Feasibility Study of Taking Back Control Together, an Intervention to Support Parents of Children with Cancer.

INTRODUCTION: Parents of children with cancer can experience increased emotional distress. This study aimed to assess the feasibility (i.e., reach, treatment fidelity, and social validity) of Taking Back Control Together (TBCT). METHODS: We assessed reach with the enrollment and dropout ratios. We assessed treatment fidelity using items from existing programs, controlling for the reliability of the items. For social validity, we used an adapted version of the Treatment Evaluation Inventory and compared means with theoretical cut-points. RESULTS: 42 participants enrolled in the intervention. The enrollment and dropout ratios were 39% and 38%, respectively. Treatment fidelity was 77.3-84.3% (95%CI 75.3-86%). Acceptability (M = 90%), satisfaction (M = 87%), and relevance (M = 82%) were significantly positive. CONCLUSION: This study suggests that certain elements of TBCT need to be reassessed before the intervention is pilot tested. Although reach was likely impacted by the COVID-19 pandemic, it could be improved with some modifications to the intervention.

Do problem-solving skills help mitigate emotional distress through perceived control and self-efficacy in parents of children with cancer?

INTRODUCTION: Parents of children with cancer face psychological challenges that can result in significant distress. It has been found that problem-solving (PS) could mitigate emotional distress (ED) in this population, but mechanisms of this relation are poorly understood. This study aimed to assess whether there is a link between PS and ED through perceived control and self-efficacy. METHODS: We included 119 parents (67 mothers, 52 fathers, including 50 couples) whose child was diagnosed with cancer. We evaluated whether PS was associated with ED through perceived control and self-efficacy in couples of parents. RESULTS: We found no direct association between PS and ED (ß = -0.01, p = 0.92). Our results indicated a significant indirect effect between ED and PS with perceived control as the intermediary variable (ß = -0.24, p < 0.001, 95% CI [-0.41, -0.11]). However, there was no indirect association between ED and PS with self-efficacy as the intermediary variable (ß = -0.04, p = 0.26, 95% CI [-0.11, 0.09]). The effect size was large in magnitude (R2  = 0.59 for ED). CONCLUSION: The mitigating role of PS on ED is better explained by an enhanced experience of control than by improved self-efficacy. Future interventions should directly target the action mechanism behind PS and ED in both mothers and fathers by targeting their perceived control.

Abnormal HDL lipid and protein composition following pediatric cancer treatment: an associative study.

BACKGROUND: Long-term childhood cancer survivors (CCS) are at high risk of having dyslipidemia including low high density lipoprotein cholesterol (HDL-C). However, little is known about the prevalence of low HDL-C and the impact of therapy exposure on HDL composition early after treatment is terminated. METHODS: This associative study included 50 children and adolescents who had completed their cancer treatments (< 4 years). Clinical characteristics (demographic, diagnosis, treatment, anthropometric parameters), fasting plasma lipids, apoliporoteins (Apo) A-I and composition of HDL fractions (HDL2 and HDL3) were assessed. Data were stratified according to the presence of dyslipidemia and median doses of therapeutic agents and compared using Fisher exact or Mann-Whitney tests. Univariate binary logistic regression analyses were carried out to evaluate the associations between the clinical and biochemical characteristics and having low HDL-C. Composition of HDL2 and HDL3 particles was assessed in a sub-group of 15 patients and compared to 15 age- and sex-matched healthy controls using Wilcoxon paired test. RESULTS: Of the 50 pediatric cancer patients included in this study (mean age: 11.30 ± 0.72 y; mean time since end of treatment: 1.47 ± 0.12 y; male: 38%), 8 had low HDL-C (16%), all of which were adolescent at diagnosis. Higher doses of doxorubicin were associated with lower HDL-C and Apo A-I levels. In hypertriglyceridemic patients and compared to normolipidemics, triglycerides (TG) content was greater in HDL2 and HDL3 fractions whereas esterified cholesterol (EC) content was lower in HDL2. Enrich TG content of HDL3 and lower EC of HDL2 was found in patients exposed to ≥ 90 mg/m2 doxorubicin. Factors positively associated with the risk of having low HDL-C were age, being overweight or obese and exposure to doxorubicin ≥ 90 mg/m2. Compared to healthy controls, a sub-group of 15 patients showed higher TG and free cholesterol (FC) content of HDL2 and HDL3 and lower EC content in HDL3. CONCLUSIONS: Overall, we found abnormalities in HDL-C and Apo A-I levels and in HDL composition early after pediatric cancer treatment that are influenced by age, overweight or obesity status and exposure to doxorubicin.

