tbuckley/cabot-search huggingface dataset:
Abstract 13725: Limited Fatty Acid Use by CD36 Deficiency Accelerates the Development of Diabetic Cardiomyopathy
Authors: Ryo Kawakami, Yogi Umbarawan, Tatsuya Iso, Norimichi Koitabashi, Hiroaki Sunaga, Hiroki Matsui, Masahiko KURABAYASHI
Journal: Circulation (2020)

Diabetes is an independent risk factor for the development of heart failure. In diabetic hearts, it has been reported that increased fatty acid (FA) uptake and deranged FA use result in accumulation of cardiotoxic lipids and reduced cardiac efficiency that compromise systolic and diastolic function. To date, lipotoxicity hypothesis is prevailing as a key event driving diabetic cardiomyopathy and it is proposed that limited FA use is beneficial for diabetic hearts. However, it has not been fully studied whether limited FA use is actually beneficial in-vivo beating hearts in diabetes. CD36, a transmembrane glycoprotein, has a major role in FA uptake in the heart. CD36 knockout (CD36KO) hearts exhibit reduced rates of FA transport and oxidation with marked enhancement of glucose use. In this study, we explored whether reduced FA use by CD36 ablation suppresses the development of streptozotocin (STZ)-induced diabetic cardiomyopathy. Contrary to our expectations, we found that cardiac contractile dysfunction was deteriorated 16 weeks after STZ treatment in CD36KO mice. Although accelerated glucose uptake, estimated by 18 F-FDG uptake, was not reduced in CD36KO-STZ hearts, total energy supply, estimated by the pool size of the TCA cycle, was significantly reduced in CD36KO-STZ hearts. Isotopomer analysis with 13 C 6 -glucose revealed that accelerated glycolysis, estimated by enrichment of 13 C 3 -lactate, 13 C 2 -alanine, 13 C 2 -citrate and 13 C 2 -malate, in CD36KO hearts was markedly suppressed by STZ treatment. On the other hand, levels of ceramides, cardiotoxic lipids from excessive FA, were not elevated in CD36KO-STZ hearts compared to WT-STZ. Further, increased energy demand induced by transverse aortic constriction resulted in synergistic exacerbation of cardiac contractile dysfunction in CD36KO-STZ mice. These findings suggest that CD36KO-STZ hearts are energetically compromised by reduced FA use and suppressed glycolysis, leading to cardiac contractile dysfunction. Therefore, it is very likely that enhanced FA use in diabetic hearts occurs to compensate for reduced glucose use, and that limitation of FA utilization could be detrimental to the development of diabetic cardiomyopathy.
Abstract 13625: Effect of Empagliflozin versus Placebo on Plasma Volume Status in Patients With Acute Myocardial Infarction and Type 2 Diabetes Mellitus: Subgroup Analysis of the Embody Trial
Authors: Yu Hoshika, Yoshiaki Kubota, Kosuke Mozawa, Shuhei Tara, Yukichi Tokita, Kenji Yodogawa, Yuki Iwasaki, Takeshi Yamamoto, Hitoshi Takano, Yayoi Tsukada, Kuniya Asai, Masaaki Miyamoto, Yasushi Miyauchi, Eitaro Kodani, Mitsunori Maruyama, Jun Tanabe, Wataru Shimizu
Journal: Circulation (2020)

