tbuckley/cabot-search huggingface dataset:
Dimensions of Personality Pathology: An Alternative to the Five-Factor Model
Authors: Jonathan Shedler, Drew Westen
Journal: American Journal of Psychiatry (2004)

OBJECTIVE: Researchers have advocated replacing the DSM-IV classification of personality disorders with an alternative diagnostic system based on the five-factor model. This study evaluates the clinical comprehensiveness of the five-factor model and addresses the broader question of how many factors, and which factors, are necessary to understand personality pathology. METHOD: A national sample of 530 psychiatrists and clinical psychologists used the Shedler-Westen Assessment Procedure (SWAP-200) to provide detailed psychological descriptions of patients with personality disorder diagnoses. The SWAP-200 is a 200-item instrument designed to capture the richness and complexity of clinical observations while also providing quantifiable data for research. We used factor analysis to identify dimensions of personality relevant to understanding personality pathology. RESULTS: The five-factor structure replicated in a content-restricted subset of 60 SWAP-200 items. However, factor analysis of the full SWAP-200 yielded a conceptually richer factor solution that did not resemble the five-factor model. The analysis identified 12 clinically relevant personality dimensions labeled psychological health, psychopathy, hostility, narcissism, emotional dysregulation, dysphoria, schizoid orientation, obsessionality, thought disorder, oedipal conflict (histrionic sexualization), dissociation, and sexual conflict. CONCLUSIONS: The five-factor model represents a sound distillation of the personality constructs used by laypersons. However, it omits key clinical constructs and may not capture the complexity of personality syndromes seen in clinical practice. The SWAP-200 factors may provide a framework for studying personality pathology that is both empirically grounded and clinically relevant.
Triple bypass: complicated paths to HIV escape
Authors: Andrew J. McMichael
Journal: The Journal of Experimental Medicine (2007)

Human immunodeficiency virus (HIV) type 1 is highly efficient at evading immune responses and persisting, ultimately causing fatal immunodeficiency in some patients. Mutation in the epitopes recognized by cytolytic CD8+ T cells (CTLs) is one such escape process. A new study now shows that one HIV-1 escape mutation may also result in impaired dendritic cell (DC) activity, possibly impairing later T cell responses to the same and other epitopes. The new data complete our understanding of the mechanisms by which the CTL response to an immunodominant gag epitope presented by human histocompatibility leukocyte antigen (HLA)-B27 is evaded. The complexity of the full escape helps to explain why patients with this HLA type progress to AIDS more slowly than average.
Orbital Wegener's granulomatosis as the initial presentation in a 9-year-old child
Authors: Moloy Dey, Lola Lawyi, Roger S Wilson
Journal: Journal of the Royal Society of Medicine (2011)

A 9-year-old child was referred by her general practioner (GP) to eye casualty clinic with a six-week history of unexplained painless swelling of her right upper lid. Her GP, having treated first as an allergy with oral antihistamine, was now concerned that this was a case of preseptal cellulits progressing to orbital cellulitis and commenced a course of Erythromycin and Fucithalmic ointment and referred for review. A detailed history had revealed four months previously she had developed right upper lid swelling in the context of a mild upper respiratory tract infection. However this was short-lived and resolved without any therapeutic intervention. She also frequently suffered from recurrent ear infections, which required eventual grommet insertion, and nose bleeds. On examination she was found to have right painless upper lid swelling with no associated proptosis (Figure 1). Her ocular movements were full with no diplopia. Best corrected vision was 6/9 both eyes, her conjunctiva was injected in the right eye, anterior segment examination was normal with pressures of 14 both eyes. Pupils were reactive and equal with, no evidence of a relative afferent pupillary defect. Colour vision was also full. Posterior segment examination was normal no evidence of disc swelling or pallor. The antibiotics were continued with a provisional diagnosis of dacroadenitis. In view of the chronicity of the symptoms an orbital computed tomography scan and bloods were ordered. Her CT scan displayed diffuse homogenous soft tissue swelling within the right lacrimal gland suggesting an inflammatory process, extraocular eye muscles were normal (Figure 2). Her chest X-ray was normal and urine analysis was also normal. Her blood tests was positive for cANCAwith a titre of 1:20 and pANCAwith a titre of 1:40, ESR was normal at 11 the rest of her blood tests including full blood count, U&Es, LFTs, autoantibody screen and sACE were also normal. She was referred on to a paediatric rheumatologist to confirm the diagnosis of Wegener’s granulomatosis and assist on further management. A biopsy of the lacrimal failed to show the classical triad of granulomatous inflammation with giant cell, necrosis and vasculitis although there was evidence of chronic inflammation with perivascular infiltrates. Further examination of the child revealed saddling of the nose and a congenital sinus in the tragus of the left ear. Systemic examination failed to reveal any renal or pulmonary involvement. In view of the positive ANCA and clinical examination, a diagnosis of Wegener’s granulomatosis was made. She was commenced initially with intravenous methylprednisolone for three days then on a tapering dose of oral steroids. The lid swelling has reduced and she is currently in remission.
Role of CXC Chemokine Receptor 3 Pathway in Renal Ischemic Injury
Authors: Paolo Fiorina, Mohammed Javeed Ansari, Mollie Jurewicz, Mark Barry, Vincent Ricchiuti, Rex Neal Smith, Susan Shea, Terry K. Means, Hugh Auchincloss, Andrew D. Luster, Mohamed H. Sayegh, Reza Abdi
Journal: Journal of the American Society of Nephrology (2006)

