Roles of high apolipoprotein E blood levels and HDL in development of familial dysbetalipoproteinemia in ε2ε2 subjects

ObjectiveFamilial dysbetalipoproteinemia (FD) or Type III hyperlipoproteinemia is a mixed hyperlipidemia closely associated with the ε2ε2 genotype of the common APOE polymorphism although not all homozygotes progress to FD. Unlike the polymorphism, few studies explore effects of apolipoprotein E (apoE) blood levels on FD development. Likewise, despite the known apoE2 lipoprotein binding preference for high-density lipoprotein (HDL); little work exists exploring HDL in FD. Accordingly, this study was undertaken to investigate potential roles in FD development for apoE and HDL. Additionally, insulin and Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) were investigated in view of reports linking insulin resistance to FD.MethodsAPOE genotyping and levels of apoE, apolipoprotein A-I (apoA-I), apolipoprotein A-II (apoA-II), insulin, HOMA-IR, lipids, and NMR lipoprotein analysis were determined in a cohort of healthy individuals (N = 7169). A lipid-based algorithm identified FD in 24 of 52 e2e2 subjects. Logistic regression modeling assessed associations of FD development with measured variables.ResultsUnivariate models revealed associations with FD significant and positive for apoE, apoA-II/apoA-I, apoA-I/HDL-C, apoA-II/HDL-C, and HOMA-IR. For HDL-C, association was significant but inverse. Results of multivariable models containing apoE with single parameters added revealed statistical significance only for the apoA-II/HDL-C ratio (OR 10.52, 95%CI 1.17–94.79, p = 0.036) concurrent with significance for apoE (OR 2.21, 95%CI 1.06–4.65, p = 0.035). Interaction was not demonstrated (p = 0.36). NMR results revealed for FD versus nonFD subjects generally higher levels of VLDL and small HDL and for IDL few differences.ConclusionHigh apoE and high apoA-II/HDL-C independently associate with FD development in ε2ε2 individuals.     

A FTO variant and risk of acute coronary syndrome

BackgroundThe FTO gene plays an important role in the determination of body weight and BMI and it has been suspected of being associated with all-case mortality.MethodsWe have analyzed the FTO rs17817449 variant in consecutive 1092 male patients with acute coronary syndrome (ACS) and in 1191 randomly selected Caucasian individuals (population controls).ResultsThe FTO variant was significantly associated with BMI both in controls (P < 0.02) and ACS patients (P < 0.01). In both groups, BMI was highest in GG homozygotes and lowest in TT homozygotes. There was a significant difference between the ACS patients and controls in the frequency of the FTO genotype GG (21.4% vs. 15.9%, P < 0.005). FTO GG homozygotes had a significantly increased risk of ACS, compared with TT homozygotes which was independent of age and BMI (odds ratio 1.49, 95% confidence interval 1.16–1.93). The odds ratio of ACS patients for the GG genotype remained significant even after the exclusion of diabetics (100 controls and 339 ACS patients), with OR 1.32 (95% CI 1.01–1.72).ConclusionsThis study provides an evidence of an association between the FTO variant and risk of ACS in Caucasian males.     

Mutations in APOA-I and ABCA1 in Norwegians with low levels of HDL cholesterol

BackgroundEpidemiological studies have shown that low levels of plasma high density lipoprotein (HDL) cholesterol are associated with increased risk of ischemic heart disease (IHD), but it appears that genetic forms of low HDL cholesterol levels, as opposed to lifestyle-induced low levels of HDL cholesterol, do not result in increased risk of IHD. Therefore, the etiology of reduced levels of plasma HDL cholesterol may represent a factor that should be considered in risk stratification with respect to primary prevention. Genes encoding proteins involved in HDL metabolism, such as the ATP-binding cassette transporter A1 (ABCA1) and apolipoprotein (apo) A-I genes, are candidate genes for harboring mutations that lead to low HDL cholesterol levels.MethodsThe ABCA1 and apoA-I genes in 56 Norwegian patients, with a mean HDL cholesterol level of 0.53 (± 0.15) mmol/l, were subjected to DNA sequencing.ResultsSeveral mutations were identified in the ABCA1 gene, and two mutations were identified in the apoA-I gene. A total of 18 patients (32%) were carriers of mutations considered to be pathogenic. Their mean HDL cholesterol level was 0.45 (± 0.15) mmol/l compared to 0.57 (± 0.14) mmol/l in noncarriers (p < 0.005).ConclusionMutations in the genes encoding ABCA1 and apoA-I are common in Norwegians, with a markedly decreased HDL cholesterol level.     

