Oncogene-dependent sloppiness in mRNA translation.

mRNA translation is a highly conserved and tightly controlled mechanism for protein synthesis. Despite protein quality control mechanisms, amino acid shortage in melanoma induces aberrant proteins by ribosomal frameshifting. The extent and the underlying mechanisms related to this phenomenon are yet unknown. Here, we show that tryptophan depletion-induced ribosomal frameshifting is a widespread phenomenon in cancer. We termed this event sloppiness and strikingly observed its association with MAPK pathway hyperactivation. Sloppiness is stimulated by RAS activation in primary cells, suppressed by pharmacological inhibition of the oncogenic MAPK pathway in sloppy cells, and restored in cells with acquired resistance to MAPK pathway inhibition. Interestingly, sloppiness causes aberrant peptide presentation at the cell surface, allowing recognition and specific killing of drug-resistant cancer cells by T lymphocytes. Thus, while oncogenes empower cancer progression and aggressiveness, they also expose a vulnerability by provoking the production of aberrant peptides through sloppiness.

Identifying ribosome heterogeneity using ribosome profiling.

Recent studies have revealed multiple mechanisms that can lead to heterogeneity in ribosomal composition. This heterogeneity can lead to preferential translation of specific panels of mRNAs, and is defined in large part by the ribosomal protein (RP) content, amongst other things. However, it is currently unknown to what extent ribosomal composition is heterogeneous across tissues, which is compounded by a lack of tools available to study it. Here we present dripARF, a method for detecting differential RP incorporation into the ribosome using Ribosome Profiling (Ribo-seq) data. We combine the 'waste' rRNA fragment data generated in Ribo-seq with the known 3D structure of the human ribosome to predict differences in the composition of ribosomes in the material being studied. We have validated this approach using publicly available data, and have revealed a potential role for eS25/RPS25 in development. Our results indicate that ribosome heterogeneity can be detected in Ribo-seq data, providing a new method to study this phenomenon. Furthermore, with dripARF, previously published Ribo-seq data provides a wealth of new information, allowing the identification of RPs of interest in many disease and normal contexts. dripARF is available as part of the ARF R package and can be accessed through https://github.com/fallerlab/ARF.

Rescue of Rare CFTR Trafficking Mutants Highlights a Structural Location-Dependent Pattern for Correction.

Cystic Fibrosis (CF) is a genetic disease caused by mutations in the gene encoding the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) channel. Currently, more than 2100 variants have been identified in the gene, with a large number being very rare. The approval of modulators that act on mutant CFTR protein, correcting its molecular defect and thus alleviating the burden of the disease, revolutionized the field of CF. However, these drugs do not apply to all patients with CF, especially those with rare mutations-for which there is a lack of knowledge on the molecular mechanisms of the disease and the response to modulators. In this work, we evaluated the impact of several rare putative class II mutations on the expression, processing, and response of CFTR to modulators. Novel cell models consisting of bronchial epithelial cell lines expressing CFTR with 14 rare variants were created. The variants studied are localized at Transmembrane Domain 1 (TMD1) or very close to the signature motif of Nucleotide Binding Domain 1 (NBD1). Our data show that all mutations analyzed significantly decrease CFTR processing and while TMD1 mutations respond to modulators, those localized in NBD1 do not. Molecular modeling calculations confirm that the mutations in NBD1 induce greater destabilization of CFTR structure than those in TMD1. Furthermore, the structural proximity of TMD1 mutants to the reported binding site of CFTR modulators such as VX-809 and VX-661, make them more efficient in stabilizing the CFTR mutants analyzed. Overall, our data suggest a pattern for mutation location and impact in response to modulators that correlates with the global effect of the mutations on CFTR structure.

The impact of COVID-19 lockdown on disordered eating behaviors: the mediation role of psychological distress.

