Altered intrahemispheric structural connectivity in Gilles de la Tourette syndrome

Gilles de la Tourette syndrome (GTS) is a common developmental neuropsychiatric disorder characterized by tics and frequent psychiatric comorbidities, often causing significant disability. Tic generation has been linked to disturbed networks of brain areas involved in planning, controlling and execution of actions, particularly structural and functional disorders in the striatum and cortico-striato-thalamo-cortical loops. We therefore applied structural diffusion tensor imaging (DTI) to characterize changes in intrahemispheric white matter connectivity in cortico-subcortical circuits engaged in motor control in 15 GTS patients without psychiatric comorbidities. White matter connectivity was analyzed by probabilistic fiber tractography between 12 predefined cortical and subcortical regions of interest. Connectivity values were combined with measures of clinical severity rated by the Yale Global Tic Severity Scale (YGTSS). GTS patients showed widespread structural connectivity deficits. Lower connectivity values were found specifically in tracts connecting the supplementary motor areas (SMA) with basal ganglia (pre-SMA-putamen, SMA-putamen) and in frontal cortico-cortical circuits. There was an overall trend towards negative correlations between structural connectivity in these tracts and YGTSS scores. Structural connectivity of frontal brain networks involved in planning, controlling and executing actions is reduced in adult GTS patients which is associated with tic severity. These findings are in line with the concept of GTS as a neurodevelopmental disorder of brain immaturity

Effect of cardiac rehabilitation on functional and emotional status in patients after transcatheter aortic-valve implantation

Background Transcatheter aortic-valve implantation (TAVI) is an established alternative therapy in patients with severe aortic stenosis and a high surgical risk. Despite a rapid growth in its use, very few data exist about the efficacy of cardiac rehabilitation (CR) in these patients. We assessed the hypothesis that patients after TAVI benefit from CR, compared to patients after surgical aortic-valve replacement (sAVR). Methods From September 2009 to August 2011, 442 consecutive patients after TAVI (n=76) or sAVR (n=366) were referred to a 3-week CR. Data regarding patient characteristics as well as changes of functional (6-min walk test. 6-MWT), bicycle exercise test), and emotional status (Hospital Anxiety and Depression Scale) were retrospectively evaluated and compared between groups after propensity score adjustment. Results Patients after TAVI were significantly older (p<0.001), more female (p<0.001), and had more often coronary artery disease (p=0.027), renal failure (p=0.012) and a pacemaker (p=0.032). During CR, distance in 6-MWT (both groups p0.001) and exercise capacity (sAVR p0.001, TAVI p0.05) significantly increased in both groups. Only patients after sAVR demonstrated a significant reduction in anxiety and depression (p0.001). After propensity scores adjustment, changes were not significantly different between sAVR and TAVI, with the exception of 6-MWT (p=0.004). Conclusions Patients after TAVI benefit from cardiac rehabilitation despite their older age and comorbidities. CR is a helpful tool to maintain independency for daily life activities and participation in socio-cultural life

Immune phenotype in children with therapy-naïve remitted and relapsed Crohn’s disease

AIM: To characterize the prevalence of subpopulations of CD4+ cells along with that of major inhibitor or stimulator cell types in therapy-naïve childhood Crohn’s disease (CD) and to test whether abnormalities of immune phenotype are normalized with the improvement of clinical signs and symptoms of disease

A Single Nucleotide Polymorphism near the CYP17A1 Gene Is Associated with Left Ventricular Mass in Hypertensive Patients under Pharmacotherapy

Cytochrome P450 17A1 (CYP17A1) catalyses the formation and metabolism of steroid hormones. They are involved in blood pressure (BP) regulation and in the pathogenesis of left ventricular hypertrophy. Therefore, altered function of CYP17A1 due to genetic variants may influence BP and left ventricular mass. Notably, genome wide association studies supported the role of this enzyme in BP control. Against this background, we investigated associations between single nucleotide polymorphisms (SNPs) in or nearby the CYP17A1 gene with BP and left ventricular mass in patients with arterial hypertension and associated cardiovascular organ damage treated according to guidelines. Patients (n = 1007, mean age 58.0 ± 9.8 years, 83% men) with arterial hypertension and cardiac left ventricular ejection fraction (LVEF) ≥40% were enrolled in the study. Cardiac parameters of left ventricular mass, geometry and function were determined by echocardiography. The cohort comprised patients with coronary heart disease (n = 823; 81.7%) and myocardial infarction (n = 545; 54.1%) with a mean LVEF of 59.9% ± 9.3%. The mean left ventricular mass index (LVMI) was 52.1 ± 21.2 g/m2.7 and 485 (48.2%) patients had left ventricular hypertrophy. There was no significant association of any investigated SNP (rs619824, rs743572, rs1004467, rs11191548, rs17115100) with mean 24 h systolic or diastolic BP. However, carriers of the rs11191548 C allele demonstrated a 7% increase in LVMI (95% CI: 1%–12%, p = 0.017) compared to non-carriers. The CYP17A1 polymorphism rs11191548 demonstrated a significant association with LVMI in patients with arterial hypertension and preserved LVEF. Thus, CYP17A1 may contribute to cardiac hypertrophy in this clinical condition

MYCN amplification predicts poor outcome for patients with supratentorial primitive neuroectodermal tumors of the central nervous system

