tbuckley/cabot-search huggingface dataset:
EFFICACY OF ACUTE HIGH-INTENSITY INTERVAL TRAINING IN LOWERING GLYCEMIA IN PATIENTS WITH TYPE 2 DIABETES: DIABETES EM MOVIMENTO® PILOT STUDY
Authors: Romeu Mendes, Nelson Sousa, Nuno Garrido, Pedro Rocha, Luís Themudo Barata José, Machado Reis Victor
Journal: British Journal of Sports Medicine (2013)

Background High-intensity interval training (HIIT) is characterized by brief periods of high-intensity aerobic exercise interspersed with periods of rest or active recovery and has been reported to be more effective than moderate-intensity continuous training for improving several health outcomes. However, safety and efficacy of HIIT in high-risk patient populations, like type 2 diabetic patients, needs to be established. This study aims to analyze the acute effects of HIIT in postprandial blood glucose levels in patients with type 2 diabetes. Methods This was a randomized crossover study. Twelve individuals with type 2 diabetes (diagnosed at 5.83±3.13 years; six men and six women; age 58.67±5.35 years; glycated hemoglobin 7.08±1.18 %; body mass index 30.07±5,64 kg/m2) treated with oral hypoglycemic agents (metformin, N=5; metformin+sitagliptin, N=4; metformin+vildagliptin, N=3) underwent a single exercise session of high-intensity interval training on treadmill and a control session of seated rest with one week apart in a random order. Exercise session consisted in a 5-min warm-up followed by 5 series of 3-min brisk walking at 70% of heart rate reserve (HRR), interspersed with 3-min at 30% HRR. In the end a 5-min cool-down was carried, totaling a 40-min exercise session. Treadmill speed and grade were adjusted to induce the defined intensity. Training zones were calculated with Karvonen HRR method. Sessions were held in the morning period during standardized breakfast postprandial state. Capillary blood glucose was measured at baseline (fasting state), immediately before sessions (0 min), during sessions (10, 20 and 30 min) immediately after sessions (40 min) and during recovery (50, 60, 70, 80 and 90 min). Results After exercise start, blood glucose levels were always lower compared to control. However, two-way ANOVA (conditionxtime) with repeated measures only identified statistically significant diferences at minute 20 (155.92±51.13 vs. 110.58±47.07 mg/dl, p=0.034), 30 (148.50±55.58 vs. 95.08±44.77 mg/dl, p=0.017), 40 (137.42±48.60 vs. 91.17±38.71 mg/dl, p=0.017) and 50 (134.00±52.91 vs. 94.25±38.33 mg/dl, p=0.047). No acute adverse events occurred during exercise or recovery: no symptomatic hypoglycemia, hyperglycemia, no symptoms of myocardial ischemia or stroke and no musculoskeletal injuries. Conclusions HIIT appears to be an effective and safe exercise strategy to acutely control blood glucose in patients with type 2 diabetes. Trial funding and registration Diabetes em Movimento® is funded by Portuguese Foundation for Science and Technology with reference SFRH/BD/47733/2008 and is registered in Current Controlled Trials with reference ISRCTN09240628 .
Meta-mining of Neuroblastoma and Neuroblast Gene Expression Profiles Reveals Candidate Therapeutic Compounds
Authors: Katleen De Preter, Sara De Brouwer, Tom Van Maerken, Filip Pattyn, Alexander Schramm, Angelika Eggert, Jo Vandesompele, Frank Speleman
Journal: Clinical Cancer Research (2009)

