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Roberto Gonzalez-Salinas,1,2 Adriano Guarnieri,3 María Concepción Guirao Navarro,3 Manuel Saenz-de-Viteri3 1Department of Biomedical Research, Universidad Autónoma de Querétaro, Querétaro, Mexico; 2Department of Research, Asociación para Evitar la Ceguera en México, Mexico City, Mexico; 3Department of Ophthalmology, Clínica Universidad de Navarra, Pamplona, Spain Abstract: Cataract, a degradation of the optical quality of the crystalline lens, progressive and age-related, is the leading cause of treatable blindness worldwide. Cataract surgery is the most common surgical procedure performed by ophthalmologists and is the only effective treatment for cataracts. Advances in the surgical techniques and better postoperative visual outcomes have progressively changed the primary concern of cataract surgery to become a procedure refined to yield the best possible refractive results. Sufficient mydriasis during cataract removal is critical to a successful surgical outcome. Poor pupil dilation can lead to serious sight-threatening complications that significantly increase the cost of surgery and decrease patients comfort. Mydriasis is obtained using anticholinergic and sympathomimetic drugs. Phenylephrine, an α1-adrenergic receptor agonist, can efficiently dilate the pupil when administered by intracameral injection. Additionally, nonsteroidal anti-inflammatory drugs (NSAIDs) like ketorolac, which inhibit the synthesis of prostaglandins, are used to decrease intraoperative miosis, control pain and inflammation associated with cataract surgery, and to prevent the development of cystoid macular edema following surgery. Recently, a new combination of phenylephrine and ketorolac (Omidria®) has been approved by United States Food and Drug Administration for use during cataract surgery to maintain intraoperative mydriasis, prevent miosis, and reduce postoperative pain and inflammation. Clinical trials have shown that this new combination is effective, combining the positive effects of both drugs with a good safety profile and patient tolerability. Moreover, recent reports suggest that this combination is also effective in patients with high risk of poor pupil dilation. In conclusion, cataract is a global problem that significantly affects patients’ quality of life. However, they can be managed with a safe and minimally invasive surgery. Advances in surgical techniques and newer pharmacological agents such as the combination of phenylephrine and ketorolac, together with better intraocular lenses, have greatly improved visual outcomes and thus patients’ expectations regarding visual recovery are also increasing. Keywords: cataract surgery, mydriasis, phenylephrine, ketorolac, Omidria®

BACKGROUND AND AIMS: An association between the polymorphism for transcription factor Sp1 in the gene COL1A1 and low bone density (BMD) and osteoporotic fractures has been described but not confirmed for all races and ages. The aim of this preliminary work was to ascertain whether this association is present in women from the Canary Islands. METHODS: Polymerase chain reaction RFLP was used to determine COL1A1 polymorphism Sp1 in 199 consecutive outpatient post-menopausal Caucasian women from the Canary Islands, aged 50-70 years. BMD was measured at lumbar spine and hip by DXA and at third lumbar vertebrae by QCT. Prevalent vertebral fractures were recorded on standard lateral X-ray film. Non-vertebral osteoporotic fractures were registered by medical record and self-reported history. Biochemical markers (serum osteocalcin, tartrate-resistant acid phosphatase), blood calcium and phosphate were also assessed. RESULTS: Distribution genotypes were 113 (50.8%) GG homozygotes, 73 (36.7%) Ss heterozygotes and 7 (3.5%) TT homozygotes. All patients with osteoporotic fractures carried the GG allele more frequently than TT homozygotic women. The odds ratio was 3.01 (95% CI 1.6-5.7) for prevalent vertebral fractures (n=62) and 2.33 (95% CI 1.2-4.4) for all osteoporotic fractures (n=65) for the T-carrying allele vs TT homozygotic women. There was no difference in BMD measured by DXA or QCT, nor in bone markers, blood calcium or phosphate. CONCLUSIONS: This preliminary study confirmed that the presence of at least one copy of the T allele is associated with osteoporotic fractures, but not with low BMD, in women from the Canary Islands. [ABSTRACT FROM AUTHOR]

In view of the lack of an effective pharmacological treatment against human anisakiosis, a disease produced by L(3) larvae of the genus Anisakis present in raw fish, we studied the in vivo larvicidal effect of certain monoterpenic derivatives against L(3) of A. simplex s.l. The aldehydic monoterpene citral and the alcoholic citronellol, when they are administered together to the larvae of the nematode at the concentration of 46.90 mg/0.5 ml in olive oil, achieve 85.90% and 67.53% dead L(3), respectively, and also stop rats suffering gastrointestinal hemorrhages produced by the larvae. [ABSTRACT FROM AUTHOR]

Background: Adverse childhood experiences (ACEs) have been associated with volume alterations of stress-related brain structures among aging and clinical populations, however, existing studies have predominantly assessed only one type of ACE, with small sample sizes, and it is less clear if these associations exist among a general population of young adults., Objective: The aims were to describe structural hippocampal volumetric differences by ACEs exposure and investigate the association between ACEs exposure and left and right hippocampal volume in a student sample of young adults., Methods: 959 young adult students (18-24 years old) completed an online questionnaire on ACEs, mental health conditions, and sociodemographic characteristics. Magnetic resonance imaging (MRI) was used to measure left and right hippocampal volume (mm 3 ). We used linear regression to explore the differences of hippocampal volumes in university students with and without ACEs., Results: Two thirds of students (65.9%) reported ACEs exposure. As ACEs exposure increased there were significant volumetric reductions in left (p < 0.0001) and right hippocampal volume (p = 0.001) and left (p = 0.0023) and right (p = 0.0013) amygdala volume. After adjusting for intracranial brain volume, sex, age, and depression diagnosis there was a negative association between ACEs exposure and left (β = -22.6, CI = -44.5, -0.7, p = 0.0412) but not right hippocampal volume (β = -18.3, CI = -39.2, 2.6, p = 0.0792). After adjusting for intracranial volume there were no associations between ACEs exposure and left (β = -9.2, CI = -26.2, 7.9 p = 0.2926) or right (β = -5.6, CI = -19.9,8.8 p = 0.4466) amygdala volume., Conclusions: Hippocampal volume varied by ACEs exposure in young adult students. ACEs appear to contribute to neuroanatomic differences in young adults from the general population., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Purpose: The recent worldwide health pandemic and related social distancing and restrictions negatively impacted adolescents' mental health, including depression, underscoring the need for comprehensive understanding beyond immediate impacts. We aimed to identify factors assessed during the first and second lockdowns that were associated with depression symptoms 2 years after restrictions easing., Methods: This study included 1,946 adolescents, aged 15-18 years, involved in the French Epidémiologie et Conditions de Vie population-based cohort. Depression symptoms were assessed twice, with the nine-item Patient Health Questionnaire, at the beginning of restrictions easing and 1 year later. Logistic regressions were used to estimate associations among sociodemographic, socioeconomics, health, substance use, lockdown conditions, and pandemic-related factors, self-reported during the first and second lockdowns in France, and depression symptoms. Elastic-Net regression was used to study the joint effect of characteristics assessed during both lockdowns., Results: A total of 472 (25.25%) adolescents reported depression symptoms in the restrictions easing period, 369 (78.18%) were girls and 103 (21.82%) were boys. Factors associated with a higher risk of reporting depression symptoms included being a girl, a smoker, frequently consuming alcohol, having spent lockdowns in a place without outdoor space, poor perceived health, and pre-existing mental disorders., Discussion: Factors associated with depression symptoms after restrictions easing were well known and mostly not related to social distancing and restrictions, suggesting that already vulnerable youth were more likely to be impacted by the stressful pandemic context. Special caution is needed for these adolescents to limit pandemic's impact on long-lasting mental health. These results also underscore the importance of early identification of at-risk adolescents and the development of interventions to enhance their resilience and support in case of future crises., (Copyright © 2024 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.)