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are a rare group of neoplasms occurring in the CNS that includes supratentorial CNS-PNETs, medulloepitheliomas, and ependymoblastomas. While ependymoblastomas frequently carry chromosome 19q13.41 amplification and show aggressive clinical behavior, the biological mechanisms and molecular alterations contributing to the pathogenesis of supratentorial CNS-PNETs remain poorly understood. Moreover, genetic alterations suitable for molecular risk stratification are undefined to date. In order to identify possible molecular markers, we performed multiplex ligation-dependent probe amplification (MLPA) and molecular inversion probe (MIP) analysis on DNA samples of 25 supratentorial CNS-PNETs (median age, 5.35 years; range, 2.41-17.28 years). Tumors with ependymoblastic rosettes (ependymoblastoma/ETANTR) and LIN28A positivity were excluded. MLPA and MIP analysis revealed large losses of genomic material of chromosomes 3, 4, 5, and 13, while frequent gains affected chromosomes 1, 17, 19, 20, and 22. High copy number gains (amplifications) were found in particular at chromosomes 2p24.3 (MYCN, n = 6 cases) and 4q12 (n = 2 cases). Patients with tumors harboring 2p gain or MYCN amplification showed unfavorable overall survival (P = .003 and P = .001, respectively).These markers were independent of the presence of metastases, which was indeed a clinical factor associated with poor overall survival (P = .01) in this series. In the era of the personalized neuro-oncology, the identification of these molecular prognostic markers associated with patient outcome may represent a significant step towards improved patient stratification and risk-adapted therapeutic strategies for patients suffering from supratentorial CNS-PNETs

MYCN amplification predicts poor outcome for patients with supratentorial primitive neuroectodermal tumors of the central nervous system

Primitive neuroectodermal tumors of the central nervous system (CNS-PNETs) are a rare group of neoplasms occurring in the CNS that includes supratentorial CNS-PNETs, medulloepitheliomas, and ependymoblastomas. While ependymoblastomas frequently carry chromosome 19q13.41 amplification and show aggressive clinical behavior, the biological mechanisms and molecular alterations contributing to the pathogenesis of supratentorial CNS-PNETs remain poorly understood. Moreover, genetic alterations suitable for molecular risk stratification are undefined to date. In order to identify possible molecular markers, we performed multiplex ligation-dependent probe amplification (MLPA) and molecular inversion probe (MIP) analysis on DNA samples of 25 supratentorial CNS-PNETs (median age, 5.35 years; range, 2.41-17.28 years). Tumors with ependymoblastic rosettes (ependymoblastoma/ETANTR) and LIN28A positivity were excluded. MLPA and MIP analysis revealed large losses of genomic material of chromosomes 3, 4, 5, and 13, while frequent gains affected chromosomes 1, 17, 19, 20, and 22. High copy number gains (amplifications) were found in particular at chromosomes 2p24.3 (MYCN, n = 6 cases) and 4q12 (n = 2 cases). Patients with tumors harboring 2p gain or MYCN amplification showed unfavorable overall survival (P = .003 and P = .001, respectively).These markers were independent of the presence of metastases, which was indeed a clinical factor associated with poor overall survival (P = .01) in this series. In the era of the personalized neuro-oncology, the identification of these molecular prognostic markers associated with patient outcome may represent a significant step towards improved patient stratification and risk-adapted therapeutic strategies for patients suffering from supratentorial CNS-PNETs

Skin conductance in neonates suffering from abstinence syndrome and unexposed newborns

The aims of this study were to compare the skin conductance (SC) of newborns with opiate-induced neonatal abstinence syndrome (NAS) to that of unexposed newborns and to evaluate the potential of SC readings to detect distress in the context of NAS objectively. The SC of 12 newborns with NAS and 12 unexposed newborns was measured at nine specific times during their first 6 weeks of life. The number of SC fluctuations per second (NSCF/s), the amplitude of SC fluctuation, and the mean level of SC were recorded and analyzed. The SC of newborns treated for symptoms of NAS differed significantly from the SC of unexposed newborns with regard to the NSCF/s (p = 0.04). With the mean level of SC, we observed an interaction between groups over time (p value for interaction = 0.02). With increasing postnatal age, we observed higher values in all three SC parameters. Conclusion: The NSCF/s and the mean level of SC appear to be suitable to reflect the distress of newborns suffering from NAS. As it is known that the sensitivity of SC increases with the level of stress experienced, its potential to indicate elevated stress levels in infants with NAS should be investigated in future studies evaluating different therapy regimens

Substantial expression of luteinizing hormone-releasing hormone (LHRH) receptor type I in human uveal melanoma

Uveal melanoma is the most common primary intraocular malignancy in adults, with a very high mortality rate due to frequent liver metastases. Consequently, the therapy of uveal melanoma remains a major clinical challenge and new treatment approaches are needed. For improving diagnosis and designing a rational and effective therapy, it is essential to elucidate molecular characteristics of this malignancy. The aim of this study therefore was to evaluate as a potential therapeutic target the expression of luteinizing hormone-releasing hormone (LHRH) receptor in human uveal melanoma. The expression of LHRH ligand and LHRH receptor transcript forms was studied in 39 human uveal melanoma specimens by RT-PCR using gene specific primers. The binding charachteristics of receptors for LHRH on 10 samples were determined by ligand competition assays. The presence of LHRH receptor protein was further evaluated by immunohistochemistry. The expression of mRNA for type I LHRH receptor was detected in 18 of 39 (46%) of tissue specimens. mRNA for LHRH-I ligand could be detected in 27 of 39 (69%) of the samples. Seven of 10 samples investigated showed high affinity LHRH-I receptors. The specific presence of full length LHRH receptor protein was further confirmed by immunohistochemistry. A high percentage of uveal melanomas express mRNA and protein for type-I LHRH receptors. Our results support the merit of further investigation of LHRH receptors in human ophthalmological tumors. Since diverse analogs of LHRH are in clinical trials or are already used for the treatment of various cancers, these analogs could be considered for the LHRH receptor-based treatment of uveal melanoma