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2.
Int J Behav Nutr Phys Act ; 16(1): 61, 2019 08 06.
Article in English | MEDLINE | ID: mdl-31387609

ABSTRACT

BACKGROUND: The objective of this study was to develop and validate a short, self-administered questionnaire to assess diet quality in clinical settings, using the Alternative Healthy Eating Index (AHEI) as reference. METHODS: A total of 1040 men and women (aged 44.6 ± 14.4 y) completed a validated web-based food frequency questionnaire (webFFQ) and had their height and weight measured (development sample). Participants were categorized arbitrarily according to diet quality (high: AHEI score ≥ 65/110, low: AHEI score < 65/110) based on dietary intake data from the webFFQ. The Brief Diet Quality Assessment Tool was developed using a classification and regression tree (CART) approach and individual answers to the webFFQ among participants considered to have a plausible energy intake (ratio of reported energy intake to basal metabolic rate ≥ 1.2 and < 2.4; n = 1040). A second sample of 3344 older adults (aged 66.5 ± 6.4 y) was used to test the external validity of the Brief Diet Quality Assessment Tool (external validation sample). RESULTS: The decision tree included sequences of 3 to 6 binary questions, yielding 21 different pathways classifying diet quality as being high or low. In the development sample, the area under the receiver operating characteristic (ROC) curve of the predictive model was 0.92, with sensitivity, specificity and agreement values of 89.5, 83.9 and 87.2%. Compared with individuals having a low-quality diet according to the Brief Diet Quality Assessment Tool (mean AHEI 56.7 ± 11.4), individuals classified as having a high-quality diet (mean AHEI 71.3 ± 11.0) were significantly older, and had lower BMI, percent body fat and waist circumference, and had lower blood pressure, triglycerides, cholesterol/HDL ratio and fasting insulin as well as higher HDL-cholesterol concentrations (all P < 0.05). Similar results were observed in the external validation sample, although overall performance of the Brief Diet Quality Assessment Tool was slightly lower than in the development sample, with an area under the ROC curve of 0.79 and sensitivity, specificity and agreement values of 73.0, 69.0 and 71.3%, respectively. CONCLUSION: The CART approach yielded a simple and rapid Brief Diet Quality Assessment Tool that identifies individuals at risk of having a low-quality diet. Further studies are needed to test the performance of this tool in primary care settings.


Subject(s)
Diet Surveys/standards , Diet/statistics & numerical data , Nutritive Value/physiology , Surveys and Questionnaires/standards , Adult , Aged , Female , Humans , Male , Middle Aged , Quebec
3.
J Nutr Sci ; 8: e26, 2019.
Article in English | MEDLINE | ID: mdl-31428333

ABSTRACT

The aim of the present study was to assess the relative validity of a new web-based 24-h dietary recall (R24W) in terms of vegetable and fruit (VF) intake assessment using serum carotenoid concentrations as reference biomarkers. A total of seventy-four women and seventy-three men (mean age 47·5 (sd 13·3) years; mean BMI 25·5 (sd 4·4) kg/m2) completed the R24W four times to assess their VF intake. Serum carotenoids were obtained from 12-h fasted blood samples and measured by HPLC. Raw and de-attenuated partial Spearman's correlations were performed to determine how usual vegetable and/or fruit intake was associated with serum carotenoids. Relevant confounders were selected using a stepwise regression analysis. Finally, cross-classification was used to determine agreement between intake of VF and serum carotenoids. Intake of total dietary carotenoids was significantly associated (r 0·40; P < 0·01) with total serum carotenoids (without lycopene). Total VF intake was also associated with total serum carotenoid concentrations without lycopene (r 0·44; P < 0·01). HDL-cholesterol, waist circumference and age were identified as confounders in the association between total VF intake and total serum carotenoids (without lycopene). De-attenuated partial correlation adjusted for these confounders increased the associations between dietary carotenoids and total serum carotenoids without lycopene (r 0·49; P < 0·01) and between total VF intake and total serum carotenoids without lycopene (r 0·48; P < 0·01). Almost 80 % of respondents were classified in the same or the adjacent quartile for total VF intake and total serum carotenoids without lycopene, while less than 6 % were classified in the opposite quartile. Overall, these observations support the appropriateness of the R24W to assess the dietary intake of VF.


