tbuckley/cabot-search huggingface dataset:
The role of apolipoprotein A5 in non-alcoholic fatty liver disease
Authors: C. Ress, A. R. Moschen, N. Sausgruber, A. Tschoner, I. Graziadei, H. Weiss, W. Schgoer, C. F. Ebenbichler, R. J. Konrad, J. R. Patsch, H. Tilg, S. Kaser
Journal: Gut (2011)

<h3>Background</h3> Apolipoprotein A5 (apoA5) is a recently described liver-specific protein that has been shown to influence triglyceride (TG) metabolism. ApoA5 transgenic mice display dramatically reduced TG levels, while in contrast apoA5 deficiency in humans was reported to result in marked hypertriglyceridemia. ApoA5 exerts its extracellular effects by increasing lipolysis of TG-rich lipoproteins, while in vitro data suggest additional intrahepatic effects. <h3>Methods</h3> In this study the authors set out to investigate a possible role of apoA5 in non-alcoholic fatty liver disease (NAFLD). We thus determined hepatic apoA5 expression in 15 obese subjects with histologically proven NAFLD undergoing bariatric surgery. In addition, the authors established a hepatic cell culture model of apoA5 knockdown by transfecting human hepatoma cells (HepG2) with apoA5 small interfering (si) RNA, and determined intracellular TG content and expression levels of key enzymes and transcription factors of intrahepatic lipid metabolism in these cells. <h3>Results</h3> Pronounced weight loss and associated histologically verified improvement of hepatic steatosis were accompanied by significant reductions of hepatic apoA5 mRNA expression levels. Significant apoA5 knockdown in HepG2 cells resulted in a marked decrease of intracellular TG content. When HepG2 cells were co-transfected with apoA5 and peroxisome proliferator-activated receptor gamma (PPARγ), reductions in hepatic TG accumulation were significantly less pronounced when compared to apoA5 siRNA transfected HepG2 cells. <h3>Conclusions</h3> In obese subjects, hepatic apoA5 mRNA expression decreases after weight loss and improvements in hepatic steatosis. The authors9 in vitro data demonstrate that apoA5 influences intrahepatic TG metabolism and that these intracellular effects of apoA5 are accompanied by changes in PPARγ mRNA expression. In summary, the data suggest that as well as several other factors, apoA5 might be involved in the pathogenesis of hepatic steatosis.
Contempo 1997: Obstetrics and Gynecology
Authors: Richard J. Levine
Journal: JAMA (1997)

<h3>To the Ediotr.</h3> —I disagree with the recommendation of Drs DeCherney and Koos<sup>1</sup>to administer 1.5 to 2 g/d of elemental calcium to pregnant women at high risk for developing preeclampsia. The studies included in the meta-analysis on which this recommendation was based were principally studies of healthy nulliparous women.<sup>2</sup>There is no information with respect to the use of calcium supplementation for prevention of preeclampsia in women with multiple pregnancies, chronic hypertension, diabetes mellitus, or prior preeclampsia. As described elsewhere,<sup>3</sup>many of the previous studies had serious methodological shortcomings. Moreover, the safety of calcium supplementation cannot be assured in women with hypercalcemia, renal disease, or a history of urolithiasis. The multicenter trial of Calcium for Preeclampsia Prevention (CPEP)<sup>3,4</sup>supported by the National Institute of Child Health and Human Development and the National Heart, Lung, and Blood Institute found that calcium did not prevent preeclampsia or
Adverse Childhood Experiences and Smoking During Adolescence and Adulthood
Authors: Robert F. Anda
Journal: JAMA (1999)