Substrate oxidation during exercise in childhood acute lymphoblastic leukemia survivors.

Children with acute lymphoblastic leukemia (ALL) are at high risk of developing long-term cardiometabolic complications during their survivorship. Maximal fat oxidation (MFO) is a marker during exercise of cardiometabolic health, and is associated with metabolic risk factors. Our aim was to characterize the carbohydrate and fat oxidation during exercise in childhood ALL survivors. Indirect calorimetry was measured in 250 childhood ALL survivors to quantify substrate oxidation rates during a cardiopulmonary exercise test. A best-fit third-order polynomial curve was computed for fat oxidation rate (mg/min) against exercise intensity (%V̇O2peak) and was used to determine the MFO and the peak fat oxidation (Fatmax). The crossover point was also identified. Differences between prognostic risk groups were assessed (ie, standard risk [SR], high risk with and without cardio-protective agent dexrazoxane [HR + DEX and HR]). MFO, Fatmax and crossover point were not different between the groups (p = .078; p = .765; p = .726). Fatmax and crossover point were achieved at low exercise intensities. A higher MFO was achieved by men in the SR group (287.8 ± 111.2 mg/min) compared to those in HR + DEX (239.8 ± 97.0 mg/min) and HR groups (229.3 ± 98.9 mg/min) (p = .04). Childhood ALL survivors have low fat oxidation during exercise and oxidize carbohydrates at low exercise intensities, independently of the cumulative doses of doxorubicin they received. These findings alert clinicians on the long-term impact of cancer treatments on childhood ALL survivors' substrate oxidation.

Cardiometabolic Health After Pediatric Cancer Treatment: Adolescents Are More Affected than Children.

This cross-sectional study aimed at comparing the cardiometabolic (CM) health of children and adolescents and identifying factors associated with CM complications shortly after cancer treatment. Cancer-related characteristics, blood pressure (BP), anthropometry, and biochemical parameters were collected in 80 patients (56.3% female, mean age: 11.8 years; range: 4.5 - 21.0) a mean of 1.4 years following therapy completion. Compared to children, adolescents had higher mean z-score of insulin (-0.47 vs. 0.20; P = 0.01), HOMA-IR (-0.40 vs. 0.25; P = 0.02), waist-to-height ratio (0.36 vs. 0.84; P = 0.01), subscapular skinfold thickness (-0.19 vs. 0.47; P = 0.02), total body fat (-1.43 vs. 0.26; P < 0.01), and lower mean z-score of HDL-C (0.07 vs. -0.53; P < 0.01). Adolescents were more likely to have high BP (42% vs. 15%; P < 0.01), dyslipidemia (64% vs. 15%; P < 0.001), and cumulating ≥ 2 CM complications (42% vs. 2%; P < 0.001) than children. Adiposity indices (z-scores) were associated with high BP [odds ratio (OR) ranging from 2.11 to 4.09] and dyslipidemia (OR ranging from 2.06 to 4.34). These results suggest that adolescents have a worse CM profile than children shortly after therapy and that adiposity parameters are associated with CM complications, highliting the importance to develop intervention strategies targeting this population.

The impact of cancer on theory of planned behavior measures and physical activity levels during the first weeks following cancer diagnosis in children.

BACKGROUND: The theory of planned behavior (TPB) is used to document children's health behaviors linked to their physical activity. The TPB model and its components have been applied to comprehend the adoption of physical activity along informational and motivational parameters. Thus, this exploratory study aims to assess the evolution of children's physical activity levels (MVLPA) during the first weeks of their cancer, in addition to documenting the evolution of the TPB measures, self-reported fitness, and self-esteem in the physical domain to better understand children's physical activity behavior. METHODS: A total of 16 children (8 boys and 8 girls) with cancer answered psychosocial questionnaires at the diagnosis of cancer (time 1) and at 6 to 8 weeks (time 2) to assess the TPB measures, self-reported fitness, self-esteem in the physical domain, and their daily physical activities. RESULTS: A significant decrease of 41.2 min/days of daily MVLPA was observed between the time at cancer diagnosis (50.5 ± 32.8 min/days) and 6 to 8 weeks after the first interview (9.3 ± 9.1 min/days). We found that the time after the diagnosis of cancer negatively impacted children's TPB measures (mean in attitude, injunctive norms, identity, facilitating factors, self-confidence, and intention) and MVLPA levels. The TPB model explains 40% of the variance in MVLPA by the injunctive norms during the first weeks following cancer diagnosis in children. CONCLUSION: The findings of this study highlight the negative impacts of cancer on children's TPB measures, self-reported fitness, and self-esteem in the physical domain and self-reported MVLPA levels over 4 to 6 weeks following the diagnosis. These findings help to better understand the effect of cancer diagnosis on children's physical activity behavior.

