tbuckley/cabot-search huggingface dataset:
The role of primary care in promoting children’s physical activity
Authors: J S Huang, J Sallis, K Patrick
Journal: British Journal of Sports Medicine (2008)

Regular physical activity enhances health during childhood and adolescence and is important in setting the stage for participation in physical activity across the lifespan. Physician-patient interactions during childhood and adolescence provide important opportunities for clinicians to influence physical activity behaviours. This article reviews current physical activity recommendations for youth and the wide range of health benefits provided to youth from engaging in regular physical activity. It also outlines a practical counselling model, the 5As approach, that can guide clinical counselling for physical activity, and reviews how an increasingly important model of practice organisation, the Care Model, can be used to promote physical activity in children and adolescents. Family, social and environmental influences on child and adolescent physical activity are also addressed.
Compliance of the Human Pulmonary Arterial System in Disease
Authors: Stuart R. Reuben
Journal: Circulation Research (1971)

Pulmonary arterial and pulmonary arterial "wedge" pressures were measured in 35 patients during cardiac catheterization. Pulmonary arterial compliance (C) was calculated from the diastolic pulmonary arterial pressure profile, left atrial pressure, and pulmonary vascular resistance (R). In the pulmonary normotensive group, compliance averaged 2.87 ml/mm Hg; in patients with severe pulmonary hypertension, values as low as 0.7 ml/mm Hg were found. In 16 of these patients, pulmonary capillary blood flow was measured by N 2 O body plethysmography. In pulmonary normotensive patients the pulsatility of capillary flow, i.e., the ratio of peak-to-mean flow rates, was 2:1; advanced pulmonary hypertension was associated with values as low as 1.2:1, suggesting marked damping of the flow pulse. The pulsatility index correlated well with the RC time constant of the pulmonary arterial system, so that damping of the pulmonary capillary flow pulse was associated with a prolonged time constant. This suggested that in severe pulmonary hypertension the pulmonary arterial walls are stiff and indistensible. A method was developed for estimating mean pulmonary arterial and left atrial pressure from the pulmonary capillary flow pulse, and the relationships between compliance and pressure and pulsatility index and RC time constant. N 2 O-plethysmography can thus provide a reliable and repeatable, noninvasive method for investigation of the pulmonary vascular bed.
An integrated MDR-TB management programme results in favourable outcomes in northern Taiwan
Authors: Ming-Chih Yu, Huang-Yao Chen, Shen-Hsuan Chien, Ruwen Jou
Journal: European Respiratory Journal (2014)

Multidrug-resistant tuberculosis (MDR-TB) is caused by Mycobacterium tuberculosis that is resistant to at least isoniazid (INH) and rifampicin (RIF). MDR-TB is difficult to treat and has become an obstacle to tuberculosis control programmes worldwide [1]. The global burden of MDR-TB has been increasing and the World Health Organization (WHO) estimated there were 450 000 incident MDR-TB cases in 2012 [2]. Based on drug-resistance surveys, 3.6% of patients newly diagnosed and 20.2% of patients previously treated for tuberculosis had MDR-TB [2]. MDR-TB demands treatment with second-line drugs that have a limited sterilising capacity, and are less effective and more toxic than first-line drugs. Among the estimated 20% of the worldwide MDR-TB cases that were enrolled in treatment in 2010, only 48% were successfully treated [2]. High mortality rates and loss to follow-up are threatening to destabilise global tuberculosis control. Despite numerous risk factors, a patient-centred management programme resulted in favourable outcomes for MDR-TB <http://ow.ly/zbNha> The authors would like to thank Mei-Hua Wu, Wei-Lun Huang, Pei-Chun Chuang and Ting-Fang Wang (Center for Research, Diagnostic and Vaccine Development, Centers for Disease Control, Taipei, Taiwan) for their excellent technical support.
Role of RyR2 Phosphorylation in Heart Failure and Arrhythmias
Authors: Dobromir Dobrev, Xander H.T. Wehrens
Journal: Circulation Research (2014)