PURPOSE: This study aimed to explore the early associations between the experienced psychosocial impact of the COVID-19 pandemic crisis during lockdown, depressive symptomatology, anxiety/stress levels, and disordered eating behaviors in adults during a first COVID-19 lockdown period. METHODS: This was a community-based cross-sectional study assessing 254 Portuguese adults (82.7% women; 35.82 ± 11.82 years) 1 week after the end of the first mandatory COVID-19 lockdown in Portugal. An online survey was conducted to evaluate psychological distress, disordered eating, and psychosocial impact of the COVID-19 pandemic. Pearson correlations and Structural Equation Modeling were performed. RESULTS: Participants reported the presence of meal skipping (52.8%), grazing eating behavior (80.9%), overeating (81.0%), loss of control over eating (47.2%), and binge eating episodes (39.2%) during lockdown. Structural equation modeling analyses, controlling for age and sex, indicated that there was a significant indirect effect of the experienced psychosocial impact of COVID-19 pandemic on disordered eating behaviors mediated through psychological distress. CONCLUSION: The psychosocial impact of the COVID-19 pandemic crisis may lead to disordered eating, and this relation may occur through the elevation of psychological distress. These findings can be used to inform interventions, to enhance mental health and manage disordered eating during similar future situations. Level of evidence V: cross-sectional descriptive study.

Rare Trafficking CFTR Mutations Involve Distinct Cellular Retention Machineries and Require Different Rescuing Strategies.

Most of the ~2100 CFTR variants so far reported are very rare and still uncharacterized regarding their cystic fibrosis (CF) disease liability. Since some may respond to currently approved modulators, characterizing their defect and response to these drugs is essential. Here we aimed characterizing the defect associated with four rare missense (likely Class II) CFTR variants and assess their rescue by corrector drugs. We produced CFBE cell lines stably expressing CFTR with W57G, R560S, H1079P and Q1100P, assessed their effect upon CFTR expression and maturation and their rescue by VX-661/VX-445 correctors. Results were validated by forskolin-induced swelling assay (FIS) using intestinal organoids from individuals bearing these variants. Finally, knock-down (KD) of genes previously shown to rescue F508del-CFTR was assessed on these mutants. Results show that all the variants preclude the production of mature CFTR, confirming them as Class II mutations. None of the variants responded to VX-661 but the combination rescued H1079P- and Q1100P-CFTR. The KD of factors that correct F508del-CFTR retention only marginally rescued R560S- and H1079P-CFTR. Overall, data evidence that Class II mutations induce distinct molecular defects that are neither rescued by the same corrector compounds nor recognized by the same cellular machinery, thus requiring personalized drug discovery initiatives.

Synergy in Cystic Fibrosis Therapies: Targeting SLC26A9.

SLC26A9, a constitutively active Cl- transporter, has gained interest over the past years as a relevant disease modifier in several respiratory disorders including Cystic Fibrosis (CF), asthma, and non-CF bronchiectasis. SLC26A9 contributes to epithelial Cl- secretion, thus preventing mucus obstruction under inflammatory conditions. Additionally, SLC26A9 was identified as a CF gene modifier, and its polymorphisms were shown to correlate with the response to drugs modulating CFTR, the defective protein in CF. Here, we aimed to investigate the relationship between SLC26A9 and CFTR, and its role in CF pathogenesis. Our data show that SLC26A9 expression contributes to enhanced CFTR expression and function. While knocking-down SLC26A9 in human bronchial cells leads to lower wt- and F508del-CFTR expression, function, and response to CFTR correctors, the opposite occurs upon its overexpression, highlighting SLC26A9 relevance for CF. Accordingly, F508del-CFTR rescue by the most efficient correctors available is further enhanced by increasing SLC26A9 expression. Interestingly, SLC26A9 overexpression does not increase the PM expression of non-F508del CFTR traffic mutants, namely those unresponsive to corrector drugs. Altogether, our data indicate that SLC26A9 stabilizes CFTR at the ER level and that the efficacy of CFTR modulator drugs may be further enhanced by increasing its expression.

Grazing in children: associations with child's characteristics and parental feeding practices.

