tbuckley/cabot-search huggingface dataset:
Exercise, smoking, and calcium intake during adolescence and early adulthood as determinants of peak bone mass
Authors: M J Valimaki, M Karkkainen, C Lamberg-Allardt, K Laitinen, E Alhava, J Heikkinen, O Impivaara, P Makela, J Palmgren, R Seppanen, I Vuori
Journal: BMJ (1994)

To evaluate the contribution to peak bone mass of exercise, smoking, and calcium intake in adolescents and young adults.Prospective cohort study with end point measurement (bone mineral density) after 11 years' follow up for lifestyle.Five university hospital clinics.264 (153 females, 111 males) subjects aged 9 to 18 years at the beginning of the follow up and 20 to 29 years at the time of measurement of bone mineral density.Bone mineral density of lumbar spine and femoral neck by dual energy x ray absorptiometry; measures of physical activity and smoking and estimates of calcium intake repeated three times during follow up.In the groups with the lowest and highest levels of exercise the femoral bone mineral densities (adjusted for age and weight) were 0.918 and 0.988 g/cm2 for women (P = 0.015, analysis of covariance) and 0.943 and 1.042 g/cm2 for men (P = 0.005), respectively; at the lumbar spine the respective values were 1.045 and 1.131 (P = 0.005) for men. In men the femoral bone mineral densities (adjusted for age, weight, and exercise) were 1.022 and 0.923 g/cm2 for the groups with the lowest and highest values of smoking index (P = 0.054, analysis of covariance). In women the adjusted femoral bone mineral density increased by 4.7% together with increasing calcium intake (P = 0.089, analysis of covariance). In multiple regression analysis on bone mineral density of the femoral neck, weight, exercise, age, and smoking were independent predictors for men; with weight, exercise, and age for women. These predictors together explained 38% of the variance in bone mineral density in women and 46% in men. At the lumbar spine, weight, smoking, and exercise were predictors for men; and only weight for women.Regular exercise and not smoking is important in achieving maximal peak bone mass in adolescents and young adults.
Abstract 15706: Survival in Children With Trisomy 21 Undergoing Single Ventricle Palliation
Authors: John Colquitt, Shaine A Morris, Susan Denfield, Charles D Fraser, William B Kyle
Journal: Circulation (2014)

Background: Children with Trisomy 21 (T21) and single ventricle anatomy (SV) may have increased mortality compared to those without T21. Supporting data are limited. Our objectives were to describe survival in children with T21 and SV and determine risk factors associated with mortality.

Methods: We performed a single-center retrospective review. All patients born since 1980 with T21 and SV were included. We used Kaplan-Meier (KM) analysis with comparison by log rank to evaluate characteristics potentially associated with mortality in this cohort.

Results: Of 28 patients with T21 and SV, 26 (93%) had unbalanced atrioventricular septal defects with 13 (50%) being RV dominant. One patient had hypoplastic left heart syndrome and one had tricuspid atresia. 22 patients (79%) underwent pulmonary artery (PA) banding. Superior cavopulmonary connection (SCPC) was performed in 17 patients (61%) at a median age of 13 months (range 3 mo [[Unable to Display Character: –]] 13 y), with a banded PA left undivided in most. Three of these (18%) went on to total cavopulmonary connection (TCPC). Single-stage TCPC was performed in 2 other patients (7%). Median age at follow-up was 5 years (range 0.1 [[Unable to Display Character: –]] 33 y) overall and 7.5 years (range 1.5 [[Unable to Display Character: –]] 33 y) in survivors. One-year KM survival was 75% (95% CI 59-91%). Of 7 patients who died < 1 year old, only 1 had undergone SCPC. Two-year KM survival was 60% (95% CI 42-79%) with limited mortality beyond 2 years (Figure). Seventeen patients (61%) reached 5 years of age with 13 having SCPC by that age. Of 5 patients with TCPC, 4 are alive (age range 7 [[Unable to Display Character: –]] 14 y). Pulmonary vascular resistance (PVR) ≥ 3 WU*m2 in the first year of life was associated with increased mortality (p = 0.028) (Figure). No patient with PVR < 3 WU*m2 died. There was a trend toward association between ≥ moderate atrioventricular valve regurgitation and mortality (p = 0.071).

