tbuckley/cabot-search huggingface dataset:
Abstract P216: PRAS40 Is a Critical Regulator of Cardiomyocyte Growth
Authors: Mirko Volkers, Mathias Konstandin, Natalie Gude, Shabana Din, Mark Sussman
Journal: Circulation Research (2011)

Background: Proline-rich Akt substrate of 40 kDa (PRAS40) is a component of the mammalian target of rapamycin complex (mTORC) 1. Whereas, PRAS40 was originally characterized as substrate for PKB/Akt, subsequent studies identified PRAS40 both as inhibitor and substrate of mTORC1. These studies identify PRAS40 as a negative regulator of mTORC1 activity and cell growth. Phosphorylation of PRAS40 by AKT, which results in dissociation of PRAS40 from mTORC1, relieves the inhibitory constraint on mTORC1. The physiological role and pathophysiological function of PRAS40 in the heart is unknown. Methods and Results PRAS40 is expressed in cardiomyocytes and highly phosphorylated in embryonic and neonatal hearts. PRAS40 phosphorylation and expression is decreased in adult cardiomyocytes. Pathological challenge in mice induced phosphorylation of PRAS40 in the border zone after myocardial infarction and globally after transaortic constriction. Subcellular, phosphorylated PRAS40 is localized in the cytoplasma after pathological challenge, whereas stimulation with Insulin or IGF1 induced nuclear localization of PRAS40. Adenoviral mediated overexpression of PRAS40 completely blocks pathological hypertrophy after stimulation with phenylephrine as well as physiological growth after stimulation with IGF1 or Insulin. Molecular, mTORC1 activity was significantly reduced after PRAS40 overexpression. Conversely, silencing of PRAS40 resulted in significant increased mTORC1 activity. Gain and loss of function studies of PRAS40 in vivo will be performed to test the therapeutically potential of PRAS40. Conclusion PRAS40 is a novel regulator of cardiomyocyte growth. Manipulation the activity or expression of PRAS40 could represent a novel therapeutic target to treat cardiac diseases.
Abstract P174: Dynamics of the Renin-Angiotensin-Aldosterone System: Implications of Angiotensin-Peptide Fingerprinting on the Clinical Use and Development of Antihypertensive Drugs
Authors: Marko Poglitsch, Manfred Schuster, Hans Loibner
Journal: Circulation Research (2011)

BACKGROUND: The Renin-Angiotensin-Aldosterone-System (RAAS) is an extensively studied peptide hormone system which is critically involved in the regulation of blood pressure and other important physiologic functions. Angiotensin-(1-10) which is liberated from angiotensinogen by kidney secreted Renin, is sequentially metabolized to different N- and C-terminal truncated fragments with partially described biologic activities. Beside Angiotensin II (Ang-(1-8)), various other angiotensin peptides including Ang-(1-7), Ang-(1-9), Ang-(2-8) and Ang-(3-8) are known to possess physiologic activity while Ang-(1-7) and more recently Ang-(1-9) were described to antagonize pathologic effects of Ang-(1-8) via vasodilation and antifibrotic action respectively. The role of Ang-(1-8) in hypertension converts enzymes participating in Ang-(1-8) generation to favorable targets for antihypertensive drugs. METHODS: Human blood was collected from healthy volunteers followed by ex-vivo incubation at 37°C in the presence of different inhibitors of angiotensin metabolism. Angiotensin concentrations were determined employing a novel sensitive LC-MS/MS based method, which allows the simultaneous quantification of a broad panel of angiotensin peptides in human plasma. RESULTS: The investigation of different angiotensin metabolism modifiers revealed agent specific patterns of angiotensin peptide levels reflecting the specificity of these inhibitors. Spiking experiments allowed the determination of turnover rates for distinct angiotensin conversion reactions surrounded by their physiological matrix. CONCLUSION: The measurement of blood concentrations of angiotensin peptides provides important information about the substrate specificities and activities of enzymes involved in their metabolism. This allows the identification of potential causes for pathologic conditions, facilitating a patient specific therapeutic modulation of the RAAS. The overall assessment of angiotensin peptide concentrations (Angiotensin-Peptide-Fingerprinting) represents a powerful tool to gain a more detailed understanding of blood pressure regulation, enabling the pharmacologic characterization of RAAS modifying agents in use and development.
Abstract 15297: Active Rheumatoid Arthritis is Associated With Subclinical Left Ventricular Systolic Myocardial Dysfunction
Authors: Helga Midtbø, Anne Grete Semb, Knut Matre, Tore K Kvien, Eva Gerdts
Journal: Circulation (2015)