PURPOSE: Grazing is a problematic eating behavior linked with poor weight loss outcomes, disordered eating psychopathology, and psychological distress in the adult population. However, no study assessed this behavior in children. Childhood is an important time frame for the development and maintenance of healthy eating habits, which can be influenced by children's psychological state, eating habits, and parental practices. This study investigates the associations between grazing behavior in children and children's psychological variables (anxiety, depression and withdrawn symptoms, body image dissatisfaction), children eating habits, and parental feeding practices. METHODS: In this cross-sectional study, 330 primary school students (6-10 years old) and their parents completed measures assessing children's grazing, anxiety/depression and withdrawn symptoms, body image dissatisfaction, children eating habits and style, and parental feeding practices. RESULTS: The path analysis tested showed that more restrictive parental feeding practices, inappropriate children eating habits, children's anxiety/depression symptoms, and body image dissatisfaction were associated with increased grazing scores (CMIN = 12.679; DF = 11; p = 0.315; RMSEA = 0.025; CFI = 0.990; NFI = 0.935; TLI = 0.982; IFI = 0.991; SRMR = 0.045). CONCLUSION: Grazing tends to occur in a context of children's psychological distress, inappropriate children eating habits, and restrictive parental feeding practices. These variables should be addressed for the improvement of healthy eating habits and in weight-loss interventions for children. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

A preliminary study on the psychosocial impact of COVID-19 lockdown in post-bariatric surgery women: the importance of eating behavior, health care access, and social support.

This study aims to characterize the psychosocial impact of COVID-19 lockdown for post-bariatric surgery (≥ 36 months) women and its association with disordered eating and psychological distress. The medium to long-time follow up is a period of increased susceptibility for poorer weight outcomes which might be triggered by the lockdown. Twenty-four participants responded to an online questionnaire and a telephone interview. About half (n = 14; 58.3%) reported perceived weight gain during the lockdown, 13 (54.1%) limited access to social support, and 12 (50%) limited access to medical care. Co-habiting with a higher number of persons during lockdown was associated with fewer difficulties in dealing with emotionally activating situations, less fear of gaining weight, less fear of losing control over eating, and less disordered eating. The global perceived psychosocial impact of lockdown was significantly correlated with difficulties in dealing with emotionally activating situations and stress symptoms. Results highlight the need to monitor post-bariatric patients, facilitate health care access, and promote social support during the lockdown period. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s12144-021-01529-6.

Mechanical Properties of Human Bronchial Epithelial Cells Expressing Wt- and Mutant CFTR.

Cystic fibrosis (CF) is caused by mutations in the gene encoding the cystic fibrosis transmembrane conductance regulator (CFTR). A single recessive mutation, the deletion of phenylalanine 508 (F508del), causes severe CF and resides on 70% of mutant chromosomes. Disorganization of the actin cytoskeleton has been previously reported in relation to the CF phenotype. In this work, we aimed to understand this alteration by means of Atomic Force Microscopy and Force Feedback Microscopy investigation of mechanical properties of cystic fibrosis bronchial epithelial (CFBE) cells stably transduced with either wild type (wt-) or F508del-CFTR. We show here that the expression of mutant CFTR causes a decrease in the cell's apparent Young modulus as compared to the expression of the wt protein.

Perceived social support before and after bariatric surgery: association with depression, problematic eating behaviors, and weight outcomes.

PURPOSE: Engaging in a healthy lifestyle after bariatric surgery is essential to optimize and sustain weight loss in the long term. There is promising evidence that social support of patients who undergo bariatric surgery plays an important role in promoting a better quality of life and adherence to the required behavioral changes and medical appointments. This study sought to investigate: (a) if post-operative patients experience different levels of perceived social support compared to pre-operative patients; (b) correlations between perceived social support, depression, disordered eating, and weight outcomes; (c) if social support is a moderator between psychological distress, and disordered eating behavior and weight outcomes. METHODS: A group of 65 patients assessed pre-surgery and another group of 65 patients assessed post-surgery (M = 26.12; SD 7.97 months since surgery) responded to a set of self-report measures assessing social support, eating disorder psychopathology, disordered eating, and depression. RESULTS: Greater social support was associated with lower depression, emotional eating, weight and shape concerns, and greater weight loss in pre- and post-surgery groups. Social support was found to be a moderator between different psychological/weight variables but only for the post-surgery group: the relation between depression and eating disorder psychopathology or weight loss was significant for patients scoring medium to high level is social support; the relation between grazing and weight regain was significant for patients scoring medium to low levels of social support. CONCLUSIONS: The associations found between perceived social support and depression, disordered eating and weight outcomes highlight the importance of considering and working with the social support network of patients undergoing bariatric surgery to optimize treatment outcomes. Level of Evidence  Level III: case-control study.

