tbuckley/cabot-search huggingface dataset:
Maternal Smoking During Pregnancy and Risk of Criminal Behavior Among Adult Male Offspring in the Northern Finland 1966 Birth Cohort
Authors: Pirkko Räsänen, Helinä Hakko, Matti Isohanni, Sheilagh Hodgins, Marjo-Riitta Järvelin, Jari Tiihonen
Journal: American Journal of Psychiatry (1999)

OBJECTIVE: The goal of this study was to test the hypothesis that maternal smoking during pregnancy is associated with greater risk for criminal behavior of the offspring in adulthood. METHOD: An unselected, general population cohort composed of 11,017 subjects (5,636 men, 5,381 women) was followed up prospectively from the sixth month of pregnancy to age 28 years. Interviews with the mother during the pregnancy, health records, and an assessment of the offspring at age 1 year provided information on risk factors. The Ministry of Justice provided information on criminal offenses for all subjects. RESULTS: Because of the low rate of criminal offenses among women, the present analyses are restricted to men (N=5,636). Compared to the sons of mothers who did not smoke, the sons of mothers who smoked during pregnancy had more than a twofold risk of having committed a violent crime or having repeatedly committed crimes, even when other biopsychosocial risk factors were controlled. While maternal smoking during pregnancy alone explained 4% of the variance associated with violent offenses among male offspring, it was not significantly associated with nonviolent offenses among male offspring. When maternal smoking during pregnancy was combined with a maternal age of less than 20 years, a single-parent family, an unwanted pregnancy, and a developmental lag in walking or talking, the odds ratios for violent offenses increased up to ninefold and for persistent offenses up to 14-fold. CONCLUSIONS: Maternal smoking during pregnancy is associated with violent offenses and persistent offenses, but not with nonviolent offenses, among male offspring in adulthood.
Intracerebral inoculation of pathological α-synuclein initiates a rapidly progressive neurodegenerative α-synucleinopathy in mice
Authors: Kelvin C. Luk, Victoria M. Kehm, Bin Zhang, Patrick O’Brien, John Q. Trojanowski, Virginia M.Y. Lee
Journal: The Journal of Experimental Medicine (2012)

The accumulation of misfolded proteins is a fundamental pathogenic process in neurodegenerative diseases. However, the factors that trigger aggregation of α-Synuclein (α-Syn), the principal component of the intraneuronal inclusions known as Lewy bodies (LBs), and Lewy neurites (LNs), which characterize Parkinson’s disease (PD) and dementia with LBs (DLB), are poorly understood. We show here that in young asymptomatic α-Syn transgenic (Tg) mice, intracerebral injections of brain homogenates derived from older Tg mice exhibiting α-Syn pathology accelerate both the formation of intracellular LB/LN-like inclusions and the onset of neurological symptoms in recipient animals. Pathological α-Syn propagated along major central nervous system (CNS) pathways to regions far beyond injection sites and reduced survival with a highly reproducible interval from injection to death in inoculated animals. Importantly, inoculation with α-Syn amyloid fibrils assembled from recombinant human α-Syn induced identical consequences. Furthermore, we show for the first time that synthetic α-Syn fibrils are wholly sufficient to initiate PD-like LBs/LNs and to transmit disease in vivo. Thus, our data point to a prion-like cascade in synucleinopathies whereby cell–cell transmission and propagation of misfolded α-Syn underlie the CNS spread of LBs/LNs. These findings open up new avenues for understanding the progression of PD and for developing novel therapeutics.
Modified low density lipoprotein and its constituents augment cytokine-activated vascular cell adhesion molecule-1 gene expression in human vascular endothelial cells.
Authors: B V Khan, S S Parthasarathy, R W Alexander, R M Medford
Journal: Journal of Clinical Investigation (1995)