Background: Plasma volume status (PVS), a parameter of the discrepancy between actual plasma volume (PV) and ideal PV, has been evaluated recently as a prognostic marker of patients with heart failure. This subgroup analysis of the EMBODY trial was designed to determine whether the sodium-glucose cotransporter 2 (SGLT2) inhibitor affect the improvement of heart failure and PVS in patients after acute myocardial infarction (AMI) with congestive heart failure (CHF). Methods: The EMBODY trial was a prospective, multicenter, randomized, double-blind, placebo-controlled trial to identify the effect of the SGLT2 inhibitor on cardiac sympathetic hyperactivity in patients with AMI and type 2 diabetes mellitus (T2DM) in Japan. A total of one hundred and five patients were randomized (1:1) to receive once-daily 10 mg empagliflozin or placebo 2 weeks after the onset of AMI. In this subanalysis, we investigated the time-course of PVS on baseline, weeks 4, 12 and 24. Results: Overall, 96 patients were included in the subgroup analysis set (64.3±10.9 years, male 80.2%, and 46 in the empagliflozin group and 50 in the placebo group). The empagliflozin group showed significant decreases in body weight, systolic blood pressure, and PVS compared with the placebo group at 24 weeks (-2.2 vs. +0.1 kg, P=0.0007; -6.6 vs. +3.5 mmHg, P=0.003; and -5.1 vs. -0.3%, P=0.0006; respectively). Decreased of PVS, defined as change of PVS &lt; -4.5 % was associated with received empagliflozin (odds ratio, 2.61; 95% confidence interval, 1.11 - 6.15; P=0.028). On the other hand, NT-Pro BNP levels significantly decreased in the empagliflozin group and placebo group (1028.7 to 370.3 pg/ml, P=0.0001 and 1270.6 to 673.7 pg/ml, P=0.006, respectively). Conclusion: Empagliflozin reduced not only body weight but also PVS. These results suggested that early SGLT2 inhibitor administration in patients with AMI, CHF and T2DM could be effective to reduce body weight and PVS.
BCG vaccination history associates with decreased SARS-CoV-2 seroprevalence across a diverse cohort of health care workers
Authors: Magali Noval Rivas, Joseph E. Ebinger, Min Wu, Nancy Sun, Jonathan Braun, Kimia Sobhani, Jennifer E. Van Eyk, Susan Cheng, Moshe Arditi
Journal: Journal of Clinical Investigation (2020)

BACKGROUND. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 1 million deaths worldwide; thus, there is an urgent need to develop preventive and therapeutic strategies. The antituberculosis vaccine bacillus Calmette-Guérin (BCG) demonstrates nonspecific, protective innate immune–boosting effects. Here, we determined whether a history of BCG vaccination was associated with decreased SARS-CoV-2 infection and seroconversion in a longitudinal, retrospective observational study of a diverse cohort of health care workers (HCWs).
Abstract 13259: Differences in Glucose Readings Between Right Arm and Left Arm Using a Continuous Glucose Monitor
Authors: Xiaohan Liu, Sonoko Kawakatsu, Brandon Tran, Brittany Tran, Lucy Manzanero, Eric Shih, Allen Shek, Jeremy Lim, Sachin A Shah
Journal: Circulation (2020)

Introduction: Poorly controlled diabetes increases the risk of cardiovascular disease and associated complications. Continuous glucose monitoring (CGM) devices are tools that allow clinicians and patients to gather real-time glucose levels to enhance glycemic control. CGM devices are increasingly used to optimize diabetes management, but there is no guidance on whether glucose readings differ when a CGM device is placed on the right versus the left arm. We assessed the hypothesis that a difference in time-matched glucose levels will be observed between the right and left arm. Methods: This prospective trial enrolled 46 adult volunteers to simultaneously wear CGM sensors on the right and left arms. Glucose readings were collected every 15 minutes over a 12-14 days study period. To assess if any observed inter-arm differences were a result of perfusion, participants were randomized to perform a daily 20-minute unilateral arm exercise using an assigned arm on Days 1-6, and to use the alternate arm from Day 7 to Days 12-14. Differences in glucose readings between the right and left arm were compared using the paired sample t-test. Results: A total of 41,288 time-matched glucose level pairs were collected and the mean glucose reading in the right arm was higher than that of the left arm by 3.7±10.6 mg/dL (p&lt;0.001). Glucose readings were in hypoglycemic range (&lt;70 mg/dL) for 22.1% of the time in the right arm and 29.8% of the time in the left arm (p&lt;0.001), in euglycemic range (70-180 mg/dL) for 75.2% of the time in the right arm and 67.5% in the left arm (p&lt;0.001), and in hyperglycemic range (&gt;180 mg/dL) for 2.8% of the time in both arms (p=0.83). The difference in glucose levels between the arms was similar before and during exercise [4.0±10.2 mg/dL vs. 4.3±10.1 mg/dL, p=0.77]. Conclusions: In conclusion, glucose levels and time in hypoglycemia and euglycemia significantly differ based on arm selection during CGM device placement. This finding is unrelated to differences in perfusion induced by unilateral arm exercise. If these findings are further validated in patients with diabetes, arm selection during CGM device placement could impact therapy decisions, clinical trial design, and interpretation.
Abstract 14913: The Impact of the Wearable Cardioverter-defibrillators on Quality of Life: Insights From the Vest Trial
Authors: Chris C Cheung, Jeffrey Olgin, Mark J Pletcher, Trisha Hue, Eric Vittinghoff, Feng Lin, Mason Lai, Byron K Lee
Journal: Circulation (2020)