Can phytotherapy with polyphenols serve as a powerful approach for the prevention and therapy tool of novel coronavirus disease 2019 (COVID-19)?

Much more serious than the previous severe acute respiratory syndrome (SARS) coronavirus (CoV) outbreaks, the novel SARS-CoV-2 infection has spread speedily, affecting 213 countries and causing ∼17,300,000 cases and ∼672,000 (∼+1,500/day) deaths globally (as of July 31, 2020). The potentially fatal coronavirus disease (COVID-19), caused by air droplets and airborne as the main transmission modes, clearly induces a spectrum of respiratory clinical manifestations, but it also affects the immune, gastrointestinal, hematological, nervous, and renal systems. The dramatic scale of disorders and complications arises from the inadequacy of current treatments and absence of a vaccine and specific anti-COVID-19 drugs to suppress viral replication, inflammation, and additional pathogenic conditions. This highlights the importance of understanding the SARS-CoV-2 mechanisms of actions and the urgent need of prospecting for new or alternative treatment options. The main objective of the present review is to discuss the challenging issue relative to the clinical utility of plants-derived polyphenols in fighting viral infections. Not only is the strong capacity of polyphenols highlighted in magnifying health benefits, but the underlying mechanisms are also stressed. Finally, emphasis is placed on the potential ability of polyphenols to combat SARS-CoV-2 infection via the regulation of its molecular targets of human cellular binding and replication, as well as through the resulting host inflammation, oxidative stress, and signaling pathways.

The VIE study: feasibility of a physical activity intervention in a multidisciplinary program in children with cancer.

BACKGROUND: Cancer is one of the leading causes of death in the world. The physiological and psychological benefits of physical activity have been shown in children with cancer. However, almost one in two cancer patients do not follow the physical activity guidelines. The aim of this study will be to assess the feasibility of a physical activity program intervention in pediatric oncology and to assess the barriers and facilitators to the success or failure of this physical activity program. METHODS: The VIE (valorization, implication, and education) intervention is a multidisciplinary program including physical activity, nutritional, and psychological interventions in pediatric oncology. This study involves one intervention group that will be followed over 2 years (evaluations and physical activity interventions) and one control group that will participate in only one evaluation. Children from the intervention group have been diagnosed and will be undergoing treatment at the Charles-Bruneau oncology center from the Sainte-Justine University Health Center (Montreal, Canada). The feasibility of this program will be measured through a comparison between sessions performed and sessions scheduled, while the security will be measured according to the number of reported incidents. DISCUSSION: This study will examine the effects of exercise in pediatric oncology from diagnosis to the expected end of treatment (i.e., 2 years of follow-up). Currently, there are only a few longitudinal studies on physical activity and pediatric cancer. Physiological and psychological tests will allow a better knowledge of the evolution of the physical fitness and mental health of the patients during the period of care. It is necessary to document and provide complementary knowledge in the pediatric oncology field in order to engage the discourse with pediatric oncology health professionals to help patients during and after treatment. This is an important study in the exercise and oncology field to help patients and their family during and after cancer treatments.

Assessment of Malnutrition Risk in Canadian Pediatric Hospitals: A Multicenter Prospective Cohort Study.

