tbuckley/cabot-search huggingface dataset:
Cardiac Innervation and Sudden Cardiac Death
Authors: Keiichi Fukuda, Hideaki Kanazawa, Yoshiyasu Aizawa, Jeffrey L. Ardell, Kalyanam Shivkumar
Journal: Circulation Research (2015)

Afferent and efferent cardiac neurotransmission via the cardiac nerves intricately modulates nearly all physiological functions of the heart (chronotropy, dromotropy, lusitropy, and inotropy). Afferent information from the heart is transmitted to higher levels of the nervous system for processing (intrinsic cardiac nervous system, extracardiac-intrathoracic ganglia, spinal cord, brain stem, and higher centers), which ultimately results in efferent cardiomotor neural impulses (via the sympathetic and parasympathetic nerves). This system forms interacting feedback loops that provide physiological stability for maintaining normal rhythm and life-sustaining circulation. This system also ensures that there is fine-tuned regulation of sympathetic–parasympathetic balance in the heart under normal and stressed states in the short (beat to beat), intermediate (minutes to hours), and long term (days to years). This important neurovisceral/autonomic nervous system also plays a major role in the pathophysiology and progression of heart disease, including heart failure and arrhythmias leading to sudden cardiac death. Transdifferentiation of neurons in heart failure, functional denervation, cardiac and extracardiac neural remodeling has also been identified and characterized during the progression of disease. Recent advances in understanding the cellular and molecular processes governing innervation and the functional control of the myocardium in health and disease provide a rational mechanistic basis for the development of neuraxial therapies for preventing sudden cardiac death and other arrhythmias. Advances in cellular, molecular, and bioengineering realms have underscored the emergence of this area as an important avenue of scientific inquiry and therapeutic intervention.
Influence of COPD exacerbations on health related quality of life
Authors: Aliona David, Alexandru Corlateanu
Journal: European Respiratory Journal (2012)

Background:

An exacerbation is the most important adverse event in the progression of chronic obstructive pulmonary disease (COPD). Exacerbations appear to accelerate the decline in lung function that characterizes COPD, resulting in reduced physical activity, poorer quality of life and an increased risk of death.

The aim of this study was to investigate the influence of chronic obstructive pulmonary disease exacerbations on health related quality of life (HRQL).

Methods: 152 consecutive patients with COPD were enrolled into the study. We measured demographics and spirometry. HRQL was assessed by the Medical Outcomes Study Short Form (SF-36) and the St. George Respiratory Questionnaire (SGRQ).

Results:

The cohort consisted of 90 patients with 2 or less exacerbations per year, mean age 53±3.2 years and 62 patients with 3 or more exacerbations, mean age 55±3.8. In frequent exacerbators COPD was more severe: the mean FEV1% was 34.2±2.1% versus 52.3±2%, p <0.05. Grade of impairment of HRQL was higher in frequent than infrequent exacerbators: SGRQ (73.6±1.1 versus 57.1±1.6, p<0.01) and SF-36 (30.2±1.5 versus 41.1±1.2, p<0.01). Pearson correlation coefficient analysis demonstrates in COPD patients a significant positive correlation between the rate of exacerbations and the total scores of the SGRQ (r=0.61, p<0.01) and SF-36 (r=0.54, p<0.01).

Conclusion: Compared with infrequent exacerbators, frequent exacerbators in our study were characterized at baseline by more severe COPD and more severe deterioration of the health related quality of life.
P-308 RAVELLO trial: Phase III study of regorafenib versus placebo as maintenance therapy in RAS wild type metastatic colorectal cancer
Authors: E. Martinelli, T. Troiani, F. Venturini, A. Cervantes, J.-Y. Douillard, A. Falcone, G. Folprecht, C.-H. Kohne, J. Taieb, J. Tabernero, C. Cardone, V. Sforza, G. Martini, N. Stefania, A. Capuano, F. Auricchio, F. Ciardiello
Journal: Annals of Oncology (2015)
Single-photon emission computed tomography quantitation of gallium citrate uptake for the differentiation of lymphoma from benign hilar uptake.
Authors: E Even-Sapir, R Bar-Shalom, O Israel, A Frenkel, G Iosilevsky, N Haim, R Epelbaum, D Gaitini, G M Kolodny, D Front
Journal: Journal of Clinical Oncology (1995)

