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Lipedema is a chronic, progressive disease of adipose tissue with lack of consistent diagnostic criteria. The aim of this study was a thorough comparative characterization of extracellular microRNAs (miRNAs) from the stromal vascular fraction (SVF) of healthy and lipedema adipose tissue. For this, we analyzed 187 extracellular miRNAs in concentrated conditioned medium (cCM) and specifically in small extracellular vesicles (sEVs) enriched thereof by size exclusion chromatography. No significant difference in median particle size and concentration was observed between sEV fractions in healthy and lipedema. We found the majority of miRNAs located predominantly in cCM compared to sEV enriched fraction. Surprisingly, hierarchical clustering of the most variant miRNAs showed that only sEVmiRNA profiles – but not cCMmiRNAs – were impacted by lipedema. Seven sEVmiRNAs (miR–16-5p, miR-29a-3p, miR-24-3p, miR-454-p, miR–144-5p, miR-130a-3p, let-7c-5p) were differently regulated in lipedema and healthy individuals, whereas only one cCMmiRNA (miR-188-5p) was significantly downregulated in lipedema. Comparing SVF from healthy and lipedema patients, we identified sEVs as the lipedema relevant miRNA fraction. This study contributes to identify the potential role of SVF secreted miRNAs in lipedema.

Vaccine hesitancy is an emerging phenomenon particularly in industrialized nations. It has led to repeated epidemic outbreaks of otherwise vaccine-preventable, infectious diseases. Compared to other countries very low rates of influenza and measles vaccination rates have been reported in Austria. We performed a single-center cross-sectional, questionnaire-based survey. A total of 350 adult patients attending our emergency room participated in this survey. We assessed knowledge and attitudes towards vaccination and the associated infectious diseases. Out of 350 participants 40 (11.4 %) declared that they deliberately refused vaccinations. Most common reasons for non-vaccination were fear of adverse effects (35.9 %), doubt of effectiveness of vaccines (35.9 %) and distrust towards the pharmaceutical industry (23.1 %). Of all 350 participants only 148 (42.3 %) thought themselves to be sufficiently informed about national vaccination recommendations as stated in the Austrian National Vaccination Program (ANVP). General practitioners (GP) were the primary source of healthcare-related information for 256 (73.1 %) participants. Furthermore, GPs as well as hospital-based physicians achieved the highest level of trust in this study population. The results of our study underline the necessity of comprehensive informational campaigns on the merits of vaccination. A lack of knowledge about the benefits of vaccination, uncertainty and unfounded fears seem to prevent the achievement of recommended vaccination rates. Family GPs enjoyed the highest levels of trust in our study population. We believe that additional information communicated by GPs could help boost the low vaccination rates. This study underlines the important role of primary care practitioners in informing patients about vaccines and healthcare topics.

Children prefer to learn from people who are like themselves. However, who is considered "like themselves" is complex for bilingual children. Thus, the current study examined whether children's language experiences affect who they prefer to imitate. A sample of 3- to 5-year-old monolingual English-speaking children (n=16), Japanese-English bilingual children (n=16), and children bilingual in English and a non-Japanese language (n=16) watched videos of a monolingual English speaker and a Japanese-English bilingual speaker playing with novel toys and were asked to play with the same novel toys. Although all children--regardless of language background--imitated the monolingual speaker at similar rates, the two bilingual groups imitated the bilingual speaker more often than did the monolingual children. Such results suggest that experience in speaking two languages affects children's imitation behaviors.

BACKGROUND Cryolipolysis combined with shockwave therapy has been previously shown to have synergistic effects in body contouring results. OBJECTIVE This open-label, prospective, multicenter, comparative study investigated the safety and efficacy of combined cryolipolysis, shockwave therapy with cryolipolysis, shockwave therapy, and injection polyenylphosphatidylcholine-based lipolysis. METHODS Enrolled patients were treated in the abdominal or flank area with cryolipolysis, shockwave therapy and injection lipolysis (n = 10) or cryolipolysis and shockwave therapy (n = 4). All treatments were conducted the same day. Evaluations were conducted 3 months after treatment and included histological analysis, standardized photography, blinded-investigator efficacy, and safety ratings, as well as patient ratings of satisfaction and tolerance. RESULTS Compared to baseline, the 3-month follow-up histological analysis revealed a more profound subcutaneous adipose tissue reaction with the triple combination therapy (cryolipolysis, injection lipolysis, radial shock wave) than with the double combination with regard to adipocyte damage and grade of inflammation. Waist circumference was significantly reduced in patients of both groups, but patients in the triple combination group were shown to have a significantly more pronounced reduction in subcutaneous fat. Factors that were shown to influence treatment outcome included baseline BMI and waist circumference. Age and gender had no effect. The abdominal area reacted better to the treatment compared to flanks. No significant side effects or adverse events were reported. The procedure was well-tolerated, and the majority of patients were satisfied with the treatment results. CONCLUSIONS Combination of cryolipolysis, radial shockwave, and injection lipolysis is a safe, well-tolerated treatment for reduction in subcutaneous fat.

Although many executive function (EF) tasks require only nonverbal responses, the language used by experimenters to explain the task may be important for young children's EF task performance. This study investigated how the vocabulary used in explaining an EF task affects 2-year-olds' performance. Experiment 1 used the standard instructions for the Reverse Categorization Task, in which children are asked to sort different-sized blocks into different-sized buckets according to one rule and then switch to a new rule. In Experiment 2, the task remained the same, but different instructions requiring less knowledge of size words were used. Children's productive vocabulary was assessed in both experiments but was only correlated with task performance in Experiment 1. These results suggest that task-specific vocabulary knowledge may play a role in children's performance on tasks designed to measure nonverbal cognitive ability.