APOLO-Teens, a web-based intervention for treatment-seeking adolescents with overweight or obesity: study protocol and baseline characterization of a Portuguese sample.

PURPOSE: APOLO-Teens is an ongoing web-based program combining a manualized intervention delivered by Facebook®, a self-monitoring web application and monthly chat sessions to optimize treatment as usual for adolescents with overweight and obesity. The aims of this paper are twofold: (1) to describe the study protocol of the APOLO-Teens randomized controlled effectiveness trial and (2) to present baseline descriptive information of the Portuguese sample. METHODS: APOLO-Teens includes adolescents aged between 13 and 18 years with BMI percentile ≥ 85 (N = 210; 60.00% girls, BMI z-score 2.40 ± 0.75) undergoing hospital ambulatory treatment for overweight/obesity. Participants completed a set of self-report measures regarding eating behaviors and habits, psychological functioning (depression, anxiety, stress, and impulsivity), physical activity, and quality of life. RESULTS: Depression, anxiety, stress, impulsivity, and percentage body fat were inversely associated with health-related quality of life (rs = - 0.39 to - 0.62), while physical activity out-of-school was positively correlated with health-related quality of life (rs = 0.22). When compared to boys, girls demonstrated statistically significant higher scores on psychological distress, disturbed eating behaviors, impulsivity, were less active at school and had lower scores on the health-related quality of life (p < 0.05). CONCLUSION: The results showed that there were gender differences in key psychological constructs that are likely to determine success with the treatment and that, therefore, need to be considered in future interventions. The results of APOLO-Teens randomized controlled trial will determine the impact of these constructs on the efficacy and adherence to a web-based intervention for weight loss in the Portuguese population. LEVEL OF EVIDENCE: Level V, cross-sectional descriptive study.

Problematic eating behaviors and psychopathology in patients undergoing bariatric surgery: The mediating role of loss of control eating.

OBJECTIVE: This study compares different problematic eating behaviors (PEBs; objective [OBE]/subjective [SBE] binge-eating and compulsive [CG]/noncompulsive [NCG] grazing) in relation to the severity of loss of control (LOC) and psychopathology. We also investigate LOC as a mediator between PEBs and psychopathology. METHOD: This cross-sectional study assessed a group of patients before bariatric surgery (n = 163), and a group of bariatric patients 12 months or more after surgery (n = 131). Face-to-face assessment: Eating Disorders Examination for binge-eating episodes; Rep(eat) for grazing. LOC was measured by five questions answered in a 5-point Likert scale. Self-report measures: disordered eating, grazing, negative urgency, depression, anxiety, and stress. RESULTS: OBEs were reported by 26(8.8%), SBE by 29(9.8%), CG by 35(11.9%), and NCG by 36(12.2%) of patients. The different PEBs differed significantly in the severity of LOC (F(3,120)= 25.81, p < .001). Patients reporting OBEs scored higher and patients with NCG scored lower in most measures than patients with other PEBs. Patients with any PEBs scored higher in all self-report measures than those not reporting any PEBs, with statistical significance reached for uncontrolled eating (F(4,288)= 20.21, p < .001), emotional eating (F(4,288)= 23.10, p < .001), repetitive eating F(4,288)= 18.34, p < .001), and compulsive grazing (F(4,288)= 27.14, p < .001). LOC was found to be a full mediator between PEBs and psychopathology. DISCUSSION: There is no evidence that the different PEBs differ in the psychopathology severity, independently of the experience of LOC eating during the eating episodes. We show evidence for the conceptualization of different PEB, including grazing, on a continuous scale of LOC and psychopathology.

