tbuckley/cabot-search huggingface dataset:
Reduced IGFBP-1 Is Associated With Thickening of the Carotid Wall in Type 2 Diabetes
Authors: Eeva S. Leinonen, Jukka T. Salonen, Riitta M. Salonen, Riitta A. Koistinen, Pekka J. Leinonen, Seppo S. Sarna, Marja-Riitta Taskinen
Journal: Diabetes Care (2002)

OBJECTIVE—The aim of the present study was to assess the role of the insulin-like growth factor (IGF) system and lipids in predicting the carotid intima-media thickness (IMT) in type 2 diabetes. RESEARCH DESIGN AND METHODS—A total of 239 type 2 diabetic participants in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study (76 women) aged 50–75 years were examined before fenofibrate intervention. Patients underwent carotid ultrasonography for determination of IMT. IGF-I, IGF binding protein 1 (IGFBP-1), IGFBP-3, cholesterol, triglycerides, HDL cholesterol, LDL cholesterol, apolipoprotein B (apoB), lipoprotein(a) (Lp(a)), glucose, HbA1c, and C-peptide were measured in fasting samples. Patients were divided in groups without (n = 168) and with (n = 71) clinical cardiovascular disease (CVD). RESULTS—Partial correlations adjusted for age, sex, BMI, and diabetes duration showed an inverse association of IGFBP-1 with C-peptide (r = −0. 24, P = 0.018) and with maximal IMT (r = −0.42, P &amp;lt; 0.001), whereas IGF I and IGFBP-3 correlated positively with several risk-promoting lipid parameters. In linear regression analysis controlling for age, sex, BMI, diabetes duration, and presence or absence of oral antihyperglycemic or insulin medication, determinants of IMT were age, IGFBP-1, pulse pressure, Lp(a), diabetes duration, and insulin treatment. IGFBP-1 persisted in the model for subjects with CVD. CONCLUSIONS—In summary, a decrease in IGFBP-1 is a marker of carotid IMT thickening in patients with type 2 diabetes.
An evolutionary theory of schizophrenia: Cortical connectivity, metarepresentation, and the social brain
Authors: Jonathan Kenneth Burns
Journal: Behavioral and Brain Sciences (2004)

Schizophrenia is a worldwide, prevalent disorder with a multifactorial but highly genetic aetiology. A constant prevalence rate in the face of reduced fecundity has caused some to argue that an evolutionary advantage exists in unaffected relatives. Here, I critique this adaptationist approach, and review – and find wanting – Crow's “speciation” hypothesis. In keeping with available biological and psychological evidence, I propose an alternative theory of the origins of this disorder. Schizophrenia is a disorder of the social brain, and it exists as a costly trade-off in the evolution of complex social cognition. Paleoanthropological and comparative primate research suggests that hominids evolved complex cortical interconnectivity (in particular, frontotemporal and frontoparietal circuits) to regulate social cognition and the intellectual demands of group living. I suggest that the ontogenetic mechanism underlying this cerebral adaptation was sequential hypermorphosis and that it rendered the hominid brain vulnerable to genetic and environmental insults. I argue that changes in genes regulating the timing of neurodevelopment occurred prior to the migration of Homo sapiens out of Africa 100,000–150,000 years ago, giving rise to the schizotypal spectrum. While some individuals within this spectrum may have exhibited unusual creativity and iconoclasm, this phenotype was not necessarily adaptive in reproductive terms. However, because the disorder shared a common genetic basis with the evolving circuitry of the social brain, it persisted. Thus schizophrenia emerged as a costly trade-off in the evolution of complex social cognition.
The impact of the granulocyte colony-stimulating factor on chemotherapy dose intensity and cancer survival: a systematic review and meta-analysis of randomized controlled trials
Authors: G.H. Lyman, D.C. Dale, E. Culakova, M.S. Poniewierski, D.A. Wolff, N.M. Kuderer, M. Huang, J. Crawford
Journal: Annals of Oncology (2013)
Long term alcohol intake and risk of rheumatoid arthritis in women: a population based cohort study
Authors: D. Di Giuseppe, L. Alfredsson, M. Bottai, J. Askling, A. Wolk
Journal: BMJ (2012)

