tbuckley/cabot-search huggingface dataset:
Attention Network Hypoconnectivity With Default and Affective Network Hyperconnectivity in Adults Diagnosed With Attention-Deficit/Hyperactivity Disorder in Childhood
Authors: Hazel McCarthy, Norbert Skokauskas, Aisling Mulligan, Gary Donohoe, Diane Mullins, John Kelly, Katherine Johnson, Andrew Fagan, Michael Gill, James Meaney, Thomas Frodl
Journal: JAMA Psychiatry (2013)

The neurobiological underpinnings of attention-deficit/hyperactivity disorder (ADHD) and particularly those associated with the persistence of ADHD into adulthood are not yet well understood.The correlation patterns in spontaneous neural fluctuations at rest are known as resting-state functional connectivity (RSFC) and could characterize ADHD-specific connectivity changes.OBJECTIVE To determine the specific location of possible ADHD-related differences in RSFC between adults diagnosed as having ADHD in childhood and control subjects.DESIGN Using resting-state functional magnetic resonance imaging, we calculated and compared functional connectivity from attention, affective, default, and cognitive control networks involved in the psychopathology of ADHD between the ADHD and control groups.SETTING University psychiatric service and magnetic resonance imaging research center.PARTICIPANTS Sixteen drug-free adults (5 women and 11 men; mean age, 24.5 years) diagnosed with combined-type ADHD in childhood and 16 healthy controls matched for age (mean age, 24.4 years), sex, handedness, and educational level recruited from the community. INTERVENTION Functional magnetic resonance imaging.MAIN OUTCOMES AND MEASURES Connectivity data from ventral and dorsal attention, affective, default, and cognitive control networks and ADHD symptoms derived from ADHD-specific rating instruments.RESULTS Adults with ADHD showed significantly decreased RSFC within the attention networks and increased RSFC within the affective and default mode and the right lateralized cognitive control networks compared with healthy controls (P < .01,familywise error for whole-brain cluster correction).Lower RSFC in the ventral and dorsal attention network was significantly correlated with higher levels of ADHD symptoms (P < .001).CONCLUSIONS AND RELEVANCE These RSFC findings might underpin a biological basis for adult ADHD and are functionally related to persistent inattention, disturbance in cognitive control, and emotional dysregulation in adults with ADHD.These findings need to be understood in the context of all aspects of brain function in ADHD.
Function and expression of endothelin receptor subtypes in the kidneys of spontaneously hypertensive rats
Authors: B. Hocher, P. Rohmeiss, R. Zart, F. Diekmann, V. Vogt, D. Metz, M. Fakhury, N. Gretz, C. Bauer, K. Koppenhagen, H. H. Neumayer, A. Distler
Journal: Cardiovascular Research (1996)

Objective: The renal endothelin system has been implicated in the development and maintenance of hypertension in spontaneously hypertensive rats (SHR). However, little is known about the function and cellular distribution of endothelin receptor subtypes in the kidneys of SHR. Methods: We analyzed the expression of endothelin receptor subtypes in the kidneys of 16-week-old SHR using Scatchard analysis, receptor autoradiography, Northern blot analysis and in situ hybridization. Wistar-Kyoto rats (WKY) served as controls. Furthermore, we investigated the effects of the mixed (A/B) endothelin receptor antagonist bosentan and the ETA receptor antagonist BQ 123 on mean arterial blood pressure (MAP), renal blood flow (RBF) and glomerular filtration rate (GFR) in conscious chronically instrumented rats. Results: In SHR, we found by receptor autoradiography an overexpression of the endothelin A receptor (ETA) in the glomeruli (2.2 ± 0.4-fold; P < 0.05) and smooth muscle cells of intrarenal arteries (1.9 ± 0.2-fold; P < 0.05) compared to age-matched WKY. In addition, our study revealed a pronounced upregulation of endothelin B receptor (ETB) in the glomeruli of SHR (5.6 ± 0.8-fold; P < 0.01). Blockade of endothelin receptors in SHR with bosentan (A and B receptor blockade) as well as with BQ 123 (A receptor blockade) led to a significant decrease in MAP (−18.6 ± 2.1 and − 19 ± 1.3 mmHg, respectively; P < 0.05 in both cases) and a significant increase in RBF (+ 2.8 ± 0.5 and +3.1 ± 0.37 ml/min, respectively; P < 0.05 in both cases). The blockade of both ETA and ETB by bosentan had no further effect on MAP reduction or RBF increase in SHR compared to the ETA blockade by BQ 123. The ETA antagonist BQ 123 had no effect on GFR either in SHR or in WKY, whereas the combined blockade of ETA and ETB by bosentan significantly decreased GFR in SHR by about 50% but not in WKY. Conclusions: Our data demonstrated a correlation between the overexpression of vascular ETA receptors and the pronounced upregulation of glomerular ETB receptors in the kidneys of SHR and their impact on the regulation of renal blood flow, glomerular filtration rate and blood pressure in these animals.
Peroxisome Proliferator-Activated Receptor γ Pathway Targeting in Carcinogenesis: Implications for Chemoprevention
Authors: Frank Ondrey
Journal: Clinical Cancer Research (2008)

