tbuckley/cabot-search huggingface dataset:
Potassium 2-(1-hydroxypentyl)-benzoate improves depressive-like behaviors in rat model
Authors: Hao Ma, Weiping Wang, Shaofeng Xu, Ling Wang, Xiaoliang Wang
Journal: Acta Pharmaceutica Sinica B (2018)

Potassium 2-(1-hydroxypentyl)-benzoate (PHPB) is a novel drug candidate for acute ischemic stroke. PHPB has been also shown to be beneficial for some neurodegenerative diseases. In this study, we demonstrated that PHPB improved depressive-like behaviors induced by chronic unpredictable mild stress (CUMS) in rats. Male SD rats were subjected to the stress for five weeks. PHPB (30 and 100 mg/kg) or fluoxetine (FLX 10 mg/kg, as positive control) was administered orally from the third week in CUMS procedure. The behavioral tests were applied and then the biochemical studies were carried out. PHPB or FLX treatment rescued the behavioral deficiency in CUMS-exposed rats. Meanwhile, PHPB normalized the enhanced level of serum corticosterone, improved hippocampal and serum BDNF levels, as well as p-CREB level in hippocampus. In addition, PHPB could reverse the reduced level of extracellular 5-HT and its metabolite 5-HIAA in prefrontal cortex (PFC) of depressed rats. In summary, our results showed that PHPB improved depression-like behaviors in CUMS-exposed rats. The mechanisms might relate to the reverse of neurotrophic disturbance in the brain, reducing excessive HPA axis response and facilitating the release of 5-HT.
Abstract P259: Genetic Risk Score, Lifestyle Cardiovascular Risk Score, and Myocardial Infarction in Hispanics
Authors: Mercedes Sotos-Prieto, Ana Baylin, Hannia Campos, Lu Qi, Josiemer Mattei
Journal: Circulation (2016)

Background: A genetic risk score (GRS) and a lifestyle cardiovascular risk score (LCRS) have been independently associated with myocardial infarction (MI) in Hispanics. However, it is unknown if there is an interaction or a joint association between these scores. Objectives: To assess the interactive and joint associations between a GRS and a LCRS, as well as each individual lifestyle risk factor on the likelihood of MI. Methods: Data included 1534 Costa Rican adults with nonfatal acute MI and 1534 without MI participating in a case-control study. The GRS was calculated by summing the number of the top three MI-associated risk alleles. The LCRS was calculated using the estimated coefficients as weights for each lifestyle risk factors (diet, physical activity, smoking, waist:hip ratio, low or high alcohol intake, and low socioeconomic status). Conditional logistic regression was used to calculate odds ratios (OR), adjusting for age, sex, and area of residence (matching condition), and to test for interaction and joint association. Results: The multivariable OR for MI was 1.14 (95% CI 1.07, 1.22) per GRS unit and 2.72 (2.33, 3.91) per LCRS unit. Participants in the highest tertile of the GRS and highest tertile of the LCRS had higher odds of MI (5.43 [3.80, 7.76]) compared to those in the lowest category. A significant joint association was detected (p &lt;0.0001), while the interaction term was non-significant (p=0.44). Similar results were found for the joint association between GRS and each individual lifestyle component: joint odds for highest risk category vs. lowest was 2.16 (1.53, 3.04) for diet, 1.85 (1.33, 2.59) for physical activity, 3.31 (2.45, 4.48) for smoking, 1.32 (0.92, 1.89) for alcohol, 2.84 (1.82, 4.42) for waist:hip ratio, and 1.86 (1.29, 2.69) for socioeconomic status. Conclusion: Although lifestyle risk factors and genetics contribute independently and in combination to the odds of MI, lifestyle risk factors were stronger among Costa Ricans. Efforts to improve lifestyle behaviors in this population, regardless of genetic susceptibility, may help prevent MI and related heart conditions.
Abstract P058: Diabetes, Frequency of Exercise, and Mortality Over 12 Years
Authors: Hyeon Chang Kim, Woo Young Shin, Taehee Lee, Da-Hye Jeon
Journal: Circulation (2018)