Children have a difficult time in generalizing among changes in background context. We examined the role of two processes that may aid in generalizing category labels in new contexts. In this study, 2-year-old children were taught novel object categories in one type of contextual condition and were tested for category generalization in a new context. In Experiment 1, children ( N = 48) learned in one of three conditions: (a) all category instances presented in the same context, (b) all category instances presented in varied contexts, or (c) some category instances presented in the same context and some presented in varied contexts. In Experiment 2, children ( N = 48) learned in one of three conditions, all of which included presentations in the same context and varied contexts but differed in order. Results from both experiments revealed that children were significantly more likely to choose the correct object when training was in both same and varied contexts regardless of order. The results suggest that contextual factors, by providing both support for aggregation and support for decontextualization, contribute to word learning and generalization for novice word learners.

Due to the central role of categorization and generalization in cognition, a considerable amount of research has examined the factors that promote generalization. One particular factor that has been shown to facilitate generalization is the timing with which instances of a category are presented. The findings of this research present a paradoxical set of results—both presenting instances at the same time, providing an opportunity to compare instances simultaneously, and presenting instances apart in time, by spacing the presentation of instances out in time, have been shown to facilitate generalization. In this study, we examine these findings by investigating how simultaneous, massed, and spaced learning schedules affect children’s in-the-moment and long-term generalization. Moreover, we identify a mechanism, ease of retrieval during learning, which may contribute to differences in performance across time.

Objective HDL modifying effects of cholesteryl ester transfer protein (CETP) and hepatic lipase (LIPC) depend in part on each other. We studied associations of CETP -Taq1B and -514C>T- LIPC polymorphisms with hepatic mRNA levels, and their combined effects on plasma lipids and carotid atherosclerosis. Methods We genotyped the CETP -Taq1B and the -514C>T- LIPC polymorphisms in 67 obese women in whom hepatic CETP and LIPC transcript levels were determined as well as in 1549 participants of the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR). Carotid atherosclerosis was assessed by intima-media thickness and extent of plaques (B-score) of the carotid arteries. Results In obese women, CETP -Taq1B and -514C>T- LIPC variant alleles were associated with reduced hepatic levels of CETP and LIPC mRNA, respectively. The CETP and LIPC polymorphisms accounted for 12.9 and 14.4% of the variability in respective transcripts. In the SAPHIR population, CETP -Taq1B showed independent effects on LDL diameter, HDL and LDL cholesterol, apolipoproteins AI and B and cholesterol/HDL cholesterol, while -514C>T- LIPC revealed independent effects on HDL cholesterol and apolipoprotein AI. The two polymorphisms displayed interactions at the level of HDL cholesterol. Compared to subjects carrying wild-type alleles at both loci, subjects homozygous for the CETP wild-type allele, but heterozygous for the LIPC polymorphism and subjects heterozygous for the CETP polymorphism, but homozygous for the LIPC wild-type allele showed an increased risk of carotid atherosclerosis (both P Conclusions CETP and LIPC polymorphisms influence the respective hepatic transcript levels, demonstrate interactions on HDL cholesterol and suggest that imbalances between CETP and LIPC activities may modulate the risk of carotid atherosclerosis.

Aims: Vascular endothelial growth factor (VEGF) is a potent hypoxia-regulated angiogenic factor. Its soluble receptor soluble (s)Flt-1 binds VEGF with high affinity inhibiting the angiogenic function of VEGF. The role of circulating VEGF in atherosclerosis is unclear. Methods and results: In 909 healthy subjects (511 male, 398 female) from the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) we determined fasting plasma VEGF and sFlt-1 concentration, cardiovascular risk factors and carotid atherosclerosis. VEGF levels were lower and sFlt-1 levels higher in men than in women. VEGF and sFlt-1 showed a positive correlation. In the entire population VEGF correlated positively with age, BMI, insulin resistance, white blood cell and platelet count, C-reactive protein (CRP) and carotid intima media thickness (IMT). After adjustment for age, VEGF showed a weak positive correlation with BMI, liver enzymes, CRP and platelet count in males. In females VEGF correlated negatively with LDL-cholesterol and positively with insulin resistance and platelet count. After adjustment for age, no significant correlation with carotid atherosclerosis could be detected. Conclusion: Plasma VEGF and sFlt-1 are only weakly correlated with cardiovascular risk factors, suggesting that circulating VEGF levels do have only a minor impact on the development of atherosclerosis.

Purpose Patients undergoing long-term treatment with valproic acid (VPA) are prone to develop different features of the metabolic syndrome (MS). The aim of the present study was to evaluate the occurrence of non-alcoholic fatty liver disease (NAFLD), insulin resistance (IR) and a pro-atherogenic lipid profile in patients undergoing VPA, carbamazepine (CBZ) and lamotrigine (LTG) monotherapy compared to healthy controls. Methods Abdominal ultrasound as well as measurement of serum fasting insulin and glucose, serum lipids and liver function parameters were performed in VPA ( n =23), CBZ ( n =22) and LTG ( n =23) treated non-diabetic and non-obese epileptic patients compared to healthy controls ( n =16). Results Ultrasound measurement demonstrated characteristics of fatty liver disease in 60.9% of VPA, in 22.7% of CBZ, in 8.7% of LTG treated patients and in 12.5% of the healthy controls, with highest level of steatosis seen in VPA treated patients. In addition, patients on VPA monotherapy showed a higher body-mass index (BMI) when compared to LTG treated patients and controls ( p ≤0.049). Total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and γ-glutamyltransferase (γGT) were greatest in the CBZ group ( p ≤0.043). Interestingly, serum fasting glucose, serum fasting insulin as well as the HOMA-IR did not differ significantly between groups. Conclusion In conclusion, VPA (and moderately CBZ) therapy is related to increased risk for ultrasonographic signs of fatty liver disease, emphasizing the importance of regular ultrasound measurements as well as monitoring of serum lipids and BMI during enzyme-modulating AED treatment.

