tbuckley/cabot-search huggingface dataset:
Effect of Bright Light and Melatonin on Cognitive and Noncognitive Function in Elderly Residents of Group Care Facilities
Authors: Rixt F. Riemersma-van der Lek
Journal: JAMA (2008)

<h3>Context</h3>Cognitive decline, mood, behavioral and sleep disturbances, and limitations of activities of daily living commonly burden elderly patients with dementia and their caregivers. Circadian rhythm disturbances have been associated with these symptoms.<h3>Objective</h3>To determine whether the progression of cognitive and noncognitive symptoms may be ameliorated by individual or combined long-term application of the 2 major synchronizers of the circadian timing system: bright light and melatonin.<h3>Design, Setting, and Participants</h3>A long-term, double-blind, placebo-controlled, 2 × 2 factorial randomized trial performed from 1999 to 2004 with 189 residents of 12 group care facilities in the Netherlands; mean (SD) age, 85.8 (5.5) years; 90% were female and 87% had dementia.<h3>Interventions</h3>Random assignment by facility to long-term daily treatment with whole-day bright (± 1000 lux) or dim (± 300 lux) light and by participant to evening melatonin (2.5 mg) or placebo for a mean (SD) of 15 (12) months (maximum period of 3.5 years).<h3>Main Outcome Measures</h3>Standardized scales for cognitive and noncognitive symptoms, limitations of activities of daily living, and adverse effects assessed every 6 months.<h3>Results</h3>Light attenuated cognitive deterioration by a mean of 0.9 points (95% confidence interval [CI], 0.04-1.71) on the Mini-Mental State Examination or a relative 5%. Light also ameliorated depressive symptoms by 1.5 points (95% CI, 0.24-2.70) on the Cornell Scale for Depression in Dementia or a relative 19%, and attenuated the increase in functional limitations over time by 1.8 points per year (95% CI, 0.61-2.92) on the nurse-informant activities of daily living scale or a relative 53% difference. Melatonin shortened sleep onset latency by 8.2 minutes (95% CI, 1.08-15.38) or 19% and increased sleep duration by 27 minutes (95% CI, 9-46) or 6%. However, melatonin adversely affected scores on the Philadelphia Geriatric Centre Affect Rating Scale, both for positive affect (−0.5 points; 95% CI, −0.10 to −1.00) and negative affect (0.8 points; 95% CI, 0.20-1.44). Melatonin also increased withdrawn behavior by 1.02 points (95% CI, 0.18-1.86) on the Multi Observational Scale for Elderly Subjects scale, although this effect was not seen if given in combination with light. Combined treatment also attenuated aggressive behavior by 3.9 points (95% CI, 0.88-6.92) on the Cohen-Mansfield Agitation Index or 9%, increased sleep efficiency by 3.5% (95% CI, 0.8%-6.1%), and improved nocturnal restlessness by 1.00 minute per hour each year (95% CI, 0.26-1.78) or 9% (treatment × time effect).<h3>Conclusions</h3>Light has a modest benefit in improving some cognitive and noncognitive symptoms of dementia. To counteract the adverse effect of melatonin on mood, it is recommended only in combination with light.<h3>Trial Registration</h3>controlled-trials.com/isrctn Identifier: ISRCTN93133646
Tumor eradication in rat glioma and bypass of immunosuppressive barriers using internal radiation with 188Re-lipid nanocapsules
Authors: Claire Vanpouille-Box, Franck Lacoeuille, Camille Belloche, Nicolas Lepareur, Laurent Lemaire, Jean-Jacques LeJeune, Jean-Pierre Benoît, Philippe Menei, Olivier F. Couturier, Emmanuel Garcion, François Hindré
Journal: Biomaterials (2011)
Transmural dispersion of repolarization as a key factor of arrhythmogenicity in a novel intact heart model of LQT3
Authors: P MILBERG, N REINSCH, K WASMER, G MONNIG, J STYPMANN, N OSADA, G BREITHARDT, W HAVERKAMP, L ECKARDT
Journal: Cardiovascular Research (2004)