OBJECTIVE: To assess the prevalence, causes, and consequences of malnutrition, as well as the evolution of nutritional status, in Canadian pediatric health care institutions. STUDY DESIGN: In this multicenter prospective cohort study, a total of 371 patients were recruited from pediatric hospitals in 5 Canadian provinces. Subjects were aged 1 month to 18 years; admitted to a medical, surgical, or oncology ward; and had a planned hospital stay of >48 hours. Data on demographics, medical condition, anthropometric measures, and dietary intake were collected. The Screening Tool Risk on Nutritional Status and Growth (STRONGkids) and Subjective Global Nutritional Assessment (SGNA) were applied at admission. Malnutrition was defined as a weight-for-age, height-for-age, body mass index-for-age, or weight-for-length/height z score <-2 SD. RESULTS: Among 307 subjects (median age, 5.3 years; median length of stay, 5 days), 19.5% were malnourished on admission. Both STRONGkids and SGNA classifications were associated with baseline nutritional status. Mean weight-for-age z score was lower at discharge compared with admission (-0.14 vs -0.09; P < .01), and nearly one-half of all patients lost weight during their hospital stay. Only one-half of the children who were malnourished or screened as high risk of malnutrition were visited by a dietitian during their stay. The percentage of patients who lost weight during hospitalization was significantly greater in the group not visited by a dietitian (76.5 vs 23.5%; P < .01). CONCLUSION: Nutritional status deterioration and malnutrition are common in hospitalized Canadian children. Screening tools, anthropometric measurements, and dietitian consultation should be used to establish adequate nutritional support.

A Bayesian multivariate latent t-regression model for assessing the association between corticosteroid and cranial radiation exposures and cardiometabolic complications in survivors of childhood acute lymphoblastic leukemia: a PETALE study.

BACKGROUND: Childhood acute lymphoblastic leukemia (cALL) is the most frequent pediatric cancer. Over the past decades, treatment of cALL has significantly improved, with cure rates close to 90%. However intensive chemotherapy and cranial radiotherapy (CRT) during a critical period of a child's development have been shown to lead to significant long-term side effects including cardiometabolic complications. Using the PETALE (Prévenir les effets tardifs des traitements de la leucémie aiguë lymphoblastique chez l'enfant) cALL survivor cohort, we investigated the association between combined cumulative corticosteroids (CS) doses and CRT exposures and obesity, insulin resistance, (pre-)hypertension, and dyslipidemia jointly. METHODS: A Bayesian multivariate latent-t model which accounted for our correlated binary outcomes was used for the analyses (n = 241 survivors). CS doses were categorized as low (LD) or high (HD). Combined exposure levels investigated were: 1) LD/no CRT; 2) LD/CRT, and; 3) HD/CRT. We also performed complementary sensitivity analyses for covariate adjustment. RESULTS: Prevalence of cardiometabolic complications ranged from 12.0% for (pre-)hypertension to 40.2% for dyslipidemia. The fully adjusted odds ratio (OR) for dyslipidemia associated with LD/CRT (vs. LD/No CRT) was OR = 1.98 (95% credible interval (CrI): 1.02 to 3.88). LD/CRT level also led to a 0.15 (95% CrI: 0.00 to 0.29) excess risk to develop at least one cardiometabolic complication. Except for obesity, adjusted results for the highest exposure category HD/CRT were generally similar to those for LD/CRT albeit not statistically significant. White blood cell count at diagnosis, a proxy for cALL burden at diagnosis, was found associated with insulin resistance (OR = 1.08 for a 10-unit increase (× 109/L), 95% CrI: 1.02 to 1.14). CONCLUSIONS: Our results indicated that combined LD/CRT exposure is a likely determinant of dyslipidemia among cALL survivors. No evidence was found to suggest that high doses of CS lead to additional risk for obesity, insulin resistance, (pre-)hypertension, and dyslipidemia beyond that induced by CRT. The multivariate model selected for analyses was judged globally useful to assess potential exposure-related concomitance of binary outcomes.

Prevention of Long-term Adverse Health Outcomes With Cardiorespiratory Fitness and Physical Activity in Childhood Acute Lymphoblastic Leukemia Survivors.

BACKGROUND: Most childhood acute lymphoblastic leukemia (ALL) survivors develop chronic treatment-related adverse effects several years after the end of therapy. A regular practice of physical activity and a good cardiorespiratory fitness have the potential to reduce the risk of chronic disease and improve quality of life. The aim of this study was to evaluate in a cohort of ALL survivors, the association between a good cardiorespiratory fitness or the respect of physical activity guidelines and major long-term health outcomes. METHODS: In total, 247 ALL survivors underwent a cardiopulmonary exercise test, completed a physical activity questionnaire and a battery of clinical examinations. We calculated the odds ratio to obtain the preventive fraction (PF) to evaluate the effects of the cardiorespiratory fitness and physical activity levels on health outcomes (ie, obesity, metabolic health, cardiac health, cognitive health and mood, bone health). RESULTS: Despite their young age, 88% of the participants presented at least one adverse health outcome, and 46% presented ≥3. Their cardiorespiratory fitness was also lower than expected with a median VO2 peak reaching 84% of the predicted value. In the analyses using cardiorespiratory fitness, statistically significant PFs were observed for obesity (0.30), low-high-density lipoprotein-cholesterol (0.21) and depression (0.26). In the physical activity level analyses, statistically significant PFs were observed for obesity, depression, and low bone mineral density, with a PF of 0.55, 0.81, and 0.60, respectively. CONCLUSIONS: Our results indicate that a good cardiorespiratory fitness and physical activity level induced a preventive action for most health outcomes studied and was associated with a lower late adverse effects prevalence in ALL survivors.