Conclusions: While T21 patients with SV remain a high-risk group, survival is excellent when PVR is < 3 WU*m2 in the first year of life with minimal attrition beyond 2 years of age.

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Current Perspectives on Coronary Chronic Total Occlusions
Authors: Paul Fefer, Merril L. Knudtson, Asim N. Cheema, P. Diane Galbraith, Azriel B. Osherov, Sergey Yalonetsky, Sharon Gannot, Michelle Samuel, Max Weisbrod, Daniel Bierstone, John D. Sparkes, Graham A. Wright, Bradley H. Strauss
Journal: Journal of the American College of Cardiology (2012)
TEG and ROTEM: Technology and clinical applications
Authors: David Whiting, James A. DiNardo
Journal: American Journal of Hematology (2013)

Initially described in 1948 by Hertert thromboelastography (TEG) provides a real-time assessment of viscoelastic clot strength in whole blood. Rotational thromboelastometry (ROTEM) evolved from TEG technology and both devices generate output by transducing changes in the viscoelastic strength of a small sample of clotting blood (300 µl) to which a constant rotational force is applied. These point of care devices allow visual assessment of blood coagulation from clot formation, through propagation, and stabilization, until clot dissolution. Computer analysis of the output allows sophisticated clot formation/dissolution kinetics and clot strength data to be generated. Activation of clot formation can be initiated with both intrinsic (kaolin, ellagic acid) and extrinsic (tissue factor) activators. In addition, the independent contributions of platelets and fibrinogen to final clot strength can be assessed using added platelet inhibitors (abciximab and cytochalasin D). Increasingly, ROTEM and TEG analysis is being incorporated in vertical algorithms to diagnose and treat bleeding in high-risk populations such as those undergoing cardiac surgery or suffering from blunt trauma. Some evidence suggests these algorithms might reduce transfusions, but further study is needed to assess patient outcomes.
How to measure the cost‐effectiveness of periodontal treatments
Authors: Chris Vernazza, Peter Heasman, Francesca Gaunt, Mark Pennington
Journal: Periodontology 2000 (2012)

Abstract There is a need to measure efficiency of periodontal treatments. Efficiency questions can be addressed through a variety of economic evaluation techniques: cost minimization, cost‐effectiveness, cost utility and cost–benefit analysis. Each of these techniques is outlined in this article, including a detailed discussion of different preference‐based outcome (utility) measures. Despite the need, few analyses have been undertaken in periodontology. There are several issues in undertaking cost‐effectiveness analyses specific to periodontology and these are examined in detail: outcome measures including patient‐based vs. clinical measures of outcome; discounting or taking into account time preference for outcomes and costs; problems of costing, including the perspective taken in an analysis; interpreting the evidence, in particular using incremental cost‐effectiveness ratios; and global variation in periodontal care delivery, including healthcare systems and the use of hygienists. The need for cost‐effectiveness analysis in periodontology is explored further, and the need to involve a health economist in such an evaluation is underlined.
Thyroid hormone receptor β1 is expressed in the human hair follicle
Authors: N. Billoni, B. Buan, B. Gautier, O. Gaillard, Y.F. MahÉ, B.A. Bernard
Journal: British Journal of Dermatology (2000)

