tbuckley/cabot-search huggingface dataset:
Abstract 16722: Perinexal Width Modulates Sodium Channel Recruitment During Extracellular Stimulation
Authors: Katrina Colucci Chang, Xiaobo Wu, Grace Blair, Alicia Lozano, Alexandra Hanlon, Steven Poelzing
Journal: Circulation (2020)

Excitability in cardiomyocytes is dependent on the subthreshold current required to raise transmembrane potential to the activation threshold of voltage gated sodium channels and sodium channel recruitment to trigger an action potential. Cardiac sodium channels are densely expressed in the intercalated disc within the perinexal nanodomain, which is 2 orders of magnitude narrower than bulk extracellular interstitium. We hypothesized that perinexal narrowing reduces extracellular induced excitability because the perinexus functions as a voltage divider. Methods: Excitability with an extracellular stimulus was quantified in isolated Langendorff perfused male retired breeder guinea pig hearts by strength duration curves using the Lapicque method. Interventions included changing extracellular potassium (K+: 3, 4.5, and 10 mM), inhibiting sodium channels (90-uM Flecainide), and narrowing the perinexus by increasing extracellular calcium (Ca2+: 1.25 to 2.5 mM). Results: Consistent with previous studies, decreasing K+ from 4.56 to 3 mM depressed excitability with 2.5 mM Ca2+ but not 1.25 mM Ca2+, and conduction velocity (CV) decreased by 10.5 % with both 1.25 and 2.5 mM Ca2+. When K+ was raised from 4.56 to 10 mM, no change was seen in excitability with both Ca2+ concentrations. However, CV decreased by 16% with both Ca2+ concentrations. Flecainide depressed excitability only with 2.5 but not 1.25 mM Ca2+. Meanwhile CV decreased by 13% with 1.25 but CV did not change with 2.5 mM Ca2+. Finally, raising Ca2+ alone at baseline decreased excitability, without substantially changing conduction. Conclusions: Elevating extracellular calcium to narrow perinexi reduces excitability measured by extracellular stimulation consistent with a hypothesis that sodium channels in the intercalated disc are electrically isolated from the bulk interstitium. Furthermore, excitability and conduction do not correlate in response to similar K+ changes when Ca2+ also varies, suggesting cardiac excitability and propagation are independent mechanisms when the excitatory current occurs through regenerative propagation as occurs through gap junctions or arrives via an extracellular field as occurs with pacing and ephaptic coupling.
Abstract 320: Posttraumatic Stress Symptoms Are Associated with Quality of Life in Both Cardiac Arrest Survivors with Good Neurologic Recovery and Caregivers
Authors: Alex Presciutti, Mary M Newman, Ana-maria Vranceanu, Jonathan Shaffer, Sarah M Perman
Journal: Circulation (2020)

Introduction: Improvements in cardiac arrest (CA) survival have led to increased attention to quality of life (QoL) of survivors and their caregivers. In survivors, posttraumatic stress symptoms (PTS) are predictive of poor clinical outcome and subjective recovery. This study tested the hypothesis that PTS is associated with QoL in survivors and caregivers. Method: We distributed an online survey to CA survivors and caregivers who were members of the Sudden Cardiac Arrest Foundation. This analysis examined the following items: participant characteristics, PTSD Checklist-5 (PCL-5), Lawton Instrumental Activities of Daily Living scale, and physical, psychological, and social QoL subscales of the WHOQOL-BREF. We followed an identical analytic plan for survivors and caregivers. We identified potential covariates through a bivariate correlation matrix. We then ran three multiple regression models examining associations between PCL-5 scores with each QoL subscale, adjusted for covariates identified from the correlation matrix. Results: A total of 163 survivors (mean age: 50.1 years, 50.3% women, 95.5% white, mean months since arrest: 63.9) and 52 caregivers (mean age: 51.8 years, 86.5% women, 88.5% white, mean months since arrest: 43.2) provided full data. For survivors, the following variables showed significant bivariate associations with any QoL subscale: Lawton scores, self-reported memory problems, male sex, low income, months since CA, age, and CA location; for caregivers, months since CA, age, and low income. In survivors and caregivers, PCL-5 scores were associated with each QoL subscale (β: -.33 - -.54, p &lt; .05) after adjusting for respective covariate sets. Further, in survivors, Lawton scores (β: .23, p &lt;.01), presence of memory problems (β: -.24, p &lt; .01), and male sex (β: .14, p &lt;.05) were associated with physical QoL; presence of memory problems (β: -.26, p &lt; .01) was associated with psychological QoL; and low income (β: -.16, p &lt; .05) was associated with social QoL. In caregivers, months since CA was associated with social QoL (β: .27, p &lt;.05). Conclusion: PTS was associated with QoL in CA survivors and caregivers. Future study should examine the feasibility of in-hospital assessment of PTS in dyads of CA survivors and their caregivers.
Emotional Regulation and Diabetes Distress in Adults With Type 1 and Type 2 Diabetes
Authors: Emil F. Coccaro, Sophie Lazarus, Joshua Joseph, Kathline Wyne, Tina Drossos, Louis Phillipson, Mary de Groot
Journal: Diabetes Care (2020)

