Epigenetic inheritance of diet-induced and sperm-borne mitochondrial RNAs.

Spermatozoa harbour a complex and environment-sensitive pool of small non-coding RNAs (sncRNAs)1, which influences offspring development and adult phenotypes1-7. Whether spermatozoa in the epididymis are directly susceptible to environmental cues is not fully understood8. Here we used two distinct paradigms of preconception acute high-fat diet to dissect epididymal versus testicular contributions to the sperm sncRNA pool and offspring health. We show that epididymal spermatozoa, but not developing germ cells, are sensitive to the environment and identify mitochondrial tRNAs (mt-tRNAs) and their fragments (mt-tsRNAs) as sperm-borne factors. In humans, mt-tsRNAs in spermatozoa correlate with body mass index, and paternal overweight at conception doubles offspring obesity risk and compromises metabolic health. Sperm sncRNA sequencing of mice mutant for genes involved in mitochondrial function, and metabolic phenotyping of their wild-type offspring, suggest that the upregulation of mt-tsRNAs is downstream of mitochondrial dysfunction. Single-embryo transcriptomics of genetically hybrid two-cell embryos demonstrated sperm-to-oocyte transfer of mt-tRNAs at fertilization and suggested their involvement in the control of early-embryo transcription. Our study supports the importance of paternal health at conception for offspring metabolism, shows that mt-tRNAs are diet-induced and sperm-borne and demonstrates, in a physiological setting, father-to-offspring transfer of sperm mitochondrial RNAs at fertilization.

METRNL decreases during adipogenesis and inhibits adipocyte differentiation leading to adipocyte hypertrophy in humans.

BACKGROUND: Meteorin-like (METRNL) is a recently described circulating protein shown to be highly expressed in white adipose tissue and to beneficially affect energy metabolism in mice. OBJECTIVE: We systematically evaluated the role of METRNL for human adipogenesis and its association with obesity, browning and hyperinsulinemia in children. In addition, we assessed the functional relevance of METRNL for human adipogenesis. RESULTS: METRNL expression decreased during human adipocyte differentiation in vitro. Coherently, METRNL expression was lower in isolated adipocytes compared with stromal vascular fraction (SVF) cells in human samples. Withdrawal of the peroxisome proliferator-activated receptor-γ (PPARγ) agonist rosiglitazone from adipogenic media partially preserved the METRNL downregulation during adipogenesis. METRNL expression was higher in adipocytes of obese compared with lean children and correlated with adipocyte size, whereas in SVF METRNL expression correlated with proliferation capacity. Concordantly, overexpression of METRNL inhibited human adipocyte differentiation as shown by decreased lipogenesis and lower expression of PPARγ and markers of adipogenesis, whereas experimental downregulation promoted adipogenesis. Proliferation, in contrast, was advanced by METRNL overexpression. These interactions with adipose tissue dynamics may contribute to the clinically observed body mass index-independent association of METRNL expression with hyperinsulinemia and adipose tissue inflammation in human samples. METRNL was not associated with UCP1 expression or induction of browning in white adipocytes. CONCLUSIONS: Taken together, the downregulation of METRNL during adipogenesis and functional induction of increased proliferation in SVF cells with concomitant inhibition of adipocyte differentiation may result in hypertrophic AT accumulation. This may also explain our observations of increased METRNL expression in adipocytes but not SVF cells in obese children compared with lean children and the subsequent hyperinsulinemia.

Adipocyte C1QTNF5 expression is BMI-dependently related to early adipose tissue dysfunction and systemic CTRP5 serum levels in obese children.

