tbuckley/cabot-search huggingface dataset:
P83correlation between glycaemic status and left ventricular diastolic function in type 2 Diabetes patients
Authors: M M Mohamed Eldeib
Journal: Cardiovascular Research (2018)

superoxide radicals.It is also known contingency effects of superoxide radical and NO in the implementation of oxidative stress.The aim of the study was to determine the level of NO production of platelets in patients with AH under the influence of EMR UHF. Materials and methods.The study included 106 men who were divided into 3 groups: Group 1 included 40 patients with hypertension at a mean age 32,566,1 years old, who worked under the influence of EMR UHF; Group 2 -40 patients with AH without prolonged exposure EMR UHF; Group 3 -26 apparently healthy men without the influence of EMR UHF (control group).EMR UHF dose for group 1 on average up to 17,151.7 6 7102,4 kW.The level of NO production was measured by platelet electron paramagnetic spectroscopy, the degree of oxidative damage to mitochondria was measured in terms of urinary excretion of 8hydroxy-2-deoksiguanozina (8-OhdG).Results: On the average in patients of Group 1 the level of NO in platelets was 2,2261,79 cu whereas in patients of Group 2 -0,5460,02 cu (P<0.05), and men of the control group 0,9560,16 cu.The level of urinary excretion of 8-OhdG in patients of the first group was also significantly higher than the average value of the group II patients and control group 3 (respectively 14,2268,68 mmol/ kg/day compared to 7,1265,08 mmol/kg/day, P<0.05 and 0,6360,15 mmol/kg/day, P<0.05.In patients of the first group was found the highest direct correlation between the level of the daily urinary excretion of 8-OhdG and the level of nitric oxide in platelets (r¼0,39; P<0.05).Conclusions: In patients with hypertension under the effect of EMR UHF the level of nitric oxide in platelets dramatically increased and correlated with urinary markers of oxidative DNA damage, indicating that the contingency of oxidative and nitrosyl stress in the genesis of the disease.
Gata4-Dependent Differentiation of c-Kit <sup>+</sup> –Derived Endothelial Cells Underlies Artefactual Cardiomyocyte Regeneration in the Heart
Authors: Bryan D. Maliken, Onur Kanisicak, Jason Karch, Hadi Khalil, Xing Fu, Justin G. Boyer, Vikram Prasad, Yi Zheng, Jeffery D. Molkentin
Journal: Circulation (2018)

Although c-Kit+ adult progenitor cells were initially reported to produce new cardiomyocytes in the heart, recent genetic evidence suggests that such events are exceedingly rare. However, to determine if these rare events represent true de novo cardiomyocyte formation, we deleted the necessary cardiogenic transcription factors Gata4 and Gata6 from c-Kit-expressing cardiac progenitor cells.Kit allele-dependent lineage tracing and fusion analysis were performed in mice following simultaneous Gata4 and Gata6 cell type-specific deletion to examine rates of putative de novo cardiomyocyte formation from c-Kit+ cells. Bone marrow transplantation experiments were used to define the contribution of Kit allele-derived hematopoietic cells versus Kit lineage-dependent cells endogenous to the heart in contributing to apparent de novo lineage-traced cardiomyocytes. A Tie2CreERT2 transgene was also used to examine the global impact of Gata4 deletion on the mature cardiac endothelial cell network, which was further evaluated with select angiogenesis assays.Deletion of Gata4 in Kit lineage-derived endothelial cells or in total endothelial cells using the Tie2CreERT2 transgene, but not from bone morrow cells, resulted in profound endothelial cell expansion, defective endothelial cell differentiation, leukocyte infiltration into the heart, and a dramatic increase in Kit allele-dependent lineage-traced cardiomyocytes. However, this increase in labeled cardiomyocytes was an artefact of greater leukocyte-cardiomyocyte cellular fusion because of defective endothelial cell differentiation in the absence of Gata4.Past identification of presumed de novo cardiomyocyte formation in the heart from c-Kit+ cells using Kit allele lineage tracing appears to be an artefact of labeled leukocyte fusion with cardiomyocytes. Deletion of Gata4 from c-Kit+ endothelial progenitor cells or adult endothelial cells negatively impacted angiogenesis and capillary network integrity.
Time to plateau as a predictor of survival in newly diagnosed multiple myeloma
Authors: Patrick W. Mellors, Moritz Binder, Francis K. Buadi, Martha Q. Lacy, Morie A. Gertz, Angela Dispenzieri, Suzanne R. Hayman, Prashant Kapoor, Wilson I. Gonsalves, Yi L. Hwa, Amie Fonder, Miriam Hobbs, Taxiarchis Kourelis, Rahma Warsame, Steven R. Zeldenrust, John A. Lust, Nelson Leung, Ronald S. Go, Robert A. Kyle, S. Vincent Rajkumar, Shaji K. Kumar
Journal: American Journal of Hematology (2018)