To understand better the mechanisms by which thyroid hormone can exert its effects on the hair follicle, we looked for the expression of members of the thyroid hormone receptor (TR) family in human hair follicles. Immunoreactive TRs were detected in both dermal and epithelial compartments of the human pilosebaceous unit. Using reverse transcriptase-polymerase chain reaction, we established that TRbeta1 was the predominant form of TR expressed in the human hair follicle. In addition, we investigated the effects of 3,3', 5-triiodo-L-thyronine (T3) on the survival of human hair follicles in vitro, to understand the role of this thyroid hormone on hair follicle homeostasis. A physiological level of free T3 significantly enhanced human hair survival in vitro.
Abstract 2556: A Comparative Analysis of Outcomes for Pediatric Patients with Biopsy-Proven Myocarditis, Clinically-Diagnosed Myocarditis and Idiopathic Dilated Cardiomyopathy.
Authors: Susan Foerster, Charles Canter, Amy Carey, Lynn A Sleeper, John L Jefferies, Paul Kantor, Jacqueline Lamour, Renee Margossian, Jane Messere, Elfriede Pahl, Paolo Rusconi, Robert Shaddy, Steven Webber, Jeffrey Towbin, Steven Lipshultz
Journal: Circulation (2007)

Background: Data on outcomes in children with myocarditis is sparse and challenging to interpret given no ``gold standard” for diagnosis. The NHLBI Pediatric Cardiomyopathy Registry provides a large, multi-center cohort with clinical and echocardiographic follow-up of up to 16 years. Methods/Results : We compared cases of biopsy-confirmed myocarditis (BCM, N=119) and clinically-diagnosed myocarditis (CDM, N=253), with idiopathic dilated cardiomyopathy (IDCM, N=1123). BCM and CDM patients were older at diagnosis than those with IDCM (median age 1.6, 1.9, 1.2 yr, respectively). For BCM, heart failure symptoms (86%) and admission (97%) at diagnosis were more common (p&lt;0.05 compared to either CDM/IDCM). LV end-diastolic dimension (EDD) Z-score was abnormal (&gt;2) in 71% with myocarditis and 86% with IDCM. Systolic function was impaired in all groups, with a median fractional shortening (FS) Z score of -9 for myocarditis and -10 for IDCM; 23% of myocarditis patients had impaired function without dilation. Two-year death/transplant rates were 24% (BCM), 24% (CDM), and 47% (IDCM). Of myocarditis survivors, 46% had normalization of both EDD and FS Z-scores at 2 years vs. 25% for IDCM (p&lt;.0001). Baseline echo status was strongly associated with later echo status for IDCM pts. Recovery from myocarditis at 2 years was not strongly associated with baseline echocardiographic characteristics, but transplant-free survival was lower in myocarditis patients when both baseline FS and EDD were abnormal (logrank p=.03). When therapeutic data were available, the BCM group received IVIG/steroids most often (44% vs. 23% CDM, 6% IDCM); this was not significantly associated with 2-year echo recovery or transplant-free survival, but power was limited. Conclusions : In this dataset, children with BCM and CDM have similar profiles and a better outcome than those with IDCM, with 76% surviving without transplant at 2 years. Nearly 1 / 2 have normalization of LV size and function, but the presence of both dilation and poor function at presentation is associated with increased risk for death or transplant. Echocardiographic normalization occurs in 25% of IDCM survivors by 2 years. This study is limited by being an analysis of available information in a database collected for other purposes.
Effect of socioeconomic deprivation on waiting time for cardiac surgery: retrospective cohort study Commentary: Three decades of the inverse care law
Authors: Jill P Pell, Alastair C H Pell, John Norrie, Ian Ford, Stuart M Cobbe
Journal: BMJ (2000)

