Male-specific bacteriophages and their potential on combating the spreading of T4SS-bearing antimicrobial resistance plasmids.

Antimicrobial resistance (AMR) has been recognized as an important health crisis in the twenty first century. Type IV secretion systems (T4SSs) play key roles in the dissemination of AMR plasmids. Novel strategies that combat AMR problem by targeting T4SS sprung up in recent years. Here, we focus on the strategy of male-specific phages that could target and kill bacteria carrying conjugative AMR plasmids encoding T4SSs. We reviewed the recent advances in male-specific phages, including anti-conjugation mechanisms, clinical isolation and identification methods, classification and characteristics, in vitro and in vivo anti-conjugation efficacy and improving strategies. Male-specific phages constitute exciting candidates for developing sustainable anti-resistance biocontrol applications.

Distinct effect of calorie restriction between congenic mating types of Cryptococcus neoformans.

Cryptococcus neoformans (Cn) is an opportunistic yeast that causes meningoencephalitis in immunocompromised individuals. Calorie restriction (CR) prolongs Cn replicative lifespan (RLS) and mimics low-glucose environments in which Cn resides during infection. The effects of CR-mediated stress can differ among strains and have only been studied in MATα cells. Cn replicates sexually, generating two mating types, MATα and MATa. MATα strains are more dominant in clinical and environmental isolates. We sought to compare the effects of CR stress and longevity regulation between congenic MATα and MATa. Although MATα and MATa cells extended their RLS in response to CR, they engaged different pathways. The sirtuins were upregulated in MATα cells under CR, but not in MATa cells. RLS extension was SIR2-dependent in KN99α, but not in KN99a. The TOR nutrient-sensing pathway was downregulated in MATa strains under CR, while MATα strains demonstrated no difference. Lower oxidative stress and higher ATP production were observed in KN99α cells, possibly due to higher SOD expression. SIR2 was important for mitochondrial morphology and function in both mating types. Increased ATP production during CR powered the upregulated ABC transporters, increasing efflux in MATα cells. This led to enhanced fluconazole tolerance, while MATa cells remained sensitive to fluconazole. Our investigation highlights differences in the response of the mating types to CR.

Intraoperative OCT to check the correct postimplant position of PreserfloTM.

INTRODUCTION: This study was designed to examine the capacity of intraoperative optical coherence tomography (OCT) to predict the postimplant position of the glaucoma drainage device PreserfloTM. METHODS: 13 eyes (mean age 65.42 (14.89) years) underwent PreserfloTM (Santen, Osaka, Japan) placement. Before surgery, participants were subjected to a comprehensive ophthalmic examination (intraocular pressure (IOP), cup to disk ratio (C/D), visual field, OCT, endothelial cell count). Anterior segment OCT scans were obtained intraoperatively using a Rescan 700 OCT system (Carl Zeiss Meditec, Inc., Oberkochen, Germany). One day postsurgery, anterior segment OCT using the Spectralis OCT (Heidelberg Engineering GmbH) was performed in a sitting position to capture the same chamber cross-section as before. The main outcome variables were tube-endothelium distance (T-E) and tube length (TL) in the anterior chamber measured using both OCT systems. Correlation between intraoperative and office measurements was examined through Pearson correlation (r) and intraclass correlation coefficients (ICC). RESULTS: Mean intraoperative and in-office T-E were 625.26 (SD 366.60) versus 561.16 (SD 364.62) µm respectively (p = 0.540). Intraoperative and in-office anterior chamber TL were 1386 (SD 701.82) and 1433.91 (SD 713.55) µm, respectively (p = 0.029). Excellent correlation was observed between both sets of T-E (r = 0.992; p = 0.008) and TL (r = 0.984; p = 0.016) values. Both OCT systems showed good agreement yielding ICCs of 0.992 (p < 0.001) for T-E and 0.995 (p = 0.001) for TL. DISCUSSION: Excellent correlation was observed between our intraoperative and postoperative OCT measurements. These results support the usefulness of intraoperative OCT to confirm the correct position of an implanted PreserfloTM microshunt.

Synergistic removal of Staphylococcus aureus biofilms by using a combination of phage Kayvirus rodi with the exopolysaccharide depolymerase Dpo7.

