tbuckley/cabot-search huggingface dataset:
Effect of Primary Care–Based Education on Reassurance in Patients With Acute Low Back Pain
Authors: Adrian C. Traeger, Markus Hübscher, Nicholas Henschke, G. Lorimer Moseley, Hopin Lee, James H. McAuley
Journal: JAMA Internal Medicine (2015)

Reassurance is a core aspect of daily medical practice, yet little is known on how it can be achieved.To determine whether patient education in primary care increases reassurance in patients with acute or subacute low back pain (LBP).Medline, EMBASE, Cochrane Central Register for Controlled Trials, and PsychINFO databases were searched to June 2014.Systematic review and meta-analysis of randomized and nonrandomized clinical trials.To be eligible, studies needed to be controlled trials of patient education for LBP that were delivered in primary care and measured reassurance after the intervention. Eligibility criteria were applied, and studies were selected by 2 independent authors.The primary outcomes were reassurance in the short and long term and health care utilization at 12 months.Data were extracted by 2 independent authors and entered into a standardized form. A random-effects meta-analysis tested the effects of patient education compared with usual care on measures of reassurance. To investigate the effect of study characteristics, we performed a preplanned subgroup analysis. Studies were stratified according to duration, content, and provider of patient education.We included 14 trials (n=4872) of patient education interventions. Trials assessed reassurance with questionnaires of fear, worry, anxiety, catastrophization, and health care utilization. There is moderate- to high-quality evidence that patient education increases reassurance more than usual care/control education in the short term (standardized mean difference [SMD], -0.21; 95% CI, -0.35 to -0.06) and long term (SMD, -0.15; 95% CI, -0.27 to -0.03). Interventions delivered by physicians were significantly more reassuring than those delivered by other primary care practitioners (eg, physiotherapist or nurse). There is moderate-quality evidence that patient education reduces LBP-related primary care visits more than usual care/control education (SMD, -0.14; 95% CI, -0.28 to -0.00 at a 12-month follow-up). The number needed to treat to prevent 1 LBP-related visit to primary care was 17.There is moderate- to high-quality evidence that patient education in primary care can provide long-term reassurance for patients with acute or subacute LBP.
Long-Term Follow-Up After Gene Therapy for Canavan Disease
Authors: Paola Leone, David Shera, Scott W.J. McPhee, Jeremy S. Francis, Edwin H. Kolodny, Larissa T. Bilaniuk, Dah-Jyuu Wang, Mitra Assadi, Olga Goldfarb, H. Warren Goldman, Andrew Freese, Deborah Young, Matthew J. During, R. Jude Samulski, Christopher G. Janson
Journal: Science Translational Medicine (2012)

Gene therapy for Canavan disease results in a decrease in pathologically elevated N -acetyl-aspartate concentrations in the brain and long-term clinical stabilization.
Macroautophagy in sporadic and the genetic form of Parkinson's disease with the A53T α-synuclein mutation
Authors: Yue Huang, Fariba Chegini, Germaine Chua, Karen Murphy, Weiping Gai, Glenda M Halliday
Journal: Translational Neurodegeneration (2012)

The A53T mutation in the α-synuclein gene causes autosomal-dominant Lewy body Parkinson's disease (PD). Cultured cell models have linked this mutation to increased cell macroautophagy, although evidence of enhanced macroautophagy in patients with this mutation has not been assessed.To determine whether macroautophagy is increased by the A53T α-synuclein gene mutation in PD patients and cell models.Formalin-fixed paraffin-embedded 10 μm-thick tissue sections from the substantia nigra and anterior cingulate cortex of two PD patients with the A53T α-synuclein gene mutation were compared with four sporadic PD cases and four controls obtained from the Sydney Brain Bank. Lewy bodies were isolated from frontal cortex of a case with late stage PD (recruited from South Australian Brain Bank). Immunohistochemistry was performed for α-synuclein and the macroautophagy markers autophagy-specific gene (ATG) 5, ATG6/Beclin1 and ATG8/LC3. SH-SY5Y cells were transfected with wild type or A53T mutant α-synuclein plasmids and observable changes in macroautophagy marker protein levels assessed using Western blotting.α-Synuclein immunoreactive neurites and dots were more numerous in patients with A53T mutations compared with late stage sporadic PD patients, and perinuclear cytoplasmic α-synuclein aggregates were observed in the α-synuclein A53T gene transfected SH-SY5Y cells compared to wild type transfections. All PD patients (with or without A53T mutations) had increased immunohistochemical evidence for macroautophagy compared with controls, and the levels of the ATG5 complex were equally increased in wild type and A53T α-synuclein gene transfected cells compared to controls.Despite increased α-synuclein accumulation with A53T mutations, macroautophagy is not increased above that observed in sporadic patients with PD or in cells transfected with wild type α-synuclein, suggesting that mutated α-synuclein protein is not removed by macroautophagy.
Qualitative study of pilot payment aimed at increasing general practitioners' antismoking advice to smokers
Authors: T. Coleman, A. T Wynn, K. Stevenson, F. Cheater
Journal: BMJ (2001)