HDL 2 Particles are associated with hyperglycaemia,lower PON1 activity and oxidative stress in type 2 diabetes mellitus patients

ObjectivesIn this study we examined the relationship of oxidative stress and hyperglycaemia to antioxidative capacity of high-density cholesterol (HDL-C) particles in type 2 diabetes mellitus (DM).Design and methodsOxidative stress status parameters (superoxide anion (O₂^?), superoxide dismutase (SOD) activity and paraoxonase (PON1) status were assessed in 114 patients with type 2 DM and 91 healthy subjects. HDL particle diameters were determined by non-denaturing polyacrylamide gradient (3–31%) gel electrophoresis.ResultsPatients had significantly higher concentrations of oxidative stress parameter O₂^?(p < 0.001) and antioxidative defence, SOD activity (p < 0.001). Paraoxonase activity was significantly lower in diabetics (p < 0.001). The PON1₁₉₂ phenotype distribution among study groups was not significantly different. HDL 3 phenotype was significantly prevalent among patients (p < 0.001). Paraoxonase activity was significantly lower in patients with predominantly HDL 2 particles than in controls.ConclusionsThe results of our current study indicate that the diabetic HDL 2 phenotype is associated with hyperglycaemia, lower PON1 activity and elevated oxidative stress.     

Cyclosporine concentration-dependent increase in concentration ratio of mycophenolic acid acyl and phenol glucuronides to mycophenolic acid in stable kidney transplant recipients

ObjectivesThe aim of this study was to evaluate the influence of cyclosporine (CyA) and tacrolimus (Tac) on the pharmacokinetics of mycophenolic acid (MPA) and its glucuronides.Design and methodsKidney transplant recipients treated with mycophenolate mofetil and CyA (n = 18) or Tac (n = 17) in the stable phase were enrolled. The dependence of the trough concentration (C₀) ratios of MPA acyl glucuronide (AcMPAG) to MPA (AcMPAG/MPA) and MPA phenol glucuronide (MPAG) to MPA (MPAG/MPA) on CyA C₀ or Tac C₀ was evaluated.ResultsAcMPAG C₀ and MPAG C₀ were significantly higher in CyA- than Tac-treated recipients (P = 0.04 and 0.02, respectively). AcMPAG/MPA and MPAG/MPA were significantly correlated to CyA C₀ (r = 0.75, P < 0.01 and r = 0.81, P < 0.01, respectively), but not to Tac C₀.ConclusionsCyA increased AcMPAG/MPA as well as MPAG/MPA in a concentration-dependent manner, suggesting that higher CyA may cause AcMPAG-related adverse reactions. Tac did not alter pharmacokinetics of MPA and its glucuronides.     

Serum amyloid A is independently related to apolipoprotein A-I but not to HDL-cholesterol in patients with angina pectoris

