tbuckley/cabot-search huggingface dataset:
Abstract 3308: Therapeutic Hypothermia Improves Survival and Neurological Outcomes by Akt-mediated Antiapoptotic Protection of the Brain
Authors: Wei-Tien Chang, Chiang-Ting Chien, Lay-San Gan, Chun-Pei Lee, Ming-Fang Wu, Chien-Hua Huang, Chiung-Yuan Hsu, Min-Shan Tsai, Hsiao-Ju Cheng, Shyr-Chyr Chen, Yuan-Teh Lee, Wen-Jone Chen
Journal: Circulation (2009)

Background:  Neurological dysfunction after cardiopulmonary resuscitation (CPR) accounts for the majority of late morbidities and mortalities. Therapeutic hypothermia has been recommended in patients resuscitated from cardiac arrest; the protective mechanism, however, is not fully understood yet. We therefore investigate the neuroprotective mechanisms underlying therapeutic hypothermia.   Methods:  Based on a rat model of asphyxia cardiac arrest (6 min) and CPR, therapeutic hypothermia (32°C) was induced immediately after resuscitation and maintained for 2 h. The rats were then rewarmed to normothermia in another 2 h. The hemodynamics, tissue blood flow of the brain (assessed by OxyFLO probe), and systemic reactive oxygen species (ROS) generation (measured by chemiluminescence method) were compared with those of normothermia control. Bax, Bcl-2 and phosphorylated Akt (Ser 473) of the brain were measured at 4 h post-resuscitation. In a subgroup with minimal invasive procedures, the survival and neurological outcomes were monitored up to 3 days. The brain tissues were sampled on day 3 for TdT-mediated dUTP nick-ends labeling (TUNEL) stain.   Results:  The survival was significantly better in the hypothermia group (log-rank  P  P    Conclusion:  Therapeutic hypothermia improves survival and neurological outcomes by early activation of Akt that leads to antiapoptotic protection. In contrast to other treatment strategies which improve gross physiological indicators, the protection is mediated by triggering of intracellular signaling pathways leading to antiapoptosis.
Abstract 2300: Selective Serotonin Reuptake Inhibitor Use is Associated with Decreased Mortality in Pulmonary Hypertension
Authors: Sanjiv J Shah, Mardi Gomberg-Maitland, Thenappan Thenappan, Stephen L Archer, Stuart Rich
Journal: Circulation (2007)

Introduction: The serotonergic pathway appears to be involved in pulmonary hypertension (PH) and selective serotonin reuptake inhibitors (SSRIs) prevent development of PH in animal models. We hypothesized that SSRIs would decrease development of PH and would be associated with decreased mortality in PH patients (pts). Methods: In a case-control study of the Surveillance of PH in America (SOPHIA) registry, we first tested whether pts without PH had increased SSRI exposure compared to those with PH. In SOPHIA, 1335 pts underwent invasive hemodynamic study and were classified as no-PH (N=155) or confirmed-PH (N=1180). We used logistic regression to see if the no-PH group had increased exposure to SSRIs. Next, we studied baseline SSRI use in the Pulmonary Hypertension Connections (PHC) cohort, a referral-based registry of adults with PH (N=542). A Cox proportional hazards analysis was used to see if SSRI use was associated with decreased mortality. Results: In SOPHIA, the no-PH group had a 1.8-fold increased odds of being exposed to SSRIs compared to the confirmed-PH group (p&lt;0.05). In PHC, 69/542 (13%) were taking SSRIs at time of referral. Pts taking SSRIs were more often obese, but otherwise had similar to those not taking SSRIs. During mean follow-up of 4.0±3.1 yrs, 12% of pts taking SSRI vs. 23% of pts not taking SSRI died (hazard ratio [HR] 0.35; p=0.023). The association between SSRI and decreased mortality persisted after adjusting for age, gender, etiology of PH, and obesity (HR 0.36; p=0.026). Conclusions: SSRI use appears to be associated with decreased development of PH and decreased mortality in PH. These findings provide rationale for a randomized trial of SSRIs in PH.
Seasonal Influenza Vaccination for Children in Thailand: A Cost-Effectiveness Analysis
Authors: Aronrag Meeyai, Naiyana Praditsitthikorn, Surachai Kotirum, Wantanee Kulpeng, Weerasak Putthasri, Ben S. Cooper, Yot Teerawattananon
Journal: PLoS Medicine (2015)

