tbuckley/cabot-search huggingface dataset:
Promoting physical activity in children: the stepwise development of the primary school-based JUMP-in intervention applying the RE-AIM evaluation framework
Authors: J S B De Meij, M J M Chinapaw, S P J Kremers, M F Van der wal, M E Jurg, W Van Mechelen
Journal: British Journal of Sports Medicine (2008)

Background There is a lack of effective intervention strategies that promote physical activity (PA) in school children. Furthermore, there is a gap between PA intervention research and the delivery of programmes in practice. Evaluation studies seldom lead to adaptations in interventions that are subsequently evaluated by implementation on a wider scale. The stepwise development and study of JUMP-in aims to add knowledge to better understand how, when and for whom intervention effects (or lack of effects) occur. Methods This paper describes the stepwise development of JUMP-in, a Dutch school-based multi-level intervention programme, aimed at the promotion of PA behaviour in 6–12-year-old children. JUMP-in incorporates education, sports, care and policy components. JUMP-in consists of six programme components: Pupil Follow-up Monitoring System; School sports clubs; In-class exercises with “The Class Moves!”; Personal workbook “This is the way you move!”; Parental Information Services; Extra lessons in physical education, Motor Remedial Teaching and extra care. The process and effect outcomes of a pilot study were translated into an improved programme and intervention organisation, using the RE-AIM framework (Reach, Efficacy, Adoption, Implementation and Maintenance). This paper presents the process and results of the application of this framework, which resulted in a widescale implementation of JUMP-in. Results The application of the RE-AIM framework resulted in challenges and remedies for an improved JUMP-in intervention. The remedies required changes at three different levels: (1) the content of the programme components; (2) the organisation and programme management; and (3) the evaluation design. Conclusions Considering factors that determine the impact of PA interventions in ‘real life’ is of great importance. The RE-AIM framework appeared to be a useful guide by which process and effect outcomes could be translated into an improved programme content and organisation.
Glucose variability measures and their effect on mortality: a systematic review
Authors: Saeid Eslami, Zhila Taherzadeh, Marcus J. Schultz, Ameen Abu-Hanna
Journal: Intensive Care Medicine (2011)

To systematically review the medical literature on the association between glucose variability measures and mortality in critically ill patients. Studies assessing the association between a measure of glucose variability and mortality that reported original data from a clinical trial or observational study on critically ill adult patients were searched in Ovid MEDLINE® and Ovid EMBASE®. Data on patient populations, study designs, glucose regulations, statistical approaches, outcome measures, and glucose variability indicators (their definition and applicability) were extracted. Twelve studies met the inclusion criteria; 13 different indicators were used to measure glucose variability. Standard deviation and the presence of both hypo- and hyperglycemia were the most common indicators. All studies reported a statistically significant association between mortality and at least one glucose variability indicator. In four studies both blood glucose levels and severity of illness were considered as confounders, but only one of them checked model assumptions to assert inference validity. Glucose variability has been quantified in many different ways, and in each study at least one of them appeared to be associated with mortality. Because of methodological limitations and the possibility of reporting bias, it is still unsettled whether and in which quantification this association is independent of other confounders. Future research will benefit from using an indicator reference subset for glucose variability, metrics that are linked more directly to negative physiological effects, more methodological rigor, and/or better reporting.
Genomic analysis reveals that Pseudomonas aeruginosa virulence is combinatorial.
Authors: Daniel G Lee, Jonathan M Urbach, Gang Wu, Nicole T Liberati, Rhonda L Feinbaum, Sachiko Miyata, Lenard T Diggins, Jianxin He, Maude Saucier, Eric Déziel, Lisa Friedman, Li Li, George Grills, Kate Montgomery, Raju Kucherlapati, Laurence G Rahme, Frederick M Ausubel
Journal: Genome biology (2006)

