Associations of body composition measures and C2, a marker for small artery elasticity: The MESA.

ObjectiveLower C2, a continuous blood pressure waveform characteristic asserted to represent small artery elasticity, predicts future cardiovascular disease events. It is hypothesized that the paradoxical positive association between body mass index (BMI) and C2 may reflect muscle instead of excess fat.MethodsIn a multi-ethnic, community-living cohort of 1,960 participants, computed tomography scans of the abdomen were used to measure visceral adipose tissue (VAT) and total abdominal muscle tissue (TAMT), and applanation tonometry of the radial arteries was used to assess C2. The period cross-sectional associations between BMI, TAMT, and VAT with C2 were ascertained.ResultsThe mean age was 62 ± 9 years and 51% were male. After adjustments for age, gender, ethnicity, pack years smoking cigarettes, diabetes, hypertension, and total and HDL cholesterol, higher BMI (standardized beta = 0.09, P-value < 0.01) and more TAMT (standardized beta = 0.12, P-value < 0.01) were significantly associated with higher C2. In contrast, more VAT (standardized beta = -0.09, P-value < 0.01) was associated with lower C2.ConclusionsIn multivariable analysis, VAT, in contrast to TAMT and BMI, was associated with less compliant small arteries. Visceral fat may be a better marker for detrimental excess body fat than BMI

Transferring the quantum state of electrons across a Fermi sea with Coulomb interaction

The Coulomb interaction generally limits the quantum propagation of electrons. However, it can also provide a mechanism to transfer their quantum state over larger distances. Here, we demonstrate such a form of teleportation, across a metallic island within which the electrons are trapped much longer than their quantum lifetime. This effect originates from the low temperature freezing of the island's charge $Q$ which, in the presence of a single connected electronic channel, enforces a one-to-one correspondence between incoming and outgoing electrons. Such high-fidelity quantum state imprinting is established between well-separated injection and emission locations, through two-path interferences in the integer quantum Hall regime. The added electron quantum phase of $2\pi Q/e$ can allow for strong and decoherence-free entanglement of propagating electrons, and notably of flying qubits

Severity of cardiovascular disease outcomes among patients with HIV is related to markers of inflammation and coagulation

BACKGROUND: In the general population, raised levels of inflammatory markers are stronger predictors of fatal than nonfatal cardiovascular disease (CVD) events. People with HIV have elevated levels of interleukin-6 (IL-6), high-sensitivity C-reactive protein (hsCRP), and D-dimer; HIV-induced activation of inflammatory and coagulation pathways may be responsible for their greater risk of CVD. Whether the enhanced inflammation and coagulation associated with HIV is associated with more fatal CVD events has not been investigated. METHODS AND RESULTS: Biomarkers were measured at baseline for 9764 patients with HIV and no history of CVD. Of these patients, we focus on the 288 that experienced either a fatal (n=74) or nonfatal (n=214) CVD event over a median of 5 years. Odds ratios (ORs) (fatal versus nonfatal CVD) (95% confidence intervals [CIs]) associated with a doubling of IL-6, D-dimer, hsCRP, and a 1-unit increase in an IL-6 and D-dimer score, measured a median of 2.6 years before the event, were 1.39 (1.07 to 1.79), 1.40 (1.10 to 1.78), 1.09 (0.93 to 1.28), and 1.51 (1.15 to 1.97), respectively. Of the 214 patients with nonfatal CVD, 23 died during follow-up. Hazard ratios (95% CI) for all-cause mortality were 1.72 (1.28 to 2.31), 1.73 (1.27 to 2.36), 1.44 (1.15 to 1.80), and 1.88 (1.39 to 2.55), respectively, for IL-6, D-dimer, hsCRP, and the IL-6 and D-dimer score. CONCLUSIONS: Higher IL-6 and D-dimer levels reflecting enhanced inflammation and coagulation associated with HIV are associated with a greater risk of fatal CVD and a greater risk of death after a nonfatal CVD event. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrial.gov Unique identifier: SMART: NCT00027352, ESPRIT: NCT00004978, SILCAAT: NCT00013611

Effects of High Flavanol Dark Chocolate on Cardiovascular Function and Platelet Aggregation.

Regular consumption of chocolate and cocoa products has been linked to reduced cardiovascular mortality. This study compared the effects of high flavanol dark chocolate (HFDC; 1064mg flavanols/day for 6 weeks) and low flavanol dark chocolate (LFDC; 88mg flavanols/day for 6 weeks) on blood pressure, heart rate, vascular function and platelet aggregation in men with pre-hypertension or mild hypertension. Vascular function was assessed by pulse wave analysis using radial artery applanation tonometry in combination with inhaled salbutamol (0.4 mg) to assess changes due to endothelium-dependent vasodilatation. HFDC did not significantly reduce blood pressure compared to baseline or LFDC. Heart rate was increased by LFDC compared to baseline, but not by HFDC. Vascular responses to salbutamol tended to be greater after HFDC. Platelet aggregation induced by collagen or the thromboxane analogue U46619 was unchanged after LFDC or HFDC, whereas both chocolates reduced responses to ADP and the thrombin receptor activator peptide, SFLLRNamide (TRAP6), relative to baseline. Pre-incubation of platelets with theobromine also attenuated platelet aggregation induced by ADP or TRAP6. We conclude that consumption of HFDC confers modest improvements in cardiovascular function. Platelet aggregation is modulated by a flavanol-independent mechanism that is likely due to theobromine.This study was supported by a grant (to R. Corder) from Barry Callebaut Belgium N