Cardiac ryanodine receptor type 2 plays a key role in excitation–contraction coupling. The ryanodine receptor type 2 channel protein is modulated by various post-translational modifications, including phosphorylation by protein kinase A and Ca 2+ /calmodulin protein kinase II. Despite extensive research in this area, the functional effects of ryanodine receptor type 2 phosphorylation remain disputed. In particular, the potential involvement of increased ryanodine receptor type 2 phosphorylation in the pathogenesis of heart failure and arrhythmias remains a controversial area, which is discussed in this review article.
Molecular remodelling of dystrophin in patients with end-stage cardiomyopathies and reversal in patients on assistance-device therapy
Authors: Matteo Vatta, Sonny J Stetson, Alejandro Perez-Verdia, Mark L Entman, George P Noon, Guillermo Torre-Amione, Neil E Bowles, Jeffrey A Towbin
Journal: The Lancet (2002)
Epigenetic Regulation by Z-DNA Silencer Function Controls Cancer-Associated ADAM-12 Expression in Breast Cancer: Cross-talk between MeCP2 and NF1 Transcription Factor Family
Authors: Bimal K. Ray, Srijita Dhar, Carolyn Henry, Alexander Rich, Alpana Ray
Journal: Cancer Research (2012)

A disintegrin and metalloprotease domain-containing protein 12 (ADAM-12) is upregulated in many human cancers and promotes cancer metastasis. Increased urinary level of ADAM-12 in breast and bladder cancers correlates with disease progression. However, the mechanism of its induction in cancer remains less understood. Previously, we reported a Z-DNA-forming negative regulatory element (NRE) in ADAM-12 that functions as a transcriptional suppressor to maintain a low-level expression of ADAM-12 in most normal cells. We now report here that overexpression of ADAM-12 in triple-negative MDA-MB-231 breast cancer cells and breast cancer tumors is likely due to a marked loss of this Z-DNA-mediated transcriptional suppression function. We show that Z-DNA suppressor operates by interaction with methyl-CpG-binding protein, MeCP2, a prominent epigenetic regulator, and two members of the nuclear factor 1 family of transcription factors, NF1C and NF1X. While this tripartite interaction is highly prevalent in normal breast epithelial cells, both in vitro and in vivo, it is significantly lower in breast cancer cells. Western blot analysis has revealed significant differences in the levels of these 3 proteins between normal mammary epithelial and breast cancer cells. Furthermore, we show, by NRE mutation analysis, that interaction of these proteins with the NRE is necessary for effective suppressor function. Our findings unveil a new epigenetic regulatory process in which Z-DNA/MeCP2/NF1 interaction leads to transcriptional suppression, loss of which results in ADAM-12 overexpression in breast cancer cells.
Antiviral CD8-mediated responses in chronic HCV carriers with HBV superinfection
Authors: Carolina Boni, Barbara Amadei, Simona Urbani, Paola Fisicaro, Alessandro Zerbini, Cristina Mori, Gabriele Missale, Roberto Bertoni, Annalisa Azzurri, Gianfranco Del Prete, Carlo Ferrari
Journal: Hepatology (2004)

Hepatitis B virus (HBV) superinfection in chronic hepatitis C represents a natural model to investigate whether or not hepatitis C virus (HCV) can influence priming and maturation of antiviral T cells; whether or not HBV superinfection, which is known to determine control of HCV replication, can restore HCV-specific T cell responsiveness; and whether or not cytokines stimulated by HBV infection can contribute to HCV control. To address these issues, the function of CD8 cells specific for HBV and HCV was studied longitudinally in two chronic HCV patients superinfected with HBV. Patients with acute hepatitis B were also examined. Frequency and function of HBV tetramer+ CD8 cells were comparable in patients acutely infected with HBV with or without chronic HCV infection. HBV-specific CD8 cell function was efficiently expressed irrespective of serum HCV-RNA levels. Moreover, fluctuations of HCV viremia at the time of HBV superinfection were not associated with evident changes of CD8 responsiveness to HCV. Finally, no correlation was found between serum levels of interferon alpha, interleukin (IL)-12, IL-10, or IL-18 and control of HCV replication. In conclusion, HCV did not affect the induction of primary and memory HBV-specific CD8 responses. HCV-specific CD8 responses were undetectable when HCV-RNA was negative, showing that inhibition of HCV replication in the setting of a HBV superinfection was not sufficient to induce a restoration of CD8 reactivity against HCV.
A CHEMICAL STUDY OF THE SPECIFIC ELEMENTS OF TUBERCULIN. I
Authors: J. Howard Mueller
Journal: The Journal of Experimental Medicine (1926)

1. The specific precipitin reaction and the skin reaction given by old tuberculin are attributable to two separate substances present in this material. The cause of the reaction first mentioned is a non-protein gum which will be fully described in the following paper. The cause of the skin reaction is probably but not surely a protein. 2. Methods which have been suggested for the standardization of tuberculin by precipitin or complement fixation reactions should be revised.
Second-line chemotherapy versus supportive cancer treatment in advanced gastric cancer: a meta-analysis
Authors: H.S. Kim, H.J. Kim, S.Y. Kim, T.Y. Kim, K.W. Lee, S.K. Baek, T.Y. Kim, M.H. Ryu, B.H. Nam, D.Y. Zang
Journal: Annals of Oncology (2013)
Effect of sympathetic nerve stimulation on cerebral and cephalic blood flow in dogs.
Authors: R J Traystman, C E Rapela
Journal: Circulation Research (1975)