Response rates in newly diagnosed multiple myeloma have improved dramatically with the introduction of highly effective novel therapies. However, survival in patients achieving optimal responses to initial treatment can vary significantly, and new prognostic indicators are required to improve risk stratification. We investigated the relationship between time to plateau (TPlat ) and survival in 1099 newly diagnosed patients treated with novel agents at our institution from 2005 to 2015. TPlat was defined as time from initiation of first-line therapy to best response to first-line therapy. The median TPlat was 4.9 months (0.7-58.6) and plateau duration was 1.8 years (0.2-11.0). Patients who required > 120 days to achieve a plateau had longer modified overall survival (mOS) and progression free survival (mPFS) calculated from a landmark of best response (P < .001 for both comparisons). Statistically significant improvement in mOS was retained in subgroup analysis based on age and whether patients received upfront autologous hematopoietic stem cell transplantation (ASCT) (P < .001 for all comparisons). Our results suggest that patients who respond more gradually to initial therapy (TPlat > 120 days) experience longer survival compared to more rapid responders. Patients with a prolonged TPlat could represent an "ongoing responder" phenotype that portends a survival advantage independent of treatment with upfront ASCT, depth of response, and biologic markers such as ISS stage and cytogenetic risk.
Novel characterization of the gut microbiome in patients with NASH and longitudinal changes associated with histological improvement
Authors: R. Loomba, Y. Gindin, O. Podlaha, Z. Jiang, E. Lawitz, S. Caldwell, S. Djedjos, R. Xu, D. Gong, M. Subramanian, R. Myers, M. Charlton, Z. Goodman, A.M. Diehl
Journal: Journal of Hepatology (2018)
Acute Colonic Diverticulitis
Authors: Sophia M. Swanson, Lisa L. Strate
Journal: Annals of Internal Medicine (2018)

Acute colonic diverticulitis is a gastrointestinal condition frequently encountered by primary care practitioners, hospitalists, surgeons, and gastroenterologists. Clinical presentation ranges from mild abdominal pain to peritonitis with sepsis. It can often be diagnosed on the basis of clinical features alone, but imaging is necessary in more severe presentations to rule out such complications as abscess and perforation. Treatment depends on the severity of the presentation, presence of complications, and underlying comorbid conditions. Medical and surgical treatment algorithms are evolving. This article provides an evidence-based, clinically relevant overview of the epidemiology, diagnosis, and treatment of acute diverticulitis.
P280Myocardial resistance against proteotoxicity
Authors: M Luciani, L Troncone, F Del Monte
Journal: Cardiovascular Research (2018)