Background: There is scant research on the effect of wearable cardioverter-defibrillators (WCDs) on quality of life (QOL). One retrospective observational study concluded that WCDs have a negative impact. The VEST Trial was a randomized controlled trial of the WCD allowing a more definitive and complete analysis of QOL among WCD users. Hypothesis: We sought to determine if the WCD impacts patient-reported QOL, including depression, anxiety, and physical activity levels. Methods: In the VEST trial, participants with severe left ventricular dysfunction (EF≤35%) after MI were randomized in a 2:1 ratio to receive a WCD plus guideline directed therapy (GDMT) versus GDMT alone. During the 3-month follow-up period, participants were asked to complete QOL assessments and health questionnaires. Results: 1524 participants were randomized to WCD plus GDMT versus 778 participants to GDMT alone. The mean age was 60.9±12.6 years and 61.4±12.3 years in the two groups, respectively. Participants were 73.5% male, had an average body-mass index of 28.4±5.5 kg/m2, and a mean EF of 28%. During a mean follow-up of 84.3±15.6 days, health questionnaires and QOL assessments were completed by 1340 participants, including 898 receiving WCD plus GDMT, and 442 receiving GDMT alone. See Table 1 for the results of QOL assessments and health questionnaires. There were no differences in QOL according to the SF-36 physical and mental component scores, and EQ-5D scores between WCD plus GDMT versus GDMT alone. There were also no differences in depression (CES-D 10), anxiety (State-Trait Anxiety Inventory), physical activity (International Physical Activity Questionnaire), or self-reported health scale between groups (all p&gt;0.05). Conclusions: In post-MI patients with low EF, the WCD does not affect QOL, depression, anxiety, physical activity, or self-reported health. Prescribers can be reassured that the WCD has no detrimental impact on patient-reported health measures.
SP0154 The bjd: experiences from sweden and (somewhat) from the nordic countries
Authors: LM Oehrsvik
Journal: Annals of the Rheumatic Diseases (2001)