<h3>Background</h3> Owing to the rising disease burden of cardiometabolic diseases (CMD), prevention programmes for CMD are increasingly implemented in primary care. Organisational practice characteristics and availability of preventive services may be associated with a more effective programme. <h3>Aim</h3> To identify possible organisational success factors from general practices related to an effective primary prevention programme for CMD. <h3>Design &amp; setting</h3> A prospective intervention study involving 37 Dutch general practices was undertaken. <h3>Method</h3> Patients aged 45–70 years without known CMD, hypertension, or hypercholesterolemia were invited for the prevention programme. The outcome measures were an improvement (yes/no) in four different CMD risk factors between baseline and 1-year follow-up on an individual level (body mass index [BMI], smoking, systolic blood pressure, and cholesterol ratio). Multivariate logistic regression analysis was used for assessing associations between practice organisational characteristics and outcomes. <h3>Results</h3> Just over half of the participants showed an improvement on one or more risk factors. Marginal differences were found in the four different outcomes between the practices with different organisational characteristics. None of the practice characteristics that were tested showed a significant association with an improvement in one of the outcome measures. <h3>Conclusion</h3> In this study, general practice organisational and preventive service characteristics showed no impact on the effectiveness of a CMD prevention programme. Possible explanations could be the effectiveness of protocolised pharmaceutical treatment and only limited contribution of lifestyle programmes on the improvement of CMD risk factors.
Vasopressin-2 Receptor Signaling and Autosomal Dominant Polycystic Kidney Disease
Authors: Markus M. Rinschen, Bernhard Schermer, Thomas Benzing
Journal: Journal of the American Society of Nephrology (2014)

Blockade of the vasopressin-2 receptor (V2R) in the kidney has recently emerged as a promising therapeutic strategy in autosomal dominant polycystic kidney disease. The pathophysiologic basis of V2R-dependent cyst proliferation and disease progression, however, is not fully understood. Recent evidence suggests that polycystic kidney disease is characterized by defects in urinary concentrating mechanisms and subsequent deregulation of vasopressin excretion by the neurohypophysis. On the cellular level, several recent studies revealed unexpected crosstalk of signaling pathways downstream of V2R activation in the kidney epithelium. This review summarizes some of the unexpected roles of V2R signaling and suggests that vasopressin signaling itself may contribute crucially to loss of polarity and enhanced proliferation in cystic kidney epithelium.
Marker antigens to assess exposure to molds and their allergens.II. <i>Alternaria alternata</i>
Authors: L. M. Wijnands, W. D. C. Deisz, F. M. Van Leusden
Journal: Allergy (2000)

The estimation of exposure to molds and their products in the indoor environment, which may lead to the occurrence of allergies or respiratory complaints, by means of enumeration of viable parts is inadequate. Therefore, other methods must be developed. When grown under various circumstances (22°C and 30°C, high and low water activity) under laboratory conditions, Alternaria alternata produces one antigen that can be found under all studied growth conditions in extracts of the water‐soluble portion of the mycelium. This common antigen may serve as marker antigen for exposure to A. alternata and its allergens. In extracts of the culture filtrate, three antigens, designated index antigens, have been identified that together may have the function of marker for the exposure to allergens of A. alternata .
MEASURING POPULATION HEALTH: A Review of Indicators
Authors: Vera Etches, John Frank, Erica Di Ruggiero, Doug Manuel
Journal: Annual Review of Public Health (2005)