Subject(s)
Carotenoids/blood , Diet , Eating , Fruit , Internet , Vegetables , Adolescent , Adult , Aged , Biomarkers/blood , Body Mass Index , Female , Humans , Male , Middle Aged , Self Report , Young Adult
4.
Rev Epidemiol Sante Publique ; 67(5): 285-294, 2019 Sep.
Article in French | MEDLINE | ID: mdl-31353238

ABSTRACT

BACKGROUND: A significant proportion of childhood sexual abuse victims suffer from psychological sequelae in adulthood. Factors that provide a better understanding for the reasons why some victims develop these sequelae remain under-explored. In this context, the main objective is to examine the specific contribution of the contextual characteristics of childhood sexual abuse, multitype childhood maltreatment and adolescent suicide attempts on the development of depression and post-traumatic stress disorder in adulthood among sexually abused women as children. A secondary objective aimed to establish the prevalence of various forms of childhood maltreatment, adult onset post-traumatic stress disorder and depression among those women. METHODS: The sample included 479 women victims of childhood sexual abuse who participated in two separate surveys taken by women in the province of Quebec. RESULTS: More than half of these women reported at least one other form of childhood maltreatment, 30% of them presented post-traumatic disorder and 40% suffered from depression in adulthood. Regression analysis indicates that post-traumatic stress disorder was associated with early onset childhood sexual abuse and intergenerational continuity of sexual victimization, as well as childhood physical maltreatment and negligence. Depression was associated with childhood psychological maltreatment and negligence, a non-supportive response following child sexual abuse related disclosure and suicide attempt in adolescence. CONCLUSION: These results confirm the need to consider the cumulative effects of various childhood adversity factors in the psychosocial assessment of sexually abused women in early life, thus helping to better understand and treat their psychological sequelae.


Subject(s)
Adult Survivors of Child Adverse Events , Child Abuse, Sexual , Crime Victims , Depression , Stress Disorders, Post-Traumatic , Adolescent , Adult , Adult Survivors of Child Adverse Events/psychology , Adult Survivors of Child Adverse Events/statistics & numerical data , Aged , Child , Child Abuse/psychology , Child Abuse/statistics & numerical data , Child Abuse, Sexual/psychology , Child Abuse, Sexual/statistics & numerical data , Child, Preschool , Crime Victims/psychology , Crime Victims/statistics & numerical data , Depression/diagnosis , Depression/epidemiology , Depression/etiology , Domestic Violence/psychology , Domestic Violence/statistics & numerical data , Female , Humans , Infant , Infant, Newborn , Life Change Events , Middle Aged , Prevalence , Quebec/epidemiology , Sexual Behavior/psychology , Sexual Behavior/statistics & numerical data , Stress Disorders, Post-Traumatic/diagnosis , Stress Disorders, Post-Traumatic/epidemiology , Stress Disorders, Post-Traumatic/etiology , Stress, Psychological/complications , Stress, Psychological/epidemiology , Stress, Psychological/psychology , Surveys and Questionnaires , Young Adult
5.
Nutr Metab Cardiovasc Dis ; 29(7): 684-691, 2019 07.
Article in English | MEDLINE | ID: mdl-31078363

ABSTRACT

BACKGROUND AND AIMS: The "Life's Simple 7" (LS7) metrics were developed by the American Heart Association (AHA) to assess and promote cardiovascular health in the American population. The purpose of this study was to assess the overall cardiovascular health of French-speaking adults from the Province of Quebec using the LS7 score. METHODS AND RESULTS: A total of 777 age and sex-representative participants of five different administrative regions in the Province of Quebec (387 men and 390 women; mean age ± SEM: 41.9 ± 0.1 years) were included in these analyses. Metrics of the LS7 score (smoking, physical activity, diet, body mass index, blood pressure, fasting total cholesterol and blood glucose) were analysed to generate a final score ranging from 0 to 7. Only 0.5% of participants met all criteria for ideal cardiovascular health. The diet metric showed the lowest prevalence of "ideal" scores (4.8%) whereas not smoking was the metric with the highest prevalence (88.1%). Women had a higher LS7 score than men, while age and education level (negative and positive association, respectively; p < 0.0001) were also associated with the LS7 score. CONCLUSION: Consistent with studies conducted among other populations, very few French-speaking adults from the Province of Quebec achieve an ideal cardiovascular health. These data indicate that further public health efforts aimed at promoting the LS7 metrics, focusing primarily on diet, are urgently needed. Specific groups, including older adults and those with lower levels of education, should be targeted when developing cardiovascular health promotion interventions.