Tumor initiation and progression rely on intricate cellular pathways that promote proliferation while suppressing differentiation, yet the importance of pathways inhibiting differentiation in cancer remains incompletely understood. Here, we reveal a novel mechanism centered on the repression of the neuronal-specific transcription factor ARNT2 by the MYC oncogene that governs the balance between proliferation and differentiation. We found that MYC coordinates the transcriptional repression of ARNT2 through the activity of polycomb repressive complex 2 (PRC2). Notably, ARNT2, highly and specifically expressed in the central nervous system, is diminished in glioblastoma, inversely correlating with patient survival. Utilizing in vitro and in vivo models, we demonstrate that ARNT2 knockout (KO) exerts no discernible effect on the in vitro proliferation of glioblastoma cells, but significantly enhances the growth of glioblastoma cells in vivo. Conversely, ARNT2 overexpression severely dampens the growth of fully transformed glioblastoma cells subcutaneously or orthotopically xenografted in mice. Mechanistically, ARNT2 depletion diminishes differentiation and enhances stemness of glioblastoma cells. Our findings provide new insights into the complex mechanisms used by oncogenes to limit differentiation in cancer cells and define ARNT2 as a tumor suppressor in glioblastoma.

Importance: Depression is a leading cause of disability. The timing and persistence of depression may be differentially associated with long-term mental health and psychosocial outcomes., Objective: To examine if depression symptoms during early and middle childhood and adolescence and persistent depression symptoms are associated with impaired young adult outcomes independent of early risk factors., Design, Setting, and Participants: Data for this prospective, longitudinal cohort study were from the Québec Longitudinal Study of Child Development, a representative population-based Canadian birth cohort. The cohort consists of infants born from October 1, 1997, to July 31, 1998. This is an ongoing study; data are collected annually or every 2 years and include those ages 5 months to 21 years. The end date for the data in this study was June 30, 2019, and data analyses were performed from October 4, 2022, to January 3, 2024., Exposures: Depression symptoms were assessed using maternal reports in early childhood (ages 1.5 to 6 years) from 1999 to 2004, teacher reports in middle childhood (ages 7 to 12 years) from 2005 to 2010, and self-reports in adolescence (ages 13 to 17 years) from 2011 to 2015., Main Outcomes and Measures: The primary outcome was depression symptoms at age 20 years, and secondary outcomes were indicators of psychosocial functioning (binge drinking; perceived stress; not being in education, employment, or training; social support; and experiencing online harrasment) at age 21 years. All outcomes were self-reported. Adult outcomes were reported by participants at ages 20 and 21 years from 2017 to 2019. Risk factors assessed when children were aged 5 months old were considered as covariates to assess the independent associations of childhood and adolescent depression symptoms with adult outcomes., Results: The cohort consisted of 2120 infants. The analytic sample size varied from 1118 to 1254 participants across outcomes (56.85% to 57.96% female). Concerning the primary outcome, adjusting for early risk factors and multiple testing, depression symptoms during adolescence were associated with higher levels of depression symptoms (β, 1.08 [95% CI, 0.84-1.32]; P < .001 unadjusted and Bonferroni adjusted) in young adulthood. Concerning the secondary outcomes, depression symptoms in adolescence were only associated with perceived stress (β, 3.63 [95% CI, 2.66-4.60]; P < .001 unadjusted and Bonferroni adjusted), while both middle-childhood (β, -1.58 [95% CI, -2.65 to -0.51]; P = .003 unadjusted and P < .001 Bonferroni adjusted) and adolescent (β, -1.97 [95% CI, -2.53 to -1.41]; P < .001 unadjusted and Bonferroni adjusted) depression symptoms were associated with lower levels of social support. There were no associations for binge drinking; not being in education, employment, or training; or experiencing online harrasment., Conclusions and Relevance: In this cohort study of Canadian children and adolescents, childhood and adolescent depression symptoms were associated with impaired adult psychosocial functioning. Interventions should aim to screen and monitor children and adolescents for depression to inform policymaking regarding young adult mental health and psychosocial outcomes.

Cancer cells exhibit distinct metabolic activities and nutritional dependencies compared to normal cells. Thus, characterization of nutrient demands by individual tumor types may identify specific vulnerabilities that can be manipulated to target the destruction of cancer cells. We find that MYC-driven liver tumors rely on augmented tryptophan (Trp) uptake, yet Trp utilization to generate metabolites in the kynurenine (Kyn) pathway is reduced. Depriving MYC-driven tumors of Trp through a No-Trp diet not only prevents tumor growth but also restores the transcriptional profile of normal liver cells. Despite Trp starvation, protein synthesis remains unhindered in liver cancer cells. We define a crucial role for the Trp-derived metabolite indole 3-pyruvate (I3P) in liver tumor growth. I3P supplementation effectively restores the growth of liver cancer cells starved of Trp. These findings suggest that I3P is a potential therapeutic target in MYC-driven cancers. Developing methods to target this metabolite represents a potential avenue for liver cancer treatment., (© 2024. The Author(s).)