Abstract Background Pseudomonas aeruginosa is a ubiquitous environmental bacterium and an important opportunistic human pathogen. Generally, the acquisition of genes in the form of pathogenicity islands distinguishes pathogenic isolates from nonpathogens. We therefore sequenced a highly virulent strain of P. aeruginosa , PA14, and compared it with a previously sequenced (and less pathogenic) strain, PAO1, to identify novel virulence genes. Results The PA14 and PAO1 genomes are remarkably similar, although PA14 has a slightly larger genome (6.5 megabses [Mb]) than does PAO1 (6.3 Mb). We identified 58 PA14 gene clusters that are absent in PAO1 to determine which of these genes, if any, contribute to its enhanced virulence in a Caenorhabditis elegans pathogenicity model. First, we tested 18 additional diverse strains in the C. elegans model and observed a wide range of pathogenic potential; however, genotyping these strains using a custom microarray showed that the presence of PA14 genes that are absent in PAO1 did not correlate with the virulence of these strains. Second, we utilized a full-genome nonredundant mutant library of PA14 to identify five genes (absent in PAO1) required for C. elegans killing. Surprisingly, although these five genes are present in many other P. aeruginosa strains, they do not correlate with virulence in C. elegans . Conclusion Genes required for pathogenicity in one strain of P. aeruginosa are neither required for nor predictive of virulence in other strains. We therefore propose that virulence in this organism is both multifactorial and combinatorial, the result of a pool of pathogenicity-related genes that interact in various combinations in different genetic backgrounds.
Use of a Chemically Modified Antisense Oligonucleotide Library to Identify and Validate Eg5 (Kinesin-Like 1) as a Target for Antineoplastic Drug Development
Authors: Erich Koller, Stephanie Propp, Hong Zhang, Chenguang Zhao, Xiaokun Xiao, MingYi Chang, Scott A. Hirsch, Peter J. Shepard, Seongjoon Koo, Cain Murphy, Robert I. Glazer, Nicholas M. Dean
Journal: Cancer Research (2006)

A library of 2'-methoxyethyl-modified antisense oligonucleotides (2'MOE ASO) targeting 1,510 different genes has been developed, validated, and used to identify cell cycle regulatory genes. The most effective molecular target identified was Eg5 (kinesin-like-1), which when inhibited gave the largest increase in 4N DNA in various tumor cells. The Eg5 ASO reduced Eg5 levels, inhibited proliferation, increased apoptosis, and altered the expression of other cell cycle proteins, including survivin and Aurora-A. To examine the therapeutic utility of the Eg5 ASO, the compound was also evaluated in xenograft models. Treatment with Eg5 ASO produced a statistically significant reduction of tumor growth, reduction in Eg5 expression in the tumors, and changes in histone phosphorylation, consistent with a loss of Eg5 protein expression. These data show, for the first time, the utility of a 2'MOE ASO library for high-throughput cell culture-based functional assays and suggest that an Eg5 ASO also has potential in a therapeutic strategy.
Association of Functional Decline With Subsequent Diabetes Incidence in U.S. Adults Aged 51 Years and Older: The Health and Retirement Study 1998–2010
Authors: Barbara H. Bardenheier, Edward W. Gregg, Xiaohui Zhuo, Yiling J. Cheng, Linda S. Geiss
Journal: Diabetes Care (2014)

OBJECTIVE We assessed whether functional decline and physical disability increase the subsequent risk of diabetes. RESEARCH DESIGN AND METHODS We used a subsample of adults aged 51 years and older with no diabetes at baseline who were followed up to 12 years (1998-2010) in the Health and Retirement Study, an observational study of a nationally representative survey. We assessed baseline disability status and incident disability with subsequent risk of diabetes, accounting for death as a competing risk and controlling for BMI, age, sex, race/ethnicity, net wealth, mother's level of education, respondents' level of education, and time of follow-up. Disability was defined as none, mild, moderate, and severe, based on a validated scale of mobility measures. Diabetes was identified by self-report of a diagnosis from a doctor. Population attributable fraction (PAF) was calculated to assess the percentage of diabetes cases that were attributable to mobility disability. RESULTS The sample included 22,878 adults with an average of 8.7 years of follow-up; 9,649 (41.2%) reported some level of disability at baseline, and 8,175 (35.7%) additional participants developed disability during follow-up; 3,546 (15.5%) participants developed diabetes; and 5,869 (25.6%) died. Regression analyses found a statistically significant dose-response relationship of increased risk of diabetes (28-95%) among those with any level of functional decline, prevalent or incident. Among the subanalytic sample, including incident disability only, the PAF was 6.9% (CI 4.2-9.5). CONCLUSIONS Our findings suggest those who become disabled, even mildly, are at increased risk of developing diabetes. This finding raises the possibility that approaches to prevent disability in older adults could also reduce diabetes incidence.
Human Neural Stem Cell Transplantation Ameliorates Radiation-Induced Cognitive Dysfunction
Authors: Munjal M. Acharya, Lori-Ann Christie, Mary L. Lan, Erich Giedzinski, John R. Fike, Susanna Rosi, Charles L. Limoli
Journal: Cancer Research (2011)