Introduction: Bacteriophages have been shown to penetrate biofilms and replicate if they find suitable host cells. Therefore, these viruses appear to be a good option to tackle the biofilm problem and complement or even substitute more conventional antimicrobials. However, in order to successfully remove biofilms, in particular mature biofilms, phages may need to be administered along with other compounds. Phage-derived proteins, such as endolysins or depolymerases, offer a safer alternative to other compounds in the era of antibiotic resistance. Methods: This study examined the interactions between phage Kayvirus rodi with a polysaccharide depolymerase (Dpo7) from another phage (Rockefellervirus IPLA7) against biofilms formed by different Staphylococcus aureus strains, as determined by crystal violet staining, viable cell counts and microscopy analysis. Results and discussion: Our results demonstrated that there was synergy between the two antimicrobials, with a more significant decreased in biomass and viable cell number with the combination treatment compared to the phage and enzyme alone. This observation was confirmed by microscopy analysis, which also showed that polysaccharide depolymerase treatment reduced, but did not eliminate extracellular matrix polysaccharides. Activity assays on mutant strains did not identify teichoic acids or PNAG/PIA as the exclusive target of Dpo7, suggesting that may be both are degraded by this enzyme. Phage adsorption to S. aureus cells was not significantly altered by incubation with Dpo7, indicating that the mechanism of the observed synergistic interaction is likely through loosening of the biofilm structure. This would allow easier access of the phage particles to their host cells and facilitate infection progression within the bacterial population.

The New SH3b_T Domain Increases the Structural and Functional Variability Among SH3b-Like CBDs from Staphylococcal Phage Endolysins.

Endolysins, proteins encoded by phages to lyse their hosts and release their progeny, have evolved to adapt to the structural features of each host. The endolysins from Staphylococcus-infecting phages typically feature complex architectures with two enzymatically active domains (EADs) and one cell wall-binding domain (CBD) belonging to the bacterial SH3 (SH3b) superfamily. This study focuses on three SH3b-like CBDs from representative staphylococcal phage endolysins (LysRODI, LysC1C and LysIPLA5) that were structurally and functionally characterized. While RODI_CBD and C1C_CBD were assigned to the well-known SH3_5 family, a new family, SH3b_T (PF24246), was identified using the CBD from LysIPLA5 as a model. GFP-fused CBDs were created to assess their differential binding to a collection of staphylococcal strains. IPLA5_CBD showed enhanced binding to Staphylococcus epidermidis, while RODI_CBD and C1C_CBD exhibited distinct binding profiles, with RODI_CBD targeting Staphylococcus aureus specifically and C1C_CBD displaying broad binding. Sequence comparisons suggested that a few differences in key amino acids could be responsible for the latter binding difference. The CBDs modulated the activity spectrum of synthetic EAD-CBD combinations in accordance with the previous binding profiles, but in a manner that was also dependent on the EAD present in the fusion protein. These results serve as a context for the diversity and versatility of SH3b domains in staphylococcal endolysins, providing insights on how (i) the CBDs from this superfamily have diverged to adapt to diverse bacterial ligands in spite of sharing a common fold; and (ii) the evolution of specificity relies on the EAD-CBD combination rather than solely the CBD.

Dispersal history of SARS-CoV-2 variants Alpha, Delta, and Omicron (BA.1) in Spain.

Different factors influence the spread of SARS-CoV-2, from the inherent transmission capabilities of the different variants to the control measurements put in place. Here we studied the introduction of the Alpha, Delta, and Omicron-BA.1 variants of concern (VOCs) into Spain. For this, we collected genomic data from the GISAID database and combined it with connectivity data from different countries with Spain to perform a phylodynamic Bayesian analysis of the introductions. Our findings reveal that the introductions of these VOCs predominantly originated from France, especially in the case of Alpha. As travel restrictions were eased during the Delta and Omicron-BA.1 waves, the number of introductions from distinct countries increased, with the United Kingdom and Germany becoming significant sources of the virus. The largest number of introductions detected corresponded to the Delta wave, which was associated with fewer restrictions and the summer period, when Spain receives a considerable number of tourists. This research underscores the importance of monitoring international travel patterns and implementing targeted public health measures to manage the spread of SARS-CoV-2.

Respectful Children's Shoes: A Systematic Review.