Introduction: Patients with rheumatoid arthritis (RA) have comparable cardiovascular risk to patients with diabetes mellitus. Lately, disease activity has emerged as a new, independent risk factor for cardiovascular disease in RA patients. Hypothesis: We tested if RA disease activity was associated with subclinical systolic left ventricular (LV) dysfunction independent of traditional cardiovascular risk factors. Methods: Echocardiography was performed in 78 patients with active RA (Simplified Disease Activity Index [SDAI] &gt;3.3), 41 patients in remission (SDAI ≤3.3), and 46 controls, all without known cardiac disease. LV endocardial systolic function was determined by biplane Simpson ejection fraction and LV myocardial function by stress-corrected midwall shortening (scMWS) and global longitudinal strain (GLS). Results: Patients with active RA had higher frequencies of hypertension, diabetes and use of disease modifying antirheumatic drugs (all p&lt;0.05) compared to patients in remission, while age and sex did not differ from RA patients in remission (Table). LV ejection fraction was normal in all groups, while mean GLS and scMWS were reduced in RA patients with active disease compared to RA in remission (p&lt;0.05) (Table). In multivariate analyses, having active RA was associated with lower GLS (β=0.21) and scMWS (β=-0.22, both p&lt;0.05) independent of cardiovascular risk factors and LV ejection fraction. Assessment of RA disease activity by other composite scores yielded similar results. Conclusions: Active RA is associated with subclinical reduced LV systolic myocardial function despite normal ejection fraction, and independent of presence of hypertension and diabetes.
Incidental Findings in Research Studies: One Student's Experience
Authors: Franklin J. Canady
Journal: Annals of Internal Medicine (2017)

On Being a Doctor4 July 2017Incidental Findings in Research Studies: One Student's ExperienceFranklin J. Canady, BAFranklin J. Canady, BAFrom University of Iowa Carver College of Medicine, Iowa City, Iowa.Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M16-2226 Audio Reading - “Incidental Findings in Research Studies: One Student's Experience” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Incidental Findings in Research Studies," by F.J. Canady. 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 During my freshman year of college, I took part in a research study that explored differences in brain structure between children with and without cleft lip and cleft palate. The study included neurocognitive, behavioral, and genetic testing; a neurologic examination; and a brain MRI. I participated one afternoon in January 2011 during my winter break, because I needed something to do and it was a way to make a little money before heading back to school. Once the study was over, I deposited my check and more or less forgot about the study and what it could mean for me ... Author, Article, and Disclosure InformationAffiliations: From University of Iowa Carver College of Medicine, Iowa City, Iowa.Corresponding Author: Franklin J. Canady, BA, University of Iowa Carver College of Medicine, 200 Hawkins Drive, Iowa City, IA 52242; e-mail, [email protected]edu. PreviousarticleNextarticle Advertisement Audio Reading - “Incidental Findings in Research Studies: One Student's Experience” Audio. Michael A. LaCombe, MD, Annals Associate Editor, reads "Incidental Findings in Research Studies," by F.J. Canady. 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 4 July 2017Volume 167, Issue 1Page: 68-69KeywordsBrainEmotionsEpileptic seizuresFearForecastingHealth information technologyResidencyRunningSurgeonsSurgery ePublished: 4 July 2017 Issue Published: 4 July 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Effects of acute concussion on centre of pressure variables during quiet stance
Authors: Jill K Dierijck, Alexander D Wright, Bryk Kelsey, Jonathan D Smirl, Paul van Donkelaar
Journal: British Journal of Sports Medicine (2017)

Objective To examine how acute sport-related concussion influences centre of pressure (COP) sway during quiet stance Design Prospective cohort Setting Laboratory Participants Eighty-seven male contact-sport (football and hockey) athletes entered the study. Seven subjects (age range 17–22) were concussed and completed follow-up testing 72-hours, two-weeks, and one-month following the injury. Intervention One-minute eyes-open and eyes-closed quiet stance trials were performed on a force plate (NDI True Impluse) with feet hip-width apart. Force plate data and SCAT3 were collected at each time point. Outcome measures Root-mean-square COP displacement (RMSd) and mean COP velocity were quantified in the anterior/posterior (AP) and medial/lateral (ML) directions. Independent variables included condition (2) and time (4) Main results RM-ANOVA indicated a main effect of time for all outcomes: AP-RMSd (p=0.006), AP mean velocity (p=0.012), ML-RMSd (p=0.001), ML mean velocity (p=0.001). Pairwise comparisons indicated reductions at 2-weeks in AP-RMSd (0.05, 95% CI: −0.672, 0.000), and AP mean velocity (p=0.039, 95% CI: −1.275, −0.036). ML-RMSd was reduced 1 month post-concussion (p=0.021, 95% CI: −0.365, −0.034). Change scores from baseline to 72-hours were correclated between: AP-RMSd and Balance Error Scoring System (r=0.878, p=0.009), AP mean velocity and Standardised Assessment of Concussion (SAC) (r=−0.822, p=0.023), and ML mean velocity and SAC (r=−0.836, p=0.019). Conclusions Measures of COP sway during quiet stance revealed alterations in displacement and velocity that persisted up to one-month following a sports-related concussion. These COP alterations exceeded the duration of clinical recovery (median return-to-play: 14 days) indicating that clinical recovery does not equal physiological recovery. Competing interests None.
Acupuncture may reduce symptoms of stress urinary incontinence, study finds
Authors: Susan Mayor
Journal: BMJ (2017)