Repetitive eating questionnaire [Rep(eat)-Q]: Enlightening the concept of grazing and psychometric properties in a Portuguese sample.

BACKGROUND/OBJECTIVE: Grazing has been associated with poor weight loss or weight regain in obese patients undergoing bariatric surgery, but research remains scarce and complicated by the use of different non-validated measures. The aim of this paper is to describe the validation of the Rep(eat)-Q, a self-report measure developed to assess grazing, and investigates its relationship with BMI and psychopathology. SUBJECTS/METHODS: 1223 university students and community participants (non-clinical; Study A) and 154 pre-bariatric and 84 post-bariatric patients (Study B) completed a set of self-report measures, including the Rep(eat)-Q (worded in Portuguese), to assess disordered eating, depression, anxiety, stress and impulsivity. Exploratory and confirmatory factor analyses tested the factor structure; internal consistency construct, convergent and divergent validity were also tested. RESULTS: The Rep(eat)-Q scales showed good internal consistency (α ≥ 0.849) and temporal stability (rsp = 0.824, p < 0.000). Factor analyses generated two subscales: compulsive grazing and repetitive eating. Significant correlations (p < 0.05) were found between the Rep(eat)-Q and BMI in the non-clinical population and weight loss and weight regain in the bariatric sample. Generally, the correlations with psychological distress were weak (rsp < 0.4). Strong and significant (rsp≥0.4; p's < 0.05) correlations were found between compulsive grazing and eating disorder psychopathology. Repetitive eating subscale was inversely correlated with cognitive restraint (rsp -0.321, p < 0.05) and directly correlated with uncontrolled eating and emotional eating (rsp = 0.754; rsp = 0.691; p < 0.05). DISCUSSION/CONCLUSION: The Rep(eat)-Q is a valid measure to assess grazing in non-clinical and in bariatric surgery populations. Grazing can be conceptualized on the spectrum of disordered eating behavior, and appears associated with loss of control over eating. Considering the link between grazing and weight outcomes, the Rep(eat)-Q represents a necessary strategy for the systematic screening of grazing.

Adversity, emotion regulation, and non-suicidal self-injury in eating disorders.

The comorbidity between non-suicidal self-injury and eating disorder behaviors suggests that psychosocial factors may play a role in both types of behaviors. This study aimed to assess the presence of non-suicidal self-injury in 66 eating disorder patients and to analyze the associations among adversity, emotion regulation, non-suicidal self-injury, and disordered eating behavior. A total of 24 participants (36.4%) reported non-suicidal self-injury. Patients endorsing self-injury had a higher severity of disordered eating behavior. More difficulties in emotion regulation and a greater number of methods of non-suicidal self-injury were associated with a higher severity of eating pathology. Clinicians should consider these relationships in the assessment and treatment of eating disorders.

Metabolic profile and psychological variables after bariatric surgery: association with weight outcomes.

PURPOSE: This study aims to examine associations between metabolic profile and psychological variables in post-bariatric patients and to investigate if metabolic and psychological variables, namely high-density lipoprotein cholesterol (HDL-C), triglycerides (TG), glycated hemoglobin (HbA 1c), impulsivity, psychological distress, depressive and eating disorder symptoms are independently associated with percentage of excess weight loss (%EWL) after bariatric surgery. METHODS: One hundred and fifty bariatric patients (BMI = 33.04 ± 5.8 kg/m(2)) who underwent to bariatric surgery for more than 28.63 ± 4.9 months were assessed through a clinical interview, a set of self-report measures and venous blood samples. Pearson's correlations were used to assess correlations between %EWL, metabolic and psychological variables. Multiple linear regression was conducted to investigate which metabolic and psychological variables were independently associated with %EWL, while controlling for type of surgery. RESULTS: Higher TG blood levels were associated with higher disordered eating, psychological distress and depression scores. HDL-C was associated with higher depression scores. Both metabolic and psychological variables were associated with %EWL. Regression analyses showed that, controlling for type of surgery, higher % EWL is significantly and independently associated with less disordered eating symptoms and lower TG and HbA_1c blood concentrations (R (2) aj = 0.383, F (4, 82) = 14.34, p < 0.000). CONCLUSION: An association between metabolic and psychological variables, particularly concerning TG blood levels, disordered eating and psychological distress/depression was found. Only higher levels of disordered eating, TG and HbA_1c showed and independent correlation with less weight loss. Targeting maladaptive eating behaviors may be a reasonable strategy to avoid weight regain and optimize health status post-operatively.

