mediated the relationship between SES and academic achievement in reading (IE = 1.017; SE = 0.12; 95%CI, -1.27, -0.77), maths (IE = -1.019; SE = 0.12; 95%CI, -1.25, -0.78), and school climate (IE = -0.46; SE = 0.52; 95%CI, -0.56, -0.35). In conclusion, PSPA was linked to positive changes in academic achievement, especially among low SES, and PSPA presented a potential mediating role in the relationship between SES of schools and academic achievement and school climate.