<h3>Objective</h3> To perform a systematic review (SR) on the effectiveness of self-management interventions, in order to inform the European League Against Rheumatism Recommendations for its implementation in patients with inflammatory arthritis (IA). <h3>Methods</h3> The SR was conducted according to the Cochrane Handbook and included adults (≥18 years) with IA. The search strategy was run in Medline through PubMed, Embase, Cochrane Library, CINAHL Plus with Full Text, and PEDro. The assessment of risk of bias, data extraction and synthesis were performed by two reviewers independently. A narrative Summary of Findings was provided according to the Grading of Recommendations, Assessment, Development and Evaluation. <h3>Results</h3> From a total 1577 references, 57 were selected for a full-text review, and 32 studies fulfilled the inclusion criteria (19 randomised controlled trials (RCTs) and 13 SRs). The most studied self-management components were specific interactive disease education in ten RCTs, problem solving in nine RCTs, cognitive–behavioural therapy in eight RCTs, goal setting in six RCTs, patient education in five RCTs and response training in two RCTs. The most studied interventions were multicomponent or single exercise/physical activity in six SRs, psychosocial interventions in five SRs and education in two SRs. Overall, all these specific components and interventions of self-management have beneficial effects on IAs-related outcomes. <h3>Conclusions</h3> The findings confirm the beneficial effect of the self-management interventions in IA and the importance of their implementation. Further research should focus on the understanding that self-management is a complex intervention to allow the isolation of the effectiveness of its different components.
Rapid Lentiviral Transduction Preserves the Engraftment Potential of Fanca−/− Hematopoietic Stem Cells
Authors: Lars UW Müller, Michael D Milsom, Mi-Ok Kim, Axel Schambach, Todd Schuesler, David A Williams
Journal: Molecular Therapy (2008)

Fanconi anemia (FA) is a rare recessive syndrome, characterized by congenital anomalies, bone marrow failure, and predisposition to cancer. Two earlier clinical trials utilizing γ-retroviral vectors for the transduction of autologous FA hematopoietic stem cells (HSCs) required extensive in vitro manipulation and failed to achieve detectable long-term engraftment of transduced HSCs. As a strategy for minimizing ex vivo manipulation, we investigated the use of a "rapid" lentiviral transduction protocol in a murine Fanca-/- model. Importantly, while this and most murine models of FA fail to completely mimic the human hematopoietic phenotype, we observed a high incidence of HSC transplant engraftment failure and low donor chimerism after conventional transduction (CT) of Fanca-/- donor cells. In contrast, rapid transduction (RT) of Fanca-/- HSCs preserved engraftment to the level achieved in wild-type cells, resulting in long-term multilineage engraftment of gene-modified cells. We also demonstrate the correction of the characteristic hypersensitivity of FA cells against the cross-linking agent mitomycin C (MMC), and provide evidence for the advantage of using pharmacoselection as a means of further increasing gene-modified cells after RT. Collectively, these data support the use of rapid lentiviral transduction for gene therapy in FA.
The development of hyaluronic acid as a targeted transport vehicle for chemotherapeutic drugs
Authors: Tracey Jean Brown, Jeanette Falzon, Minh Hue Pho, Erin Hatherell, Kaushaliya Virjibhai Vaghela, Jennifer C Wilson, Richard Fox, Peter Gibbs, Mark A Rosenthal, J Robert E Fraser, Gary Russell Brownlee
Journal: Cancer Research (2005)