Loss of control eating and weight outcomes after bariatric surgery: a study with a Portuguese sample.

The present study aim is to investigate the frequency of loss of control eating (LOC) episodes in three groups with different assessment times: one before, one at short and one at long-term after bariatric surgery; as well as to explore the association of postoperative problematic eating behaviors and weight outcomes and psychological characteristics. This cross-sectional study compared a group of preoperative bariatric surgery patients (n = 176) and two postoperative groups, one at short-term with <2 years follow-up (n = 110), and one at long-term >2 years follow-up (n = 53). Assessments included the EDE diagnostic interview and a set of self-report measures assessing eating disordered symptomatology, depression, and body image. We found the presence of LOC in 26.7 and 16.9 % of the pre-operative and long-term patients, respectively, and in about 11.8% of the short-term patients. One patient (0.9%) reported objective binge eating episodes at short-time, but subjective binge eating episodes were present in about 10% of the patients in all groups. LOC eating was related with the highest BMIs, the least weight loss, most weight regain, and most psychological impairment in the long-term assessments, but not at short-term. Despite the lower frequencies of disordered eating behavior in the short-term group, patients reporting LOC seem to represent a subgroup of individuals with poorest outcomes after surgery and most psychological distress.

Latent profiles of emotion regulation among university students: links to repetitive negative thinking, internet addiction, and subjective wellbeing.

Recent years have seen a deterioration in the mental health of university students and notable surge in the need for psychological support. Due to its links to psychopathology and high-risk behaviors, difficulty in emotion regulation frequently serves as a transdiagnostic dimension. This cross-sectional study used a person-centered analytical approach (latent profile analysis; LPA) to identify groups of Portuguese university students with similar profiles of emotion regulation difficulties (N = 261; Mage = 22.5 ± 1.2 years; n = 213 female) and describe how these groups differ in their presentation of repetitive negative thinking, internet addiction, and subjective wellbeing. The analyses identified four latent profiles: 14.5% of students showed global dysregulation (the Low Emotion Regulation Profile), 23% were moderately dysregulated with elevated problems in goal-directed behavior (the Moderate Emotion Regulation Profile), 8% showed specific difficulties with low emotional awareness and clarity (the Low Insight Profile), and 54.4% showed adaptive emotion regulation (the High Emotion Regulation Profile). As anticipated, the Low Emotion Regulation Profile had the lowest subjective wellbeing and the highest prevalence of repetitive negative thinking and internet addiction. Students with a Low Insight Profile also showed low subjective wellbeing, but less repetitive negative thinking compared to the Low Emotion Regulation Profile. Our findings suggest that interventions aimed at improving health and wellbeing among university students should consider each student's unique set of emotion regulation difficulties, rather than focusing on particular strategies. Further research may help determine whether emotion regulation profiles can serve as predictive indicators of varying mental health trajectories and subjective wellbeing in university students.

Diversity, habitat endemicity and trophic ecology of the fauna of Loki's Castle vent field on the Arctic Mid-Ocean Ridge.

