tbuckley/cabot-search huggingface dataset:
Assessing the Causal Relationships Between Insulin Resistance and Hyperuricemia and Gout Using Bidirectional Mendelian Randomization
Authors: Natalie McCormick, Mark J. O’Connor, Chio Yokose, Tony R. Merriman, David B. Mount, Aaron Leong, Hyon K. Choi
Journal: Arthritis & Rheumatology (2021)

Hyperuricemia is closely associated with insulin resistance syndrome (and its many cardiometabolic sequelae); however, whether they are causally related has long been debated. We undertook this study to investigate the potential causal nature and direction between insulin resistance and hyperuricemia, along with gout, by using bidirectional Mendelian randomization (MR) analyses.We used genome-wide association data (n = 288,649 for serum urate [SU] concentration; n = 763,813 for gout risk; n = 153,525 for fasting insulin) to select genetic instruments for 2-sample MR analyses, using multiple MR methods to address potential pleiotropic associations. We then used individual-level, electronic medical record-linked data from the UK Biobank (n = 360,453 persons of European ancestry) to replicate our analyses via single-sample MR analysis.Genetically determined SU levels, whether inferred from a polygenic score or strong individual loci, were not associated with fasting insulin concentrations. In contrast, genetically determined fasting insulin concentrations were positively associated with SU levels (0.37 mg/dl per log-unit increase in fasting insulin [95% confidence interval (95% CI) 0.15, 0.58]; P = 0.001). This persisted in outlier-corrected (β = 0.56 mg/dl [95% CI 0.45, 0.67]) and multivariable MR analyses adjusted for BMI (β = 0.69 mg/dl [95% CI 0.53, 0.85]) (P < 0.001 for both). Polygenic scores for fasting insulin were also positively associated with SU level among individuals in the UK Biobank (P < 0.001). Findings for gout risk were bidirectionally consistent with those for SU level.These findings provide evidence to clarify core questions about the close association between hyperuricemia and insulin resistance syndrome: hyperinsulinemia leads to hyperuricemia but not the other way around. Reducing insulin resistance could lower the SU level and gout risk, whereas lowering the SU level (e.g., allopurinol treatment) is unlikely to mitigate insulin resistance and its cardiometabolic sequelae.
Pandemic lessons from India
Authors: K Srinath Reddy
Journal: BMJ (2021)

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Abstract 13114: <i> P22 <sup>phox</sup> </i> Protects the Heart Against Pressure Overload
Authors: Yasuki Nakada, Wataru Mizushima, Yanfei Yang, Peiyong Zhai, Shinichi Oka, Nadezhda Fefelova, Lai-hua Xie, Tong Liu, Hong Li, Junichi Sadoshima
Journal: Circulation (2020)

Introduction: p22 phox forms a complex with NADPH oxidases, major sources of O 2 - and H 2 O 2 . However, the role of p22 phox during stress remains to be elucidated. Purpose: To investigate the role of endogenous p22 phox during pressure overload (PO). Methods and Results: The level of p22 phox protein in isolated cardiomyocytes after 4 weeks of transverse aortic constriction (TAC) was significantly higher than after sham operation (1.7-fold, p&lt;0.05). The cardiac phenotype of cardiac-specific p22 phox knockout ( p22 phox cKO) mice was normal at baseline. However, four weeks after TAC, p22 phox cKO mice exhibited a lower left ventricular ejection fraction (32.0±10.0 vs 53.2±8.4%, p&lt;0.05), a higher lung weight to tibial length ratio (23.0±6.0 vs 13.1±6.6, p&lt;0.05), and more interstitial fibrosis (6.1±1.0 vs 4.4±1.1%, p&lt;0.05) than control mice, indicating that the loss of p22 phox exacerbates TAC-induced cardiac dysfunction. The level of oxidative stress in the heart, evaluated by dityrosine immunoblot, was significantly lower in p22 phox cKO mice than in control mice (0.71±0.04 vs 1.00±0.04, p&lt;0.01). The peak Ca 2+ amplitude in isolated cardiomyocytes was lower in p22 phox cKO mice than in control mice at baseline (2.4±0.1 vs 3.0±0.2, p&lt;0.01). Although mRNA expression of SERCA2a did not differ, there was significantly less SERCA2a protein in p22 phox cKO mice than in control mice (0.62±0.10 vs 1.00±0.23, p&lt;0.01) at baseline. The amount of biotinylated iodoacetamide labeled SERCA2a was significantly smaller in p22 phox cKO hearts than in control mouse hearts (0.4-fold, p&lt;0.01), indicating that cysteine residues in SERCA2a are oxidized to a greater extent in p22 phox cKO hearts than in control mouse hearts. Since cysteine oxidation decreases the stability of SERCA2a, our results suggest that p22 phox stabilizes SERCA2a by preventing cysteine oxidation. Conclusions: Endogenous p22 phox is protective against PO, possibly by maintaining SERCA2a stability.
Abstract 16567: Long-Term Vascular Function in CTO Recanalization. A Randomized Clinical Trial of Ticagrelor vs. Clopidogrel
Authors: Juan Jose Rodriguez Arias, Josep Gomez-Lara, Juan Caballero-Borrego, Luis Ortega-Paz, Luis Teruel, Teresa Gil-Jimenez, Loreto Oyarzabal, Rafael Romaguera, Gerardo Moreno Terribas, Joan Antoni Gomez, Manel Sabate, Salvatore Brugaletta
Journal: Circulation (2020)