Introduction: -Protein quality is assured at a cellular level by a finely tuned biological machinery called unfolded protein response (UPR) devoted to recognize, unfold, and refold abnormally arranged proteins.A growing set of previously unrelated disorders has been associated to adverse effects deriving from the accumulation of non-functional aggregates of unfolded proteins named oligomers.Those can perturb the homeostasis, and ultimately the survival of the cell itself.As far as the heart is concerned, an elevated oligomer presence was detected within the myocardium of idiopathic dilated cardiomyopathy (iDCM) cases compared to matched controls.Purpose: -A defective UPR system in the myocardium of iDCM could represent a possible biological foundation leading to or a consequence of a toxic proteic buildup.Methods: -Lysates from left ventricle specimens of iDCM (n¼8), and matched control cases (n¼8) were employed for transcript and protein analysis in order to evaluate components of the UPR system.Both groups were subdivided into young and old subjects (n¼4 for each subgroup).Results: -Young and old subgroups mean ages for iDCM subjects were 30 and 58.8 respectively and 29.5 and 56.8 for controls.Men and women were equally represented in every subgroup.Significant differences (P <0.05) and diverse defects along the pathway were detected by comparing same age subjects.Young iDCM patients showed a significant increase in PERK as well as CHOP, Caspase-12 and the spliced form of XBP-1.Consistent with previous findings Proteasome 20S5b was found to be diminished.On the other hand, older iDCM cases expressed significantly lower levels of spliced XBP-1, ATF6 ratio and higher levels of ATF4 and eIF2a.In addition, significant differences with aging were appreciated throughout the pathway in control subjects in contrast with the iDCM cohort.Conclusion: -These findings shed light on the pivotal role of proteotoxcity overwhelming UPR control as an additional etiology of heart failure.The combined alteration of several target proteins of this pathway configures as a condition of misfolded peptides accumulation ultimately exhausting the cell survival capabilities.
Greetings from the editor
Authors: Josef S Smolen
Journal: Annals of the Rheumatic Diseases (2018)

The June issue of the Annals of the Rheumatic Diseases ( ARD ) that you are holding in your hands today constitutes an usual annual breaking point. While the ARD volume numbers relate to a full calendar year, January–December, the June issue of each volume marks the first issue for the subscription to ARD that participants of the Annual European League Against Rheumatism (EULAR) Congress receive every year in the Congress educational package and that lasts until May of the following year. Long ago, when EULAR and the BMJ Publishing Group agreed on the venture to elect ARD as ‘The EULAR Journal’, EULAR was faced by the fact that it did not have individual members (but rather national societies as official members) and, therefore, …
On treatment HCV-RNA evaluation in real-life: Still a role in the era of direct acting antiviral agents?
Authors: V.C. Di Maio, V. Cento, V. Micheli, C. Masetti, C.F. Magni, E. Teti, I. Lenci, S. Passerini, S. Francioso, M. Milana, A. Bertoli, M. Ciotti, M. Aragri, L. Sarmati, M. Schiavini, G. Gubertini, M. Andreoni, A. Mario, C.F. Perno, G. Rizzardini, F.C. Silberstein
Journal: Journal of Hepatology (2018)
Increased incidence of HBsAg seroclearance in HBeAg negative chronic hepatitis B patients discontinued Nuc therapy comparing to natural course-a propensity score matched study
Authors: W.-J. Jeng, H.-I. Yang, Y.-C. Chen, J. Liu, R.-N. Chien, I.-S. Sheen, C.-J. Chen, Y.-F. Liaw
Journal: Journal of Hepatology (2018)
Persistent variations in national asthma mortality, hospital admissions and prevalence by socioeconomic status and region in England
Authors: Ramyani P Gupta, Mome Mukherjee, Aziz Sheikh, David P Strachan
Journal: Thorax (2018)