Subject(s)
American Heart Association , Cardiovascular Diseases/prevention & control , Health Status Indicators , Health Status , Healthy Lifestyle , Language , Primary Prevention , Risk Reduction Behavior , Adolescent , Adult , Aged , Biomarkers/blood , Blood Glucose/analysis , Blood Pressure , Body Mass Index , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Cholesterol/blood , Cross-Sectional Studies , Exercise , Female , Humans , Male , Middle Aged , Prevalence , Protective Factors , Quebec/epidemiology , Risk Assessment , Risk Factors , Smoking Cessation , United States , Young Adult
6.
Nutr Metab Cardiovasc Dis ; 28(12): 1275-1284, 2018 12.
Article in English | MEDLINE | ID: mdl-30459054

ABSTRACT

BACKGROUND AND AIMS: The metabolic syndrome (MS) is an emerging complication in patients with type 1 diabetes (T1D), with no preventive or therapeutic treatment reported yet. We wanted to compare the impact of two 6-month nutritional interventions, based on a Mediterranean (MED) or a low-fat diet, on waist circumference, anthropometric and metabolic outcomes in patients with both T1D and the MS. METHODS AND RESULTS: Participants were randomized into 2 intervention groups: 1) MED-diet or 2) low-fat diet. The 6-month study included 9 teaching sessions with a registered dietitian. Anthropometric (primary outcome: waist circumference), metabolic and nutritional assessments were performed at inclusion, 3 and 6-month. We used mixed effects models to assess the effects of both interventions. 28 participants were included (50.9 ± 10.3 years old) with a mean BMI of 30.7 ± 3.3 kg/m2 and a waist circumference of 105.5 ± 8.9 cm at inclusion. A trend towards a greater reduction of dietary fat intakes in the low-fat diet group was observed (P-interaction = 0.09). Waist circumference was reduced at 6-month in both groups (-3.5 cm low-fat; -1.5 cm MED-diet) with no significant difference between groups (P-interaction = 0.43). Body mass index also significantly decreased in both groups (-0.7 kg/m2 low-fat; -1.1 kg/m2 MED-diet; P-interaction = 0.56). No significant differences between groups were observed for other metabolic parameters. CONCLUSIONS: This study suggests that a 6-month non-restrictive dietary intervention in patients with T1D and MS could contribute to weight management, without significant differences between interventions for anthropometric and metabolic parameters. Further studies should investigate the long-term benefits of these diets. CLINICAL TRIAL REGISTRY: NCT02821585 (https://clinicaltrials.gov/).


Subject(s)
Diabetes Mellitus, Type 1/diet therapy , Diet, Fat-Restricted , Diet, Mediterranean , Metabolic Syndrome/diet therapy , Weight Loss , Adult , Biomarkers/blood , Body Mass Index , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/physiopathology , Female , Humans , Male , Metabolic Syndrome/blood , Metabolic Syndrome/diagnosis , Metabolic Syndrome/physiopathology , Middle Aged , Nutritional Status , Nutritive Value , Quebec , Time Factors , Treatment Outcome , Waist Circumference
7.
Blood Cancer J ; 7(2): e529, 2017 02 17.
Article in English | MEDLINE | ID: mdl-28211886

ABSTRACT

Appropriate culture methods for the interrogation of primary leukemic samples were hitherto lacking and current assays for compound screening are not adapted for large-scale investigation of synergistic combinations. In this study, we report a novel approach that efficiently distills synthetic lethal interactions between small molecules active on primary human acute myeloid leukemia (AML) specimens. In single-dose experiments and under culture conditions preserving leukemia stem cell activity, our strategy considerably reduces the number of tests needed for the identification of promising compound combinations. Initially conducted with a selected library of 5000 small molecules and 20 primary AML specimens, it reveals 5 broad classes of sensitized therapeutic target pathways along with their synergistic patient-specific fingerprints. This novel method opens new avenues for the development of AML personalized therapeutics and may be generalized to other tumor types, for which in vitro cancer stem cell cultures have been developed.