Neuroblastoma poses significant challenges in clinical management. Despite its relatively low incidence, this malignancy contributes disproportionately to cancer-related childhood mortality. Tailoring treatments based on risk stratification, including MYCN oncogene amplification, remains crucial, yet high-risk cases often confront therapeutic resistance and relapse. Here, we explore the aryl hydrocarbon receptor (AHR), a versatile transcription factor implicated in diverse physiological functions such as xenobiotic response, immune modulation, and cell growth. Despite its varying roles in malignancies, AHR's involvement in neuroblastoma remains elusive. Our study investigates the interplay between AHR and its ligand kynurenine (Kyn) in neuroblastoma cells. Kyn is generated from tryptophan (Trp) by the activity of the enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO2). We found that neuroblastoma cells displayed sensitivity to the TDO2 inhibitor 680C91, exposing potential vulnerabilities. Furthermore, combining TDO2 inhibition with retinoic acid or irinotecan (two chemotherapeutic agents used to treat neuroblastoma patients) revealed synergistic effects in select cell lines. Importantly, clinical correlation analysis using patient data established a link between elevated expression of Kyn-AHR pathway genes and adverse prognosis, particularly in older children. These findings underscore the significance of the Kyn-AHR pathway in neuroblastoma progression, emphasizing its potential role as a therapeutic target., (© 2024 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

Socioeconomic status (SES) influences the risk of both physical diseases, such as asthma, and neurodevelopmental conditions, including attention-deficit/hyperactivity disorder (ADHD). Using Causal Mediation Analysis on French birth-cohort data, we found a causal pathway from SES to ADHD symptoms, in part mediated by asthma. An increase in family income at age 3 by one unit resulted in lower ADHD symptoms at age 5, by -0.37 [95% CI: -0.50, -0.24] SDQ-score-points, with additional -0.04 [95% CI: -0.08, -0.01] points reduction indirectly via asthma at age 3, both with statistical significance. Importantly, family income at age 3 exerted both direct and indirect (via asthma) negative effects on later ADHD symptoms with much higher magnitudes for the direct effect. Our findings underscore the importance of apprehending ADHD symptoms in the broader context of socioeconomic disparities, along with their comorbidities with asthma, potentially influencing public health interventions and clinical practice in managing ADHD., (© 2024. The Author(s).)

Objectives: The aim of this study was to show the process of elaboration and the results obtained of the list of "do not do" recommendations for pain management and sedoanalgesia procedures in pediatric patients within the Working Group on Analgesia and Sedation of the Spanish Society of Pediatric Emergencies (Grupo de Trabajo de Analgesia y Sedación de la Sociedad Española de Urgencias de Pediatría [GTAS-SEUP])., Methods: The process of drawing up the list was carried out in 3 phases: (1) "brainstorming," open to all members of the GTAS-SEUP; (2) selection of recommendations, after a modified Delphi methodology; and (3) drafting and consensus of the final document., Results: Initially, 57 proposed recommendations were obtained, which were reduced to 39 by unifying those that were similar. Of the 14 "do not do" in pain management, 6 were accepted: 3 in the first round and 3 in the second round. Of the 25 "do not do" recommendations for sedoanalgesia procedures, 6 were accepted: 4 in the first round and 2 in the second round. The final text consisted of 12 actions to avoid, 6 referring to pain management and 6 to sedoanalgesia procedures., Conclusions: The list of "do not do" recommendations for pain management and sedoanalgesia procedures in the pediatric patient is a consensual tool, within the GTAS-SEUP. These recommendations promote an improvement in the quality of care offered to these patients, based on avoiding unnecessary measures, which can sometimes be harmful., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The nucleolus, a membrane-less organelle, is responsible for ribosomal RNA transcription, ribosomal RNA processing, and ribosome assembly. Nucleolar size and number are indicative of a cell's protein synthesis rate and proliferative capacity, and abnormalities in the nucleolus have been linked to neurodegenerative diseases and cancer. In this study, we demonstrated that the nucleolar protein ZNF692 directly interacts with nucleophosmin 1 (NPM1). Knocking down ZNF692 resulted in the nucleolar redistribution of NPM1 in ring-like structures and reduced protein synthesis. Purified NPM1 forms spherical condensates in vitro but mixing it with ZNF692 produces irregular condensates more closely resembling living cell nucleoli. Our findings indicate that ZNF692, by interacting with NPM1, plays a critical role in regulating nucleolar architecture and function in living cells., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Balneotherapy has demonstrated clinical efficacy in the management of pathologies involving low-grade inflammation and stress. In rheumatic conditions such as osteoarthritis (OA), this therapy presents anti-inflammatory properties and potential to improve psychological well-being. Although the neurohormones serotonin and dopamine are known to be involved in these processes, surprisingly they have not been studied in this context. The objective was to evaluate the effect of a cycle of balneotherapy with peloids (pelotherapy) on circulating serotonin and dopamine concentrations in a group of aged individuals with OA, after comparing their basal state to that of an age-matched control group. In our pilot study, a pelotherapy program (10 days) was carried out in a group of 16 elderly patients with OA, evaluating its effects on circulating serotonin and dopamine concentrations (measured by ELISA). Individuals with OA showed higher levels of serotonin and lower dopamine levels, in line with the inflammatory roles of these mediators. After pelotherapy, serotonin concentrations significantly decreased, potentially contributing to the previously reported anti-inflammatory effects of balneotherapy., (© 2023. The Author(s).)

