Targets For Intervention Research Articles

Pathways to health: A longitudinal examination of protective factors in children with and without preschool anxiety.

Preschool anxiety is highly prevalent and well known to predict risk for future psychopathology. The present study explores whether a diagnosis of an anxiety disorder in preschool interacts with (a) social skills and (b) cognitive ability to longitudinally predict psychopathology, two well-known protective factors, among a sample of 207 children measured at preschool (Mage = 4.34 years) and early childhood (Mage = 6.61 years). To assess social skills and cognitive ability, we utilized the Social Skills Rating Scale and the Differential Abilities Scale, respectively. To assess psychopathology, we utilized the parent report of the Preschool Age Psychiatric Assessment. Hierarchical linear regression models revealed significant interactions between both social skills and cognitive ability with preschool anxiety. We observed that social skills protected against emergent psychopathology for both children with and without anxiety, although this association was stronger for children with preschool anxiety. Contrastingly, cognitive ability served as a protective factor against future psychopathology primarily among children without preschool anxiety. Results from this study identify targets for future intervention and inform our understanding of how preschool anxiety, a common disorder among young children, shapes future psychopathology risk in childhood.

Cancer Therapies Targeting Cellular Metabolism.

Cancer is caused by mutations that drive aberrant growth, proliferation, and invasion, thus overriding regulatory mechanisms that normally link these processes to organismal needs and cellular physiology. This imposes demands for the production of energy and biomass and for survival in microenvironments that are often nonphysiologic and nutrient-poor, which are met by rewiring of cellular metabolism. The resultant dependence of tumor cells on altered metabolism can induce sensitivity to specific metabolic perturbations that can be exploited for cancer therapy. Some cancers are caused by mutations that impart a novel function to metabolic enzymes, leading to the production of a tumor-promoting metabolite that is dispensable in normal cells, representing an ideal therapeutic target. Tumors can also exploit metabolic regulation of cellular immunity to evade antitumor immune responses, and deciphering this biology has revealed potential targets for therapeutic intervention. Here, we discuss a number of illustrative examples highlighting the therapeutic potential and the challenges of targeting metabolism for cancer therapy.

Long-Term Moderating Effect of Resilience Capacity on the Impact of Stressful Life Events on Depressive Symptoms After 6 Years in Outpatients With Depression and/or Anxiety

Abstract Previous cross-sectional studies have utilized scales to explore potential indications of the moderating effect of resilience on the relationship between stressful life events (SLEs) and mental health. However, there remains a notable dearth of psychometrically driven models in longitudinal resilience research, especially concerning the prognosis of individuals with affective disorders and/or anxiety. This study aimed to investigate whether baseline resilience capacity, measured by the Connor-Davidson Resilience Scale, could mitigate the impact of SLEs on depressive symptoms assessed using the Beck Depression Inventory-II among 66 outpatients with depression and/or anxiety disorders during a follow-up period ranging from 4–8 years. Hierarchical linear regression analysis revealed that baseline resilience capacity significantly moderated the effect of SLEs on depressive symptoms at the end point, but neither SLEs nor baseline resilience capacity was significantly correlated with depressive symptoms at the end point after controlling for potential confounders. Patients with higher levels of baseline resilience capacity showed fewer depressive symptoms in response to SLEs. These findings underscore the potential of resilience capacity as a promising target for therapeutic interventions.

Pralatrexate represses the resistance of HCC cells to molecular targeted agents via the miRNA-34a/Notch pathway