Neuroblastoma is a heterogeneous childhood tumor with poor survival outcome for the aggressive type despite intensive multimodal therapies. In this study, we aimed to identify new treatment options for neuroblastoma based on integrative genomic analysis.The Connectivity Map is a database comprising expression profiles in response to known therapeutic compounds. This renders it a useful tool in the search for potential therapeutic compounds based on comparison of gene expression profiles of diseased cells and a database of profiles in response to known therapeutic compounds. We have used this strategy in the search for new therapeutic molecules for neuroblastoma based on data of an integrative meta-analysis of gene copy number and expression profiles from 146 primary neuroblastoma tumors and normal fetal neuroblasts.In a first step, a 132-gene classifier was established that discriminates three major genomic neuroblastoma subgroups, reflecting inherent differences in gene expression between these subgroups. Subsequently, we screened the Connectivity Map database using gene lists generated by comparing expression profiles of fetal adrenal neuroblasts and the genomic subgroups of neuroblastomas. A putative therapeutic effect was predicted for several compounds of which six were empirically tested. A significant reduction in cell viability was shown for five of these molecules: 17-allylamino-geldanamycin, monorden, fluphenazine, trichostatin, and rapamycin.This proof-of-principle study indicates that an integrative genomic meta-analysis approach with inclusion of neuroblast data enables the identification of promising compounds for treatment of children with neuroblastoma. Further studies are warranted to explore in detail the therapeutic potential of these compounds.
ADAMTS-7 forms a positive feedback loop with TNF-α in the pathogenesis of osteoarthritis
Authors: Yongjie Lai, Xiaohui Bai, Yunpeng Zhao, Qingyun Tian, Ben Liu, Edward A Lin, Yuqing Chen, Brendan Lee, C Thomas Appleton, Frank Beier, Xiu-Ping Yu, Chuan-ju Liu
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Objective</h3> To examine the expression of ADAMTS-7 during the progression of osteoarthritis (OA), defining its role in the pathogenesis of OA, and elucidating the molecular events involved. <h3>Methods</h3> ADAMTS-7 expression in cartilage of a rat OA model was assayed using immunohistochemistry. Cartilage-specific ADAMTS-7 transgenic mice and ADAMTS-7 small interfering (si)RNA knockdown mice were generated and used to analyse OA progression in both spontaneous and surgically induced OA models. Cartilage degradation and OA was evaluated using Safranin-O staining, immunohistochemistry, ELISA and western blotting. In addition, mRNA expression of tumour necrosis factor (TNF)-α and metalloproteinases known to be involved in cartilage degeneration in OA was analysed. Furthermore, the transactivation of ADAMTS-7 by TNF-α and its downstream NF-κB signalling was measured using reporter gene assay. <h3>Results</h3> ADAMTS-7 expression was elevated during disease progression in the surgically induced rat OA model. Targeted overexpression of ADAMTS-7 in chondrocytes led to chondrodysplasia characterised by short-limbed dwarfism and a delay in endochondral ossification in 'young mice' and a spontaneous OA-like phenotype in 'aged' mice. In addition, overexpression of ADAMTS-7 led to exaggerated breakdown of cartilage and accelerated OA progression, while knockdown of ADAMTS-7 attenuated degradation of cartilage matrix and protected against OA development, in surgically induced OA models. ADAMTS-7 upregulated TNF-α and metalloproteinases associated with OA; in addition, TNF-α induced ADAMTS-7 through NF-κB signalling. <h3>Conclusions</h3> ADAMTS-7 and TNF-α form a positive feedback loop in the regulation of cartilage degradation and OA progression, making them potential molecular targets for prevention and treatment of joint degenerative diseases, including OA.
The Use of Coping Peer Support and MP3 Technology to Improve Adherence to Inhaled Corticosteroids Among Low-Income Minority Adolescents
Authors: Giselle Mosnaim, Hong Li, Molly Martin, Paula Jo Belice, Elizabeth Avery, Norman Ryan, Bruce G. Bender, Lynda Powell
Journal: Journal of Allergy and Clinical Immunology (2013)
Polymyositis after propylthiouracil treatment for hyperthyroidism.
Authors: W J Shergy, D S Caldwell
Journal: Annals of the Rheumatic Diseases (1988)

An additional disorder in the spectrum of thyroid related muscle disease is presented. Hypothyroid and hyperthyroid disease are both associated with a variety of muscle abnormalities, from myalgias to myopathy. Polymyositis, however, has never been reported immediately after treatment for active hyperthyroidism. A patient is presented with typical hyperthyroidism, who developed a severe proximal muscle weakness and a raised creatine phosphokinase after treatment for hyperthyroidism with propylthiouracil (100 mg orally, three times a day). Electromyography, muscle biopsy, and the course of the patient9s illness were consistent with polymyositis. Whether this represents a cause-effect association or a chance occurrence is unknown. Physician awareness of the occurrence of a variety of muscle disorders including polymyositis in thyroid disease is emphasised. A brief discussion of thyroid myopathy, thionamide drug reactions, and polymyositis is included.
Intrinsic heterogeneity in repolarization is increased in isolated failing rabbit cardiomyocytes during simulated ischemia
Authors: J DEGROOT, C SCHUMACHER, A VERKERK, A BAARTSCHEER, J FIOLET, R CORONEL
Journal: Cardiovascular Research (2003)

