The association between inflammatory biomarkers and metabolically healthy obesity depends of the definition used.

BACKGROUND/OBJECTIVES: To assess the distribution of interleukin (IL)-1β, IL-6, tumour necrosis factor (TNF)-α and C-reactive protein (CRP) according to the different definitions of metabolically healthy obesity (MHO). SUBJECTS/METHODS: A total of 881 obese (body mass index (BMI) > or =30 kg/m2) subjects derived from the population-based CoLaus Study participated in this study. MHO was defined using six sets of criteria including different combinations of waist, blood pressure, total high-density lipoprotein cholesterol or low-density lipoprotein -cholesterol, triglycerides, fasting glucose, homeostasis model, high-sensitivity CRP, and personal history of cardiovascular, respiratory or metabolic diseases. IL-1β, IL-6 and TNF-α were assessed by multiplexed flow cytometric assay. CRP was assessed by immunoassay. RESULTS: On bivariate analysis some, but not all, definitions of MHO led to significantly lower levels of IL-6, TNF-α and CRP compared with non-MH obese subjects. Most of these differences became nonsignificant after multivariate analysis. An posteriori analysis showed a statistical power between 9 and 79%, depending on the inflammatory biomarker and MHO definition considered. Further increasing sample size to overweight+obese individuals (BMI > or =25 kg/m2, n=2917) showed metabolically healthy status to be significantly associated with lower levels of CRP, while no association was found for IL-1β. Significantly lower IL-6 and TNF-α levels were also found with some but not all MHO definitions, the differences in IL-6 becoming nonsignificant after adjusting for abdominal obesity or percent body fat. CONCLUSIONS: MHO individuals present with decreased levels of CRP and, depending on MHO definition, also with decreased levels in IL-6 and TNF-α. Conversely, no association with IL-1β levels was found.

New loci associated with birth weight identify genetic links between intrauterine growth and adult height and metabolism.

Birth weight within the normal range is associated with a variety of adult-onset diseases, but the mechanisms behind these associations are poorly understood. Previous genome-wide association studies of birth weight identified a variant in the ADCY5 gene associated both with birth weight and type 2 diabetes and a second variant, near CCNL1, with no obvious link to adult traits. In an expanded genome-wide association meta-analysis and follow-up study of birth weight (of up to 69,308 individuals of European descent from 43 studies), we have now extended the number of loci associated at genome-wide significance to 7, accounting for a similar proportion of variance as maternal smoking. Five of the loci are known to be associated with other phenotypes: ADCY5 and CDKAL1 with type 2 diabetes, ADRB1 with adult blood pressure and HMGA2 and LCORL with adult height. Our findings highlight genetic links between fetal growth and postnatal growth and metabolism.

The role of alliance in the relationship between therapist competence and outcome in brief psychodynamic psychotherapy.

Therapist competence is a key variable for psychotherapy research. Empirically, the relationship between competence and therapeutic outcome has shown contradictory results and needs to be clarified, especially with regard to possible variables influencing this relationship. A total of 78 outpatients were treated by 15 therapists in a very brief 4-session format, based on psychoanalytic theory. Data were analyzed by means of a nested design using hierarchical linear modeling. No direct link between therapist competence and outcome has been found, however, results corroborated the importance of alliance patterns as moderator in the relationship between therapist competence and outcome. Only in dyads with alliance change over the course of treatment was it clear that competence is positively related to outcome. These findings are discussed with regard to the importance for outcome of therapist competence and alliance construction processes.

Does introduction of thresholds in decision aids benefit the patient?: Comparison between findings-based and threshold-based diagnostic decision aids.

