Relativistic nuclear structure effects in quasielastic neutrino scattering

Charged-current cross sections are calculated for quasielastic neutrino and antineutrino scattering using a relativistic meson-nucleon model. We examine how nuclear-structure effects, such as relativistic random-phase-approximation (RPA) corrections and momentum-dependent nucleon self-energies, influence the extraction of the axial form factor of the nucleon. RPA corrections are important only at low-momentum transfers. In contrast, the momentum dependence of the relativistic self-energies changes appreciably the value of the axial-mass parameter, $M_A$, extracted from dipole fits to the axial form factor. Using Brookhaven's experimental neutrino spectrum we estimate the sensitivity of M$_A$ to various relativistic nuclear-structure effects.Comment: 26 pages, revtex, 6 postscript figures (available upon request

Establishing a hepatitis C continuum of care among HIV/hepatitis C virus-coinfected individuals in EuroSIDA

Objectives The aim of the study was to establish a methodology for evaluating the hepatitis C continuum of care in HIV/hepatitis C virus (HCV)-coinfected individuals and to characterize the continuum in Europe on 1 January 2015, prior to widespread access to direct-acting antiviral (DAA) therapy. Methods Stages included in the continuum were as follows: anti-HCV antibody positive, HCV RNA tested, currently HCV RNA positive, ever HCV RNA positive, ever received HCV treatment, completed HCV treatment, follow-up HCV RNA test, and cure. Sustained virological response (SVR) could only be assessed for those with a follow-up HCV RNA test and was defined as a negative HCV RNA result measured > 12 or 24 weeks after stopping treatment. Results Numbers and percentages for the stages of the HCV continuum of care were as follows: anti-HCV positive (n = 5173), HCV RNA tested (4207 of 5173; 81.3%), currently HCV RNA positive (3179 of 5173; 61.5%), ever HCV RNA positive (n = 3876), initiated HCV treatment (1693 of 3876; 43.7%), completed HCV treatment (1598 of 3876; 41.2%), follow-up HCV RNA test to allow SVR assessment (1195 of 3876; 30.8%), and cure (629 of 3876; 16.2%). The proportion that achieved SVR was 52.6% (629 of 1195). There were significant differences between regions at each stage of the continuum (P <0.0001). Conclusions In the proposed HCV continuum of care for HIV/HCV-coinfected individuals, we found major gaps at all stages, with almost 20% of anti-HCV-positive individuals having no documented HCV RNA test and a low proportion achieving SVR, in the pre-DAA era.Peer reviewe

P763 Asymptomatic severe organic mitral regurgitation: Does the anatomic substrate affect the functional response to supine ergometry?

Abstract Asymptomatic severe mitral regurgitation (MR) remains a grey zone in decision making for intervention. The predictive role of left ventricular (LV) functional reserve remains uncertain and the potential role of the anatomical substrate has not been elucidated. Aim of the study was to compare the LV function and hemodynamic changes during supine ergometry (Ex) in asymptomatic severe MR between myxomatous (Myx) and degenerative (Deg) substrate. Methods 32 patients with Deg (male M/female F = 15/17) and 19 with MyxS (M/F = 7/12) were studied at rest (R) and Ex. We estimated heart rate (HR), rate-pressure product (HRxBP), LV endsystolic (LVESV)- enddiastolic volume (LVEDV), ejection fraction (EF), LV longitudinal strain (GLS), transmitral E wave (E), ratio E/e, peak tricuspid gradient (TrPG). To adjust for a potential volume effect on GLS, GLS was normalized to volumes and respective ratios were considered (GLS/LVESV, GLS/LVEDV). Parameters were measured at R and Ex and % changes were calculated : %d (Ex-R). Results Myx and Deg had similar chronotropic reserve and HR-BP. Myx were younger, and during Ex they had a greater LVEDV, a greater EF. a smaller E/e, and a smaller TrPG compared with Deg. Myx group, despite having a better GLS both at R and Ex, revealed a smaller % GLS improvement from R to Ex (15% vs 32%). The normalized GLS/LVESV and GLS/LVEDV were similar at R between Myx and Deg, but they showed a smaller improvement during Ex in Myx. (table-results) Conclusion Despite similar severity of MR, asymptomatic patients with MyxS revealed a different dynamic profile during Ex compared with Deg. The underlying MV substrate in organic MR might be related with a different LV adaptation to volume loading combined with subsequent uneven stress induced hemodynamic response. The disparities found might have implications both in the nature history of MR as well as in the decision making for intervention. RESULTS Parameter DegS MyxS p Age(years) 65 ± 11 44 ± 12 &amp;lt;0. 001 LVEDV Ex (ml) 85 + 32 117 ± 41 =0. 007 EF Ex(%) 65 + 7 69 ± 8 =0. 05 GLS R(%) -17.6 ± 6.8 -22.2 ± 4.3 =0. 04 GLS Ex(%) -22 ± 4 -25.0 ± 5.7 =0. 05 % d (Ex-R) LV strain/endsystolic volume 0.84 ± 0.4 -0.54 ± 0.5 =0. 05 E/e" Ex 16.7 ± 8.8 9.7 ± 2.2 =0. 004 TrPG Ex(mmHg) 59 ± 11 44 ± 11 =0. 0001 </jats:sec