BACKGROUND: Child footwear, both in pathologies and in normal situations, can affect the foot in various ways depending on its characteristics. Below, some features of child footwear are described, and how they can influence the foot, including suitable size, shape and design, flexibility, and transpirable material; inadequate footwear includes situations with flat foot, equine foot, and hammer toes. It is important to highlight that each child is unique and may have different footwear needs. In case of specific pathologies or concerns, it is recommended to consult a specialist in podology or foot medicine for personalized assessment and recommendations. METHODS: The present systematic review was conducted in accordance with the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. RESULTS: Children's footwear must adapt to all stages of children's growth, starting from when they begin to walk, to promote the correct evolution of their musculoskeletal system. For up to six months, they do not need to wear shoes; socks and similar clothing are enough to warm your feet like a second skin. The flexibility of respectful footwear is essential between six months and three or four years. From that age onwards, the soles can be somewhat thicker, and the buttress can have a certain firmness, but the shoes should remain flexible. CONCLUSIONS: Eco-friendly footwear, which typically comes from small businesses and factories, is sometimes described as "ergonomic footwear". However, there is some reluctance towards this term. When choosing this type of footwear for children, it is important to not just look at the label; rather, one should verify that it meets all the necessary characteristics to be considered respectful.

Oral ß-RA induces metabolic rewiring leading to the rescue of diet-induced obesity.

Obesity represents a significant health challenge, intricately linked to conditions such as type II diabetes, metabolic syndrome, and hepatic steatosis. Several existing obesity treatments exhibit limited efficacy, undesirable side effects or a limited capability to maintain therapeutics effects in the long-term. Recently, modulation Coenzyme Q (CoQ) metabolism has emerged as a promising target for treatment of metabolic syndrome. This potential intervention could involve the modulation of endogenous CoQ biosynthesis by the use of analogs of the precursor of its biosynthesis, such as ß-resorcylic acid (ß-RA). Here, we show that oral supplementation with ß-RA, incorporated into the diet of diet-induced obese (DIO) mice, leads to substantial weight loss. The anti-obesity effects of ß-RA are partially elucidated through the normalization of mitochondrial CoQ metabolism in white adipose tissue (WAT). Additionally, we identify an HFN4α/LXR-dependent transcriptomic activation of the hepatic lipid metabolism that contributes to the anti-obesity effects of ß-RA. Consequently, ß-RA mitigates WAT hypertrophy, prevents hepatic steatosis, counteracts metabolic abnormalities in WAT and liver, and enhances glucose homeostasis by reducing the insulin/glucagon ratio and plasma levels of gastric inhibitory peptide (GIP). Moreover, pharmacokinetic evaluation of ß-RA supports its translational potential. Thus, ß-RA emerges as an efficient, safe, and translatable therapeutic option for the treatment and/or prevention of obesity, metabolic dysfunction-associated steatotic liver disease (MASLD).

Cardiac stasis imaging, stroke, and silent brain infarcts in patients with nonischemic dilated cardiomyopathy.

Cardioembolic stroke is one of the most devastating complications of nonischemic dilated cardiomyopathy (NIDCM). However, in clinical trials of primary prevention, the benefits of anticoagulation are hampered by the risk of bleeding. Indices of cardiac blood stasis may account for the risk of stroke and be useful to individualize primary prevention treatments. We performed a cross-sectional study in patients with NIDCM and no history of atrial fibrillation (AF) from two sources: 1) a prospective enrollment of unselected patients with left ventricular (LV) ejection fraction <45% and 2) a retrospective identification of patients with a history of previous cardioembolic neurological event. The primary end point integrated a history of ischemic stroke or the presence intraventricular thrombus, or a silent brain infarction (SBI) by imaging. From echocardiography, we calculated blood flow inside the LV, its residence time (TR) maps, and its derived stasis indices. Of the 89 recruited patients, 18 showed a positive end point, 9 had a history of stroke or transient ischemic attack (TIA) and 9 were diagnosed with SBIs in the brain imaging. Averaged TR, [Formula: see text] performed well to identify the primary end point [AUC (95% CI) = 0.75 (0.61-0.89), P = 0.001]. When accounting only for identifying a history of stroke or TIA, AUC for [Formula: see text] was 0.92 (0.85-1.00) with odds ratio = 7.2 (2.3-22.3) per cycle, P < 0.001. These results suggest that in patients with NIDCM in sinus rhythm, stasis imaging derived from echocardiography may account for the burden of stroke.NEW & NOTEWORTHY Patients with nonischemic dilated cardiomyopathy (NIDCM) are at higher risk of stroke than their age-matched population. However, the risk of bleeding neutralizes the benefit of preventive oral anticoagulation. In this work, we show that in patients in sinus rhythm, the burden of stroke is related to intraventricular stasis metrics derived from echocardiography. Therefore, stasis metrics may be useful to personalize primary prevention anticoagulation in these patients.

Dispersal history of SARS-CoV-2 in Galicia, Spain.