The effect of sympathetic stimulation (stellate ganglion) on dog cerebral and cephalic blood flows was studied via a cervical or a thoracic approach to the stellate ganglion under sodium pentobarbital or chloralose anesthesia. Two different stimulation voltages (3v and 5v) of monophasic pulses were applied for 1 minute. Venous outflow was measured at the confluence of the sagittal, straight and lateral sinuses with the lateral sinuses occluded and with them patent. When the lateral sinuses were occluded, stellate ganglion stimulation resulted in a marked decrease in common carotid blood flow to 38 plus or minus 2.5% (SE) of control and dilation of the ipsilateral pupil, but cerebral blood flow did not change. Similar effects were observed with each of the anatomic approaches, anesthetics, and voltages used and in dogs with low cerebral vascular tone induced by hypercapnia. When the lateral sinuses were kept patent, sympathetic nerve stimulation decreased the venous outflow to 89 plus or minus 2.9% of control and clamping both of the external jugular veins increased venous outflow to 120 plus or minus 2.7% of control. When the lateral sinuses were kept patent and the extracranial venous pressure was increased by clamping both of the external jugular veins, the decrease in venous outflow in response to sympathetic stimulation was even larger: venous outflow was only 65 plus or minus 4.9% of control. We conclude that stimulation of the stellate ganglion has no effect on the cerebral vasculature. Sympathetic stimulation significantly decreases venous blood flow measured at the confluence of the sinuses only when communications between the intracranial and extracranial venous vasculatures are present.
Phase II Trial of Ixabepilone Administered Daily for Five Days in Children and Young Adults with Refractory Solid Tumors: A Report from the Children's Oncology Group
Authors: Shana Jacobs, Elizabeth Fox, Mark Krailo, Gwen Hartley, Fariba Navid, Leonard Wexler, Susan M. Blaney, Anne Goodwin, Wendy Goodspeed, Frank M. Balis, Peter C. Adamson, Brigitte C. Widemann
Journal: Clinical Cancer Research (2010)

Ixabepilone is a microtubule-stabilizing agent with activity in adult solid tumors and in pediatric tumor xenograft models that are resistant to paclitaxel. The maximum tolerated dose on the daily-for-5-days i.v. schedule was 6 mg/m(2)/dose in adults and 8 mg/m(2)/dose in children, and the primary dose-limiting toxicity (DLT) was neutropenia. This study aimed to determine the response rate to ixabepilone in six solid tumor strata in children and young adults.We conducted a phase II trial of ixabepilone (8 mg/m(2)/dose for 5 days every 21 days) using a two-stage design in taxane-naïve children and young adults with treatment-refractory, measurable rhabdomyosarcoma, Ewing sarcoma family tumors, osteosarcoma, synovial sarcoma, or malignant peripheral nerve sheath tumor, neuroblastoma, and Wilms tumor.Sixty-one eligible patients (36 male) were enrolled. Median (range) age was 13 years (range, 3-36). Fifty-nine patients were fully evaluable for toxicity and response. DLTs, most commonly myelosuppression, occurred in 11 patients (15% incidence in 3-18 years old and 33% in 19-36 years old; P = 0.2) during cycle 1. The median (range) number of cycles was 2 (range, 1-38). No partial or complete responses (response evaluation criteria in solid tumors) were observed. Seven patients received >or=3 cycles, and two had prolonged stable disease (Wilms' tumor, 38 cycles; synovial sarcoma, 8 cycles).Ixabepilone at 8 mg/m(2)/dose daily for 5 days was tolerable in children and adolescents, but did not show evidence of clinical activity in the childhood solid tumors studied.
X‐linked agammaglobulinaemia and squamous lung cancer
Authors: J.M. Echave-Sustaeta, V. Villena, M. Verdugo, A. López-Encuentra, P. de Agustín, N. Alberti
Journal: European Respiratory Journal (2001)