PURPOSE To assess the role of quantitative gallium citrate (Ga 67) single-photon emission computed tomography (SPECT) in differentiating lymphoma from benign hilar uptake, concentrations of Ga 67 in 29 sites of documented lymphoma and in 75 benign lesions were compared. PATIENTS AND METHODS One hundred seven thoracic Ga 67 SPECT studies obtained in 101 consecutive lymphoma patients were reviewed. Fifty-nine studies detected Ga 67 uptake in the hilar and or mediastinal regions. Forty-eight studies showed no such abnormality. The concentration of Ga 67 in the thoracic lesions was measured using a quantitative SPECT technique and its nature was determined by correlation with computed tomographic (CT) scans and follow-up evaluation of the sites. RESULTS In 20 of 59 abnormal studies (34%), there was lymphoma in the hilar and or mediastinal regions. In the remaining 39 abnormal studies (66%), Ga 67 uptake was benign. There were 29 sites of lymphoma and 75 benign lesions. The concentration of Ga 67 in lymphoma was significantly higher than in benign hilar uptake (13.2 +/- 5.4 %ID/mL x 10(-3) v 5.6 +/- 1.5 % injected dose (ID)/mL x 10(-3); P &lt; .001). A concentration value of 8.3 %ID/mL x 10(-3) was found to best separate lymphoma and benign uptake, with a sensitivity of 90%, a specificity of 93%, a positive predictive value of 84%, and a negative predictive value of 96%. CONCLUSION Lymphoma and benign hilar uptake differ significantly in their concentration of Ga 67. The present study shows that quantitative Ga-67 SPECT reliably differentiates lymphoma and benign uptake.
Critical immunoregulatory role for activin-A in human allergic asthma
Authors: Sofia Tousa, Maria Semitekolou, Ioanna Christopoulou, Konstantinos Samitas, Giannis Paraskevopoulos, Catherine Hawrylowicz, Mina Gaga, Georgina Xanthou
Journal: European Respiratory Journal (2011)

Our studies have revealed that activin-A, a cytokine increased in the sera and lungs of asthmatics, is a critical controller of experimental asthma as it suppresses allergic responses and protects against airway hyperresponsiveness and linked disease in mice. Still, the role of activin-A in human asthma remains elusive. Here, we investigated the effects of activin-A in the suppression of allergic responses of atopics and asthmatics. Peripheral blood (PB) was obtained from atopics and mild/moderate or severe asthmatics (n=12/group). Bronchoalveolar lavage (BAL) was obtained from severe asthmatics (n=5). The effects of recombinant activin-A or control on allergen-specific CD4+ T cell proliferation and cytokine release were investigated during stimulation with allergen ex vivo. Activin-A's role in the generation of suppressive human regulatory T cells (Tregs) was studied. Our findings reveal that activin-A significantly suppresses allergen-driven CD4+ T cell proliferation and IL-5, IL-13, IL-17, IFN-γ, IL-10 release in atopics and asthmatics. Activin-A suppresses BAL mononuclear cell responses of severe asthmatics. Importantly, activin-A enhances dexamethasone-induced suppression of allergic Th2 responses of severe, treatment refractory, asthmatics. Activin-A mediated suppression is associated with the generation of human CD4+Foxp3+ Tregs that completely inhibit allergic Th2 responses. Our results uncover activin-A as a novel protective cytokine that controls human asthma. Our findings have important clinical implications for the use of activin-A, or activin-A-induced human Tregs, as novel immunotherapies for asthma.
The roles of cell Ca2+, protein kinase C and the Na(+)-H+ antiport in the development of hypertension and insulin resistance.
Authors: A Aviv
Journal: Journal of the American Society of Nephrology (1992)

There is evidence that the cytosolic free Ca2+, protein kinase C, and the Na(+)-H+ antiport cross-communicate with one another through positive and negative feedback mechanisms, thereby maintaining cellular Ca2+ and pH homeostasis. This triumvirate may play a role in the development of insulin resistance--a common characteristic of both essential hypertension and non-insulin-dependent diabetes mellitus. Circulating cells from patients with essential hypertension and non-insulin-dependent diabetes mellitus demonstrate elevated cytosolic free Ca2+, increased protein kinase C activity, or both, and these perturbations are associated with augmented activity of the Na(+)-H+ antiport. If present in other cells (e.g., striated muscle cells and adipocytes), these alterations could underlie insulin resistance in essential hypertension and non-insulin-dependent diabetes mellitus.
Viral etiology, disease severity and treatment effect in acute bronchiolitis in South-Eastern Norway
Authors: Håvard Ove Skjerven, Spyridon Megremis, Nikolaos G. Papadopoulus, Kai-Håkon Carlsen, Karin C. Lødrup Carlsen
Journal: European Respiratory Journal (2013)