Congenital and acquired long QT syndrome (LQTS) are caused by abnormalities of ionic currents underlying ventricular repolarization. For a better understanding of the mechanisms by which functional electrical instability at the level of the whole heart leads to torsade de pointes (TdP), a novel model of LQT3 was developed and the role of transmural dispersion of repolarization for the development of proarrhythmia was evaluated.In 11 Langendorff-perfused rabbit hearts, veratridine (0.1-0.5 microM), an inhibitor of sodium channel inactivation, led to a concentration-dependent increase in QT-interval and simultaneously recorded monophasic ventricular action potentials (MAPs) (p<0.05) and thereby mimicked LQT3. Veratridine reproducibly induced early afterdepolarizations (EADs) and TdP after lowering potassium concentration. In bradycardic (AV-blocked) hearts, the increase in MAP duration showed marked regional differences. It was significantly more pronounced on the left endocardium as compared to left or right epicardium. This resulted in a significant increase in dispersion of repolarization (24% at 0.1 microM, 92% at 0.25 microM, 208% at 0.5 microM; p<0.01). Left ventricular transmural dispersion of repolarization increased significantly more than interventricular dispersion (104 to 33 ms at 0.5 microM veratridine; p<0.05).By inhibition of sodium channel inactivation, veratridine mimics LQT3 in this intact heart model. In bradycardic, hypokalemic hearts, it reproducibly induced EADs and TdP in the setting of significantly increased left ventricular transmural dispersion of repolarization. Based on these experimental data, reduction of transmural dispersion of repolarization may be considered an important target for the prevention of TdP in patients with LQT3.
AN EXPLORATORY STUDY OF THE USEFULNESS OF A BATTERY OF PSYCHOLOGICAL TESTS WITH NURSERY SCHOOL CHILDREN
Authors: SARAH SCHAFER, MARY LEITCH
Journal: American Journal of Psychiatry (1948)

In general it was possible for the psychologist, on the basis of psychological test results, to distinguish between 3 groups of nursery school children rated by the psychiatrist as adequately adjusted, moderately maladjusted, and severely maladjusted. The following test features appeared to be related to the presence of maladjustment tendencies: on the Rorschach test—no color responses, pure color responses only, arbitrary use of color, color naming, more than one-half of the record consisting of perseverated responses, failures, and accumulation of responses using black as color; on the Thematic Apperception test—accumulation of unusual violently aggressive themes, blocking, and absurd perceptual distortions; on the Stanford-Binet—more scatter below the mental age than above it, using a modification of the Pressey measure of scatter. The Rorschach test proved to be the single most useful test for determining maladjustment, but the value of using a battery of tests was indicated. In conclusion, the authors wish to stress that the study reported was exploratory and based on a small number of cases(22). It by no means covered all the aspects of the problems involved, and the results must be considered tentative. More systematic and extensive studies are required to determine the specific implications of our findings and to point up other significant potentialities of psychological testing in the preschool age group.
Individualizing kinase-targeted cancer therapy: the paradigm of chronic myeloid leukemia
Authors: Anna M Eiring, Michael W Deininger
Journal: Genome biology (2014)

Abstract The success of tyrosine kinase inhibitors in treating chronic myeloid leukemia highlights the potential of targeting oncogenic kinases with small molecules. By using drug activity profiles and individual patient genotypes, one can guide personalized therapy selection for patients with resistance.
Host cell-derived cardiomyocytes in sex-mismatch cardiac allografts
Authors: A Bayes-Genis
Journal: Cardiovascular Research (2002)

Background: Mesenchymal precursor cells are able to respond to tissue signals and differentiate into a phenotype characteristic of mature cells of that tissue. We sought to investigate whether adult human cardiomyocytes can be derived from recipient precursor cells in sex-mismatched cardiac allografts. Methods: We studied four male patients who received hearts from female donors, and four female patients who received an allograft from a male donor. Four sex-matched transplant patients, two of each sex served as controls. Combined fluorescence in situ hybridization with probes specific for X- and Y-chromosomes and immunohistochemistry with α-actin was used to identify cardiac muscle cells 4 and 12 months after transplantation. Slides were examined with a fluorescence microscope to detect the presence of male cells with one X and one Y signal in the nucleus, and female cells containing two X signals. Results: Mature cardiomyocytes from the host (1–2%) were found in five endomyocardial biopsy specimens at 4 months, and in three specimens at 12 months. In addition, recipient cells negative for cytoplasmic α-actin were also identified (1–21% per slide). The number of infiltrating recipient cells was not associated with the degree of rejection of the sample or with the number of prior rejection episodes. Echocardiographic evaluation showed no improvement in cardiac performance in hearts from patients with more than 10% chimeric recipient cells. Conclusions: Our data confirm the existence of mature cardiomyocytes derived from host cells, likely mesenchymal precursors, in the adult cardiac allograft in vivo.
Upper airway collapsibility, dilator muscle activation and resistance in sleep apnoea
Authors: R. Pierce, D. White, A. Malhotra, J. K. Edwards, D. Kleverlaan, L. Palmer, J. Trinder
Journal: European Respiratory Journal (2007)