Lipase adsorption on solid supports can be mediated by a precise balance of electrostatic and hydrophobic interactions. A suitable fine-tuning could allow the immobilized enzyme to display high catalytic activity. The objective of this work was to investigate how pH and ionic strength fluctuations affected protein-support interactions during immobilization via physical adsorption of a Candida rugosa lipase (CRL) on MgFe 2 O 5 . The highest amount of immobilized protein (IP) was measured at pH 4, and an ionic strength of 90 mM. However, these immobilization conditions did not register the highest hydrolytic activity (HA) in the biocatalyst (CRLa@MgFe 2 O 4 ), finding the best values also at acidic pH but with a slight shift towards higher values of ionic strength around 110 mM. These findings were confirmed when the adsorption isotherms were examined under different immobilization conditions so that the maximum measurements of IP did not coincide with that of HA. Furthermore, when the recovered activity was examined, a strong interfacial hyperactivation of the lipase was detected towards acidic pH and highly charged surrounding environments. Spectroscopic studies, as well as in silico molecular docking analyses, revealed a considerable involvement of surface hydrophobic protein-carrier interactions, with aromatic aminoacids, especially phenylalanine residues, playing an important role. In light of these findings, this study significantly contributes to the body of knowledge and a better understanding of the factors that influence the lipase immobilization process on magnetic inorganic oxide nanoparticle surfaces., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Increased nucleolar size and activity correlate with aberrant ribosome biogenesis and enhanced translation in cancer cells. One of the first and rate-limiting steps in translation is the interaction of the 40S small ribosome subunit with mRNAs. Here, we report the identification of the zinc finger protein 692 (ZNF692), a MYC-induced nucleolar scaffold that coordinates the final steps in the biogenesis of the small ribosome subunit. ZNF692 forms a hub containing the exosome complex and ribosome biogenesis factors specialized in the final steps of 18S rRNA processing and 40S ribosome maturation in the granular component of the nucleolus. Highly proliferative cells are more reliant on ZNF692 than normal cells; thus, we conclude that effective production of small ribosome subunits is critical for translation efficiency in cancer cells., Competing Interests: Declaration of interests The authors declare no competing interest., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

In a cross sectional study of 13,837 university students, we aimed to explore the association between attention deficit hyperactivity disorder (ADHD) symptoms and lifetime psychoactive substance use (LPSU) on a wide range of illicit substances. Logistic and Hurdel multivariable regressions were used. ADHD symptoms were significantly associated with the lifetime use of ketamine, magic mushrooms, poppers, and nine other psychoactive substances. There was an association between ADHD symptoms and both LPSU and truncated count of lifetime psychoactive substance use. High levels of ADHD symptoms are associated with the use of a large variety and multiple LPSU., Competing Interests: Declaration of Competing Interest None., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The current study provides a comprehensive look of the adsorption process of Candida rugosa lipase (CRL) on Ca 2 Fe 2 O 5 iron oxide nanoparticles (NPs). Protein-support interactions were identified across a broad range of pH and ionic strengths (mM) through a response surface methodology, surface charge determination, and spectroscopic and in silico analyses. The maximum quantity of immobilized protein was achieved at an ionic strength of 50 mM and pH 4. However, this condition did not allow for the greatest hydrolytic activity to be obtained. Indeed, it was recorded at acidic pH, but at 150 mM, where evaluation of the recovered activity revealed hyperactivation of the enzyme. These findings were supported by adsorption isotherms performed under different conditions. Based on zeta potential measurements, electrostatic interactions contributed differently to protein-support binding under the conditions tested, showing a strong correlation with experimentally determined immobilization parameters. Raman spectra revealed an increase in hydrophobicity around tryptophan residues, whereas the enzyme immobilization significantly reduced the phenylalanine signal in CRL. This suggests that this residue was involved in the interaction with Ca 2 Fe 2 O 2 and molecular docking analysis confirmed these findings. Fluorescence spectroscopy showed distinct behaviors in the CRL emission patterns with the addition of Ca 2 Fe 2 O 5 at pH 4 and 7. The calculated thermodynamic parameters indicated that the contact would be mediated by hydrophobic interactions at both pHs, as well as by ionic ones at pH 4. In this approach, this work adds to our understanding of the design of biocatalysts immobilized in iron oxide NPs.

Background: Peer victimization is associated with a wide range of mental health problems in youth, yet few studies described its association with mental health comorbidities., Methods: To test the association between peer victimization timing and intensity and mental health comorbidities, we used data from 1216 participants drawn from the Quebec Longitudinal Study of Child Development, a population-based birth cohort. Peer victimization was self-reported at ages 6-17 years, and modeled as four trajectory groups: low, childhood-limited, moderate adolescence-emerging, and high-chronic. The outcomes were the number and the type of co-occurring self-reported mental health problems at age 20 years. Associations were estimated using negative binomial and multinomial logistic regression models and adjusted for parent, family, and child characteristics using propensity score inverse probability weights., Results: Youth in all peer victimization groups had higher rates of co-occurring mental health problems and higher likelihood of comorbid internalizing-externalizing problems [odds ratios ranged from 2.06, 95% confidence interval (CI) 1.52-2.79 for childhood-limited to 4.34, 95% CI 3.15-5.98 for high-chronic victimization] compared to those in the low victimization group. The strength of these associations was highest for the high-chronic group, followed by moderate adolescence-emerging and childhood-limited groups. All groups also presented higher likelihood of internalizing-only problems relative to the low peer victimization group., Conclusions: Irrespective of timing and intensity, self-reported peer victimization was associated with mental health comorbidities in young adulthood, with the strongest associations observed for high-chronic peer victimization. Tackling peer victimization, especially when persistent over time, could play a role in reducing severe and complex mental health problems in youth.