OBJECTIVE To explore the correlates of diabetes-related distress (DD) with psychometrically valid assessments of emotional regulation in individuals with type 1 and type 2 diabetes. RESEARCH DESIGN AND METHODS Adults with diabetes (n = 298) were assessed for psychological issues possibly associated with diabetes and were further evaluated with measures of negative emotional experience (ER-Exp) and skill at regulating such experiences (ER-Skill) and measures of DD, perceived psychosocial stress, diabetes literacy, and diabetes self-care. RESULTS ER-Exp was directly related to DD, while ER-Skill was inversely related to DD. Together, these ER variables displayed a medium-size relationship (β = 0.45) with DD. Inclusion of variables related to diabetes self-care and perceived psychosocial stress was associated with only an 18% reduction (i.e., β = 0.45 to β = 0.38) in the strength of this relationship, while the magnitude of relationships between DD and perceived psychosocial stress (β = 0.15) and diabetes self-care (β = −0.09) was relatively small. CONCLUSIONS These data suggest that DD is meaningfully linked with negative emotionality, and skill at regulating such emotions, in adults with diabetes. This relationship appears to be stronger than that between DD and perceived psychological stress or diabetes self-care. If so, DD (and possibly A1C) may be improved in those with diabetes and difficulties with negative emotionality.
A 2021 Horizon Scan of Emerging Global Biological Conservation Issues
Authors: William J. Sutherland, Philip W. Atkinson, Steven Broad, Sam Brown, Mick Clout, Maria P. Dias, Lynn V. Dicks, Helen Doran, Erica Fleishman, Elizabeth L. Garratt, Kevin J. Gaston, Alice C. Hughes, Xavier Le Roux, Fiona A. Lickorish, Luke Maggs, James E. Palardy, Lloyd S. Peck, Nathalie Pettorelli, Jules Pretty, Mark D. Spalding, Femke H. Tonneijck, Matt Walpole, James E.M. Watson, Jonathan Wentworth, Ann Thornton
Journal: Trends in Ecology & Evolution (2020)
Abstract 15033: Chronic Inhibition of Mitochondrial Reactive Oxygen Species Protects Against Endothelial SK Channel Dysfunction in Diabetes
Authors: Hang Xing, Zhiqi Zhang, Yi Song, guangbin shi, Elizabeth Harrington, Jun Feng
Journal: Circulation (2020)

Introduction: Oxidative stress plays an important role in the development of pathological condition in diabetes. Persistent oxidative stress during diabetes may result in impaired endothelium-independent vasodilation, by reducing small-conductance Ca 2+ -activated K + (SK) channel activity. The mitochondria are main sources of reactive oxygen species (ROS) in diabetes, and mitochondria-targeted antioxidant mito-TEMPO (MT) prevents ROS generation has been found in a variety of disorders. However, few studies are available on the dysfunction of vasodilation and endothelial SK channels in diabetes after a chronic use of MT. Purpose: We investigated the chronic administration of MT on vasodilation in coronary arteries, and endothelial SK channel activity with or without diabetes. Methods: MT (1mg/kg) was applied to diabetic and health mice (n = 6/group) for 1 month. In-vitro relaxation response of pre-contracted arteries was examined in the presence or absence of the vasodilatory agents. Isolated endothelium was studied using whole-cell patch clamp recording SK channels currents. Results: Coronary arteries dilation was decreased in diabetic mice compared with that in health ( p &lt;0.05). After one month treatment with MT, coronary arteries dilation was significantly improved when compared with that in non-treatment diabetic mice ( p &lt;0.05). Interestingly, coronary arteries dilation was no significantly changed in health mice whether to treat with MT or not. Similar changes were seen in patch clamp recording, impaired currents of SK channels in endothelial cells of diabetic mice were significantly improved after chronic treatment with MT ( p &lt;0.05, Fig) and currents of SK channels were no changed in health mice whether to treat with MT or not. Conclusions: MT appears to improve coronary endothelial function/dilation by protection of SK channel activity in diabetes, and administration of MT may be a novel strategy to treat vascular complications in diabetes.
Hotspots of Human Mutation
Authors: Alex V. Nesta, Denisse Tafur, Christine R. Beck
Journal: Trends in Genetics (2020)