<h3>Abstract</h3> <b>Objectives:</b> To elicit general practitioners9 and practice nurses9 accounts of changes in their clinical practice or practice organisation made to claim a pilot health promotion payment. To describe attitudes towards the piloted and previous health promotion payments. <b>Design:</b> Qualitative, semistructured interview study. <b>Setting:</b> 13 general practices in Leicester. <b>Participants:</b> 18 general practitioners and 13 practice nurses. <b>Results:</b> Health professionals did not report substantially changing their clinical practice to claim the new payments and made only minimal changes in practice organisation. The new health promotion payment did not overcome general practitioners9 resistance towards raising the issue of smoking when they felt that doing so could cause confrontation with patients. General practitioners who made the largest number of claims altered the way in which they recorded patients9 smoking status rather than raising the topic of smoking more frequently with patients. Participants had strong negative views on the new payment, feeling it would also be viewed negatively by patients. They were, however, more positive about health promotion payments that rewarded "extra" effort — for example, setting up practice based smoking cessation clinics. <b>Conclusions:</b> General practitioners and practice nurses were negative about a new health promotion payment, despite agreeing to pilot it. Health promotion payments do not automatically generate effective health promotion activity, and policymakers should consider careful piloting and evaluation of future changes in health promotion payments.
Annual variability in methacholine responsiveness in nonasthmatic working adults
Authors: WS Beckett, PA Pace, SJ Sferlazza, VJ Carey, ST Weiss
Journal: European Respiratory Journal (1997)

Change in airway responsiveness is used frequently as a clinical as well as an epidemiological tool. Changes in airway responsiveness can be superior to other measures of lung function in that they are more sensitive indicators of an environmental effect. However, normal variation in test results must be defined before change can be interpreted. To characterize annual variability in airways responsiveness, we administered a high-dose methacholine challenge at 1 yr intervals for up to 4 yrs to 105 healthy, nonasthmatic working subjects. Using this high-dose protocol, the majority of tests (83%) produced at least a 20 % fall in forced expiratory volume in one second (FEV1), allowing standard calculation of the provocative dose of methacholine causing a 20% fall in FEV1 (PD20). An annual change in methacholine responsiveness by one or more doubling doses was seen in at least 30% of subjects each year. The components of variance of airways responsiveness measures were estimated to allow direct comparison of within-subject and between-subject variability. The within-subject variability in PD20, was markedly greater than the comparable within-subject variability in FEV1. Level of FEV1 and age were both significant determinants of methacholine responsiveness. Comparison of two methods of expressing methacholine responsiveness (PD20 using the full challenge up to 250 mg x mL(-1) methacholine, and the dose-response slope using data up to 32 mg x mL(-1) methacholine as the maximum dose) had similar annual variability in censored data and mixed-effects models. We then developed an approach to statistical analysis of "right-censored" methacholine challenge data using a maximum likelihood estimation under a censored Gaussian model. These studies of methacholine responsiveness provide normative data on annual test variability in healthy, nonasthmatic working adults, and show that a shorter low-dose challenge has comparable annual variability to a lengthier high-dose challenge.
Decreasing Restenosis Following Angioplasty
Authors: Vivian A. Fonseca, Jose Diez, Dennis B. McNamara
Journal: Diabetes Care (2004)