<h3></h3> The work with the Bone and Joint Decade is well underway in many countries by now. In Sweden the practical work is led by a small 5 person steering group and as a complement to this there is a foundation used to gather funds for the project. There is also a larger reference group whose opinions and ideas are tapped every once in a while. In this group there are representatives from the rheumatologists as well as orthopaedics, other health professionals but also patients. In this short summary the activities undertaken on part of the Bone and Jone Decade in Sweden will not be listed. Our intention is to cease every opportunity to spread the message, different conferences for doctors and health professionals, and in the patient societies but it also gives us a good opportunity to spread information through the media and directly to decision makers at different levels. The main benefits of the work with the decade are the following: It increases co-operation between the patients and doctors and all the health professionals. The decade also puts focus on the need for more co-operation between the different disciplines within medicine, which is of great importance. In order to lessen the suffering and bring down the costs for the individual as well as societies we must spread information and influence politicians. In the other Nordic countries the work has been organised in a somewhat different manner and as the chair of the Nordic Rheuma Council (www.nrr.nu) I will take the liberty of giving some examples from the other Nordic countries in the cases where they are not speaking of this themselves. At a purely Nordic level the Nordic Rheuma Council has been active and has managed to get the Committee for Nordic Affairs inside the Nordic Council, a body made up of Nordic parliamentarians, to urge the Nordic governments to all sign the declaration of the Bone and Joint Decade.
Abstract 16245: <i>Lactobacillus Plantarum</i> Probiotic Preserves Endothelial Function and Diastolic Performance in the Ischemic Myocardium Through Redox Nrf2 Antioxidant Signaling
Authors: Ahmed M Aboulgheit, Zhiqi Zhang, guangbin shi, Catherine Karbasiafshar, Neel Sodha, Ruhul Abid, Frank W Sellke
Journal: Circulation (2020)

Introduction: Oxidative homeostasis is critical to the viability of the vascular endothelium. Nrf2 is a redox-sensitive transcription factor that induces several cyto-protective and antioxidant genes in response to stress. Lactobacillus plantarum , a probiotic bacterium, can convert caffeic acid to 4-vinyl catechol, a natural activator of Nrf2. Hypothesis: We hypothesized that a diet consisting of applesauce, which is rich in caffeic acid, supplemented with L. plantarum can generate sufficient concentrations of 4-vinyl catechol to enhance Nrf2 activity and thereby ameliorate ischemic injury in the myocardium. Methods: Fourteen Yorkshire swine received a standard diet with 10 ml of 10% ethanol vehicle for three weeks (NDC; n=7); the treatment group was additionally fed unsweetened applesauce with L. plantarum supplements (ND-LP; n=7). Subsequently, an ameroid constrictor was placed around their left coronary circumflex artery (Lcx). Dietary regimens were continued for a period of fourteen weeks thereafter. Finally, cardiac function, myocardial perfusion, vascular density, and molecular signaling were examined. Results: The L. plantarum -applesauce diet upregulated Nrf2 signaling in the ischemic myocardium, thus inducing several antioxidant enzymes including heme oxygenase1 (HO-1), NADPH dehydrogenase quinone 1 (NQO-1), and thioredoxin reductase (TRXR-1). Reduced ischemic myocardial density of alpha smooth muscle actin (αSMA) and improved myocardial relaxation seen in the treatment cohort may reflect less ischemic fibrosis. Nrf2 activation increased expression of endothelial nitric oxide synthase (eNOS) and lowered concentrations of asymmetric dimethyl arginine (ADMA) in ischemic myocardial tissue, but did not significantly affect blood flow nor endothelial cell density. The expression of hypoxia inducible factor 1α (HIF-1α) and phosphorylated MAPK (pMAPK) was reduced in ischemic myocardial lysates from treatment animals. Conclusions: Dietary supplementation with L. plantarum and caffeic acid is a safe and effective mean of enhancing Nrf2 activity, which supported endothelial function and diastolic performance, while diminishing hypoxic stimulation of collateral vessel formation in the ischemic myocardium.
Broaching partially-shared identities: Critically interrogating power and intragroup dynamics in counseling practice with trans people of Color
Authors: Adrienne N. Erby, Mickey E. White
Journal: International Journal of Transgender Health (2020)