This article reviews the historical development of population health indicators. We have long known that environmental, socioeconomic, early life conditions, individual actions, and medical care all interact to affect health. Present quantitative reporting on the impact of these factors on population health grew out of Bills of Mortality published in the 1500s. Since then, regular censuses, civil registration of vital statistics, and international classification systems have improved data quality and comparability. Regular national health interview surveys and application of administrative data contributed information on morbidity, health services use, and some social determinants of health. More recently, traditional health databases and datasets on "nonhealth" sector determinants have been linked. Statistical methods for map-making, risk adjustment, multilevel analysis, calculating population-attributable risks, and summary measures of population health have further helped to integrate information. Reports on the health of populations remain largely confined to focused areas. This paper suggests a conceptual framework for using indicators to report on all the domains of population health. Future ethical development of indicators will incorporate principles of justice, transparency, and effectiveness.
The Role of Adiposity in Cardiometabolic Traits: A Mendelian Randomization Analysis
Authors: Tove Fall, Sara Hägg, Reedik Mägi, Alexander Ploner, Krista Fischer, Momoko Horikoshi, Antti-Pekka Sarin, Gudmar Thorleifsson, Claes Ladenvall, Mart Kals, Maris Kuningas, Harmen H. M. Draisma, Janina S. Ried, Natalie R. van Zuydam, Ville Huikari, Massimo Mangino, Emily Sonestedt, Beben Benyamin, Christopher P. Nelson, Natalia V. Rivera, Kati Kristiansson, Huei-yi Shen, Aki S. Havulinna, Abbas Dehghan, Louise A. Donnelly, Marika Kaakinen, Marja-Liisa Nuotio, Neil Robertson, Renée F. A. G. de Bruijn, M. Arfan Ikram, Najaf Amin, Anthony J. Balmforth, Peter S. Braund, Alexander S. F. Doney, Angela Döring, Paul Elliott, Tõnu Esko, Oscar H. Franco, Solveig Gretarsdottir, Anna-Liisa Hartikainen, Kauko Heikkilä, Karl-Heinz Herzig, Hilma Holm, Jouke Jan Hottenga, Elina Hyppönen, Thomas Illig, Aaron Isaacs, Bo Isomaa, Lennart C. Karssen, Johannes Kettunen, Wolfgang Koenig, Kari Kuulasmaa, Tiina Laatikainen, Jaana Laitinen, Cecilia Lindgren, Valeriya Lyssenko, Esa Läärä, Nigel W. Rayner, Satu Männistö, Anneli Pouta, Wolfgang Rathmann, Fernando Rivadeneira, Aimo Ruokonen, Markku J. Savolainen, Eric J. G. Sijbrands, Kerrin S. Small, Jan H. Smit, Valgerdur Steinthorsdottir, Ann-Christine Syvänen, Anja Taanila, Martin D. Tobin, Andre G. Uitterlinden, Sara M. Willems, Gonneke Willemsen, Jacqueline Witteman, Markus Perola, Alun Evans, Jean Ferrières, Jarmo Virtamo, Frank Kee, David-Alexandre Tregouet, Dominique Arveiler, Philippe Amouyel, Marco M. Ferrario, Paolo Brambilla, Alistair S. Hall, Andrew C. Heath, Pamela A. F. Madden, Nicholas G. Martin, Grant W. Montgomery, John B. Whitfield, Antti Jula, Paul Knekt, Ben Oostra, Cornelia M. van Duijn, Brenda W. J. H. Penninx, George Davey Smith, Jaakko Kaprio, Nilesh J. Samani, Christian Gieger, Annette Peters, H.-Erich Wichmann, Dorret I. Boomsma, Eco J. C. de Geus, TiinaMaija Tuomi, Chris Power, Christopher J. Hammond, Tim D. Spector, Lars Lind, Marju Orho-Melander, Colin Neil Alexander Palmer, Andrew D. Morris, Leif Groop, Marjo-Riitta Järvelin, Veikko Salomaa, Erkki Vartiainen, Albert Hofman, Samuli Ripatti, Andres Metspalu, Unnur Thorsteinsdottir, Kari Stefansson, Nancy L. Pedersen, Mark I. McCarthy, Erik Ingelsson, Inga Prokopenko
Journal: PLoS Medicine (2013)