Background: Coronary vascular function of a chronic coronary total occlusion (CTO) immediately after recanalization is known to be poor and to be partially improved by pre-treatment with loading dose of ticagrelor vs. clopidogrel. It is unknown if this vascular dysfunction is maintained at long-term follow-up and may be improved by 1-year dual antiplatelet therapy (DAPT) with ticagrelor vs. clopidogrel. Methods: The TIGER is a prospective, open-label, two parallel-group controlled clinical trial, which 1:1 randomized 50 CTO patients to pre-PCI loading dose and subsequent 1-year DAPT with ticagrelor vs. clopidogrel. Coronary blood flow (CBF) under stepwise adenosine infusion was assessed after drug loading dose and at follow-up and compared between the two drug groups, adjusting for time of follow-up. Results: Out of 50 patients with index CBF evaluation, 38 (76%) patients underwent angiographic follow-up (23 and 15 at 1 and 3-year, respectively). A higher CBF area under the curve (AUC), already observed after loading dose in ticagrelor vs. clopidogrel group (p=0.027), was maintained at follow-up (AUC 34815.22±24206.06 vs. AUC 22712.47±13768.95; p=0.071). Specifically, whereas high ticagrelor loading dose-related CBF was sustained at follow-up (p=0.933), clopidogrel loading dose-related CBF increased at follow-up (p=0.039). Conclusion: The TIGER trial showed that DAPT with ticagrelor may maintain a higher CBF in a recanalized CTO as compared to clopidogrel, whose treated patients exhibit a lower CBF immediately after PCI with slight increase at follow-up. The clinical value of such sustained higher coronary flow should be evaluated in a larger group of patients.
Audio Interview: Vaccination in Nursing Homes and New Pulmonary/Critical Care Research
Authors: Eric J. Rubin, Lindsey R. Baden, Jeffrey M. Drazen, Darren B. Taichman, Stephen Morrissey
Journal: New England Journal of Medicine (2021)

Vaccination in Nursing Homes and New Pulmonary/Critical Care Research In this audio interview conducted on May 18, 2021, the editors discuss the effectiveness of Covid vaccination in nursing homes ...
Abstract 15970: Risk of Heart Failure Preserved Ejection Fraction in Obstructive Sleep Apnea: A Single Center Retrospective Analysis
Authors: Bertrand Ebner, Diego Celli, Morgan Karetnick, Neal Olarte, Marina D Byer, Jennifer Maning, Edgar Acuna Morin, Kunal Kapoor, Vijay Mehta, Beteal Ashinne, Gerardo Zablah, Camilo A Gomez, Eduardo de Marchena
Journal: Circulation (2020)