PURPOSE: To assess how different diagnostic decision aids perform in terms of sensitivity, specificity, and harm. METHODS: Four diagnostic decision aids were compared, as applied to a simulated patient population: a findings-based algorithm following a linear or branched pathway, a serial threshold-based strategy, and a parallel threshold-based strategy. Headache in immune-compromised HIV patients in a developing country was used as an example. Diagnoses included cryptococcal meningitis, cerebral toxoplasmosis, tuberculous meningitis, bacterial meningitis, and malaria. Data were derived from literature and expert opinion. Diagnostic strategies' validity was assessed in terms of sensitivity, specificity, and harm related to mortality and morbidity. Sensitivity analyses and Monte Carlo simulation were performed. RESULTS: The parallel threshold-based approach led to a sensitivity of 92% and a specificity of 65%. Sensitivities of the serial threshold-based approach and the branched and linear algorithms were 47%, 47%, and 74%, respectively, and the specificities were 85%, 95%, and 96%. The parallel threshold-based approach resulted in the least harm, with the serial threshold-based approach, the branched algorithm, and the linear algorithm being associated with 1.56-, 1.44-, and 1.17-times higher harm, respectively. Findings were corroborated by sensitivity and Monte Carlo analyses. CONCLUSION: A threshold-based diagnostic approach is designed to find the optimal trade-off that minimizes expected harm, enhancing sensitivity and lowering specificity when appropriate, as in the given example of a symptom pointing to several life-threatening diseases. Findings-based algorithms, in contrast, solely consider clinical observations. A parallel workup, as opposed to a serial workup, additionally allows for all potential diseases to be reviewed, further reducing false negatives. The parallel threshold-based approach might, however, not be as good in other disease settings.

Relationships between anthropometric measures and athletic performance, with special reference to repeated-sprint ability, in the Qatar national soccer team.

The aim of this study was to determine potential relationships between anthropometric parameters and athletic performance with special consideration to repeated-sprint ability (RSA). Sixteen players of the senior male Qatar national soccer team performed a series of anthropometric and physical tests including countermovement jumps without (CMJ) and with free arms (CMJwA), straight-line 20 m sprint, RSA (6 × 35 m with 10 s recovery) and incremental field test. Significant (P < 0.05) relationships occurred between muscle-to-bone ratio and both CMJs height (r ranging from 0.56 to 0.69) as well as with all RSA-related variables (r < -0.53 for sprinting times and r = 0.54 for maximal sprinting speed) with the exception of the sprint decrement score (Sdec). The sum of six skinfolds and adipose mass index were largely correlated with Sdec (r = 0.68, P < 0.01 and r = 0.55, P < 0.05, respectively) but not with total time (TT, r = 0.44 and 0.33, P > 0.05, respectively) or any standard athletic tests. Multiple regression analyses indicated that muscular cross-sectional area for mid-thigh, adipose index, straight-line 20 m time, maximal sprinting speed and CMJwA are the strongest predictors of Sdec (r(2) = 0.89) and TT (r(2) = 0.95) during our RSA test. In the Qatar national soccer team, players' power-related qualities and RSA are associated with a high muscular profile and a low adiposity. This supports the relevance of explosive power for the soccer players and the larger importance of neuromuscular qualities determining the RSA.

Merlin, a "Magic" Linker between Extracellular Cues and Intracellular Signaling Pathways that Regulate Cell Motility, Proliferation, and Survival.

Genetic alterations of neurofibromatosis type 2 (NF2) gene lead to the development of schwannomas, meningiomas, and ependymomas. Mutations of NF2 gene were also found in thyroid cancer, mesothelioma, and melanoma, suggesting that it functions as a tumor suppressor in a wide spectrum of cells. The product of NF2 gene is merlin (moesin-ezrin-radixin-like protein), a member of the Band 4.1 superfamily proteins. Merlin shares significant sequence homology with the ERM (Ezrin-Radixin-Moesin) family proteins and serves as a linker between transmembrane proteins and the actin-cytoskeleton. Merlin is a multifunctional protein and involved in integrating and regulating the extracellular cues and intracellular signaling pathways that control cell fate, shape, proliferation, survival, and motility. Recent studies showed that merlin regulates the cell-cell and cell-matrix adhesions and functions of the cell surface adhesion/extracellular matrix receptors including CD44 and that merlin and CD44 antagonize each other's function and work upstream of the mammalian Hippo signaling pathway. Furthermore, merlin plays important roles in stabilizing the contact inhibition of proliferation and in regulating activities of several receptor tyrosine kinases. Accumulating data also suggested an emerging role of merlin as a negative regulator of growth and progression of several non-NF2 associated cancer types. Together, these recent advances have improved our basic understanding about merlin function, its regulation, and the major signaling pathways regulated by merlin and provided the foundation for future translation of these findings into the clinic for patients bearing the cancers in which merlin function and/or its downstream signaling pathways are impaired or altered.