Patients with type 2 diabetes are disproportionately affected by cardiovascular disease (CVD), and cardiovascular events are a major cause for morbidity and mortality in this population. Despite significant improvements in the management of CVD, patients with diabetes continue to be seriously impacted by this problem (1). While treatments with lipid-lowering therapy and aggressive blood pressure lowering have been particularly effective in reducing cardiovascular events, treatments to reduce blood glucose have had a less impressive impact on macrovascular complications (2). In the UKPDS (U.K. Prospective Diabetes Study), only treatment with metformin led to a significant reduction in cardiovascular events in a subgroup of obese subjects (3). Since its original description there has been much experimental, clinical, and epidemiological data to support the association of the insulin resistance syndrome with CVD (4). Additionally, other “nontraditional” cardiovascular risk factors associated with insulin resistance have been frequently implicated in the causation and progression of vascular disease in diabetes (5).

Following cardiovascular interventions such as balloon angioplasty, patients with diabetes appear to have a higher rate of restenosis (6). Although the development of stents has led to an improvement in outcomes, people with diabetes continue to have a worse prognosis than those without this disorder (7–10). Our understanding of the pathophysiology of restenosis has improved significantly, and increased attention has been focused on the role of insulin resistance in the development of …
The Use of Anencephalic Neonates as Organ Donors
Authors: John Glasson
Journal: JAMA (1995)

HUNDREDS of children die each year of cardiac, hepatic, or renal failure because there are not enough hearts, livers, or kidneys available for transplantation from other children. Consequently, various measures have been considered over the years to increase the organ supply for pediatric transplantation. One approach that has received particular attention is the possibility of using organs from anencephalic neonates.<sup>1-3</sup>Because anencephalic neonates face a certain and generally imminent death and because they lack any degree of consciousness, many commentators have proposed that organs of anencephalic neonates be used for transplantation, and many parents of such neonates request that their child's organs be given to other children. Permitting such organ donation would allow some good to come from a truly tragic situation, sustaining the lives of other children and providing psychological relief for those parents who wish to give meaning to the short life of the anencephalic neonate. Indeed,
“Nonmonotonic” does not mean “probabilistic”
Authors: Keith Stenning, Michiel van Lambalgen
Journal: Behavioral and Brain Sciences (2009)

Abstract Oaksford &amp; Chater (O&amp;C) advocate Bayesian probability as a way to deal formally with the pervasive nonmonotonicity of common sense reasoning. We show that some forms of nonmonotonicity cannot be treated by Bayesian methods.
Influence of<i>CRTC1</i>Polymorphisms on Body Mass Index and Fat Mass in Psychiatric Patients and the General Adult Population
Authors: Eva Choong
Journal: JAMA Psychiatry (2013)