The nucleolus is a large nuclear membraneless organelle responsible for ribosome biogenesis. Ribosomes are cytoplasmic macromolecular complexes comprising RNA and proteins that link amino acids together to form new proteins. The biogenesis of ribosomes is an intricate multistep process that involves the transcription of ribosomal DNA (rDNA), the processing of ribosomal RNA (rRNA), and the assembly of rRNA with ribosomal proteins to form active ribosomes. Nearly all steps necessary for ribosome production and maturation occur in the nucleolus. Nucleolar shape, size, and number are directly linked to ribosome biogenesis. Errors in the steps of ribosomal biogenesis are sensed by the nucleolus causing global alterations in nucleolar function and morphology. This phenomenon, known as nucleolar stress, can lead to molecular changes such as stabilization of p53, which in turn activates cell cycle arrest or apoptosis. In this review, we discuss recent work on the association of nucleolar stress with degenerative diseases and developmental defects. In addition, we highlight the importance of de novo nucleotide biosynthesis for the enhanced nucleolar activity of cancer cells and discuss targeting nucleotide biosynthesis as a strategy to activate nucleolar stress to specifically target cancer cells., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: The aim of our study was to describe the prevalence of burnout syndrome (BOS) in paediatricians working in paediatric emergency care settings and to analyse its association with potential risk factors., Material and Methods: Multicentre cross-sectional study through a survey of paediatricians working in paediatric emergency care settings in hospitals affiliated to the Research Network of the Spanish Society of Paediatric Emergency Medicine (SEUP) between September 2019 and January 2020. We analysed the association between social/family-related, demographic, occupational and satisfaction factors and the presence of BOS by means of multivariate and multilevel mixed-effects logistic regression models., Results: The estimated prevalence of BOS was 36.5% (95% confidence interval [CI], 31.7 %-41.2%). In the multivariate analysis, lacking a stable group of friends (OR, 2.57; 95% CI, 1.10-5.97), problems in and out of the work setting (OR, 3.06; 95% CI, 1.60-5.88) and a work experience of 9 years or less (OR, 2.31; 95% CI, 1.37-3.90) were identified as individual factors that increased the risk of SBO, while feeling acknowledged by coworkers (OR, 0.48; 95% CI, 0.30-0.79) and acknowledged by one's supervisor (OR, 0.62; 95% CI, 0.41-0.93) were protective factors. In relation to the hospital, the paediatric emergency unit being a subdepartment of the Department of Paediatrics (OR, 3.81; 95% CI, 1.85-7.85), the presence of an on-call emergency medicine specialist around the clock (OR, 3.53; 95% CI,1.62-7.73) and a volume of 28 or more paediatric emergency encounters a day to be managed per on-call physician (OR, 2.05; 95% CI, 1.01-4.16) were identified as independent risk factors for SBO. There was no variability in the prevalence of BOS attributable to differences between hospitals and autonomous communities, save for the described situations., Conclusions: The prevalence of SBO among these providers is high. There are modifiable factors that we can intervene on to address BOS, independently of the hospital or region., (Copyright © 2022 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: Adequate pain control is essential to the comprehensive management of pediatric patients within the emergency department.The aim of this study is to evaluate parents' knowledge about pain in the pediatric population patient and secondarily describe erroneous concepts that can affect a correct children's pain management., Methods: A single-center descriptive study of cross-sectional surveys was performed between October and December 2018, with a previously validated ad hoc and anonymous questionnaire consisting of 9 items. All parents/guardians participating in the study had a child aged 0 to 18 years who had been admitted to the emergency department., Results: Sixty-nine percent (n = 315) were women, 49.9% (n = 226) had university degrees and only 11% (n = 50) had professions related to the healthcare system. A linear association was observed between the number of correct answers and the level of education (β = 1.04; 95% confidence interval, 0.76-1.32; P < 0.001), as well as between parents with professions related to the healthcare system compared with other professions (61.4% vs 51.2% with P = 0.005). The responses of Spanish parents offered better results than answers obtained from parents from the American continent (56.4% vs 41.4% with P < 0.001). No differences were observed between parents of children with chronic diseases., Conclusions: In our study, we observed that a considerable percentage of parents hold misconceptions about how children express pain, and therefore, it would be necessary to encourage formation programs for parents to help identify, evaluate, and correctly treat pain in their children., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Pain and the anxiety that it produces are the main sources of suffering in children managed in emergency departments, eliciting a growing interest in parents and health care providers in the adequate provision of sedation and analgesia. In consequence, the number of diagnostic and therapeutic procedures that require sedation and/or analgesia in paediatric emergency departments has increased in recent years, which has generated a need to train non-anaesthesiologists on how to provide this care without affecting patient safety. The objective of this document is to establish evidence-based recommendations, developed by consensus by the Working Group on Sedation and Analgesia of the Sociedad Española de Urgencias de Pediatría, regarding the competencies and training of staff who perform sedation or analgesia procedures to achieve the greatest possible quality in the management of paediatric patients before, during and after these procedures in the paediatric emergency care setting. The consensus document has been structured in two parts: the first addresses the competencies of non-anaesthesiologists who perform sedoanalgesia procedures, and the second how to obtain the necessary training. A list of research questions was prepared, keywords defined and a literature search carried out to break down and summarise the available evidence. The results are presented in the form of conclusions, which were subjected to anonymous voting by each of the members of the working group. For each of the conclusions, we provide the percent agreement obtained in the voting., (Copyright © 2022 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

The ligand-activated transcription factor aryl hydrocarbon receptor (AHR) regulates cellular detoxification, proliferation and immune evasion in a range of cell types and tissues, including cancer cells. In this study, we used RNA-sequencing to identify the signature of the AHR target genes regulated by the pollutant 2,3,7,8-tetrachlorodibenzodioxin (TCDD) and the endogenous ligand kynurenine (Kyn), a tryptophan-derived metabolite. This approach identified a signature of six genes (CYP1A1, ALDH1A3, ABCG2, ADGRF1 and SCIN) as commonly activated by endogenous or exogenous ligands of AHR in multiple colon cancer cell lines. Among these, the actin-severing protein scinderin (SCIN) was necessary for cell proliferation; SCIN downregulation limited cell proliferation and its expression increased it. SCIN expression was elevated in a subset of colon cancer patient samples, which also contained elevated β-catenin levels. Remarkably, SCIN expression promoted nuclear translocation of β-catenin and activates the WNT pathway. Our study identifies a new mechanism for adhesion-mediated signaling in which SCIN, likely via its ability to alter the actin cytoskeleton, facilitates the nuclear translocation of β-catenin. This article has an associated First Person interview with the first authors of the paper., Competing Interests: Competing interests The authors declare no competing or financial interests., (© 2022. Published by The Company of Biologists Ltd.)