The goal of this study was to analyze the relationship between exercise frequency and all-cause mortality for individuals diagnosed with and without diabetes mellitus (DM). We analyzed data for 505,677 participants (53.9% men) in the National Health Insurance Service - National Health Screening (NHIS-HEALS) cohort. The study endpoint variable was all-cause mortality. Frequency of exercise and covariates including age, sex, smoking status, household income, blood pressure, fasting glucose, body mass index, total cholesterol, and Charlson Comorbidity Index were determined at baseline. Cox’s proportional hazard regression models were developed to assess the effects of exercise frequency (0, 1-2, 3-4, 5-6, and 7 days per week) on mortality, separately in individuals with and without DM. We found a U-shaped association between exercise frequency and mortality in individuals with and without DM. However, the frequency of exercise associated with the lowest risk of all-cause mortality was 3-4 times per week (hazard ratio [HR] 0.69; 95% confidence interval [CI]: 0.65-0.73) in individuals without DM, and 5-6 times per week in those with DM (HR 0.93; 95%: CI 0.78-1.10). A moderate frequency of exercise may reduce mortality regardless of the presence or absence of DM; however, when compared to those without the condition, people with DM may need to exercise more often.
Beneficial effects of lifestyle intervention in non-obese patients with non-alcoholic fatty liver disease
Authors: Vincent Wai-Sun Wong, Grace Lai-Hung Wong, Ruth Suk-Mei Chan, Sally She-Ting Shu, Bernice Ho-Ki Cheung, Liz Sin Li, Angel Mei-Ling Chim, Carmen Ka-Man Chan, Julie Ka-Yu Leung, Winnie Chiu-Wing Chu, Jean Woo, Henry Lik-Yuen Chan
Journal: Journal of Hepatology (2018)
Abstract 13136: Physically Frail Adults With Heart Failure Have Worse Physical and Affective Symptoms
Authors: Quin E Denfeld, James O Mudd, Kerri Winters-Stone, Shirin O Hiatt, Jill M Gelow, Christopher V Chien, Christopher S Lee
Journal: Circulation (2016)

Introduction: Heart failure (HF) is a complex clinical syndrome associated with significant symptom burden; however, our understanding of the relationship between symptoms and physical frailty in HF is limited. Hypothesis: There is a significant relationship between physical frailty and symptoms among adults with HF. Methods: A sample of adults with symptomatic HF were enrolled in a cross-sectional study. Physical frailty was measured according to the five dimensions of the Frailty Phenotype Criteria: shrinking, weakness, slowness, physical exhaustion and low physical activity. Physical symptoms were measured with the HF Somatic Perception Scale-Dyspnea subscale, the Epworth Sleepiness Scale, and the Brief Pain Inventory short form. Affective symptoms were measured with the Patient Health Questionnaire-9 and the Brief Symptom Inventory-Anxiety scale. Generalized linear modeling was used to quantify associations between physical frailty and symptoms, controlling for Seattle HF Model (SHFM) score. Results: The mean age of the sample ( n = 50) was 57.5±9.7 years, 66% were male, 92% had New York Heart Association class III/IV HF, and 66% had non-ischemic etiology. Half of the sample (50%) had physical frailty. Those with physical frailty had more than twice the level of dyspnea ( p = 0.001), 73% worse wake disturbances ( p &lt; 0.001), and 86% worse depressive symptoms ( p = 0.001) compared with those not physically frail, adjusting for SHFM score. There were no differences in pain or anxiety. Conclusions: Physically frail adults with HF have considerably worse dyspnea, wake disturbances, and depression. Targeting physical frailty may help identify and improve physical and affective symptoms in HF.
What Once Was
Authors: Hilary Boyd
Journal: Annals of Internal Medicine (2018)