Seasonal influenza is a major cause of mortality worldwide. Routine immunization of children has the potential to reduce this mortality through both direct and indirect protection, but has not been adopted by any low- or middle-income countries. We developed a framework to evaluate the cost-effectiveness of influenza vaccination policies in developing countries and used it to consider annual vaccination of school- and preschool-aged children with either trivalent inactivated influenza vaccine (TIV) or trivalent live-attenuated influenza vaccine (LAIV) in Thailand. We also compared these approaches with a policy of expanding TIV coverage in the elderly.We developed an age-structured model to evaluate the cost-effectiveness of eight vaccination policies parameterized using country-level data from Thailand. For policies using LAIV, we considered five different age groups of children to vaccinate. We adopted a Bayesian evidence-synthesis framework, expressing uncertainty in parameters through probability distributions derived by fitting the model to prospectively collected laboratory-confirmed influenza data from 2005-2009, by meta-analysis of clinical trial data, and by using prior probability distributions derived from literature review and elicitation of expert opinion. We performed sensitivity analyses using alternative assumptions about prior immunity, contact patterns between age groups, the proportion of infections that are symptomatic, cost per unit vaccine, and vaccine effectiveness. Vaccination of children with LAIV was found to be highly cost-effective, with incremental cost-effectiveness ratios between about 2,000 and 5,000 international dollars per disability-adjusted life year averted, and was consistently preferred to TIV-based policies. These findings were robust to extensive sensitivity analyses. The optimal age group to vaccinate with LAIV, however, was sensitive both to the willingness to pay for health benefits and to assumptions about contact patterns between age groups.Vaccinating school-aged children with LAIV is likely to be cost-effective in Thailand in the short term, though the long-term consequences of such a policy cannot be reliably predicted given current knowledge of influenza epidemiology and immunology. Our work provides a coherent framework that can be used for similar analyses in other low- and middle-income countries.
Learning from differences within the NHS
Authors: A. G Mulley
Journal: BMJ (1999)

We learn by making comparisons and trying to understand the sources of variation. Variation in the rates at which healthcare professionals use interventions in the care of seemingly similar populations creates opportunities to learn about and improve the quality of clinical decision making. And variations in outcomes between different professionals or institutions providing the same interventions create opportunities to learn how to improve the quality of clinical care.1 Yet too often variation is seen more as a challenge to authority and competence than as an opportunity to learn.

Last month the NHS Executive published comparative data for 100 health authorities and 280 NHS hospital trusts on six clinical indicators developed to measure aspects of clinical care that affect quality.2 The indicators measure in-hospital 30 day mortality rates after admission for emergency or elective surgery, for myocardial infarction, and for hip fracture. They also include rates of emergency readmission with any diagnosis and discharge to usual place of residence following admission for either stroke or hip fracture There is considerable variation across England that cannot readily be explained by characteristics of the populations served or of the hospitals. One pattern that did emerge is higher readmission rates and the highest death rates after surgery among health authorities in coalfields and ports and industrial areas.