BACKGROUND/OBJECTIVES: The recently identified adipocytokine C1QTNF5 (encodes for CTRP5) has been demonstrated to inhibit pro-metabolic insulin signaling in adipocytes. We hypothesized that adipocyte C1QTNF5 expression in subcutaneous (sc) adipose tissue (AT) would correlate with the degree of obesity, systemic CTRP5 serum levels, and early AT and metabolic dysfunction in children. SUBJECTS/METHODS: Sc AT samples were obtained from 33 healthy Caucasian lean children aged 10.06±4.84 years and 42 overweight and obese children aged 13.34±3.12 years. C1QTNF5 expression in sc AT as well as in investigated cell lines was assessed by quantitative real-time PCR. Systemic CTRP5 levels were assessed by ELISA. RESULTS: C1QTNF5 expression in sc adipocytes increased with body mass index (BMI) standard deviation score (SDS; R=0.48, P<0.001), body fat percentage (R=0.4, P=0.004), adipocyte number (R=0.69, P<0.001) and systemic CTRP5 serum levels (R=0.28, P=0.025) whereas expression in the stromal vascular fraction (SVF) was inversely correlated with BMI SDS (R=-0.24, P=0.04). Multiple regression analysis confirmed that BMI SDS was the strongest independent predictor for C1QTNF5 expression in sc adipocytes. SVF C1QTNF5 levels strongly correlated with SVF CD31 expression (R=0.54, P<0.001) indicating expression by endothelial cells. Primary human endothelial cells demonstrated stronger expression compared with human Simpson-Golahbi-Behmel syndrome pre-adipocytes and adipocytes. Adipocyte C1QTNF5 expression levels were BMI-dependently related to fasting insulin (R=0.3, P=0.03) and leptin serum levels (R=0.5, P<0.001). Sc AT samples containing crown-like structures (CLS) demonstrated increased adipocyte C1QTNF5 expression compared to CLS-negative samples (P=0.03). Functionally, tumor necrosis factor (TNF)α caused a fourfold induction of C1QTNF5 in human adipocytes (P<0.001) and a 50% reduction in primary human endothelial cells (P<0.001). CONCLUSIONS: In children adipocyte C1QTNF5 expression is already strongly related to the degree of obesity and is associated with obesity-related AT alterations, systemic CTRP5 serum levels as well as circulating markers of metabolic disease and is positively regulated by TNFα in vitro.

Self-efficacy and comfort with partner-assisted skin examination in patients receiving follow-up care for melanoma.

The objective of this study was to examine the role of interpersonal variables on melanoma survivors' self-efficacy for performing skin self-examinations (SSEs) during melanoma follow-up care. Specifically, the impact of comfort with partner assistance for SSE, SSE support received from one's partner, general partner support, relationship satisfaction, as well as partner attendance at a SSE education session, were examined. One hundred and thirty-seven patients with melanoma between the ages of 18 and 70 years, who also reported being involved in a romantic relationship, received a standardized education on SSE, and completed self-report questionnaires. Results indicate that SSE support and SSE comfort predicted patients' SSE self-efficacy. Partner attendance at the SSE education moderated the relationship between SSE comfort and SSE self-efficacy. In other words, SSE self-efficacy was found to be affected by partner attendance at the SSE education only in cases where the patient reported lower levels of comfort having his or her partner assist with SSE. Results highlight the importance of partner involvement in SSE education, as well as patient comfort with a partner's assistance during skin examinations. Findings inform potential modifications to the follow-up care provided to melanoma survivors by demonstrating the importance of partner involvement in SSE education.

Insulin-Like Peptide 5 Interacts with Sex Hormones and Metabolic Parameters in a Gender and Adiposity Dependent Manner in Humans.

Insulin-like peptide 5 (INSL5) is a gut hormone produced by L-cells in the colorectal epithelium and may play a role in the regulation of metabolic processes. The biological role of INSL5 is poorly investigated and nothing is known about the role of this hormone in obese and lean humans. Two cohorts were analyzed in the study. In the first cohort (n=76) the relationship between serum levels of INSL5 and different metabolic and hormonal parameters in obese and lean men and women were investigated. In the second cohort 14 male subjects underwent bariatric surgery. Circulating levels of INSL5 were then measured before and after interventions.We report for the first time that circulating INSL5 interacts with multiple metabolic and hormonal variables in lean and obese men and women and is affected by bariatric surgery. Serum levels of INSL5 negatively correlated with testosterone and blood lipids but positively with cortisol in obese men. In contrast to males, obese women had a strong negative correlation of plasma levels of INSL5 with C-reactive protein (CRP). We observed that adipose tissue loss after bariatric surgery significantly reduced serum levels of INSL5 in obese men with and without Type 2 Diabetes Mellitus (T2DM) that was associated with the restoration of circulating levels of testosterone. All together, our data demonstrated that INSL5 may interact with some metabolic parameters in obese humans and this process is dependent of gender and obesity state.