On Being a Patient21 August 2018What Once WasHilary Boyd, MA, MCWHilary Boyd, MA, MCWAuckland District Health Board, Auckland, New Zealand (H.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M18-0704 Audio Reading - “What Once Was” Audio. Virginia L. Hood, MD, reads "What Once Was," by H. Boyd. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail “Imagine your hero,” Kate says. You are sitting in a bar, cradling your third glass of wine, desperate for some sort of salvation. “Mine is a big, hunky fireman. He lives inside my chest and helps me through the tough times.” Kate pauses and downs her glass. “Sounds silly saying it out loud … but it really does work.”She gives you that poor-you-your-life-must-be-shit smile. You get that a lot nowadays. It's a brilliant idea, this hero thing. You swipe a pen from the barman; scrawl ideas on a napkin—fireman, policeman, Superman, God—cross them out. Another wine.Mr. Bean.Mrs. ... Author, Article, and Disclosure InformationAffiliations: Auckland District Health Board, Auckland, New Zealand (H.B.)Corresponding Author: Hilary Boyd, MA, MCW, Auckland District Health Board, Private Bag 92024, Auckland Mail Centre, Auckland 1142, New Zealand; e-mail, [email protected]govt.nz. PreviousarticleNextarticle Advertisement Audio Reading - “What Once Was” Audio. Virginia L. Hood, MD, reads "What Once Was," by H. Boyd. Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 21 August 2018Volume 169, Issue 4Page: 260-261KeywordsCyclophosphamideFallsHeroinMouthNursesRacial and ethnic issuesSleepTeaThoraxWine ePublished: 21 August 2018 Issue Published: 21 August 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Abstract 14601: Vegetarianism is Independently Associated With Lower Risk of Left Ventricular Diastolic Dysfunction and Stage B Heart Failure Burden
Authors: Ramdas G Pai, Padmini Varadarajan, Brice Jabo, Andrew Maschak, Patti Herring, Gary E Fraser, Synnpve F Knutsen
Journal: Circulation (2015)

Introduction: Heart failure (HF) affects about 6 million Americans at an annual direct cost of $40 billion. Left ventricular (LV) diastolic dysfunction and stage B HF are predictors of clinical HF and reduction of stage B HF burden may help reduce HF disease burden in the community. In our Adventist Health Study-2 (AHS-2) of 96,000 subjects, a vegetarian compared to a non-vegetarian diet was associated with lower body mass index, and risk of diabetes and hypertension despite similar caloric intake. Hypothesis: We hypothesized that vegetarianism would also lead to a lower risk of LV diastolic dysfunction and stage B HF. Methods: We invited a random sample of 206 subjects from AHS-2 stratified by diet (vegetarians, lacto-ovo vegetarians, pescovegetarians and nonvegetarians), aged &gt;60 years and living within 50 miles of Loma Linda for a clinic visit consisting of a history, anthropometrics, blood pressure measurement, food frequency questionnaire and a full echocardiogram. LV volume, EF, wall motion, diastolic function and mass and left atrial size were assessed based on guidelines of American society of Echocardiography. Results: The mean age was 74 (10) years, 49% were males and subjects were equally distributed in 4 food groups. LV diastolic dysfunction was present in 60%, LV hypertrophy in 10%, LVEF &lt;50% in 5% and increased left atrial volume index in 45% of the subjects. After adjusting for age, gender, race, body surface area, prevalent MI, diabetes and hypertension, a vegan diet (no animal products), compared to non-vegetarian diet, was associated with a lower prevalence of LV diastolic dysfunction (OR 0.42, 95% CI 0.24-0.73) and LV hypertrophy (OR 0.30, 95% CI 0.08-0.86) Vegetarians also had a lower number of stage A risk factors and stage B components (p&lt;0.05). There was a trend towards graded increase in risk of stage B HF with increasing degree of nonvegetarianism. Conclusions: A vegan diet is independently associated with lower risk of LV diastolic dysfunction, LV mass and stage B HF burden.
Upregulation of lncRNA ADAMTS9-AS2 Promotes Salivary Adenoid Cystic Carcinoma Metastasis via PI3K/Akt and MEK/Erk Signaling
Authors: Shule Xie, Xin Yu, Yingru Li, Hanyu Ma, Song Fan, Weixiong Chen, Guokai Pan, Weiwei Wang, Hanqing Zhang, Jinsong Li, Zhaoyu Lin
Journal: Molecular Therapy (2018)