The data come from health episode statistics for 1995-6 to 1997-8, comprising 11 000 000 consultant episodes a year. They are imperfect Data reporting itself is highly variable, and locations with evidently poor reporting were …
Mind and body split
Authors: P. A Sugarman
Journal: BMJ (2003)

Self reported patterns of sexual activity in 4624 British men Age group (years) Men with self reported activity greater than once weekly (n=4624) Men with self reported activity greater than once weekly minus men with no sexual activity over 4 week study period (n=4316) No (%) 95% CI No (%) 95% CI 40-44 742 (51) 48 to 55 687 (55) 52 to 59 45-49 545 (41) 37 to 45
Doctors should expect to repay state investment with NHS service
Authors: M. J. Taggart
Journal: BMJ (2015)

The vigorous debate instigated by Dean about the ethics of private practice1 has set me pondering what seem to be a few incongruities.

As a university based academic scientist I receive no pay for any overtime work, of which there is plenty, and I am contractually obliged to seek permission from my current employer if I wish to undertake additional salaried employment. From …
Abstract 926: Oxidative Stress Induces GLUT4 Translocation by dual AMPK Kinase Activation in Cardiac Myocytes
Authors: Horie Takahiro, Koh Ono, Yukiko Abe, Teruhisa Kawamura, Hiromichi Wada, Minako Kinoshita, Kazuya Nagao, Hitoo Nishi, Akira Shimatsu, Toru Kita, Koji Hasegawa
Journal: Circulation (2007)
Abstract 10910: Adipokines are Associated with Lower Extremity Venous Disease: The San Diego Population Study
Authors: Matthew A Allison, Mary Cushman, Peter Callas, Julie Denenberg, Nicole Jensky, Michael Criqui
Journal: Circulation (2010)

Background: Obesity is a risk factor for venous disease. We tested the associations between adipokines and the presence and severity of venous disease. Methods: Participants for this analysis were ...
The Multiple Myeloma Research Consortium (MMRC): A Model For Accelerating Development Of Novel Therapies For Multiple Myeloma
Authors: Beverly Harrison, Kenneth C. Anderson, Noopur Raje, Paul Richardson, Diane Warren, Ajai Chari, Sundar Jagannath, Lisa La, Jesus Berdeja, Meredith Zimlich, Joseph W. Fay, Sheila Powell, Craig C Hofmeister, Nita Williams, Andrzej J. Jakubowiak, Todd M. Zimmerman, Kathryn McDonnell, Amrita Y. Krishnan, Lupe Duarte, Ccrc Ccrc, Shaji K Kumar, Ann Birgin, Cra Cra, Sagar Lonial, Kenisha Baron, Thomas Martin, Jeffrey L Wolf, Geraldine Pelle-Day, Glenna Auerback, Gregory Orloff, Nikki Hodge, Donna E Reece, Suzanne Trudel, Engin Gul, HonBSc HonBSc, Vivek Roy, Michele Maharaj, David S. Siegel, Adolfo Aleman, A. Keith Stewart, Rachel Hagerty, Moshe Talpaz, Roxane Collins, Ravi Vij, Mark A. Fiala, Jeffrey Zonder, Silva Pregja, Sharon Goldberg, Joan Levy, Karen Dietz, Walter Capone, Daniel Auclair, Anne Quinn Young, Kathy Giusti
Journal: Blood (2013)
Abstract 497: Normalization of Intracellular Calcium Signaling by Chronic Cardiac Resynchronization Involves Redox Modulation of Ryanodine Receptors.
Authors: Inna Gyorke, Radmila Terentyeva, Serge Viatchenko-Karpinski, Dmitry Terentyev, Yoshinori Nishijima, David S Feldman, Cynthia A Carnes, Sandor Gyorke
Journal: Circulation (2007)