Constitutive Activation of the Thyroid-Stimulating Hormone Receptor (TSHR) by Mutating Ile691 in the Cytoplasmic Tail Segment

/inositol phosphate (IP) pathways, which stimulate thyroid hormone production and thyroid proliferation./IP signaling pathway./IP cascade

Markers of Inflammation, Coagulation, and Renal Function Are Elevated in Adults with HIV Infection

(See the article by Kalayjian et al, on pages 1796-1805, and the editorial commentary by Dubé and Sattler, on pages 1783-1785.) Background. Human immunodeficiency virus (HIV) replication and immune activation may increase inflammation and coagulation biomarkers. Limited data exist comparing such biomarkers in persons with and without HIV infection. Methods. For persons 45-76 years of age, levels of high-sensitivity C-reactive protein (hsCRP), interleukin (IL)-6, D-dimer, and cystatin C were compared in 494 HIV-infected individuals in the Strategies for Management of Anti-Retroviral Therapy (SMART) study and 5386 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) study. For persons 33-44 years of age, hsCRP and IL-6 levels were compared in 287 participants in the SMART study and 3231 participants in the Coronary Artery Development in Young Adults (CARDIA) study. Results. hsCRP and IL-6 levels were 55% (P<.001) and 62% (P<.001) higher among HIV-infected participants than among CARDIA study participants. Compared with levels noted in MESA study participants, hsCRP, IL-6, D-dimer, and cystatin C levels were 50%, 152%, 94%, and 27% higher, respectively (P<.001 , for each), among HIV-infected participants. HIV-infected participants receiving antiretroviral therapy who had HIV RNA levels ≤400 copies/mL had levels higher (by 21% to 60%) (P<.001) than those in the general population, for all biomarkers. Conclusions. hsCRP, IL-6, D-dimer, and cystatin C levels are elevated in persons with HIV infection and remain so even after HIV RNA levels are suppressed with antiretroviral therapy. Additional research is needed on the pathophysiology of HIV-induced activation of inflammatory and coagulation pathways, to guide potential intervention

Early Antiretroviral Therapy at High CD4 Counts Does Not Improve Arterial Elasticity: A Substudy of the Strategic Timing of AntiRetroviral Treatment (START) Trial

BACKGROUND: Both human immunodeficiency virus (HIV) infection and antiretroviral therapy (ART) may increase cardiovascular disease (CVD) risk. Vascular function assessments can be used to study CVD pathogenesis. We compared the effect of immediate versus deferred ART initiation at CD4 counts >500 cells/mm(3) on small arterial elasticity (SAE) and large artery elasticity (LAE). METHODS: Radial artery blood pressure waveforms were recorded noninvasively. Small arterial elasticity and LAE were derived from analysis of the diastolic pulse waveform. Randomized treatment groups were compared with linear models at each visit and longitudinal mixed models. RESULTS: Study visits involved 332 participants in 8 countries: mean (standard deviation [SD]) age 35 (10), 70% male, 66% nonwhite, 30% smokers, and median CD4 count 625 cells/mm(3) and 10-year Framingham risk score for CVD 1.7%. Mean (SD) SAE and LAE values at baseline were 7.3 (2.9) mL/mmHg × 100 and 16.6 (4.1) mL/mmHg × 10, respectively. Median time on ART was 47 and 12 months in the immediate and deferred ART groups, respectively. The treatment groups did not demonstrate significant within-person changes in SAE or LAE during the follow-up period, and there was no difference in mean change from baseline between treatment groups. The lack of significant differences persisted after adjustment, when restricted to early or late changes, after censoring participants in deferred group who started ART, and among subgroups defined by CVD and HIV risk factors. CONCLUSIONS: Among a diverse global population of HIV-positive persons with high CD4 counts, these randomized data suggest that ART treatment does not have a substantial influence on vascular function among younger HIV-positive individuals with preserved immunity

Triad3a induces the degradation of early necrosome to limit RipK1-dependent cytokine production and necroptosis.

Understanding the molecular signaling in programmed cell death is vital to a practical understanding of inflammation and immune cell function. Here we identify a previously unrecognized mechanism that functions to downregulate the necrosome, a central signaling complex involved in inflammation and necroptosis. We show that RipK1 associates with RipK3 in an early necrosome, independent of RipK3 phosphorylation and MLKL-induced necroptotic death. We find that formation of the early necrosome activates K48-ubiquitin-dependent proteasomal degradation of RipK1, Caspase-8, and other necrosomal proteins. Our results reveal that the E3-ubiquitin ligase Triad3a promotes this negative feedback loop independently of typical RipK1 ubiquitin editing enzymes, cIAPs, A20, or CYLD. Finally, we show that Triad3a-dependent necrosomal degradation limits necroptosis and production of inflammatory cytokines. These results reveal a new mechanism of shutting off necrosome signaling and may pave the way to new strategies for therapeutic manipulation of inflammatory responses