Loki's Castle Vent Field (LCVF, 2300 m) was discovered in 2008 and represents the first black-smoker vent field discovered on the Arctic Mid-Ocean Ridge (AMOR). However, a comprehensive faunal inventory of the LCVF has not yet been published, hindering the inclusion of the Arctic in biogeographic analyses of vent fauna. There is an urgent need to understand the diversity, spatial distribution and ecosystem function of the biological communities along the AMOR, which will inform environmental impact assesments of future deep-sea mining activities in the region. Therefore, our aim with this paper is to provide a comprehensive inventory of the fauna at LCVF and present a first insight into the food web of the vent community. The fauna of LCVF has a high degree of novelty, with five new species previously described and another ten new species awaiting formal description. Most of the new species from LCVF are either hydrothermal vent specialists or have been reported from other chemosynthesis-based ecosystems. The highest taxon richness is found in the diffuse venting areas and may be promoted by the biogenic habitat generated by the foundation species Sclerolinum contortum. The isotopic signatures of the vent community of LCVF show a clear influence of chemosynthetic primary production on the foodweb. Considering the novel and specialised fauna documented in this paper, hydrothermal vents on the AMOR should be regarded as vulnerable marine ecosystems and protective measures must therefore be implemented, especially considering the potential threat from resource exploration and exploitation activities in the near future.

Loss of Control over Eating, Inhibitory Control, and Reward Sensitivity in Children and Adolescents: A Systematic Review.

OVERVIEW: In recent years, there has been increasing clinical and empirical interest in the concept of pediatric loss of control over eating, particularly about its link with the executive functions related to the concept of impulsivity, such as inhibitory control and reward sensitivity. However, there has yet to be a comprehensive literature synthesis about the associations between these variables. A comprehensive literature synthesis would help identify future research directions to advance the field in this area. Therefore, this systematic review aimed to synthesize evidence concerning the associations between loss of control over eating, inhibitory control, and reward sensitivity in children and adolescents. METHODS: The systematic review was conducted according to the guidelines proposed by PRISMA in Web of Science, Scopus, PubMed, and PsycINFO. The Quality Assessment Tool for Observational Cohort and Cross-Sectional Studies was used to assess the risk of bias. RESULTS: Twelve studies met the selection criteria and were included in the final review. Overall, methodological heterogeneity, variability in assessment methods, and the age of participants make it difficult to draw general conclusions. Nevertheless, most studies with community samples of adolescents indicate that inhibitory control difficulties are linked to the concept of loss of control eating. The presence of obesity seems to be associated with inhibitory control difficulties, regardless of the presence of loss of control eating. Studies on reward sensitivity are scarcer. However, it has been suggested that higher reward sensitivity is related to loss of control eating behaviors in young people, particularly binge eating. CONCLUSIONS: The literature on the link between loss of control eating and trait-level facets of impulsivity (low inhibitory control and higher reward sensitivity) among young people remains limited, and more studies on children are needed. Findings from this review may make healthcare professionals more aware of the potential clinical importance of targeting the trait-level facets of impulsivity and help to inform existing and future weight-loss/maintenance interventions in childhood and adolescence.

Personalized medicine: Function of CFTR variant p.Arg334Trp is rescued by currently available CFTR modulators.

Most of the 2,100 CFTR gene variants reported to date are still unknown in terms of their disease liability in Cystic Fibrosis (CF) and their molecular and cellular mechanism that leads to CFTR dysfunction. Since some rare variants may respond to currently approved modulators, characterizing their defect and response to these drugs is essential for effective treatment of people with CF (pwCF) not eligible for the current treatment. Here, we assessed how the rare variant, p.Arg334Trp, impacts on CFTR traffic and function and its response to existing CFTR modulators. To this end, we performed the forskolin-induced swelling (FIS) assay on intestinal organoids from 10 pwCF bearing the p.Arg334Trp variant in one or both alleles of the CFTR gene. In parallel, a novel p.Arg334Trp-CFTR expressing CFBE cell line was generated to characterize the variant individually. Results show that p.Arg334Trp-CFTR does not significantly affect the plasma membrane traffic of CFTR and evidences residual CFTR function. This CFTR variant is rescued by currently available CFTR modulators independently of the variant in the second allele. The study, predicting clinical benefit for CFTR modulators in pwCF with at least one p.Arg334Trp variant, demonstrates the high potential of personalized medicine through theranostics to extend the label of approved drugs for pwCF carrying rare CFTR variants. We recommend that this personalized approach should be considered for drug reimbursement policies by health insurance systems/national health services.