In this study, Prokopenko and colleagues provide novel evidence for causal relationship between adiposity and heart failure and increased liver enzymes using a Mendelian randomization study design. Please see later in the article for the Editors' Summary
Intracerebral Hemorrhage and Delirium Symptoms. Length of Stay, Function, and Quality of Life in a 114-Patient Cohort
Authors: Andrew M. Naidech, Jennifer L. Beaumont, Neil F. Rosenberg, Matthew B. Maas, Adam R. Kosteva, Michael L. Ault, David Cella, E. Wesley Ely
Journal: American Journal of Respiratory and Critical Care Medicine (2013)

Rationale: The prognostic significance of delirium symptoms in intensive care unit (ICU) patients with focal neurologic injury is unclear.Objectives: To determine the relationship between delirium symptoms and subsequent functional outcomes and quality of life (QOL) after intracerebral hemorrhage.Methods: We prospectively enrolled 114 patients. Delirium symptoms were routinely assessed twice daily using the Confusion Assessment Method for the ICU by trained nurses. Functional outcomes were recorded with modified Rankin Scale (scored from 0 [no symptoms] to 6 [dead]), and QOL outcomes with Neuro-QOL at 28 days, 3 months, and 12 months.Measurements and Main Results: Thirty-one (27%) patients had delirium symptoms (“ever delirious”), 67 (59%) were never delirious, and the remainder (14%) had persistent coma. Delirium symptoms were nearly always hypoactive, were detected mean 6 days after intracerebral hemorrhage presentation, and were associated with longer ICU length of stay (mean 3.5 d longer in ever vs. never delirious patients; 95% confidence interval, 1.5–8.3; P = 0.004) after correction for age, admit National Institutes of Health (NIH) Stroke Scale, and any benzodiazepine exposure. Delirium symptoms were associated with increased odds of poor outcome at 28 days (odds ratio, 8.7; 95% confidence interval, 1.4–52.5; P = 0.018) after correction for admission NIH Stroke Scale and age, and with worse QOL in the domains of applied cognition–executive function and fatigue after correcting for the NIH Stroke Scale, age, benzodiazepine exposure, and time of follow-up.Conclusions: After focal neurologic injury, delirium symptoms were common despite low rates of infection and sedation exposure, and were predictive of subsequent worse functional outcomes and lower QOL.
Adipose-Derived Stem Cells for Regenerative Medicine
Authors: Jeffrey M. Gimble, Adam J. Katz, Bruce A. Bunnell
Journal: Circulation Research (2007)

The emerging field of regenerative medicine will require a reliable source of stem cells in addition to biomaterial scaffolds and cytokine growth factors. Adipose tissue represents an abundant and accessible source of adult stem cells with the ability to differentiate along multiple lineage pathways. The isolation, characterization, and preclinical and clinical application of adipose-derived stem cells (ASCs) are reviewed in this article.
P<scp>HYSIOLOGY AND</scp> M<scp>OLECULAR</scp> B<scp>IOLOGY OF</scp> D<scp>IETARY</scp> I<scp>RON</scp> A<scp>BSORPTION</scp>
Authors: Silvia Miret, Robert J. Simpson, Andrew T. McKie
Journal: Annual Review of Nutrition (2003)
Mutations of the cystic fibrosis gene in patients with bronchiectasis associated with rheumatoid arthritis
Authors: Xavier Puéchal, Thierry Bienvenu, Emmanuelle Génin, Jean-Marie Berthelot, Jean Sibilia, Philippe Gaudin, Christian Marcelli, Sandra Lasbleiz, Laëtitia Michou, François Cornélis, André Kahan, Daniel J Dusser
Journal: Annals of the Rheumatic Diseases (2010)