Morphological and compositional monitoring of a new cell-free cartilage repair hydrogel technology - GelrinC by MR using semi-quantitative MOCART scoring and quantitative T2 index and new zonal T2 index calculation.

OBJECTIVE: To evaluate cartilage repair tissue (RT) using MOCART scoring for morphological and T2 mapping for biochemical assessment following implantation of GelrinC, a biosynthetic, biodegradable hydrogel implant. DESIGN: MR imaging (1.5/3T) was performed on 21 patients at six sites. Standard protocols were used for MOCART evaluation at 1 week (baseline) 1, 3, 6, 12, 18 and 24 months. Multi-echo SE was used for T2 mapping. Global (T2 in RT divided by T2 in normal cartilage) and zonal T2 index (deep T2 divided by superficial T2) of RT were calculated. RESULTS: Average MOCART score was 71.8 (95% CI 62.2 to 81.3) at six, 75.2 (95% CI 62.8 to 87.5) at twelve, 71.8 (95% CI 55.4 to 88.2) at eighteen and 84.4 (95% CI 77.7 to 91.0) at twenty-four months. The global T2 index ranged between 0.8 and 1.2 (normal healthy cartilage) in 1/11 (9%) patients at baseline, 8/12 (67%) at 12 months, 11/13 (85%) at 18 months and 13/16 (81%) at 24 months. The zonal T2 index for RT was <20% difference to the zonal T2 index for normal cartilage in: 6/12 patients (50%) at 12 months, 7/13 (53.8%) at 18 months and 10/16 (63.5%) at 24 months. The standard deviation for T2 showed a significant decrease over the study. CONCLUSIONS: The increase of MOCART scores over follow-up indicates improving cartilage repair tissue. Global and zonal T2 repair values at 24 months reached normal cartilage in 81% and 63.5% of the patients respectively, reflecting collagen organization similar to hyaline cartilage.

One-to-one peer support in cancer care: a review of scholarship published between 2007 and 2014.

The primary goal of this review was to determine whether one-to-one peer support programmes benefit cancer patients. The secondary goal was to assess the quality of the research methodology and of the peer programme description as reported in original research studies. MEDLINE and PsycINFO databases were systematically searched in order to identify relevant studies published between May 2007 and July 2014. Eligible articles were evaluated using pre-existing criteria based on the Consolidated Standards of Reporting Trials Statement Checklist. This review included 13 studies: four randomised controlled trials, one non-randomised comparative study and eight one-group descriptive studies. All studies reported high participant satisfaction with the peer support intervention, and the majority noted positive outcomes regarding psychological adjustment. The quality of the description of the peer support programmes as well as the research methodology of the studies was rated as fair. Methodological weaknesses included biased recruitment strategies and limited information regarding peer volunteers, non-users of peer support and those who withdrew from support programmes. One-to-one peer support programmes have the unique advantage of being a low-cost intervention approach, but also showing potential for relieving the health-care system by reallocating some aspects of the cancer care to community settings. Future research should address the methodological weaknesses in study design and reporting.

The Brief Symptom Inventory-9 (BSI-9): Development and validation in a German general population sample.

BACKGROUND: The Brief Symptom Inventory-18 (BSI-18) is a self-report questionnaire with three subscales, somatisation, anxiety, and depression, based on longer measures of distress. The present study proposes a shorter, nine-item version (BSI-9) of the BSI-18 as a brief screening tool for distress. METHODS: Confirmatory factor analyses and reliability and validity analyses were carried out using a representative sample of the German general population. Confirmatory factor analysis demonstrates a good model fit for the three-dimensional BSI-9. RESULTS: The total scale was found to have strong internal consistency (αCronbach = 0.87 for the global severity index). The internal consistency coefficients of the three-item subscales reflect the brevity of these scales (somatisation αCronbach = 0.72, depression ï»¿α Cronbach = 0.79, anxiety αCronbach = 0.68). The subscales were found to be significantly related with subscales of the Patient Health Questionnaire-4 and Hopkins Symptom Checklist-25. LIMITATIONS: The present study used a limited number of distress measures, and a more recent dataset would be useful to provide a more current picture of the general population's distress levels. CONCLUSIONS: The BSI-9 provides a short, valid, and reliable screener for distress in the general population. Future work should examine its utility in clinical settings and different cultural contexts.