Abstract The peroxisome proliferator-activated receptor (PPAR) γ is one member of the nuclear receptor superfamily that contains in excess of 80 described receptors. PPARγ activators are a diverse group of agents that range from endogenous fatty acids or derivatives (linolenic, linoleic, and 15-deoxy-Δ12,14-prostaglandin J2) to Food and Drug Administration-approved thiazolidinedione drugs [pioglitazone (Actos) and rosiglitazone (Avandia)] for the treatment of diabetes. Once activated, PPARγ will preferentially bind with retinoid X receptor α and signal antiproliferative, antiangiogenic, and prodifferentiation pathways in several tissue types, thus making it a highly useful target for down-regulation of carcinogenesis. Although PPAR-γ activators show many anticancer effects on cell lines, their advancement into human advanced cancer clinical trials has met with limited success. This article will review translational findings in PPARγ activation and targeting in carcinogenesis prevention as they relate to the potential use of PPARγ activators clinically as cancer chemoprevention strategies.
An update on the use and investigation of probiotics in health and disease
Authors: Mary Ellen Sanders, Francisco Guarner, Richard Guerrant, Peter R Holt, Eamonn MM Quigley, R Balfour Sartor, Philip M Sherman, Emeran A Mayer
Journal: Gut (2013)

Probiotics are derived from traditional fermented foods, from beneficial commensals or from the environment. They act through diverse mechanisms affecting the composition or function of the commensal microbiota and by altering host epithelial and immunological responses. Certain probiotic interventions have shown promise in selected clinical conditions where aberrant microbiota have been reported, such as atopic dermatitis, necrotising enterocolitis, pouchitis and possibly irritable bowel syndrome. However, no studies have been conducted that can causally link clinical improvements to probiotic-induced microbiota changes. Whether a disease-prone microbiota pattern can be remodelled to a more robust, resilient and disease-free state by probiotic administration remains a key unanswered question. Progress in this area will be facilitated by: optimising strain, dose and product formulations, including protective commensal species; matching these formulations with selectively responsive subpopulations; and identifying ways to manipulate diet to modify bacterial profiles and metabolism.
Syngeneic antiidiotypic immune responses to a B cell lymphoma. Comparison between heavy chain hypervariable region peptides and intact Ig as immunogens.
Authors: K Thielemans, J B Rothbard, S Levy, R Levy
Journal: The Journal of Experimental Medicine (1985)

The nucleic acid sequence of the heavy chain variable region (VH) expressed by 38C13, a B cell tumor of C3H origin, was determined by a combination of direct (messenger RNA) mRNA sequencing by primer extension and complementary DNA (cDNA) isolation and sequencing in M13. The VH amino acid sequence was deduced, and hypervariable regions were identified. From an analysis of predicted secondary structure, regions of predicted antigenicity were chosen, and a series of synthetic peptides corresponding to CDR2 and CDR3 (complementarity-determining region) were produced. These peptides were coupled to protein carriers and used to immunize syngeneic C3H mice. All peptides gave rise to a vigorous antibody response. However, only the CDR3 peptides induced antibodies that crossreacted with the isolated H chain protein. Only one CDR3 peptide induced antibody-producing clones, isolated as hybridomas, that reacted with the intact IgM protein. However, the appearance of these clones was a low-frequency event. All antibodies reacting with the H chain or the intact IgM protein were idiotypically specific for 38C13. These monoclonal antiidiotype (anti-Id) antibodies, raised against CDR3 peptides, gave strong reactions in enzyme-linked immunosorbent assays and immunoblots, but they were of low affinity compared to syngeneic anti-Id raised against the intact IgM protein. Moreover, while the intact IgM was capable of inducing tumor immunity, the CDR peptides were not able to do so.
GHb Level and Subsequent Mortality Among Adults in the U.S.
Authors: Sharon Saydah, Min Tao, Giuseppina Imperatore, Edward Gregg
Journal: Diabetes Care (2009)