Objectives In cystic fibrosis, mutations of the CFTR gene lead to diffuse bronchiectasis (DB). DB is also associated with other diseases including rheumatoid arthritis (RA) in which the role of genetic factors in the predisposition to DB remains unclear. Methods A family-based association study was carried out to determine whether the frequency of CFTR mutations was higher in patients with RA-associated DB and to determine whether a causal relationship could be established between the variant and the disease by evaluating its cosegregation with DB within families. Families of probands with RA-DB were included if one first-degree relative had RA and/or DB. The controls comprised healthy subjects requesting genetic counselling because their partner had cystic fibrosis. Results The frequency of CFTR mutations was higher in family members with RA-DB or DB only than in unaffected relatives (p&lt;0.005 for each comparison) and in unrelated healthy controls (p&lt;0.001 for each comparison) but not in family members with RA only. CFTR mutations were more frequent in family members with RA-DB than in those with RA only (OR 5.30, 95% CI 2.48 to 11.33; p&lt;5×10 −5 ). They cosegregated with RA-DB in the families (sib-TDT=10.82, p=0.005). Conclusions RA-DB should be added to the list of phenotypes in which CFTR mutations are pathogenic. CFTR mutation is the first genetic defect linked to an extra-articular feature of RA to be described. CFTR mutations in patients with RA appear to be an important marker of the risk of associated DB, which has been linked to a less favourable prognosis.
Decline of the lung function related to the type of tobacco smoked and inhalation.
Authors: P Lange, S Groth, J Nyboe, J Mortensen, M Appleyard, G Jensen, P Schnohr
Journal: Thorax (1990)

Data from a five year follow up study on 4372 smokers and 3753 non-smokers were analysed to investigate the influence of the type of tobacco smoked and whether the subjects said they inhaled or not on the decline in forced expiratory volume in one second (FEV1). The study sample comprised 1492 smokers of plain cigarettes and 1936 smokers of filter cigarettes, 1711 smokers of cheroots or cigars, and 233 male pipe smokers. Over the five years, smokers, especially those who said that they inhaled, had a higher rate of decline of FEV1 than non-smokers, in whom the average decline in FEV1 was 25 ml/year for women and 30 ml/year for men. There was no significant difference in the decline in FEV1 between filter cigarette smokers and plain cigarette smokers. The decline in FEV1 in cigar or cheroot smokers was the highest for all the smoking groups, and associated with a very high tobacco consumption in this group. Among pipe smokers who inhaled, the decline in FEV1 was slightly higher than in the cigarette smokers, whereas non-inhaling pipe smokers had a decline in FEV1 that was similar to that of non-smokers. In general, the smokers who said that they did not inhale had a smaller decline in FEV1 than those who said that they did. The effect of inhalation varied in magnitude in different smoking groups, being most pronounced in pipe smokers.
Laryngopharyngeal pepsin reflux in chest clinic patients with upper airways symptoms
Authors: Alexander Spyridoulias, Siobhan Lillie, Jemma Haines, Aashish Vyas, Stephen Fowler
Journal: European Respiratory Journal (2012)

Introduction: Laryngopharyngeal reflux (LPR) may underlie both chronic cough and vocal cord dysfunction, and one explanation for a lack of response to standard anti-reflux therapy may be the persistence of non-acid-reflux. Salivary pepsin is a potential biomarker for LPR. The aim of this study was to evaluate if the detection of pepsin in saliva was associated with signs of laryngopharyngeal reflux in patients having nasendoscopy for investigation of upper airway symptoms.  Methods: We recruited patients from the Airways Clinic requiring nasendoscopy. All patients had the Reflux Finding Score (RFS) recorded at nasendoscopy. Salivary pepsin was quantified with a lateral flow device using monoclonal antibody labelling (Peptest, RD Biomed, UK).  Results: Of 20 patients recruited, 12 were confirmed to have VCD and 13 a clinical suspicion of LPR (based on an RFS > 7). Pepsin was detected in the saliva of 11/20 subjects (55%), including 67% of the VCD patients and 61% of those with a high RFS, although 43% of those with a low RFS also had a positive pepsin. Salivary pepsin had a sensitivity of 62% and specificity of 57% for predicting a high RFS. There was no significant correlation between RFS scores and salivary pepsin. Seven of the 10 patients already on treatment for a clinical diagnosis of reflux had a positive pepsin assay.  Conclusions: Salivary pepsin was frequently present in patients with upper airway symptoms, and not strongly related to clinical findings of reflux, suggesting a high prevalence of sub-clinical LPR. Further investigation should determine the clinical relevance of this, and whether LPR treatment results in an improvement in pepsin levels and the associated upper airway symptoms.
H11 Kinase/Heat Shock Protein 22 Deletion Impairs Both Nuclear and Mitochondrial Functions of STAT3 and Accelerates the Transition Into Heart Failure on Cardiac Overload
Authors: Hongyu Qiu, Paulo Lizano, Lydie Laure, Xiangzhen Sui, Eman Rashed, Ji Yeon Park, Chull Hong, Shumin Gao, Eric Holle, Didier Morin, Sunil K. Dhar, Thomas Wagner, Alain Berdeaux, Bin Tian, Stephen F. Vatner, Christophe Depre
Journal: Circulation (2011)