Hydrogen isotope fractionations between amphiboles, micas, and fluids in alkaline igneous intrusions

RÉSUMÉ DE LA THÈSE Les teneurs des amphiboles en éléments majeurs et en isotopes stables ont été analysées dans plusieurs complexes ignés alcalins et hyperalcalins, dans le but de déterminer l'importance des variations de composition des minéraux pour le fractionnement isotopique de l'hydrogène dans un système naturel minéral-magma-fluide. Cette étude se concentre principalement sur les syénites néphéliniques de complexes intrusifs alcalins bien connus mais à chimie variable, dont les amphiboles, ainsi que d'autres silicates hydratés tels que micas et eudialytes, lorsque cela était possible, ont été séparés. L'intérêt principal s'est porté sur le complexe alcalin d'Ilímaussaq de la Province du Gardar, au Sud du Groenland. Dans une optique de comparaison, nous avons collecté et analysé d'autres échantillons provenant du complexe de Tugtutôq (Sud Groenland), des complexes de Khibina et Lovozero (Péninsule de Kola, Russie), du Mont St-Hilaire et du Mont Royal (Canada) et de 6 autres du nord-ouest de la Namibie (Cape Cross, Okenyenya, Messum, Etaneno, Kalkfeld,et Okorusu). Les compositions isotopiques de l'hydrogène des amphiboles des ces différentes zones présentent de grandes variations (-227 à -700/00), ce qui est atypique pour des magmas d'origine mantellique. Les valeurs comprises entre -80 et -400/00 indiquent une provenance du manteau. Ces larges variations de compositions ainsi que l'extrême appauvrissement en isotope lourd de l'hydrogène (D), en comparaison avec d'autres roches ignées, semblent être propres.aux roches alcalines et hyperalcalines de ce type, ce qui indiquerait un processus commun. Les différents complexes alcalins choisis présentent un large intervalle de composition chimique des amphiboles. La caractérisation des amphiboles par microscopie électronique et par spectroscopie Mössbauer contribuent à observer le contrôle du Fe sur le fractionnement des isotopes de l'hydrogène. En effet, cela a mis en évidence un contrôle du Fe sur le fractionnement et même, dans le cas du complexe hyperalcalin d'Ilímaussaq, une relation entre le rapport Fei3+/FeT et les variations du rapport D/H. Les complexes étudiés diffèrent de par leur index agpaïtique (Na+K/Al) et également de par leur contenu en fer. Les plus hautes valeurs en Fe (27-35 wt%) et en éléments alcalins dans les amphiboles, ainsi que les teneurs de D/H les plus basses et leur grande variation, sont celles du complexe d'Ilímaussaq. Les amphiboles de la Péninsule de Kola et du Canada sont similaires, mais toutefois moins appauvries en D. En ce qui concerne les amphiboles des complexes du NO de la Namibie, elles présentent des compositions isotopiques de l'hydrogène magmatiques normales (-73 à -100 0/00), contiennent moins de Fe (15-17 wt%) et sont fortement enrichies en Ca et moins en Na. Dans ce cas, l'alcalinité est moins importante en comparaison des autres complexes étudiés. En dehors des teneurs en éléments alcalins des amphiboles, l'alcalinité des fluides s'avère également un facteur important, ce qui est cohérent avec certaines suggestions à partir de systèmes expérimentaux. Afin de mieux contraindre ce facteur, des expériences d'échanges hydrothermaux entre les amphiboles et les fluides de salinité différente ont été effectuées en simulant des conditions naturelles. L'approximation d'amphiboles naturelles de complexes ignés alcalins, couplée aux expériences d'échange, aide à préciser les facteurs contrôlant le fractionnement des isotopes de l'hydrogène dans les roches alcalines. Les valeurs extrêmement basses de 3D des amphiboles de ces complexes alcalins peuvent être dues à une combinaison de différents facteurs, telles qu'une haute alcalinité, une haute teneur en Fe et une faible profondeur d'intrusion. Les grandes variations ainsi que les faibles valeurs de SD des amphiboles étudiées peuvent résulter d'un processus magmatique interne et il