Subject(s)
Combined Modality Therapy/methods , Leukemia, Myeloid, Acute/drug therapy , Humans , Leukemia, Myeloid, Acute/pathology , Tumor Cells, Cultured
8.
Blood Cancer J ; 6(6): e431, 2016 06 03.
Article in English | MEDLINE | ID: mdl-27258612

ABSTRACT

Acute myeloid leukemia (AML) is associated with poor clinical outcome and the development of more effective therapies is urgently needed. G protein-coupled receptors (GPCRs) represent attractive therapeutic targets, accounting for approximately 30% of all targets of marketed drugs. Using next-generation sequencing, we studied the expression of 772 GPCRs in 148 genetically diverse AML specimens, normal blood and bone marrow cell populations as well as cord blood-derived CD34-positive cells. Among these receptors, 30 are overexpressed and 19 are downregulated in AML samples compared with normal CD34-positive cells. Upregulated GPCRs are enriched in chemokine (CCR1, CXCR4, CCR2, CX3CR1, CCR7 and CCRL2), adhesion (CD97, EMR1, EMR2 and GPR114) and purine (including P2RY2 and P2RY13) receptor subfamilies. The downregulated receptors include adhesion GPCRs, such as LPHN1, GPR125, GPR56, CELSR3 and GPR126, protease-activated receptors (F2R and F2RL1) and the Frizzled family receptors SMO and FZD6. Interestingly, specific deregulation was observed in genetically distinct subgroups of AML, thereby identifying different potential therapeutic targets in these frequent AML subgroups.


Subject(s)
High-Throughput Nucleotide Sequencing , Leukemia, Myeloid, Acute/genetics , Neoplasm Proteins/genetics , Receptors, G-Protein-Coupled/genetics , Transcriptome/genetics , Adult , Aged , Aged, 80 and over , Antigens, CD34/genetics , Bone Marrow Cells/metabolism , Bone Marrow Cells/pathology , Female , Gene Expression Regulation, Neoplastic , Humans , Leukemia, Myeloid, Acute/blood , Leukemia, Myeloid, Acute/pathology , Male , Middle Aged , Molecular Targeted Therapy , Neoplasm Proteins/blood , Signal Transduction/genetics
10.
Leukemia ; 30(6): 1344-54, 2016 06.
Article in English | MEDLINE | ID: mdl-26857467

ABSTRACT

Pre-clinical studies have shown that injection of allogeneic T cells primed against a single minor histocompatibility antigen (MiHA) could cure hematologic cancers (HC) without causing any toxicity to the host. However, translation of this approach in humans has been hampered by the paucity of molecularly defined human MiHAs. Using a novel proteogenomic approach, we have analyzed cells from 13 volunteers and discovered a vast repertoire of MiHAs presented by the most common HLA haplotype in European Americans: HLA-A*02:01;B*44:03. Notably, out of >6000 MiHAs, we have identified a set of 39 MiHAs that share optimal features for immunotherapy of HCs. These 'optimal MiHAs' are coded by common alleles of genes that are preferentially expressed in hematopoietic cells. Bioinformatic modeling based on MiHA allelic frequencies showed that the 39 optimal MiHAs would enable MiHA-targeted immunotherapy of practically all HLA-A*02:01;B*44:03 patients. Further extension of this strategy to a few additional HLA haplotypes would allow treatment of almost all patients.


Subject(s)
Hematologic Neoplasms/therapy , Immunotherapy/methods , Minor Histocompatibility Antigens/therapeutic use , Proteogenomics/methods , Cells, Cultured , Female , HLA-A2 Antigen , HLA-B44 Antigen , Haplotypes , Humans , Male
11.
Prostaglandins Leukot Essent Fatty Acids ; 102-103: 37-45, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26525102

ABSTRACT

This clinical trial investigated the impact of a six-week supplementation with fish oil and single nucleotide polymorphisms (SNPs) in PLA2G4A and PLA2G6 genes on total omega-6 fatty acid (n-6 FA) levels in plasma phospholipids (PL) and plasma C-reactive protein (CRP) levels in 191 subjects. Interaction effects between SNPs and supplementation modulated total n-6 FAs and CRP levels in both men and women. Associations between SNPs and total n-6 FA levels and between SNPs and CRP levels were identified in men, independently of supplementation. Supplementation decreased total n-6 FAs without affecting plasma CRP levels. Changes in CRP levels correlated positively with changes in total n-6 FAs in men (r=0.25 p=0.01), but not in women. In conclusion, total n-6 FA levels in plasma PL and plasma CRP levels are modulated by SNPs within PLA2G4A and PLA2G6 genes alone or in combination with fish oil supplementation.