Background: Inherent characteristics of patients with Obstructive Sleep Apnea (OSA), such as age, obesity, diabetes and hypertension increase the risk for cardiovascular diseases including heart failure (HF). Herein, we sought to elucidate if there is an increased likelihood of having heart failure with preserved ejection fraction (HFpEF) as OSA severity increases. Furthermore, we correlated a validated H2FpEF score system in this cohort with clinical and imaging findings for HFpEF. Results: Out of 585 charts reviewed from patients diagnosed with OSA, a total of 108 patients with a concomitant transthoracic echocardiogram (TTE) and electrocardiogram performed were identified. The median age was 59 years old with 55.6% being males and Hispanic predominance 64.5%. The comorbidities found in our cohort involved hypertension (63.9%), diabetes mellitus (30.6%), coronary artery disease (15.7%), HF (13%), atrial fibrillation (8.3%), and stroke (7.4%). Mean BMI was 32.48 kg/m 2 and average neck size 16.02 inches. TTE findings demonstrated an average ejection fraction of 58±7% and mean pulmonary artery systolic pressure of 24±10 mmHg. OSA severity distribution is shown in Table 1. No significant association was found between grade of severity of OSA with clinical diagnosis of HF, nor with diastolic dysfunction by TTE. The average probability of HFpEF by validated score was 50%, and the distribution of the score was the same across severity of OSA (p=0.260). Pearson’s correlation showed a significant positive relationship between age, BMI and PASP, and H2FpEF score (p&lt;0.01 for all), however, no relation was found when correlating with neck size, apnea-hypopnea index and mean oxygen saturation. Conclusion: Although patients with OSA might have a higher H2FpEF score due to inherent characteristics, the clinical diagnosis of HFpEF in our population was lower than expected by H2FpEF score, in which the degree of severity was not associated with a higher H2FpEF score.
The Effects of Chronic Exposure to Ambient Traffic-Related Air Pollution on Alzheimer’s Disease Phenotypes in Wildtype and Genetically Predisposed Male and Female Rats
Authors: Kelley T. Patten, Anthony E. Valenzuela, Christopher Wallis, Elizabeth L. Berg, Jill L. Silverman, Keith J. Bein, Anthony S. Wexler, Pamela J. Lein
Journal: Environmental Health Perspectives (2021)

BACKGROUND: Epidemiological data link traffic-related air pollution (TRAP) to increased risk of Alzheimer's disease (AD).Preclinical data corroborating this association are largely from studies of male animals exposed acutely or subchronically to high levels of isolated fractions of TRAP.What remains unclear is whether chronic exposure to ambient TRAP modifies AD risk and the influence of sex on this interaction.OBJECTIVES: This study sought to assess effects of chronic exposure to ambient TRAP on the time to onset and severity of AD phenotypes in a preclinical model and to determine whether sex or genetic susceptibility influences outcomes.METHODS: Male and female TgF344-AD rats that express human AD risk genes and wildtype littermates were housed in a vivarium adjacent to a heavily trafficked tunnel in Northern California and exposed for up to 14 months to filtered air (FA) or TRAP drawn from the tunnel and delivered to animals unchanged in real time.Refractive particles in the brain and AD phenotypes were quantified in 3-, 6-, 10-, and 15-month-old animals using hyperspectral imaging, behavioral testing, and neuropathologic measures.RESULTS: Particulate matter (PM) concentrations in TRAP exposure chambers fluctuated with traffic flow but remained below 24-h PM with aerodynamic diameter less than or equal to 2.5 micrometers (PM 2:5 ) U.S. National Ambient Air Quality Standards limits.Ultrafine PM was a predominant component of TRAP.Nano-sized refractive particles were detected in the hippocampus of TRAP animals.TRAP-exposed animals had more amyloid plaque deposition, higher hyperphosphorylated tau levels, more neuronal cell loss, and greater cognitive deficits in an age-, genotype-, and sexdependent manner.TRAP-exposed animals also had more microglial cell activation, but not astrogliosis.DISCUSSION: These data demonstrate that chronic exposure to ambient TRAP promoted AD phenotypes in wildtype and genetically susceptible rats.TRAP effects varied according to age, sex, and genotype, suggesting that AD progression depends on complex interactions between environment and genetics.These findings suggest current PM 2:5 regulations are insufficient to protect the aging brain.
BMA demands urgent meeting with health secretary over GP appointments row
Authors: Gareth Iacobucci
Journal: BMJ (2021)

The BMA has urged the government to provide clarity to general practices and patients about the expectation to deliver more face-to-face appointments.

In a letter sent to England’s health secretary, Matt Hancock, on 18 May, Richard Vautrey, chair of the BMA’s General Practitioners Committee, wrote of “widespread anger, frustration and disappointment” in the workforce after NHS England and NHS Improvement (NHSE/I) wrote to practices last week12 instructing them to return to offering face-to-face appointments without prior triage, after negative media coverage about the issue.

Vautrey said that practices were feeling “increasingly demoralised” by suggestions that they had been failing …
My Mother Schedules Heart Surgery
Authors: Jeneva Stone
Journal: JAMA (2021)