Early features in the pathogenesis of atherosclerosis include accumulation of oxidized LDL (oxLDL) and endothelial expression of the vascular adhesion molecule VCAM-1. Because antioxidants inhibit endothelial VCAM-1 expression, we tested the hypothesis that oxLDL functions as a prooxidant signal in atherogenesis to augment VCAM-1 activation by inflammatory signals. Cultured human aortic endothelial cells (HAECs) or human umbilical vein endothelial cells (HUVECs) were incubated with unmodified LDL, oxLDL, or glycated LDL for 48 h. No change in VCAM-1, intercellular cell adhesion molecule-1 (ICAM-1), or E-selectin expression from control was observed by ELISA. However, dose-response and time course studies demonstrated that oxLDL enhanced VCAM-1 expression induced by the cytokin tumor necrosis factor alpha (TNF alpha) 63% in HAECs and 45% in HUVECs over unmodified LDL or control. Using flow cytometry analysis, oxLDL augmented TNF alpha-induced VCAM-1 expression in a uniform HAEC population. oxLDL had no effect on E-selection induction. oxLDL augmented TNF alpha-induced ICAM-1 expression 44% in HAECs but not in HUVECs. Glycated LDL augmented TNF alpha-induced VCAM-1 expression 35% in HAECs but not HUVECs. Similar results were obtained with 13-HPODE or lysophosphatidylcholine, significant components of oxLDL. 13-HPODE augmented TNF alpha-induced mRNA accumulation and transcriptional activation of VCAM-1 in HAECs. These results suggest that as long-term regulatory signals, specific oxidized fatty acid and phospholipid components of oxLDL augment the ability of vascular endothelial cells to express cytokine-mediated VCAM-1. These studies link oxidant signals conferred by oxLDL to oxidation-sensitive regulatory mechanisms controlling the expression of endothelial cell adhesion molecules involved in early atherosclerosis.
Late-breaking abstract: Effectiveness of individualized self management support for children with asthma in Dutch outpatient clinics, preliminary results of a randomized controlled trial
Authors: Stephanie van Bragt, Lisette van den Bemt, Anja Vaessen-Verberne, Anne Nieuwenhuis, Leonie van Veen, Hein Brackel, Han Hendriks, Peter Merkus, Tjard Schermer
Journal: European Respiratory Journal (2014)

Aim: Suboptimal paediatric asthma management leads to uncontrolled asthma and impaired health-related quality of life (HRQL). Aim of this study was to assess whether individualized self-management support (ISM) supplementary to usual care (UC) is able to improve HRQL in a relevant proportion (≥25%) of children with asthma.  Methods: We performed a 9-month RCT in five Dutch hospital paediatric outpatient clinics. Nurse-led ISM support was tailored to the needs of each child based on a validated online HRQL tool, individual goal setting and action plan (van Bragt S et al. BMC Pediatr 2012;12:137). Study subjects were children (6-11 yr) diagnosed with asthma. Primary outcome was a 9-months change in Paediatric Asthma-related Quality of Life Questionnaire (PAQLQ) score ≥ 0.5 points. A secondary outcome was change in asthma control as measured with the Childhood Asthma Control Test (C-ACT)≥ 2. Intention-to-treat uncorrected and corrected logistic regression analyses were performed.  Results: 93 children (mean age 9.0 yr [SD 1.6], 57 boys) were randomised (ISM n=42; UC n=51). In both groups, a substantial proportion showed ≥ 0.5 points improvement in PAQLQ scores (ISM 52.4%, UC 25.5%). Uncorrected and corrected analyses showed differences in favour of ISM: Odds Ratio (OR) 3.22 (95%CI 1.34; 7.74 p  Conclusion: Our ISM intervention appeared to be effective in improving asthma-specific HRQL in a relevant proportion of primary school aged children with asthma that are managed in paediatric outpatient clinics.
Histomolecular Phenotypes and Outcome in Adenocarcinoma of the Ampulla of Vater
Authors: David K. Chang, Nigel B. Jamieson, Amber L. Johns, Christopher J. Scarlett, Marina Pajic, Angela Chou, Mark Pinese, Jeremy L. Humphris, Marc D. Jones, Christopher Toon, Adnan M. Nagrial, Lorraine A. Chantrill, Venessa T. Chin, Andreia V. Pinho, Ilse Rooman, Mark J. Cowley, Jianmin Wu, R. Scott Mead, Emily K. Colvin, Jaswinder S. Samra, Vincenzo Corbo, Claudio Bassi, Massimo Falconi, Rita T. Lawlor, Stefano Crippa, Nicola Sperandio, Samantha Bersani, Euan J. Dickson, Mohamed A.A. Mohamed, Karin A. Oien, Alan K. Foulis, Elizabeth A. Musgrove, Robert L. Sutherland, James G. Kench, C. Ross Carter, Anthony J. Gill, Aldo Scarpa, Colin J. McKay, Andrew V. Biankin
Journal: Journal of Clinical Oncology (2013)