BackgroundInflammation processes are considered important links between classical lipid risk factors and the progression of atherosclerosis. The interrelationship of high density lipoproteins (HDL) and apolipoprotein apoA-1 with acute phase proteins and cytokines was examined in a clinical setting of patients with angina pectoris.MethodsOn exclusion criteria (myocardial infarction, heart failure, CHD > 2 years, anticoagulant therapy), 198 patients were recruited and were subdivided according to angiographically documented stenosis, no stenosis vs. = 50% stenosis, in accordance with CASS guidelines. Lipids, apoA-1 and apoB, C-reactive protein (hs-CRP), fibrinogen, serum amyloid A (SAA) and cytokines (IL-6, IL-8, IL-10, IL2R, TNFα) were measured.ResultsLow HDL-C (and apoA-I) is associated with advanced coronary stenosis (= 50%) and with the number of diseased vessels, independent of age, gender, diabetes, smoking and lipid-lowering therapy. In contrast to hs-CRP and fibrinogen, SAA as well as cytokine levels were not significantly associated with stenosis. SAA (P = 0.0003) and diabetes (P = 0.0002) were strong predictors of apoA-I concentration independent of age, gender, BMI, smoking, CRP, as well as IL-6 in a multiple regression model. High SAA (P = 0.0067) and TG (P = 0.0123) were significant predictors of apoA-I/HDL-C ratio. However, SAA was not independently related to HDL-C.ConclusionsSAA is independently and inversely related to apoA-I but not to HDL-C in patients with angina pectoris, reflecting the effect of SAA on the quality of HDL particles. However, HDL-c but not SAA is inversely related to the degree of coronary artery stenosis.     

HDL in humans with cardiovascular disease exhibits a proteomic signature

BackgroundAlterations in protein composition and oxidative damage of high density lipoprotein (HDL) have been proposed to impair the cardioprotective properties of HDL. We tested whether relative levels of proteins in HDL₂ could be used as biomarkers for coronary artery disease (CAD).MethodsTwenty control and eighteen CAD subjects matched for HDL-cholesterol, age, and sex were studied. HDL₂ isolated from plasma was digested with trypsin and analyzed by high-resolution matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS) and pattern recognition analysis.ResultsPartial least squares discriminant analysis (PLS-DA) of mass spectra clearly differentiated CAD from control subjects with area under the receiver operating characteristic curve (ROC_AUC) of 0.94. Targeted tandem mass spectrometric analysis of the model's significant features revealed that HDL₂ of CAD subjects contained oxidized methionine residues of apolipoprotein A-I and elevated levels of apolipoprotein C-III. A proteomic signature composed of MALDI-MS signals from apoA-I, apoC-III, Lp(a) and apoC-I accurately classified CAD and control subjects (ROC_AUC = 0.82).ConclusionsHDL₂ of CAD subjects carries a distinct protein cargo and that protein oxidation helps generate dysfunctional HDL. Moreover, models based on selected identified peptides in MALDI-TOF mass spectra of the HDL may have diagnostic potential.     

Effects of common FTO gene variants associated with BMI on dietary intake and physical activity in Koreans

BackgroundAssociations with FTO (fat mass and obesity associated) gene variants and BMI have been reported in western adult populations. To widen the ethnic and age coverage of the FTO studies, we investigated the effects of FTO gene variants on being overweight and related phenotypes in Korean children and adult with a consideration of lifestyle factors.MethodsWe genotyped 711 children for 2 FTO SNPs (rs9939973 and rs9939609), analyzed lifestyle factors, and investigated the potential involvement of FTO variants in being overweight comparing with 8842 adults in the KSNP database.ResultsWith a strong association between FTO gene variants and BMI levels, we further identified an association between rs9939973 or rs9939609 and being overweight both children (P = 0.025, OR = 1.47, 95% CI = 1.05–2.06; P = 0.023, OR = 1.53, 95% CI = 1.06–2.22) and adults (P = 0.018, OR = 1.10, 95% CI = 1.02–1.19; P = 0.001, OR = 1.16, 95% CI = 1.06–1.27). Significant association was observed between rs9939609 and dietary fat intake in children (P = 0.008) but not in adults. In low physical activity subgroup of children, rs9939609 A allele carriers had a higher BMI than TT carriers (P = 0.0147). A significant interaction effect of rs9939609 on BMI across 3 levels of adult physical activity was found.ConclusionsFTO variant rs9939609 is an overweight susceptibility gene in Koreans. By low physical activity, A allele greatly influenced greater BMI.     