Background: Much of the literature on transgender and nonbinary (TGNB) experiences in counseling focuses on White experiences with few recommendations for trans people of Color (TPOC). Research suggests mental health care providers lack intersectional sensitivity with TPOC, lack knowledge of TGNB issues and engage in microaggressive behaviors, notably with Queer-identified clinicians. Aim: To explore issues of power and privilege in the counseling relationship with Queer-identified clinicians and apply the multidimensional model of broaching behavior with TGNB clients of Color. Method: A critical review of conceptual and empirical literature focusing on the interaction and impact of client and clinician race, gender, and sexual/affectional identities in the counseling relationship is presented. Informed by the authors' counseling experiences and respective positionalities as a Black Queer ciswoman and a White Queer transman, the multidimensional model of broaching behavior is applied to a composite case vignette. Results: The model provides a practical tool to facilitate critical conversations of power, privilege and identity in the counseling relationship. Conclusion: With a dearth of scholarship addressing the role of cisgender or White privilege in the counseling relationship, this article outlines strategies to broach issues partially-shared identities with TGNB clients of Color. Recommendations for culturally informed counseling practice, supervision and research are also provided.
Combination of magnesium ions and vitamin C alleviates synovitis and osteophyte formation in osteoarthritis of mice
Authors: Hao Yao, Jiankun Xu, Jiali Wang, Yifeng Zhang, Nianye Zheng, Jiang Yue, Jie Mi, Lizhen Zheng, Bingyang Dai, Wenhan Huang, Shuhang Yung, Peijie Hu, Yechun Ruan, Qingyun Xue, Kiwai Ho, Ling Qin
Journal: Bioactive Materials (2020)

We previously demonstrated that magnesium ions (Mg2+) was a novel therapeutic alternative for osteoarthritis (OA) through promoting the hypoxia inducible factor-1α (HIF-1α)-mediated cartilage matrix synthesis. However, oxidative stress can inhibit the expression of HIF-1α, amplify the inflammation that potentially impairs the therapeutic efficacy of Mg2+ in OA. Vitamin (VC), a potent antioxidant, may enhance the efficacy of Mg2+ in OA treatment. This study aims to investigate the efficacy of combination of Mg2+ and VC on alleviating joint destruction and pain in OA. Anterior cruciate ligament transection with partial medial meniscectomy induced mice OA model were randomly received intra-articular injection of either saline, MgCl2 (0.5 mol/L), VC (3 mg/ml) or MgCl2 (0.5 mol/L) plus VC (3 mg/ml) at week 2 post-operation, twice weekly, for 2 weeks. Joint pain and pathological changes were assessed by gait analysis, histology, western blotting and micro-CT. Mg2+ and VC showed additive effects to significantly alleviate the joint destruction and pain. The efficacy of this combined therapy could sustain for 3 months after the last injection. We demonstrated that VC enhanced the promotive effect of Mg2+ on HIF-1α expression in cartilage. Additionally, combination of Mg2+ and VC markedly promoted the M2 polarization of macrophages in synovium. Furthermore, combination of Mg2+ and VC inhibited osteophyte formation and expressions of pain-related neuropeptides. Intra-articular administration of Mg2+ and VC additively alleviates joint destruction and pain in OA. Our current formulation may be a cost-effective alternative treatment for OA.
Amyloid-like oligomerization of AIMP2 contributes to α-synuclein interaction and Lewy-like inclusion
Authors: Sangwoo Ham, Seung Pil Yun, Hyojung Kim, Donghoon Kim, Bo Am Seo, Heejeong Kim, Jeong-Yong Shin, Mohamad Aasif Dar, Gum Hwa Lee, Yun Il Lee, Doyeun Kim, Sunghoon Kim, Hee-Seok Kweon, Joo-Ho Shin, Han Seok Ko, Yunjong Lee
Journal: Science Translational Medicine (2020)

Pathological AIMP2 aggregation leads to α-synuclein inclusion and dopaminergic toxicity in Parkinson’s disease.
Abstract 17107: CHA2DS2VASC Score and Frailty Index as Mortality Predictors in Patients Hospitalized With SARS-CoV-2 Infection
Authors: Ibett Colina, Efehi Igbinomwanhia, Alejandro Sanchez, Miguel Treminio Quezada, Christopher Kabir, Peter Brady
Journal: Circulation (2020)