Purpose Individuals with adenocarcinoma of the ampulla of Vater demonstrate a broad range of outcomes, presumably because these cancers may arise from any one of the three epithelia that converge at that location. This variability poses challenges for clinical decision making and the development of novel therapeutic strategies. Patients and Methods We assessed the potential clinical utility of histomolecular phenotypes defined using a combination of histopathology and protein expression (CDX2 and MUC1) in 208 patients from three independent cohorts who underwent surgical resection for adenocarcinoma of the ampulla of Vater. Results Histologic subtype and CDX2 and MUC1 expression were significant prognostic variables. Patients with a histomolecular pancreaticobiliary phenotype (CDX2 negative, MUC1 positive) segregated into a poor prognostic group in the training (hazard ratio [HR], 3.34; 95% CI, 1.69 to 6.62; P &lt; .001) and both validation cohorts (HR, 5.65; 95% CI, 2.77 to 11.5; P &lt; .001 and HR, 2.78; 95% CI, 1.25 to 7.17; P = .0119) compared with histomolecular nonpancreaticobiliary carcinomas. Further stratification by lymph node (LN) status defined three clinically relevant subgroups: one, patients with histomolecular nonpancreaticobiliary (intestinal) carcinoma without LN metastases who had an excellent prognosis; two, those with histomolecular pancreaticobiliary carcinoma with LN metastases who had a poor outcome; and three, the remainder of patients (nonpancreaticobiliary, LN positive or pancreaticobiliary, LN negative) who had an intermediate outcome. Conclusion Histopathologic and molecular criteria combine to define clinically relevant histomolecular phenotypes of adenocarcinoma of the ampulla of Vater and potentially represent distinct diseases with significant implications for current therapeutic strategies, the ability to interpret past clinical trials, and future trial design.
IL-1 Trap rilonacept in refractory adult onset Still's disease
Authors: Olga Petryna, J Jack Cush, Petros Efthimiou
Journal: Annals of the Rheumatic Diseases (2012)

Adult onset Still's disease (AOSD) is a seronegative polyarthritis associated with rash and fever.1 The innate immune system has been implicated in its pathogenesis and hypersecretion of interleukin 1 (IL-1) has been associated with increased disease activity.2 We report the first successful use of rilonacept, a long-acting IL-1 Trap, in the management of three patients with refractory AOSD. Rilonacept is a soluble dimeric fusion protein (IL-1 receptor extracellular domain +hIgG1-Fc) administered as a weekly subcutaneous injection (220 mg loading dose and 160 mg maintenance dose).3

Patient 1 was a 41 year-old woman who presented with spiking fevers, sore throat, urticaria, arthritis and splenomegaly accompanied by leucocytosis, elevated erythrocyte sedimentation rate (>100 mm/h), increased lung function tests and hyperferritinaemia (8442 ng/ml). She …
Both β <sub>2</sub> - and β <sub>1</sub> -Adrenergic Receptors Mediate Hastened Relaxation and Phosphorylation of Phospholamban and Troponin I in Ventricular Myocardium of Fallot Infants, Consistent With Selective Coupling of β <sub>2</sub> -Adrenergic Receptors to G <sub>s</sub> -Protein
Authors: Peter Molenaar, Sabine Bartel, Andrew Cochrane, Donathe Vetter, Homayoun Jalali, Peter Pohlner, Kylie Burrell, Peter Karczewski, Ernst-Georg Krause, Alberto Kaumann
Journal: Circulation (2000)

Background —In adult human heart, both β 1 - and β 2 -adrenergic receptors mediate hastening of relaxation; however, it is unknown whether this also occurs in infant heart. We compared the effects of stimulation of β 1 - and β 2 -adrenergic receptors on relaxation and phosphorylation of phospholamban and troponin I in ventricle obtained from infants with tetralogy of Fallot. Methods and Results —Myocardium dissected from the right ventricular outflow tract of 27 infants (age range 21/2 to 35 months) with tetralogy of Fallot was set up to contract 60 times per minute. Selective stimulation of β 1 -adrenergic receptors with (−)-norepinephrine (NE) and β 2 -adrenergic receptors with (−)-epinephrine (EPI) evoked phosphorylation of phospholamban (at serine-16 and threonine-17) and troponin I and caused concentration-dependent increases in contractile force (−log EC 50 [mol/L] NE 5.5±0.1, n=12; EPI 5.6±0.1, n=13 patients), hastening of the time to reach peak force (−log EC 50 [mol/L] NE 5.8±0.2; EPI 5.8±0.2) and 50% relaxation (−log EC 50 [mol/L] NE 5.7±0.2; EPI 5.8±0.1). Ventricular membranes from Fallot infants, labeled with (−)-[ 125 I]-cyanopindolol, revealed a greater percentage of β 1 - (71%) than β 2 -adrenergic receptors (29%). Binding of (−)-epinephrine to β 2 -receptors underwent greater GTP shifts than binding of (−)-norepinephrine to β 1 -receptors. Conclusions —Despite their low density, β 2 -adrenergic receptors are nearly as effective as β 1 -adrenergic receptors of infant Fallot ventricle in enhancing contraction, relaxation, and phosphorylation of phospholamban and troponin I, consistent with selective coupling to G s -protein.
Rad GTPase inhibits cardiac fibrosis through connective tissue growth factor
Authors: Ji Zhang, Lin Chang, Chunlei Chen, Meiling Zhang, Yan Luo, Milton Hamblin, Luis Villacorta, Jing-Wei Xiong, Y. Eugene Chen, Jifeng Zhang, Xiaojun Zhu
Journal: Cardiovascular Research (2011)