Genetic variant in visfatin gene promoter is associated with decreased risk of coronary artery disease in a Chinese population

BackgroundVisfatin is a newly identified pro-inflammatory adipokine expressed predominantly in visceral fat. Previous studies have suggested a role for visfatin in low-grade inflammation and regulation of lipid metabolism. Most recently, a genetic polymorphism ? 1535C > T located in the visfatin gene promoter has been identified, and suggested to be associated with the regulation of visfatin expression, lipid levels. However, it is unclear whether this polymorphism has a linkage with CAD.MethodsWe conducted a hospital-based case-control study with 257 CAD patients and 292 controls to examine the potential association of the Visfatin ? 1535C > T polymorphism with CAD.ResultsThe frequencies of the CC, CT, and TT genotypes in cases were significantly different from those of controls (χ² = 6.223, P = 0.045). Subjects with the variant genotypes (CT + TT) had a 40% decreased risk of CAD relative to CC carriers (adjusted OR = 0.60, 95%CI = 0.40–0.89). Furthermore, the adjusted OR of a TT genotype for CAD was 0.52 (95%CI = 0.31–0.87). There was a significant association between Visfatin ? 1535C > T polymorphism and triglyceride levels in both CAD patients and controls (P = 0.003, 0.018, respectively). In stratified analyses, the T allele was significantly associated with reduced risk of CAD in males, subjects with age < 59 years, and non-smokers. Moreover, a borderline statistical significance (P = 0.058 for trend) was observed between the variant genotypes and severity of CAD.ConclusionOur results suggested that Visfatin ? 1535C > T polymorphism might be associated with reduced risk of CAD in a Chinese population.     

The association between transforming growth factor β3 polymorphisms and left ventricular structure in hypertensive subjects

BackgroundTransforming growth factor β (TGF-β) may be a crucial regulator of cardiac remodeling. We investigated the association between the TGF-β gene polymorphisms and left ventricular structure.MethodsA total of 658 hypertensive subjects were genotyped for the TGF-β1 T869C and TGF-β3 (rs3917187 and rs4252338) polymorphisms.ResultsTGF-β3 rs3917187 AA homozygotes had, while accounting for covariates, greater left ventricular end-systolic (LVESD, P = 0.004) and end-diastolic dimension (LVEDD, P = 0.007) than G allele carriers. Moreover, left ventricular mass index (LVMI) in AA genotype was 123.0 ± 3.1 g/m² significantly higher than that in AG (114.6 ± 1.6 g/m²) and GG (115.4 ± 2.1 g/m², P = 0.03) genotypes. In multivariate regression analysis, TGF-β3 rs3917187 genotype as an independent predictor had statistically significant effects on LVESD (β = 0.164, P = 0.002), LVEDD (β = 0.172, P = 0.003) and LVMI (β = 0.136, P = 0.016), respectively. In further analyses, we observed a significant interaction between the rs3917187 and alcohol intake in relation to LVESD (P_int = 0.04) and left ventricular fractional shortening (LVFSH, P_int = 0.012). However, no relationship could be found between left ventricular parameters and the T869C or the rs4252338.ConclusionThe present results demonstrated that the TGF-β3 rs3917187 polymorphism was associated with left ventricular structure, and had an interactive influence with alcohol on LVESD and LVFSH in hypertensive subjects.     

Reverse modulation of the HDL Anionic Peptide Factor and phospholipid transfer protein activity in coronary artery disease and type 2 diabetes mellitus

