1,072 research outputs found
Microvascular function is selectively impaired in patients with hypertrophic cardiomyopathy and sarcomere myofilament gene mutations.
ObjectivesThe purpose of this study was to assess myocardial blood flow (MBF) using positron emission tomography in patients with hypertrophic cardiomyopathy (HCM) according to genetic status.BackgroundCoronary microvascular dysfunction is an important feature of HCM, associated with ventricular remodeling and heart failure. We recently demonstrated the increased prevalence of systolic dysfunction in patients with HCM with sarcomere myofilament gene mutations and postulated an association between genetic status and coronary microvascular dysfunction.MethodsMaximum MBF (intravenous dipyridamole, 0.56 mg/kg; Dip-MBF) was measured using 13N-labeled ammonia in 61 patients with HCM (age 38 ± 14 years), genotyped by automatic DNA sequencing of 8 myofilament-encoding genes (myosin-binding protein C, beta-myosin heavy chain, regulatory and essential light chains, troponin T, troponin I, troponin C, alpha-tropomyosin, and alpha-actin). In 35 patients, cardiac magnetic resonance imaging was performed.ResultsFifty-three mutations were identified in 42 of the 61 patients (genotype positive; 69%). Despite similar clinical profiles, genotype-positive patients with HCM showed substantially lower Dip-MBF compared with that of genotype-negative patients (1.7 ± 0.6 ml/min/g vs. 2.4 ± 1.2 ml/min/g; p < 0.02). A Dip-MBF <1.5 ml/min/g had 81% positive predictive value for genotype-positive status and implied a 3.5-fold independent increase in likelihood of carrying myofilament gene mutations (hazard ratio: 3.52; 95% confidence interval: 1.05 to 11.7; p = 0.04). At cardiac magnetic resonance imaging, the prevalence of late gadolinium enhancement was greater in genotype-positive patients (22 of 23 [96%] compared with 8 of 12 [67%] genotype-negative patients; p = 0.038).ConclusionsPatients with HCM with sarcomere myofilament mutations are characterized by more severe impairment of microvascular function and increased prevalence of myocardial fibrosis, compared with genotype-negative individuals. These findings suggest a direct link between sarcomere gene mutations and adverse remodeling of the microcirculation in HCM, accounting for the increased long-term prevalence of ventricular dysfunction and heart failure in genotype-positive patients
Multifield Dynamics in Higgs-otic Inflation
In Higgs-otic inflation a complex neutral scalar combination of the and
MSSM Higgs fields plays the role of inflaton in a chaotic fashion. The
potential is protected from large trans-Planckian corrections at large inflaton
if the system is embedded in string theory so that the Higgs fields parametrize
a D-brane position. The inflaton potential is then given by a DBI+CS D-brane
action yielding an approximate linear behaviour at large field. The inflaton
scalar potential is a 2-field model with specific non-canonical kinetic terms.
Previous computations of the cosmological parameters (i.e. scalar and tensor
perturbations) did not take into account the full 2-field character of the
model, ignoring in particular the presence of isocurvature perturbations and
their coupling to the adiabatic modes. It is well known that for generic
2-field potentials such effects may significantly alter the observational
signatures of a given model. We perform a full analysis of adiabatic and
isocurvature perturbations in the Higgs-otic 2-field model. We show that the
predictivity of the model is increased compared to the adiabatic approximation.
Isocurvature perturbations moderately feed back into adiabatic fluctuations.