Neurotropic infiltrative growth and distant metastasis are the main causes of death in salivary adenoid cystic carcinoma (SACC) patients. Long noncoding RNAs (lncRNAs) are involved in many human neoplasms, however, their potential roles in SACC are unclear. In our study, we found that ADAM metallopeptidase with thrombospondin type 1 motif, 9 (ADAMTS9) antisense RNA 2 (ADAMTS9-AS2) was significantly upregulated in SACC patients with metastasis and SACC-lung metastasis (LM) cells. Moreover, ADAMTS9-AS2 expression was closely associated with the prognosis and distant metastasis in SACC patients. Next, we found that c-myc could specifically bind to the promoter of ADAMTS9-AS2 and activated its transcription. Knockdown of ADAMTS9-AS2 significantly inhibited migration and invasion of SACC cells in vitro and distant lung metastasis in vivo. Furthermore, ADAMTS9-AS2, which mainly expressed in the cytoplasm, shared microRNA (miRNA) response elements with Integrin α6 (ITGA6). Overexpression of ADAMTS9-AS2 competitively bound to miR-143-3p that inhibited ITGA6 from miRNA-mediated degradation, and thus it activated the activity of PI3K/Akt and MEK/Erk signaling and facilitated SACC metastasis. In summary, ADAMTS9-AS2 promotes migration and invasion in SACC by competing with miR-143-3p. This sheds a new insight into the regulation mechanism of ADAMTS9-AS2, and it provides a possible application for the SACC treatment. Neurotropic infiltrative growth and distant metastasis are the main causes of death in salivary adenoid cystic carcinoma (SACC) patients. Long noncoding RNAs (lncRNAs) are involved in many human neoplasms, however, their potential roles in SACC are unclear. In our study, we found that ADAM metallopeptidase with thrombospondin type 1 motif, 9 (ADAMTS9) antisense RNA 2 (ADAMTS9-AS2) was significantly upregulated in SACC patients with metastasis and SACC-lung metastasis (LM) cells. Moreover, ADAMTS9-AS2 expression was closely associated with the prognosis and distant metastasis in SACC patients. Next, we found that c-myc could specifically bind to the promoter of ADAMTS9-AS2 and activated its transcription. Knockdown of ADAMTS9-AS2 significantly inhibited migration and invasion of SACC cells in vitro and distant lung metastasis in vivo. Furthermore, ADAMTS9-AS2, which mainly expressed in the cytoplasm, shared microRNA (miRNA) response elements with Integrin α6 (ITGA6). Overexpression of ADAMTS9-AS2 competitively bound to miR-143-3p that inhibited ITGA6 from miRNA-mediated degradation, and thus it activated the activity of PI3K/Akt and MEK/Erk signaling and facilitated SACC metastasis. In summary, ADAMTS9-AS2 promotes migration and invasion in SACC by competing with miR-143-3p. This sheds a new insight into the regulation mechanism of ADAMTS9-AS2, and it provides a possible application for the SACC treatment.
Drawing the Line on Prophylactic Aortic Replacement
Authors: Thoralf M. Sundt
Journal: JAMA Network Open (2018)

Ming Hao Guo, MD; Jehangir J. Appoo, MDCM; Richard Saczkowski, MHSc, CPC; Holly N. Smith, MD; Maral Ouzounian, MD, PhD; Alexander J. Gregory, MD; Eric J. Herget, MD; Munir Boodhwani, MD, MSc, FRCSC
Abstract 17143: The Oncometabolite D2-hydroxyglutarate Redirects Krebs Cycle Flux and Impairs Contractile Function in Rodent Heart
Authors: Anja Karlstaedt, Xioatian Zhang, Radhika Khanna, Heidi Vitrac, Romain Hermancey, Hernan Vasquez, Margaret A. Goodell, Heinrich Taegtmeyer
Journal: Circulation (2016)