The dynamics of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission are influenced by a variety of factors, including social restrictions and the emergence of distinct variants. In this study, we delve into the origins and dissemination of the Alpha, Delta, and Omicron-BA.1 variants of concern in Galicia, northwest Spain. For this, we leveraged genomic data collected by the EPICOVIGAL Consortium and from the GISAID database, along with mobility information from other Spanish regions and foreign countries. Our analysis indicates that initial introductions during the Alpha phase were predominantly from other Spanish regions and France. However, as the pandemic progressed, introductions from Portugal and the United States became increasingly significant. The number of detected introductions varied from 96 and 101 for Alpha and Delta to 39 for Omicron-BA.1. Most of these introductions left a low number of descendants (<10), suggesting a limited impact on the evolution of the pandemic in Galicia. Notably, Galicia's major coastal cities emerged as critical hubs for viral transmission, highlighting their role in sustaining and spreading the virus. This research emphasizes the critical role of regional connectivity in the spread of SARS-CoV-2 and offers essential insights for enhancing public health strategies and surveillance measures.

Management of paediatric monomorphic post-transplant lymphoproliferative disorders with low-intensity treatment: A multicentre international experience.

BACKGROUND: Monomorphic post-transplant lymphoproliferative disorder (mPTLD) is a major cause of morbidity/mortality following solid organ transplant (SOT), with infection, mPTLD progression and organ rejection presenting equal risks. Balancing these risks is challenging, and the intensity of therapy required by individual patients is not defined. Although an increasing body of evidence supports the use of a stepwise escalation of therapy through reduction in immunosuppression (RIS) to rituximab monotherapy and low-dose chemo-immunotherapy, many centres still use B-cell non-Hodgkin lymphoma (B-NHL) protocols, especially when managing Burkitt/Burkitt-like (BL) PTLD. This study sought to define outcomes for children managed in the UK or Spanish centres using low-intensity first-line treatments. PROCEDURE: Retrospective data were anonymously collected on patients younger than 18 years of age, with post-SOT mPTLD diagnosed between 2000 and 2020. Only patients given low-intensity treatment at initial diagnosis were included. RESULTS: Fifty-six patients were identified. Age range was 0.9-18 years (median 10.7). Most (62.5%) had early-onset PTLD. Haematopathological analysis showed 75% were diffuse large B-cell like, 14.3% were BL and nine of 33 (27%) harboured a MYC-rearrangement. Stage III-IV disease was present in 78.6%. All but one had RIS, 26 received rituximab monotherapy and 24 low-dose chemo-immunotherapy, mostly R-COP. Intensified B-NHL chemotherapy was required in 10/56 (17.9%). There were a total of 13 deaths in this cohort, three related to PTLD progression. The 1-year overall survival (OS), event-free survival (EFS) and progression-free survival (PFS) were 92.8%, 78.6% and 80.2%, respectively. CONCLUSIONS: R-COP provides an effective low-dose chemotherapy option. Escalation to more intensive therapies in the minority of inadequately controlled patients is an effective strategy.

4-Hydroxybenzoic acid rescues multisystemic disease and perinatal lethality in a mouse model of mitochondrial disease.

Coenzyme Q (CoQ) deficiency syndrome is conventionally treated with limited efficacy using exogenous CoQ10. Poor outcomes result from low absorption and bioavailability of CoQ10 and the clinical heterogenicity of the disease. Here, we demonstrate that supplementation with 4-hydroxybenzoic acid (4HB), the precursor of the benzoquinone ring in the CoQ biosynthetic pathway, completely rescues multisystemic disease and perinatal lethality in a mouse model of CoQ deficiency. 4HB stimulates endogenous CoQ biosynthesis in tissues of Coq2 mutant mice, normalizing mitochondrial function and rescuing cardiac insufficiency, edema, and neurodevelopmental delay. In contrast, exogenous CoQ10 supplementation falls short in fully restoring the phenotype. The treatment is translatable to human use, as proven by in vitro studies in skin fibroblasts from patients with pathogenic variants in COQ2. The therapeutic approach extends to other disorders characterized by deficiencies in the production of 4HB and early steps of CoQ biosynthesis and instances of secondary CoQ deficiency.

Crykey: Rapid identification of SARS-CoV-2 cryptic mutations in wastewater.