Cardiac resynchronization therapy (CRT) represents a promising treatment modality to alleviate LV dysfunction in humans with heart failure (HF). Using a canine chronic model of HF, we recently showed that CRT improves abnormal Ca2+ handling by reducing the diastolic Ca2+ leak from the SR through cardiac ryanodine receptors (RyR2s). Using the same models of HF and CRT therapy, we now demonstrate that the specific molecular mechanism for improved RyR2-mediated Ca2+ signaling involves partial restoration of RyR2s from post-translational oxidative modifications. RyR2 expression was markedly reduced in HF and restored to control levels after CRT. Single RyR2 channel activity from HF and CRT groups were recorded using the lipid bilayer technique. In both HF and CRT groups two functional types of RyR2s could be clearly distinguished based on their overall activity as well as sensitivities to luminal ( trans ) Ca2+ and cytosolic ( cis ) Mg2+: high-Po (open probability) and low-Po RyR2s; in contrast to normal controls (only low-Po). High-Po RyR2s in both groups exhibited enhanced sensitivity to trans Ca2+ and increased resistance to inhibition with cis Mg2+. These properties of the high Po RyR2s define the hyperactive, i.e. leaky RyR2 behavior in HF. Low-Po RyR2s had functional properties which did not differ from those observed in RyR2s from normal hearts. In HF ~80% of the RyR2s were high Po, while only ~20% were low Po RyR2s. Following CRT, the fraction of low Po RyR2s increased (to ~60%) while the remainder had high-Po behavior. High-Po channels could be partially normalized by the reducing agent DTT; whereas low-Po channels could be converted to the high Po type by treatment with the oxidative agent DTDP. These results suggest that RyR2 alterations in HF and normalization by CRT occur by redox modulation of a small number of critical sites susceptible to reversible oxidative modification. Additionally, the altered balance of the RyR2 functional fractions following CRT could reflect replacement of irreversibly modified RyR2s by newly synthesized protein, under condition of reduced oxidative stress. These data suggest that altered redox modulation contributes to abnormal function of the RyR2s in HF and that improved RyR2 redox balance may contribute to the efficacy of CRT.
Biodegradable cationic polymers with lower transfection cytotoxicity
Authors: Lei Yu
Journal: Cancer Research (2004)

4591  A major problem involving cell transfection using current cationic polymer gene carriers is the relative high cytotoxicity encountered while approaching the desired transfection efficiency. To overcome this problem, a biodegradable cationic polymer library was constructed by a parallel chemical synthesis method which varied the structure and molecular size. High throughput transfection screening assays (GFP, Luciferase, and MTT) were used in combination with GPC and NMR to study the relationship between polymer size, structure, transfection efficiency, and cytotoxicity. Human transformed cells (HEK 293) and primary cells (HUVEC cells) were used in this study. Several of the best candidates were selected from the samples screened. The results showed that the novel biodegradable cationic polymers had significantly improved the transfection performances in HEK 293 cells (0%-10% cytotoxicity at 93%-98% transfection efficiency) compared to the most common polymer transfection reagent, JetPEI™ (10-25% cytotoxicity at 85%-92% transfection efficiency) and SuperFect (12%-30% cytotoxicity at 85%-90% transfection efficiency). Using human umbilical vascular endothelial primary cells (HUVEC), the biodegradable cationic polymers showed dramatically higher transfection efficiencies (60%) with low cytotoxicities (20% to 30%) compared to JetPEI™ (10% transfection efficiency and 50% cytotoxicity) and SuperFect™ (8% transfection efficiency and 60% cytotoxicity). The results indicated that the biodegradable polymers are useful reagents for reducing transfection cytotoxicities while attaining high transfection efficiencies when used for in vitro applications. These biodegradable polymers may also prove to be useful tools for gene delivery for in vivo applications.
Abstract 4068: Long Working Hours and Delay in Seeking Care during Acute Coronary Events in U.S. and Japanese Samples
Authors: Yoshimi Fukuoka, Masako Takeshima, Noriko Ishii, Miyuki Makaya, Linda Groah, Erick Kyriakidis, Kathleen Dracup
Journal: Circulation (2008)

