APOLIPOPROTEIN E (epsilon) genotype has a greater impact on apoB-48 than apoB-100 responses to dietary fat manipulation- insights from the SATgenε study

SCOPE: To determine the contribution of intestinally and liver-derived lipoproteins to the postprandial plasma triacylglycerol (TAG) response in APOE3/E3 and E3/E4 individuals following chronic dietary fat manipulation. METHODS AND RESULTS: In sequential order, participants (n = 12 E3/E3, n = 11 E3/E4) followed low fat (LF); high-fat, high-saturated fat (HSF); and HSF with 3.45 g/day docosahexaenoic acid (HSF-DHA) diets, each for 8 weeks. After each dietary period, an acute test meal with a macronutrient profile representative of the dietary intervention was consumed. Apolipoprotein (apo)B isoforms were determined in isolated TAG-rich lipoprotein fractions (Sf >400, Sf 60-400 and Sf 20-60) by specific ELISA. A genotype*meal/diet interaction for the Sf >400 fraction apoB-48 response (P400 particles. Fasting Sf 60-400 and 20-60 apoB-48 concentrations were also significantly higher in E4 carriers. No impact of genotype on the apoB-100 responses was evident. CONCLUSION: Our study revealed marked effects of dietary fat composition on the Sf >400 apoB-48 response and particle TAG content in E4 carriers relative to the 'wild-type' E3/E3 genotype, which suggest APOE genotype is a potential modulator of chylomicron particle synthesis. This article is protected by copyright. All rights reserved

The topology of connections between rat prefrontal, motor and sensory cortices

The connections of prefrontal cortex (PFC) were investigated in the rat brain to determine the order and location of input and output connections to motor and somatosensory cortex. Retrograde (100 nl Fluoro-Gold) and anterograde (100 nl Biotinylated Dextran Amines, BDA; Fluorescein and Texas Red) neuronanatomical tracers were injected into the subdivisions of the PFC (prelimbic, ventral orbital, ventrolateral orbital, dorsolateral orbital) and their projections studied. We found clear evidence for organized input projections from the motor and somatosensory cortices to the PFC, with distinct areas of motor and cingulate cortex projecting in an ordered arrangement to the subdivisions of PFC. As injection location of retrograde tracer was moved from medial to lateral in PFC, we observed an ordered arrangement of projections occurring in sensory-motor cortex. There was a significant effect of retrograde injection location on the position of labelled cells occurring in sensory-motor cortex (dorsoventral, anterior-posterior and mediolateral axes p < 0.001). The arrangement of output projections from PFC also displayed a significant ordered projection to sensory-motor cortex (dorsoventral p < 0.001, anterior-posterior p = 0.002 and mediolateral axes p < 0.001)

Hierarchical Star Formation in Nearby LEGUS Galaxies

Hierarchical structure in ultraviolet images of 12 late-type LEGUS galaxies is studied by determining the numbers and fluxes of nested regions as a function of size from ~1 to ~200 pc, and the number as a function of flux. Two starburst dwarfs, NGC 1705 and NGC 5253, have steeper number-size and flux-size distributions than the others, indicating high fractions of the projected areas filled with star formation. Nine subregions in 7 galaxies have similarly steep number-size slopes, even when the whole galaxies have shallower slopes. The results suggest that hierarchically structured star-forming regions several hundred parsecs or larger represent common unit structures. Small galaxies dominated by only a few of these units tend to be starbursts. The self-similarity of young stellar structures down to parsec scales suggests that star clusters form in the densest parts of a turbulent medium that also forms loose stellar groupings on larger scales. The presence of super star clusters in two of our starburst dwarfs would follow from the observed structure if cloud and stellar subregions more readily coalesce when self-gravity in the unit cell contributes more to the total gravitational potential.Comment: 9 pages, 4 figures, accepted for ApJ