Metabolism-related pathways are important targets for intervention in the treatment of hepatocellular carcinoma (HCC), but few studies have reported on the combination of inhibitors of folate metabolism-related enzymes and molecularly targeted drugs for HCC. The results of the present work are the first to reveal the effects of an inhibitor of dihydrofolate reductase (DHFR), pralatrexate, on the sensitivity of HCC cells to molecularly targeted agents examined using multiple assays. In HCC cells, knockdown of DHFR or treatment with pralatrexate enhanced the sensitivity of HCC cells to molecularly targeted agents, such as sorafenib, regorafenib, lenvatinib, cabozantinib, or anlotinib. Mechanically, pralatrexate decreased the methylation rates of miRNA-34a’s promoter region to enhance the expression of miRNA-34a. Treatment with pralatrexate inhibited the expression of Notch and its downstream factors by enhancing the expression of miRNA-34a in HCC cells. In clinical specimens, the expression of miRNA-34a was negatively correlated with DHFR expression, while DHFR expression was positively correlated with the Notch intracellular domain (NICD) and downstream factors of the Notch pathway. The expression of miRNA-34a was negatively correlated with DHFR expression, while the methylation rates of miRNA-34a’s promoter were positively related to DHFR. The effect of pralatrexate on the metabolic profile of HCC cells is very different from that of small molecule inhibitors related to glycolipid metabolism. Therefore, pralatrexate upregulates the sensitivity of HCC cells to molecularly targeted drugs. These results expand our understanding of folate metabolism and HCC and can help provide more options for HCC treatment.

HEAL-D Online: Exploring the potential for the spread and adoption of a virtual culturally tailored diabetes self-management programme for adults of African and Caribbean heritage.

People of African and Caribbean heritage in the UK have a higher prevalence of Type 2 Diabetes (T2D) and poorer health outcomes than white Europeans. Healthy Eating and Active Lifestyles for Diabetes Online (HEAL-D Online) is a co-designed, culturally tailored T2D self-management programme for black African and Caribbean adults, which, due to online delivery, is well positioned for spread. This qualitative evaluation uses the Exploration-Preparation-Implementation-Sustainment (EPIS) framework to explore factors affecting scale-up from delivery and commissioning perspectives. Semi-structured interviews were conducted with nine commissioners and providers of T2D services from three English areas with varying population characteristics to explore scale-up. Focus groups were held with 15 people of African and Caribbean heritage with T2D lived experience to explore the impact of a digital model of participation. Data were analysed using thematic analysis, with themes mapped onto the EPIS framework exploration phase constructs to consider the outer and inner contextual factors for planning implementation. Six EPIS constructs were identified by commissioners and providers as key in scaling HEAL-D Online. People with T2D lived experience explored the online mode of delivery, using the patient advocacy construct as the analytical lens. In delivering an online T2D programme, two themes were identified: (1) aligning course content with people's preferences; (2) practicalities to ensure online delivery was acceptable and accessible to the community. HEAL-D Online was acceptable with the potential to help address health inequalities. The EPIS framework provided a structure to understand factors in planning scale-up for an intervention targeting underserved communities.

Urinary Proteomics and Systems Biology Link Eight Proteins to the Higher Risk of Hypertension and Related Complications in Blacks Versus Whites.

Blacks are more prone to salt-sensitive hypertension than Whites. This cross-sectional analysis of a multi-ethnic cohort aimed to search for proteins potentially involved in the susceptibility to salt sensitivity, hypertension, and hypertension-related complications. The study included individuals enrolled in African Prospective Study on the Early Detection and Identification of Cardiovascular Disease and Hypertension (African-PREDICT), Flemish Study of the Environment, Genes and Health Outcomes (FLEMENGHO), Prospective Cohort Study in Patients with Type 2 Diabetes Mellitus for Validation of Biomarkers (PROVALID)-Austria, and Urinary Proteomics Combined with Home Blood Pressure Telemonitoring for Health Care Reform Trial (UPRIGHT-HTM). Sequenced urinary peptides detectable in 70% of participants allowed the identification of parental proteins and were compared between Blacks and Whites. Of 513 urinary peptides, 300 had significantly different levels among healthy Black (n=476) and White (n=483) South Africans sharing the same environment. Analyses contrasting 582 Blacks versus 1731 Whites, and Sub-Saharan Blacks versus European Whites replicated the findings. COL4A1, COL4A2, FGA, PROC, MGP, MYOCD, FYXD2, and UMOD were identified as the most likely candidates underlying the racially different susceptibility to salt sensitivity, hypertension, and related complications. Enriched pathways included hemostasis, platelet activity, collagens, biology of the extracellular matrix, and protein digestion and absorption. Our study suggests that MGP and MYOCD being involved in cardiovascular function, FGA and PROC in coagulation, FYXD2 and UMOD in salt homeostasis, and COL4A1 and COL4A2 as major components of the glomerular basement membrane are among the many proteins potentially incriminated in the higher susceptibility of Blacks compared to Whites to salt sensitivity, hypertension, and its complication. Nevertheless, these eight proteins and their associated pathways deserve further exploration in molecular and human studies as potential targets for intervention to reduce the excess risk of hypertension and cardiovascular complications in Blacks versus Whites.