Subject(s)
C-Reactive Protein/analysis , Dietary Supplements , Fatty Acids, Omega-6/blood , Fish Oils/administration & dosage , Group IV Phospholipases A2/genetics , Group VI Phospholipases A2/genetics , Polymorphism, Single Nucleotide , Adolescent , Adult , Anti-Inflammatory Agents, Non-Steroidal/administration & dosage , Anti-Inflammatory Agents, Non-Steroidal/metabolism , Body Mass Index , Fatty Acids, Omega-6/administration & dosage , Fatty Acids, Omega-6/analysis , Fatty Acids, Omega-6/antagonists & inhibitors , Female , Fish Oils/metabolism , Genetic Association Studies , Group IV Phospholipases A2/metabolism , Group VI Phospholipases A2/metabolism , Humans , Male , Middle Aged , Nutrigenomics/methods , Overweight/blood , Overweight/genetics , Overweight/metabolism , Phospholipids/blood , Phospholipids/chemistry , Quebec , Sex Characteristics , Young Adult
12.
Diabet Med ; 32(12): 1530-40, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26104021

ABSTRACT

AIM: To assess the efficacy and safety of third-line adjuvant antihyperglycaemic agents in people with Type 2 diabetes mellitus failing metformin and sulphonylurea combination therapy. METHODS: We searched MEDLINE, CENTRAL, clinicaltrials.gov and regulatory websites, and conducted a manual search of references in the identified studies. Randomized trials evaluating antihyperglycaemic agents in adults with Type 2 diabetes experiencing poor glycaemic control despite optimized metformin and sulphonylurea therapy (≥ 1500 mg metformin or maximum tolerated dose; ≥ 50% of maximum sulphonylurea dose for ≥ 3 weeks) were included. Data extraction included: study characteristics; change in HbA1c concentration; weight; systolic blood pressure; and relative risk of hypoglycaemia, urinary tract infections; and genital tract infections. A network meta-analysis was performed. RESULTS: A total of 20 trials evaluating 13 antihyperglycaemic agents were included. Compared with placebo/control, all antihyperglycaemic agents reduced HbA1c levels, albeit by differing magnitudes [range 7 mmol/mol (0.6%) for acarbose to 13 mmol/mol (1.20%) for liraglutide]. Sodium glucose cotransporter-2 inhibitors reduced weight (1.43-2.07 kg) whereas thiazolidinediones, glargine and sitagliptin caused weight gain (1.48-3.62 kg) compared with placebo/control. Sodium glucose cotransporter-2 inhibitors, rosiglitazone and liraglutide decreased systolic blood pressure compared with placebo/control, pioglitazone, glargine and sitagliptin (2.41-8.88 mm Hg). Glargine, thiazolidinediones, liraglutide, sitagliptin and canagliflozin increased hypoglycaemia risk compared with placebo/control (relative risk 1.92-7.47), while glargine and rosiglitazone increased hypoglycaemia compared with most antihyperglycaemic agents (relative risk 2.81-7.47). No antihyperglycaemic agent increased the risk of urinary tract infection, but canagliflozin increased the risk of genital tract infection by 3.9-fold compared with placebo/control. CONCLUSIONS: When added to metformin and a sulphonylurea, antihyperglycaemic agents had varying effects on efficacy and safety endpoints. These conclusions should be considered when clinicians choose between possible adjunctive agents.


Subject(s)
Diabetes Mellitus, Type 2/drug therapy , Drug Resistance , Evidence-Based Medicine , Hypoglycemic Agents/therapeutic use , Metformin/therapeutic use , Precision Medicine , Sulfonylurea Compounds/therapeutic use , Diabetes Mellitus, Type 2/blood , Drug Monitoring , Drug Therapy, Combination/adverse effects , Glycated Hemoglobin/analysis , Humans , Hyperglycemia/prevention & control , Hypoglycemic Agents/adverse effects , Metformin/adverse effects , Randomized Controlled Trials as Topic , Sulfonylurea Compounds/adverse effects
13.
J Hum Nutr Diet ; 28(1): 37-46, 2015 Feb.
Article in English | MEDLINE | ID: mdl-24527882