Chemokines play a major role in the recruitment of leukocytes in inflammation and in the regulation of T helper 1 (Th1)/Th2 immune responses. These mechanisms have been recognized to be important in the pathogenesis of renal ischemia-reperfusion (I/R) injury. The interaction of the CXC chemokine receptor 3 (CXCR3) receptor with its ligands is a key pathogenic pathway in promoting inflammation and in enhancing Th1 immune responses. After the induction of ischemia in the mouse model of renal ischemia, an increase in intrarenal expression of CXCR3 and its ligands was observed. Compared with the wild-type (WT) mice, CXCR3-deficient mice (CXCR3-/-) had significantly lower serum creatinine levels, better survival rate, and significantly less acute tubular necrosis and cellular infiltrates. In the kidney, intracellular staining of infiltrating cells that were recovered from kidneys revealed a lower percentage of CD4+IFN-gamma+ cells in the CXCR3-/- mice compared with the WT mice. Furthermore, adoptive transfer of WT CD3+ cells into CXCR3-/- mice before induction of I/R injury abrogated the protection of CXCR3-/- mice from I/R injury. It is concluded that CXCR3 plays an important role in orchestrating the recruitment of Th1 cells to the ischemic kidney and in mediating I/R injury and therefore may serve as a novel target for the therapy of I/R injury.
Defining the Optimal Treatment for Clinical Stage I Nonseminomatous Germ Cell Testicular Cancer Using Decision Analysis
Authors: Carvell T. Nguyen, Alex Z. Fu, Timothy D. Gilligan, Brian J. Wells, Eric A. Klein, Michael W. Kattan, Andrew J. Stephenson
Journal: Journal of Clinical Oncology (2009)