Pain in children population is prevalent, but its proper diagnosis and management are frequently insufficient in pediatrics daily practice. Lack of knowledge of the professionals in charge is a recognized barrier to ensure an appropiate approach to pain in this population. Our present study reflects the current status of pain management and the challenges in diagnosis and treatment that pediatricians face in their daily work. This information is obtained from a survey made with a voluntary questionaire, desinged and distributed online by "Grupo Español para el Estudio del Dolor Pediátrico (GEEDP)" to pediatricians in Spain from october 2021 to march 2022. The final objective of the questionaire was to shed some light into the problem and find out which areas of pain management knowledge are in need of improvent., (Copyright © 2022 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

Objective: To determine the validity of the five-level TRIPED-GM pediatric triage system., Methods: Unicentric, observational, descriptive, cross-sectional study of 485 patients aged 0-16 years in the pediatric emergency department of the HGU Gregorio Marañon. Two measures of validity were used: a direct measure calculated by the sensitivity and specificity obtained based on the number of infratriages and overtriages of the priorities given by classification nurses compared with a panel of experts and another indirect measure by the length of stay, the resources consumed and the percentage of income for each priority level., Results: 10 patients were incorrectly classified, 4 (0.8%) were considered infratriages and 6 (1.2%) overtriages. The results showed a sensitivity of 99.45% (95% CI 96.5-99.97%) and a specificity of 99.01% (95% CI 96.9-99.7%) for high priorities (P2 and P3) and 98.99% (95% CI 96.8-99.6%) and 98.4% (95% CI 96.84-99.74%) respectively for low priorities (P4 and P5). The quadratic weighted Kappa index was 0.96 (95% CI 0.94-0.98; p = 0.0000). Resource consumption showed moderate Spearman correlation coefficients as the priority level increased. The percentage of admissions and the need for observation increased as the priority level p = 0,000 increased, not requiring observation or admitting any patients with priority 5., Conclusions: The TRIPED-GM pediatric triage system is valid for use in emergency departments with similar patients., (Copyright © 2021 Elsevier España, S.L.U. All rights reserved.)

Objectives: The main purpose of this study was to investigate the prevalence, characteristics, and intensity of children's pain in emergency departments. The secondary purpose was to evaluate the interobserver agreement regarding the level of pain perceived by professionals, parents, and children., Methods: This was a multicenter, survey-based research study on 0- to 18-year-old patients visiting 1 of the 15 hospitals that form part of the Working Group on Analgesia and Sedation of the Spanish Society of Pediatric Emergency Medicine between October and December 2018. The surveys recorded pain presence, intensity, characteristics, and location., Results: The study included 1216 surveys. At the time of the interview, 646 patients were experiencing pain, a prevalence of 53.1% (95% confidence interval, 50.3%-55.9%), with 25.38% reporting mild, 36.68% moderate, and 37.46% intense pain. Among the patients, 29.9% had abdominal pain and 14.1% pain in their legs.The pain lasted less than 24 hours in 48.2% of the patients, whereas only 3.0% experienced pain during more than 15 days. The parents of 50.7% of the children had provided an analgesic at home.Interrater agreement regarding pain levels was k = 0.35 between professionals and children, k = 0.38 between children and parents, and k = 0.17 between parents and professionals. For children unable to cooperate, the agreement between professional/child and the parents was k = 0.11., Conclusions: Pain is a common symptom among emergency department patients, and its evaluation should therefore be obligatory. We found low interrater agreement on pain levels between patients, professionals, and parents, which confirms how difficult it is to accurately evaluate pain intensity., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The nucleolus harbors the machinery necessary to produce new ribosomes which are critical for protein synthesis. Nucleolar size, shape, and density are highly dynamic and can be adjusted to accommodate ribosome biogenesis according to the needs for protein synthesis. In cancer, cells undergo continuous proliferation; therefore, nucleolar activity is elevated due to their high demand for protein synthesis. The transcription factor and universal oncogene MYC promotes nucleolar activity by enhancing the transcription of ribosomal DNA (rDNA) and ribosomal proteins. This review summarizes the importance of nucleolar activity in mammalian cells, MYC's role in nucleolar regulation in cancer, and discusses how a better understanding (and the potential inhibition) of aberrant nucleolar activity in cancer cells could lead to novel therapeutics.

Obesity is characterized by low-grade inflammation and more susceptibility to infection, particularly viral infections, as clearly demonstrated in COVID-19. In this context, immunometabolism and metabolic flexibility of macrophages play an important role. Since inflammation is an inherent part of the innate response, strategies for decreasing the inflammatory response must avoid immunocompromise the innate defenses against pathogen challenges. The concept "bioregulation of inflammatory/innate responses" was coined in the context of the effects of exercise on these responses, implying a reduction in excessive inflammatory response, together with the preservation or stimulation of the innate response, with good transitions between pro- and anti-inflammatory macrophages adapted to each individual's inflammatory set-point in inflammatory diseases, particularly in obesity. The question now is whether these responses can be obtained in the context of weight loss by dietary interventions (low-fat diet or abandonment of the high-fat diet) in the absence of exercise, which can be especially relevant for obese individuals with difficulties exercising such as those suffering from persistent COVID-19. Results from recent studies are controversial and do not point to a clear anti-inflammatory effect of these dietary interventions, particularly in the adipose tissue. Further research focusing on the innate response is also necessary.

Introduction: A cross-sectional descriptive study was conducted to evaluate the factor structure of Spanish translation and adaptation of the Cognitive Flexibility Inventory (CFI) in a sample of Colombian adults., Method: The sample of the study was n = 968. Respondents were aged between 18 and 52 years old (Mage=22.81, SD=4.42). Descriptive analyses, confirmatory factor analysis, and Cronbach's Alpha calculation were carried out., Results: Internal consistency for the global scale was high (α=.89). Likewise, the coefficients of the Alternative factor and the Control factor were similar (α=.90, 95% CI=.89-.90 and α=.83, 95% CI=.81-.85, respectively). A two-factor structure performed best according to the results of model selection criteria. This model suggested the existence of two correlated factors, with correlated items within factors (Item19 Item20 and Item8 Item10)., Conclusions: Overall, the results suggest that the CFI scale exhibits construct validity and adequate reliability, both for the general scale and the subscales in the Colombian sample, enabling their use in contexts such as clinical or research., Competing Interests: Conflict of interests: The authors have declared that there is no conflict of interest.