ABSTRACT

BACKGROUND: Differences between men and women with respect to dietary intakes and eating behaviours have been reported and could be explained by gender differences in motivational variables associated with the regulation of food intake. The main objectives of the present study were to identify gender differences in dietary intakes, eating behaviours and motivational variables and to determine how motivational variables were associated with dietary intakes and eating behaviours in men and women. METHODS: Sixty-four men and 59 premenopausal women were included in the present study and presented cardiovascular risk factors. The Regulation of Eating Behaviours scale was completed to assess motivational variables. A validated food frequency questionnaire was administered to evaluate dietary intakes and subjects completed the Three-Factor Eating questionnaire to assess eating behaviours. RESULTS: Men had higher energy intake, energy density and percentage of energy from lipids and lower percentage of energy from carbohydrates than women (P ≤ 0.04). Men also had a lower emotional susceptibility to disinhibition than women (P = 0.0001). Women reported a higher score for eating-related self-determined motivation [i.e., eating-related self-determination index (SDI)] than men (P = 0.002). The most notable gender difference in the pattern of associations was that eating-related SDI was negatively associated with energy density (r = -0.30; P = 0.02), only in women. CONCLUSIONS: Women had a better dietary profile and higher eating-related SDI than men. However, gender differences in dietary variables might be explained by a potential gender-specific pattern of association of eating-related SDI with dietary intakes and eating behaviours.


Subject(s)
Eating/psychology , Feeding Behavior/psychology , Motivation , Sex Factors , Adult , Diet/psychology , Emotions , Energy Intake , Female , Humans , Male , Middle Aged , Risk Factors , Self Concept , Surveys and Questionnaires
14.
Opt Lett ; 39(8): 2403-6, 2014 Apr 15.
Article in English | MEDLINE | ID: mdl-24979004

ABSTRACT

Bright squeezed vacuum, a macroscopic nonclassical state of light, can be obtained at the output of a strongly pumped nonseeded traveling-wave optical parametric amplifier (OPA). By constructing the OPA of two consecutive crystals separated by a large distance, we make the squeezed vacuum spatially single-mode without a significant decrease in the brightness or squeezing.

15.
Eur J Clin Nutr ; 68(5): 561-6, 2014 May.
Article in English | MEDLINE | ID: mdl-24595221

ABSTRACT

BACKGROUND/OBJECTIVES: Most of the interventional studies have investigated the impact of the diet on adiponectin and leptin concentrations only in men or in women. Consequently, it is still unknown whether the consumption of a healthy diet influences in a sex-specific manner these adipocytokines. We examined sex differences in the effects of the Mediterranean diet (MedDiet) on adiponectin and leptin concentrations, and determined whether changes in these adipocytokines are associated with changes in cardiovascular risk factors in both sexes. SUBJECTS/METHODS: Participants were 38 men and 32 premenopausal women (24-53 years) with slightly elevated low-density lipoprotein cholesterol concentrations (3.4-4.9 mmol/l) or total cholesterol/high-density lipoprotein cholesterol (HDL-C)⩾5.0. Adiponectin, leptin and cardiovascular risk factors were measured before and after a 4-week fully controlled isoenergetic MedDiet. RESULTS: Adiponectin concentration decreased in response to the MedDiet, but this decrease reached statistical significance only in men (P<0.001 for men and P=0.260 for women; sex-by-time interaction, P=0.072). Adjustments for body weight or waist circumference did not change results obtained. Changes in adiponectin were positively associated with concomitant variations in HDL-C in men (r=0.52, P=0.003) and with variations in apolipoprotein A-1 and insulin sensitivity as calculated by both the homeostasis model assessment index for insulin sensitivity and Cederholm indices in women (respectively, r=0.44, P=0.021; r=0.79, P<0.001 and r=0.47, P=0.020). The MedDiet had no impact on leptin and the leptin-to-adiponectin ratio in both sexes. CONCLUSIONS: Results suggest a sex difference in adiponectin response to the short-term consumption of the MedDiet, with only men experiencing a decrease. Also sex-specific patterns of associations between changes in adiponectin concentration and changes in cardiovascular risk factors were observed.


Subject(s)
Adiponectin/blood , Diet, Mediterranean , Leptin/blood , Sex Factors , Adult , Apolipoprotein A-I/blood , Blood Pressure , Body Weight , Cardiovascular Diseases/prevention & control , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Female , Homeostasis , Humans , Insulin Resistance , Male , Middle Aged , Premenopause , Risk Factors , Triglycerides/blood , Waist Circumference , Young Adult
16.
Leukemia ; 28(8): 1617-26, 2014 Aug.
Article in English | MEDLINE | ID: mdl-24514424