PURPOSE There is equipoise regarding the optimal treatment of clinical stage (CS) I nonseminomatous germ cell testicular cancer (NSGCT). Formal mechanisms that enable patients to consider cancer outcomes, treatment-related morbidity, and personal preferences are needed to facilitate decision making between retroperitoneal lymph node dissection (RPLND), primary chemotherapy, and surveillance. METHODS Decision analysis was performed using a Markov model that incorporated likelihoods of survival, treatment-related morbidity, and utilities for seven undesired post-treatment health states to estimate the quality-adjusted survival (QAS) for each treatment option. Utilities were obtained from 24 hypothetical NSGCT patients using a visual analog (rating) scale and standard gamble. Results Overall, QAS associated with each treatment was high and differences in QAS were small. Surveillance was the preferred intervention for patients with a risk of relapse less than 33% and 37% using the rating scale and standard-gamble method of utility assessment, respectively. Active treatment was favored over surveillance for patients with relapse risk on surveillance greater than 33% and 37% by the rating scale (RPLND preferred) and standard-gamble methods (primary chemotherapy preferred), respectively. Substantial differences in average utilities were seen depending on the method used. By the rating scale, patients substantially devalued life in six of seven undesired health states but they were surprisingly tolerant of treatment-related morbidity using standard gamble. CONCLUSION A decision model has been developed for CS I NSGCT that estimates QAS for RPLND, primary chemotherapy, and surveillance by considering cancer outcomes, morbidity, and patient preferences. Surveillance was the preferred intervention for all except those patients at high risk for relapse.
Zinc alleviates pain through high-affinity binding to the NMDA receptor NR2A subunit
Authors: Chihiro Nozaki, Angela Maria Vergnano, Dominique Filliol, Abdel-Mouttalib Ouagazzal, Anne Le Goff, Stéphanie Carvalho, David Reiss, Claire Gaveriaux-Ruff, Jacques Neyton, Pierre Paoletti, Brigitte L Kieffer
Journal: Nature Neuroscience (2011)
VEGF Levels in Plasma in Relation to Platelet Activation, Glycemic Control, and Microvascular Complications in Type 1 Diabetes
Authors: Reinier O. Schlingemann, Cornelis J.F. Van Noorden, Mattheus J.M. Diekman, Anna Tiller, Joost C.M. Meijers, Pieter Koolwijk, Wilmar M. Wiersinga
Journal: Diabetes Care (2013)

Increased levels of vascular endothelial growth factor (VEGF) in human plasma samples have suggested that circulating VEGF is a cause of endothelial dysfunction in diabetes mellitus. However, artificial release of VEGF from platelets as a source of VEGF in plasma samples, as also occurs in serum samples, has not been ruled out in these studies.We determined VEGF levels in plasma collected in both citrate and PECT, a medium that inactivates platelets, in a cross-sectional cohort of 21 healthy subjects and 64 patients with type 1 diabetes. In addition, we evaluated whether VEGF levels in both types of plasma correlated with the presence of diabetes, glycemic control, markers of in vivo or ex vivo platelet activation, and degree of diabetic retinopathy and nephropathy.VEGF levels were invariably low in PECT plasma of both nondiabetic and diabetic subjects and were unrelated to any other diabetes-related variable studied. In contrast, VEGF levels in citrate plasma were 150% higher in diabetic patients than in control subjects and correlated with diabetes-related variables. Multiple linear regression analysis showed that levels of platelet factor 4, a marker for ex vivo platelet activation, and HbA1c were the independent predictors of VEGF levels in citrate plasma. Platelet activation, in vivo and ex vivo, was similar in diabetic persons and control subjects.Like serum, citrate plasma is not suitable for reliable measurements of circulating VEGF. The low levels of VEGF in vivo, as represented by measurements in PECT plasma in our study, do not support a role of circulating VEGF in endothelial dysfunction in type 1 diabetes. Higher levels of VEGF in citrate plasma samples of diabetic persons do not represent the in vivo situation, but mainly originate from higher artificial ex vivo release from platelets correlating with the degree of glycemic control.
Recovery of regional contractile function and oxidative metabolism in stunned myocardium induced by 1-hour circumflex coronary artery stenosis in chronically instrumented dogs.
Authors: G R Heyndrickx, W Wijns, D Vogelaers, Y Degrieck, A Bol, G Vandeplassche, J A Melin
Journal: Circulation Research (1993)