Using state space grids for analysing teacher–student interaction in an intervention: The complex dynamics of teaching for musical creativity

ABSTRACT This paper highlights the use of State Space Grids (SSGs) for studying real-time classroom discourse in an intervention targeting professional development. State Space Grid analysis is both a powerful way to visualise patterns in interactional data, and a starting point for further quantitative analysis. In the present study SSGs were used to explore patterns in teacher–student interactions. The study shows the importance of using micro-level time-serial data and illustrates how change in interactions during and after an intervention can be studied. SSG analysis was applied to study interaction in terms of the coupling of a teacher and a student variable: autonomy support and musical creativity. Video data from 40 music lessons of five teachers and their classes was used as input for plotting teacher–student interactions in SSGs, consisting of two dimensions. SSGs allow visualising change in the situation of interactions in the grid and identifying change in patterns to different grid areas. The findings show how interactions tended to settle in areas representing more productive interaction for all but one class. We discuss the benefits of using SSGs in intervention studies and the implications for educational practice and research of using this time-serial approach.

The Interaction of Second Trimester Prenatal Maternal Inflammation and Psychosocial Stress on Offspring Depressive Symptoms in Adolescence

BackgroundHigher second trimester (T2) prenatal maternal inflammation (PNMI) and prenatal maternal psychosocial stress have been shown to independently contribute to offspring depression risk. Similarly, interactions between sources of inflammation and maternal daily life stress in T2, previously have been associated with increased offspring adolescent depressive symptoms. We aimed to extend previous findings by examining the potential interaction between exposure to higher T2 PNMI and maternal daily life stress on offspring depressive symptoms in adolescence. Methods614 mother-offspring dyads from the Child Health and Development Studies (CHDS) had data available for T2 maternal serum interleukin (IL)-6, IL-8, IL-1 receptor antagonist (IL-1ra), and soluble TNF receptor-II (sTNF-RII), presence/absence of maternal reported daily life stress coded from interviews primarily conducted in T2, and adolescent offspring (ages 15-18 years) depressive symptoms assessed via self-report. Interactions were evaluated using hierarchical multiple regressions, controlling for maternal education. ResultsMaternal daily life stress interacted with higher serum levels of maternal T2 IL-6 and T2 IL-8 to predict adolescent offspring depressive symptoms. Higher IL-6 and higher IL-8 were only associated with offspring depression in the presence of daily life stress. Maternal T2 IL-1ra and sTNF-RII were not associated with offspring adolescent depressive symptoms. ConclusionThe interaction of the adverse impacts of maternal daily life stress and higher maternal IL-6 and/or IL-8 levels during the second trimester may contribute significantly to exacerbate depression risk in adolescent offspring. These results have potential implications for multiple targets of future early intervention and prevention research.

Hepatitis B small surface protein hijacking Bip is initial and essential to promote lipid synthesis