Introduction: Somatic mutations in the isocitrate dehydrogenase 1 and 2 (IDH1/2) have been described in a large subset of patients with acute myeloid leukemia (AML) and lead to increased production...
Abstract 16054: Ventricular-Arterial Coupling Biphasically Correlates to Ventricular Diastolic Chamber Stiffness in Children–Association With Aldosterone Activation
Authors: Satoshi Masutani, JeongHye Kim, Seiko Kuwata, Clara Kurishima, Hirofumi Saiki, Masanori Tamura, Hideaki Senzaki
Journal: Circulation (2014)

Introduction: Left ventricular–arterial coupling (LVAC), the ratio of end–systolic to effective arterial elastance (Ees/Ea), determines end–systolic pressure and stroke volume in a given preload. LV diastolic chamber stiffness (LV–K) is an important diastolic property to affect LV filling. However, the relationship between Ees/Ea and LV–K in children remains unestablished. Aldosterone (ALD) accelerates LV and arterial stiffening. Hypothesis: This study was undertaken to test the hypothesis that Ees/Ea may affect LV–K through ALD regulation in children. Methods: During catheterizations for children with biventricular circulation (N=75, median 2.5 years), blood samples for ALD were collected, and LV pressure and area relationships (PAR) were recorded using high-fidelity pressure–guidewire and echocardiographic AQ method during steady state and transient IVC occlusion. LV–K was obtained by dividing the pressure difference between LV minimal and end-diastolic pressure (EDP) by stroke volume. ALD levels were transformed into common logarithm. Results: Ees/Ea biphasically correlated to LV–K, which was approximated by downward convex parabola with a minimum at 0.9 of Ees/Ea (R=0.61, P&lt;0.0001). Ees/Ea also bipahsically correlated to log ALD, which was approximated by downward convex parabola with a minimum at 0.8 of Ees/Ea (R=0.45, P&lt;0.005). Moreover, LV–K linearly correlated to log ALD (R=0.38, P&lt;0.005). There was no significant relationship between LV–K and relative wall thickness. Conclusions: To our knowledge, this is the first study to demonstrate that Ees/Ea bipahsically correlated to LV–K and ALD. Dilated LV with low Ees/Ea accompanies elevated filling pressure and shows restrictive physiology with higher LV–K. On the other hand, when Ees/Ea is higher than normal range, this study indicates that there should be an increased LV diastolic stiffness which is not always associated with wall hypertrophy. Because LVAC abnormality may induce LV stiffening associated with ALD activation, chronic inhibition therapy of renin–angiotensin system to keep Ees/Ea within appropriate range may inhibit LV stiffening directly and through LVAC &amp; LV–K interaction.
Expression profile of translation initiation factor eIF2B5 in diffuse large B-cell lymphoma and its correlation to clinical outcome
Authors: Julia J. Unterluggauer, Katharina Prochazka, Peter V. Tomazic, Heinrich J. Huber, Rita Seeboeck, Karoline Fechter, Elisabeth Steinbauer, Verena Gruber, Julia Feichtinger, Martin Pichler, Marc A. Weniger, Ralf Küppers, Heinz Sill, Rudolf Schicho, Peter Neumeister, Christine Beham-Schmid, Alexander J. A. Deutsch, Johannes Haybaeck
Journal: Blood Cancer Journal (2018)
Sputum microbiota is predictive of long-term clinical outcomes in young adults with cystic fibrosis
Authors: Nicole Acosta, Alya Heirali, Ranjani Somayaji, Michael G Surette, Matthew L Workentine, Christopher D Sibley, Harvey R Rabin, Michael D Parkins
Journal: Thorax (2018)