est peu probable que de l'eau météorique soit impliquée et/ou que le dégazage magmatique ait joué un rôle. THESIS ABSTRACT Major element and stable isotope compositions of amphiboles were analyzed from a number of alkaline and peralkaline igneous complexes in order to determine the importance of compositional variations in minerals to hydrogen isotope fractionations in natural mineral-melt-fluid systems. The thesis mainly focuses on nepheline syenites of well-studied, but chemically variable alkaline intrusive rocks, from which amphiboles and, if possible, other hydrous silicates such as micas and eudialytes were separated. The system of primary interest was the alkaline Ilímaussaq Complex of the Gardar Province of South Greenland. For the purpose of comparison additional samples were collected and examined from the Tugtutôq Complex (South Greenland), the Khibina and Lovozero Complexes (Kola Peninsular, Russia), Mount St-Hilaire and Mount Royal (Canada) and six further complexes from NW Namibia (Cape Cross, Okenyenya, Messum, Etaneno, Kalkfeld, and Okorusu). The hydrogen isotope compositions of amphiboles from the localities studied differ greatly, which is atypical for amphiboles from mantle, range between - 227 and - 700/00 (latter compatible with a simple mantle origin). As this wide range in compositions and the extreme depletion in the heavy hydrogen isotope (D) content relative to other igneous rocks appear to be unique to alkaline to peralkaline rocks of this type, a common process is indicated. The different alkaline complexes chosen cover a wide range of amphibole chemical compositions. Detailed chemical characterization of amphiboles by electron microprobe and Mössbauer spectroscopy analyses helped to constrain the control of Fe on the H-isotope fractionations. Complete characterization of the chemical compositions of the amphiboles support Fe-control on fractionations and at least for the peralkaline Ilímaussaq complex a relationship between Fe3+/FeT ratios and variations in D/H. The studied complexes differ in their agpaitic index (Na+K/Al) and also in their Fe-content. The most iron (27-35 wt. %) and alkaline element rich amphiboles, with the lowermost D/H ratio, as well with very wide range, are the ones from Ilímaussaq complex. Similar, but less D depleted amphiboles are from the Kola Peninsula and the Canadian localities. The complexes described from NW Namibia have amphiboles with normal magmatic hydrogen isotope composition (-730/00 to -1000/00), and have less Fe-content (15-17 wt. %), and are more Ca-and less Na-rich. In this case alkalinity is not that important in comparison to the other studied complexes. Beside the alkaline element contents in the amphiboles, the alkalinity of the fluids has been found to be an important factor, in conjunction with earlier suggestions from experimental systems. To further constrain this factor, hydrothermal exchange experiments between amphiboles and fluids of different salinity simulating natural conditions were performed. The approach of examining natural amphiboles from alkaline igneous complexes in parallel to performing exchange experiments - helped to further constrain the factors controlling the H-isotope fractionations in alkaline rocks. The observed changes between the hydrogen and oxygen isotope compositions of amphiboles and fluids before and after the experiments suggest that another phase was produced during the experiments, which influenced the final hydrogen isotope composition of the system. This presumably hydrous phase has also influenced the Fe3 +/Fe2+ ratio of the amphiboles, which became more oxidized. The extremely low SD values of amphiboles in these alkaline complexes may be due to a combination of different factors such as high alkalinity, high Fe-content, and shallow intrusion depths. This wide range and the low SD values of the amphiboles studied might be a result of internal, magmatic processes and it is unlikely that meteoric water was