Testing Matter Effects in Very Long Baseline Neutrino Oscillation Experiments

Assuming three-neutrino mixing, we study the capabilities of very long baseline neutrino oscillation experiments to verify and test the MSW effect and to measure the lepton mixing angle theta_13. We suppose that intense neutrino and antineutrino beams will become available in so-called neutrino factories. We find that the most promising and statistically significant results can be obtained by studying nu_e ->nu_mu and \bar{nu}_e-> \bar{nu}_mu oscillations which lead to matter enhancements and suppressions of wrong sign muon rates. We show the theta_13 ranges where matter effects could be observed as a function of the baseline. We discuss the scaling laws of rates, significances and sensitivities with the relevant mixing angles and experimental parameters. Our analysis includes fluxes, event rates and statistical aspects so that the conclusions should be useful for the planning of experimental setups. We discuss the subleading Delta m^2_{21} effects in the case of the LMA MSW solution of the solar problem, showing that they are small for L >= 7000 km. For shorter baselines, Delta m^2_{21} effects can be relevant and their dependence on L offers a further handle for the determination of the CP-violation phase \delta. Finally we comment on the possibility to measure the specific distortion of the energy spectrum due to the MSW effect.Comment: 30 pages, 13 figures, figures and more discussion added, results and conclusions unchange

The impact of hyperhidrosis on patients' daily life and quality of life : A qualitative investigation

Background: An understanding of the daily life impacts of hyperhidrosis and how patients deal with them, based on qualitative research, is lacking. This study investigated the impact of hyperhidrosis on the daily life of patients using a mix of qualitative research methods. Methods: Participants were recruited through hyperhidrosis patient support groups such as the Hyperhidrosis Support Group UK. Data were collected using focus groups, interviews and online surveys. A grounded theory approach was used in the analysis of data transcripts. Data were collected from 71 participants, out of an initial 100 individuals recruited. Results: Seventeen major themes capturing the impacts of hyperhidrosis were identified; these covered all areas of life including daily life, psychological well-being, social life, professional /school life, dealing with hyperhidrosis, unmet health care needs and physical impact. Conclusions: Psychosocial impacts are central to the overall impacts of hyperhidrosis, cutting across and underlying the limitations experienced in other areas of life.Peer reviewe

A prospective open-label treatment trial of olanzapine monotherapy in children and adolescents with bipolar disorder

OBJECTIVE: The goal of this study was to assess the effectiveness and tolerability of olanzapine in the treatment of acute mania in children and adolescents. METHODS: This was an 8-week, open-label, prospective study of olanzapine monotherapy (dose range 2.5-20 mg/day) involving 23 bipolar youths (manic, mixed, or hypomanic; 5-14 years old). Weekly assessments were made using the Young Mania Rating Scale (YMRS), Clinical Global Impressions Severity Scale (CGI-S), Brief Psychiatric Rating Scale, and Children\u27s Depression Rating Scale. Adverse events were assessed through self-reports, vital sign and weight monitoring, laboratory analytes, and extrapyramidal symptom rating scales (Barnes Akathisia Scale, Simpson-Angus Scale, and Abnormal Involuntary Movement Scale). RESULTS: Twenty-two of the 23 youths (96%) completed the study. Olanzapine treatment was associated with significant improvement in mean YMRS score (-19.0 +/- 9.2, p \u3c 0.001). Using predefined criteria for improvement of \u3e or = 30% decline in the YMRS and a CGI-S Mania score of \u3c or = 3 at endpoint, the overall response rate was 61%. Overall, olanzapine was well tolerated, and extrapyramidal symptom measures were not significantly different from baseline. Body weight increased significantly over the study (5.0 +/- 2.3 kg, p \u3c 0.001). CONCLUSIONS: Open-label olanzapine treatment was efficacious and well tolerated in the treatment of acute mania in youths with bipolar disorder. Future placebo-controlled, double-blind studies are warranted