The spacing effect describes the robust phenomenon whereby memory is enhanced when learning events are distributed, instead of being presented in succession. We investigated the effect of spacing on children's memory and category induction. Three-year-old children were presented with two tasks, a memory task and a category induction task. In the memory task, identical instances of an object were presented and then tested in a multiple choice test. In the category induction task, different instances of a category were presented and tested in a multiple choice test. In both tasks, presenting the instances in a spaced sequence resulted in more learning than presenting the instances in a massed sequence, despite the difficulty created by the spaced sequence. The spaced sequence increased the difficulty of the task by allowing children time to forget the previous instance during the spaced interval.

The metabolic syndrome is associated with low high-density lipoprotein-cholesterol (HDL-C) and decreased low-density lipoprotein (LDL) particle size. The Taq1B-polymorphism in the cholesteryl ester-transfer protein (CETP)-gene influences HDL-C, CETP concentration, and LDL-size. We investigated the effect of the Taq1B-polymorphism on the risk of the metabolic syndrome in 1,503 participants (973 men, 530 women) of the Salzburg Atherosclerosis Prevention program in subjects at High Individual Risk study. CETP concentration was determined in a subgroup (n = 486) by an enzyme-linked immunosorbent assay. Prevalence of the metabolic syndrome was 16.7% (18.5% in men, 13.5% in women). The Taq1B-polymorphism influenced significantly CETP concentrations, HDL-C levels, and LDL-size (P < 0.001 for all). The relative risk of the metabolic syndrome was reduced by 32% (odds ratio (OR) 0.68 (95% CI: 0.51-0.89), P = 0.005) in carriers of the B2 variant. This risk reduction persisted after adjustment for age and sex (OR 0.69 (0.53-0.92), P = 0.01) and after further adjustment for body mass index, waist-to-hip ratio, blood pressure, insulin resistance (IR), HDL-C, and triglycerides (TGs) (OR 0.43 (0.26-0.72), P = 0.001). Furthermore, the risk reduction was more pronounced in men than in women. We conclude that CETP plays an important role in the metabolic syndrome, possibly involving novel functions of CETP.

In eleven patients with chronic renal insufficiency treated by intermittent haemodialysis and in ten normal subjects, hepatic and extrahepatic triglyceride lipase activity of post heparin plasma was selectively measured, utilizing the different sensitivity of both enzymes to inhibition by protamine sulphate. In uraemic patients, hepatic triglyceride lipase activity was significantly decreased and extrahepatic triglyceride lipase activity was normal when compared with the control group. The uraemic subjects showed a moderate hypertri-glyceridaemia; their serum cholesterol level, however, was normal. The high triglyceride concentration was due to an increase of very low density lipoproteins and low density lipoproteins of the density between 1.006 and 1.019g/ml (LDL1) The concentration of low density lipoproteins of the density between 1.019 and 1.063g/ml (LDL2) was decreased. LDL2 were relatively rich in triglycerides when compared with LDL2 from the control group.

Genetic variations of the scavenger receptor class B type I (SR-BI) have been demonstrated to be associated with plasma lipid parameters, anthropomorphic parameters, and coronary artery disease. We determined the frequency of 3 single-nucleotide polymorphisms within the SR-BI gene (SCARB1) in 354 patients with peripheral arterial disease (PAD) and 354 controls matched for age, sex, and diabetes and related to lipids and disease state, that is, PAD. SCARB1 combined genotype exon 1/intron 5/exon 8 were found to be associated with plasma total and low-density lipoprotein cholesterol levels, respectively. In terms of disease, a significant risk for PAD was observed in female subjects carrying the common allele of exon 8 (odds ratio, 2.623; 95% confidence interval, 1.321-5.208; P = .003). The variant allele of intron 5 was found to be a risk factor for PAD in men (odds ratio, 2.182; 95% confidence interval, 1.288-3.698; P = .005). Furthermore, the SCARB1 combined genotype intron 5/exon 8 proved predictive for PAD in the whole population (P = .006), which remained significant after correction for traditional risk factors. In conclusion, in the present study population, SCARB1 polymorphisms not only show associations with plasma levels of total and low-density lipoprotein cholesterol, respectively, but also with the risk for PAD.

