Patterns of cortical thickness associated with impulse control disorders in Parkinson's disease

Previous functional neuroimaging studies in Parkinson's disease (PD) patients with impulse control disorders (ICDs) demonstrated dysfunction of the reward network, although the extent of anatomical changes is unclear. The aim of this study was to measure brain cortical thickness and subcortical volumes, and to assess their relationship with presence and severity of symptoms, in PD patients with and without ICDs. We studied 110 PD patients (N = 58 with ICDs) and 33 healthy controls (all negative for ICDs) who underwent an extensive neurological, neuropsychological, and behavioral assessment as well as structural 1.5 Tesla magnetic resonance imaging (MRI). Between‐group differences in brain cortical thickness and subcortical volumes, assessed with the FreeSurfer 5.1 tool, were analyzed. In patients with ICDs, we found significant cortical thinning in fronto‐striatal circuitry, specifically in the right superior orbitofrontal, left rostral middle frontal, bilateral caudal middle frontal region, and corpus callosum, as well as volume reduction in the right accumbens and increase in the left amygdala. Finally, we observed a positive association relationship between severity of impulsive symptoms and left rostral middle frontal, inferior parietal, and supramarginal areas. These results support the involvement of both reward and response inhibition networks in PD patients with ICDs. Moreover, their severity is associated with alterations in brain regions linked with reward and top‐down control networks. Increased understanding of the mechanisms underlying impulsive and compulsive behaviors might help improve therapeutic strategies for these important disorders. © 2015 International Parkinson and Movement Disorder Society     

Possible prognostic role of IL-17R in osteosarcoma

Purpose An intense vascularization of primary tumor mass is associated with a fatal outcome in various types of invasive solid tumors. Interleukin 17 (IL-17), a CD4+ T-cell-derived cytokine, stimulates some tumor cells to secrete angiogenic factors, among which venous endothelial growth factor (VEGF). We assessed whether the expression of IL-17 receptor (IL-17R) represents a marker for the metastasizing ability of osteosarcoma (OS), a very malignant bone tumor. Methods We immunoassayed the amount of VEGF secreted by three OS cell lines expressing IL-17R in differing amounts: HOS, MG63 and U-2 OS, and their sensitivity to IL-17 stimulation to secrete VEGF. Results U-2 OS, which best expresses IL-17R, secreted the highest amounts of VEGF and was the most sensitive to IL-17, whereas MG63 expressed the lowest level of IL-17R, secreted the lowest amount of VEGF and was not sensitive to IL-17. IL-17R expression correlated with VEGF secretion and IL-17 sensitivity. U-2 OS expressed the most dedifferentiated phenotype, which is associated with tumor malignancy. Conclusions These results suggest that IL-17R in OS might represent a marker of tumor metastasis potential.     

Relationships between blood pressure,anthropometric characteristics and blood lipids in high- and low-altitude populations from Central Asia

We studied the relationships between blood pressure, anthropometric characteristics and blood lipids in 72 low altitude (LA) Uighurs (600m), 91 LA-Kirghizs (900 m), 117 medium altitude (MA) Kazakhs (2100m) and 94 high altitude (HA) Kirghizs (3200 m). All subjects were male and had a similar age (p = ns, ANOVA; range for all 374 subjects: 18-66 yr). Body weight (Wt), body mass index (BMI) and the sum of four skinfolds (4SF) were significantly lower in HA-Kirghizs than the remaining groups (p < 0:0005, p < 0:0005 and p < 0:05 respectively, ANOVA). However, no difference was found in body fat distribution as detected by waist: hip circumference (WHR) and triceps : subscapular skinfold ratios (TSR; p = ns, ANOVA). Stage 1 hypertension was detected in 18% of LA-Uighurs, 2% of LA-Kirghizs, 4% of MA-Kazakhs and 1% of HA-Kirghizs; stage 2 hypertension was detected in 2% of LA-Uighurs and none of the remaining groups; no subject had stage 3 hypertension (The Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure 1997). Blood cholesterol (CH) and triglycerides (TG) did not differ between groups (p = ns, ANOVA). The relationships between systolic (SBP) or diastolic (DBP) blood pressure and age, Wt, BMI, 4SF, WHR, TSR, CH and TG were independent from altitude (p = ns, ANCOVA). In the pooled sample (n = 374), age explained 1 and 3% of SBP (p < 0:05) and DBP (p < 0:005) variance respectively, Wt was the best predictor of SBP and DBP explaining 11 and 10% of their variance respectively (p < 0:0001) and CH explained 5% of DBP variance (p < 0:0001). In conclusion, hypertension is more frequent in LA- than MA- and HA-subjects from Central Asia. However, anthropometric characteristics and blood lipids do similarly contribute to explain blood pressure in these subjects.