To date, the molecular pathogenic mechanisms between HBsAg and liver metabolic disorders have not been fully understood. To explore the overall effects of HBsAg on liver tissues from HBV transgenic mice, proteome, interactome, and signal pathway analysis were employed to uncover the underlying mechanisms. Bioinformatics analysis of 191 differentially expressed proteins suggested that HBV upregulated the expression of multiple enzymes involved in lipid synthesis, and small HBs (SHBs) caused lipid accumulation in cells. Further studies showed that SHBs bound to binding immunoglobulin protein (Bip), which normally functions in cell homeostasis against the unfolded protein response (UPR) signaling via occupying inositol-requiring enzyme 1 (IRE1). Hijacking Bip by SHBs alleviated the inhibition of post-endoplasmic reticulum (ER) signaling and sequential activation of the IRE1 downstream transcription factors involved in lipid synthesis, such as spliced X-box binding protein 1 (sXBP1) and sterol regulatory element-binding protein 1 (SREBP1), leading to lipid metabolism disorder. The restoration of Bip can alleviate ER stress, and block the sequential post-ER signaling caused by SHBs. This study revealed a new pathway through which SHBs promote lipid disorder, and suggests that Bip may serve as a novel target for intervention in HBV related liver diseases. SignificanceIn this study, we found a new pathway promoting the lipid disorder by SHBs through quantitative proteomics studies, and Bip may serve as a novel target for intervention in HBV related liver diseases. These findings highlight a novel role of SHBs in regulating cell lipid metabolism and provide an insight into the relationship between HBV infection and liver fatty disorders, which may serve as a potential therapeutic target for intervention of HBV related liver diseases.

Exploring the gut-inflammation connection: A Mendelian randomization study on gut microbiota, inflammatory factors, and uterine fibroids risk

This study employs Mendelian randomization (MR) approach to investigate the potential causal association between genetic variants associated with gut microbiota, inflammatory factors, and the risk of uterine fibroids development. We extracted data on 211 types of gut microbiota, 91 inflammatory factors, and uterine fibroids occurrence from genome-wide association studies and applied the inverse-variance weighted (IVW) method for analysis. To further assess the robustness of our MR analysis, we conducted sensitivity tests including Cochrane’s Q test, the MR-Egger intercept test, the MR-PRESSO global test, and a leave-one-out analysis. IVW analysis identified a potential causal association between 14 types of gut microbiota and 8 inflammatory factors with the risk of uterine fibroids. When using 91 inflammation-related proteins as the outcome variable, 13 proteins demonstrated a potential causal association with uterine fibroids risk (IVW, all P < .05). Additionally, the MR-Egger intercept and MR-PRESSO global tests indicated no evidence of horizontal pleiotropy (P > .05), and the leave-one-out analysis confirmed the robustness of the results. This MR approach suggests that specific gut microbiota and inflammatory factors may have a causal association with the development of uterine fibroids, shedding light on the pathogenesis of uterine fibroids and potentially identifying targets for future therapeutic interventions.

Reduced striatal M4-cholinergic signaling following dopamine loss contributes to parkinsonian and l-DOPA-induced dyskinetic behaviors.

A dynamic equilibrium between dopamine and acetylcholine (ACh) is essential for striatal circuitry and motor function, as imbalances are associated with Parkinson's disease (PD) and levodopa-induced dyskinesia (LID). Conventional theories posit that cholinergic signaling is pathologically elevated in PD as a result of increased ACh release, which contributes to motor deficits. However, using approaches to measure receptor-mediated signaling, we found that, rather than the predicted enhancement, the strength of cholinergic transmission at muscarinic M4 receptor synapses on direct pathway medium spiny neurons was decreased in dopamine-depleted mice. This adaptation was due to a reduced postsynaptic M4 receptor function, resulting from down-regulated receptors and downstream signaling. Restoring M4 transmission unexpectedly led to a partial alleviation of motor deficits and LID dyskinetic behavior, revealing an unexpected prokinetic effect in addition to the canonical antikinetic role of M4 receptors. These findings indicate that decreased M4 function differentially contributes to parkinsonian and LID pathophysiology, representing a promising target for therapeutic intervention.