In recent years, biomimetic synthetic apatite nanoparticles (AP-NPs), having chemical similarity with the mineral phase of bone, have attracted a great interest in nanomedicine as potential drug carriers. To evaluate the therapeutic perspectives of AP-NPs through the mechanisms of action and organs they interact with, the noninvasive monitoring of their in vivo behavior is of paramount importance. To this aim, here the feasibility to radiolabel AP-NPs ("naked" and surface-modified with citrate to reduce their aggregation) with two positron emission tomographic (PET) imaging agents ([F-18]NaF and Ga-68-NO(2)AP(BP)) was investigated. [F-18]NaF was used for the direct incorporation of the radioisotope into the crystal lattice, while the labeling by surface functionalization was accomplished by using Ga-68-NO(2)AP(BP) (a new radio-metal chelating agent). The labeling results with both tracers were fast, straightforward, and reproducible. AP-NPs demonstrated excellent ability to bind relevant quantities of both radiotracers and good in vitro stability in clinically relevant media after the labeling. In vivo PET studies in healthy Wistar rats established that the radiolabeled AP-NPs gave significant PET signals and they were stable over the investigated time (90 min) since any tracer desorption was detected. These preliminary in vivo studies furthermore showed a clear ability of citrated versus naked AP-NPs to accumulate in different organs. Interestingly, contrary to naked AP-NPs, citrated ones, which unveiled higher colloidal stability in aqueous suspensions, were able to escape the first physiological filter, i.e., the lungs, being then accumulated in the liver and, to a lesser extent, in the spleen. The results of this work, along with the fact that AP-NPs can be also functionalized with targeting ligands, with therapeutic agents, and also with metals for a combination of different imaging modalities) make AP-NPs very encouraging materials for further investigations as theranostic agents in nanomedicine.

Objective. The B1B1 variant of the cholesteryl ester transfer protein (CETP) TaqIB polymorphism and high plasma CETP concentrations are associated with favourable angiographic outcomes in pravastatin-treated patients suffering from coronary artery disease (CAD). The purpose of the present study was to test whether CETP TaqIB genotypes and/or plasma CETP concentrations at baseline also predict clinical end-points in patients with CAD. Design. Prospective longitudinal observational study. Setting. Primary care doctors (n = 88) and hospitals (n = 7) in Austria. Subjects. A total of 1620 men and women with preexisting CAD were recruited and plasma lipids were determined at study entry. 1389 hypercholesterolaemic patients were included and 1002 patients completed the follow-up. Interventions. In all patients treatment with pravastatin was started and patients were followed up for 2 years. Main outcome measures. Cardiovascular events. Results. One hundred patients suffered at least one cardiovascular event. We observed significantly more events in patients within the lowest compared with the highest quartile of plasma CETP concentrations (odds ratio 3.20, CI95 1.65–6.23; P = 0.001, adjusted for known risk factors of CAD). No significantly different numbers of cardiovascular events were found between CETP TaqIB genotypes. Conclusions. Plasma CETP concentrations, but not CETP TaqIB genotypes, predict cardiovascular events in patients with CAD treated with pravastatin. Despite higher LDL cholesterol concentrations, high plasma CETP concentrations at baseline are associated with fewer cardiovascular events compared with low plasma CETP concentrations in CAD patients treated with pravastatin.

OBJECTIVE Low high-density lipoprotein cholesterol (HDL-C), hypertriglyceridemia, and small dense-low density lipoprotein (LDL) are key components of metabolic syndrome (MS). Cholesteryl ester transfer protein (CETP) mediates the transfer of triglycerides (TGs) from TG-rich lipoproteins to HDL and LDL particles in exchange for cholesteryl esters, leading to low HDL-C and small dense-LDL. The aim of this study was to investigate the role of CETP in subjects with MS. RESEARCH METHODS AND PROCEDURES In a cross-sectional cohort of 234 middle-aged men and 252 women randomly selected from the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study, MS was diagnosed according to the National Cholesterol Education Program guidelines. CETP mass was determined by enzyme-linked immunosorbent assay and LDL size-by-gradient polyacrylamide gel electrophoresis. RESULTS Men and women with MS had lower HDL-C (45 +/- 7 vs. 58 +/- 13 and 48 +/- 10 vs. 71 +/- 14 mg/dL for men and women, respectively; p < 0.001 for all) and higher TG levels (222 +/- 71 vs. 98 +/- 54 and 167 +/- 67 vs. 90 +/- 35 mg/dL for men and women, respectively; p < 0.001 for all) than healthy subjects. LDL size was lower in subjects with MS (256 +/- 11 A vs. 267 +/- 11 A and 262 +/- 10 A vs. 273 +/- 8 A for men and women, respectively; p < 0.001 for all). CETP mass was higher in men with MS (1.87 +/- 0.78 vs. 1.40 +/- 0.65 mug/mL; p < 0.001) but not in women (1.74 +/- 0.79 vs. 1.62 +/- 0.62 mug/mL). CETP mass correlated inversely with LDL size in both men and women (r = -0.19, p < 0.01 and r = -0.13, p < 0.05 in men and women, respectively). DISCUSSION MS is associated with increased CETP mass in men. Increased CETP mass may be responsible for reduced HDL-C and reduced LDL particle diameter in MS.

Objective: In obesity, plasma leptin is high and soluble leptin receptor (sOb-R) levels are low, resulting in a low fraction of bound leptin. The aim of this study was to investigate the influence of insulin resistance (IR) and the metabolic syndrome (MS) on sOb-R concentration and the bound-free ratio of leptin. Research Methods and Procedures: sOb-R, leptin levels, and homeostasis model assessment (HOMA) index for IR were determined in 76 middle-aged obese or overweight men. Results: Concentration of sOb-R and soluble receptor-bound fraction of leptin were lowest in the highest tertile of HOMA-IR. sOb-R and the bound-free ratio of leptin correlated with HOMA-IR, leptin concentration, and waist-to-hip ratio independently of age, BMI, and fat mass. Leptin and waist-to-hip ratio were the sole independent determinants of sOb-R concentration, and BMI, HOMA-IR, and visceral adipose tissue were independent determinants of the bound fractin of leptin. sOb-R concentration and the bound fraction of leptin decreased with increasing numbers of components of the MS, resulting in lower sOb-R concentration and a lower fraction of bound leptin in men with the MS. Discussion: IR and abdominal obesity are associated with low sOb-R concentration and low bound-free ratio of leptin independent of fat mass. Low sOb-R concentration and low bound-free ratio of leptin segregate with components of the MS. We suggest that low sOb-R levels and a low fraction of specifically bound leptin are markers of leptin resistance, which is independently associated with IR and abdominal obesity and may constitute an additional component of the MS.