Direct comparison of adenosine- versus exercise echo-derived distal left anterior descending artery velocity reserve

Abstract Introduction Distal left anterior descending (LAD) velocity reserve (CVR) estimated by vasodilators has been introduced in stress echocardiography as both diagnostic and prognostic parameter. Exercise echocardiography in the form of supine ergometry (Erg) is currently extensively used and provides an alternative means to evaluate CVR. Aim Aim of the study was to assess the relationship between the CVR estimated by Erg and the respective one by adenosine (Ad) immediately after Erg recovery. Methods Among 73 patients who underwent Erg and were initially screened, 59 (80.8%, age 63±12 years, 45 male, 14 female) with an efficient detection of LAD flow during Erg were studied (19 interrogated for coronary artery disease-CAD, 16 for heart failure with preserved ejection fraction-HFpEF, 7 for asymptomatic aortic stenosis-AS, 17 for mitral regurgitation-MR). Distal LAD velocity was measured at rest and every 2 min during Erg, provided that a clear envelope was feasible. Time elapsed for the detection of peak velocity and the respective achieved heart rate (Peak V-HR) were measured. CVR-Ad was estimated blindly by a different operator 30 minutes after Erg recovery. Absolute (dCVR) and % difference (%dCVR) between CVR-Erg and CVR-Ad were calculated. Results In 62.7% of cases the maximum CVR-Erg was detected earlier than 3 min during Erg. The respective Peak-V-HR was 81±11% of the maximum HR achieved during Erg. CVR-Erg was lower than CVR-Ad (2.17±0.61 vs 2.95±0.60, p=0.0001). The underlying substrate did not affect the difference dCVR (CAD: 0.81±0.70, HFpEF: 0.84±0.72, AS: 0.86±0.60, MR: 0.62±0.65, p=0.76). dCVR and %dCVR were inversely related with the CVR-Erg (r=−0.63, p=0.0001, r=−0.69, p=0.0001 respectively). A greater than 1.7 CVR-Erg had a 100% predictive accuracy for CVR-Ad greater than 2.0. CVR-Ad was predicted by the CFR-Erg using the following linear regression: CVR-Ad = 0.258 x CVR − Erg + 2.290 Conclusion CVR-Erg evaluation is feasible in the majority of patients undergoing Erg for contemporary guidelines indications, even at a relatively low workload, and may be used as a surrogate for CVR-Ad for either diagnostic or prognostic purposes. The observed metric discrepancies may be explained by the different coronary artery/microvasculature dynamics applied by exercise and vasodilators. Funding Acknowledgement Type of funding sources: None. LAD velocity at baselineLAD velocity at peak exercise </jats:sec

Polymorphisms of uridine glucuronosyltransferase gene and irinotecan toxicity: Low dose does not protect from toxicity