ObjectivesThe high density lipoprotein Anionic Peptide Factor (HDL₃-APF) was previously described as an apolipoprotein that promotes the reverse cholesterol transport. Since phospholipid transfer protein (PLTP) is involved in such mechanism we attempted to focus on the two APF and PLTP proteins.Design and methodsWe recruited 56 type 2 diabetic patients with (n = 36) or without (n = 20) coronary artery disease (CAD) and 19 CAD patients. The three groups were compared to 39 healthy control subjects. In all groups, lipid profile was determined and plasma APF concentrations and PLTP activity were measured.ResultsIn all patients, the PLTP activity was significantly increased in comparison with controls (p < 0.01), in concomitance with a plasma APF level decrease in groups with CAD (with and without type 2 diabetes) (p < 0.01). Multiple linear regression analysis demonstrated that, when apoA-I, HDL-C, HDL-phospholipids and PLTP activity were taken into account as independent variables (after univariate regression analysis), HDL-PL was positively and independently related to APF (p < 0.0001 in whole population; p = 0.0090 in controls) and PLTP activity was negatively and independently related to APF in whole population and all patients' groups (all p < 0.05), but positively and independently associated to APF in controls (p = 0.0005).ConclusionsAPF could be considered as a specific marker against CAD and type 2 diabetes mellitus and our results confirm the atherogenic behavior of PLTP in CAD. Thus, these two proteins are likely to be regulated in a reverse manner.     

Changes in lipid measures and incident coronary heart disease: Tehran Lipid & Glucose Study

BackgroundData on the impact of changes in lipid measures on subsequent coronary heart disease (CHD) outcomes are not consistent.MethodsStudy was conducted in 4459 adults, aged ≥ 30 years, free of cardiovascular disease at baseline who attended two consecutive examinations first in 1999–2001 and second in 2001–2003, and were followed up until March 31, 2010. Multivariate Cox proportional hazard regression adjusted for baseline lipid measures and other risk factors was calculated for a 1 standard deviation (SD) change in total cholesterol (TC), log-transformed triglyceride (TG), high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C) (calculated using modified Friedewald formula), non-HDL-C, TC/HDL-C and log-transformed TG/HDL-C. Effect of change in dyslipidemia (TC ≥ 6.21 mmol/L or TG ≥ 2.26 mmol/L or HDL-C < 1.03 mmol/L or non-HDL-C ≥ 4.91 mmol/L) on incident CHD was examined, considering those with no dyslipidemia at baseline and follow-up as the reference group.ResultsDuring a mean follow-up of 9.5 years, 303 cases of CHD occurred. A 1-SD increase in TC, TG, non-HDL-C, TC/HDL-C and TG/HDL-C was associated with 14, 20, 19, 16 and 14% increase in risk of CHD event, respectively (all p values < 0.05); the corresponding risk for LDL-C was [1.12 (0.99–1.27), P = 0.07]. Participants with maintained dyslipidemia during follow-up had a significant risk for incident CHD [HR: 1.67(1.21–2.49)] compared to those with no dyslipidemia at baseline or follow-up.ConclusionChanges in TC, TG, and non-HDL-C, TC/HDL-C, TG/HDL-C were independent predictors of CHD events. Furthermore, maintained dyslipidemia was a strong predictor for CHD events.     

Lemon balm: A promising herbal therapy for patients with borderline hyperlipidemia—A randomized double-blind placebo-controlled clinical trial

ObjectiveMelissa officinalis is a perennial herb from the Lamiaceae family which has shown to have modulating effects on serum lipid profile. The aim of the current study is to explore the effects of M. officinalis supplementation on serum biochemical parameters of patients with borderline hyperlipidemia.Methods58 hyperlipidemic patients were allocated randomly to 2 groups: first group received capsules containing 1000 mg M. officinalis leaf powder (MO group), and the second group received placebo capsules (P group) 3 times per day for 2 months. Fasting blood glucose (FBG), HDL, LDL, Triglyceride, Creatinine and liver function enzymes including AST and ALT were evaluated before and after study.ResultsThe mean of LDL in MO group significantly decreased compared with P group after the supplementation (P = 0.02). Although the level of Cholesterol, FBG, HDL, Triglyceride, Creatinine and ALT did not show significant difference between two groups after 2 months (P ≥ 0.05), the level of AST exhibited a significant difference between two groups (P = 0.009).ConclusionsOur findings demonstrated that M. officinalis supplementation as a rich source of antioxidants and bioactive compounds can be effective in remission of LDL and AST levels in patients with borderline hyperlipidemia.     