G protein-coupled estrogen receptor 1 and its role in sex-specific differences in neurological and cardiovascular diseases

Estrogen receptors (ERs) and their ligands play a crucial role in physiological and pathophysiological processes, particularly in the central nervous and cardiovascular systems. There is increasing evidence that besides the two cytosolic and nuclear ERs, namely, ERα and ERβ, the seven-transmembrane G protein-coupled ER 1 (GPER1) is of great importance in the molecular mechanisms underlying various neurological and cardiovascular diseases and is probably responsible for sex-specific differences. In contrast to ERα and ERβ, GPER1 mediates its effects through not only transcriptional regulation but also rapid nongenomic signaling. This emphasizes the role of GPER1 in the modulation of acute pathophysiological mechanisms involving changes in diverse signaling pathways related to neurological and cardiological aspects. In this review, we have summarized the role of GPER1 in disorders of excitable tissues, including neuroinflammation, learning and memory, Alzheimer’s disease, Parkinson’s disease, depression and mood disorders, schizophrenia, epilepsy, autism spectrum disorders and attention-deficit/hyperactivity disorder, migraine and pain, cardiovascular hypertension, cardiovascular function and fibrosis, hypertrophy, and atrial fibrillation, with a special focus on its involvement in sex-specific differences. We have assessed reports investigating the role of GPER1 in rodents and humans using in vivo and in vitro data. We have also reviewed the role of nutraceuticals, especially phytoestrogens, in this context. Furthermore, we have discussed the potential of GPER1 as a target for novel therapeutic interventions and prognostic indicator of neurological and cardiovascular diseases with a focus on sex-specific differences.

Built environment and chronic kidney disease: current state and future directions.

Despite emerging studies on neighborhood-level risk factors for chronic kidney disease (CKD), our understanding of the causal links between neighborhood characteristics and CKD is limited. In particular, there is a gap in identifying modifiable neighborhood factors, such as the built environment, in preventing CKD, that could be targets for feasible place-based interventions. Most published studies on neighborhood factors and CKD have focused on a single social attribute, such as neighborhood disadvantage, while research on the role of the built environment is more nascent. Early studies on this topic have yielded inconsistent results, particularly regarding whether food deserts are an environmental risk factor for CKD onset. International studies have shown that walkable neighborhoods - characterized by features such as urban design, park access, and green spaces - can be protective against both the onset and progression of CKD. However, these findings are inconclusive and understudied in the context of United States, where neighborhood environments differ from those in other countries. Future research on modifiable neighborhood factors and CKD using advanced study designs and population-representative datasets can yield stronger evidence on potential causal associations and suggest feasible place-based interventions as strategies for preventing CKD. As an example, we demonstrated the potential of electronic health record-based studies to advance research in this area.

Maintaining a sense of normality with the help of others: Lived experiences of facilitators and barriers to Lupus adjustment.

Systemic lupus erythematosus (SLE) has a high detrimental impact on individuals' quality of life. Identifying key factors associated with SLE adjustment is crucial for intervention development, yet there is no previous research exploring the perspectives of individuals with SLE regarding illness adjustment' facilitating or hindering factors. In this qualitative study, 16 individual semi-structured interviews with Portuguese adults with SLE (13 women) were conducted to explore perceived facilitators and barriers to illness adjustment. A reflexive thematic analysis revealed that efforts toward maintaining a normal life, optimism, keeping engaged in meaningful activities, accessing reliable illness-related information, and having supportive relationships were core facilitators of SLE adjustment. Main barriers included inability to maintain normality, engaging in excessive activity, pessimism, being unsupported or stigmatized, and not having access to reliable illness-related information. These findings unveil potential targets for psychosocial and behavioral interventions aimed at enhancing the quality of life for individuals with SLE.

Hypertension self-management trajectory patterns and associated factors among Chinese patients with aortic dissection after surgical repair: A longitudinal study.