Objective: Myocardial ischemia and ventricular arrhythmias often complicate congestive heart failure. Ischemia-induced dispersion in repolarization is an important arrhythmogenic factor that might be caused by intrinsic cellular differences in response to simulated ischemia (SI) or by changed coupling of myocytes. We hypothesized that intrinsic heterogeneity in action potential duration (APD) or the occurrence of rigor is larger in failing than in normal rabbit myocytes during SI. Methods: Heart failure (HF) was induced with volume and pressure overload. Left ventricular myocytes from apex, free wall and base were enzymatically isolated and exposed to SI with NaCN. Results: There were no baseline differences in APD before SI. During SI no differences in time to inexcitability occurred but the range in APD increased more in HF than in normal cells. Rigor occurred after 16.8±3.5 and 23.0±7.5 min (P<0.05) in normal and HF myocytes, with no differences between apical, free wall or base cells. Variance in time to rigor was larger in HF than in normal cells (55.7 versus 12.4 min2). Blockade of anaerobic reserve decreased variance in time to rigor, also when normalized to mean, in HF and normal myocytes. In coupled normal and HF cell pairs, no delay in action potential propagation or differences in APD occurred during SI, and time to rigor was synchronized (P<0.05 vs. single cells). Conclusions: Intercellular differences in APD and in time of rigor arise in normal and HF myocytes subjected to SI, and are inhibited by blockade of anaerobic glycolysis. Dispersion in APD and tolerance to SI is increased in HF cells. APD and time to rigor are completely synchronized in coupled cell pairs.
Patterns of Professional Activities of Psychiatrists: A Follow-Up of 100 Psychiatric Residents
Authors: FLOYD K. GARETZ, RICHARD W. ANDERSON
Journal: American Journal of Psychiatry (1973)

The authors attempted to identify predictors of professional achievement from data that are routinely collected from applicants for psychiatric residency training. The strongest predictors were the subject's rank in his medical school class and his age at the beginning of his training. The authors point out, however, that achievement indices frequently correlate highly with each other and that many factors must be considered in selecting psychiatric residents.
Current Treatment Strategies for Chronic Hepatitis B and C
Authors: Otto S. Lin, Emmet B. Keeffe
Journal: Annual Review of Medicine (2001)

▪ Abstract For chronic hepatitis B, treatment with a 4-month course of interferon alfa-2b can achieve hepatitis B e antigen seroconversion, normalization of aminotrans-ferase levels, reduced hepatic inflammation, and possibly reduced progression to cirrhosis and improvement in survival in 20%–30% of patients. Similar results can be achieved with a 12-month course of lamivudine, with response rates increasing to 40%–65% after 3 years of therapy. Interferon can also be used in early cirrhotic patients, and lamivudine can be used in advanced cirrhotics and immunosuppressed patients. Combination interferon and lamivudine therapy does not confer additional benefits. For chronic hepatitis C, the combination of interferon alfa-2b and ribavirin is the treatment of choice, offering superior sustained response rates (40%) compared with interferon alone (15%). Therapy should be administered for 12 months to patients with genotype 1 virus but for only 6 months to patients with genotypes 2 and 3. Patients experiencing relapse after 6 months of interferon monotherapy can be re-treated with interferon and ribavirin or high-dose interferon, with 45%–56% sustained response rates. However, relatively few patients who are prior nonresponders to interferon monotherapy will have sustained response to further interferon-based treatments, including combination therapy with ribavirin. Successful therapy not only leads to the eradication of viral RNA but also may delay progression to cirrhosis and hepatocellular carcinoma. Interferon combined with polyethylene glycol (PEG), shows promise as an improved formulation of interferon with yet higher sustained response rates.
Circadian Proteins and Genotoxic Stress Response
Authors: Marina P. Antoch, Roman V. Kondratov
Journal: Circulation Research (2010)