Diurnal rythm of Nampt is gender and weight dependent.

RESEARCH AIM: Nicotinamide phosphoribosyltransferase (Nampt) is an adipocytokine that is elevated in obesity, type 2 diabetes and increased levels are associated with inflammatory processes. Nampt serum concentrations have been suggested to follow a diurnal rhythm peaking in the afternoon in lean males. However, no data exists regarding the effects of gender and body weight. MATERIAL AND METHODS: We measured Nampt serum levels over 24 h in a cohort of healthy individuals living with either normal weight or obesity. Furthermore, effects of meals, oral glucose tolerance test and physical exercise on Nampt concentrations were evaluated. Correlation analyses to other hormonal- and lab parameters and anthropometric measurements were performed. RESULTS: Nampt showed a diurnal rhythm with increased levels at daytime and a peak in the early afternoon. This diurnal rhythm was significant for all groups but obese males. The Nampt amplitude, measured both relatively and absolutely, was significantly higher in females than in males. Meals did not influence Nampt serum levels, whereas physical exercise and an OGTT did significantly influence Nampt serum levels. CONCLUSION: In conclusion, we found gender specific differences in Nampt amplitude and coefficient variation with both being higher in females. The circadian rhythm of Nampt was independent of gender in healthy lean individuals, whereas it was disturbed in men with obesity.

Functional relevance of genes implicated by obesity genome-wide association study signals for human adipocyte biology.

AIMS/HYPOTHESIS: Genome-wide association studies (GWAS) have identified numerous single-nucleotide polymorphisms associated with obesity, consequently implying a role in adipocyte biology for many closely residing genes. We investigated the functional relevance of such genes in human adipocytes. METHODS: We selected eight genes (BDNF, MAF, MTCH2, NEGR1, NPC1, PTER, SH2B1 and TMEM18) from obesity GWAS and analysed their effect in human adipogenesis using small interfering (si)RNA-mediated knockdown, their regulation by metabolic agents in adipocytes and pre-adipocytes, and gene expression in paired samples of human fat biopsies (68 non-obese, 165 obese) by quantitative real-time PCR. RESULTS: We show a two- to threefold upregulation of MAF, MTCH2 and NEGR1 and a two- to fourfold downregulation of BDNF and PTER during adipogenesis. Knockdown of BDNF (mean ± SEM; 83.8 ± 4.7% of control; p = 0.0002), MTCH2 (72.7 ± 9.5%; p = 0.0006), NEGR1 (70.2 ± 5.7%; p < 0.0001) and TMEM18 (70.8 ± 6.1%; p < 0.0001) significantly inhibited adipocyte maturation, while knockdown of the other proteins had no effect. Insulin slightly induced MAF (1.65-fold; p = 0.0009) and MTCH2 (1.72-fold; p < 0.0001), while it suppressed BDNF (59.6%; p = 0.0009), NEGR1 (58.0%; p = 0.0085) and TMEM18 (69.3%; p = 0.0377) in adipocytes. The synthetic glucocorticoid dexamethasone suppressed MAF (45.7%; p = 0.0022), BDNF (66.6%; p = 0.0012) and TMEM18 (63.5%; p = 0.0181), but induced NEGR1 (3.2-fold; p = 0.0117) expression. Furthermore, MTCH2, NEGR1 and TMEM18 were differentially expressed in subcutaneous and visceral adipose tissue. TMEM18 expression was decreased in the adipose tissue of obese patients, and negatively correlated with anthropometric variables and adipocyte size. CONCLUSIONS/INTERPRETATION: Our results imply a regulatory role for TMEM18, BDNF, MTCH2 and NEGR1 in adipocyte differentiation and biology. In addition, we show a variation of MAF expression during adipogenesis, while NPC1, PTER and SH2B1 were not regulated.

Longitudinal multicenter analysis on the course of glucose metabolism in obese children.