In patients with aortic dissection (AD) after surgical repair, especially those with hypertension, better management of blood pressure is associated with better health outcomes. The aim of this study is to identify hypertension self-management trajectory patterns and associated factors among Chinese aortic dissection patients after surgical repair to assist in developing tailored behavioural interventions for this population. 178 patients with aortic dissection who underwent surgical repair were followed for 3 months. Data on hypertension self-management, hypertension knowledge, self-efficacy, and social support were collected before discharge and at 1 and 3 months after discharge. Sociodemographic and clinical data were also collected. A latent class growth model and generalized estimating equations were used to explore hypertension self-management trajectory patterns and factors associated with each pattern. The participants' average age was 57.95 (± 11.27) years. Two hypertension self-management trajectory patterns were identified: 'rapid ascent then suppressed growth' (93.4%) and 'continuously slow ascent' (6.6%). For the 'rapid ascent then suppressed growth' pattern, age, educational background, type of health insurance, family monthly income, self-efficacy, and social support were associated with this pattern (P < 0.05). Healthcare providers may prioritize hypertension self-management for patients who are younger, have lower educational levels, have resident or employee medical insurance and have a family monthly income between 5001 and 10 000 yuan. Self-efficacy and social support might serve as targets for future intervention to improve hypertension self-management. ChiCTR2100050542.

Dynamic transition of Tregs to cytotoxic phenotype amid systemic inflammation in Graves' ophthalmopathy.

Graves' disease (GD) is an autoimmune condition that can progress to Graves' ophthalmopathy (GO), leading to irreversible damage to orbital tissues and potential blindness. The pathogenic mechanism is not fully understood. In this study, we conducted single-cell multi-omics analyses on healthy individuals, patients with GD without GO, newly diagnosed patients with GO, and treated patients with GO. Our findings revealed gradual systemic inflammation during GO progression, marked by overactivation of cytotoxic effector T cell subsets, and expansion of specific T cell receptor clones. Importantly, we observed a decline in the immunosuppressive function of activated Treg (aTreg) accompanied by a cytotoxic phenotypic transition. In vitro experiments revealed that dysfunction and transition of GO-autoreactive Treg were regulated by the yin yang 1 (YY1) upon secondary stimulation of thyroid stimulating hormone receptor (TSHR) under inflammatory conditions. Furthermore, adoptive transfer experiments of the GO mouse model confirmed infiltration of these cytotoxic Treg into the orbital lesion tissues. Notably, these cells were found to upregulate inflammation and promote pathogenic fibrosis of orbital fibroblasts (OFs). Our results reveal the dynamic changes in immune landscape during GO progression and provide direct insights into the instability and phenotypic transition of Treg, offering potential targets for therapeutic intervention and prevention of autoimmune diseases.

Happiness with recovery from alcohol and substance use disorders predicts abstinence and treatment retention

ABSTRACT Knowledge of the association between wellbeing and substance use disorder (SUD) treatment outcomes can guide recovery definitions, measurement strategies, and intervention development. This study recruited individuals in treatment for SUD (N = 81, M = 39 years old, 53% female, 26% BIPOC). Wellbeing indicators included positive affect, serenity, flourishing, satisfaction with life, gratitude, quality of life, commitment to sobriety, and confidence staying sober. Outcomes included abstinence during treatment and treatment retention. After adjusting for urges to use, recruitment site, previous treatment episodes, legal issues, and days of sobriety in logistic regression analyses, only happiness with recovery remained significantly associated with either outcome (and was significantly associated with both outcomes: OR = 1.8 and 1.5, respectively, p < .05). Assessed via a single item (‘In general, I am happy with my recovery’), this construct shows promise as a novel, simple indicator of wellbeing in recovery and a potential target for intervention.

Liver disease-linked metabolic and behavioral factors associated with cognitive performance in an observational study of community dwelling adults