Kaser S, Sandhofer A, Holzl B, Gander R, Ebenbichler CF, Paulweber B, Patsch JR (University Hospital Innsbruck, Innsbruck; and General Hospital Salzburg, Salzburg, Austria). Phospholipid and cholesteryl ester transfer are increased in lipoprotein lipase deficiency. J Intern Med 2003; 253: 208–216. Objectives. Phospholipid transfer protein (PLTP) and cholesteryl ester transfer protein (CETP) are key enzymes in lipoprotein metabolism by mediating the transfer and exchange of phospholipids (PL) and neutral lipids between lipoproteins. Lipoprotein lipase (LPL) deficiency is associated with low HDL-cholesterol (HDL-C) levels in both, the homozygous and heterozygous state. In the present study we set out to investigate the role of lipid transfer proteins, which are known to strongly determine HDL-C levels, in LPL deficiency. Design/subjects. Phospholipid acceptor and donor properties of lipoproteins, PLTP activity, CETP mass, activity and cholesteryl ester (CE) transfer were determined in two homozygous and six heterozygous LPL-deficient subjects and in 10 healthy, normolipidaemic controls, respectively. Results. The HDL isolated from LPL-deficient subjects showed strongly increased PL-acceptance when compared with controls (homozygotes versus heterozygotes versus control: 26.46 ± 15.26 vs. 3.41 ± 1.61 vs. 1.89 ± 0.33 μmol mL−1 h−1/μmol mL−1 PL; all P

Heat waves result in excess deaths, excess emergency department visits, and intensive care unit admissions for heat stroke. We describe the clinical features and 3-month outcome of a patient with near-fatal heat stroke, admitted to our intensive care unit in July, 2001. After heavily working for hours at a construction site during a heat wave, the 28-year-old male presented with 41.4 degrees C body temperature and multiorgan failure, consisting of neurological impairment, rhabdomyolysis, acute renal failure, disseminated intravascular coagulation, and acute respiratory distress syndrome (ARDS). In the first week there was no evidence of infection. Treatment included cooling, aggressive volume resuscitation, administration of antithrombin-III concentrates and steroids. The patient survived and recovered normal neurological, renal, respiratory and haematological function, and no disability persisted. This case illustrates survival and complete recovery after multiorgan failure in heat stroke with vigorous intensive care. Treatment with antithrombin and steroids and may well have contributed to the favourable outcome. Correction of reduced antithrombin III levels to supranormal by therapeutic administration of antithrombin III concentrate in disseminated intravascular coagulation of heat stroke was not associated with any bleeding complications.

To understand how generalization develops across the lifespan, researchers have examined the factors of the learning environment that promote the acquisition and generalization of categories. One such factor is the timing of learning events, which recent findings suggest may play a particularly important role in children's generalization. In the current study, we build on these findings by examining the impact of equally spaced versus expanding learning schedules on children's ability to generalize from studied exemplars of a given category to new exemplars presented on a later test. We found no significant effects of learning schedule when the generalization test was administered immediately after the learning phase, but there was a clear difference when the generalization test was delayed by 24. h, with children in the expanding condition significantly outperforming children in the equally spaced learning condition. These results suggest that forgetting and retrieval dynamics may be lower level cognitive mechanisms promoting generalization and have several implications for broad theories of learning, cognition, and development. © 2014 Elsevier Inc.

An insertion/deletion polymorphism in the gene coding for the angiotensin-converting enzyme (ACE) is strongly associated with ACE activity. This polymorphism may be a marker for an increased risk for cardiovascular events. Our study examined a possible relationship between the D/I polymorphism and myocardial release of atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP). Ninety-six individuals with normal or impaired left ventricular function were included in the study. ANP and BNP plasma levels were measured at rest and after exposure to physical stress. At rest no association of ACE genotypes with ANP and BNP was found. After exercise homozygotes with the genotype DD had significantly higher ANP plasma levels than homozygotes with the genotype II. In contrast to ANP, BNP levels were not significantly different between genotype groups after exercise. Differences in site of production and mode of release between ANP and BNP might explain this difference. We hypothesize that our result might represent a variability gene effect of the ACE gene locus on endocrine processes in the heart during exposure to physical stress.

In order to understand how generalization develops across the lifespan, researchers have examined the factors of the learning environment that promote the acquisition and generalization of categories. One such factor is the timing of learning events, which recent findings suggest may play a particularly important role in children's generalization. In the current study, we build upon these findings by examining the impact of equally spaced versus expanding learning schedules on children's ability to generalize from studied exemplars of a given category to new exemplars presented on a later test. We found no significant effects of learning schedule when the generalization test was administered immediately after the learning phase, but there was a clear difference when the generalization test was delayed by 24 hours: Children in the expanding condition significantly outperformed children in the equally spaced learning condition. These results suggest forgetting and retrieval dynamics may be lower-level cognitive mechanisms promoting generalization and have several implications for broad theories of learning, cognition, and development.