Introduction: The current pandemic with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has impacted healthcare around the globe. The CHADS2VASC and frailty scores have not been studied as tool predictors for outcomes in this population. Hypothesis: CHA2DS2VASC and frailty scores can be used as predictors of mortality and unfavorable outcomes in patients hospitalized with SARS-CoV-2 infection. Methods: We included patients ages 18 years and older who required in-hospital treatment for SARS-CoV-2 infection at a Community Hospital between February and April of 2020. CHA2DS2VASC score and frailty index (FI) were calculated at time of admission and were used as continuous variables in a multivariate logistic regression model. Cardiovascular (CV) outcome was a composite variable that included non-fatal MI, decompensated heart failure, unstable arrhythmia and CVA. Results: Amongst 109 patients, 55% were male, mean age was 61.7 years (standard deviation 17.7) and 73% of the patients were admitted from home. 21.1% (23) of the patients died during their stay. The mean CHA2DS2VASC score was 2.5 (SD 1.7). For every point increase in the CHA2DS2VASC score the odds of mortality increased by 78% (aOR 1.78; 95% CI; 1.07-2.97). The mean frailty score was 6.2 (SD 5.7). For every point increase in the frailty score the odds of mortality increased by 22% (aOR: 1.22; 95% CI 1.07-1.39) [Figure]. There was a trend between higher CHA2DS2VASC and frailty scores with worse CV outcomes during hospital stay but this did not meet statistical significance (aOR: 1.31; 95% CI 0.86-2.0, aOR: 1.04; CI 0.93-1.17 respectively). Conclusions: Higher CHA2DS2VASC and frailty scores are associated with increased risk of mortality. Although statistical significance was not reached for predicting CV outcomes, this was likely related to a small sample size. CHA2DS2VASC and frailty scores are a readily available and novel tool that can be used to predict mortality in hospitalized patients.
Abstract 17283: The Impact of Fetal Congenital Heart Disease on <i>In Vivo</i> Regional Brainstem Development
Authors: Yuanchiao Lu, Lily Carroll, Kushal Kapse, Catherine Lopez, Jessica Quistorff, Anita Krishnan, Gilbert Vezina, Mary Donofrio, Catherine Limperopoulos
Journal: Circulation (2020)

Introduction: Brain injury and delayed brain development have been reported in fetuses with congenital heart disease (CHD). While reduced volumes of fetal brain structures have been discovered, the shape alternations of the brainstem affected by CHD were not fully investigated. Hypothesis: We assessed the hypothesis that the morphology of the brainstem in CHD fetuses was altered when compared to healthy controls. Methods: A total of 146 pregnant women were recruited for this longitudinal observational study (99 controls and 47 CHD; median gestational age (GA) and range: 33.4 [24.4-39.1] weeks), in which 207 MRI scans were performed. Single shot fast spin echo T2-weighted images were acquired on a 1.5T GE MRI scanner. Anatomical landmarks of brainstem were manually identified on 1 mm 3 isotropic 3D reconstructed images using RView software. Anterior-posterior and transverse diameters of mesencephalon, pons, and medullary were determined based on 12 landmarks on the midsagittal and coronal planes correspondingly. The inter-landmark distances and 2D areas enclosed by landmarks on the midsagittal plane of the two groups were analyzed using generalized estimating equations, adjusting for GA and fetal gender. Results: Results indicated lower regional anterior-posterior diameters of the pons in CHD fetuses [landmarks 2-3, 2-6, 3-4, and 4-6 ( p-values &lt;0.05)]. The 2D areas enclosed by landmarks on the midsagittal plane were overall smaller in CHD fetuses (control: 183±10 mm 2 ; CHD: 175±10 mm 2 ; p =0.016). No differences in transverse diameters were observed between control and CHD fetuses on the three coronal planes. All measured diameters and areas were significantly increased with advancing GA ( p-values &lt;0.05), while no gender differences were detected. Conclusions: We report for the first time impaired regional growth of the pons in fetuses with CHD. The pons may play a role in altered emerging cerebral-cerebellar structure and functional connections in fetal CHD.