The calibre of the upper airway is thought to be dependant upon its passive anatomy/collapsibility and the activation of pharyngeal dilator muscles. During awake periods, the more collapsible upper airway in obstructive sleep apnoea (OSA) increases the dilator muscle activity through a negative-pressure reflex. A direct correlation between the critical closing pressure (P(crit)), as a measure of anatomy/collapsability and electromyogram (EMG) activity of genioglossus EMG (GG-EMG) and tensor palatini EMG (TP-EMG), was hypothesised. The relationship between these indices and pharyngeal resistance (R(phar)) was also examined. The study involved eight males with a mean age of 48 (interquartile range 46-52) yrs with OSA, and an apnoea/hypopnoea index of 75 (65-101).hr(-1) on two nights breathing normally and on nasal continuous positive airway pressure (nCPAP). The P(crit )was measured during nonrapid eye movement sleep on nCPAP using brief, incremental reductions in mask pressure. GG-EMG and TP-EMG were measured breath-by-breath, awake, during sleep onset and on nCPAP. R(phar) was measured using airway pressures and flow. Wakeful GG-EMG, early sleep TP-EMG and the sleep decrement in TP-EMG were directly related to P(crit). Muscle activation was negatively correlated with R(phar) for TP-EMG awake and GG-EMG early in sleep. In conclusion these results confirm that dilator muscle activation is directly related to airway narrowing and reduces resistance across patients with obstructive sleep apnoea.
Viral and host factors determine innate immune responses in airway epithelial cells from children with wheeze and atopy
Authors: Kirsten M Spann, Engin Baturcam, Johanna Schagen, Carmen Jones, Claire P Straub, F Maxine Preston, Linping Chen, Simon Phipps, Peter D Sly, Emmanuelle Fantino
Journal: Thorax (2014)

Airway epithelial cells (AEC) from patients with asthma, appear to have an impaired interferon (IFN)-β and -λ response to infection with rhinovirus.To determine if impaired IFN responses can be identified in young children at risk of developing asthma due to atopy and/or early life wheeze, and if the site of infection or the infecting virus influence the antiviral response.Nasal (N) and tracheal (T) epithelial cells (EC) were collected from children categorised with atopy and/or wheeze based on specific IgE to locally common aeroallergens and a questionnaire concerning respiratory health. Submerged primary cultures were infected with respiratory syncytial virus (RSV) or human metapneumovirus (hMPV), and IFN production, inflammatory cytokine expression and viral replication quantified.Nasal epithelial cells (NEC), but not tracheal epithelial cells (TEC), from children with wheeze and/or atopy produced less IFN-β, but not IFN-λ, in response to RSV infection; this was associated with higher viral shedding. However, IFN-regulated factors IRF-7, Mx-1 and CXCL-10, and inflammatory cytokines were not differentially regulated. NECs and TECs from children with wheeze and/or atopy demonstrated no impairment of the IFN response (β or λ) to hMPV infection. Despite this, more hMPV was shed from these cells.AECs from children with wheeze and/or atopy do not have an intrinsic defect in the production of IFN-β or -λ, however, this response is influenced by the infecting virus. Higher viral load is associated with atopy and wheeze suggesting an impaired antiviral response to RSV and hMPV that is not influenced by production of IFNs.
Nervous system involvement in systemic lupus erythematosus
Authors: T. Gibson, A. R. Myers
Journal: Annals of the Rheumatic Diseases (1976)

In a retrospective analysis of 80 patients with systemic lupus erythematosus (SLE) seen over a 10-year period, 41 (51%) exhibited neurological manifestations. Nervous system involvement was characterized by a significantly greater involvement of black patients (P less than 0-02), a higher incidence of renal failure after the first appearance of neurological features (P less than 0-05), and a significantly worse 10-year survival rate (P less than 0-05). Specific neurological investigations were generally unhelpful in diagnosis. The finding of hypoglycorrhachia in 4 patients was striking and may have pathogenetic significance. The lack of a specific diagnostic test for central nervous system involvement may have hindered recognition of a cerebral abscess in one patient. Treatment with massive doses of corticosteroids was not obviously more effective than treatment with smaller doses. Autopsy findings showed scattered small cerebral infarcts but vasculitis was apparent in only one case.
Does Age at Diabetes Diagnosis Influence Long-Term Physical and Behavioral Outcomes?
Authors: Aaron E. Carroll, Ronald T. Ackermann, Edward J. Brizendine, Changyu Shen, David G. Marrero
Journal: Diabetes Care (2007)