Background Complex polymicrobial communities infect cystic fibrosis (CF) lower airways. Generally, communities with low diversity, dominated by classical CF pathogens, associate with worsened patient status at sample collection. However, it is not known if the microbiome can predict future outcomes. We sought to determine if the microbiome could be adapted as a biomarker for patient prognostication. Methods We retrospectively assessed prospectively collected sputum from a cohort of 104 individuals aged 18–22 to determine factors associated with progression to early end-stage lung disease (eESLD; death/transplantation &lt;25 years) and rapid pulmonary function decline (&gt;−3%/year FEV 1 over the ensuing 5 years). Illumina MiSeq paired-end sequencing of the V3-V4 region of the 16S rRNA was used to define the airway microbiome. Results Based on the primary outcome analysed, 17 individuals (16%) subsequently progressed to eESLD. They were more likely to have sputum with low alpha diversity, dominated by specific pathogens including Pseudomonas . Communities with abundant Streptococcus were observed to be protective. Microbial communities clustered together by baseline lung disease stage and subsequent progression to eESLD. Multivariable analysis identified baseline lung function and alpha diversity as independent predictors of eESLD. For the secondary outcomes, 58 and 47 patients were classified as rapid progressors based on absolute and relative definitions of lung function decline, respectively. Patients with low alpha diversity were similarly more likely to be classified as experiencing rapid lung function decline over the ensuing 5 years when adjusted for baseline lung function. Conclusions We observed that the diversity of microbial communities in CF airways is predictive of progression to eESLD and disproportionate lung function decline and may therefore represent a novel biomarker.
Abstract 13901: Spatial Distribution of the Late Gadolinium Enhancement on Cardiac MRI Strongly Affects Maximal T-wave Alternans Sites on the 12-lead Holter ECG in Hypertrophic Cardiomyopathy
Authors: Naka Sakamoto, Nobuyuki Sato, Ahmed Talib, Keisuke Otsu, Eitaro Sugiyama, Akiho Minoshima, Yasuko Tanabe, Toshiharu Takeuchi, Yuichiro Kawamura, Naoyuki Hasebe
Journal: Circulation (2015)

[Background]: Late gadolinium enhancement (LGE) on cardiac MRI (CMR) predicts the mortality in hypertrophic cardiomyopathy (HCM) patients. T-wave alternans (TWA) is a potential cardiac mortality predictor. However, whether LGE localization affects TWA is unclear. [Purpose]: To elucidate the localization relationship between the LGE and maximal TWA lead (TWAmax-lead) and maximal TWA voltage (TWAmax) using 12-lead Holter ECGs (Holter12) in HCM. [Methods]: Holter12s and CMR were performed in 46 HCM patients. TWA was assessed using a modified moving average method and the TWAmax was determined in each lead. The average transmural LGE extent was scored using a 4 point score (Score 0:no LGE, 1:1-25%, 2:26-50%, 3:51-75%, 4:76-100%) in 12 left ventricular segments and the sum (LGEtotal) was calculated. Left ventricular LGE sites were classified into anterior, septal, inferior, and lateral. Corresponding ECG lead groups were defined as V3-4 for anterior, V1-2 for septal, II, III, aVF for inferior, and I, aVL, and V5-6 for lateral. The TWAmax was analyzed depending on the Score of the 5 stages, and the coincidence between the LGE distribution and TWAmax-lead was investigated. Furthermore, the differences in the TWAmax, LGEtotal, and left ventricular ejection fraction (LVEF) in the presence or absence of ventricular tachycardia (VT) were also studied. [Results]: The TWAmax was 50±11μV for Score=0, 54±13μV for Score=1, 61±18μV for Score=2, 67±20μV for Score=3, and 47±16μV for Score=4. The TWAmax for Scores 2 and 3 was significantly greater than for Score=0 (p&lt;0.001, p&lt;0.001, respectively), but there was no significant difference between Scores 1 and 4, and Score=0 (p=0.14, p=0.41). The TWAmax-lead revealed scores ranging from 1 to 3 in all segments. The LGEtotal and TWAmax were significantly greater in patients with VT (n=23) than without (17±7 vs. 10±7 [p&lt;0.01], 83±17μV vs. 64±18μV [p&lt;0.001], respectively). The LVEF did not statistically differ between the two groups (48±16% vs. 54±10%, p=0.21). [Conclusions]: The LGE distribution correlated with the TWA, i.e., a 50-75% transmural extent of the LGE yielded the maximal local TWA. The spatial distribution of the LGE strongly affects myocardial repolarization abnormalities indicated by TWA as VT substrates in HCM.