Treating women with stress urinary incontinence with electroacupuncture—passing an electric current between acupuncture needles on the lower back—reduced urine leakage after six weeks, a randomised trial has shown.1

Previous studies have suggested that electroacupuncture is beneficial in stress urinary incontinence, but the evidence came from small trials that were poorly designed.

The new study randomly allocated 504 women (mean age 55.3) who were being treated for stress urinary incontinence at 12 hospitals in China …
Re: Eric A. Klein, Arnon Chait, Jason M. Hafron, et al. The Single-parameter, Structure-based IsoPSA Assay Demonstrates Improved Diagnostic Accuracy for Detection of Any Prostate Cancer and High-grade Prostate Cancer Compared to a Concentration-based Assay of Total Prostate-specific Antigen: A Preliminary Report. Eur Urol 2017;72:942–9
Authors: Parham Habibzadeh, Farrokh Habibzadeh
Journal: European Urology (2017)
Infliximab in Patients with Moderate to Severe Ulcerative Colitis with a Failed Response to Medical Therapy
Authors: MM Anwar, S Sarwar, BJ Egan, S Veerapan, B Ryan, N Breslin, C O'Morain
Journal: Endoscopy (2006)

Aims: Severe to moderately severe exacerbations of ulcerative colitis (UC) have a high colectomy rate despite currently available medical therapy. We studied the efficacy and safety of infliximab in this group of patients.
Outcome of patients with intracranial non-germinomatous germ cell tumors—lessons from the SIOP-CNS-GCT-96 trial
Authors: Gabriele Calaminus, Didier Frappaz, Rolf Dieter Kortmann, Barbara Krefeld, Frank Saran, Torsten Pietsch, Alexandre Vasiljevic, Maria Luisa Garre, Umberto Ricardi, Jillian R Mann, Ulrich Göbel, Claire Alapetite, Matthew J Murray, James C Nicholson
Journal: Neuro-Oncology (2017)

Following promising results to increase survival and reduce treatment burden in intracranial non-germinomatous germ cell tumors (NGGCTs), we conducted a European study using dose-intense chemotherapy followed by risk-adapted radiotherapy.All patients received 4 courses of cisplatin/etoposide/ifosfamide. Non-metastatic patients then received focal radiotherapy only (54 Gy); metastatic patients received 30 Gy craniospinal radiotherapy with 24 Gy boost to primary tumor and macroscopic metastatic sites.Patients with localized malignant NGGCT (n = 116) demonstrated 5-year progression-free survival (PFS) and overall survival (OS) of 0.72 ± 0.04 and 0.82 ± 0.04, respectively. Primary tumor sites were: 67 pineal, 35 suprasellar, 5 bifocal, 9 others. One patient died postsurgery in clinical remission; 3 patients progressed during treatment and 27 (23%) relapsed afterward. Fourteen were local, 6 combined, and 7 distant relapses (outside radiation field). Seventeen of the 27 relapsed patients died of disease. Patients with metastatic disease (n = 33) demonstrated 5-year PFS and OS of 0.68 ± 0.09 and 0.75 ± 0.08, respectively; 1 patient died following progression on treatment and 9 (27%) relapsed afterward (5 local, 1 combined, 3 distant). Only one metastatic patient with recurrence was salvaged. Multivariate analysis identified diagnostic alpha-fetoprotein level (serum and/or cerebrospinal fluid level >1000 ng/mL, 19/149 patients, of whom 11 relapsed; P < 0.0003) and residual disease following treatment, including after second-look surgery (n = 52/145 evaluable patients, 26 relapsed; P = 0.0002) as significant prognostic indicators in this cohort.In localized malignant NGGCT, craniospinal radiotherapy could be avoided without increased relapses outside the radiotherapy field. Chemotherapy and craniospinal radiotherapy remain the gold standard for metastatic disease.
Analysis of risk factors of early recurrence and ideal surgical margin for hepatocellular carcinoma
Authors: Hidetoshi Nitta, Antoine Allard Marc, Mylène Sebagh, Oriana Ciacio, Gabriella Pittau, Eric Vibert, Antonio Sa-cunha, Daniel Cherqui, Denis Castaing, Henri Bismuth, Hideo Baba, René Adam
Journal: Annals of Oncology (2017)
Serum 25-hydroxy vitamin D and nutritional status: Implications for vitamin D assessment and dietary supplementation in oncology
Authors: K. Trukova, D. Gupta, P. G. Vashi, A. Adams, G. M. Lambert, J. F. Grutsch, C. A. Lammersfeld
Journal: Journal of Clinical Oncology (2009)