Background— Cardiac overload, a major cause of heart failure, induces the expression of the heat shock protein H11 kinase/Hsp22 (Hsp22). Methods and Results— To determine the specific function of Hsp22 in that context, a knockout mouse model of Hsp22 deletion was generated. Although comparable to wild-type mice in basal conditions, knockout mice exposed to pressure overload developed less hypertrophy and showed ventricular dilation, impaired contractile function, increased myocyte length and accumulation of interstitial collagen, faster transition into heart failure, and increased mortality. Microarrays revealed that hearts from knockout mice failed to transactivate genes regulated by the transcription factor STAT3. Accordingly, nuclear STAT3 tyrosine phosphorylation was decreased in knockout mice. Silencing and overexpression experiments in isolated neonatal rat cardiomyocytes showed that Hsp22 activates STAT3 via production of interleukin-6 by the transcription factor nuclear factor-κB. In addition to its transcriptional function, STAT3 translocates to the mitochondria where it increases oxidative phosphorylation. Both mitochondrial STAT3 translocation and respiration were also significantly decreased in knockout mice. Conclusions— This study found that Hsp22 represents a previously undescribed activator of both nuclear and mitochondrial functions of STAT3, and its deletion in the context of pressure overload in vivo accelerates the transition into heart failure and increases mortality.
Phase II study of biomarker-guided neoadjuvant treatment strategy for IIIA-N2 non-small cell lung cancer based on epidermal growth factor receptor mutation status
Authors: Wenzhao Zhong, Xuening Yang, Honghong Yan, Xuchao Zhang, Jian Su, Zhihong Chen, Riqiang Liao, Qiang Nie, Song Dong, Qing Zhou, Jinji Yang, Haiyan Tu, Yi-Long Wu
Journal: Journal of Hematology & Oncology (2015)

Neoadjuvant erlotinib and customized adjuvant therapy are appealing but controversial. The purpose of this study was to evaluate the role of biomarker-guided neoadjuvant treatment strategy in patients with IIIA-N2 non-small cell lung cancer (NSCLC) stratified by epidermal growth factor receptor (EGFR) mutation status. Patients with resectable histologically documented stage IIIA-N2 NSCLC were assigned to a neoadjuvant erlotinib arm or a gemcitabine/carboplatin (GC) arm based on EGFR mutation status. The primary endpoint was response rate (RR). Secondary endpoints were progression-free survival (PFS) and overall survival (OS). Twenty-four patients with IIIA-N2 NSCLC were enrolled in the trial from January 2008 until May 2011. The overall response rate was 41.7% and the PFS and OS were 7.9 and 23.2 months, respectively, in overall population. The RR was 58.3% (7/12) for the erlotinib arm with mutant EGFR and 25.0% (3/12) for the GC arm with wild type EGFR (P = 0.18). Median PFS was 6.9 months versus 9.0 months, respectively (P = 0.071). Median OS was 14.5 months for the erlotinib arm and 28.1 months for the GC arm (P = 0.201). No unexpected toxicities were observed. The primary endpoint was met and biomarker-guided neoadjuvant treatment strategy in patients with IIIA-N2 NSCLC is feasible. Erlotinib alone in neoadjuvant setting of EGFR mutant population showed an improved response but without survival benefits. ClinicalTrials.gov NCT00600587 https://www.clinicaltrials.gov/ct2/show/NCT00600587?term=NCT00600587&rank=1.