Interaction of common sequence variants and selected risk factors in determination of HDL cholesterol levels

ObjectivesThe aim of our study was to assess the association of common sequence variants, and selected interactions, with HDL-c plasma levels.Design and methodsWe analysed 743 individuals (340 men and 403 women) with high mean triglyceride and LDL-c levels. The association of five polymorphic sites (ABCA1 g.1051G>A, APOA1 g.­75G>A, CETP g.­629C>A, HNF1A g.102A>C, and LIPG g.584C>T), apoE isoforms and selected interactions with HDL-c levels were evaluated using linear regression models.ResultsAfter adjusting for triglycerides, sex, and BMI the only genotype with a statistically significant effect on HDL-c levels (p-value = 0.004) was the CETP promoter variant. Further, linear regression model with interactions included indicated possible interplay between APOA1 genotype and menopause (p-value = 0.002) and ABCA1 and APOE isoforms (p-value = 0.017) on HDL-c plasma concentration.ConclusionsOur study indicated that not only the CETP variant but also apoE isoforms and menopause could operate as potent modulators of HDL-c concentrations.     

Axial and torsional stiffness of pediatric prosthetic feet

BackgroundProsthetic stiffness likely affects the walking biomechanics of toddlers and children with leg amputations, but the actual stiffness values for prostheses are not reported by manufacturers or in standardized testing procedures.AimWe measured axial (k_A) and torsional (k_T) stiffness from four brands of pediatric prosthetic feet (Trulife, Kingsley Mfg. Co., TRS Incorporated, and College Park Industries) over a range of foot sizes.MethodsWe applied forces and torques onto prostheses with a materials testing machine that replicated those exhibited in vivo by using the kinetics measured from four non-amputee toddlers (2–3 years) during walking.FindingsAcross brands, k_A averaged 35.2 kN/m during heel loading, was more stiff during midfoot loading (121.8 kN/m,  P < 0.001) and less stiff during forefoot loading (11.8 kN/m,  P = 0.013). k_A was similar across brands with no statistically significant effect of prosthetic foot size, with the exception of the TRS feet. Plantarflexion torsional stiffness (k_T1), was not statistically different across brands. For every 1 cm increase in foot size, k_T1 increased 0.16 kN·m/rad ( P < 0.001). College Park prostheses had 4.54 kN·m/rad lower dorsiflexion torsional stiffness (k_T2) ( P < 0.001) compared to other brands. For every 1 cm increase in foot size, the k_T2 applied on the foot increased 0.63 kN·m/rad.InterpretationThe axial and torsional stiffness testing methods are reproducible and should be adopted by prosthetic foot manufacturers. Axial and torsional stiffness values of commercially available prosthetic feet should be publically reported to health practitioners to ensure evidence-based decisions and meet the specific needs of each patient with a leg amputation.     

Increased serum brain-derived neurotrophic factor with high-intensity interval training in stroke patients: A randomized controlled trial

BackgroundPhysiological adaptations of stroke patients after high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) remain unclear.ObjectiveThis study determined the HIIT and MICT effects on aerobic capacity, cerebral oxygenation, peak cardiac output (CO), and serum brain-derived neurotrophic factor (BDNF) in stroke patients.MethodsWe included 23 stroke patients with age about 55 years and stroke duration > 24 months; participants completed 36 sessions of exercise training for 30 min; 13 were randomly assigned to perform MICT at 60% of peak oxygen consumption (VO_2peak) and 10 to perform HIIT at alternating 80% (3 min) and 40% (3 min) VO_2peak. Before and after interventions, we evaluated VO_2peak, peak CO, arteriovenous oxygen difference (AV O_2diff), bilateral frontal cortex oxygenation (relative changes of oxyhemoglobin Δ[O₂Hb], deoxyhemoglobin Δ[HHb], and total hemoglobin Δ[THb] levels), serum brain-derived neurotrophic factor (BDNF) level, and fluorescent cell staining for neuron morphology and percentage of cell-bearing neurites (% neurites).ResultsHIIT induced significant increases in VO_2peak (P = 0.008), CO (P = 0.038), Δ[HHb] (P = 0.046), Δ[THb] (P = 0.046), and serum BDNF level (P = 0.012). The improvement in VO_2peak was significantly greater with HIIT than MICT (20.7% vs. 9.8%, P = 0.031), as was AV O_2diff (P = 0.041), Δ[HHb] (P = 0.027), and serum BDNF level (P < 0.001). HIIT facilitated neuron dendritic protrusions (greater % neurites, P = 0.012) with prominent redistribution of mitochondria.ConclusionAs compared with MICT, HIIT-improved aerobic capacity by increasing systemic tissue O₂ extraction in stroke patients. Increased cerebral O₂ utilization in the involved hemisphere was also identified after HIIT. These physiological adaptations may be associated with increased serum BDNF level. In vitro dendritic growth in neurons treated with serum from HIIT participants may imply significant effects on neuron activities as compared with MICT.ClinicalTrials.gov identifierNCT04135391.     