Abstract Cranial radiotherapy induces progressive and debilitating declines in cognition that may, in part, be caused by the depletion of neural stem cells. The potential of using stem cell replacement as a strategy to combat radiation-induced cognitive decline was addressed by irradiating athymic nude rats followed 2 days later by intrahippocampal transplantation with human neural stem cells (hNSC). Measures of cognitive performance, hNSC survival, and phenotypic fate were assessed at 1 and 4 months after irradiation. Irradiated animals engrafted with hNSCs showed significantly less decline in cognitive function than irradiated, sham-engrafted animals and acted indistinguishably from unirradiated controls. Unbiased stereology revealed that 23% and 12% of the engrafted cells survived 1 and 4 months after transplantation, respectively. Engrafted cells migrated extensively, differentiated along glial and neuronal lineages, and expressed the activity-regulated cytoskeleton-associated protein (Arc), suggesting their capability to functionally integrate into the hippocampus. These data show that hNSCs afford a promising strategy for functionally restoring cognition in irradiated animals. Cancer Res; 71(14); 4834–45. ©2011 AACR.
Level of G protein–Coupled Receptor Kinase-2 Determines Myocardial Ischemia/Reperfusion Injury via Pro- and Anti-Apoptotic Mechanisms
Authors: Henriette Brinks, Matthieu Boucher, Erhe Gao, J. Kurt Chuprun, Stéphanie Pesant, Philip W. Raake, Z. Maggie Huang, Xiaoliang Wang, Gang Qiu, Anna Gumpert, David M. Harris, Andrea D. Eckhart, Patrick Most, Walter J. Koch
Journal: Circulation Research (2010)

Activation of prosurvival kinases and subsequent nitric oxide (NO) production by certain G protein-coupled receptors (GPCRs) protects myocardium in ischemia/reperfusion injury (I/R) models. GPCR signaling pathways are regulated by GPCR kinases (GRKs), and GRK2 has been shown to be a critical molecule in normal and pathological cardiac function.A loss of cardiac GRK2 activity is known to arrest progression of heart failure (HF), at least in part by normalization of cardiac β-adrenergic receptor (βAR) signaling. Chronic HF studies have been performed with GRK2 knockout mice, as well as expression of the βARKct, a peptide inhibitor of GRK2 activity. This study was conducted to examine the role of GRK2 and its activity during acute myocardial ischemic injury using an I/R model.We demonstrate, using cardiac-specific GRK2 and βARKct-expressing transgenic mice, a deleterious effect of GRK2 on in vivo myocardial I/R injury with βARKct imparting cardioprotection. Post-I/R infarct size was greater in GRK2-overexpressing mice (45.0±2.8% versus 31.3±2.3% in controls) and significantly smaller in βARKct mice (16.8±1.3%, P<0.05). Importantly, in vivo apoptosis was found to be consistent with these reciprocal effects on post-I/R myocardial injury when levels of GRK2 activity were altered. Moreover, these results were reflected by higher Akt activation and induction of NO production via βARKct, and these antiapoptotic/survival effects could be recapitulated in vitro. Interestingly, selective antagonism of β(2)ARs abolished βARKct-mediated cardioprotection, suggesting that enhanced GRK2 activity on this GPCR is deleterious to cardiac myocyte survival.The novel effect of reducing acute ischemic myocardial injury via increased Akt activity and NO production adds significantly to the therapeutic potential of GRK2 inhibition with the βARKct not only in chronic HF but also potentially in acute ischemic injury conditions.
Inhibition of Glutaminase Preferentially Slows Growth of Glioma Cells with Mutant IDH1
Authors: Meghan J. Seltzer, Bryson D. Bennett, Avadhut D. Joshi, Ping Gao, Ajit G. Thomas, Dana V. Ferraris, Takashi Tsukamoto, Camilo J. Rojas, Barbara S. Slusher, Joshua D. Rabinowitz, Chi V. Dang, Gregory J. Riggins
Journal: Cancer Research (2010)

Mutation at the R132 residue of isocitrate dehydrogenase 1 (IDH1), frequently found in gliomas and acute myelogenous leukemia, creates a neoenzyme that produces 2-hydroxyglutarate (2-HG) from α-ketoglutarate (α-KG). We sought to therapeutically exploit this neoreaction in mutant IDH1 cells that require α-KG derived from glutamine. Glutamine is converted to glutamate by glutaminase and further metabolized to α-KG. Therefore, we inhibited glutaminase with siRNA or the small molecule inhibitor bis-2-(5-phenylacetamido-1,2,4-thiadiazol-2-yl)ethyl sulfide (BPTES) and found slowed growth of glioblastoma cells expressing mutant IDH1 compared with those expressing wild-type IDH1. Growth suppression of mutant IDH1 cells by BPTES was rescued by adding exogenous α-KG. BPTES inhibited glutaminase activity, lowered glutamate and α-KG levels, and increased glycolytic intermediates while leaving total 2-HG levels unaffected. The ability to selectively slow growth in cells with IDH1 mutations by inhibiting glutaminase suggests a unique reprogramming of intermediary metabolism and a potential therapeutic strategy.
Effect of Smoking Reduction on Lung Cancer Risk
Authors: Nina S Godtfredsen, Eva Prescott, Merete Osler
Journal: JAMA (2005)