OBJECTIVE: Although there is evidence of increasing prevalence of impaired glucose metabolism in obese children from smaller single cohorts, data are lacking on the progression of glucose metabolism in this patient group.We aimed to assess the prevalence and the longitudinal course of impaired glucose metabolism assessed by oral glucose tolerance test (oGTT) in a large multi-center pediatric obesity registry. SUBJECTS: We performed an observational multicenter (n=84) cross-sectional (n=11 156) and longitudinal analysis (n=1008) on the course of glucose metabolism evaluated by oGTT in obese children documented in the Adiposity Patients Verlaufsbeobachtung (APV) registry. Patients were stratified with impaired fasting glucose (IFG), impaired glucose tolerance (IGT) and Type 2 diabetes (T2D), according to American Diabetes Association criteria. RESULTS: A total of 12.6% of the children presented with abnormal glucose metabolism (5.99% IFG, 5.51% IGT, 1.07% T2D). Body mass index (BMI) correlated modestly with 2-h blood glucose (r=0.04, P<0.001).In the 1008 patients with follow-up oGTT, metabolic parameters improved and the percentage of abnormal glucose metabolism decreased from 18.7 to 14.2%. Of the children with initial IGT, 70.6% converted to normal glucose tolerance. The improvement in oGTT results was associated with, but not dependent on, a reduction of BMI s.d. score. CONCLUSION: In summary, we provide evidence for significant improvement of oGTT parameters in obese children treated in specialized treatment centers, even though reduction in BMI was modest.

Patient participation in the medical decision-making process in haemato-oncology--a qualitative study.

Cancer patients are showing increased interest in shared decision-making. Patients with haematological illnesses, however, express considerably less desire for shared decision-making as compared with other oncological patient groups. The goal of the current project was to identify the reasons for the lower desire for shared decision-making among patients with haematological illness. We conducted qualitative, semi-structured interviews with 11 haematological patients (39-70 years old) after the beginning of therapy concerning the course and evaluation of medical shared decision-making. The patients were often overwhelmed by the complexity of the illness and the therapy and did not want to assume any responsibility in medical decision-making. They reported a great deal of distress and very traditional paternalistic role expectations with regards to their health care providers, which limited the patients' ability to partake in the decision-making process. In contrast to the socio-cultural support for many other oncological diseases, haematological diseases are not as well supported, e.g. there is a lack of self-help materials, systematic provision of information and support groups for patients, which may be related to a lower empowerment of this patient population. Results show the limits of patient participation in the context of highly complicated medical conditions. In addition to already researched preferences of the physicians and patients for shared decision-making, future research should pay greater attention to the process and other variables relevant to this aspect of the doctor-patient relationship.

[High blood pressure in obese children and adolescents]. / Bluthochdruck bei Adipositas im Kindes- und Jugendalter.

Obesity is also an important risk factor in children and adolescents for "essential" arterial hypertension, and contrary to what was assumed earlier, high blood pressure does cause damage to the cardiovascular system. As known from adults, elevated blood pressure induces cardiac hypertrophy, calcifications and atherosclerosis at the coronary vessels and thickens the small blood vessels. These early vascular alterations are particularly pronounced, when increased blood pressure is accompanied by other risk factors, such as dyslipidemia, hyperinsulinemia or smoking. As in any child with elevated blood pressure, the diagnostic evaluation should focus on confirmation of hypertension, determine if an underlying cause can be identified and whether hypertensive target organ damage is present. New reference office blood pressure values were recently published by a large representative community-based study in Germany. Therapy should begin with lifestyle modifications; however, antihypertensive medications will often be needed. Hypertension in obese adolescents occurs frequently and must be diagnosed and treated adequately.

[Carbohydrate metabolism disorders among obese children and adolescents. Diabetes mellitus type 2]. / Störungen des Kohlenhydratstoffwechsels bei Kindern und Jugendlichen mit Adipositas. Diabetes mellitus Typ 2.

As obesity has become more prevalent, the incidence of type 2 diabetes mellitus in children and adolescents has also increased. Obesity during adolescence leads to an increased risk for disease and premature death during adulthood, independent of obesity during adulthood. Obesity is the major risk factor impacting insulin sensitivity. Subjects with insulin resistance are at risk for progression to diabetes. Type 2 diabetes mellitus in obese children and adolescents is frequently asymptomatic. It is essential to identify children at high risk who need aggressive lifestyle modification focused on weight reduction and increased physical activity. Early detection and therapy of obese children and adolescents with type 2 diabetes may reduce the risk of cardiometabolic consequences and other long-term complications in adulthood.

[Does childhood obesity affect sexual development?]. / Beeinflusst die kindliche Adipositas die Pubertätsentwicklung?