Background The UK-wide National Review of Asthma Deaths sought to identify avoidable factors from the high numbers of deaths, but did not examine variation by socioeconomic status (SES) or region. Methods We used asthma deaths in England over the period 2002–2015 obtained from national deaths registers, summarised by quintiles of Index of Multiple Deprivation (IMD) and Government Office Region. Emergency asthma admissions were obtained from Hospital Episode Statistics for England 2001–2011. The prevalence of asthma was derived from the Health Survey for England 2010. Associations of mortality, admissions and prevalence with IMD quintile and region were estimated cross-sectionally using incidence rate ratios (IRRs) adjusted for age and sex and, where possible, smoking. Results Asthma mortality decreased among more deprived groups at younger ages. Among 5–44 year olds, those in the most deprived quintile, mortality was 19% lower than those in the least deprived quintile (IRR 0.81 (95% CI 0.69 to 0.96). In older adults, this pattern was reversed (45–74 years: IRR 1.37 (1.24–1.52), ≥75 years: IRR 1.30 (1.22–1.39)). In 5–44 year olds the inverse trend with asthma mortality contrasted with large positive associations for admissions (IRR 3.34 (3.30–3.38)) and prevalence of severe symptoms (IRR 2.38 (1.70–3.33)). Prevalence trends remained after adjustment for smoking. IRRs for asthma mortality, admissions and prevalence showed significant heterogeneity between English regions. Conclusions Despite asthma mortality, emergency admissions and prevalence decreasing over recent decades, England still experiences significant SES and regional variations. The previously undocumented inverse relation between deprivation and mortality in the young requires further investigation.
Prevalence and correlates of critical malnutrition (CMN) among gastrointestinal (GI) and non-GI participants in phase I/II (P1/2) clinical trials.
Authors: Rishi Jain, Elizabeth Handorf, Vipin Khare, Matthew Blau, Yana Chertock, Steven K. Clinton, Michael J. Hall
Journal: Journal of Clinical Oncology (2018)

770 Background: Patients (pts) with cancer, in particular GI malignancies, are vulnerable to CMN from both tumor-related digestive symptoms and treatment-related toxicity (TRT). CMN is associated with poor cancer outcomes, including reduced quality of life, poor treatment tolerance and decreased survival. P1/2 trial participants are not routinely screened for CMN or potentially associated psychological and physical activity impairments. Methods: Baseline assessments of nutrition (PG-SGA), distress (NCCN-DT), anxiety (HADS-A), depression (HADS-D), and sedentary lifestyle (SL, Godin-LTQ) were conducted in pts beginning a P1/2 trial. CMN was defined as a PG-SGA score of ≥9. Statistical significance was determined by Fisher’s exact test. A regression model was used to identify a composite predictor of CMN. Results: 100 pts (87% P1, 13% P2) were enrolled. Results of assessments are shown in Table 1. 39% of pts had CMN and 52% had a SL. CMN was more common in non-whites (p = 0.05) and those on P1 trials (p = 0.073). No differences were noted by age, gender, or prior lines of therapy. CMN was strongly associated with depression (p &lt; 0.001) and SL (p &lt; 0.001). 31 pts had GI malignancies [CRC (15), pancreas (8), and other (8)]. CMN was more prevalent in GI pts than non-GI (61% vs 29%, p = 0.004). When evaluating the predictive value of commonly used clinical indicators for CMN such as BMI ( &lt; 25), weight loss (WL) past 2 weeks, or WL past month, having 2/3 of these indicators was the optimal cut-point predictor of CMN (76% sensitivity, 85% specificity). TRT data collection is ongoing. Conclusions: CMN and SL are highly prevalent in P1/2 trial pts, particularly in those with GI cancers and minorities. CMN is strongly associated with depression and SL. A composite clinical indicator (BMI + WL) may be most useful in screening for CMN. Urgent nutritional interventions in these participants may be warranted in light of magnified mortality and toxicity risks. [Table: see text]
P520The metabolic modulator trimetazidine inhibits AF-induced atrial structural remodelling
Authors: D Opacic, A Weseler, P Schoenleitner, A Van Hunnik, M Kuiper, I Akomianakis, P Pasdois, C Antoniades, U Schotten, S Verheule
Journal: Cardiovascular Research (2018)