9638 Background: There is emerging evidence in the literature to suggest a protective role of vitamin D in cancer survival. Vitamin D status is not routinely assessed, despite the high prevalence of malnutrition in this population. We hypothesized that malnutrition could contribute to vitamin D deficiency, and therefore expected mean serum 25-hydroxy-vitamin D [25(OH)D] levels to be significantly lower in malnourished oncology patients. Methods: A consecutive case series of 737 cancer patients seen at Cancer Treatment Centers of America between Jan-June 08. Nutritional status was assessed using Subjective Global Assessment (SGA) and serum albumin. SGA categorizes patients into 3 distinct classes of nutritional status; well nourished (SGA-A), moderately malnourished (SGA-B) and severely malnourished (SGA-C). Serum albumin was divided into 2 groups: &gt;=3.6 g/dl and &lt;=3.5 g/dl. Mean serum 25(OH)D was compared across 3 categories of SGA using ANOVA and across 2 categories of serum albumin using 2 sample t test. Results: Of 737 patients, 302 were males and 435 females. The mean age at presentation was 55.7 years (SD = 10.2). The most common cancer types were lung (133, 18%), breast (131, 17.8%), colorectal (97, 13.2%), pancreas (86, 11.7%), prostate (44, 6%) and ovarian (38, 5.2%). The mean serum albumin and serum 25(OH)D was 3.5g/dl (SD = 0.6) and 21.9 ng/ml (SD = 13.5) respectively. There was no significant difference in the mean vitamin D levels across serum albumin (p = 0.76). The mean vitamin D levels across the 3 classes of SGA also showed no statistically significant difference ( Table ). Conclusions: Contrary to what we expected, vitamin D deficiency was found to be prevalent in cancer regardless of nutritional status. No significant differences were found across the 3 classes of SGA. Based on these results, screening for vitamin D deficiency and aggressive vitamin D repletion should be considered for all people with cancer. [Table: see text] No significant financial relationships to disclose.
Winning the Fight to End Alzheimer Disease
Authors: Walter Dawson
Journal: JAMA Neurology (2017)

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Abstract 308: Chronic Aspirin Treatment Possibly Poses a Risk to Ischemic Heart via Impairment of Cardiac Proteasome Functions
Authors: Chunjiang Tan, Wenlie Chen, Yanbing Wu, Jiumao Lin, Ruhui Lin, Xuerui Tan, Songming Chen
Journal: Circulation Research (2012)

Background: Impaired cardiac proteasome (CP) has been reported in ischemia and heart failure. Recent data highlighted aspirin as an inhibitor of the ubiquitin-proteasome system, however, it’s unclear whether it affects CP functions. Objective: We investigated the influence of aspirin on CP in the rat model of myocardial infarction (MI). Methods and Results: MI, sham or normal male SD rats were injected intraperitoneally with high (300mg/kg), low (5mg/kg) aspirin or saline (control) once a day for seven weeks. Parallel experiments were performed in the hypoxia/reoxygenated cell model of primary human ventricular myocytes incubated with different concentrations of aspirin. Myocardial hypertrophy, cardiac function, cell viability and the functions of 26S, 20S and 19S, including the β1, β2 and β5 subunits of 20S were determined. The activity of 26S, 20S and 19S declined by about 30%, and β5, β2 and β1 by 40%, 20% and 30%, respectively, in the MI rats compared with the non-MI rats ( P &lt;0.05). Compared with the saline-treated MI rats, 26S and 20S in high or low dose aspirin-treated MI rats further decreased by 30% and 20%, and β5 further decreased by 30% and 12%, and β1 by 40% and 30%, respectively, and their lost activity was correlated with compromised cardiac function in the MI rats. The dose-related and selective inhibition of β5 and β1 by aspirin was comparable to their protein expressions in the MI rats and in the cultured cells. However, the CP in the normal settings, or 19S and β2 in all the groups of animals or cultured cells were less affected by aspirin treatment. The impaired CP, dose-dependently enhanced by aspirin, led to the elevation of oxidative and ubiquitinated proteins in the MI rat hearts or in the hypoxia/reoxygenated cells. These aberrant proteins in turn constituted the ultimate causal factor for the cardiac dysfunction and the loss of cell viability. In vitro experiments confirmed that the purified CP from the MI rats or hypoxic cells, but was more susceptible to aspirin treatment, whereas the complexes in the normal settings appeared less affected by aspirin. Conclusions: Chronic aspirin treatment, via the dose-dependent and selective inhibition of CP, enhanced the ischemic CP dysfunction, which constitutes a potential risk factor for the ischemic heart.