OBJECTIVE To examine the association of hyperglycemia, as measured by GHb, with subsequent mortality in a nationally representative sample of adults. RESEARCH DESIGN AND METHODS We included adults aged > or =20 years who participated in Third National Health and Nutrition Examination Survey (1988-1994) and had complete information, including baseline diabetes status by self-report and measured GHb (n = 19,025) and follow-up through the end of 2000 for mortality. RESULTS In the overall population, higher levels of GHb were associated with increased risk of mortality from all causes, heart disease, and cancer. After adjustment for potential risk factors, the relative hazard (RH) for adults with GHb > or =8% compared with adults with GHb <6% was 2.59 (95% CI 1.88-3.56) for all-cause mortality, 3.38 (1.98-5.77) for heart disease mortality, and 2.64 (1.17-5.97) for cancer mortality. Among adults with diagnosed diabetes, having GHb > or =8% compared with GHb <6% was associated with higher all-cause mortality (RH 1.68, 95% CI 1.03-2.74) and heart disease mortality (2.48, 1.09-5.64), but there was no increased risk of cancer mortality by GHb category. Among adults without diagnosed diabetes, there was no significant association of all-cause, heart disease, or cancer mortality and GHb category. CONCLUSIONS These results highlight the importance of GHb levels in mortality risk among a nationally representative sample of adults with and without diagnosed diabetes and indicate that higher levels are associated with increased mortality in adults with diabetes.
Mania and schizo-affective disorder, main type: a comparison
Authors: R Abrams, M A Taylor
Journal: American Journal of Psychiatry (1976)

The authors report data gathered from a consecutive sample of 88 psychiatric inpatients who were diagnosed as having either manic disorder or schizo-affective disorder, manic type, according to Research Diagnostic Criteria (1) similar to those proposed for DSM-III. There were no differences between diagnostic groups on clinical psychopathological or demographic variables, individual or family history, or treatment response.
Publication and Reporting Conduct for Pharmacodynamic Analyses of Tumor Tissue in Early-Phase Oncology Trials
Authors: Georgina A. Freeman, Jonathan Kimmelman
Journal: Clinical Cancer Research (2012)

In principle, nondiagnostic biopsies for pharmacodynamic (PD) studies are carried out to inform decision-making in drug development. Because such procedures have no therapeutic value, their ethical justification requires that results be published. We aimed to assess the frequency of nonpublication of PD data in early phase cancer trials and to identify factors that prevent full publication of data.We identified a sample of early-phase cancer trials containing invasive nondiagnostic tissue procurement for PD analysis from American Society of Clinical Oncology and American Association for Cancer Research meeting abstracts published between 1995 and 2005. These trials were followed to publication to determine frequency of nonpublication of PD data. Corresponding authors on early-phase cancer trials using invasive nondiagnostic research procedures were also surveyed to identify factors preventing full publication of PD data.In a sample of 90 trials, 22.2% (20 trials) resulted in no trial publication. Of published trials expected to contain PD reports, 16 (17.8%) did not include any PD data, and 21 (23.3%) reported incomplete PD data. We surveyed 92 authors; nonpublication was regarded as a frequent occurrence, and the most commonly cited barrier to full publication of PD data was strategic considerations in publication (58.8% of responding authors).Our results suggest ways that investigators, study planners, and reviewers can improve the burden/knowledge value balance in PD studies.
Assessing fitness to fly in young infants and children
Authors: G L Hall, M Verheggen, S M Stick
Journal: Thorax (2007)

Commercial aircrafts cruise between 9150 and 13000 m above sea level, with a cabin pressure equivalent to 1530–2440 m at which passengers breathe the equivalent of 15–17% of fractional inspired oxygen (FiO2) at sea level.