Psychosocial Intervention Programs for Parents of Children with Cancer: A Systematic Review and Critical Comparison of Programs' Models and Development.

Intervention programs have been developed to help parents cope with their child's cancer. Despite some studies reporting a high level of evidence, it is unclear how these programs build on each other. Appraising models of change is critical to advance scientific knowledge and provide evidence-based interventions. This review aims to identify existing programs, explicitly formulate their underlying models, evaluate how they translate into concrete activities, as well as identify and discuss their development process. Eleven programs based on models of change from cognitive-behavioral, systemic and counselling theories were identified. Many models included a sound theoretical framework, targeted outcomes, as well as implementation strategies. In most cases, preliminary development studies were conducted, but details were rarely provided on how development stages informed the redesign of intervention programs. Acceptability and treatment fidelity were not available for one-third of the programs. Future reports should document the development and design redesign stages prior to conducting efficacy trials, as this step would provide crucial details to critically appraise programs.

Development and relative validation of a food frequency questionnaire for French-Canadian adolescent and young adult survivors of acute lymphoblastic leukemia.

BACKGROUND: Survivors of childhood acute lymphoblastic leukemia (cALL) experience cardiometabolic and bone complications after treatments. This study aimed at developing and validating an interview-administrated food frequency questionnaire (FFQ) that will serve to estimate the impact of nutrition in the development of long-term sequalea of French-Canadian cALL survivors. METHODS: The FFQ was developed to assess habitual diet, Mediterranean diet score, nutrients promoting bone health and antioxidants. It was validated using a 3-day food record (3-DFR) in 80 cALL survivors (50% male) aged between 11.4 and 40.1 years (median of 18.0 years). Reproducibility was evaluated by comparing FFQs from visit 1 and 2 in 29 cALL survivors. RESULTS: When compared to 3-DFR, the mean values for macro- and micronutrient intake were overestimated by our FFQ with the exception of lipid-related nutrients. Correlations between nutrient intakes derived from the FFQs and the 3-DFRs showed moderate to very good correlations (0.46-0.74). Intraclass correlation coefficients assessing FFQ reproducibility ranged from 0.62 to 0.92, indicating moderate to good reliability. Furthermore, classification into quartiles showed more than 75% of macro- and micronutrients derived from FFQs 1 and 2 classified into the same or adjacent quartile. CONCLUSIONS: Overall, our results support the reproducibility and accuracy of the developed FFQ to appropriately classify individuals according to their dietary intake. This validated tool will be valuable for future studies analyzing the impact of nutrition on cardiometabolic and bone complications in French-speaking populations.

Lipid and lipoprotein abnormalities in acute lymphoblastic leukemia survivors.

Survivors of acute lymphoblastic leukemia (ALL), the most common cancer in children, are at increased risk of developing late cardiometabolic conditions. However, the mechanisms are not fully understood. This study aimed to characterize the plasma lipid profile, Apo distribution, and lipoprotein composition of 80 childhood ALL survivors compared with 22 healthy controls. Our results show that, despite their young age, 50% of the ALL survivors displayed dyslipidemia, characterized by increased plasma triglyceride (TG) and LDL-cholesterol, as well as decreased HDL-cholesterol. ALL survivors exhibited lower plasma Apo A-I and higher Apo B-100 and C-II levels, along with elevated Apo C-II/C-III and B-100/A-I ratios. VLDL fractions of dyslipidemic ALL survivors contained more TG, free cholesterol, and phospholipid moieties, but less protein. Differences in Apo content were found between ALL survivors and controls for all lipoprotein fractions except HDL3 HDL2, especially, showed reduced Apo A-I and raised Apo A-II, leading to a depressed Apo A-I/A-II ratio. Analysis of VLDL-Apo Cs disclosed a trend for higher Apo C-III1 content in dyslipidemic ALL survivors. In conclusion, this thorough investigation demonstrates a high prevalence of dyslipidemia in ALL survivors, while highlighting significant abnormalities in their plasma lipid profile and lipoprotein composition. Special attention must, therefore, be paid to these subjects given the atherosclerotic potency of lipid and lipoprotein disorders.