AimsOur previous studies documented that Rad (Ras associated with diabetes), a member of the RGK (Rad, Gem, and Kir) family of Ras-related small G protein, is significantly decreased in human failing hearts and plays an important role in attenuating cardiac hypertrophy. The goal of this study is to identify the effect of Rad on cardiac fibrosis and the underlying mechanisms.
Estimation of myocardial hemodynamics before and after intervention in children with kawasaki disease
Authors: Shunichi Ogawa, Takashi Ohkubo, Ryuji Fukazawa, Mitsuhiro Kamisago, Yukio Kuramochi, Yohko Uchikoba, Ei Ikegami, Miki Watanabe, Yasuhiro Katsube
Journal: Journal of the American College of Cardiology (2004)
Association of Panic Disorder With a History of Traumatic Suffocation
Authors: Colin Bouwer, Dan J. Stein
Journal: American Journal of Psychiatry (1997)

OBJECTIVE: An important recent hypothesis suggests that panic disorder results from a false suffocation alarm. However, the association of panic disorder with a history of traumatic suffocation experiences (e.g., near-drowning and near-choking) has not been well studied. This study examined whether a history of traumatic suffocation might be more common in patients with panic disorder who have predominantly respiratory symptoms. METHOD: Patients with panic disorder (N=176) and psychiatric comparison subjects (N=60) were questioned about a history of traumatic suffocation experiences. The panic disorder patients were classified as having predominantly respiratory, cardiovascular, occulovestibular, or gastrointestinal symptoms in order to determine a possible association between traumatic suffocation and symptom subtype. RESULTS: The frequency of traumatic suffocation was significantly higher among the panic disorder patients (19.3%) than among the comparison subjects (6.7%). Within the panic disorder group, patients with a history of traumatic suffocation were significantly more likely to exhibit predominantly respiratory symptoms and nocturnal panic attacks, while patients without such a history were significantly more likely to have predominantly cardiovascular symptoms, occulovestibular symptoms, and agoraphobia. CONCLUSIONS: There may be a specific association between panic disorder and a history of traumatic suffocation, and such a history in turn appears associated with predominantly respiratory symptoms and nocturnal panic attacks. Although additional studies are needed to confirm these data, a history of traumatic suffocation might be hypothesized to play a role in the etiology of panic disorder in some patients and may provide a useful window on understanding the psychobiology of this disorder. (Am J Psychiatry 1997; 154:1566–1570)
Medication Errors and Adverse Drug Events in Pediatric Inpatients
Authors: Rainu Kaushal
Journal: JAMA (2001)

Context Iatrogenic injuries, including medication errors, are an important problem in all hospitalized populations.However, few epidemiological data are available regarding medication errors in the pediatric inpatient setting.Objectives To assess the rates of medication errors, adverse drug events (ADEs), and potential ADEs; to compare pediatric rates with previously reported adult rates; to analyze the major types of errors; and to evaluate the potential impact of prevention strategies. Design, Setting, and PatientsProspective cohort study of 1120 patients admitted to 2 academic institutions during 6 weeks in April and May of 1999.Main Outcome Measures Medication errors, potential ADEs, and ADEs were identified by clinical staff reports and review of medication order sheets, medication administration records, and patient charts. ResultsWe reviewed 10 778 medication orders and found 616 medication errors (5.7%), 115 potential ADEs (1.1%), and 26 ADEs (0.24%).Of the 26 ADEs, 5 (19%) were preventable.While the preventable ADE rate was similar to that of a previous adult hospital study, the potential ADE rate was 3 times higher.The rate of potential ADEs was significantly higher in neonates in the neonatal intensive care unit.Most potential ADEs occurred at the stage of drug ordering (79%) and involved incorrect dosing (34%), anti-infective drugs (28%), and intravenous medications (54%).Physician reviewers judged that computerized physician order entry could potentially have prevented 93% and ward-based clinical pharmacists 94% of potential ADEs. ConclusionsMedication errors are common in pediatric inpatient settings, and further efforts are needed to reduce them.
Differential effects of PARP inhibition on vascular cell survival and ACAT-1 expression favouring atherosclerotic plaque stability
Authors: C. P. Hans, M. Zerfaoui, A. S. Naura, A. Catling, A. H. Boulares
Journal: Cardiovascular Research (2008)