Objective: Timely reperfusion therapy with fibrinolytic therapy or primary percutaneous coronary intervention reduces infarct size and adverse clinical consequences. However, prolonged prehospital delay (symptom onset to hospital arrival) continues to be a problem. Numerous studies have examined factors associated with prehospital delay. Yet, the association between job characteristics and delay has never been examined. The purpose of the study was to examine the association between working hours/job strain and duration of prehospital delay in employed patients with acute coronary syndrome (ACS) in the United States (U.S.) and Japan. Methods: In this cross-sectional study, a total of 234 consecutive patients (Americans n= 148 and Japanese n =86) admitted with ACS and who worked more than 20 hours/week were recruited. A structured interview was conducted while patients were still in a hospital to assess symptom onset time, ambulance use, number of working hours/week, and job strain. In the U.S. sample, the...
Abstract P317: Cognitive Impairment in Coronary Artery Disease Patients: Do Exercise Tolerance and Cerebral Oxygenation During Exercise Matter?
Authors: Vincent Gremeaux, Joffrey Drigny, Mathieu Gayda, Martin Juneau, Louis Bherer, Anil Nigam
Journal: Circulation (2012)

Introduction: Cardiovascular diseases have been associated with impaired cognitive performances, especially in functions. In contrast, it is clearly established that regular physical activity maintained throughout life protects against age-related cognitive decline. Purpose: to assess maximal oxygen uptake (VO2max), cardiac output, and cerebral hemodynamic changes, assessed by Near-Infrared Spectroscopy (NIRS), during a graded maximal exercise tests, and cognitive performance at rest in patients with stable coronary heart disease (CHD) and healthy matched adults. Methods: Ten stable CHD patients (67.1±10.5 years) and 9 age-matched controls (62.2± 11.4 years) were included in this pilot study. Measurements included: body composition (bioelectrical impedance), complete blood analysis in a fasting state, cognitive performance using validated neuropsychological tests, graded maximal exercise testing on ergocycle with gas exchange analysis, non-invasive cardiac output measurement (cardiac bioimpedance) and NIRS signals measurement at the left prefrontal brain level (oxyhaemoglobin: O2Hb, deoxyhaemoglobin: HHb ; total haemoglobin: THb, and differential haemoglogin: Hbdiff). Results: Several cognitive performance items were lower in the CHD group, especially regarding executive functions (Backward digit span score, p&lt;0.05; trail making test B, p=0.05; Stroop test (inhibition/flexibility), p&lt;0.05). There was no difference between CHD and controls in VO2 max (29.7±8.5 Vs 32±6.3 ml/kg/min) and maximal cardiac output (15.5±3.9 Vs 17±2.6 l/min), whereas cardiac output and cardiac index at the ventilatory threshold were lower in CHD (5.75±1 Vs 7.06±0.6 l/min/m2, p&lt;0.05, and 11.2±2.2 Vs 14.1±2.8 l/min, p&lt;0.01, respectively). There was a significant difference in the kinetics of NIRS signal with higher amplitude for CHD patients vs. controls for O2Hb (p&lt;0.01); THb (p&lt;0.05) and Hbdiff (p&lt;0.05). Significant higher amplitude were also found for O2Hb, THb, Hbdiff (p&lt;0.0001) in younger (62 years) participants. HHb (p&lt;0.0001) and Hbdiff (p&lt;0.01) amplitude was higher for fit (≥120% theoretical VO2max) vs. less fit (&lt;120%) participants. Discussion: Compared to age-matched controls, our sample of stable fit CHD patients had a comparable maximal exercise tolerance and cardiac output, with higher NIRS cerebral signals amplitude for O2Hb, THb and Hbdiff. This latter parameter thus does not seem to influence cognitive performance at rest, that was lower in CHD patients, especially in executive functions. However, an important inter-individual variability of cerebral NIRS signal amplitude was observed, with age and fitness appearing as major contributors. We plan to recruit a larger sample of subjects to assess more clearly relationships between exercise, tolerance hemodynamic parameters and cognitive performance.
Abstract 3490: Formal Comparison between absolute and relative cut points for Coronary Artery Calcification in At Intermediate Risk Community-Based Men and Women: The Framingham Heart Study
Authors: Udo Hoffmann, Joseph M Massaro, Caroline S Fox, Emily Manders, Christopher J O’Donnell
Journal: Circulation (2007)