British Thoracic Society recommendations for passengers with chronic respiratory disorders planning air travel1 suggest that infants and young children unable to perform spirometry, with a history of neonatal respiratory disease consult a paediatrician and a hypoxia test be considered. The recommended hypoxia test method in young children is to place the child in a body plethysmograph while seated on the parent’s lap and introduce nitrogen until FiO2 equals 15%. This method relies on equipment not readily available outside the tertiary hospital setting. We have reported a review of hypoxia testing in …
Symptom Dimensions of Depression Following Myocardial Infarction and Their Relationship With Somatic Health Status and Cardiovascular Prognosis
Authors: Peter de Jonge, Johan Ormel, Rob H.S. van den Brink, Joost P. van Melle, Titia A. Spijkerman, Astrid Kuijper, Dirk J. van Veldhuisen, Maarten P. van den Berg, Adriaan Honig, Harry J.G.M. Crijns, Aart H. Schene
Journal: American Journal of Psychiatry (2006)

OBJECTIVE: The reporting of depressive symptoms following myocardial infarction may be confounded by complaints originating from the myocardial infarction. Therefore, it is difficult to estimate the effects of post-myocardial infarction depression and its treatment on cardiovascular prognosis. The authors' goal was to study the relationship between depressive symptom dimensions following myocardial infarction and both somatic health status and prospective cardiovascular prognosis. METHOD: In two studies of myocardial infarction patients (N=494 and 1,972), the Beck Depression Inventory was used to determine the dimensional structure of depressive symptoms following myocardial infarction. Three symptom dimensions—somatic/affective, cognitive/affective, and appetitive—were compared with baseline left ventricular ejection fraction, Charlson comorbidity index, Killip class, and previous myocardial infarction. The relationship between depressive symptom dimensions and prospective cardiovascular mortality and cardiac-related readmissions was also examined (mean follow-up duration=2.5 years). RESULTS: Somatic/affective symptoms were associated with poor health status (left ventricular ejection fraction, Charlson comorbidity index, Killip class, and previous myocardial infarction) and predicted cardiovascular mortality and cardiac events. Cognitive/affective symptoms were only marginally associated with somatic health status and not with cardiovascular death and cardiac events. Appetitive symptoms were related to somatic health status but did not predict cardiovascular death or cardiac events. CONCLUSIONS: Somatic/affective depressive symptoms following myocardial infarction were confounded by somatic health status yet were prospectively associated with cardiac prognosis even after somatic health status was controlled. Cognitive/affective depressive symptoms were only marginally related to health status and not to cardiac prognosis. These findings suggest that treatment of depression following myocardial infarction might improve cardiovascular prognosis when it reduces somatic/affective symptoms.
Dietary Protein Intake and Incidence of Type 2 Diabetes in Europe: The EPIC-InterAct Case-Cohort Study
Authors: Monique van Nielen, Edith J.M. Feskens, Marco Mensink, Ivonne Sluijs, Esther Molina, Pilar Amiano, Eva Ardanaz, Beverly Balkau, Joline W.J. Beulens, Heiner Boeing, Françoise Clavel-Chapelon, Guy Fagherazzi, Paul W. Franks, Jytte Halkjaer, José Maria Huerta, Verena Katzke, Timothy J. Key, Kay Tee Khaw, Vittorio Krogh, Tilman Kühn, Virginia V.M. Menéndez, Peter Nilsson, Kim Overvad, Domenico Palli, Salvatore Panico, Olov Rolandsson, Isabelle Romieu, Carlotta Sacerdote, Maria-José Sánchez, Matthias B. Schulze, Annemieke M.W. Spijkerman, Anne Tjonneland, Rosario Tumino, Daphne L. van der A, Anne M.L. Würtz, Raul Zamora-Ros, Claudia Langenberg, Stephen J. Sharp, Nita G. Forouhi, Elio Riboli, Nicholas J. Wareham
Journal: Diabetes Care (2014)

The long-term association between dietary protein and type 2 diabetes incidence is uncertain. We aimed to investigate the association between total, animal, and plant protein intake and the incidence of type 2 diabetes.
Access Flow Monitoring of Patients with Native Vessel Arteriovenous Fistulae and Previous Angioplasty
Authors: Marcello Tonelli, David Hirsch, Timothy W.I. Clark, Colleen Wile, Paula Mossop, Joanne Marryatt, Kailash Jindal
Journal: Journal of the American Society of Nephrology (2002)