Dynamical Systems Approach to Magnetised Cosmological Perturbations

Assuming a large-scale homogeneous magnetic field, we follow the covariant and gauge-invariant approach used by Tsagas and Barrow to describe the evolution of density and magnetic field inhomogeneities and curvature perturbations in a matter-radiation universe. We use a two parameter approximation scheme to linearize their exact non-linear general-relativistic equations for magneto-hydrodynamic evolution. Using a two-fluid approach we set up the governing equations as a fourth order autonomous dynamical system. Analysis of the equilibrium points for the radiation dominated era lead to solutions similar to the super-horizon modes found analytically by Tsagas and Maartens. We find that a study of the dynamical system in the dust-dominated era leads naturally to a magnetic critical length scale closely related to the Jeans Length. Depending on the size of wavelengths relative to this scale, these solutions show three distinct behaviours: large-scale stable growing modes, intermediate decaying modes, and small-scale damped oscillatory solutions.Comment: 15 pages RevTeX, 5 figures. Accepted for publication in Physical Review

Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex-vivo cytokine production – insights from the SATgenε study

Apolipoprotein E (APOE) genotype is believed to play an important role in cardiovascular risk. APOE4 carriers have been associated with higher blood lipid levels and a more pro-inflammatory state compared with APOE3/E3 individuals. Although dietary fat composition has been considered to modulate the inflammatory state in humans, very little is known about how APOE genotype can impact on this response. In a follow-up to the main SATgene study, we aimed to explore the effects of APOE genotype, as well as, dietary fat manipulation on ex vivo cytokine production. Blood samples were collected from a subset of SATgene participants (n = 52/88), prospectively recruited according to APOE genotype (n = 26 E3/E3 and n = 26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45 g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24 h with either 0.05 or 1 lg/ml of bacterial lipopolysaccharide (LPS). Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-a and IL-10 production; TNF-a concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P < 0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P < 0.05). In conclusion, our study has revealed the amount and type of dietary fat can significantly modulate the production of TNF-a and IL-10 by ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects

TACI-Ig Neutralizes Molecules Critical for B Cell Development and Autoimmune Disease Impaired B Cell Maturation in Mice Lacking BLyS

AbstractBLyS and APRIL have similar but distinct biological roles, mediated through two known TNF receptor family members, TACI and BCMA. We show that mice treated with TACI-Ig and TACI-Ig transgenic mice have fewer transitional T2 and mature B cells and reduced levels of circulating immunoglobulin. TACI-Ig treatment inhibits both the production of collagen-specific Abs and the progression of disease in a mouse model of rheumatoid arthritis. In BLyS-deficient mice, B cell development is blocked at the transitional T1 stage such that virtually no mature B cells are present, while B-1 cell numbers are relatively normal. These findings further elucidate the roles of BLyS and APRIL in modulating B cell development and suggest that BLyS is required for the development of most but not all mature B cell populations found in the periphery

Constraints on Non-Newtonian Gravity from Recent Casimir Force Measurements

Corrections to Newton's gravitational law inspired by extra dimensional physics and by the exchange of light and massless elementary particles between the atoms of two macrobodies are considered. These corrections can be described by the potentials of Yukawa-type and by the power-type potentials with different powers. The strongest up to date constraints on the corrections to Newton's gravitational law are reviewed following from the E\"{o}tvos- and Cavendish-type experiments and from the measurements of the Casimir and van der Waals force. We show that the recent measurements of the Casimir force gave the possibility to strengthen the previously known constraints on the constants of hypothetical interactions up to several thousand times in a wide interaction range. Further strengthening is expected in near future that makes Casimir force measurements a prospective test for the predictions of fundamental physical theories.Comment: 20 pages, crckbked.cls is used, to be published in: Proceedings of the 18th Course of the School on Cosmology and Gravitation: The Gravitational Constant. Generalized Gravitational Theories and Experiments (30 April- 10 May 2003, Erice). Ed. by G. T. Gillies, V. N. Melnikov and V. de Sabbata, 20pp. (Kluwer, in print, 2003