Genomic determinants of long-term cardiometabolic complications in childhood acute lymphoblastic leukemia survivors.

BACKGROUND: While cure rates for childhood acute lymphoblastic leukemia (cALL) now exceed 80%, over 60% of survivors will face treatment-related long-term sequelae, including cardiometabolic complications such as obesity, insulin resistance, dyslipidemia and hypertension. Although genetic susceptibility contributes to the development of these problems, there are very few studies that have so far addressed this issue in a cALL survivorship context. METHODS: In this study, we aimed at evaluating the associations between common and rare genetic variants and long-term cardiometabolic complications in survivors of cALL. We examined the cardiometabolic profile and performed whole-exome sequencing in 209 cALL survivors from the PETALE cohort. Variants associated with cardiometabolic outcomes were identified using PLINK (common) or SKAT (common and rare) and a logistic regression was used to evaluate their impact in multivariate models. RESULTS: Our results showed that rare and common variants in the BAD and FCRL3 genes were associated (p<0.05) with an extreme cardiometabolic phenotype (3 or more cardiometabolic risk factors). Common variants in OGFOD3 and APOB as well as rare and common BAD variants were significantly (p<0.05) associated with dyslipidemia. Common BAD and SERPINA6 variants were associated (p<0.05) with obesity and insulin resistance, respectively. CONCLUSIONS: In summary, we identified genetic susceptibility loci as contributing factors to the development of late treatment-related cardiometabolic complications in cALL survivors. These biomarkers could be used as early detection strategies to identify susceptible individuals and implement appropriate measures and follow-up to prevent the development of risk factors in this high-risk population.

Vitamin D Reduces Colitis- and Inflammation-Associated Colorectal Cancer in Mice Independent of NOD2.

Inflammatory bowel disease (IBD) patients are at increased risk of developing colorectal cancer (CRC). Vitamin D (vD) induces NOD2 gene expression, enhancing immunity, while deficiency impairs intestinal epithelial integrity, increasing inflammation. This study investigated the effect of vD on CRC in colitis, and if preventive benefits are mediated via NOD2. Inflammation-associated CRC was induced by treating C57BL/6J and Nod2-/- mice with azoxymethane (AOM) and dextran sodium sulfate (DSS) cycles (×3). vD-deficient mice displayed more severe colitis compared to vD-supplemented mice, with greater weight loss, higher colitis activity index, increased colonic weight/length ratios, and lower survival rates. Increased histological inflammation score and increased IL-6 were observed in the mucosa of vD-deficient mice. Overall incidence of colonic tumors was not significantly different between vD-deficient and vD-supplemented mice. Higher tumor multiplicity was observed in vD-deficient vs vD-supplemented groups (both mouse strains). After AOM/DSS treatment, decreased plasma 25(OH)D3 levels and downregulation of vD target genes Cyp24 and Vdr were observed in both mice strains (vD-deficient or vD-supplemented diet), compared to saline-treated controls on the vD-deficient diet. In conclusion, vD supplementation reduced colitis severity and decreased the number of inflammation-associated colorectal tumors in both C57BL/6J and Nod2-/- mice, independent of NOD2.

Cardiometabolic risk factors and lactoferrin: polymorphisms and plasma levels in French-Canadian children.