Introduction: The non-selective nature of systemic chemotherapeutic drugs necessitates the administration of high doses to achieve and maintain therapeutic levels within the tumor, which often results in severe side-effects. The efficacy of the drug could be maintained and the toxicity alleviated by direct targeting of anticancer agents to the tumor. The observation that the naturally occurring polysaccharide, hyaluronic acid (HA) has high affinity for tumors and that numerous tumors over-express HA receptors has lead to the development of a series of proprietary HA/cytotoxic drug formulations. The purpose of this study was to evaluate if such formulations could target and expedite the delivery of anticancer agents to solid tumors and enhance their function. Methodology: The mode of interaction between HA and the cytotoxic drugs was investigated using CD and NMR spectroscopy. The ability of HA to target anticancer agents to the HA receptor, CD44, was demonstrated by IV injection of radioactive anticancer agents ᠱ2.5mg/kg of HA (Mr 750 kDa) into nude mice bearing human breast cancer xenografts. The effect of HA on the therapeutic index of chemotherapeutic drugs was established by treatment of nude mice carrying human breast xenografts with methotrexate, 5-fluorouracil (5FU) and doxorubicin (DOX) + HA for six cycles of one week. The safety of HyFIVETM (HA/5-FU) and HyDOXTM (HA/DOX) drug formulations was established in Phase l clinical trials where 30 patients with metastatic cancer were administered 500mg/m2 HA in combination with escalating doses of DOX (30-60mg/m2) or 5FU (cumulative dose of 1350-2250mg/m2 per cycle). Results: Chemical interaction studies demonstrated that no ionic, hydrophobic or covalent interaction existed between the HA and drugs but instead, the small anti-cancer agents were entrained within the HA matrix through a viscosity related effect. It was demonstrated that HA could target anticancer drugs to tumors where, within 10min, HA directed up to 400% more anticancer agent to the tumor and lymph nodes whilst reducing the gastrointestinal (GI) and cardiac drug content by up to 660%. Efficacy studies in breast cancer xenograft models demonstrated a greater tumor response, elimination of secondary cancer and a significant reduction in both Gl and cardiac toxicities. The Phase l studies showed that the HA formulations were well tolerated; tumour responses were observed and the co-administration of HA did not alter the pharmacokinetics of clinically relevant doses of 5FU or DOX. Conclusions: These studies demonstrate that HA can act as a targeted transport vehicle for chemotherapeutic drugs thereby potentially increasing treatment efficacy while reducing treatment toxicity.
Contemporary Outcomes After the Fontan Procedure
Authors: Page A.W. Anderson, Lynn A. Sleeper, Lynn Mahony, Steven D. Colan, Andrew M. Atz, Roger E. Breitbart, Welton M. Gersony, Dianne Gallagher, Tal Geva, Renee Margossian, Brian W. McCrindle, Stephen Paridon, Marcy Schwartz, Mario Stylianou, Richard V. Williams, Bernard J. Clark
Journal: Journal of the American College of Cardiology (2008)
Abstract 314: Inactivation-Resistant GSK3{alpha}{beta} Dual Isoform Expression Attenuates Isoproterenol-Induced Myocardial Hypertrophy and Preserves Cardiac Function
Authors: Ian G Webb, Yasuhiro Nishino, James E Clark, Colin E Murdoch, Ajay M Shah, Michael S Marber
Journal: Circulation (2008)

Glycogen synthase kinase-3 (GSK-3) is implicated as an important signalling mediator in normal developmental myocardial growth and adverse hypertrophic remodelling. Upstream phosphorylation of isof...
Abstract 49: Performance of North American Prehospital Termination of Resuscitation Rules in Osaka, Japan.
Authors: Kentaro Kajino, Taku Iwami, Mohamud Daya, Tetsuhisa Kitamura, Tomohiko Sakai, Tatsuya Nishiuchi, Yasuyuki Hayashi, Atushi Hiraide, Masashi Kishi, Shigeru Yamayoshi
Journal: Circulation (2010)