Stunned myocardium produced by 1 hour of critical coronary artery stenosis was evaluated for alteration in regional mechanical function and overall oxidative and fatty acid metabolism by positron emission tomography (PET) in chronically instrumented dogs. Twenty-seven dogs, chronically instrumented for measurements of left ventricular pressure and regional myocardial wall thickening in normal and ischemic zones, were subjected to a 1-hour period of myocardial ischemia produced by graded left circumflex coronary artery stenosis, resulting in minimal residual flow. Mean transmural myocardial flow during 1-hour coronary stenosis decreased to 0.34 +/- 0.04 ml/min per gram in the ischemic zones (normal zone transmural flow, 0.96 +/- 0.10 ml/min per gram). Systolic wall thickening in the ischemic zone was almost completely abolished (-97 +/- 4%). On reperfusion, systolic wall thickening immediately resumed but remained depressed. Progressive recovery was noted with time. At 24 hours, systolic wall thickening was still depressed (-20 +/- 6%, p &lt; 0.01). At 1 week, wall thickening had completely recovered and was no longer significantly different from the control condition. In addition, the absence of necrosis at the site of wall thickness measurements was confirmed at autopsy in all dogs. No abnormalities were found by electron microscopy in four dogs undergoing myocardial biopsies at the time of PET studies. Dynamic PET studies using [1-11C]acetate tracer (performed at 6 hours, 1 week, and 2 weeks after reperfusion) and [1-11C]palmitic acid tracer (performed at 6 hours, 12 hours, 24 hours, 1 week, and 2 weeks after reperfusion) allowed the computation of regional tissue time-activity curves in different regions of interest at different times during follow-up. Despite full reperfusion, abnormal [1-11C]acetate and [1-11C]palmitic acid kinetics were observed in the posterior segments, previously subjected to ischemia, as evidenced by a significant decrease in the slope of the early 11C clearance curve component. Repeat PET studies revealed progressive normalization of overall oxidative metabolism and fatty acid metabolism, which paralleled the time course of recovery of mechanical function. Thus, myocardial ischemia, produced by 1-hour coronary artery stenosis, followed by full reperfusion is associated with a prolonged period of postischemic mechanical and metabolic dysfunction. This transient reduction in oxygen delivery induced a prolonged impairment in fatty acid beta-oxidation as well as a reduction in overall oxidative metabolism despite full reoxygenation. A similar time course for recovery of function and metabolism was observed.
ABL-BCR expression does not correlate with deletions on the derivative chromosome 9 or survival in chronic myeloid leukemia
Authors: Josu de la Fuente, Kirsten Merx, E. Joanna Steer, Martin Müller, Richard M. Szydlo, Ole Maywald, Ute Berger, Rüdiger Hehlmann, John M. Goldman, Nicholas C. P. Cross, Junia V. Melo, Andreas Hochhaus
Journal: Blood (2001)
An Alien Promoter Capture as a Primary Step of the Evolution of Testes-Expressed Repeats in the Drosophila melanogaster Genome
Authors: Lev A. Usakin, Galina L. Kogan, Alla I. Kalmykova, Vladimir A. Gvozdev
Journal: Molecular Biology and Evolution (2005)

Fertility of Drosophila melanogaster males is impaired due to the disruption of the silencing of the X-linked, testis-expressed, repeated Stellate (Ste) genes. Ste silencing is mediated by symmetric transcription of the paralogous Y-linked repeats and exerted by an RNA interference (RNAi) mechanism. Here we present a scenario for the origin of the Ste genes and their suppressors. The primary intermediate of their evolution emerged as a result of the acquisition of a preformed alien, testis-specific promoter. This intermediate is identified as a chimeric gene containing coding region of an autosomal gene for testis-specific protein kinase CK2. The 5' region of the chimera has been acquired from a member of a family of testis-expressed X-linked genes of unknown function. We propose that the evolution and amplification of the novel chimeric gene have led to the overproduction of the regulatory CK2 subunit in testes. The evolution of the Y-linked descendants of the primary intermediate resulted in the RNAi-mediated suppression of excessive expression of the X-linked paralogs. The newly detected "dead family" of cognate repeats on the Y chromosome has contributed to the evolution of Ste and its suppressors via gene conversion. Our results show that RNAi silencing, considered as a defense against viruses and transposable elements, may be involved in the evolution of eukaryotic genomes.
Movement imitation as faithful copying in the absence of insight
Authors: Ludwig Huber
Journal: Behavioral and Brain Sciences (1998)

Byrne &amp; Russon use novelty as the primary requirement for providing evidence of true imitation in animals. There are three reasons to object to this. First, experiential learning cannot always be completely excluded as an alternative explanation of the observed behavior. Second, the imitator's manipulations performed during ontogeny cannot be known in full detail. Finally, there is at present only a weak understanding of how novel forms emerge. Data from our own recent experiments will be used to emphasize the need for a tighter methodology in imitation experiments.
THE CLINICAL IMPORTANCE OF FIBROSITIS IN GENERAL PRACTICE
Authors: W. H. M. Telling
Journal: BMJ (1935)