Type 1 diabetes is a complex chronic illness. Because self-care is such an essential element of successful diabetes management, cognitive and behavioral aspects of childhood development may interfere with effective self-care behaviors and impact the probability of later complications. The objective of this study was to examine whether the age at diagnosis of diabetes is significantly related to physical and behavioral outcomes in adulthood. It may be that children diagnosed in adolescence spend their first few years with diabetes rebelling against the therapeutic demands of treatment. An intense phase of inadequate care could lead to health consequences later in life; behaviors adopted in adolescence could also linger long into adulthood. Conversely, it is possible that being diagnosed very early in life leads to a dependence on others that affects health and behavior long into the future.

This study used the patient survey data collected as part of the Translating Research into Action for Diabetes (TRIAD) study, which has been previously described (1). All patients with diabetes who participated in the TRIAD study, had baseline patient survey and chart review data for the period between July 2000 and October 2001, and reported being diagnosed with diabetes at or before 21 years of age were selected for inclusion in this study. The CASRO response rate was 69% (2).

We extracted information about health and social outcomes. Health outcomes included reported weight, BMI, prevalences …
Ca <sup>2+</sup> /Calmodulin-Dependent Protein Kinase IIδ and Protein Kinase D Overexpression Reinforce the Histone Deacetylase 5 Redistribution in Heart Failure
Authors: Julie Bossuyt, Kathryn Helmstadter, Xu Wu, Hugh Clements-Jewery, Robert S. Haworth, Metin Avkiran, Jody L. Martin, Steven M. Pogwizd, Donald M. Bers
Journal: Circulation Research (2008)

Cardiac hypertrophy and heart failure (HF) are associated with reactivation of fetal cardiac genes, and class II histone deacetylases (HDACs) (eg, HDAC5) have been strongly implicated in this process. We have shown previously that inositol trisphosphate, Ca2+/calmodulin-dependent protein kinase II (CaMKII), and protein kinase (PK)D are involved in HDAC5 phosphorylation and nuclear export in normal adult ventricular myocytes and also that CaMKIIdelta and inositol trisphosphate receptors are upregulated in HF. Here we tested whether, in our rabbit HF model, nucleocytoplasmic shuttling of HDAC5 was altered either at baseline or in response to endothelin-1, which would indicate HDAC5 phosphorylation and transcription effects. The fusion protein HDAC5-green fluorescent protein (HDAC5-GFP) was more cytosolic in HF myocytes (F(nuc)/F(cyto) 3.3+/-0.3 vs 7.2+/-0.4 in control), and HDAC5 was more phosphorylated. Despite this baseline cytosolic HDAC5 shift, endothelin-1 produced more rapid HDAC5-GFP nuclear export in HF versus control myocytes. We also find that PKD and CaMKIIdelta(C) expression and activation state are increased in both rabbit and human HF. Inhibition of either CaMKII or PKD in HF myocytes partially restored the HDAC5-GFP F(nuc)/F(cyto) toward control, and simultaneous inhibition restored F(nuc)/F(cyto) to that in control myocytes. Moreover, adenovirus-mediated overexpression of PKD, CaMKIIdelta(B), or CaMKIIdelta(C) reduced baseline HDAC5 F(nuc)/F(cyto) in control myocytes (3.4+/-0.5, 3.8+/-0.5, and 5.2+/-0.5, respectively), approaching that seen in HF. We conclude that chronic upregulation and activation of inositol trisphosphate receptors, CaMKII, and PKD in HF shifts HDAC5 out of the nucleus, derepressing transcription of hypertrophic genes. This may directly contribute to the development and/or maintenance of HF.
Defense Mechanisms of Pregnant Mothers Predict Attachment Security, Social-Emotional Competence, and Behavior Problems in Their Toddlers
Authors: John H. Porcerelli, Alissa Huth-Bocks, Steven K. Huprich, Laura Richardson
Journal: American Journal of Psychiatry (2015)