involved and/or magmatic degassing played an important role. RÉSUMÉ DE LA THÈSE (pour le grand public) Fractionnement isotopique de l'hydrogène entre amphiboles, micas et fluides dans des intrusions alcalines Zsófia Wáczek Directeur de thèse, Prof. Torsten W. Vennemann Institut de Minéralogie et Géochimie, Université de Lausanne Les roches alcalines et celles qui leurs sont associées sont des sources importantes de nombreux minéraux et minerais, tels l'apatite, le niobium, le diamant et autres pierres précieuses. Cette étude se concentre sur des complexes alcalins localisés dans le sud du Groenland, au Canada, dans la péninsule de Kola en Russie et au nord-ouest de la Namibie. Ces complexes sont composés de roches ayant cristallisé à partir de magmas et de fluides très enrichis en alcalins. Cet enrichissement permet la précipitation de minéraux inhabituels riches en potassium et/ou sodium, telles les amphiboles sodiques, également enrichies en fer. Les amphiboles étudiées ont des compositions calciques, sodi-calciques et sodiques, qui reflètent leurs différents environnements de formation. Des études précédentes ont révélé une large gamme de rapports isotopiques de l'hydrogène dans les amphiboles de roches hyperalcalines, dont certains extrêmement bas. Cette variation importante est très intrigante, sachant que des valeurs entre -40 et -800/00 correspondent à des silicates ignés hydratés et non altérés, alors que des valeurs descendant jusqu'a -1500/00 nécessiteraient une altération par de l'eau météorique et/ou une contamination par les roches environnantes ou des sédiments riches en matière organique. Dans lé cas précis du complexe d'Ilímaussaq (sud du Groenland), aucune de ces explications n'a pu être démontrée et des valeurs encore plus faibles ont été trouvées. Le complexe d'Ilímaussaq présente des valeurs de rapport isotopique de l'hydrogène entre -227 et -500/00 dans les amphiboles. Une origine mantellique permet d'expliquer les valeurs élevées, mais d'autres processus doivent entrer en jeu pour engendrer les valeurs les plus négatives. C'est à l'identification de ces processus que nous nous sommes attachés dans ce travail. Les grandes variations observées dans les teneurs en fer et dans le rapport Fe3+/FeT des roches et des minéraux de ces complexes sont corrélées avec d'autres paramètres chimiques, tels que la composition isotopique de l'hydrogène dans les amphiboles. Nous avons dès lors abordé les questions suivantes: quelle est la relation entre la teneur en fer des amphiboles et leur composition isotopique? Que nous apprennent les changements de la teneur en fer et les changements dans le rapport Fe3+/FeT sur les processus pétrologiques dans ces roches? Pour répondre à ces questions, nous avons analysé les compositions isotopiques de l'oxygène et de l'hydrogène dans les amphiboles et d'autres silicates hydratés. La composition chimique et le rapport Fe3+/FeT des amphiboles ont également été déterminés. Des expériences hydrothermales simulant des conditions naturelles ont été entreprises afin de mieux comprendre les processus de fractionnement isotopiques dans ces systèmes très alcalins. Nos conclusions sont les suivantes: (1) Les valeurs extrêmement faibles ainsi que les larges variations des rapports isotopiques de l'hydrogène des amphiboles de ces complexes alcalins sont dues à une combinaison de facteurs tels que la forte alcalinité, la haute teneur en fer et la profondeur très faible de l'intrusion. (2) Ces valeurs sont probablement le résultat de processus magmatiques internes. (3) Il est peu probable que les eaux météoriques et/ou le dégazage magmatique aient joué un rôle lors de la formation de ces amphiboles. (4) Certaines corrélations, en accord avec les études précédentes, ont pu être trouvées au niveau des concentrations en fer. (5) Dans le cas du complexe d'Ilímaussaq exclusivement, une relation a été trouvée entre le rapport Fe3+/FeT et la composition isotopique de l'hydrogène des amphiboles.