An Bewohnern des Tieflandes (LA), mittlerer Hohen (MA) und an Hochlandbevolkerungen (HA) wurde der Zusammenhang zwischen dem Blutdruck, anthropometrischen Charakteristika und Blutlipiden untersucht. Im einzelnen handelt es sich bei den untersuchten Bevolkerungen um 72 LA-Uiguren (600m), 91 LA-Kirgis (900 m), 117 MA-Kasaks (2100 m) und 94 HA-Kirgis (3200 m). Es handelt sich ausschliesslich um mannliche Probanden ahnlichen Alters (p = ns, ANOVA; Variationsbreite fur alle 374 Probanden: 18-66 Jahre). Das Korpergewicht (Wt), der Body Mass Index (BMI) und die Summe von vier Hautfaltendicken (4SF) war bei den HA-Kirgis signifikant niedriger als in den ubrigen Gruppen (p < 0:0005; p < 0:0005 bzw. p < 0:05, ANOVA). In der Verteilung des Korperfetts, die uber das Verhaltnis von Taillen- zu Huftumfang (WHR) sowie das Verhaltnis von Trizeps-Hautfaltendicke zur Dicke der subskapularen Hautfalte (TSR; p = ns, ANOVA) erfasst wurde, liessen sich jedoch keine Unterschiede beobachten. Ein Bluthochdruck im Stadium 1 liess sich bei 18% der LA-Uiguren, 2% der LA.Kirgis 4% der MA-Kasaks und 1% der HA-Kirgis beobachten; ein Bluthochdruck des Stadiums 2 wurde lediglich bei 2% der LA-Uiguren beobachtet, wahrend er in den ubrigen Bevolkerungen nicht vorkam; ein Bluthochdruck des Stadiums 3 wurde in keiner Bevolkerung beobachtet (The Joint National Committee on Prevention, Detection, Evaluation and Treatment of Hypertension 1997). In den Blutkonzentrationen von Cholesterin (CH) und Triglyzeriden (TG) wurden keine Unterschiede zwischen den Gruppen beobachtet (p = ns, ANOVA). Der Zusammenhang zwischen dem systolischen (SBP) bzw. dem diastolischen Blutdruck (DBP) und dem Alter, Wt, BMI, 4SF, WHR, TSR, CH und TG war von der Hohenlage des Wohnortes unabhangig (p = ns; ANCOVA). In der gepoolten Stichprobe (n = 374), erklarte das Alter 1 bzw. 3% der Varianz des SBP (p < 0:05) bzw. des DBP (p < 0:005). Das Gewicht erwies sich als bester Pradiktor des SBP und DBP, es erklarte 11 bzw. 10% der Varianz (p < 0:0001). CH erklarte 5% der Varianz des DBP (p < 0:0001). Zusammenfassend lasst sich festhalten, dass Bluthochdruck in Zentralasien bei LA-Bevolkerungen haufiger vorkommt als in MA- und HA-Bevolkerungen. Anthropometrische Charakteristika und Blutfette tragen jedoch in ahnlicher Weise zur Erklarung des Blutdruckes bei allen Probanden bei.

On a etudie les associations entre la pression arterielle, les caracteristiques anthropometriques et les lipides sanguins chez 72 Ouigour d'altitude basse (AB) (600 m), 91 AB-Khirghiz (900 m), 117 Kazakhs d'altitude moyenne (AM) (2100m) et 94 Kirghiz d'altitude haute (AH) (3200 m). Tous les sujets etaient des hommes adultes de moyenne d'age similaire (p = ns, ANOVA; etendue de variation pour l'ensemble des 374 sujets: 18-66 ans). Le poids corporel (Pds), l'indice de masse corporelle (IMC) et la somme des quatre plis cutanes (S4PC) etaient significativement plus bas chez les AH-Kirghiz que dans les autres groupes (respectivement p < 0:0005, p < 0:0005 et p < 0:05 ANOVA). Cependant, on n'a pas trouve de difference dans la distribution de la graisse corporelle telle que determinee par les rapports des circonferences taille/hanches (RTH) et par le rapport des plis cutanes triceps/sous-scapulaire (RTS; p = ns, ANOVA). L'hypertension de niveau 1 est presente chez 18% des AB-Ouigour, 2% des AB-Kirghiz, 4% des AMKazakh et 1% des AH-Kirghiz. Le niveau 2 d'hypertension a ete detecte chez 2% des AB-Ouigour seulement. Aucun des sujets n'avait atteint le niveau 3 d'hypertension (Comite de Prevention, Detection, Evaluation et Traitement de la Haute Pression Arterielle, 1997). Le cholesterol sanguin (CS) et les triglycerides (TG) ne differaient pas entre groupes (p = ns, ANOVA). Les associations entre pressions arterielle systolique (PAS), diastolique (PAD) et l'age, le Pds, l'IMC, la S4PC, le RTH, le RTS, le CS et les TG sont independantes de l'altitude (p = ns, ANCOVA). L'age expliquait respectivement 1 et 3% des variances de la PAS (p < 0:05) et de la PSD (p < 0:005), le Pds etant le meilleur predicteur de la PAS et de la PAD, expliquant respectivement 11% et 10% de leur variance (p, < 0:0001), le CS expliquant 5% de la variance en PAD (p < 0:0001). En conclusion, l'hypertension est plus frequente chez les sujets d'AB- que d'AM- et d'AH- en Asie Centrale. Les caracteristiques anthropometriques et les lipides sanguins contribuent demaniere semblable a expliquer la pression arterielle chez les sujets examines.     