Background: Coronary artery calcification (CAC) may improve risk stratification of individuals at intermediate Framingham Risk. We determined the agreement between absolute and relative cut points to identify subjects with elevated CAC in individuals at intermediate Framingham Risk. Methods : The amount of CAC was quantified in 3238 participants from the Framingham Heart Study (FHS) Offspring and Third Generation cohorts (48% women, mean age 53 years) free of cardiovascular disease who underwent ECG triggered cardiac MDCT. We included subjects at intermediate Framingham risk, defined as 6 –20% ten year event risk, (n = 1177) and subjects free of cardiovascular risk factors (n = 1586). Distribution of CAC according to absolute (Agatston Score [AS] &gt; 400) and relative (90 th percentile stratified by age as derived from the healthy reference subset) cut-points were determined for men and women Results: Among men with intermediate FRS, 17.7% had CAC above the 90 th percentile of the healthy referent sample, whereas 14% had CAC &gt; 400. Similar findings were observed in women: 11.5% had CAC above the 90 th percentile of the healthy referent sample, whereas 2% had CAC &gt; 400. Among all individuals at intermediate FRS Only 10.8% of subjects above the 90 th percentile had an AS &lt; 400. Conclusions: The fraction of subjects with elevated CAC as determined by an AS &gt; 400 is lower than subjects above the 90 th percentile especially among women at intermediate FRS in the community-based FHS. Overall, the agreement between absolute and relative cut points to identify subjects with elevated CAC is poor in this population. Prospective outcomes studies are necessary to test the hypothesis that relative rather than absolute cutpoints of CAC should be used to further stratify subjects at intermediate risk.
Lack of efficacy of carbamazepine in the treatment of panic disorder
Authors: T W Uhde, M B Stein, R M Post
Journal: American Journal of Psychiatry (1988)

The authors conducted a controlled study of carbamazepine in the treatment of 14 patients with panic disorder. Although there was a statistically significant reduction in symptoms of anxiety on several measures, only one of the patients was judged to have a marked and sustained clinical improvement while taking carbamazepine. Forty percent of the patients had a decrease in frequency of panic attacks during carbamazepine treatment, 50% had an increase, and 10% showed no change. The presence of either EEG abnormalities or prominent psychosensory symptoms did not predict response to carbamazepine. These findings are discussed within the context of an epileptiform model for panic disorder.
The concept of subcortical dementia
Authors: S J Huber, G W Paulson
Journal: American Journal of Psychiatry (1985)

The authors review the concept of subcortical dementia, specifically the dementia associated with Huntington's disease, Parkinson's disease, and progressive supranuclear palsy, all subcortical processes that involve deterioration of mental abilities. Subcortical dementia affords a unique opportunity to study the progressive memory loss associated with dementia because, in contrast to cortical dementias such as Alzheimer's disease, this relatively circumscribed syndrome does not involve dysfunction of language (aphasia) and perception (agnosia and apraxia). Research strategies are proposed to examine the concept of subcortical dementia, an entity that remains controversial and not well understood. The subcortical dementias may constitute a group of partially treatable forms of dementia.
Triple Negative (JAK2 exon 12 /14 and MPL wild type) Myelofibrosis Have Higher Expression Of CDC25A and Greater Sensitivity To CDC25A Inhibition Compared To JAK2 Mutant Cases
Authors: Ali Tabarroki, Valeria Visconte, Heesun J. Rogers, Juraj Bodo, Li Zhang, Felicitas Lacbawan, Edy Hasrouni, John Barnard, Alan E. Lichtin, Daniel Lindner, Mikkael A. Sekeres, Ramon V. Tiu
Journal: Blood (2013)