Introduction:  In Japan, EMS guidelines require that all patients with out-of-hospital cardiac arrest (OHCA) be transported to a hospital regardless of the success or failure of prehospital resuscitation efforts. In an attempt to better utilize health care resources, Basic Life Support (BLS) and Advanced Life Support (ALS) prehospital termination of resuscitation (TOR) rules have been developed, validated and implemented in North America.   Purpose:  The aim of this study was to assess the performance and impact of these BLS and ALS TOR rules in Osaka, Japan.   Materials and methods:  This was a retrospective cohort analysis of all persons aged 18 years or older who suffered OHCA of presumed cardiac etiology in Osaka Prefecture, Japan from January 2005 through December 2008. All data were prospectively collected an Utstein-style database. Primary outcome measure was one month neurologically favorable survival (CPC ≤ 2). Cases were dichotomized on the basis of whether they met the criteria for the BLS TOR rule (OHCA not witnessed by EMS personnel and no prehospital AED use or return of spontaneous circulation) or the ALS TOR rule (BLS rule criteria plus OHCA not witnessed by a bystander and no bystander CPR). We calculated the specificity and positive predictive value of each TOR rule for identifying patients without one-month survival with favorable neurological outcome.   Results:  Of 14,921 cardiac arrests of presumed cardiac etiology, 607 cases (4.1%) had neurologically favorable survival. Of 11,038 cases (74%) who met BLS criteria for TOR efforts, only 26 cases (0.2%) survived to neurologically favorable survival. Of 4,752 (32%) who met the ALS criteria for TOR efforts, only 10 cases (0.2%) survived to neurologically favorable survival.   Conclusion:  The North American BLS and ALS TOR rules both performed well in Osaka with misclassification rates of 0.2%. Implementation of these guidelines into current resuscitation practices in Japan deserves further consideration.
Article was disappointing
Authors: M C Bateson
Journal: BMJ (2007)

Sanders and Kingsnorth gave a less than comprehensive view of their subject.1 Really important gallstones that must be dealt with occur in the bile ducts. Where is the discussion about diagnosis with magnetic resonance imaging and computed tomography, management with therapeutic endoscopic retrograde cholangiopancreatography, the place of open surgery, and discussion of optimal antibiotic therapy of ascending cholangitis in 2007?

Of course …
Murine typhus in children: clinical and laboratory features from 41 cases in Crete, Greece
Authors: A. Gikas, S. Kokkini, C. Tsioutis, D. Athenessopoulos, E. Balomenaki, S. Blasak, C. Matheou, Y. Tselentis, A. Psaroulaki
Journal: Clinical Microbiology and Infection (2009)
Abstract 2597: Direct inhibition of oncogenic KRAS by hydrocarbon-stapled SOS1 helices
Authors: Elizaveta Leshchiner, Joseph Bellairs, Gregory H. Bird, Kwadwo Opoku-Nsiah, Marina Godes, Lored D. Walensky
Journal: Cancer Research (2014)

Abstract Activating mutations in KRAS represent the most frequent oncogenic driving force among the RAS homologs K-, N- and H-RAS, and are associated with poor prognosis and chemoresistance. KRAS mutations are present in approximately 30% of tumors, and at even higher frequencies in cancers of the pancreas, lung, thyroid gland, colon, and liver. In pancreatic ductal adenocarcinomas (PDAC), which carries a 5-year survival rate of less than 5%, activating KRAS mutations are present in over 90% of tumors. Moreover, these mutations have been causally linked to the initiation and progression of PDAC. Despite the mechanistic insights into KRAS-mediated oncogenesis, development of high affinity targeted inhibitors remains a formidable challenge. Here, we report the synthesis and application of hydrocarbon-stapled peptides as prototype therapeutics for blocking wild type and mutant KRAS in vitro and in cancer cells. Stabilized Alpha-Helices of SOS1 (SAH-SOS1) were generated by inserting hydrocarbon staples into SOS1 peptide sequence to recapitulate the alpha-helical structure of the native KRAS-interaction domain. SAH-SOS1 peptides, but not negative control analogs, bound to a variety of KRAS constructs with nanomolar affinity, inhibiting nucleotide exchange. This sequence-specific biochemical activity correlated with impairment of KRAS-driven cancer cell viability and signal transduction. These studies provide proof-of-concept for the utility of SAH-SOS1 peptides in dissecting and targeting the oncogenic KRAS pathway in human cancer. Citation Format: Elizaveta Leshchiner, Joseph Bellairs, Gregory H. Bird, Kwadwo Opoku-Nsiah, Marina Godes, Lored D. Walensky. Direct inhibition of oncogenic KRAS by hydrocarbon-stapled SOS1 helices. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2597. doi:10.1158/1538-7445.AM2014-2597