Many smokers are unable or unwilling to completely quit smoking. A proposed means of harm reduction is to reduce the number of cigarettes smoked per day. However, it is not clear whether this strategy decreases the risk for tobacco-related diseases.To assess the effects of smoking reduction on lung cancer incidence.Observational population-based cohort study with up to 31 years of follow-up from the Copenhagen Centre for Prospective Population Studies, which administrates data from 3 longitudinal studies conducted in Copenhagen and suburbs, the Copenhagen City Heart Study, the Copenhagen Male Study, and the Glostrup Population Studies, Denmark. Participants were 11,151 men and 8563 women (N = 19,714) aged 20 to 93 years, who attended 2 consecutive examinations with a 5- to 10-year interval between 1964 and 1988. Participants underwent a physical examination and completed self-filled questionnaires about lifestyle habits. The study population was divided into 6 groups according to smoking habits: continued heavy smokers (> or =15 cigarettes/d), reducers (reduced from > or =15 cigarettes/d by minimum of 50% without quitting), continued light smokers (1-14 cigarettes/d), quitters (stopped between first and second examination), stable ex-smokers, and never smokers.Incident primary lung cancer cases assessed by record linkage with the National Cancer Registry until December 31, 2003.There were 864 incident lung cancers during follow-up. Using Cox regression, the adjusted hazard ratio (HR) for lung cancer in reducers was 0.73 (95% confidence interval [CI], 0.54-0.98) compared with persistent heavy smokers. The HR for light smokers was 0.44 (95% CI, 0.35-0.56); for quitters, HR 0.50 (95% CI, 0.36-0.69), for stable ex-smokers, HR 0.17 (95% CI, 0.13-0.23), and for never smokers, HR 0.09 (95% CI, 0.06-0.13).Among individuals who smoke 15 or more cigarettes per day, smoking reduction by 50% significantly reduces the risk of lung cancer.
Efficacy of adjuvant chemotherapy according to Prion protein expression in patients with estrogen receptor-negative breast cancer
Authors: F. Meslin, R. Conforti, C. Mazouni, N. Morel, G. Tomasic, F. Drusch, M. Yacoub, J.C. Sabourin, J. Grassi, S. Delaloge, M.C. Mathieu, S. Chouaib, F. Andre, M. Mehrpour
Journal: Annals of Oncology (2007)

Prion protein (PrPc) has been previously reported to be associated with resistance to proapoptotic stimuli. We evaluated whether the expression of PrPc was associated with the resistance to adjuvant chemotherapy in patients with estrogen receptor (ER) -negative breast cancer.The expression of PrPc by primary tumors was assessed by immunohistochemistry in a series of 756 patients included in two randomized trials that compared anthracycline-based chemotherapy to no chemotherapy. The PrPc expression was correlated with ER expression and the benefit of adjuvant chemotherapy was assessed according to PrPc expression in patients with ER-negative tumors.Immunostaining analysis showed that PrPc was mainly expressed by myoepithelial cells in normal breast tissue. Tissue microarray analysis from 756 breast tumors showed that PrPc was associated with ER-negative breast cancer subsets (P < 0.001). Adjuvant chemotherapy was not associated with a significant risk reduction for death in patients with ER-negative/PrPc-positive disease [adjusted hazard ratio (HR) for death = 0.98, 95% confidence interval (CI) 0.45-2.1, P = 0.95], while it decreased the risk for death (HR = 0.39, 95% CI 0.2-0.74, P = 0.004) in patients with ER-negative/PrPc-negative tumors.These data indicate that ER-negative/PrPc-negative phenotype is associated with a high sensitivity to adjuvant chemotherapy.
Insulin Resistance after Renal Transplantation
Authors: Karsten Midtvedt, Jøran Hjelmesaeth, Anders Hartmann, Kirsten Lund, Dag Paulsen, Thore Egeland, Trond Jenssen
Journal: Journal of the American Society of Nephrology (2004)