the number (DADinc¼ 4.7260.6#/min) and amplitude of DAD (DADampl¼2.760.4 mV) as well as the number of spontaneous APs in myocytes from the MI adjacent region, without affecting the overall global Ca2þ transient kinetics in both regions.Conclusion: Both in vitro and in vivo studies showed the peri-infarct region having a higher arrhythmogenic potential compared to the non-infarcted remote region.Hyperactive non-coupled RyRs are at the origin of these spontaneous Ca2þ releases and are responsive to drug treatment without affecting the overall global Ca2þ transient.
THE VITAMIN K–DEPENDENT CARBOXYLASE
Authors: Kathleen L. Berkner
Journal: Annual Review of Nutrition (2005)

▪ Abstract The vitamin K–dependent (VKD) carboxylase uses the oxygenation of vitamin K to convert glutamyl residues (Glus) to carboxylated Glus (Glas) in VKD proteins, rendering them active in a broad range of physiologies that include hemostasis, apoptosis, bone development, arterial calcification, signal transduction, and growth control. The carboxylase has a high-affinity site that selectively binds VKD proteins, usually through their propeptide, and also has a second low-affinity site of VKD protein interaction. Propeptide binding increases carboxylase affinity for the Glu substrate, and the coordinated binding of the VKD propeptide and Glu substrate increases carboxylase affinity for vitamin K and activity, possibly through a mechanism of substrate-assisted catalysis. Tethering of VKD proteins to the carboxylase allows clusters of Glus to be modified to Glas by a processive mechanism that becomes disrupted during warfarin therapy. Warfarin inhibits a vitamin K oxidoreductase that generates the reduced vitamin K cofactor required for continuous carboxylation and causes decreased carboxylase catalysis and increased dissociation of partially carboxylated, inactive VKD proteins. The availability of reduced vitamin K may also control carboxylation in r-VKD protein-expressing cells, where the amounts of reduced vitamin K are sufficient for full carboxylation of low, but not high, expression levels of VKD proteins, and where carboxylation is not improved by overexpression of r-carboxylase. This review discusses these recent advances in understanding the mechanism of carboxylation. Also covered is the identification of functional carboxylase residues, a brief description of the role of VKD proteins in mammalian and lower organisms, and the potential impact of quality control components on carboxylation, which occurs in the endoplasmic reticulum during the secretion of VKD proteins.
P476Intraventricular measurement of electrophysiological parameters in pre- or post-conditioned myocardial infarction
Authors: A Spannbauer, D Traxler, N Pavo, M Riesenhuber, C Mueller, A Gugerell, J Winkler, K Zlabinger, D Lukovic, M Gyongyosi
Journal: Cardiovascular Research (2018)

Results: Echocardiography presented no difference between the groups compared to the initial measurements.The length and the variability parameters of the RR intervals were greater in the trained groups.Dofetilide administration tended to increase the QTc in greater extent both in 'exercised ' and 'doping' groups compared to 'sedentary' group (252.8613.2 and 251.8614.6 vs. 221.860.8ms).Atropine treatment resulted in moderate heart frequency increase in the 'exercised ' and 'doping' animals (127.6611.9 and 135.960.9 vs. 166.1613.5).Conclusions: The lengthened RR intervals, the increased heart rate variability are the signs of the increased parasympathetic tone and are characteristics of the exercise-induced autonomic changes.Repolarization changes may indicate the sensibility of the hearts to arrhythmia, however, further investigations with higher 'n' numbers are warranted.
Abstract 17175: Isometric Handgrip Exercise Reduces 24hr Ambulatory Blood Pressure
Authors: Debra J Carlson, Gudrun Dieberg, James R McFarlane, Neil A Smart
Journal: Circulation (2017)