Uridine glucuronosyltransferase (UGT) gene polymorphisms have been linked to irinotecan toxicity. Our purpose was to study the association between UGT1A1*28, UGT1A7*2, and UGT1A7*3 polymorphisms and irinotecan toxicity in Greek patients receiving low-dose weekly irinotecan. Blood samples were collected for 46 patients. DNA was extracted and UGT1A1 promoter and UGT1A7 exon 1 genotyping was carried out. Laboratory tests and physical examination were performed on regular basis for the assessment of toxicity. UGT1A1*28 was significantly correlated with both haematologic and non-haematologic toxicity. Moreover, patients carrying UGT1A7 polymorphisms had significant incidence of toxicity. To conclude, UGT polymorphisms play a role in the toxicity of irinotecan, even if the drug is administered in low doses. The genotyping test may be a useful tool for the management of patients who are going to receive irinotecan. © the authors; licensee ecancermedicalscience

Gut microbiome-gut dysbiosis-arterial hypertension: New horizons

Arterial hypertension is a progressive cardiovascular syndrome arising from complex and interrelated etiologies. The human microbiome refers to the community of microorganisms that live in or on the human body. They influence human physiology by interfering in several processes such as providing nutrients and vitamins in Phase I and Phase II drug metabolism. The human gut microbiota is represented mainly by Firmicutes and Bacteroidetes and to a lesser degree by Actinobacteria and Proteobacteria, with each individual harbouring at least 160 such species. Gut microbiota contributes to blood pressure homeostasis and the pathogenesis of arterial hypertension through production, modification, and degradation of a variety of microbial-derived bioactive metabolites. Animal studies and to a lesser degree human research has unmasked relative mechanisms, mainly through the effect of certain microbiome metabolites and their receptors, outlining this relationship. Interventions to utilize these pathways, with probiotics, prebiotics, antibiotics and fecal microbiome transplantation have shown promising results. Personalized microbiome-based disease prediction and treatment responsiveness seem futuristic. Undoubtedly, a long way of experimental and clinical research should be pursued to elucidate this novel, intriguing and very promising horizon. © Bentham Science Publishers

P6314Left- versus Bi-Ventricular Assist Device-mediated anti-HLA alloantibody induction in bridge-to-transplantation patients

Abstract Background Presence of anti-Human Leukocyte Antigen (anti-HLA) alloantibodies (allosensitization) in a heart transplantation candidate impedes the chance of finding a compatible transplant. Left Ventricular Assist Devices (LVADs) have been shown to induce allosensitization. Purpose The purpose of this study is to characterize anti-HLA allosensitization in adult patients receiving left (LVAD) versus biventricular- (BiVAD) assist devices as bridge to transplantation (BTT). Methods This study retrospectively assessed anti-HLA antibody induction in all adult patients who have received either LVAD or BiVAD as BTT at our institution. Anti-HLA alloantibody screening was performed before, and at multiple time-points after VAD implantation. Anti-HLA antibody detection was performed with a cytotoxic panel-reactive antibody (PRA) method until 2003, enzyme-linked immunoassay (ELISA) method from 2003 to 2005 and SAB assays on the Luminex platform from 2005 to 2017. Sensitization was defined either as PRA &gt;10%, or as peak anti-HLA antibody mean fluorescence intensity (MFI) values of more than 1000. Baseline characteristics and sensitization in the two patient groups were evaluated using descriptive statistics. Results Between 2003 and 2018, 154 patients were placed on VAD support at our institution as BTT. Sensitization data were available for 130 patients. Fifty five (36.6%) patients were supported with an LVAD (median age, 48 years, 26% female) and 95 (63.4%) with a BiVAD (median age, 45 years, 28% female). Twenty-five (45.4%) of the LVAD and 49 (51.2%) of the BiVAD patients were eventually transplanted (p=0.47) with an average time to transplantation 588 and 562 days respectively. Fifteen (27.2%) LVAD and 35 (36.8%) BiVAD patients died before transplantation (p=0.23) with an average time on VAD support before death 269 and 302 days respectively. Evidence of sensitization pre-VAD was found in 17.1% of the LVAD and 12.5% of the BiVAD patients (p=0.53); these percentages rose to 40.0% (p=0.001) and 43.7% (p=0.0001) respectively at 2 to 12 months post-VAD implantation. However, the post-VAD allosensitization status was not statistically different between the LVAD and the BiVAD group. Among the 25 LVAD patients who were transplanted 7 (30.4%) were sensitized immediately before transplantation, compared to 22 (46.8%) out of 49 BiVAD patients (p=0.16). Conclusion Both LVADs and BiVADs are a factor of de novo anti-HLA antibody development in adult patients after implantation. Sensitization pattern does not seem to differ between LVAD and BiVAD patients. Additionally, patients supported by LVAD or BiVAD have similar chances of finding a suitable donor heart. </jats:sec