Cardiovascular disease is a prevalent and serious complication after solid organ transplantation. Treatment with glucocorticoids is associated with increased risk for diabetes mellitus, insulin resistance, weight gain, hypercholesterolemia, and hypertension, all shown to be independent risk factors for cardiovascular disease. We sought to test the hypothesis that tapering of prednisolone (TAP) the first year after renal transplantation improves insulin sensitivity (IS), and to assess the effect of complete steroid withdrawal (SW) on IS in patients on a cyclosporine-based immunosuppressive regimen. All patients (n = 57) completed two consecutive hyperinsulinemic euglycemic glucose clamp procedures, a TAP group (n = 34) and a control group (n = 12) at 3 and 12 mo after transplantation, and a SW group (n = 11) before and 5 mo after SW. The IS index (ISI) was calculated as the glucose disposal rate divided by mean serum insulin the last 60 min of the clamp. In the TAP group, the mean (range) daily prednisolone was reduced from 16 (10 to 30) to 9 (5 to 12.5) mg accompanied by an average increased ISI of 24% (P = 0.008). In contrast, no significant change in ISI was observed in the control group (0%, P = 0.988). In the SW group, withdrawal of 5 mg prednisolone did not influence mean ISI significantly (-8%, P = 0.206). Lowering daily prednisolone toward 5 mg/d has beneficial effects on insulin action after renal transplantation, but withdrawal of 5 mg prednisolone may not influence IS significantly.
Revision of the Atlanta classification of acute pancreatitis: the editorial perspective
Authors: Thomas M Gress, Emad M El-Omar
Journal: Gut (2012)

In the present issue of Gut , we publish the revision of the Atlanta classification of acute pancreatitis1 together with two commentaries from expert pancreatologists.2 ,3 Revision of any international classification of disease is always fraught with difficulty and controversy. On behalf of the editorial committee of Gut , we wish to present our journal's perspective on this process.

Most pancreatologists recognised the strong need for revision of the original and long outdated Atlanta classification, which dates back to 1992.4 To revise the …
Sternoclavicular erosions in polymyalgia rheumatica.
Authors: E W Paice, F W Wright, A G Hill
Journal: Annals of the Rheumatic Diseases (1983)

The incidence of erosive arthropathy of the sternoclavicular joints in 25 consecutive cases of polymyalgia rheumatica was studied by means of sternoclavicular tomography. Definite erosions were found in 11 patients. Erosions were most likely to be found in patients whose symptoms had been present for more than 6 months.
Enzymatic Activity of Lysosomal Carboxypeptidase (Cathepsin) A Is Required for Proper Elastic Fiber Formation and Inactivation of Endothelin-1
Authors: Volkan Seyrantepe, Aleksander Hinek, Junzheng Peng, Michael Fedjaev, Sheila Ernest, Yoshito Kadota, Maryssa Canuel, Kohji Itoh, Carlos R. Morales, Julie Lavoie, Johanne Tremblay, Alexey V. Pshezhetsky
Journal: Circulation (2008)

Background— Lysosomal carboxypeptidase, cathepsin A (protective protein, CathA), is a component of the lysosomal multienzyme complex along with β-galactosidase (GAL) and sialidase Neu1, where it activates Neu1 and protects GAL and Neu1 against the rapid proteolytic degradation. On the cell surface, CathA, Neu1, and the enzymatically inactive splice variant of GAL form the elastin-binding protein complex. In humans, genetic defects of CathA cause galactosialidosis, a metabolic disease characterized by combined deficiency of CathA, GAL, and Neu1 and a lysosomal storage of sialylated glycoconjugates. However, several phenotypic features of galactosialidosis patients, including hypertension and cardiomyopathies, cannot be explained by the lysosomal storage. These observations suggest that CathA may be involved in hemodynamic functions that go beyond its protective activity in the lysosome. Methods and Results— We generated a gene-targeted mouse in which the active CathA was replaced with a mutant enzyme carrying a Ser190Ala substitution in the active site. These animals expressed physiological amounts of catalytically inactive CathA protein, capable of forming lysosomal multienzyme complex, and did not develop secondary deficiency of Neu1 and GAL. Conversely, the mice showed a reduced degradation rate of the vasoconstrictor peptide, endothelin-1, and significantly increased arterial blood pressure. CathA-deficient mice also displayed scarcity of elastic fibers in lungs, aortic adventitia, and skin. Conclusions— Our results provide the first evidence that CathA acts in vivo as an endothelin-1–inactivating enzyme and strongly confirm a crucial role of this enzyme in effective elastic fiber formation.
Preferentially high prevalence of hepatitis G virus (HGV) infection as compared to HCV infection in patients undergoing chronic hemodialysis
Authors: L. Sheng, A. Widyastuti, H. Kosala, J. Donck, Y. Vanrenterghem, E. Setijoso, A. Soumillion, C. Verslype, R. Schelstraete, M-P. Emonds, G. Hess, S.H. Yap
Journal: Journal of Hepatology (1998)