Background:  Acute bronchiolitis is a frequent cause of hospitalization in infants worldwide. The etiology is predominantly viral, occurring in seasonal patterns, with Respiratory Syncytial Virus (RSV) as the most common. Inhaled adrenaline (iRA) is a commonly used treatment. The influence of viral etiology on treatment effect and disease severity is not clear.  Aims:  We aimed to assess the association between viral etiology and 1) disease severity and 2) treatment effect with inhaled adrenaline.  Methods:  In a RCT of bronchiolitis treatment (Bronchiolitis ALL-SE Study) assessing medication (iRAvs saline(iNS)) and strategy (on demand(OD) versus fixed schedule(FS))(Figure below), nasopharynx aspirate of 363/404 patients (mean age 4.2 months, 60% boys) were analyzed with modern sensitive viral detection techniques. Associations between etiology (virus type and number of simultaneous viruses detected in each individual) and measures of disease severity (length of hospital stay, use of supportive care, clinical score, SpO2 and respiratory frequency) were analyzed by regression analyses. The impact of viral etiology (number of simultaneous viruses and subgroups) on the effect of treatment were assessed by interaction analyses.  Results and conclusion:  The types of virus detected or the number of simultaneous viruses found were not significantly associated with disease severity nor did they interact treatment efficacy.
Elevated IL-17A in very severe COPD is localized to mast cells and correlates with lung function decline
Authors: Abraham Roos, Leif Bjermer, Martin Stampfli, Jonas Erjefält
Journal: European Respiratory Journal (2014)

Escalation and progression of chronic obstructive pulmonary disease (COPD) is poorly understood. Interleukin (IL)-17A plays a complex role in immunity and is increased in peripheral lung tissue of mild/moderate COPD and in the bronchial mucosa of severe COPD, suggesting a potential role in pathogenesis. The expression of IL-17A has, however, not been determined in very severe COPD. We hypothesized that the expression of IL-17A is increased in peripheral lung tissue of very severe COPD, and is associated with lung function decline.  Automated immunodetection of IL-17A and cell specific markers was performed in lung tissue specimens collected from patients with GOLD stage I-IV COPD, as well as from smoking and never-smoking controls. Expression of immunoreactivity was quantified using digital image analysis.  Increased expression of IL-17A was observed in COPD compared to smoking and never-smoking controls, and expression of IL-17A correlated with lung function decline. Further analysis revealed that IL-17A was only significantly elevated in severe-very severe COPD (GOLD III/IV), compared to asymptomatic never-smokers as well as current smokers. While small a proportion of CD3+ T cells expressed IL-17A in very severe COPD, the majority of IL-17A+ cells were identified as tryptase+ mast cells.  The increased expression of IL-17A in the peripheral lung of patients with advanced COPD correlates with lung function decline and is suggestive of a potential role in disease progression. Furthermore, IL-17A was foremost localized to mast cells underscoring a role of this cell type in the immunopathology of COPD.
Presentations and treatment response of pulmonary tuberculosis in type 2 diabetes mellitus
Authors: Safaa Wafy
Journal: European Respiratory Journal (2012)

Introduction,   The association between diabetes and tuberculosis and their synergistic role in causing human disease has been recognized for centuries.They have serious implications on each other.The   Aim   was to study the coexistence between Tuberculosis and Diabetes,and to determine whether diabetes alters the radiological manifestations of pulmonary tuberculosis.    Methods:  Patients with both Tuberculosis and Diabetes(28patients),were compared with another TB patients without diabetes(30patients).All were subjected to sputum smear for AFB examination and X ray chest.Bronchoalveolar lavage and tuberculin test were performed in selected cases.  Results    :  Diabetes diagnosed in48.3%of TB patients.The majority were old females(60.7%)with mean age51.80±11.32.All patients associated with diabetes had type 2 DM.Most of them had diabetes before TB infection(57.1%).TB caused uncontrolled diabetes in71.4%of cases,while diabetes decreased the response to anti-TB drugs in32.1%.In diabetic patients;lesions of tuberculosis were found to be bilateral in39.3%,followed by left lung.It was significantly different from control group as it affected either right or left lung.Lower lung zone affection was significantly higher among diabetic patients 71.4% vs3.3%.Atypical radiological features were significantly common in diabetic patients.Cavitating lesion and pneumonia were the most common presentation(42.9% and25%).Patchy shadows reported in21.4% while one case presented with normal x ray.Broncectasis was reported in upper lobe in 7.1%.  Conclusion  :DM and TB had an adverse affect on each other.The atypical radiological images masked the diagnosis of tuberculosis in diabetic patients,which may delay the proper treatment.
Microbiological and molecular diagnosis of deep localized cutaneous infection with Trichophyton mentagrophytes
Authors: None Sommer, None Barton, None Wilkinson, None Merchant, None Evans, None Moore
Journal: British Journal of Dermatology (1999)