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2018年の小児におけるヒトメタニューモウイルスと関連した急性下気道感染の世界的負担: 系統的レビューとモデリング研究【JST・京大機械翻訳】
Authors: Wang Xin, Li You, Deloria-Knoll Maria, Madhi Shabir A, Cohen Cheryl, Ali Asad, Basnet Sudha, Bassat Quique, Brooks W Abdullah, Chittaganpitch Malinee, Echavarria Marcela, Fasce Rodrigo A, Goswami Doli, Hirve Siddhivinayak, Homaira Nusrat, Howie Stephen R C, Kotloff Karen L, Khuri-Bulos Najwa, Krishnan Anand, Lucero Marilla G, Lupisan Socorro, Mira-Iglesias Ainara, Moore David P, Moraleda Cinta, Nunes Marta, Oshitani Histoshi, Owor Betty E, Polack Fernando P, O’Brien Katherine L, Rasmussen Zeba A, Rath Barbara A, Salimi Vahid, Scott J Anthony G, Simoees Eric A F, Strand Tor A, Thea Donald M, Treurnicht Florette K, Vaccari Linda C, Yoshida Lay-Myint, Zar Heather J, Campbell Harry, Nair Harish
Journal: The Lancet Global Health (2021)
The importance of ongoing international surveillance for Creutzfeldt–Jakob disease
Authors: Neil Watson, Jean-Philippe Brandel, Alison Green, Peter Hermann, Anna Ladogana, Terri Lindsay, Janet Mackenzie, Maurizio Pocchiari, Colin Smith, Inga Zerr, Suvankar Pal
Journal: Nature Reviews Neurology (2021)

Creutzfeldt–Jakob disease (CJD) is a rapidly progressive, fatal and transmissible neurodegenerative disease associated with the accumulation of misfolded prion protein in the CNS. International CJD surveillance programmes have been active since the emergence, in the mid-1990s, of variant CJD (vCJD), a disease linked to bovine spongiform encephalopathy. Control measures have now successfully contained bovine spongiform encephalopathy and the incidence of vCJD has declined, leading to questions about the requirement for ongoing surveillance. However, several lines of evidence have raised concerns that further cases of vCJD could emerge as a result of prolonged incubation and/or secondary transmission. Emerging evidence from peripheral tissue distribution studies employing high-sensitivity assays suggests that all forms of human prion disease carry a theoretical risk of iatrogenic transmission. Finally, emerging diseases, such as chronic wasting disease and camel prion disease, pose further risks to public health. In this Review, we provide an up-to-date overview of the transmission of prion diseases in human populations and argue that CJD surveillance remains vital both from a public health perspective and to support essential research into disease pathophysiology, enhanced diagnostic tests and much-needed treatments. Despite the declining incidence of variant Creutzfeldt–Jakob disease, prion diseases remain a threat to public health. In this Review, Suvankar Pal and colleagues provide an up-to-date overview of the transmission of prion diseases in human populations and argue that CJD surveillance is still vital.
Abstract 2203: “One-Beat Whole Heart Coronary CT-Angiography” Using the 256-Multislice CT
Authors: Akira Kurata, Teruhito Mochizuki, Shin-ichiro Mori, Teruhito Kido, Shuji Tanada, Masahiro Endo, Kazuhiro Katada, HIroshi Higashino, Makoto Saito, Akiyoshi Ogimoto, Tomoaki Ohtsuka, Hideki Okayama, Jitsuo Higaki
Journal: Circulation (2006)

PURPOSE: Since the 2nd spec 256-detector row computed tomography (256CT) covers 12.8 cm along z-axis (0.5mm slice thickness x 256-slice), it covers whole heart within one rotation (0.5 sec). The ai...
Renin Cell Baroreceptor, a Nuclear Mechanotransducer Central for Homeostasis
Authors: Hirofumi Watanabe, Brian C. Belyea, Robert L. Paxton, Minghong Li, Bette J. Dzamba, Douglas W. DeSimone, R. Ariel Gomez, Maria Luisa S. Sequeira-Lopez
Journal: Circulation Research (2021)

[Figure: see text].
Abstract 13029: Sonothrombolysis Improves Left Atrial Pressure and Volume in Patients With ST Elevation Acute Myocardial Infarction
Authors: Hsu Po Chiang, Miguel Aguiar, Bruno Tavares, Wilson Mathias, Bruno C Borges, Mucio Oliveira, Alexandre d Soeiro, Jose C Nicolau, Joao Sbano, Andrew M Goldsweig, Roberto Kalil Filho, Jose A Ramires, Thomas R Porter, Jeane M Tsutsui
Journal: Circulation (2020)