ABSTRACT

The GATA2 gene encodes a zinc-finger transcription factor that acts as a master regulator of normal hematopoiesis. Mutations in GATA2 have been implicated in the development of myelodysplastic syndrome and acute myeloid leukemia (AML). Using RNA sequencing we now report that GATA2 is either mutated with a functional consequence, or expressed at low levels in the majority of normal karyotype AML (NK-AML). We also show that low-GATA2-expressing specimens (GATA2(low)) exhibit allele-specific expression (ASE) (skewing) in more than half of AML patients examined. We demonstrate that the hypermethylation of the silenced allele can be reversed by exposure to demethylating agents, which also restores biallelic expression of GATA2. We show that GATA2(low) AML lack the prototypical R882 mutation in DNMT3A frequently observed in NK-AML patients and that The Cancer Genome Atlas AML specimens with DNMT3A R882 mutations are characterized by CpG hypomethylation of GATA2. Finally, we validate that several known missense single-nucleotide polymorphisms in GATA2 are actually loss-of-function variants, which, when combined with ASE, represent the equivalent of homozygous GATA2 mutations. From a broader perspective, this work suggests for the first time that determinants of ASE likely have a key role in human leukemia.


Subject(s)
Epigenesis, Genetic , GATA2 Transcription Factor/genetics , Leukemia, Myeloid, Acute/genetics , Alleles , Cell Line, Tumor , DNA (Cytosine-5-)-Methyltransferases/genetics , DNA Methylation , DNA Methyltransferase 3A , Humans , Karyotype , Mutation , Polymorphism, Single Nucleotide
17.
Neuroscience ; 254: 61-9, 2013 Dec 19.
Article in English | MEDLINE | ID: mdl-24045100

ABSTRACT

Using structural magnetic resonance imaging in a clinical scanner at 3.0T, we describe results showing that following 12weeks on a diet of 2% cholesterol, rabbits experience a significant increase in the volume of the third ventricle compared to rabbits on a diet of 0% cholesterol. Using time-of-flight magnetic resonance angiography, we find cholesterol-fed rabbits also experience a decrease in the diameter of a number of cerebral blood vessels including the basilar, posterior communicating, and internal carotid arteries. Taken together, these data confirm that, despite the inability of dietary cholesterol to cross the blood-brain barrier, it does significantly enlarge ventricular volume and decrease cerebrovascular diameter in the rabbit - effects that are also seen in patients with Alzheimer's disease.


Subject(s)
Alzheimer Disease/pathology , Cerebral Arteries/pathology , Cerebral Ventricles/pathology , Cholesterol, Dietary/adverse effects , Disease Models, Animal , Alzheimer Disease/etiology , Animals , Cerebrovascular Circulation/physiology , Cholesterol, Dietary/administration & dosage , Male , Rabbits
18.
Genes Immun ; 14(2): 115-26, 2013 Mar.
Article in English | MEDLINE | ID: mdl-23328844

ABSTRACT

Transforming growth factor-ß (TGF-ß) maintains self-tolerance through a constitutive inhibitory effect on T-cell reactivity. In most physiological situations, the tolerogenic effects of TGF-ß depend on the canonical signaling molecule Smad3. To characterize how TGF-ß/Smad3 signaling contributes to maintenance of T-cell tolerance, we characterized the transcriptional landscape downstream of TGF-ß/Smad3 signaling in resting or activated CD4 T cells. We report that in the presence of TGF-ß, Smad3 modulates the expression of >400 transcripts. Notably, we identified 40 transcripts whose expression showed Smad3 dependence in both resting and activated cells. This 'signature' confirmed the non-redundant role of Smad3 in TGF-ß biology and identified both known and putative immunoregulatory genes. Moreover, we provide genomic and functional evidence that the TGF-ß/Smad3 pathway regulates T-cell activation and metabolism. In particular, we show that TGF-ß/Smad3 signaling dampens the effect of CD28 stimulation on T-cell growth and proliferation. The impact of TGF-ß/Smad3 signals on T-cell activation was similar to that of the mTOR inhibitor Rapamycin. Considering the importance of co-stimulation on the outcome of T-cell activation, we propose that TGF-ß-Smad3 signaling may maintain T-cell tolerance by suppressing co-stimulation-dependent mobilization of anabolic pathways.