IMPORTANCEThere is a high prevalence of obesity in psychiatric patients, possibly leading to metabolic complications and reducing life expectancy.The CREB-regulated transcription coactivator 1 (CRTC1) gene is involved in energy balance and obesity in animal models, but its role in human obesity is unknown.OBJECTIVE To determine whether polymorphisms within the CRTC1 gene are associated with adiposity markers in psychiatric patients and the general population.DESIGN, SETTING, AND PARTICIPANTS Retrospective and prospective data analysis and population-based samples at Lausanne and Geneva university hospitals in Switzerland and a private clinic in Lausanne, Switzerland.The effect of 3 CRTC1 polymorphisms on body mass index (BMI) and/or fat mass was investigated in a discovery cohort of psychiatric outpatients taking weight gain-inducing psychotropic drugs (sample 1, n = 152).The CRTC1 variant that was significantly associated with BMI and survived Bonferroni corrections for multiple comparison was then replicated in 2 independent psychiatric samples (sample 2, n = 174 and sample 3, n = 118) and 2 white population-based samples (sample 4, n = 5338 and sample 5, n = 123 865). INTERVENTION Noninterventional studies.MAIN OUTCOME AND MEASURE Difference in BMI and/or fat mass between CRTC1 genotype groups.RESULTS Among the CRTC1 variants tested in the first psychiatric sample, only rs3746266A>G was associated with BMI (P adjusted = .003).In the 3 psychiatric samples, carriers of the rs3746266 G allele had a lower BMI than noncarriers (AA genotype) (sample 1, P = .001;sample 2, P = .05;and sample 3, P = .0003).In the combined analysis, excluding patients taking other weight gain-inducing drugs, G allele carriers (n = 98) had a 1.81-kg/m 2 lower BMI than noncarriers (n = 226; P < .0001).The strongest association was observed in women younger than 45 years, with a 3.87-kg/m 2 lower BMI in G allele carriers (n = 25) compared with noncarriers (n = 48; P < .0001),explaining 9% of BMI variance.In the population-based samples, the T allele of rs6510997C>T (a proxy of the rs3746266 G allele; r 2 = 0.7) was associated with lower BMI (sample 5, n = 123 865; P = .01)and fat mass (sample 4, n = 5338; P = .03).The strongest association with fat mass was observed in premenopausal women (n = 1192; P = .02).CONCLUSIONS AND RELEVANCE These findings suggest that CRTC1 contributes to the genetics of human obesity in psychiatric patients and the general population.Identification of high-risk subjects could contribute to a better individualization of the pharmacological treatment in psychiatry.
Signal 3 Determines Tolerance versus Full Activation of Naive CD8 T Cells
Authors: Julie M. Curtsinger, Debra C. Lins, Matthew F. Mescher
Journal: The Journal of Experimental Medicine (2003)

Activation of naive CD8 T cells to undergo clonal expansion and develop effector function requires three signals: (a) Ag, (b) costimulation, and (c) IL-12 or adjuvant. The requirement for the third signal to stimulate Ag-dependent proliferation is variable, making the greatest contribution when Ag levels are low. At high Ag levels, extensive proliferation can occur in vitro or in vivo in the absence of a third signal. However, despite having undergone the same number of divisions, cells that expand in the absence of a third signal fail to develop cytolytic effector function. Thus, proliferation and development of cytolytic function can be fully uncoupled. Furthermore, these cells are rendered functionally tolerant in vivo, in that subsequent restimulation with a potent stimulus results in limited clonal expansion, impaired IFN-γ production, and no cytolytic function. Thus, the presence or absence of the third signal appears to be a critical variable in determining whether stimulation by Ag results in tolerance versus development of effector function and establishment of a responsive memory population.
CLINICAL GUIDELINE: Diagnosing Syncope: Part 1: Value of History, Physical Examination, and Electrocardiography
Authors: Mark Linzer
Journal: Annals of Internal Medicine (1997)

To review the literature on diagnostic testing in syncope and provide recommendations for a comprehensive, cost-effective approach to establishing its cause.Studies were identified through a MEDLINE search (1980 to present) and a manual review of bibliographies of identified articles.Papers were eligible if they addressed diagnostic testing in syncope or near syncope and reported results for at least 10 patients.The usefulness of tests was assessed by calculating diagnostic yield: the number of patients with diagnostically positive test results divided by the number of patients tested or, in the case of monitoring studies, the sum of true-positive and true-negative test results divided by the number of patients tested.Despite the absence of a diagnostic gold standard and the paucity of data from randomized trials, several points emerge. First, history, physical examination, and electrocardiography are the core of the syncope workup (combined diagnostic yield, 50%). Second, neurologic testing is rarely helpful unless additional neurologic signs or symptoms are present (diagnostic yield of electroencephalography, computed tomography, and Doppler ultrasonography, 2% to 6%). Third, patients in whom heart disease is known or suspected or those with exertional syncope are at higher risk for adverse outcomes and should have cardiac testing, including echocardiography, stress testing. Holter monitoring, or intracardiac electrophysiologic studies, alone or in combination (diagnostic yields, 5% to 35%). Fourth, syncope in the elderly often results from polypharmacy and abnormal physiologic responses to daily events. Fifth, long-term loop electrocardiography (diagnostic yield, 25% to 35%) and tilt testing (diagnostic yield < or = 60%) are most useful in patients with recurrent syncope in whom heart disease is not suspected. Sixth, psychiatric evaluation can detect mental disorders associated with syncope in up to 25% of cases. Seventh, hospitalization may be indicated for patients at high risk for cardiac syncope (those with an abnormal electrocardiogram, organic heart disease, chest pain, history of arrhythmia, age > 70 years) or with acute neurologic signs.Many tests for syncope have a low diagnostic yield. A careful history, physical examination, and electrocardiography will provide a diagnosis or determine whether diagnostic testing is necessary in most patients.
Promoter Hypermethylation Identifies Progression Risk in Bladder Cancer
Authors: David R. Yates, Ishtiaq Rehman, Maysam F. Abbod, Mark Meuth, Simon S. Cross, Derek A. Linkens, Freddie C. Hamdy, James W.F. Catto
Journal: Clinical Cancer Research (2007)