However, the isocurvature component is exponentially damped by the end of
inflation. The tensor to scalar ratio varies in a region ,
consistent with combined Planck/BICEP results.Comment: 35 pages, 11 figure
Naturally derived phenethyl isothiocyanate modulates induction of oxidative stress via Its N-acetylated cysteine conjugated form in malignant melanoma
This is the final version. Available on open access from MDPI via the DOI in this record.âŻData Availability Statement: Data are contained within the article.Phenethyl isothiocyanate (PEITC) is a secondary metabolic product yielded upon the hydrolysis of gluconasturtiin and it is highly accumulated in the flowers of watercress. The aim of the current study was to assess the role of a naturally derived PEITC-enriched extract in the induction of oxidative stress and to evaluate its anti-melanoma potency through the regulation of its metabolism with the concurrent production of the N-acetyl cysteine conjugated by-product. For this purpose, an in vitro melanoma model was utilized consisting of human primary (A375) cells as well as metastatic (COLO-679) malignant melanoma cells together with non-tumorigenic immortalized keratinocytes (HaCaT). Cytotoxicity was assessed via the Alamar Blue assay whereas the antioxidant/prooxidant activity of PEITC was determined via spectrophotometric assays. Finally, kinetic characterization of the end-product of PEITC metabolism was monitored via UPLC coupled to a tandem mass spectrometry (MS/MS). Our results indicate that although PhEF showed very minor antioxidant activity in a cell-free system, in a cell-based system, it can modulate the activity of key enzyme(s) involved in cellular antioxidant defense mechanism(s). In addition, we have shown that PhEF induces lipid and protein oxidation in a concentration-dependent manner, while its cytotoxicity is not only dependent on PEITC itself but also on its N-acetylated cysteine conjugated form.Hellenic Foundation for Research and Innovation (H.F.R.I.)Cyprus Institute of Neurology and Genetics (Telethon Cyprus
Dynamic SU(2) Structure from Seven-branes
We obtain a family of supersymmetric solutions of type IIB supergravity with
dynamic SU(2) structure, which describe the local geometry near a stack of four
D7-branes and one O7-plane wrapping a rigid four-cycle. The deformation to a
generalized complex geometry is interpreted as a consequence of nonperturbative
effects in the seven-brane gauge theory. We formulate the problem for
seven-branes wrapping the base of an appropriate del Pezzo cone, and in the
near-stack limit in which the four-cycle is flat, we obtain an exact solution
in closed form. Our solutions serve to characterize the local geometry of
nonperturbatively-stabilized flux compactifications.Comment: 49 pages, 2 figures; v2: minor corrections, references adde
Un-oriented Quiver Theories for Majorana Neutrons
In the context of un-oriented open string theories, we identify quivers
whereby a Majorana mass for the neutron is indirectly generated by exotic
instantons. We discuss two classes of (Susy) Standard Model like quivers,
depending on the embedding of SU(2)_W in the Chan-Paton group. In both cases,
the main mechanism involves a vector-like pair mixing through a
non-perturbative mass term. We also discuss possible relations between the
phenomenology of Neutron-Antineutron oscillations and LHC physics in these
models. In particular, a vector-like pair of color-triplet scalars or
color-triplet fermions could be directly detected at LHC, compatibly with
n-\bar{n} limits. Finally we briefly comment on Pati-Salam extensions of our
models.Comment: More comments on phenomenology and fluxes, Re-discussion of
SM-quivers compatible with n-cycles conditions Version accepted by JHE
Oral chondroitin sulfate and prebiotics for the treatment of canine Inflammatory Bowel Disease: a randomized, controlled clinical trial
BACKGROUND
Canine inflammatory bowel disease (IBD) is a chronic enteropathy of unknown etiology, although microbiome dysbiosis, genetic susceptibility, and dietary and/or environmental factors are hypothesized to be involved in its pathogenesis. Since some of the current therapies are associated with severe side effects, novel therapeutic modalities are needed. A new oral supplement for long-term management of canine IBD containing chondroitin sulfate (CS) and prebiotics (resistant starch, ÎČ-glucans and mannaoligosaccharides) was developed to target intestinal inflammation and oxidative stress, and restore normobiosis, without exhibiting any side effects. This double-blinded, randomized, placebo-controlled trial in dogs with IBD aims to evaluate the effects of 180Â days administration of this supplement together with a hydrolyzed diet on clinical signs, intestinal histology, gut microbiota, and serum biomarkers of inflammation and oxidative stress.
RESULTS
Twenty-seven client-owned biopsy-confirmed IBD dogs were included in the study, switched to the same hydrolyzed diet and classified into one of two groups: supplement and placebo. Initially, there were no significant differences between groups (pâ>â0.05) for any of the studied parameters. Final data analysis (supplement: nâ=â9; placebo: nâ=â10) showed a significant decrease in canine IBD activity index (CIBDAI) score in both groups after treatment (pâ<â0.001). After treatment, a significant decrease (1.53-fold; pâ<â0.01) in histologic score was seen only in the supplement group. When groups were compared, the supplement group showed significantly higher serum cholesterol (pâ<â0.05) and paraoxonase-1 (PON1) levels after 60Â days of treatment (pâ<â0.01), and the placebo group showed significantly reduced serum total antioxidant capacity (TAC) levels after 120Â days (pâ<â0.05). No significant differences were found between groups at any time point for CIBDAI, WSAVA histologic score and fecal microbiota evaluated by PCR-restriction fragment length polymorphism (PCR-RFLP). No side effects were reported in any group.
CONCLUSIONS
The combined administration of the supplement with hydrolyzed diet over 180Â days was safe and induced improvements in selected serum biomarkers, possibly suggesting a reduction in disease activity. This study was likely underpowered, therefore larger studies are warranted in order to demonstrate a supplemental effect to dietary treatment of this supplement on intestinal histology and CIBDAI
Holographic Vitrification
We establish the existence of stable and metastable stationary black hole
bound states at finite temperature and chemical potentials in global and planar
four-dimensional asymptotically anti-de Sitter space. We determine a number of
features of their holographic duals and argue they represent structural
glasses. We map out their thermodynamic landscape in the probe approximation,
and show their relaxation dynamics exhibits logarithmic aging, with aging rates
determined by the distribution of barriers.Comment: 100 pages, 25 figure
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