Everyone will agree that any contribution to the under- standing and treatment of pain is of fundamental im- portance in practice.My remarks are directed solely to one cause of pain, that arising from some pathological condition of, or injury to, white fibrous tissue.There is need for much clearer clinical appreciation of white fibrous tissue pain.Such a conception should be taught
Response of unexplained chest pain to proton pump inhibitor treatment in patients with and without objective evidence of gastro-oesophageal reflux disease
Authors: P. J. Kahrilas, N. Hughes, C. W. Howden
Journal: Gut (2011)

<h3>Introduction</h3> Unexplained chest pain is potentially attributable to gastro-oesophageal reflux disease (GORD) or oesophageal motility disorders. Reflux chest pain may occur without heartburn. We explored the response of unexplained chest pain to proton pump inhibitor (PPI) therapy in randomised clinical trials (RCTs), differentiating patients with and without objective evidence of GORD. <h3>Methods</h3> PubMed and Embase were systematically searched for RCTs that reported chest pain response to PPIs in patients who had had pH-monitoring and/or endoscopy to differentiate GORD-positive from GORD-negative subpopulations. Heterogeneity among studies was assessed using the Cochran Q and I<sup>2</sup> statistics, and a fixed effect model was applied. Possible publication bias was assessed by Egger9s test. <h3>Results</h3> Six RCTs met the inclusion criteria. All used 24 h pH monitoring and/or endoscopy to define GORD-positive patients and improvement in chest pain to define response (five used ≥50%; one used ≥20%). The therapeutic gain of &gt;50% improvement with PPIs relative to placebo was 56–85% in GORD-positive and 0–17% in GORD-negative patients. The RR of &gt;50% improvement in chest pain with PPI versus placebo was 4.3 (95% CI 2.8 to 6.7; p&lt;0.0001) for GORD-positive and 0.4 (95% CI 0.3 to 0.7; p=0.0004) for GORD-negative patients. Concomitant heartburn varied among trials from being an exclusion criterion to being essentially concordant with GORD-positive status. <h3>Conclusions</h3> Unexplained chest pain in patients with endoscopic or pH-monitoring evidence of GORD tends to improve, but not resolve, with PPI therapy, whereas GORD-negative patients have little or no response. Heartburn was a poor predictor of whether patients with chest pain were GORD-positive or GORD-negative by objective testing.
Primary Myocardial Disease
Authors: NOBLE O. FOWLER, MOSCHE GUERON, DAVID T. ROWLANDS
Journal: Circulation (1961)

This study describes 18 patients from the University of Cincinnati Hospitals who died of congestive heart failure without clinical or pathologic evidence of a primary cause. Clinical features. Their ages were from 18 months to 68 years at death. Fourteen were male and four female; 11 were white and seven were Negro. Seven patients had heart failure for 5 years or more; three had heart failure for over 10 years. Seven patients were alcoholic and three had nutritional cirrhosis. Transient mitral or tricuspid systolic murmurs and apical protodiastolic gallop rhythms were common. Atrial fibrillation was present in six patients. The electrocardiograms revealed abnormal left axis deviation in three and left bundle-branch block in two. Right heart catheterization was performed in four of these patients and showed low cardiac output, increased arteriovenous oxygen difference, and elevation of pulmonary arterial, pulmonary wedge, right ventricular diastolic, and right atrial pressures. Pathologic features. Heart weights were over 500 Gm. in 13 patients; all 18 had left ventricular hypertrophy. Mural thrombi were present in 10; six had pulmonary emboli and three had systemic arterial emboli. One patient had gross myocardial scarring; only two had small accumulations of inflammatory cells in the myocardium. Ten had focal increase of elastic tissue. Primary myocardial disease may simulate coronary artery disease because of the abnormal electrocardiogram; it may simulate hypertensive heart disease because of elevation of diastolic blood pressure during heart failure in some patients; it may simulate pericardial effusion because of the poor cardiac pulsations, narrow pulse pressure, and paradoxical pulse. It may simulate rheumatic heart disease because of the apical systolic and diastolic murmurs, left atrial enlargement, and presence of Kerley lines. The cause is unknown. Only one patient in this group had a familial history of similar heart disease.