Mutation of the human genome results in three classes of genomic variation: single nucleotide variants; short insertions or deletions; and large structural variants (SVs). Some mutations occur during normal processes, such as meiotic recombination or B cell development, and others result from DNA replication or aberrant repair of breaks in sequence-specific contexts. Regardless of mechanism, mutations are subject to selection, and some hotspots can manifest in disease. Here, we discuss genomic regions prone to mutation, mechanisms contributing to mutation susceptibility, and the processes leading to their accumulation in normal and somatic genomes. With further, more accurate human genome sequencing, additional mutation hotspots, mechanistic details of their formation, and the relevance of hotspots to evolution and disease are likely to be discovered.
Cardiovascular and Renal Outcomes of Mineralocorticoid Receptor Antagonist Use in PARAGON-HF
Authors: Karola S. Jering, Faiez Zannad, Brian Claggett, Finnian R. Mc Causland, João Pedro Ferreira, Akshay Desai, Ebrahim Barkoudah, John J.V. McMurray, Marc A. Pfeffer, Scott D. Solomon
Journal: JACC Heart Failure (2020)
Risk of colorectal cancer in patients with diabetes mellitus: A Swedish nationwide cohort study
Authors: Uzair Ali Khan, Mahdi Fallah, Kristina Sundquist, Jan Sundquist, Hermann Brenner, Elham Kharazmi
Journal: PLoS Medicine (2020)

Background Colorectal cancer (CRC) incidence is increasing among young adults below screening age, despite the effectiveness of screening in older populations. Individuals with diabetes mellitus are at increased risk of early-onset CRC. We aimed to determine how many years earlier than the general population patients with diabetes with/without family history of CRC reach the threshold risk at which CRC screening is recommended to the general population. Methods and findings A nationwide cohort study (follow-up:1964–2015) involving all Swedish residents born after 1931 and their parents was carried out using record linkage of Swedish Population Register, Cancer Registry, National Patient Register, and Multi-Generation Register. Of 12,614,256 individuals who were followed between 1964 and 2015 (51% men; age range at baseline 0–107 years), 162,226 developed CRC, and 559,375 developed diabetes. Age-specific 10-year cumulative risk curves were used to draw conclusions about how many years earlier patients with diabetes reach the 10-year cumulative risks of CRC in 50-year-old men and women (most common age of first screening), which were 0.44% and 0.41%, respectively. Diabetic patients attained the screening level of CRC risk earlier than the general Swedish population. Men with diabetes reached 0.44% risk at age 45 (5 years earlier than the recommended age of screening). In women with diabetes, the risk advancement was 4 years. Risk was more pronounced for those with additional family history of CRC (12–21 years earlier depending on sex and benchmark starting age of screening). The study limitations include lack of detailed information on diabetes type, lifestyle factors, and colonoscopy data. Conclusions Using high-quality registers, this study is, to our knowledge, the first one that provides novel evidence-based information for risk-adapted starting ages of CRC screening for patients with diabetes, who are at higher risk of early-onset CRC than the general population.
Abstract 14451: Bone Marrow Cell Therapy Improves Cardiac Function, Survival, and Clinical Outcomes in Patients With Chronic Ischemic Heart Disease
Authors: Jane Ha, Muhammad R Afzal, Anweshan Samanta, Ewa Zuba-Surma, Ji Yoo, Buddhadeb Dawn
Journal: Circulation (2020)