Adherence to a low-calorie diet often results in a decrease in blood glucose concentration in persons with non-insulin-dependent diabetes mellitus (NIDDM). Whether this is due to the resultant weight loss or to a decrease in caloric intake has been uncertain. We have obtained data previously that indicated a very short-term reduction in caloric intake (5 hours) resulted in a significant decrease in plasma glucose concentration in subjects with NIDDM. The purpose of the present study was to determine if a further decrease in glucose would occur if the fast was extended from 5 to 24 hours. Seven male subjects with untreated NIDDM were studied after an 11-hour overnight fast. For the subsequent 24-hour period, subjects were given only water. Blood was obtained for glucose, insulin, C-peptide, triglycerides, nonesterified fatty acids (NEFA) alpha-amino acid nitrogen, urea nitrogen, and glucagon at hourly intervals for 24 hours beginning at 8 AM. The amount of glycogen degraded was calculated based on the potassium balance. Plasma glucose decreased from 158 mg/dL at 8 AM to a nadir of 104 mg/dL at 7 PM. It then increased by 30 mg/dL. Corresponding changes occurred in insulin and C-peptide. Serum glucagon remained unchanged. Serum alpha-amino acid nitrogen and urea nitrogen decreased. Triglycerides and NEFA increased. The calculated glycogen utilized over this period was approximately 167 g. This would provide approximately 700 kcal energy. The elevated blood glucose concentration in mild to moderately severe untreated NIDDM subjects was normalized following short-term fasting. Plasma insulin concentrations also decreased to within normal limits. These decreases were highly significant. Glycogenolysis is an important source of fuel during this period.

Silicone gel has for many years had a primary role in the treatment and prevention of abnormal scars, in the form of hypertrophic scars and keloids after epithelialization. The authors report preliminary findings on the use of a new, medical-grade, film-forming silicone gel dressing approved for use on open wounds and injured skin as monotherapy and in combination with other treatments prior to re-epithelialization. An observational study involving 105 patients examined the silicone gel's effectiveness in promoting accelerated epithelialization, reducing the inflammatory response and in the prevention of scarring. The study was conducted on a range of dermatological surgical interventions. The authors' observations confirmed silicone's role in promoting accelerated wound healing, scar prevention, and the utility of this new film-forming silicone dressing when used in combination with various other treatment modalities.

This study examined a possible relationship between genetic variation in the gene coding for the angiotensin converting enzyme (ACE) and increased risk for coronary heart disease (CHD) in an Austrian population. Polymerase chain reaction (PCR) was used to determine the genotypes for an insertion/deletion polymorphism in intron 16 of the ACE gene in 315 patients with CHD and in 149 normal controls. In the control group, the relative allele frequencies of the polymorphism were similar to those of previously published European studies. The genotype distribution among our patients was not significantly different from that among controls. We were not able to show a significant association of the DD genotype with coronary heart disease in subgroups containing patients considered at low coronary risk. There was no association of lipid parameters and ACE genotype. From these data we conclude that, in the Austrian population, the insertion/deletion polymorphism in the ACE gene cannot be used as a marker for coronary risk assessment.

Valproic acid (VPA), as one of the most widely prescribed antiepileptic drugs (AED) for many types of epilepsy in adults and children, is associated with weight gain, alteration of adipocytokine homeostasis, insulin resistance and Non-Alcoholic Fatty Liver Disease (NAFLD). Retinol-binding protein 4 (RBP4) and Glucagon-like peptide-1 (GLP-1) are considered as important new targets in modern type 2 diabetes mellitus therapy linked to insulin resistance, NAFLD and visceral obesity acting via peripheral or central mechanisms. We herein demonstrate the lack of an influence of VPA treatment on RBP4 and GLP-1 in otherwise healthy patients. In summary, the absence of any relationship with RBP4 and GLP-1 concentrations does not suggest a role of these novel insulin resistance parameters as potential regulators of glucose and fat metabolism during VPA-therapy.

The spacing effect describes the robust finding that long-term learning is promoted when learning events are spaced out in time, rather than presented in immediate succession. Studies of the spacing effect have focused on memory processes rather than for other types of learning, such as the acquisition and generalization of new concepts. In this study, early elementary school children (5–7 year-olds; N = 36) were presented with science lessons on one of three schedules: massed, clumped, and spaced. The results revealed that spacing lessons out in time resulted in higher generalization performance for both simple and complex concepts. Spaced learning schedules promote several types of learning, strengthening the implications of the spacing effect for educational practices and curriculum.