The circadian clock is an evolutionarily conserved time-keeping system that coordinates the physiology of the organism with daily changes in the environment. A growing body of evidence gradually leads to the conception that virtually all aspects of the biochemical, physiological, and behavioral functions of the animal are linked to circadian regulation. Moreover, proper synchronization of various processes through the activity of circadian components is important for the well-being of many organisms, including humans. The focus of this review is the circadian control of an organism's response to genotoxic stress, which is a major contributor to life-threatening human pathologies such as cancer and cardiovascular disease.
Cerebrospinal-fluid HIV-1 RNA and drug concentrations after treatment with lamivudine plus zidovudine or stavudine
Authors: Norbert A Foudraine, Richard MW Hoetelmans, Joep MA Lange, Frank de Wolf, Birgit HB van Benthem, Jaap J Maas, Ireneus PM Keet, Peter Portegies
Journal: The Lancet (1998)
Airway hyperresponsiveness in the elderly: prevalence and clinical implications
Authors: N. Scichilone, M. Messina, S. Battaglia, F. Catalano, V. Bellia
Journal: European Respiratory Journal (2005)

Airway hyperresponsiveness is associated with an increased risk of developing respiratory symptoms. The assessment of airway hyperresponsiveness can provide valuable information regarding the natural course of respiratory diseases. However, little information is available for populations of more advanced age, and data are conflicting. It was assessed whether age influences the occurrence of airway hyperresponsiveness by reviewing those studies that specifically addressed this issue, and attempting to identify the factors responsible for discrepancies between studies. Eighteen studies, published between 1983 and 2002, are included in this review. Overall, the results of the analysis are in favour of a positive association between age and airway hyperresponsiveness, the prevalence of which appears to increase in the elderly. The most important determinants were reduced lung function, probably due to geometric factors, and a history of smoking, primarily because of the length of exposure, although acute effects were also demonstrated. Atopy should also be considered as an independent determinant of airway hyperresponsiveness in the elderly population. In addition, inflammatory and neuronal mechanisms could be involved. Finally, the role of sex requires further investigation. Assessing the impact of age on the occurrence of airway hyperresponsiveness has important implications: the age-associated alterations to the lung provide a model for evaluating the contribution of structural changes to the pathogenesis of airway hyperresponsiveness. From a clinical standpoint, evaluation of the magnitude of airway hyperresponsiveness could permit the early identification of individuals who are at risk, even at more advanced age. Assessment of airway hyperresponsiveness in the aged should be considered as an additional tool in the diagnostic work-up in the subset of elderly subjects with long-term smoking exposure and/or documented atopy.
Long-Acting Glucagon-Like Peptide 1 Receptor Agonists
Authors: Alan J. Garber
Journal: Diabetes Care (2011)

Targeting the incretin system has become an important therapeutic approach for treating type 2 diabetes. Two drug classes have been developed: glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase 4 (DPP-4) inhibitors. Clinical data have revealed that these therapies improve glycemic control while reducing body weight (GLP-1 receptor agonists, specifically) and systolic blood pressure (SBP) in patients with type 2 diabetes. Furthermore, incidence of hypoglycemia is relatively low with these treatments (except when used in combination with a sulfonylurea) because of their glucose-dependent mechanism of action. There are currently two GLP-1 receptor agonists available (exenatide and liraglutide), with several more currently being developed. This review considers the efficacy and safety of both the short- and long-acting GLP-1 receptor agonists. Head-to-head clinical trial data suggest that long-acting GLP-1 receptor agonists produce superior glycemic control when compared with their short-acting counterparts. Furthermore, these long-acting GLP-1 receptor agonists were generally well tolerated, with transient nausea being the most frequently reported adverse effect.

Careful consideration should be given to the selection of therapies for managing type 2 diabetes. In particular, antidiabetic agents that offer improved glycemic control without increasing cardiovascular risk factors or rates of hypoglycemia are warranted. At present, many available treatments for type 2 diabetes fail to maintain glycemic control in the longer term because of gradual disease progression as β-cell function declines. Where sulfonylureas or thiazolidinediones (common oral antidiabetic drugs) are used, the risk of hypoglycemia and weight gain can increase (1,2). The development of new therapies for the treatment of type 2 diabetes that, in addition to maintaining glycemic control, could reduce body weight and hypoglycemia risk (3,4), may help with patient management. Indeed, guidelines have been developed that support the consensus that blood pressure, weight reduction, and avoidance of hypoglycemic events should be targeted in …
Identification of a Highly Effective Rapamycin Schedule that Markedly Reduces the Size, Multiplicity, and Phenotypic Progression of Tobacco Carcinogen–Induced Murine Lung Tumors
Authors: Courtney A. Granville, Noel Warfel, Junji Tsurutani, M. Christine Hollander, Matthew Robertson, Stephen D. Fox, Timothy D. Veenstra, Haleem J. Issaq, R. Ilona Linnoila, Phillip A. Dennis
Journal: Clinical Cancer Research (2007)