A 32 yr-old nonsmoking male, diagnosed as having X‐linked agammaglobulinemia, presented with fever, cough with purulent sputum, a very intense back pain and a mass of 10 centimetres in lower left lobe. Diagnostic evaluation revealed a squamous cell carcinoma with very aggressive metastases at L3. Malignancies are the second leading cause of death in children and adults with congenital immunodeficiency disorders, mostly non-Hodgkin lymphomas and gastric and colon adenocarcinomas, but this is the first report of lung cancer in a patient with X‐linked agammaglobulinemia. Lung cancer incidence has been reported to be higher in patients with other diseases of the lung, however, there is no clear evidence of the role of bronchiectasis in developing lung cancer. It is possible that a longer survival for patients with X‐LA recently diagnosed, and an association of chronic bronchial infection, could favour the development of pulmonary neoplasm.
Resistance of Natural Killer T Cell–Deficient Mice to Systemic Shwartzman Reaction
Authors: Francesco Dieli, Guido Sireci, Domenica Russo, Masaru Taniguchi, Juraj Ivanyi, Carmen Fernandez, Marita Troye-Blomberg, Giacomo De Leo, Alfredo Salerno
Journal: The Journal of Experimental Medicine (2000)

The generalized Shwartzman reaction in mice which had been primed and challenged with lipopolysaccharide (LPS) depends on interleukin (IL)-12–induced interferon (IFN)-γ production at the priming stage. We examined the involvement in the priming mechanism of the unique population of Vα14 natural killer T (NKT) cells because they promptly produce IFN-γ after IL-12 stimulation. We report here that LPS- or IL-12–primed NKT cell genetically deficient mice were found to be resistant to LPS-elicited mortality. This outcome can be attributed to the reduction of IFN-γ production, because injection of recombinant mouse IFN-γ, but not injection of IL-12, effectively primed the NKT cell–deficient mice. However, priming with high doses of LPS caused mortality of severe combined immunodeficiency, NKT cell–deficient, and CD1-deficient mice, indicating a major contribution of NKT cells to the Shwartzman reaction elicited by low doses of LPS, whereas at higher doses of LPS NK cells play a prominent role. These results suggest that the numerically small NKT cell population of normal mice apparently plays a mandatory role in the priming stage of the generalized Shwartzman reaction.
Therapeutic targeting of GSK3β enhances the Nrf2 antioxidant response and confers hepatic cytoprotection in hepatitis C
Authors: Yongfang Jiang, Hui Bao, Yan Ge, Wei Tang, Du Cheng, Kaizhong Luo, Guozhong Gong, Rujun Gong
Journal: Gut (2014)

Impaired adaptive response to oxidative injuries is a fundamental mechanism central to the pathogenesis of chronic hepatitis C (CHC). Glycogen synthase kinase (GSK) 3β is an indispensable regulator of the oxidative stress response. However, the exact role of GSK3β in CHC is uncertain and was examined.GSK3β and Nrf2 signalling pathways were examined in JFH1 HCV infected Huh7.5.1 hepatocytes, and also in liver biopsy specimens from CHC patients.HCV infection elicited prominent Nrf2 antioxidant response in hepatocytes, marked by elevated expression of the Nrf2-dependent molecule haem oxygenase-1 and subsequent protection from apoptotic cell death. Inhibitory phosphorylation of GSK3β seems to be essential and sufficient for HCV-induced Nrf2 response. Mechanistically, GSK3β associated and physically interacted with Nrf2 in hepatocytes. In silico analysis revealed that Nrf2 encompasses multiple GSK3β phosphorylation consensus motifs, denoting Nrf2 as a cognate substrate of GSK3β. In the presence of TGFβ1, the HCV-induced GSK3β phosphorylation was blunted via a protein phosphatase 1-dependent mechanism and the cytoprotective Nrf2 response drastically impaired. This effect was counteracted by lithium, a selective inhibitor of GSK3β. In liver biopsy specimens from CHC patients, the expression of phosphorylated GSK3β positively correlated with Nrf2 expression and was inversely associated with the degree of liver injury. Moreover, CHC patients who received long-term lithium carbonate therapy primarily for concomitant psychiatric disorders exhibited much less liver injury, associated with enhanced hepatic expression of Nrf2.Inhibition of GSK3β exerts hepatoprotection in CHC possibly through its direct regulation of Nrf2 antioxidant response.
Sports medicine and science gearing up for London, enjoy the ICSEMIS congress in Glasgow
Authors: Lars Engebretsen, Kathrin Steffen
Journal: British Journal of Sports Medicine (2012)