Craniofacial bone atrophy in Parry Romberg syndrome demonstrated using a Bayesian hierarchical model

PurposeParry Romberg syndrome (PRS) is a condition characterized by progressive hemifacial atrophy, predominantly affecting the soft tissues. Associated bone retraction is a common clinical feature of PRS but has never been assessed. Here we used 3D imaging and Bayesian statistics in order to demonstrate and quantify bone atrophy in PRS.Materials and methodsTen non-operated patients with PRS (4/10 males) and 12 age-matched controls (7/12 males) were included into the study. The average age at CT-scan was 9.67 ± 4.13 years for PRS patients and 12.5 ± 4.37 years for controls. Soft and hard tissue atrophy levels were quantified using computed tomography scans, based on the distances between surfaces of the affected side and the non-affected contralateral side, both for the skin and the bone. We used a hierarchical Bayesian model with clinical priors in order to assess the relationship between hard and soft tissue atrophies.ResultsPRS patients had significant hard tissue atrophy, and atrophy extents were similar for soft and hard tissues. There was a trend for a correlation between the extent of hard tissue retraction and the extent of soft tissue retraction, and we could not demonstrate that the relationship between hard and soft tissue retractions was different in PRS and controls.ConclusionOur results indicated that bone atrophy was most probably a primary process rather than a phenomenon secondary to soft tissue retraction. We have provided the first assessment of bone atrophy in PRS patients using Bayesian statistics.     

Insulin resistance, hyperinsulinemia, and dyslipidemia in nonobese individuals with a family history of hypertension.

Various facets of glucose, insulin, and lipid metabolism were compared in 76 normal volunteers--38 with and 38 without a family history of hypertension. The two groups were comparable in terms of age, gender distribution, and degree of obesity (both generalized and abdominal). Although the plasma glucose response to oral glucose was similar in both groups, glucose-stimulated insulin concentrations were significantly greater in volunteers with a family history of hypertension (P < .001). Furthermore, the steady state plasma glucose concentration during a constant infusion of glucose, insulin and somatostatin was significantly greater in subjects with a family history of hypertension (8.1 +/- 0.6 v 6.2 +/- 0.6 mmol/L, P < .001). Since the steady-state plasma insulin levels during the infusion were similar, these results indicate that normotensive individuals with a family history of hypertension are relatively insulin resistant. Finally, plasma very low density lipoprotein (VLDL) triglyceride and VLDL cholesterol were higher in those with a family history of hypertension, as was the ratio of total to high density lipoprotein cholesterol. Thus, normotensive individuals with a family history of high blood pressure are insulin resistant, hyperinsulinemic and dyslipidemic when compared to a matched group of healthy volunteers without a family history of hypertension.     

Evaluation of ex vivo expansion and engraftment in NOD-SCID mice of umbilical cord blood CD34+ cells using the DIDECO "Pluricell System"

The Dideco "Pluricell System" is a commercially available closed device composed of an expansion chamber and a kit of certified reagents that allow haematopoietic stem cell expansion. We have expanded seven umbilical cord blood (UCB) samples following the manufacturer's instructions; two groups of irradiated NOD-SCID mice have been transplanted with expanded and nonexpanded cells from the same UCB, and bone marrow was analysed for the presence of human cells. Average UCB volume was 61.6+/-8.8 ml; mean nucleated cell content was 1090.5+/-189.9 x 10(6). Percentage and number of CD34+ cells were 0.37+/-0.13% and 3.9+/-1.2 x 10(6). After separation, CD34+ cell purity was 82+/-11%. Mean number of inoculated cells was 760 000; mean NC and CD34+ fold expansion at 12 days was 230.4+/-91.5 and 21.0+/-11.9. Both groups of mice showed successful engraftment: the percentage of human cells was higher in the group receiving expanded cells (3.4+/-2.01%) compared to the group receiving nonexpanded cells (1.5+/-0.66%) (P<0.00018, Mann-Whitney test). The cell population obtained after 12 days expansion consisted mainly of myeloid and megakaryocytic progenitors. The CD34+ antigen reached the maximum expression level at day 12 (7.5+/-2.0%). Analysis of lineage-markers for human myelomonocytic, megakaryocytic, B, T, CD34 and erythroid cells, gave evidence that all the lineages were represented in the marrow of transplanted mice.