Two novel mutations in the lipoprotein lipase (LPL) gene are described in an Austrian family: a splice site mutation in intron 1 (3 bp deletion of nucleotides -2 to -4) which results in skipping of exon 2, and a missense mutation in exon 5 which causes an asparagine for histidine substitution in codon 183 and complete loss of enzyme activity. A 5-year-old boy who exhibited all the clinical features of primary hyperchylomicronemia was a compound heterozygote for these two mutations. Nine other family members were investigated: seven were heterozygotes for the splice site mutation, one was a heterozygote for the missense mutation, and one had two wild-type alleles of the LPL gene. LPL activity in the post-heparin plasma of the heterozygotes was reduced to 49;-79% of the mean observed in normal individuals. Two of the heterozygotes had extremely high plasma triglyceride levels; in three of the other heterozygotes the plasma triglycerides were also elevated. As plasma triglycerides in carriers of one defective LPL allele can be normal or elevated, the heterozygotes of this family have been studied for a possible additional cause of the expression of hypertriglyceridemia in these subjects. Body mass index, insulin resistance, mutations in other candidate genes (Asn291Ser and Asp9Asn in the LPL gene, apoE isoforms, polymorphisms in the apoA-II gene and in the apoAI-CIII-AIV gene cluster, and in the IRS-1 gene) could be ruled out as possible factors contributing to the expression of hypertriglyceridemia in this family. A linkage analysis using the allelic marker D1S104 on chromosome 1q21;-q23 suggested that a gene in this region could play a role in the expression of hypertriglyceridemia in the heterozygous carriers of this family, but the evidence was not sufficiently strong to prove this assumption. Nevertheless, this polymorphic marker seems to be a good candidate for further studies.

The accuracy of anthropometric surrogate markers such as the body adiposity index (BAI) and other common indexes like the body mass index (BMI), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) to predict metabolic sequelae is essential for its use in clinical practice.Thus, we evaluated the strength of BAI and other indexes to relate with anthropometric parameters, adipocytokines, blood lipids, parameters of glucose-homeostasis and blood pressure in 1,770 patients from the Salzburg Atherosclerosis Prevention Program in Subjects at High Individual Risk (SAPHIR) study in a crosssectional design. Measurements were BAI, BMI, WHR, WHtR, abdominal subcutaneous and visceral adipose tissue (aSAT and VAT), total body adipose tissue mass, body weight, waist- and hip circumference (WC and HC), leptin, adiponectin, high-density lipoprotein-cholesterol (HDL-C), low-density lipoprotein-cholesterol (LDL-C), triglycerides (TG), fasting plasma glucose, fasting plasma insulin, the homeostasis model assessment of insulin resistance (HOMAIR), systolic and diastolic blood pressure.BAI was significantly associated with leptin and HC. We conclude that BAI was the best calculator for leptin. BAI was inferior to BMI to predict anthropometric parameters other than HC, adiponectin, blood lipids, parameters of glucose homeostasis, and blood pressure in this cross-sectional study.

In this study, 2.5-, 3-, and 4-year-olds (N = 108) participated in a novel noun generalization task in which background context was manipulated. During the learning phase of each trial, children were presented with exemplars in one or multiple background contexts. At the test, children were asked to generalize to a novel exemplar in either the same or a different context. The 2.5-year-olds’ performance was supported by matching contexts; otherwise, children in this age group demonstrated context dependent generalization. The 3-year-olds’ performance was also supported by matching contexts; however, children in this age group were aided by training in multiple contexts as well. Finally, the 4-year-olds demonstrated high performance in all conditions. The results are discussed in terms of the relationship between word learning and memory processes; both general memory development and memory developments specific to word learning (e.g., retention of linguistic labels) are likely to support word learning and generalization.

Aims To bridge the beneficial metabolic effects of pronounced weight loss on one side and the data on morbidity and mortality on the other side, we investigated the impact of profound weight loss on structural and functional markers of early atherosclerosis. Methods and results Thirty-seven obese adults were examined before and 18 months after bariatric surgery. Carotid intima–media thickness (CIMT), brachial flow-mediated dilation (FMD), nitroglycerine-mediated dilation, and abdominal fat distribution were assessed by high-resolution ultrasound. Surgery resulted in a body mass index decrease of 9.1 ± 4.9 kg/m2 with concomitant improvements in glucose and lipid metabolism. Carotid intima–media thickness diminished from 0.56 ± 0.09 to 0.53 ± 0.08 mm ( n = 37; P = 0.004). Flow-mediated dilation improved from 5.81 ± 3.25 to 9.01 ± 2.93% ( n = 25; P < 0.001). Both CIMT and FMD were associated with intra-abdominal fat diameter. Conclusion The present results demonstrate that bariatric surgery-induced diminution of visceral fat improves both functional and structural markers of early atherosclerosis, providing a link between the weight loss-associated improvements of traditional and non-traditional risk factors and the reduced long-term morbidity and mortality after bariatric surgery.

Endothelial dysfunction and increased intima-media thickness (IMT) have been found in obese patients. Both regional fat distribution and liver steatosis may influence these markers of subclinical atherosclerosis. We sought to determine the interrelationships of endothelial function, carotid IMT, visceral and subcutaneous adipose tissue accumulation, and liver steatosis in severely obese subjects. In 64 severely obese patients (BMI 42.3 +/- 4.3 kg/m(2)), we determined (i) endothelial function as flow-mediated dilation (FMD) of the brachial artery, (ii) carotid IMT, (iii) visceral fat diameter, and (iv) degree of liver steatosis using ultrasound. FMD was associated inversely with visceral fat diameter and degree of steatosis (r = -0.577, P < 0.0001 and r = -0.523, P < 0.0001, respectively). Carotid IMT correlated with visceral fat mass (r = 0.343, P = 0.007) but not with liver steatosis. After adjustment for conventional cardiovascular risk factors, FMD was predicted independently by the visceral fat diameter, age, and sex (r(2) = 0.48, P < 0.0001), but not by the degree of liver steatosis or plasma adiponectin levels. In contrast, age and sex were the only predictors of IMT (r(2) = 0.33, P < 0.001). In obese patients, visceral fat diameter is a major determinant of endothelial dysfunction, independent of traditional risk factors or the degree of liver steatosis and plasma adiponectin. Measurement of visceral fat diameter by ultrasound is a novel and simple method to identify subjects with an increased risk for atherosclerosis within an obese population.