Wastewater surveillance for SARS-CoV-2 provides early warnings of emerging variants of concerns and can be used to screen for novel cryptic linked-read mutations, which are co-occurring single nucleotide mutations that are rare, or entirely missing, in existing SARS-CoV-2 databases. While previous approaches have focused on specific regions of the SARS-CoV-2 genome, there is a need for computational tools capable of efficiently tracking cryptic mutations across the entire genome and investigating their potential origin. We present Crykey, a tool for rapidly identifying rare linked-read mutations across the genome of SARS-CoV-2. We evaluated the utility of Crykey on over 3,000 wastewater and over 22,000 clinical samples; our findings are three-fold: i) we identify hundreds of cryptic mutations that cover the entire SARS-CoV-2 genome, ii) we track the presence of these cryptic mutations across multiple wastewater treatment plants and over three years of sampling in Houston, and iii) we find a handful of cryptic mutations in wastewater mirror cryptic mutations in clinical samples and investigate their potential to represent real cryptic lineages. In summary, Crykey enables large-scale detection of cryptic mutations in wastewater that represent potential circulating cryptic lineages, serving as a new computational tool for wastewater surveillance of SARS-CoV-2.

Stasis imaging predicts the risk of cardioembolic events related to acute myocardial infarction: the ISBITAMI study.

INTRODUCTION AND OBJECTIVES: In the setting of ST-segment elevation myocardial infarction (STEMI), imaging-based biomarkers could be useful for guiding oral anticoagulation to prevent cardioembolism. Our objective was to test the efficacy of intraventricular blood stasis imaging for predicting a composite primary endpoint of cardioembolic risk during the first 6 months after STEMI. METHODS: We designed a prospective clinical study, Imaging Silent Brain Infarct in Acute Myocardial Infarction (ISBITAMI), including patients with a first STEMI, an ejection fraction ≤ 45% and without atrial fibrillation to assess the performance of stasis metrics to predict cardioembolism. Patients underwent ultrasound-based stasis imaging at enrollment followed by heart and brain magnetic resonance at 1-week and 6-month visits. From the stasis maps, we calculated the average residence time, RT, of blood inside the left ventricle and assessed its performance to predict the primary endpoint. The longitudinal strain of the 4 apical segments was quantified by speckle tracking. RESULTS: A total of 66 patients were assigned to the primary endpoint. Of them, 17 patients had 1 or more events: 3 strokes, 5 silent brain infarctions, and 13 mural thromboses. No systemic embolisms were observed. RT (OR, 3.73; 95%CI, 1.75-7.9; P<.001) and apical strain (OR, 1.47; 95%CI, 1.13-1.92; P=.004) showed complementary prognostic value. The bivariate model showed a c-index=0.86 (95%CI, 0.73-0.95), a negative predictive value of 1.00 (95%CI, 0.94-1.00), and positive predictive value of 0.45 (95%CI, 0.37-0.77). The results were confirmed in a multiple imputation sensitivity analysis. Conventional ultrasound-based metrics were of limited predictive value. CONCLUSIONS: In patients with STEMI and left ventricular systolic dysfunction in sinus rhythm, the risk of cardioembolism may be assessed by echocardiography by combining stasis and strain imaging. Registered at ClinicalTrials.gov (NCT02917213).

EGFR amplification and EGFRvIII predict and participate in TAT-Cx43266-283 antitumor response in preclinical glioblastoma models.

BACKGROUND: Glioblastoma (GBM) commonly displays epidermal growth factor receptor (EGFR) alterations (mainly amplification and EGFRvIII) and TAT-Cx43266-283 is a Src-inhibitory peptide with antitumor properties in preclinical GBM models. Given the link between EGFR and Src, the aim of this study was to explore the role of EGFR in the antitumor effects of TAT-Cx43266-283. METHODS: The effect of TAT-Cx43266-283, temozolomide (TMZ), and erlotinib (EGFR inhibitor) was studied in patient-derived GBM stem cells (GSCs) and murine neural stem cells (NSCs) with and without EGFR alterations, in vitro and in vivo. EGFR alterations were analyzed by western blot and fluorescence in situ hybridization in these cells, and compared with Src activity and survival in GBM samples from The Cancer Genome Atlas. RESULTS: The effect of TAT-Cx43266-283 correlated with EGFR alterations in a set of patient-derived GSCs and was stronger than that exerted by TMZ and erlotinib. In fact, TAT-Cx43266-283 only affected NSCs with EGFR alterations, but not healthy NSCs. EGFR alterations correlated with Src activity and poor survival in GBM patients. Finally, tumors generated from NSCs with EGFR alterations showed a decrease in growth, invasiveness, and vascularization after treatment with TAT-Cx43266-283, which enhanced the survival of immunocompetent mice. CONCLUSIONS: Clinically relevant EGFR alterations are predictors of TAT-Cx43266-283 response and part of its mechanism of action, even in TMZ- and erlotinib-resistant GSCs. TAT-Cx43266-283 targets NSCs with GBM-driver mutations, including EGFR alterations, in an immunocompetent GBM model in vivo, suggesting a promising effect on GBM recurrence. Together, this study represents an important step toward the clinical application of TAT-Cx43266-283.