FTO and MC4R gene variants determine BMI changes in children after intensive lifestyle intervention

ObjectivesThis study aimed to determine whether there is a relationship between common FTO (rs17817449) and MC4R (rs17782313) gene variants and body mass reduction or weight loss after a one-month lifestyle intervention in overweight/obese children.Design and methodsWe genotyped 357 unrelated non-diabetic Czech children (age 13.7 ± 4.9 years, average BMI at baseline 30.8 ± 4.6 kg/m²). Biochemical and anthropometrical measurements were performed before and after 4 weeks of lifestyle interventions (comprising a reduction in energy intake to the age-matched optimum and a supervised exercise program consisting of 5 exercise units per day, 50 min each).ResultsThe mean weight loss achieved was 6.2 ± 2.1 kg (P < 0.001). Significant associations were found between a BMI decrease and the FTO and MC4R variants. Carriers of the FTO GG genotype and/or MC4R CC genotype lost significantly more body weight compared to noncarriers (P < 0.0009 for BMI and P < 0.002 for body weight). These differences remained significant following adjustment for sex, age and baseline values (P = 0.004 for BMI and P = 0.01 for body weight).ConclusionsFTO and MC4R gene variants modify the impact of an intensive lifestyle intervention on BMI decrease in overweight/obese children. Carriers of the FTO GG genotype and MC4R CC genotype benefit significantly more from the lifestyle intervention.     

A ventilation technique for oxygenation and carbon dioxide elimination in CPR: Continuous insufflation of oxygen at three levels of pressure in a pig model

AimPulmonary ventilation remains an important part of cardiopulmonary resuscitation, affecting gas exchange and haemodynamics. We designed and studied an improved method of ventilation for CPR, constructed specifically to support both gas exchange and haemodynamics. This method uses continuous insufflation of oxygen at three levels of pressure, resulting in tri-level pressure ventilation (TLPV). We hypothesized that TLPV improves gas exchange and haemodynamics compared to manual gold standard ventilation (GSV).MethodsIn 14 pigs, ventricular fibrillation was induced and automated CPR performed for 10 min with either TLPV or GSV. After defibrillation, CPR was repeated with the other ventilation method. Gas exchange and haemodynamics were monitored. Data are presented as mean ± standard error of the mean.ResultsTLPV was superior to GSV for PaO₂ (163 ± 36 mmHg difference; P = 0.001), and peak AWP (−20 ± 2 cmH₂O difference; P = 0.000) and higher for mean AWP (8 ± 0.2 cmH₂O difference; P = 0.000). TLPV was comparable to GSV for CPP (5 ± 3 mmHg difference; P = 0.012), VCO₂ (0.07 ± 0.3 mL/min/kg difference; P = 0.001), SvO₂ (4 ± 3%-point; P = 0.001), mean carotid flow (−0.5 ± 4 mL/min difference; P = 0.016), and pH_a (0.00 ± 0.03 difference; P = 0.002). The PaCO₂ data do not provide a conclusive result (4 ± 4 mmHg difference).ConclusionWe conclude that the ventilation strategy with a tri-level pressure cycle performs comparable to an expert, manual ventilator in an automated-CPR swine model.