From the outset of the COVID-19 pandemic we, the nuclear medicine (NM) community, expediently mobilized to enable continuity of essential services to the best of our abilities. For example, we effectuated adapted guidelines for NM standard operating procedures (SOPs) and enacted heightened infection protection measures for staff, patients, and the public, alike. Challenges in radionuclide supply chains were identified and often met. NM procedural volumes declined globally and underwent restoration of varying degrees, contingent upon local contexts. Serial surveys have gauged and chronicled such geographical variance of the impact of COVID-19 on NM service delivery and, though it may be too early to fully understand the long-term consequences of reduced NM services, overall, we can certainly expect that this era adversely affected the management of many patients afflicted with non-communicable diseases. Today we are unquestionably better prepared to face unforeseen outbreaks, but a degree of uncertainty lingers. Which lessons learned will endure in the form of permanent NM pandemic preparedness procedures and protocols? In this spirit, the present manuscript presents a revision of prior recommendations issued mid-pandemic to NM centers, some of which may become mainstays in NM service delivery and implementation. Discussed herein are (1) comparative worldwide survey results of the measurable impact of COVID-19 on the practice of nuclear medicine (2) the definitions of a pandemic and its phases (3) relevant, recently developed or updated guidelines specific to nuclear medicine (4) incidental findings of COVID-19 on hybrid nuclear medicine studies performed primarily for oncologic indications and (5) how pertinent pedagogical methods for medical education, research, and development have been re-invented in a suddenly more virtual world. NM professionals shall indefinitely adopt many of the measures implemented during this pandemic, to enable continuity of essential services while preventing the spread of the virus. Which ones? Practices must remain ready for possible new peaks or variants of the roiling COVID-19 contagion and for the emergence of potential new pathogens that may incite future outbreaks or pandemics. Communications technologies are here to stay and will continue to be used in a broad spectrum of applications, from telemedicine to education, but how best? NM departments must align synergistically with these trends, considering what adaptations to a more virtual professional environment should not only last but be further innovated. The paper aims to provide recent history, analysis, and a springboard for continued constructive dialogue. To best navigate the future, NM must continue to learn from this crisis and must continue to bring new questions, evidence, ideas, and warranted systematic updates to the figurative table., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objectives: The objective of this study was to compare the risk of contamination for urine samples collected from patients younger than 90 days using 2 different techniques: bladder stimulation and "clean catch" (CC) and urinary catheterization (CATH)., Methods: A case-control study was carried out in the pediatric emergency room of a tertiary hospital between January 2016 and September 2017. All urine samples collected from patients younger than 90 days by CC or CATH were included. The incidence of contaminated urine samples was compared for both methods, and the risk of contamination was estimated using univariate and multivariate analyses., Results: A total of 473 urine samples were collected, 310 via CATH (65.5%) and 163 via CC (34.5%). The median age was 1.4 months (interquartile range, 0.8-2.1 months), and 54.1% were males. Seventeen patients had a history of urinary tract infection (3.6%), and 16 were diagnosed with a congenital urorenal anomaly (3.4%). Sixteen urine samples were found to be contaminated (3.4%): 5 collected via CATH (1.6%) and 11 via CC (6.8%). The univariate analysis revealed a greater risk of contamination in specimens obtained using CC versus CATH (odds ratio, 4.41; 95% confidence interval, 1.51-12.93), and the multivariate analysis confirmed CC collection as an independent risk factor for contamination (odds ratio, 5.61; 95% confidence interval, 1.83-17.19)., Conclusions: The number of contaminated urine samples in infants younger than 90 days in our pediatric emergency department is low. However, using the CC urine collection technique seems to be an independent risk factor for sample contamination., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Lipase immobilization using adsorption on magnetic nanoparticles, cross-linked enzyme aggregates (CLEA), and a combination of both techniques was investigated. Experimental designs were used for the optimization of the immobilization observing that the pH and ionic strength play a principal role during the lipase immobilization and its activity. For adsorption on magnetic nanoparticles and CLEA synthesis the optimal condition was pH and 100 mM. Besides, during the CLEA synthesis, glutaraldehyde concentration showed to be a significant effect on the enzyme activity. A comparison between a magnetic CLEA prepared with (Lip@mCLEA) and without (mCLEA) biological functionalized magnetic nanoparticles was made observing that the use of functionalized support showed the best performance activity. All biocatalytic systems developed gives to the enzyme thermal stability between 45 and 70 °C, being Lip@mCLEA the more stable biocatalyst. Similar behavior was observed at different pH, where both Lip@mCLEA and mCLEA showed stability at a range of pH 5 to 8. The immobilized biocatalysts showed the same affinity of the subtract that the free enzyme suggested that the enzyme structure not modified the active site. The combination of both types of immobilization show evidenced the importance of the biological functionalization of the support when magnetic CLEA is produced., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Competing Interests: Disclosure: The authors declare no conflict of interest.

Purpose: To report a case of bilateral iatrogenic pigmentary glaucoma secondary to cosmetic iris-lightening laser treatment., Case Report: A 39-year-old patient presented with bilateral iatrogenic pigmentary glaucoma. She had elevated intraocular pressures (IOPs), scattered iris pitting, and intense angle pigmentation secondary to the cosmetic laser treatment she underwent 4 weeks prior to presentation. Her IOPs were refractory to maximal medical treatment and she subsequently underwent trabeculectomy., Conclusion: The true scale of complications related to cosmetic laser treatments is as yet unknown. Robust clinical investigations into its safety profile, including long-term data, are required. Prospective patients should consider this with great care. Clinicians should be aware of the potential risks of this procedure, as early recognition of cosmetic laser-induced pigmentary glaucoma may avert further sequelae.

In this work, we study the development of vortical structures generated in a rotating cylinder non-homogeneously cooled on the top. In the axisymmetric regime, for moderate vertical temperature differences and any rotation rate, cyclonic and anticyclonic rotations coexist in the flow: a counterclockwise motion at upper levels, giving place to a vertical top-down vortex, and a clockwise rotation at lower levels that generates a spin up motion. For lower rotation rates and high enough vertical temperature differences, only cyclonic top-down vortices survive and get stronger. We perform a force balance analysis to explain the phenomena. In the non-axisymmetric regime, no anticyclonic rotation at the bottom is reported and the cyclonic top-down vortex either disappears or splits up in two top-down vortices, depending on the ambient rotation rate. The intensity of the cooling on the top and how localized this cool region is affect the flow developed. When the horizontal temperature difference on the top is larger than the vertical temperature difference between top and bottom, stable axisymmetric top-down vortices with an inner updraft of warmer air are reported. The more localized the cooling above, the more difficult the development of the inner updraft becomes. Results may contribute to the understanding of the relevance of thermal processes in tornadogenesis.