Dispersal history of SARS-CoV-2 in Galicia, Spain.

The dynamics of SARS-CoV-2 transmission are influenced by a variety of factors, including social restrictions and the emergence of distinct variants. In this study, we delve into the origins and dissemination of the Alpha, Delta, and Omicron variants of concern in Galicia, northwest Spain. For this, we leveraged genomic data collected by the EPICOVIGAL Consortium and from the GISAID database, along with mobility information from other Spanish regions and foreign countries. Our analysis indicates that initial introductions during the Alpha phase were predominantly from other Spanish regions and France. However, as the pandemic progressed, introductions from Portugal and the USA became increasingly significant. Notably, Galicia's major coastal cities emerged as critical hubs for viral transmission, highlighting their role in sustaining and spreading the virus. This research emphasizes the critical role of regional connectivity in the spread of SARS-CoV-2 and offers essential insights for enhancing public health strategies and surveillance measures.

Risk of Type 2 Diabetes in University Students at the University of Extremadura: A Cross-Sectional Study.

The prevalence of type 2 diabetes is increasing worldwide. The aim of our study was to detect people susceptible to DM among a university population aged 18 to 45 years and analyze the existence of modifiable risk factors in order to implement prevention programs, in addition to analyzing BMI data related to the variables under study. We proposed a descriptive, cross-sectional study following the recommendations of cross-sectional studies (STROBE), with a sample of 341 subjects, students enrolled at the University of Extremadura, carried out by two researchers. The research protocol was approved by the Bioethics Committee of the University of Extremadura (165/2021). The study considered the Findrisk questionnaire in Spanish, validated by the Blackboard Study, a stadiometer to measure height, a bioimpedance meter to evaluate weight and body composition parameters, and a blood pressure monitor to measure blood pressure. The results indicated that the participants had a low risk of suffering T2DM. The highest Findrisk test scores were found in those with a BMI value above 25, lower physical activity, poor dietary intake of fruits and vegetables, and increased fat mass. Our future research will be the implementation of T2DM prevention programs, acting on modifiable factors.

Effectiveness of a Serious Video Game (MOON) for Attention Deficit Hyperactivity Disorder: Protocol for a Randomized Clinical Trial.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in childhood and adolescence, with a prevalence of 5% and associated difficulties and worse prognosis if undetected. Multimodal treatment is the treatment of choice. However, sometimes treatment can be insufficient or have drawbacks. OBJECTIVE: This study protocol aims to demonstrate the effectiveness of cognitive training through the serious video game The Secret Trail of Moon (MOON) in improving emotional regulation in people with ADHD. METHODS: This is a prospective, unicenter, randomized, unblinded, pre- and postintervention study. The groups will be randomized (MOON vs control) via an electronic case report form. The MOON intervention will be performed 2 times per week for 10 weeks (30 minutes per session). The first 5 weeks (10 sessions) will be conducted face-to-face at the Puerta de Hierro University Hospital, and the remaining weeks will be conducted via the internet at the participants' homes. The total sample consists of 152 patients aged between 7 and 18 years. All participants have a clinical diagnosis of ADHD under pharmacological treatment. Data collection will be used to obtain demographic and clinical data. The data will be recorded using REDCap. Measures will be made through clinical scales for parents and objective tests of cognitive functioning in patients. Additional information on academic performance will be collected. The study has a power greater than 80% to detect differences. Student t test, 2-factor analysis of variance (ANOVA), and Mann-Whitney analyses will be performed according to each variable's characteristics. RESULTS: The study was approved by the Research Ethics Committee of the Puerta de Hierro University Hospital on December 14, 2022. As of September 26, 2023, we have enrolled 62 participants, and 31 participants have completed the study. This clinical trial was funded by the Comunidad de Madrid (IND2020/BMD-17544). The approximate completion date is March 2024. CONCLUSIONS: Serious video games such as MOON can be motivational tools that complement multimodal treatment for ADHD. TRIAL REGISTRATION: ClinicalTrials.gov; NCT06006871; https://clinicaltrials.gov/study/NCT06006871. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/53191.