The aim of this study was to take a combination of animal and cell culture approaches to examine the individual responses of vascular cells to varying inflammatory factors in order to gain insights on the mechanism(s) by which poly(ADP-ribose) polymerase (PARP) inhibition promotes factors of plaque stability. Apolipoprotein (ApoE−/−) mice fed a high-fat diet were used as a model of atherosclerosis. Primary endothelial cells, smooth muscle cells (SMCs), and ex-vivo generated foam cells (FCs) were used in our in vitro studies. PARP inhibition significantly decreased the markers of oxidative stress and caspase-3 activation and increased smooth muscle actin within plaques from ApoE−/− mice fed a high-fat diet. PARP inhibition protected against apoptosis and/or necrosis in SMCs and endothelial cells in response to H2O2 or tumour necrosis factor (TNF). Remarkably, PARP inhibition in FCs resulted in significant sensitization to 7-ketocholesterol (7-KC) by increasing cellular-toxic-free cholesterol, potentially through a down-regulation of acyl-CoA:cholesterol acyltransferase-1 (ACAT-1) expression. 7-KC induced necrosis exclusively in endothelial cells, which was, surprisingly, unaffected by PARP inhibition indicating that PARP inhibition does not prevent all forms of necrotic cell death. In SMCs, PARP-1 inhibition by gene deletion conferred protection against 7-KC or TNF, potentially by reducing caspase-3-like activation, preventing induction of c-Jun N-terminal protein kinase phosphorylation, and inducing extracellular signal-regulated kinase phosphorylation independently of PARP classical enzymatic activity. These data present PARP-1 as an important player in the death of cells constituting atherosclerotic plaques contributing to plaque dynamics. PARP inhibition may be a protective, a neutral, or a sensitizing factor. Additionally, PARP-1 may be a novel factor that can alter lipid metabolism. These novel functions of PARP not only challenge the current understanding of the role of the enzyme in cell death but also provide insights on the intricate contribution of PARP in cellular responses to predominant inflammatory factors within atherosclerotic plaques, presenting additional evidence for the viability of PARP inhibition as a therapeutic strategy for atherosclerosis.
Massive thymic hyperplasia presenting with respiratory insufficiency in a 2-year-old child
Authors: G. Szarf, T. C. M. de Andrade, R. de Oliveira, L. H. Ota, H. M. Lederman
Journal: Thorax (2010)

<h3>Introduction</h3> Lower urinary tract symptoms (LUTS) is a bothersome condition affecting older men which can lead to poor quality of life. General practitioners (GPs) currently have no easily available assessment tools to help effectively diagnose causes of LUTS and aid discussion of treatment with patients. Men are frequently referred to urology specialists who often recommend treatments that could have been initiated in primary care. GP access to simple, accurate tests and clinician decision tools are needed to facilitate accurate and effective patient management of LUTS in primary care. <h3>Methods and analysis</h3> PRImary care Management of lower Urinary tract Symptoms (PriMUS) is a prospective diagnostic accuracy study based in primary care. The study will determine which of a number of index tests used in combination best predict three urodynamic observations in men who present to their GP with LUTS. These are detrusor overactivity, bladder outlet obstruction and/or detrusor underactivity. Two cohorts of participants, one for development of the prototype diagnostic tool and other for validation, will undergo a series of simple index tests and the invasive reference standard (invasive urodynamics). We will develop and validate three diagnostic prediction models based on each condition and then combine them with management recommendations to form a clinical decision support tool. <h3>Ethics and dissemination</h3> Ethics approval is from the Wales Research Ethics Committee 6. Findings will be disseminated through peer-reviewed journals and conferences, and results will be of interest to professional and patient stakeholders. <h3>Trial registration number</h3> ISRCTN10327305.