Screening strategies based on measurement of access blood flow (Qa) allow detection and angioplasty of subclinical stenosis in native vessel arteriovenous (AV) fistulae. However, little is known about the efficacy of Qa measurements for detecting recurrent stenoses in fistulae and that of angioplasty for correcting them. A total of 303 patients were studied over 30 mo; 69 (23%) of these had stenoses, of whom 53 underwent angioplasty. Of those undergoing angioplasty, 30 patients had 46 episodes of recurrent positive studies and underwent repeat fistulography. In 31 of these episodes (19 patients), stenosis was again identified and treated successfully with angioplasty. Overall positive predictive values for stenosis were similar in first and subsequent episodes of stenosis (71% versus 67%), and angioplasty was associated with sustained increases in Qa for both first and subsequent episodes. Assisted patency in fistulae that required repeat angioplasty was 87% (median follow-up 10 mo after the second angioplasty). In conclusion, Qa is effective for detecting first and subsequent lesions in patients with AV fistulae, and angioplasty of first or subsequent lesions is associated with sustained increments in Qa. Continued screening after correction of first stenoses appears reasonable, because of both the frequency of recurrent stenosis and the success of repeat intervention.
Rhinovirus Species and Asthma Exacerbations in Inner-City Children
Authors: Ann T. Esquivel, Peter J. Gergen, Rebecca S. Gruchalla, Meyer Kattan, Haejin Kim, Petra Lebeau, Andrew H. Liu, Jacqueline A. Pongracic, Stephen J. Teach, Joseph B. West, Jeremy Wildfire, James E. Gern
Journal: Journal of Allergy and Clinical Immunology (2015)
Transmural dispersion of repolarization and the T wave
Authors: C Antzelevitch
Journal: Cardiovascular Research (2001)

See article by Taggart et al. [50] (pages 454-462) in this issue. 

Studies conducted over the past dozen years or so have demonstrated that ventricular myocardium is not homogeneous, as previously thought, but is comprised of at least three electrophysiologically distinct cell types: epicardial, M and endocardial cells (see [1,2] for reviews). These three cell types have also been shown to possess different pharmacologic profiles and to respond differently to a variety of pathophysiologic states [3–8].

The three cells types differ principally with respect to repolarization characteristics. Ventricular epicardial and M cells display action potentials with a prominent transient outward current ( I to)-mediated phase 1, giving rise to a notched appearance of the action potential. The absence of a prominent notch in the endocardium is a consequence of a much smaller I to. Similar regional differences in I to are found in canine, feline, rabbit, rat and human ventricular myocytes (see [1] for references). Recent studies also indicate that I to and the action potential notch are much larger in right vs. left ventricular epicardial [9] and M [10] cells. The transmural gradient in the amplitude of the I to-mediated action potential notch underlies the normal J wave or J point elevation in the ECG [11] and its accentuation, particularly in the right ventricle, contributes to the development of life-threatening arrhythmias in patients with the Brugada syndrome and various forms of idiopathic ventricular fibrillation [12,13]. The presence of a prominent I to in right ventricular epicardium has also been shown to sensitize this tissue to the effects of ischemia [14]. Accentuation of the action potential notch and eventual loss of the dome in right ventricular epicardium but not endocardium has been shown to contribute to ischemia-induced ST segment elevation [12].

The M cells are … 

*Tel.: +1-315-735-2217; fax: +1-315-735-5648 ca{at}mmrl.edu
Plasminogen activator inhibitor-1 in acute hyperoxic mouse lung injury.
Authors: C Barazzone, D Belin, P F Piguet, J D Vassalli, A P Sappino
Journal: Journal of Clinical Investigation (1996)

Hyperoxia-induced lung disease is associated with prominent intraalveolar fibrin deposition. Fibrin turnover is tightly regulated by the concerted action of proteases and antiproteases, and inhibition of plasmin-mediated proteolysis could account for fibrin accumulation in lung alveoli. We show here that lungs of mice exposed to hyperoxia overproduce plasminogen activator inhibitor-1 (PAI-1), and that PAI-1 upregulation impairs fibrinolytic activity in the alveolar compartment. To explore whether increased PAI-1 production is a causal or only a correlative event for impaired intraalveolar fibrinolysis and the development of hyaline membrane disease, we studied mice genetically deficient in PAI-1. We found that these mice fail to develop intraalveolar fibrin deposits in response to hyperoxia and that they are more resistant to the lethal effects of hyperoxic stress. These observations provide clear and novel evidence for the pathogenic contribution of PAI-1 in the development of hyaline membrane disease. They identify PAI-1 as a major deleterious mediator of hyperoxic lung injury.
The dynamics of what?
Authors: Fred A. Keijzer, Sacha Ben, Lex van der Heijden
Journal: Behavioral and Brain Sciences (1998)

Van Gelder presents the distinction between dynamical systems and digital computers as the core issue of current developments in cognitive science. We think this distinction is much less important than a reassessment of cognition as a neurally, bodily, and environmentally embedded process. Embedded cognition lines up naturally with dynamical models, but it would also stand if combined with classic computation.