Introduction: The effects of bone marrow cell (BMC) therapy in patients with chronic ischemic heart disease (CIHD) remain controversial. Hypothesis: We hypothesized that injection of BMCs in patients with CIHD would improve left ventricular (LV) structure and function. We also hypothesized that BMC therapy would improve clinical outcomes in CIHD patients. Methods: We performed a systemic review and meta-analysis of pooled data from published randomized controlled trials (RCTs) that evaluated the efficacy of BMC administration in patients with CIHD. The effects of BMC injection on LV ejection fraction (LVEF), LV end-systolic volume (LVESV), LV end-diastolic volume (LVEDV), infarct size, and patient outcomes were analyzed using random-effects meta-analysis. Results: The literature search yielded 30 RCTs enrolling 1,548 patients. Transplantation of BMCs resulted in an improvement in LVEF in cell-treated patients compared with controls (2.89%; 95% confidence interval (CI): 1.80 to 3.97; P &lt;0.001). There was a trend toward reduced LVESV (-4.96 ml; 95% CI: -11.64 to 1.71 ml; P = 0.14) and LVEDV (-5.95 ml; 95% CI: -12.09 to 0.18 ml; P =0.06). The improvement in LVEDV was more pronounced (-7.42 ml; 95% CI: -13.68 to -1.17ml; P =0.02) in patients with baseline LVEF &lt;40%, indicating improved LV remodeling. BMC injection was also associated with marked reduction in the risk of all-cause mortality, rehospitalization due to heart failure, and ventricular arrhythmias in CIHD patients. Conclusions: BMC injection improves cardiac function and remodeling in patients with CIHD. These benefits are more pronounced in patients with LVEF &lt;40% at baseline. Perhaps more importantly, BMC therapy also improves clinical outcomes that are critically important for this patient population with LV dysfunction, including survival, rehospitalization due to heart failure, and ventricular arrhythmias.
Abstract 17272: Frequency of Acute Vasodilator Response in Incident and Prevalent Patients With Pulmonary Arterial Hypertension (Group 1): Results From the Pulmonary Vascular Disease Omics (PVDOMICS) Study
Authors: Paul Hassoun, Armand Larive, Erika B Rosenzweig, Robert Frantz, Anna R Hemnes, Evelyn M Horn, Miriam Jacob, Jane A Leopold, Franz Rischard
Journal: Circulation (2020)

Introduction: The prevalence of acute vasodilator response (AVR) to inhaled NO (defined as a reduction in mPAP ≥ 10 mmHg with an absolute value of mPAP ≤ 40 mmHg with increased/unchanged CO) is reported to be around 12% in incident patients with idiopathic PAH (IPAH). The prevalence of AVR, however, is reportedly lower in other disease-associated PAH in Group 1, such as connective tissue disease (CTD). Furthermore, the prevalence of AVR for combined inhaled NO and oxygen, and in patients on PAH therapy (prevalent cohort), is less known. Hypothesis: We hypothesized there would be differences in the prevalence of AVR in PAH subgroups in the large PVDOMICS cohort of incident and prevalent patients. Methods: Group 1 PAH patients enrolled in PVDOMICS underwent right heart catheterization for baseline measurements. AVR was then measured in response to 100% inhaled oxygen (O 2 ) and 100% O 2 plus NO at 40 ppm (O 2 +NO) for 5 min each before hemodynamic measurements. Details of the PVDOMICS methodology and core adjudication of hemodynamic measurements were reported previously. Rates of AVR to 100% O 2 and 100% O 2 +NO were compared between incident and prevalent patients in each PAH subgroup. Results: 351 patients, mostly female (73%), average age of 52.9 years, with mostly prevalent disease (87%) and an average of 4 years from PAH diagnosis, underwent AVR assessment. A positive AVR was found in 0.6% of patients in response to 100% oxygen and 6% of patients in response to 100%+NO for the overall cohort. AVR was similar in incident and prevalent IPAH patients (6 and 6.9%, respectively). It was, however, 0% and 6.9%, in incident vs. prevalent CTD-PAH patients, respectively. There were no responders to either challenge in any other PAH subgroup. Conclusions: The prevalence of AVR is relatively rare in IPAH and CTD-PAH (~ 6%) and absent in other subgroups. There was no response to 100% O2 alone, suggesting specificity of AVR to NO in PAH. AVR is more common than previously reported in CTD-PAH, but only in prevalent disease. Whether the latter is related to long-term PAH therapy affecting pulmonary vasomotor response and/or vascular remodeling in these patients would warrant further studies.
Abstract 14515: The Prognostic Impact of Human Epididymis Protein 4 Levels in Patients With Dilated Cardiomyopathy
Authors: Takahiro OKUMURA, Hideo Oishi, Yuki Kimura, Takashi Araki, Takashi Mizutani, Shingo Kazama, Naoki Shibata, Tasuku Kuwayama, Hiroaki Hiraiwa, Toru Kondo, Ryota Morimoto, Mikito Takefuji, Toyoaki Murohara
Journal: Circulation (2020)