Introduction: Preclinical studies in ST elevation myocardial infarction (STEMI) indicate that high mechanical index impulses guided with transthoracic diagnostic ultrasound associated with intravenously administered microbubbles results in the dissolution of the thrombus (sonothrombolysis), improving coronary microcirculation and epicardial coronary recanalization rate. Hypothesis: Left atrial (LA) echocardiographic parameters are compromised in STEMI and can be accurately measured by two-dimensional echocardiography. To study the effect of sonotrombolysis on the LA pressure and volume we propose our study. Methods: A total of 100 patients were randomized, 50 for the control group and 50 for the therapy group. Echocardiographic analysis of LA pressure and volume were performed immediately before and after percutaneous coronary intervention (PCI), 72 hours, 1 month and 6 months of follow-up. LA pressure was classified in normal or elevated, depending on the grade of left ventricular diastolic disfunction (DD): normal diastolic function and DD grade 1 have normal LA pressure, and DD grades 2 and 3 have elevated LA pressure, according to the American and European guideline. LA volume was evaluated by Simpson method and indexed to the body surface area. Results: The LA pressure and volume had lower values in the therapy group after 6 months of PCI. The comparison of LA pressure between the therapy and control groups respectively was: before PCI (72% vs. 70% normal; 28% vs. 30% elevated; p=0.826), after PCI (68% vs. 65% normal; 32% vs. 35% elevated; p=0.777), 72 hours (75% vs. 62% normal; 25% vs. 38% elevated; p=0.147), 1 month (68% vs. 52% normal; 32% vs. 48% elevated; p=0.123) and 6 months (84% vs. 64% normal; 16% vs. 36% elevated; p=0.035). The comparison of LA volumes between the therapy and control groups respectively was: before PCI (19.0±6.2 vs. 22.4±9.8 ml/m 2 ; p=0.061), after PCI (22.8±7.9 vs. 24.4±12.1 ml/m 2 ; p=0.469), 72 hours (25.9±8.5 vs. 26.4±12.7 ml/m 2 ; p=0.815), 1 month (27.2±8.3 vs. 29.1±13.1 ml/m 2 ; p=0.410) and 6 months (26.7±7.5 vs. 33.1±14.9 ml/m 2 ; p=0.013). Conclusions: The use of sonothrombolysis as adjuvant therapy in STEMI patients results in better values of LA pressure and volume, demonstrating the benefit of using this new therapy.
肺送達による肺炎の治療増強のためのマクロファージ食作用を回避するためのフムアリールジケトピペラジンに基づく発泡微粒子【JST・京大機械翻訳】
Authors: Wang Qiyue, Shen Yan, Mi Gujie, He Dongsheng, Zhang Yue, Xiong Yerong, J Webster Thomas, Tu Jiasheng
Journal: Biomaterials (2020)
Abstract 12999: Correcting the Current: Modeling the Hemodynamic Impact of Transcatheter Aortic Valve Replacement in Multiple Valvular Heart Disease Precipitating Cardiogenic Shock
Authors: Michael I Brener, Amisha Patel, Torsten Vahl, Nadira Hamid, Melana Yuzefpolskaya, Daniel Burkhoff, Susheel K Kodali
Journal: Circulation (2020)

Introduction: Multiple valvular heart disease (mVHD) caused by mixed stenotic and regurgitant lesions involving at least two valves is a common condition which is poorly understood and challenging to manage. Herein, we simulate the hemodynamics of a patient with mVHD before and after transcatheter aortic valve replacement (TAVR) to better understand the physiology of this complex disease. Case: A 67-year-old man with celiac enteropathy presented to a local hospital with dyspnea, hypotension, and oliguria. Echocardiography revealed a dilated left ventricle (end-diastolic diameter [LVEDD] 6.7 cm) with an ejection fraction (EF) of 20% and multiple severe valvulopathies, including aortic stenosis (AS), aortic regurgitation (AR), and mitral regurgitation (MR). Right heart catheterization revealed a low cardiac index (1.76 L/min/m 2 ) and a high wedge pressure (36 mmHg) with V-waves exceeding 50 mmHg. The patient’s severe AR precluded mechanical circulatory support, so TAVR was emergently performed in the setting of worsening cardiogenic shock (CS) with a 29 mm self-expanding bioprosthesis via transfemoral access. Valve deployment was successfully guided by fluoroscopy and transthoracic echocardiography alone. CS resolved in the subsequent 48 hours, and at 3-month follow-up, his LV EF returned to 55% and LVEDD decreased to 4.4 cm. LV pressure-volume loops pre- and post-TAVR were generated using a cardiovascular physiology simulator (Fig. 1). TAVR’s correction of the patient’s severe AS and AR produced immediate energetic benefits, with pressure-volume area declining 13% and cardiac power output increasing 2.24-fold. Conclusions: This challenging case and the accompanying pressure-volume analysis affirms the feasibility of emergent TAVR in highly selected patients, the procedure’s ability to immediately improve ventricular performance, and the LV’s capacity to remodel when operating under more physiologic loading conditions.