The Olympic Games are not the only premier sports event for the Olympic athletes. Increasingly, sports medicine and various science organisations are taking advantage of the Olympic Games and conducting world sports medicine major events. One of those premier events is probably the International Convention on Science, Education and Medicine in Sport (ICSEMIS), taking place in Glasgow between 19 and 24 July 2012, preceding the Games in London. Several organisations has built ICSEMIS namely, the International Council of Sport Science and Physical Education, the International Federation of Sports Medicine, IOC – the International Olympic Committee and the International Paralympic Committee, and worked with a …
Prevalence of Muscle Cramps in Patients With Diabetes
Authors: Hans Katzberg, Seint Kokokyi, Elise Halpern, Eric Lovblom, Carolina Barnett, Drew Hume, Vera Bril, Bruce Perkins
Journal: Diabetes Care (2013)

There are limited epidemiological studies addressing the prevalence of muscle cramps in the general population and diseases like diabetes (1). Common long-term complications of diabetes, such as neuropathy and nephropathy, have been associated with higher rates of muscle cramps (2).

We aimed to determine the prevalence and characteristics of muscle cramps in patients with diabetes compared with healthy volunteers. Frequency, severity (using visual analog scale [VAS]), duration, and disability due to muscle cramps were evaluated, as is standard in clinical trials. Information about each patient’s clinical status was collected, including patient demographics, neuropathy (diagnosed using established clinical and electrophysiological criteria and quantitated using the Toronto Clinical Neuropathy Score) (3), diabetes complications, duration and type of diabetes, concurrent cramp-inducing (β-blockers, diuretics, statins) and cramp-protecting (quinine, calcium channel blockers, antiepileptics) medications, and markers of glycemic control (HbA1c).

Baseline demographics and cramp characteristics for 269 patients with diabetes (type 1 diabetes, n = …
Genomic Alterations and Allelic Imbalances Are Strong Prognostic Predictors in Osteosarcoma
Authors: Jan Smida, Daniel Baumhoer, Michael Rosemann, Axel Walch, Stefan Bielack, Christopher Poremba, Klaus Remberger, Eberhard Korsching, Wolfram Scheurlen, Christian Dierkes, Stefan Burdach, Gernot Jundt, Michael J. Atkinson, Michaela Nathrath
Journal: Clinical Cancer Research (2010)

Abstract Purpose: Osteosarcoma, the most common primary malignant tumor of the bone, is characterized by complex karyotypes with numerous structural and numerical alterations. Despite attempts to establish molecular prognostic markers at the time of diagnosis, the most accepted predictive factor remains the histologic evaluation of necrosis after neoadjuvant chemotherapy. The present approach was carried out to search for genome-wide recurrent loss of heterozygosity and copy number variations that could have prognostic and therapeutic impact for osteosarcoma patients. Experimental Design: Pretherapeutic biopsy samples of 45 osteosarcoma patients were analyzed using Affymetrix 10K2 high-density single nucleotide polymorphism arrays. Numerical aberrations and allelic imbalances were correlated with the histologically assessed response to therapy and clinical follow-up. Results: The most frequent genomic alterations included amplifications of chromosome 6p21 (15.6%), 8q24 (15.6%, harboring MYC), and 12q14 (11.1%, harboring CDK4), as well as loss of heterozygosity of 10q21.1 (44.4%). All these aberrations and the total degree of heterozygosity of each tumor were significantly associated with an adverse outcome of patients and were used to define a chromosomal alteration staging system with a superior predictive potential compared with the histologic regression grading. Conclusions: Structural chromosomal alterations detected by single nucleotide polymorphism analysis provide a simple but robust parameter to anticipate response to chemotherapy. The proposed chromosomal alteration staging system might therefore help to better predict the clinical course of osteosarcoma patients at the time of initial diagnosis and to adapt neoadjuvant treatment in patients resistant to the current protocols. Clin Cancer Res; 16(16); 4256–67. ©2010 AACR.
Molecular genetics of B-precursor acute lymphoblastic leukemia
Authors: Charles G. Mullighan
Journal: Journal of Clinical Investigation (2012)

B-precursor acute lymphoblastic leukemia (B-ALL) is the most common childhood tumor and the leading cause of cancer-related death in children and young adults. The majority of B-ALL cases are aneuploid or harbor recurring structural chromosomal rearrangements that are important initiating events in leukemogenesis but are insufficient to explain the biology and heterogeneity of disease. Recent studies have used microarrays and sequencing to comprehensively identify all somatic genetic alterations in acute lymphoblastic leukemia (ALL). These studies have identified cryptic or submicroscopic genetic alterations that define new ALL subtypes, cooperate with known chromosomal rearrangements, and influence prognosis. This article reviews these advances, discusses results from ongoing second-generation sequencing studies of ALL, and highlights challenges and opportunities for future genetic profiling approaches.