The SOD2 C47T polymorphism influences NAFLD fibrosis severity: evidence from case-control and intra-familial allele association studies.

AIMS: Non-alcoholic fatty liver disease (NAFLD) is a complex disease trait where genetic variations and environment interact to determine disease progression. The association of PNPLA3 with advanced disease has been consistently demonstrated but many other modifier genes remain unidentified. In NAFLD, increased fatty acid oxidation produces high levels of reactive oxygen species. Manganese-dependent superoxide dismutase (MnSOD), encoded by the SOD2 gene, plays an important role in protecting cells from oxidative stress. A common non-synonymous polymorphism in SOD2 (C47T; rs4880) is associated with decreased MnSOD mitochondrial targeting and activity making it a good candidate modifier of NAFLD severity. METHODS: The relevance of the SOD2 C47T polymorphism to fibrotic NAFLD was assessed by two complementary approaches: we sought preferential transmission of alleles from parents to affected children in 71 family trios and adopted a case-control approach to compare genotype frequencies in a cohort of 502 European NAFLD patients. RESULTS: In the family study, 55 families were informative. The T allele was transmitted on 47/76 (62%) possible occasions whereas the C allele was transmitted on only 29/76 (38%) occasions, p=0.038. In the case control study, the presence of advanced fibrosis (stage>1) increased with the number of T alleles, p=0.008 for trend. Multivariate analysis showed susceptibility to advanced fibrotic disease was determined by SOD2 genotype (OR 1.56 (95% CI 1.09-2.25), p=0.014), PNPLA3 genotype (p=0.041), type 2 diabetes mellitus (p=0.009) and histological severity of NASH (p=2.0×10(-16)). CONCLUSIONS: Carriage of the SOD2 C47T polymorphism is associated with more advanced fibrosis in NASH

Interdisciplinary rehabilitation in morbidly obese subjects: an observational pilot study.

BACKGROUND AND AIM: To assess the clinical effectiveness of a interdisciplinary rehabilitation programme (CR), in a population of morbidly obese subjects we have undertaken a observational study. METHODS: The study included fifty-nine adult subjects (18 M, 60+/-10 years, BMI 47+/-8) with sleep-disturbance related symptoms and disabilities. Assessment and correction of sleep disordered breathing (SDB) abnormalities, improvement of exercise tolerance, body weight and associated psychological features were the aims of this CR, which has been carried out over a 1 month period.Lung functions, apnea/hypopnea index (AHI), 6-minute walking distance (6MWD), body weight (BW), quality of life by means of Sat-P questionnaire and serum metabolic data has been recorded at baseline (TO), at the end (Ti) and 6 months after (T2) the CR. RESULTS: The percentage of patients with AHI > 10 declined from 65% (at TO) to 20% (at both T1 and T2). 6MWD and BW significantly improved (p < 0.005) at T1 and still maintained at T2; a significant relationship (r = 0.379, p < 0.01) has been found between changes of BW and 6MWD recorded in between TO and T2. Sat-P item scores dealing with sleep efficiency, problem solving, and social interactions improved (p < 0.01) at T1 and still maintained at T2. CONCLUSIONS: This hospital-based CR provides indication for effectiveness in advanced morbidly obese subjects and warrants further controlled trials to confirm the results

Interdisciplinary rehabilitation in morbidly obese subjects: an observational pilot study

Background and aim. To assess the clinical effectiveness of a interdisciplinary rehabillitation programme (CR), in a population of morbidly obese subjects we have undertaken a observational study. Methods. The study included fifty-nine adult subjects (18 M, 60±10 years, BMI 47±8) with sleep-disturbance related symptoms and disabilities. Assessment and correction of sleep disordered breathing (SDB) abnormalities, improvement of exercise tolerance, body weight and associated psychological features were the aims of this CR, which has been carried out over a 1 month period.Lung functions, apnea/hypopnea index (AHI), 6-minute walking distance (6MWD), body weight (BW), quality of life by means of Sat-P questionnaire and serum metabolic data has been recorded at baseline (T0), at the end (T1) and 6 months after (T2) the CR. Results. The percentage of patients with AHI>10 declined from 65% (at T0) to 20% (at both T1 and T2). 6MWD and BW significantly improved (p<0.005) at T1 and still maintained at T2; a significant relationship (r=0.379, p<0.01) has been found between changes of BW and 6MWD recorded in between T0 and T2. Sat-P item scores dealing with sleep efficiency, problem solving, and social interactions improved (p<0.01) at T1 and still maintained at T2. Conclusions. This hospital-based CR provides indication for effectiveness in advanced morbidly obese subjects and warrants further controlled trials to confirm the results

Atomic Resonance and Scattering

Contains reports on four research projects.U.S. Air Force - Office of Scientific Research (Grant AFOSR-76-2972)National Science Foundation (Grant CHE79-02967)National Science Foundation (Grant PHY79-09743)Joint Services Electronics Program (Contract DAAG29-78-C-0020)Joint Services Electronics Program (Contract DAAG29-80-C-0104

Association between 8 P-glycoprotein (MDR1/ABCB1) gene polymorphisms and antipsychotic drug-induced hyperprolactinaemia