Introduction: Interstitial fibrosis of myocardium is an important component of cardiac dysfunction. Myofibroblasts, which are activated fibroblasts, contribute to interstitial fibrosis in dilated cardiomyopathy (DCM). Recently, human epididymal body protein 4 (HE4) has attracted attention as a marker specific to myofibroblasts. Hypothesis: We hypothesized that the circulating serum HE4 levels were associated with future cardiac events in DCM. Methods: We enrolled 44 DCM patients with stable heart failure (HF) condition. Patients with cancer were excluded. We collected blood samples from peripheral vain (PV), ascending aorta (Ao), and coronary sinus (CS) during cardiac catheterization. They were divided into two groups at the median of PV HE4 levels: High PV group (&gt;69 pmol/L); n=22, Low PV group (&lt;69 pmol/L); n=22. Furthermore, they were also divided into groups with median of CS-Ao HE4 levels: High CS-Ao group (&gt;-0.15 pmol/L); n=22, Low CS-Ao group (&lt;-0.15 pmol/L); n=22. Cardiac events were defined as composite of cardiac deaths and hospitalization for worsening HF. Results: The mean age, left ventricular ejection fraction (LVEF), and plasma BNP level were 56 years, 32%, and 205 pg/mL. Between two groups, there were no significant differences in age, gender, LVEF, left ventricular end-diastolic diameter, cardiac index, and pulmonary capillary wedge pressure. However, estimated glomerular filtration rate was significantly lower in the High PV group (p=0.025). Survival analysis revealed that the High PV group had a higher rate of cardiac events ( Figure ). However, there was no difference between two CS-Ao groups. As for the pathological analysis, not only the peripheral HE4 level but CS-Ao HE4 level did not significantly correlate with collagen volume fraction in biopsy samples. Conclusion: Elevated circulating HE4 is associcated with poor prognosis in ambulatory patients with NIDCM. However, transcardiac gradient of plasma HE4 level might not be associated.
Correspondence on ‘Prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases: a systematic review and meta-analysis’
Authors: Haiyan Yang, Jie Xu, Li Shi, Guangcai Duan, Yadong Wang
Journal: Annals of the Rheumatic Diseases (2021)

With great interest, we have read the recent article entitled ‘Prevalence and clinical outcomes of COVID-19 in patients with autoimmune diseases: a systematic review and meta-analysis’, which is published online in Annals of the Rheumatic Diseases .1 In this paper, Akiyama et al performed a meta-analysis to investigate the prevalence and clinical outcomes of coronavirus disease 2019 (COVID-19) in patients with autoimmune diseases.1 The authors observed that there was no significant difference in death between COVID-19 patients with autoimmune diseases and those without (odds ratio (OR)=0.545, 95% confidence interval (CI): 0.081 to 3.682).1 It is an extremely interesting study. But, their findings were based on only five published studies. Up to now, a considerable number of studies on this topic are emerging. Therefore, the association between autoimmune diseases and COVID-19 mortality is needed to be clarified on the basis of updated data by a quantitative meta-analysis.

We performed this meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines.2 A comprehensive literature search was performed in electronic databases including PubMed, Web of Science and EMBASE to identify eligible studies from 1 January 2020 to 23 December 2020 using the following keywords: ‘coronavirus disease 2019’ or ‘COVID-19’ or ‘severe acute respiratory syndrome coronavirus-2’ or ‘SARS-CoV-2’ and ‘autoimmune diseases’ or ‘rheumatic diseases’ or ‘inflammatory bowel disease’ or ‘psoriasis’ or ‘systemic lupus erythematosus’ and ‘mortality’ or ‘death’ or ‘fatality’ or ‘non-survivor’ or ‘deceased’. The reference lists of relevant literatures were also reviewed to identify missing studies. We included articles …