Relationship between cigarette smoking and abdominal obesity

BACKGROUND: Although smokers tend to have a lower body-mass index (BMI) than non-smokers, smoking may affect body fat (BF) distribution. Some studies have assessed the association between smoking, BMI and waist circumference (WC), but, to our knowledge, no population-based studies assessed the relation between smoking and BF composition. We assessed the association between amount of cigarette smoking, BMI, WC and BF composition. METHODS: Data was analysed from a cross-sectional population-based study including 6187 Caucasians aged 32-76 and living in Switzerland. Height, weight and WC were measured. BF, expressed in percent of total body weight, was measured by electrical bioimpedance. Obesity was defined as a BMI>=30 kg/m2 and normal weight as a BMI<25 kg/m2. Abdominal obesity was defined as a WC>=102 cm for men and >=88 cm for women and normal WC as <94 cm for men and <80 cm for women. In men, excess BF was defined as %BF >=28.1, 28.7, 30.6 and 32.6 for age groups 32-44, 45-54, 55-64 and 65-76, respectively; the corresponding values for women were 35.9, 36.5, 40.5 and 44.4. Cigarette smoking was assessed using a self-reported questionnaire. RESULTS: 29.3% of men and 25.0% of women were smokers. Prevalence of obesity, abdominal obesity, and excess of BF was 16.9% and 26.6% and 14.2% in men and 15.0%, 33.0% and 27.5% in women, respectively. Smokers had lower age-adjusted mean BMI, WC and percent of BF compared to non-smokers. However, among smokers,mean age-adjusted BMI,WC and BF increased with the number of cigarettes smoked per day: among light (1-10 cig/day), moderate (11-20) and heavy smokers (>20), mean +/-SE %BF was 22.4 +/−0.3, 23.1+/−0.3 and 23.5+/−0.4 for men, and 31.9+/−0.3, 32.6+/−0.3 and 32.9+/−0.4 for women, respectively. Mean WC was 92.9+/−0.6, 94.0+/−0.5 and 96.0+/−0.6 cm for men, and 80.2+/−0.5, 81.3+/−0.5 and 83.3+/−0.7 for women, respectively. Mean BMI was 25.7+/−0.2, 26.0+/−0.2, and 26.1+/−0.2 kg/m2 for men; and 23.6+/−0.2, 24.0+/−0.2 and 24.1+/−0.3 for women, respectively. Compared with light smokers, the age-adjusted odds ratio (95% Confidence Interval) for excess of BF was 1.04 (0.58 to 1.85) formoderatesmokers and 1.06 (0.57 to 1.99) for heavy smokers in men (p-trend = 0.9), and 1.35 (0.92 to 1.99) and 2.26 (1.38 to 3.72), respectively, in women (p-trend = 0.04). Odds ratio for abdominal obesity vs. normal WC was 1.32 (0.81 to 2.15) for moderate smokers and 1.95 (1.16 to 3.27) for heavy smokers in men (p-trend < 0.01), and 1.15 (0.79 to 1.69) and 2.36 (1.41 to 3.93) in women (p-trend = 0.03). Odds ratio for obesity vs. normal weight was 1.35 (0.76 to 2.41) for moderate smokers and 1.33 (0.71 to 2.49) for heavy smokers in men (p-trend = 0.9) and 0.78 (0.45 to 1.35) and 1.44 (0.73 to 2.85), in women (p-trend = 0.08). CONCLUSIONS: WC and BF were positively and dose-dependently associated with the number of cigarettes smoked per day in women, whereas onlyWC was dose dependently and significantly associated with the amount of cigarettes smoked per day in men. This suggests that heavy smokers, especially women, are more likely to have an excess of BF and to accumulate BF in the abdomen compared to lighter smokers.

Type I IFNs at the interface between cutaneous immunity and epidermal remodeling.