We describe a healthy young woman with a localized deep dermal infection on the right side of the chest wall. It was caused by the dermatophyte Trichophyton mentagrophytes, and resolved after two pulses of oral itraconazole 200 mg twice daily for 1 week. As cultural and microscopic features did not enable a precise identification of the fungus, molecular investigation was undertaken. Patterns of HaeIII restriction digests of genomic DNA from the culture matched those from Arthroderma incurvata and A. benhamiae, which is the teleomorph of T. mentagrophytes var. mentagrophytes.
Montelukast, a potent leukotriene receptor antagonist, causes dose-related improvements in chronic asthma. Montelukast Asthma Study Group
Authors: MJ Noonan, P Chervinsky, M Brandon, J Zhang, S Kundu, J McBurney, TF Reiss
Journal: European Respiratory Journal (1998)

The leukotrienes are known to be important mediators of bronchial asthma. The ability of montelukast, a potent and selective CysLT1 leukotriene receptor antagonist, to cause a dose-related improvement in chronic asthma was investigated in a placebo-controlled, multicentre, parallel-group study. After a two week placebo run-in period, chronic asthmatic patients with a forced expiratory volume in one second (FEV1) 40-80% predicted with &gt; or = 15% increase (absolute value) after beta2-agonist were randomly assigned to one of four treatment groups (placebo or montelukast 2, 10, or 50 mg once daily in the evening) for a three week, double-blind treatment period. For patient-reported end-points (daytime symptom score, use of as needed inhaled beta2 agonist, asthma-specific quality of life) and frequency of asthma exacerbations, montelukast 10 and 50 mg caused similar responses, superior to 2 mg and significantly (p&lt;0.05; linear trend test) different from placebo. All three doses caused improvements in FEV1 and morning and evening peak expiratory flow rate (PEFR) that were significantly (p&lt;0.05) different from placebo. Differences (least square mean) between the pooled 10 and 50 mg montelukast treatment groups and placebo were: 7.1% change from baseline in FEV1, 19.23 L x min(-1) in morning PEFR, -0.29 in daytime asthma symptom score (absolute value), and -0.82 in beta2-agonist use (puff x day(-1)). The incidence of adverse experiences was neither dose-related nor different between montelukast and placebo treatments. We conclude that montelukast causes a dose-related improvement in patient-reported asthma end-points over the range 2-50 mg. Montelukast causes benefit to chronic asthmatic patients by improving asthma control end-points.
Evaluation of disease knowledge in children with cystic fibrosis and their families
Authors: Irmak Dicle Sargin, Yasemin Gokdemir, Refika Ersu, Bulent Karadag, Pinar Ay, Ahmet Topuzoglu, Cagatay Cimsit, Fazilet Karakoc
Journal: European Respiratory Journal (2011)

Introduction:  Increasing the disease knowledge of patients with cystic fibrosis (CF) and their families is important for treatment adherence.   Aim:  To determine the knowledge levels and associated factors in CF patients and their families.   Methods:  Parents of 82 CF patients and 39 children >10 years followed at Paediatric Pulmonology Division were included to the study.Knowledge levels were evaluated with a standardized questionnaire which assesses 3 domains of knowledge: respiratory,digestion and nutrition. Knowledge was compared with demographic features and disease severity determined by Shwachman-Kulczycki Scores (SKS) and pulmonary function tests (FEV1%).   Findings:  82 patients were included to the study (44 girls; median age:9,5 years [25-75percentiles:5.1-14.1]).Median follow up was 8.0 years (25-75percentiles:4.6-11.4).Median SKS was 75“good” (25-75percentiles: 55“good”- 85“good”).Mean FEV1% was 66.5±28.0. Knowledge level was 65.8%±14.7 for children and 69.9%±14.6 for families.Children9s knowledge increased with age (p=0.04), but there was no relation with children9s age and family knowledge.Although no correlation was found with children9s knowledge and socio-economic status (SES), families9 knowledge was related with SES (p=0.04).There was no relation with disease severity and children9s or families9 knowledge.Knowledge level was higher for patients who were followed for longer period at our clinic (p=0.04).Knowledge of children and families were not related.   Conclusion:  CF patients9 and their families9 knowledge are fairly good but needs improvement.Families9 knowledge is associated with SES.Knowledge of children increases with age and follow up time, but is independent from family knowledge and SES.
Characteristics of youth soccer players aged 13–15 years classified by skill level
Authors: Robert M Malina, Basil Ribeiro, João Aroso, Sean P Cumming
Journal: British Journal of Sports Medicine (2007)