The process of pubertal development is only partly understood and is influenced by many different factors. During the twentieth century there was a general trend toward earlier pubertal development. Fat mass is thought to be a major inducer of puberty. Owing to the rising epidemic of childhood obesity, the relationship between body composition in children and the rate and timing of puberty needs to be investigated. Some studies suggest that central obesity is associated with an earlier onset of pubertal development. Rapid weight gain in early life is linked to advanced puberty in both sexes. A clear correlation exists between increasing body mass index (BMI) and earlier pubertal development in girls. In boys the data are controversial: The majority of studies propose that there is an earlier puberty and voice break in obese boys, but some studies show the opposite. There are several factors and mechanisms that seem to link obesity and puberty, for example, leptin, adipocytokines, and gut peptides. Important players include genetic variation and environmental factors (e.g., endocrine-disrupting chemicals). This article presents the latest studies and evidence on this topic, underlining the inconsistencies in the data and, therefore, the need for further research in this area.

Quality of life of parents diagnosed with cancer: change over time and influencing factors.

Suffering from cancer while having parental responsibilities can amplify the psychosocial strain that the disease puts on the individual as well as on the whole family system. Our longitudinal study examines changes in the quality of life of cancer patients in relation to parenthood. The quality of life of cancer patients is assessed with the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire 30-item version during the initial treatment period (T1) and compared to the quality of life 2 years later (T2). Two groups of patients are compared: those who have children below the age of 18 years (n= 41) and those who do not have children (n= 28). Shortly after being diagnosed with cancer (T1), both groups report a similarly low quality of life. Two years later (T2), individuals with children below the age of 18 report better quality of life on the majority of the dimensions assessed. However, variance analysis did not show that this is an independent effect of parenthood. In fact, having a partner and being female proved to impact the quality of life. These findings support the existing body of research on the influence of social support and gender on quality of life. The resulting limitations and suggestions on how to overcome them in further research are discussed.

Leucocytes are a major source of circulating nicotinamide phosphoribosyltransferase (NAMPT)/pre-B cell colony (PBEF)/visfatin linking obesity and inflammation in humans.

AIMS/HYPOTHESIS: Nicotinamide phosphoribosyltransferase (NAMPT) is a multifunctional protein potentially involved in obesity and glucose metabolism. We systematically studied the association between circulating NAMPT, obesity, interventions and glucose metabolism and investigated potential underlying inflammatory mechanisms. METHODS: Fasting morning NAMPT serum levels were measured in cohorts of lean vs obese children, cohorts of intervention by lifestyle, exercise and bariatric surgery, and during an OGTT. In addition, mRNA expression, protein production and enzymatic activity of NAMPT were assessed from isolated leucocytes and subpopulations. RESULTS: Circulating NAMPT was significantly elevated in obese compared with lean children and declined after obesity interventions concomitantly with the decline in BMI, high-sensitivity C-reactive protein (hsCrP) and leucocyte counts. Circulating NAMPT significantly correlated with glucose metabolism and cardiovascular variables in univariate analyses, but only the association with glucose response during an OGTT was independent from BMI. We therefore assessed the NAMPT dynamic following an oral glucose load and found a significant decline of NAMPT levels to 77.0 ± 0.1% as a function of time, and insulin-to-glucose ratio during an OGTT in obese insulin-resistant adolescents. Circulating NAMPT was, however, most strongly associated with leucocyte counts (r = 0.46, p < 0.001). The leucocyte count itself determined significantly and independently from BMI insulin resistance in multiple regression analyses. We systematically evaluated NAMPT expression among several tissues and found that NAMPT was predominantly expressed in leucocytes. In subsequent analyses of leucocyte subpopulations, we identified higher NAMPT protein concentrations in lysates of granulocytes and monocytes compared with lymphocytes, whereas granulocytes secreted highest amounts of NAMPT protein into cell culture supernatant fractions. We confirmed nicotinamide mononucleotide enzymatic activity of NAMPT in all lysates and supernatant fractions. In monocytes, NAMPT release was significantly stimulated by lipopolysaccharide (LPS) exposure. CONCLUSIONS: Leucocytes are a major source of enzymatically active NAMPT, which may serve as a biomarker or even mediator linking obesity, inflammation and insulin resistance.