Modifiable risk factors associated with cognitive functioning are important for identifying potential targets for intervention development. Although there are a few recognized modifiable risk factors (e.g., diabetes mellitus, diet, physical activity), there are limitations in the conclusions that can be drawn due to limited data. Therefore, this study examined the relationship between modifiable liver disease-linked metabolic and behavioral factors in a sample of community dwelling adults who do not currently experience functional limitations due to cognitive abilities. Individuals aged 19 to 69 were recruited to participate in this cross-sectional study in the Washington, DC area. Participants were assessed using anthropometric measures, ultrasound of the liver, glycated hemoglobin A1C, self-reported fatigue, clinical history, and 7 domains of cognitive function: processing speed, short- and long-term visual memory, working memory, inhibition, shifting, and abstract reasoning. The study included 104 participants (44% female, 51.1 ± 13.5 years old). The modifiable factors that were most consistently related to cognitive performance were waist-to-height ratio, which was related to a decrease in performance in 4 of the domains (short-term and long-term visual memory, working memory, and abstract reasoning), and the presence of nonalcoholic fatty liver disease, which was related to an increase in performance in the same 4 domains. This study suggests that liver disease-linked modifiable factors are associated with cognitive performance, even in middle-aged individuals without self-reported cognitive dysfunction. Further research is needed to explore the mechanisms that impact cognitive performance in relation to these factors to establish early intervention targets for reducing future cognitive deficits.

The impact of behavioral weight management interventions on eating behavior traits in adults with overweight or obesity: A systematic review and meta-analysis.

Eating behavior traits (EBTs), defined as personal tendencies determining food intake, can be useful targets for behavioral weight management interventions. Previous reviews have examined the impact of specific intervention types on EBTs, not reflecting the breadth of interventions used in practice. This systematic review and meta-analysis synthesized evidence on the impact of all types of behavioral weight management interventions on EBTs. We searched seven databases and included randomized controlled trials reporting EBT outcomes following behavioral weight management interventions delivered to adults with overweight or obesity. Using random-effects meta-analyses, we synthesized findings from 27 trials at the end of intervention and 12 months (±3months) post intervention. We found evidence to suggest that interventions improved uncontrolled eating, external eating, susceptibility to hunger, restraint and intuitive eating at intervention end when compared with waitlist, minimal or usual care control. We found no evidence of effects on emotional eating, disinhibition, and hedonic hunger. At follow-up, effects on restraint remained, but we found no evidence of an effect on emotional eating, hedonic hunger and uncontrolled eating. Findings were limited by low numbers of contributing trials. More high-quality trials reporting EBTs are needed to better understand the impact of adult behavioral weight management interventions on EBTs. PROSPERO registration number: CRD42022367505.

Generation and characterization of two induced pluripotent stem cell lines (ICGi052-A and ICGi052-B) from a patient with frontotemporal dementia with parkinsonism-17 associated with the pathological variant c.2013T&gt;G in the MAPT gene

Frontotemporal dementia with parkinsonism-17 is a neurodegenerative disease characterised by pathological aggregation of the tau protein with the formation of neurofibrillary tangles and subsequent neuronal death. The inherited form of frontotemporal dementia can be caused by mutations in several genes, including the MAPT gene on chromosome 17, which encodes the tau protein. As there are currently no medically approved treatments for frontotemporal dementia, there is an urgent need for research using in vitro cell models to understand the molecular genetic mechanisms that lead to the development of the disease, to identify targets for therapeutic intervention and to test potential drugs to prevent neuronal death. Analysis of exome sequencing data from a 46-year-old patient with a clinical diagnosis of Parkinson’s disease revealed the presence of the pathological variant c.2013T&gt;G (rs63750756) in the MAPT gene, which is associated with frontotemporal dementia with parkinsonism-17. By reprogramming the patient’s peripheral blood mononuclear cells, we obtained induced pluripotent stem cells (iPSCs). Two iPSC lines were characterised in detail. Reprogramming was performed by transfection with non-integrating episomal vectors expressing the OCT4, SOX2, KLF4, LIN28, L-MYC and mp53DD proteins. The iPSC lines ICGi052-A and ICGi052-B proliferate stably, form colonies with a morphology characteristic of human pluripotent cells, have a normal diploid karyotype (46,XX), express endogenous alkaline phosphatase and pluripotency markers (OCT4, NANOG, SSEA-4 and TRA-1-60) and are able to differentiate into derivatives of three germ layers: ento-, ecto- and mesoderm. The iPSC lines obtained and characterised in detail in this work represent a unique tool for studying the molecular genetic mechanisms of the pathogenesis of frontotemporal dementia with parkinsonism-17, as well as for testing potential drugs in vitro.