Introduction: Hyperprolactinaemia, a common adverse effect of antipsychotic drugs, is primarily linked to blockade of dopamine D2 receptors in the pituitary gland. Certain antipsychotic drugs, such as, for example risperidone and paliperidone, are more likely to induce hyperprolactinaemia compared to others. This effect is probably caused by a relatively high blood/brain concentration ratio, a consequence of being a substrate of P-glycoprotein. Genetic variants of P-glycoprotein with changed functional activity might influence the potential of risperidone and paliperidone to cause hyperprolactinaemia as the altered blood/brain concentration ratio would lead to a reduced therapeutic drug level within essential brain areas making dose adaptations necessary. This increases exposure of dopamine D2 receptors within the pituitary gland. Aims: To investigate possible associations between MDR1/ABCB1 gene polymorphisms and antipsychotic drug-induced hyperprolactinaemia in Russian patients with schizophrenia and to determine possible differences between risperidone/paliperidone and other antipsychotics. Methods: In total, 446 patients with schizophrenia were included from 3 psychiatric hospitals in Siberia. Blood samples were obtained in a cross-sectional study design for DNA extraction and prolactin measurement. Associations between hyperprolactinaemia and 8 MDR1/ABCB1 gene-polymorphisms were assessed using logistic regression analysis accounting for covariates. The analysis was repeated in a patient subgroup using risperidone or paliperidone. Results: We did not observe an association between any of the 8 single nucleotide polymorphisms and the prevalence of antipsychotic-induced hyperprolactinaemia in the total patient population. However, in the risperidone/paliperidone subgroup, the single nucleotide polymorphism rs2032582 (G2677T) was found to be negatively associated with risperidone/paliperidone-induced hyperprolactinaemia. Conclusion: This study revealed a significant association between the ABCB1 gene polymorphism rs2032582 (G2677T) and risperidone/paliperidone-induced hyperprolactinaemia

Imaging aortic regurgitation: The incremental benefit of speckle tracking echocardiography

Aortic regurgitation (AR) affects global left ventricular mechanics. However, limited literature is available on how it may affect regional longitudinal strain. We present a case where severe AR jet is thrashing the anterior-septal wall and reducing its overall longitudinal performance most likely secondary to increased wall shear stress in diastole. This new insight into patho-physiological process using deformation study may have supplementary impact in decision making for surgical intervention. Transthoracic echocardiography is the primary imaging modality for the assessment of AR as it offers evaluation of severity of AR, aetiology of AR, left ventricular (LV) dilatation, LV systolic function, left ventricular mass, diastolic function and global strain. This case highlights the regional disturbances in longitudinal strain in eccentric AR

Preliminary clinical study of left ventricular myocardial strain in patients with non-ischemic dilated cardiomyopathy by three-dimensional speckle tracking imaging

<p>Abstract</p> <p>Background</p> <p>Non-ischemic dilated cardiomyopathy (DCM) is the most common cardiomyopathy worldwide, with significant mortality. Correct evaluation of the patient's myocardial function has important clinical significance in the diagnosis, therapeutic effect assessment and prognosis in non-ischemic DCM patients. This study evaluated the feasibility of three-dimensional speckle tracking imaging (3D-STE) for assessment of the left ventricular myocardial strain in patients with non-ischemic dilated cardiomyopathy (DCM).</p> <p>Methods</p> <p>Apical full-volume images were acquired from 65 patients with non-ischemic DCM (DCM group) and 59 age-matched normal controls (NC group), respectively. The following parameters were measured by 3D-STE: the peak systolic radial strain (RS), circumferential strain (CS), longitudinal strain (LS) of each segment. Then all the parameters were compared between the two groups.</p> <p>Results</p> <p>The peak systolic strain in different planes had certain regularities in normal groups, radial strain (RS) was the largest in the mid region, the smallest in the apical region, while circumferential strain (CS) and longitudinal strain (LS) increased from the basal to the apical region. In contrast, the regularity could not be applied to the DCM group. RS, CS, LS were significantly decreased in DCM group as compared with NC group (<it>P </it>< 0.001 for all). The interobserver, intraobserver and test-retest reliability were acceptable.</p> <p>Conclusions</p> <p>3D-STE is a reliable tool for evaluation of left ventricular myocardial strain in patients with non-ischemic DCM, with huge advantage in clinical application.</p

Emergent magnetism at transition-metal–nanocarbon interfaces

Charge transfer at metallo–molecular interfaces may be used to design multifunctional hybrids with an emergent magnetization that may offer an eco-friendly and tunable alternative to conventional magnets and devices. Here, we investigate the origin of the magnetism arising at these interfaces by using different techniques to probe 3d and 5d metal films such as Sc, Mn, Cu, and Pt in contact with fullerenes and rf-sputtered carbon layers. These systems exhibit small anisotropy and coercivity together with a high Curie point. Low-energy muon spin spectroscopy in Cu and Sc–C60 multilayers show a quick spin depolarization and oscillations attributed to nonuniform local magnetic fields close to the metallo–carbon interface. The hybridization state of the carbon layers plays a crucial role, and we observe an increased magnetization as sp3 orbitals are annealed into sp2−π graphitic states in sputtered carbon/copper multilayers. X-ray magnetic circular dichroism (XMCD) measurements at the carbon K edge of C60 layers in contact with Sc films show spin polarization in the lowest unoccupied molecular orbital (LUMO) and higher π*-molecular levels, whereas the dichroism in the σ*-resonances is small or nonexistent. These results support the idea of an interaction mediated via charge transfer from the metal and dz–π hybridization. Thin-film carbon-based magnets may allow for the manipulation of spin ordering at metallic surfaces using electrooptical signals, with potential applications in computing, sensors, and other multifunctional magnetic devices

Atomic Resonance and Scattering

Contains reports on eight research projects.National Science Foundation (Grant PHY77-09155)Joint Services Electronics Program (Contract DAAG29-78-C-0020)U. S. Department of Energy (Grant EG-77-S-02-4370)National Science Foundation (Grant DMR 77-10084)National Aeronautics and Space Administration (Grant NSG-1551)U. S. Air Force - Office of Scientific Research (Grant AFOSR-76-2972)National Science Foundation (Grant CHE76-81750