BackgroundLactoferrin (LTF) could play a beneficial role in insulin resistance and diabetes, but the association of its gene variants with cardio-metabolic disorders in children has not been investigated. This study aimed to examine the relationship between LTF variants, plasma LTF concentrations, and cardio-metabolic risk factors in French-Canadian children.MethodsThe study cohort comprises 1,749 French Canadians aged 9, 13, and 16 years. The association of 13 LTF polymorphisms, metabolic parameters, and plasma LTF levels was tested in this cross-sectional, province-wide school-based survey.ResultsNone of the genetic association remained significant after correction for multiple testing and LTF SNPs were not associated with LTF levels. Plasma LTF was positively correlated with body mass index (r2=0.2245, P=0.0011) and weight (r2=0.2515, P=0.0008). After segregating according to high-density lipoprotein cholesterol (HDL-C), the association remained only in subjects exhibiting low HDL-C (r2=0.3868, P=0.0002 for body mass index and r2=0.3665, P=0.0004 for weight). In girls, plasma LTF was positively correlated with total cholesterol (r2=0.2231, P=0.0378), LDL cholesterol (r2=0.2409, P=0.0246), and apolipoprotein B (r2=0.2478, P=0.0207).ConclusionsWe found no association between LTF gene variants and metabolic parameters following correction for multiple testing. HDL-C and gender-specific positive associations were evidenced between plasma LTF, anthropometric profile, and lipid levels.

The PETALE study: Late adverse effects and biomarkers in childhood acute lymphoblastic leukemia survivors.

BACKGROUND: Childhood cancer survivorship issues represent an established public health challenge. Most late adverse effects (LAEs) have been demonstrated to be time and treatment dependent. The PETALE study is a multidisciplinary research project aiming to comprehensively characterize LAEs and identify associated predictive biomarkers in childhood acute lymphoblastic leukemia (cALL) survivors. METHODS: cALL survivors treated at Sainte-Justine University Health Center with Dana-Farber Cancer Institution-ALL protocols 87-01 through 2005-01 were eligible. During Phase I of the study, the participants underwent comprehensive clinical, biologic, and psychosocial investigation targeting metabolic syndrome, cardiotoxicity, bone morbidity, neurocognitive problems, and quality of life issues. Whole-exome sequencing was performed for all participants. Subjects identified with an extreme phenotype during Phase I were recalled for additional testing (Phase II). RESULTS: Phase I included 246 survivors (recall rate 71.9%). Of those, 85 participants completed Phase II (recall rate 88.5%). Survivors agreeing to participate in Phase I (n = 251) were similar to those who refused (n = 31) in terms of relapse risk profile, radiotherapy exposure, and age at the time of study. Participants, however, tended to be slightly older at diagnosis (6.1 vs. 4.7 years old, P = 0.08), with a higher proportion of female agreeing to participate compared with males (93.2 vs. 86.5%, P = 0.07). CONCLUSION: The PETALE study will contribute to comprehensively characterize clinical, psychosocial, biologic, and genomic features of cALL survivors using an integrated approach. Expected outcomes include LAE early detection biomarkers, long-term follow-up guidelines, and recommendations for physicians and health professionals.

New Insights In Intestinal Sar1B GTPase Regulation and Role in Cholesterol Homeostasis.

Sar1B GTPase is a key component of Coat protein complex II (COPII)-coated vesicles that bud from the endoplasmic reticulum to export newly synthesized proteins. The aims of this study were to determine whether Sar1B responds to lipid regulation and to evaluate its role in cholesterol (CHOL) homeostasis. The influence of lipids on Sar1B protein expression was analyzed in Caco-2/15 cells by Western blot. Our results showed that the presence of CHOL (200 µM) and oleic acid (0.5 mM), bound to albumin, increases Sar1B protein expression. Similarly, supplementation of the medium with micelles composed of taurocholate with monooleylglycerol or oleic acid also stimulated Sar1B expression, but the addition of CHOL (200 µM) to micelle content did not modify its regulation. On the other hand, overexpression of Sar1B impacted on CHOL transport and metabolism in view of the reduced cellular CHOL content along with elevated secretion when incubated with oleic acid-containing micelles for 24 h, thereby disclosing induced CHOL transport. This was accompanied with higher secretion of free- and esterified-CHOL within chylomicrons, which was not the case when oleic acid was replaced with monooleylglycerol or when albumin-bound CHOL was given alone. The aforementioned cellular CHOL depletion was accompanied with a low phosphorylated/non phosphorylated HMG-CoA reductase ratio, indicating elevated enzymatic activity. Combination of Sar1B overexpression with micelle incubation led to reduction in intestinal CHOL transporters (NPC1L1, SR-BI) and metabolic regulators (PCSK9 and LDLR). The present work showed that Sar1B is regulated in a time- and concentration-dependent manner by dietary lipids, suggesting an adaptation to alimentary lipid flux. Our data also suggest that Sar1B overexpression contributes to regulation of CHOL transport and metabolism by facilitating rapid uptake and transport of CHOL.