Introduction: Despite increased awareness, treatment and control of hypertension, it is still a major health concern with over 1 billion adults worldwide diagnosed with hypertension. The 2014 NHANE...
Abstract 21016: Left Atrial Dysfunction Persists After Transapical but Not Transfemoral Transcatheter Aortic Valve Replacement and is Associated With Worse Outcomes
Authors: Mirette A Fahim, Sorin V Pislaru, Patricia A Pellikka, Vuyisile T Nkomo, Mackram F Eleid, Kevin L Greason, Cristina Pislaru
Journal: Circulation (2017)

Introduction and Aims of The Study: The relief of outflow obstruction after transcatheter aortic valve replacement (TAVR) is expected to improve cardiac output, LV systolic and diastolic function and to regress left ventricular (LV) mass. The impact of these changes on left atrial (LA) reservoir, conduit and contractile function remains unknown. Our aims were to compare LA functions in patients with transfemoral (TF) vs transapical (TA) TAVR and test whether they have an impact on patient outcomes. Methods: Retrospective analysis of LA deformation by speckle tracking strain echocardiography in 54 patients with TA TAVR and 54 TF TAVR, matched for age, sex and STS score. Measurements were performed pre TAVR and 1 month and 1 year post TAVR. Follow up data was available up to 5 years. Results: At baseline, there were no significant differences between the TF and TA groups with regard to patient age (81 ± 8 vs 82 ± 8 years), male gender (44% vs. 44%) or STS score (8.3 ± 4.4 vs 9.7 ± 4.5, respectively). LV filling pressures (E/e’) at baseline and 1 month were higher in TA vs. TF group (see table). LV global longitudinal strain (GLS) were similar at baseline and improved at 1 month only in the TF group (p=0.0001), while in the TA group it showed an improvement only at 1 year. LA reservoir, conduit and contractile functions improved within 1 month post TAVR in the TF group. In contrast, despite similar baseline LA functions in both groups, no improvement was observed in the TA group (see Table). At Cox proportional hazard analysis, lower LA reservoir function predicted major adverse events (death, cardiac rehospitalization or stroke) even after adjusting for age, gender and group allocation (p=0.034; risk ratio per unit decrease in LA function 1.04). Conclusion: These findings suggest that patients with TA TAVR have poor (if any) recovery of LA functions post TAVR. Presence of a stiff LA, best reflected by a persistently reduced LA reservoir strain, may contribute to the excess morbidity seen in TA patients.
Response by Packer to Letter Regarding Article, “Activation and Inhibition of Sodium-Hydrogen Exchange Is a Mechanism That Links the Pathophysiology and Treatment of Diabetes Mellitus With That of Heart Failure”
Authors: Milton Packer
Journal: Circulation (2018)

In Response: I very much appreciate the kind comments from Drs Gazmuri and Karmazyn.I agree fully with their view that it is imperative to rekindle efforts to investigate the potential utility of inhibitors of the sodium-hydrogen exchanger isoforms 1 and 3 (NHE1 and NHE3) in the treatment of both heart failure and diabetes mellitus. 1That was my primary reason for writing the article.Drs Gazmuri and Karmazyn correctly note that the NHE1 inhibitor cariporide was shown to reduce myocardial injury and the short-term risk of cardiovascular death or injury in patients undergoing coronary artery bypass surgery.However, cariporide inhibited NHE1 in platelets and thereby increased their thrombogenic potential. 2Such an action likely explains the increased risk of stroke seen in postsurgical patients in a large-scale trial, because platelets are already marked activated in this clinical setting.The challenge for future development of NHE1 inhibitors is to minimize this thrombogenic effect, possibly by synthesizing analogs that are more organ selective.I am particularly excited about the potential of agents that can produce selective inhibition of NHE3 in the proximal renal tubule.Kidney-specific NHE3 knockout models have been developed. 3 In theory, innovative agents can be synthesized that may target the binding proteins or kinases that are required for the phosphorylation, trafficking, or membrane localization of NHE3 in renal tubular cells. 4,5 The development of such novel compounds might allow clinicians to directly address one of the primary mechanisms responsible for the glomerular hyperfiltration that leads to diabetic nephropathy.