Data on eNOS T786 and G894T polymorphisms and peripheral blood eNOS mRNA levels in Sickle Cell Disease

In this article, we present data on endothelial Nitric Oxide Synthase (eNOS) gene T786C and G894T polymorphisms in Greek steady-state Sickle Cell Disease patients in comparison to healthy controls. Moreover, eNOS mRNA levels were determined in peripheral blood samples from 18 patients and 9 controls. This article complements our recently published article named “Prognostic value of eNOS T786C and G894T polymorphisms in Sickle Cell Disease” (I. Armenis, V. Kalotychou, R. Tzanetea, Z. Kontogeorgiou, D. Anastasopoulou, M. Mantzourani, M. Samarkos, K. Pantos, K. Konstantopoulos, I. Rombos, 2016) [1]. © 2016 The Author

Prognostic value of T786C and G894T eNOS polymorphisms in sickle cell disease

Endothelial Nitric Oxide Synthase (eNOS) is crucial for vascular homeostasis. Polymorphisms T786C and G894T affect eNOS regulation and have been related to various diseases. Sickle Cell Disease (SCD), a clinically diverse chronic hemolytic anemia, implies impaired nitric oxide bioavailability. Our aim was to determine eNOS genotype for T786C and G894T polymorphisms in Greek patients with SCD and to elucidate its consequences and effects if any on clinical phenotype. Seventy nine steady state cases, mostly compound heterozygous for Sickle Cell anemia/beta thalassemia and 48 controls were measured. Peripheral blood DNA was extracted and genotyped with PCR-RFLPs and Sanger sequencing. Total RNA was extracted from 18 patients and 9 controls and eNOS mRNA levels were determined by real-time PCR. Genotypes, allele distribution and eNOS mRNA levels did not differ between patients and controls, or among patients with different beta globin gene mutations. The 786CC genotype was more common in S/S and β0/S patients with retinopathy. Moreover, 894TT S/S and β0/S patients tended to have a higher hematocrit than 894GG and GT ones. However, the T786C eNOS genotype does not seem to affect peripheral blood cell-derived eNOS mRNA levels, at least in steady state conditions. This work is the first one describing the effects of eNOS polymorphisms on different forms of SCD, the first enrolling SCD patients of Caucasian origin and the first determining eNOS mRNA levels in peripheral blood from steady-state SCD patients. © 2016 Elsevier Inc

IkB kinase a Is required for development and progression of KRAS-mutant lung adenocarcinoma.

Although oncogenic activation of NFkB has been identified in various tumors, the NFkB–activating kinases (inhibitor of NFkB kinases, IKK) responsible for this are elusive. In this study, we determined the role of IKKa and IKKb in KRAS-mutant lung adenocarcinomas induced by the carcinogen urethane and by respiratory epithelial expression of oncogenic KRASG12D. Using NFkB reporter mice and conditional deletions of IKKa and IKKb, we identified two distinct early and late activation phases of NFkB during chemical and genetic lung adenocarcinoma development, which were characterized by nuclear translocation of RelB, IkBb, and IKKa in tumor-initiated cells. IKKa was a cardinal tumor promoter in chemical and genetic KRAS-mutant lung adenocarcinoma, and respiratory epithelial IKKa-deficient mice were markedly protected from the disease. IKKa specifically cooperated with mutant KRAS for tumor induction in a cell-autonomous fashion, providing mutant cells with a survival advantage in vitro and in vivo. IKKa was highly expressed in human lung adenocarcinoma, and a heat shock protein 90 inhibitor that blocks IKK function delivered superior effects against KRAS-mutant lung adenocarcinoma compared with a specific IKKb inhibitor. These results demonstrate an actionable requirement for IKKa in KRAS-mutant lung adenocarcinoma, marking the kinase as a therapeutic target against this disease. Significance: These findings report a novel requirement for IKKa in mutant KRAS lung tumor formation, with potential therapeutic applications