This study experimentally tested the relationship between children’s lexicon size and their ability to learn new words within the domain of color. We manipulated the size of 25 20-month-olds’ color lexicons by training them with two, four, or six different color words over the course of eight training sessions. We subsequently tested children’s ability to extend new color words to new instances. We found that training with a broader number of color words led to increased extension of new words. The results suggest that children’s learning history predicts their ability to learn new words within domains.

Adiponectin is an insulin-sensitizing, antiatherogenic and anti-inflammatory adipocytokine that circulates in three isoforms: a trimer [low-molecular weight (LMW)], a hexamer (trimer-dimer) of medium molecular weight (MMW) and a multimeric high molecular weight (HMW) isoform. Evidence is accumulating that HMW adiponectin is the active isoform of the adipocytokine. We investigated the impact of adipose tissue and insulin sensitivity on adiponectin isoform distribution.One hundred and eighty-seven normolipidaemic, non-diabetic lean or obese subjects with or without insulin resistance participating in the Salzburg Atherosclerosis Prevention program in subjects at High Individual Risk (SAPHIR) were included in the study. Insulin sensitivity was determined by the short insulin tolerance test and the homeostasis model assessment (HOMA) index. Serum adiponectin isoform distribution was determined by an enzyme immunoassay.Total adiponectin as well as HMW/total adiponectin ratio was significantly increased in female subjects. Circulating total adiponectin levels were lowest in obese patients due to reduced concentrations of HMW adiponectin. As determined by stepwise regression analysis, besides age and high density lipoprotein (HDL) cholesterol, visceral fat area and waist-to-hip ratio predicted concentrations of HMW adiponectin, while insulin sensitivity had no influence on either total adiponectin or its isoforms.Our results underline that determination of adiponectin isoforms are more useful than measurement of total adiponectin in clinical settings. Our data suggest that adiponectin concentrations are strongly associated with visceral fat area but not with insulin sensitivity. Thus, we hypothesize that insulin resistance is a consequence rather than the cause of hypoadiponectinaemia in obese subjects.

The role of genetic variation at the 3' end of the apolipoprotein B gene locus in the development of coronary heart disease and the regulation of the serum levels of various lipoproteins was studied by using two common restriction fragment length polymorphisms detected with the enzymes Xba I and EcoR I. A group of 106 male patients with coronary heart disease and 118 matched controls of Austrian origin were investigated. The frequency of the R2 allele of the EcoR I polymorphism at cDNA position 12,669 defined by the absence of the polymorphic EcoR I cutting site was significantly higher among patients than among controls. The controls with the R2 allele had significantly higher levels of total triglycerides, very low density lipoprotein (VLDL) triglycerides, and VLDL cholesterol than did the controls without this allele. Among the patients, the R2 allele was associated with higher serum VLDL apolipoprotein B levels. The chemical composition of VLDL in individuals with different genotypes for the EcoR I polymorphism did not differ significantly. For the Xba I polymorphism at cDNA position 7673, no correlation with coronary risk could be demonstrated. Patients and controls homozygous for the X2 allele characterized by the presence of the polymorphic Xba I cutting site showed a higher total and low density lipoprotein cholesterol level than did subjects with the genotype X1X1 or X1X2. This difference, however, was not statistically significant. These findings indicate that the R2 allele of the EcoR I polymorphism is associated with the occurrence of coronary heart disease and that variation at the 3' end of the apo B gene is involved in the regulation of VLDL metabolism.

Objectives Microsomal triglyceride transfer protein (MTP) transfers lipids into apoprotein B-containing lipoproteins for secretion from liver, intestine, and heart. We hypothesized the −493T single nucleotide polymorphism in the MTP promoter region to be associated with altered lipoprotein levels and with presence of peripheral arterial disease (PAD). Design and methods 433 patients with symptomatic PAD and 433 controls matched for sex and age from the Linz Peripheral Arterial Disease (LIPAD) study were genotyped cross-sectionally for the −493T single nucleotide polymorphism in the promoter region of the MTP gene. Results The frequency of the −493T allele in patients with PAD was 0.320, whereas it was 0.255 in controls (p

Variants in the adenosine triphosphate–binding-cassette transporter 1 (ABCA1) gene are known to affect high-density lipoprotein cholesterol and plasma triglycerides and the development of atherosclerosis. We investigated the influence of the R219K and I883M variants in the ABCA1 gene on plasma lipids and carotid intima media thickness and plaque extent in 688 healthy men (40-60 years old). The R219K variant showed no effect on plasma lipids, but carriers of the K allele displayed a lower intima media thickness (P = .001) and a reduced risk of advanced plaque extent (odds ratio [OR], 0.59; 0.39-0.88; P = .009) compared with noncarriers. However, this risk reduction was observed in nonsmokers only (OR, 0.47; 0.27-0.80; P < .001), but not in smokers (OR, 0.75; 0.41-1.39; P = .2). The I883M variant showed no effect on plasma lipids or carotid atherosclerosis. Risk of advanced plaque extent was reduced in subjects carrying the R219K variant alone (OR, 0.59; 0.38-0.94; P = .025), but not in subjects carrying both variants. Haplotype distribution did not differ between subjects with and without advanced atherosclerosis irrespective of smoking history. We conclude that smoking abrogates the protective effect of the R219K.