Serum visfatin and vaspin levels in prepubertal children: effect of obesity and weight loss after behavior modifications on their secretion and relationship with glucose metabolism.

OBJECTIVE: To investigate the impact of obesity, weight loss and oral glucose ingestion on serum visfatin and vaspin levels in prepubertal children. SUBJECTS AND METHODS: A total of 100 prepubertal obese Caucasian children (OB) and 42 controls (C) were studied. The OB group was studied at baseline and after moderate (n=46) and extensive (n=14) body mass index (BMI) reduction by conservative treatment, undergoing body composition studies (dual-energy X-ray absorptiometry) and oral glucose tolerance tests (OGTTs). Serum visfatin and vaspin levels were studied throughout the OGTT, as were their relationships with insulin, leptin, leptin soluble receptor (sOB-R), adiponectin (total and high molecular weight), resistin, interleukin-6 (IL-6) and tumor necrosis factor-α levels at every time point. RESULTS: OB had higher visfatin (P<0.001), but similar vaspin than C. BMI reduction decreased visfatin levels (P<0.001), with BMI, waist circumference and the surrogate markers of body fat (leptin and sOB-R) showing significant correlations (P<0.05) with this peptide, but not with vaspin. Visfatin and vaspin decreased during the OGTT (P<0.001). Weight reduction did not alter visfatin dynamics in the OGTT, but decreased the area under the curve (AUC) for vaspin (P<0.001), with a correlation between the AUCs for vaspin and insulin after weight loss (P<0.05). Visfatin levels were positively correlated with resistin and IL-6, after controlling for BMI and HOMA (homeostatic model assessment) index at every time point in the study. CONCLUSION: Serum visfatin, but not vaspin, levels are influenced by body fat content in obese children, whereas both adipokines are modulated by glucose intake in a BMI-dependent manner.

Vaspin is related to gender, puberty and deteriorating insulin sensitivity in children.

BACKGROUND: Visceral adipose tissue-derived serine protease inhibitor (vaspin) has been suggested as a novel adipocytokine related to obesity and insulin sensitivity in adults. DESIGN: We quantified vaspin serum concentrations in 65 lean and 67 obese children and aimed to evaluate the relationship of vaspin with physical development, obesity, and metabolic and cardiovascular phenotypes in children. We further assessed the acute vaspin response to glucose provocation in 20 obese adolescents and evaluated tissue expression patterns of vaspin in humans. RESULTS: Vaspin levels were significantly higher in girls than in boys. In girls, vaspin increased with age and pubertal stage, whereas there was no change with development in boys. Obese girls had lower vaspin serum levels than those of lean controls, but there was no significant correlation with body mass index (BMI). Independent of sex, age and BMI, lower vaspin was associated with better insulin sensitivity, with higher systolic blood pressure and impaired endothelial function. In response to glucose provocation during an oral glucose tolerance test, vaspin serum levels declined by approximately 25% in adolescents with hyperinsulinemia, whereas there was no significant decline in normoinsulinemic patients. In support of our clinical data, we not only confirmed vaspin mRNA expression in adipose tissue but also found consistent expression of vaspin in the liver and indications for expression in the pancreas and the skin. CONCLUSION: We showed that gender differences in circulating vaspin levels develop during pubertal progression in girls. Although vaspin's association with obesity remains controversial, vaspin was increased with worsening insulin resistance already in children and was acutely down-regulated following glucose provocation in insulin-resistant adolescents independent of obesity. Besides adipose tissue, vaspin expression in the liver and the pancreas may potentially contribute to circulating vaspin levels and their regulation.

Participation of haemato-oncological patients in medical decision making and their confidence in decisions.

Increasingly more clinical care and research acknowledge the patients' interest in participating in medical decision making. However, for haematological patients, there are as yet only modest findings. The current study explores patients' perceptions of their role in the medical decision-making process in a sample of 117 haematological patients. The majority of patients surveyed (63.9%) took a passive role in the medical decision-making process, which is a significantly greater proportion compared with individuals suffering from solid cancers. Despite passive majority, most of the participants reported a positive evaluation of the decision-making process. Importantly, patients' evaluations were significantly more negative either if patients were treated as inpatients (vs. outpatients), or if they experienced no control over the decision (vs. collaboration with the doctor, or deciding autonomously). The results and limitations of the study are discussed.