Objective: To evaluate the growth, maturity status and functional capacity of youth soccer players grouped by level of skill. Subjects: The sample included 69 male players aged 13.2–15.1 years from clubs that competed in the highest division for their age group. Methods: Height and body mass of players were measured and stage of pubic hair (PH) was assessed at clinical examination. Years of experience in football were obtained at interview. Three tests of functional capacity were administered: dash, vertical jump and endurance shuttle run. Performances on six soccer-specific tests were converted to a composite score which was used to classify players into quintiles of skill. Multiple analysis of covariance, controlling for age, was used to test differences among skill groups in experience, growth status and functional capacity, whereas multiple linear regression analysis was used to estimate the relative contributions of age, years of training in soccer, stage of PH, height, body mass, the height×weight interaction and functional capacities to the composite skill score. Results: The skill groups differed significantly in the intermittent endurance run (p&lt;0.05) but not in the other variables. Only the difference between the highest and lowest skill groups in the endurance shuttle run was significant. Most players in the highest (12 of 14) and high (11 of 14) skill groups were in stages PH 4 and PH 5. Pubertal status and height accounted for 21% of the variance in the skill score; adding aerobic resistance to the regression increased the variance in skill accounted for to 29%. In both regressions, the coefficient for height was negative. Conclusion: Adolescent soccer players aged 13–15 years classified by skill do not differ in age, experience, body size, speed and power, but differ in aerobic endurance, specifically at the extremes of skill. Stage of puberty and aerobic resistance (positive coefficients) and height (negative coefficient) are significant predictors of soccer skill (29% of the total explained variance), highlighting the inter-relationship of growth, maturity and functional characteristics of youth soccer players.
Increased Lifespan with Altered Sequence of Administration of BCNU and Cytoxan in L1210 Leukemic Mice
Authors: Marc J. Straus, Sung C. Choi, Abraham Goldin
Journal: JNCI Journal of the National Cancer Institute (1973)

Journal Article Increased Lifespan with Altered Sequence of Administration of BCNU and Cytoxan in L1210 Leukemic Mice Get access Marc J. Straus, M.D., Marc J. Straus, M.D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Sung C. Choi, Ph. D., Sung C. Choi, Ph. D. Search for other works by this author on: Oxford Academic PubMed Google Scholar Abraham Goldin, Ph. D. Abraham Goldin, Ph. D. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 50, Issue 2, February 1973, Pages 475–480, https://doi.org/10.1093/jnci/50.2.475 Published: 01 February 1973 Article history Received: 10 August 1972 Accepted: 24 October 1972 Published: 01 February 1973
Targeting Siglecs with a sialic acid–decorated nanoparticle abrogates inflammation
Authors: Shaun Spence, Michelle K. Greene, François Fay, Emily Hams, Sean P. Saunders, Umar Hamid, Marianne Fitzgerald, Jonathan Beck, Baljinder K. Bains, Peter Smyth, Efrosyni Themistou, Donna M. Small, Daniela Schmid, Cecilia M. O’Kane, Denise C. Fitzgerald, Sharif M. Abdelghany, James A. Johnston, Padraic G. Fallon, James F. Burrows, Daniel F. McAuley, Adrien Kissenpfennig, Christopher J. Scott
Journal: Science Translational Medicine (2015)

A nanoparticle coated with sialic acid activates Siglec receptors on macrophages, improving survival from sepsis in mice and reducing inflammation in human tissues.
Response to Comment on Anjana et al. Incidence of Diabetes and Prediabetes and Predictors of Progression Among Asian Indians: 10-Year Follow-up of the Chennai Urban Rural Epidemiology Study (CURES). Diabetes Care 2015;38:1441–1448
Authors: Ranjit Mohan Anjana, Mohan Deepa, Viswanathan Mohan
Journal: Diabetes Care (2016)

We thank Drs. Yamauchi and Aizawa for their comment (1) in response to our article (2). They question the exclusion of HbA1c in the definition of prediabetes in our study, because we defined prediabetes as fasting plasma glucose (FPG) 100–125 mg/dL (5.6–6.9 mmol/L) or 2-h plasma glucose 140–199 mg/dL (7.8–11.0 mmol/L).

Undoubtedly, the use of HbA1c has several advantages: the test can be performed at any time of the day and does not require a fasting sample. However, in developing countries such as India there are several limitations to using HbA1c for epidemiological/community screening. These include its high cost; the lack of standardization …