Subject(s)
CD28 Antigens/metabolism , CD4-Positive T-Lymphocytes/physiology , Signal Transduction , Smad3 Protein/metabolism , Transforming Growth Factor beta/metabolism , Animals , CD4-Positive T-Lymphocytes/metabolism , Cell Proliferation , Immunosuppressive Agents/pharmacology , Lymphocyte Activation , Mice , Mice, Knockout , Sirolimus/pharmacology , Smad3 Protein/genetics , TOR Serine-Threonine Kinases/antagonists & inhibitors
19.
Nutr Metab Cardiovasc Dis ; 21(4): 254-60, 2011 Apr.
Article in English | MEDLINE | ID: mdl-20153614

ABSTRACT

BACKGROUND AND AIMS: To investigate associations between plasma adiponectin concentration and very-low density lipoprotein-triglyceride (VLDL-TG) secretion and catabolism in postmenopausal women. METHODS AND RESULTS: This cross-sectional study included 30 postmenopausal women. Plasma adiponectin concentration was measured by ELISA. Insulin sensitivity was assessed by a 2-h euglycemic-hyperinsulinemic clamp. Fasting plasma glucose (FPG) and 2-hour plasma glucose (2hPG) were measured during an oral glucose tolerance test. The calculation of VLDL-TG fractional catabolic rate (FCR) and VLDL-TG total secretion rate (TSR) were based on the monoexponential decrease of TG-[²H5] glycerol values obtained following the administration of a ²H5-glycerol bolus. Plasma adiponectin concentration was negatively associated with VLDL-TG TSR (r=-0.50; p=0.005) and positively associated with VLDL-TG FCR (r=0.54; p<0.002). This latter association remained significant after further adjustments for insulin sensitivity, visceral adipose tissue, HDL-C, FPG and 2hPG concentrations. In a multivariate model including adiponectin, insulin sensitivity and 2hPG, plasma adiponectin level was the strongest correlate of VLDL-TG FCR. CONCLUSIONS: Elevated plasma adiponectin concentration is associated with a favourable VLDL-TG metabolism.


Subject(s)
Lipoproteins, VLDL/metabolism , Postmenopause , Triglycerides/metabolism , Adiponectin/blood , Adiposity , Aged , Blood Glucose , Body Mass Index , Cross-Sectional Studies , Female , Glucose Clamp Technique , Glucose Tolerance Test , Humans , Insulin Resistance , Intra-Abdominal Fat , Kinetics , Middle Aged
20.
Metab Syndr Relat Disord ; 8(4): 365-72, 2010 Aug.
Article in English | MEDLINE | ID: mdl-20698803

ABSTRACT

BACKGROUND: In postmenopausal women, a population at risk for the metabolic syndrome, the relative contribution of central fat versus peripheral muscle fat to the metabolic risk profile is unknown. This study explored the relationship between muscle fat infiltration derived from computed tomography (CT) scans and metabolic syndrome. METHODS: Mid-thigh CT scans measured the surface of muscle with low attenuation (LAMS) [0-34 Hounsfield units (HU)], which represented the specific component of fat-rich muscle. Insulin sensitivity was evaluated by an euglycemic-hyperinsulinemic clamp. National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria were used to determine the presence of the metabolic syndrome. RESULTS: A total of 103 postmenopausal women were studied. Metabolic syndrome was found in 43 women with significantly higher levels of abdominal adiposity, higher LAMS (27 +/- 8 vs. 23 +/- 7 cm(2)), and lower insulin sensitivity compared to those without the metabolic syndrome. Women with higher levels of LAMS presented higher metabolic risk features such as higher blood pressure, abdominal adiposity, inflammatory markers, and blood lipid levels. LAMS and visceral adipose tissue correlated significantly with the presence of metabolic syndrome, but these relationships were lost when LAMS was adjusted for visceral adipose tissue but not when visceral adipose tissue was adjusted for LAMS. CONCLUSIONS: These results suggest that postmenopausal women who present with metabolic syndrome had increased fat-rich mid-thigh muscle. Moreover, women with more fat-rich muscle had many features of the metabolic syndrome. These relations were weakened when visceral adipose tissue was taken into account suggesting that LAMS may play a relatively smaller role, compared to VAT, in the contribution to the metabolic syndrome.


Subject(s)
Adiposity/physiology , Metabolic Syndrome/pathology , Postmenopause/physiology , Thigh/anatomy & histology , Thigh/pathology , Aged , Anthropometry , Biomarkers/blood , Body Composition/physiology , Female , Glucose Clamp Technique , Glucose Tolerance Test , Hemodynamics , Humans , Inflammation/blood , Lipids/blood , Lipoproteins/blood , Middle Aged , Tomography, X-Ray Computed
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