Type I IFNs are key cytokines in antiviral host defense. Preferentially expressed by plasmacytoid dendritic cells, type I IFNs are induced by viral infection and in common skin wounds. In this issue, Tohyama et al. identify a new link between type I IFNs and epidermal remodeling, by showing that type I IFNs specifically upregulate IL-22R expression on keratinocytes and, thereby, IL-22-mediated Stat3 phosphorylation in keratinocytes. The findings suggest that type I IFNs play dual roles in human skin: first, they induce immune activation with the induction of IL-22-producing T cells; second, they provide the interface between immune activation and epidermal remodeling by increasing keratinocyte responsiveness to IL-22.

An ultrastructural approach to analogies between fungal structures and needle fibre calcite

Needle fiber calcite (NFC) is an ubiquitous terrestrial secondary calcium carbonate mineral often associated with calcitic nanofibers. NFC's origin has been debated for a long time and a fungal origin is often proposed. Fungi are known to be involved in mineral weathering and production of metal oxalate, but little information exists regarding the genesis of other minerals, such as calcite. In this study, a comparison of similar ultrastructural characteristics of fungal hyphae and NFC has been performed to highlight analogies between both features. These analogies clearly demonstrate the probable close relationship between fungal filaments (hyphae and rhizomorphs) and NFC and its associated nanofibers.

Relationship between autonomic neuropathy and thermogenesis in non diabetic and diabetic obese patients.

Autonomic neuropathy is a well known complication of diabetes. Diabetes is often superimposed on obesity. A reduction in the variability of the heart rate in the resting state has been demonstrated in 16 obese diabetic subjects as well as in 34 obese non-diabetic subjects. The coefficient of variation (CV) of the heart rate during 30 minutes of resting was significantly decreased in both obese groups (3.9 +/- 0.2% for the diabetics; 5.2 +/- 0.2%, p less than 0.01 for the non diabetics) as compared to their own controls (4.5 +/- 0.6% and 6.5 +/- 0.4%, respectively). Age also contributes to decreased heart rate variability. Furthermore, this defect of autonomic function has been correlated with the blunted glucose-induced thermogenesis (GIT) seen in both obese groups (r = 0.52, p. less than 0.001): the increase in energy expenditure over basal values following a 100 g oral glucose load was only 4.8 +/- 0.8% for the diabetic obese group (p less than 0.001), and 8.5 +/- 0.7% for the non-diabetic obese group (p less than 0.001) as opposed to their own controls (12.4 +/- 1.3% and 13.3 +/- 0.6% respectively). Measurement of the variability of heart rate in obese individuals may be of predictive value in assessing blunted glucose-induced thermogenesis in non diabetic and diabetic obese patients.

Association between foot growth and musculoskeletal loading in children with Prader-Willi syndrome before and during growth hormone treatment

OBJECTIVE: To explore how foot growth relates to musculoskeletal loading in children with Prader-Willi syndrome (PWS). STUDY DESIGN: In 37 children with PWS, foot length (FL) before and after 6 years of growth hormone therapy (GHT) was retrospectively evaluated with parental and sibling's FL, height, and factors reflecting musculoskeletal loading, such as weight for height (WfH), lean body mass (LBM; dual energy X-ray absorptiometry, deuterium labeled water), physical activity (accellerometry), and walk age. Because of the typically biphasic evolution of body mass and the late walk age in PWS, 2 age groups were separated (group 1, >2.5 years; group 2, < or =2.5 years). RESULTS: Children with PWS normalized height, but not FL after 6 years of GHT. Parental FL correlation with PWS's FL was lower than with sibling's FL. In group 1, FL positively correlated with WfH, LBM, and physical activity. In group 2, FL negatively correlated with age at onset of independent ambulation. Foot catch-up growth with GHT was slower in group 2 compared with group 1. CONCLUSION: In PWS, FL is positively associated with musculoskeletal loading. Small feet in children with PWS before and during long-term GHT may be more than just another dysmorphic feature, but may possibly reflect decreased musculoskeletal loading influencing foot growth and genetic and endocrine factors.