Abstract Purpose: New methods to accurately predict an individual tumor behavior are urgently required to improve the treatment of cancer. We previously found that promoter hypermethylation can be an accurate predictor of bladder cancer progression, but it is not cancer specific. Here, we investigate a panel of methylated loci in a prospectively collected cohort of bladder tumors to determine whether hypermethylation has a useful role in the management of patients with bladder cancer. Experimental Design: Quantitative methylation-specific PCR was done at 17 gene promoters, suspected to be associated with tumor progression, in 96 malignant and 30 normal urothelial samples. Statistical analysis and artificial intelligence techniques were used to interrogate the results. Results: Using log-rank analysis, five loci were associated with progression to more advanced disease (RASSF1a, E-cadherin, TNFSR25, EDNRB, and APC; P &amp;lt; 0.05). Multivariate analysis revealed that the overall degree of methylation was more significantly associated with subsequent progression and death (Cox, P = 0.002) than tumor stage (Cox, P = 0.008). Neuro-fuzzy modeling confirmed that these five loci were those most associated with tumor progression. Epigenetic predictive models developed using artificial intelligence techniques identified the presence and timing of tumor progression with 97% specificity and 75% sensitivity. Conclusion: Promoter hypermethylation seems a reliable predictor of tumor progression in bladder cancer. It is associated with aggressive tumors and could be used to identify patients with either superficial disease requiring radical treatment or a low progression risk suitable for less intensive surveillance. Multicenter studies are warranted to validate this marker.
Presence of anti-Sm reactivity in autoimmune mouse strains
Authors: RA Eisenberg, EM Tan, FJ Dixon
Journal: The Journal of Experimental Medicine (1978)

The investigation of the fine specificities of antinuclear antibodies (ANAs) has been fruitful in terms of the nosology and immunopathogenesis of human autoimmune syndromes. Particular reactivities serve as markers, in that patients with certain syndromes have a much higher incidence of such ANAs than do patients with other diseases. In this category is the almost exclusive against the nuclear acidic protein Sm. Reactivity to Sm can be detected by precipitation in agar, complement fixation, or passive hemagglutination (1,2). Autoimmune mouse strains have also provided a fertile field for the investigation of the basic phenomena of self-activity. In particular, the NZB strain and its hybrid NZB x NZW have been considered excellent models for human SLE and have therefore been studied in great detail (3,4). In addition, Murphy et al at The Jackson Laboratory, Bar Harbor, Maine, have developed several new inbred mouse strains that spontaneously develop SLE-like syndromes (5,6). These are the BXSB strain, which has a male dominant disease characterized by little antiative DNA antibody; the MRL/1, which develops massive, nonmalignant lymphadenopathy, associated with enormous increases in serum immunoglobulin levels and fulminant renal disease; and the MRL/n, which does not develop SLE-like disease until well into the 2nd yr of life, but like the MRL/1 develops high titers of ANA and fatal glomerulonephritis. The MRL/1 differs from MRL/n in only about 10 percent of its genome, including the gene responsible for the MRL/1's lymphoproliferation. In the current study, we have used the technique of double immunodiffusion (ID) in agarose with standard human reference sera (of known ANA specificity) to survey a large number of mice from the NZB x NZW, MRL/1, MRL/n, BXSB, and other strains. We report here the finding of the anti-Sm marker antibody almost uniquely in MRL/1 and MRL/n animals. These two related strains may serve as experimental models to explore the mechanism stimulating the production of this unique autoantibody in SLE.