Abstract Purpose: Human and murine preneoplastic lung lesions induced by tobacco exposure are characterized by increased activation of the Akt/mammalian target of rapamycin (mTOR) pathway, suggesting a role for this pathway in lung cancer development. To test this, we did studies with rapamycin, an inhibitor of mTOR, in A/J mice that had been exposed to the tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Experimental Design: Tumorigenesis was induced by i.p. injection of NNK, and rapamycin was administered 1 or 26 weeks after NNK administration. Biomarkers associated with mTOR inhibition were assessed in lung and/or surrogate tissues using immunohistochemistry and immunoblotting. Rapamycin levels were measured using mass spectroscopy. Results: Rapamycin was administered on a daily (5 of 7 days) regimen beginning 26 weeks after NNK decreased tumor size, proliferative rate, and mTOR activity. Multiplicity was not affected. Comparing this regimen with an every-other-day (qod) regimen revealed that rapamycin levels were better maintained with qod administration, reaching a nadir of 16.4 ng/mL, a level relevant in humans. When begun 1 week after NNK, this regimen was well tolerated and decreased tumor multiplicity by 90%. Tumors that did develop showed decreased phenotypic progression and a 74% decrease in size that correlated with decreased proliferation and inhibition of mTOR. Conclusions: Tobacco carcinogen–induced lung tumors in A/J mice are dependent upon mTOR activity because rapamycin markedly reduced the development and growth of tumors. Combined with the Food and Drug Administration approval of rapamycin and broad clinical experience, these studies provide a rationale to assess rapamycin in trials with smokers at high risk to develop lung cancer.
Sacramental and spiritual use of hallucinogenic drugs
Authors: Levente Móró, Valdas Noreika
Journal: Behavioral and Brain Sciences (2011)

Abstract Arguably, the religious use of hallucinogenic drugs stems from a human search of metaphysical insight rather than from a direct need for cognitive, emotional, social, physical, or sexual improvement. Therefore, the sacramental and spiritual intake of hallucinogenic drugs goes so far beyond other biopsychosocial functions that it deserves its own category in the drug instrumentalization list.
Ultrasound-guided transbronchial biopsy of solitary pulmonary nodules less than 20 mm
Authors: R. Eberhardt, A. Ernst, F. J. F. Herth
Journal: European Respiratory Journal (2009)

Transbronchial biopsy of solitary pulmonary nodules (SPNs) is usually performed under fluoroscopic guidance, but success varies widely. Endobronchial ultrasonography (EBUS) may increase the likelihood of success. The ability of EBUS-guided transbronchial biopsy to sample SPNs of &lt;20 mm in diameter was assessed. All patients seen between June 2004 and August 2007 in whom computed tomography identified a SPN of &lt;20 mm underwent bronchoscopic general anaesthesia or moderate sedation for a radial EBUS-guided examination. If a typical ultrasonographic picture of solid tissue could be identified, specimens were taken through a catheter with forceps. If the node was not detected within 20 min, the procedure was terminated. Of 100 nodules detected in 100 consecutive patients, 67 (mean diameter 15 mm) were visualised using EBUS and biopsy specimens taken. A diagnosis was established for 46 (46%) patients. If the lesion was visualised by EBUS, the diagnostic success was 69% (46 out of 67). The 33 patients whose nodules could not be sampled underwent surgical biopsy. Pneumothorax occurred in three patients. For SPNs of &lt;20 mm that can be detected using ultrasound, EBUS-guided transbronchial biopsy is safe and effective.
Resistance to antiviral drugs is climbing
Authors: Zosia Kmietowicz
Journal: BMJ (2005)

Public health experts have warned of a worrying increase in resistance to antiviral drugs that is making infections such as HIV and hepatitis B more difficult to manage.

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HIV particles (yellow and pink) budding from the surface of a T4 lymphocyte cell (blue) in a coloured transmission electron micrograph 

Credit: DR STEVE PATTERSON / SPL

Evidence from research that followed 4500 British patients infected with HIV indicates that after two years of standard treatment with a combination of three different classes of …

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