Objective: For at-risk (single parent, low income, low support) mothers, healthy adaptation and the ability to manage stress have clear implications for parenting and the socialemotional well-being of their young offspring.The purpose of this longitudinal study was to examine associations between defense mechanisms in pregnant women and their toddlers' attachment security, social-emotional, and behavioral adjustment.Method: Participants were 84 pregnant women during their last trimester of pregnancy, recruited from community agencies primarily serving low-income families.Women were followed prospectively from pregnancy through 2 years after birth and completed several multimethod assessments during that period.Observations of mother-child interactions were also coded after the postnatal visits.Results: Multiple regression analyses revealed that mothers' defense mechanisms were significantly associated with several toddler outcomes.Mature, healthy defenses were significantly associated with greater toddler attachment security and social-emotional competence and fewer behavior problems, and less mature defenses (disavowal in particular) were associated with lower levels of attachment security and social-emotional competence.Associations remained significant, or were only slightly attenuated, after controlling for demographic variables and partner abuse during pregnancy. Conclusions:The study findings suggest that defensive functioning in parents preparing for and parenting toddlers influences the parent-child attachment relationship and social-emotional adjustment in the earliest years of life.Possible mechanisms for these associations may include parental attunement and mentalization, as well as specific caregiving behavior toward the child.Defensive functioning during times of increased stress (such as the prenatal to postnatal period) may be especially important for understanding parental influences on the child.
effect of additional temporary glycoprotein IIb/IIIa receptor inhibition on troponin release in elective percutaneous coronary interventions after pretreatment with aspirin and clopidogrel (TOPSTAR trial)
Authors: Andreas W Bonz, Björn Lengenfelder, Jörg Strotmann, Stefanie Held, Oliver Turschner, Kerstin Harre, Christian Wacker, Christiane Waller, Nikolaus Kochsiek, Malte Meesmann, Ludwig Neyses, Peter Schanzenbächer, Georg Ertl, Wolfram Voelker
Journal: Journal of the American College of Cardiology (2002)
Sirtuin-1 Regulates Acinar-to-Ductal Metaplasia and Supports Cancer Cell Viability in Pancreatic Cancer
Authors: Elke Wauters, Victor J. Sanchez-Arévalo Lobo, Andreia V. Pinho, Amanda Mawson, Daniel Herranz, Jianmin Wu, Mark J. Cowley, Emily K. Colvin, Erna Ngwayi Njicop, Rob L. Sutherland, Tao Liu, Manuel Serrano, Luc Bouwens, Francisco X. Real, Andrew V. Biankin, Ilse Rooman
Journal: Cancer Research (2013)

Abstract The exocrine pancreas can undergo acinar-to-ductal metaplasia (ADM), as in the case of pancreatitis where precursor lesions of pancreatic ductal adenocarcinoma (PDAC) can arise. The NAD+-dependent protein deacetylase Sirtuin-1 (Sirt1) has been implicated in carcinogenesis with dual roles depending on its subcellular localization. In this study, we examined the expression and the role of Sirt1 in different stages of pancreatic carcinogenesis, i.e. ADM models and established PDAC. In addition, we analyzed the expression of KIAA1967, a key mediator of Sirt1 function, along with potential Sirt1 downstream targets. Sirt1 was co-expressed with KIAA1967 in the nuclei of normal pancreatic acinar cells. In ADM, Sirt1 underwent a transient nuclear-to-cytoplasmic shuttling. Experiments where during ADM, we enforced repression of Sirt1 shuttling, inhibition of Sirt1 activity or modulation of its expression, all underscore that the temporary decrease of nuclear and increase of cytoplasmic Sirt1 stimulate ADM. Our results further underscore that important transcriptional regulators of acinar differentiation, that is, Pancreatic transcription factor-1a and β-catenin can be deacetylated by Sirt1. Inhibition of Sirt1 is effective in suppression of ADM and in reducing cell viability in established PDAC tumors. KIAA1967 expression is differentially downregulated in PDAC and impacts on the sensitivity of PDAC cells to the Sirt1/2 inhibitor Tenovin-6. In PDAC, acetylation of β-catenin is not affected, unlike p53, a well-characterized Sirt1-regulated protein in tumor cells. Our results reveal that Sirt1 is an important regulator and potential therapeutic target in pancreatic carcinogenesis. Cancer Res; 73(7); 2357–67. ©2012 AACR.