The Mediterranean fruit fly, Ceratitis capitata (Wied.), is an endemic pest in fruit-growing areas of the Spanish Mediterranean coast. In the Valencian Community, it represents a serious problem in the cultivation of citrus and numerous species of fruit, such as peach, cherry, apricot, persimmon, etc. For over 50 years, the Department of Agriculture of Valencia has led, promoted, and carried out a C. capitata control programme to protect crops, especially citrus fruits, because this community is the largest national producer and the leading region for fresh citrus exports in the world. Traditionally, pest control has been based on the use of insecticides. However, a reduction of more than 90% of a target wild population was achieved in the frame of a pilot integrated pest management (IPM) project based on the sterile insect technique (SIT), which was implemented from 2003 to 2006. Based on this successful result, in 2007 the Department of Agriculture of Valencia initiated an area-wide integrated pest management (AW-IPM) programme for the suppression of C. capitata , using the SIT as the primary control method. Complementary activities are implemented periodically in hotspots and during different time periods depending on the pest population dynamics. As a result, there has been a reduction of more than 90% in the use of insecticides by aerial means to control C. capitata , as well as a growth trend in exports of citrus and fresh fruits from the Valencian Community in recent years. This paper provides a historical review of the Valencian programme and briefly describes how technological innovations and decision-making tools have contributed to programme efficiency.

Importance: Although longitudinal studies have reported associations between early life factors (ie, in-utero/perinatal/infancy) and long-term suicidal behavior, they have concentrated on 1 or few selected factors, and established associations, but did not investigate if early-life factors predict suicidal behavior., Objective: To identify and evaluate the ability of early-life factors to predict suicide attempt in adolescents and young adults from the general population., Design, Setting, and Participants: This prognostic study used data from the Québec Longitudinal Study of Child Development, a population-based longitudinal study from Québec province, Canada. Participants were followed-up from birth to age 20 years. Random forest classification algorithms were developed to predict suicide attempt. To avoid overfitting, prediction performance indices were assessed across 50 randomly split subsamples, and then the mean was calculated. Data were analyzed from November 2019 to June 2020., Exposures: Factors considered in the analysis included 150 variables, spanning virtually all early life domains, including pregnancy and birth information; child, parents, and neighborhood characteristics; parenting and family functioning; parents' mental health; and child temperament, as assessed by mothers, fathers, and hospital birth records., Main Outcomes and Measures: The main outcome was self-reported suicide attempt by age 20 years., Results: Among 1623 included youths aged 20 years, 845 (52.1%) were female and 778 (47.9%) were male. Models show moderate prediction performance. The areas under the curve for the prediction of suicide attempt were 0.72 (95% CI, 0.71-0.73) for females and 0.62 (95% CI, 0.60-0.62) for males. The models showed low sensitivity (females, 0.50; males, 0.32), moderate positive predictive values (females, 0.60; males, 0.62), and good specificity (females, 0.76; males, 0.82) and negative predicted values (females, 0.75; males, 0.71). The most important factors contributing to the prediction included socioeconomic and demographic characteristics of the family (eg, mother and father education and age, socioeconomic status, neighborhood characteristics), parents' psychological state (specifically parents' antisocial behaviors) and parenting practices. Birth-related variables also contributed to the prediction of suicidal behavior (eg, prematurity). Sex differences were also identified, with family-related socioeconomic and demographic characteristics being the top factors for females and parents' antisocial behavior being the top factor for males., Conclusions and Relevance: These findings suggest that early life factors contributed modestly to the prediction of suicidal behavior in adolescence and young adulthood. Although these factors may inform the understanding of the etiological processes of suicide, their utility in the long-term prediction of suicide attempt was limited.

In recent decades, hyperthermia has been used to raise oxygenation levels in tumours undergoing other therapeutic modalities, of which radiotherapy is the most prominent one. It has been hypothesized that oxygenation increases would come from improved blood flow associated with vasodilation. However, no test has determined whether this is a relevant assumption or other mechanisms might be acting. Additionally, since hyperthermia and radiotherapy are not usually co-administered, the crucial question arises as to how temperature and perfusion in tumours will change during and after hyperthermia. Overall, it would seem necessary to find a research framework that clarifies the current knowledge, delimits the scope of the different effects and guides future research. Here, we propose a simple mathematical model to account for temperature and perfusion dynamics in brain tumours subjected to regional hyperthermia. Our results indicate that tumours in well-perfused organs like the brain might only reach therapeutic temperatures if their vasculature is highly disrupted. Furthermore, the characteristic times of return to normal temperature levels are markedly shorter than those required to deliver adjuvant radiotherapy. According to this, a mechanistic coupling of perfusion and temperature would not explain any major oxygenation boost in brain tumours immediately after hyperthermia., Competing Interests: We declare we have no competing interests., (© 2021 The Authors.)

MNT, a transcription factor of the MXD family, is an important modulator of the oncoprotein MYC. Both MNT and MYC are basic-helix-loop-helix proteins that heterodimerize with MAX in a mutually exclusive manner, and bind to E-boxes within regulatory regions of their target genes. While MYC generally activates transcription, MNT represses it. However, the molecular interactions involving MNT as a transcriptional regulator beyond the binding to MAX remain unexplored. Here we demonstrate a novel MAX-independent protein interaction between MNT and REL, the oncogenic member of the NF-κB family. REL participates in important biological processes and it is altered in a variety of tumors. REL is a transcription factor that remains inactive in the cytoplasm in an inhibitory complex with IκB and translocates to the nucleus when the NF-κB pathway is activated. In the present manuscript, we show that MNT knockdown triggers REL translocation into the nucleus and thus the activation of the NF-κB pathway. Meanwhile, MNT overexpression results in the repression of IκBα, a bona fide REL target. Both MNT and REL bind to the IκBα gene on the first exon, suggesting its regulation as an MNT-REL complex. Altogether our data indicate that MNT acts as a repressor of the NF-κB pathway by two mechanisms: (1) retention of REL in the cytoplasm by MNT interaction, and (2) MNT-driven repression of REL-target genes through an MNT-REL complex. These results widen our knowledge about MNT biological roles and reveal a novel connection between the MYC/MXD and NF-κB pathways, two of the most prominent pathways in cancer.