ContextIn recent years, smoking among adolescents has increased and the decline of adult smoking has slowed to nearly a halt; new insights into tobacco dependency are needed to correct this situation. Long-term use of nicotine has been linked with self-medicating efforts to cope with negative emotional, neurobiological, and social effects of adverse childhood experiences.ObjectiveTo assess the relationship between adverse childhood experiences and 5 smoking behaviors.DesignThe ACE Study, a retrospective cohort survey including smoking and exposure to 8 categories of adverse childhood experiences (emotional, physical, and sexual abuse; a battered mother; parental separation or divorce; and growing up with a substance-abusing, mentally ill, or incarcerated household member), conducted from August to November 1995 and January to March 1996.SettingA primary care clinic for adult members of a large health maintenance organization in San Diego, Calif.ParticipantsA total of 9215 adults (4958 women and 4257 men with mean [SD] ages of 55.3 [15.7] and 58.1 [14.5] years, respectively) who responded to a survey questionnaire, which was mailed to all patients 1 week after a clinic visit.Main Outcome MeasuresSmoking initiation by age 14 years or after age 18 years, and status as ever, current, or heavy smoker.ResultsAt least 1 of 8 categories of adverse childhood experiences was reported by 63% of respondents. After adjusting for age, sex, race, and education, each category showed an increased risk for each smoking behavior, and these risks were comparable for each category of adverse childhood experiences. Compared with those reporting no adverse childhood experiences, persons reporting 5 or more categories had substantially higher risks of early smoking initiation (odds ratio [OR], 5.4; 95% confidence interval [CI], 4.1-7.1), ever smoking (OR, 3.1; 95% CI, 2.6-3.8), current smoking (OR, 2.1; 95% CI, 1.6-2.7), and heavy smoking (OR, 2.8; 95% CI, 1.9-4.2). Each relationship between smoking behavior and the number of adverse childhood experiences was strong and graded (P&lt;.001). For any given number of adverse childhood experiences, recent problems with depressed affect were more common among smokers than among nonsmokers.ConclusionsSmoking was strongly associated with adverse childhood experiences. Primary prevention of adverse childhood experiences and improved treatment of exposed children could reduce smoking among both adolescents and adults.
Protection of mice against leukemia after vaccination with bone marrow-derived dendritic cells loaded with apoptotic leukemia cells.
Authors: Sophie Paczesny, Simone Beranger, Jean-Loup Salzmann, David Klatzmann, Bruno M. Colombo
Journal: Cancer Research (2001)

Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that need to be activated before they can function to initiate primary and secondary immune responses in vivo. DCs are also specialized to maintain peripheral tolerance to self after uptake of apoptotic material, likely corresponding to both apoptotic bodies and whole apoptotic cells. Here, we report that murine bone marrow-derived DCs can be activated in vitro by exogenous signals received from apoptotic leukemia cells expressing on the cell surface a model tumor-associated antigen. Injected in vivo, these exogenously activated DCs can function as adjuvants to protect mice against leukemia by stimulating an antigen-specific cellular-mediated cytotoxic immune response. To our knowledge, this is the first report indicating that DCs loaded with apoptotic leukemia cells protect mice against leukemia development.
Estrogen Receptor-α Methylation Predicts Melanoma Progression
Authors: Takuji Mori, Steve R. Martinez, Steven J. O'Day, Donald L. Morton, Naoyuki Umetani, Minoru Kitago, Atsushi Tanemura, Sandy L. Nguyen, Andy N. Tran, He-Jing Wang, Dave S.B. Hoon
Journal: Cancer Research (2006)

Abstract The role of estrogen receptor α (ER-α) in melanoma is unknown. ER-α expression may be regulated in melanoma via hypermethylation of promoter CpG islands. We assessed ER-α hypermethylation in primary and metastatic melanomas and sera as a potential tumor progression marker. ER-α methylation status in tumor (n = 107) and sera (n = 109) from American Joint Committee on Cancer (AJCC) stage I to IV melanoma patients was examined by methylation-specific PCR. The clinical significance of serum methylated ER-α was assessed among AJCC stage IV melanoma patients receiving biochemotherapy with tamoxifen. Rates of ER-α methylation in AJCC stage I, II, and III primary melanomas were 36% (4 of 11), 26% (5 of 19), and 35% (8 of 23), respectively. Methylated ER-α was detected in 42% (8 of 19) of stage III and 86% (30 of 35) of stage IV metastatic melanomas. ER-α was methylated more frequently in metastatic than primary melanomas (P = 0.0003). Of 109 melanoma patients' sera in AJCC stage I, II, III, and IV, methylated ER-α was detected in 10% (2 of 20), 15% (3 of 20), 26% (5 of 19), and 32% (16 of 50), respectively. Serum methylated ER-α was detected more frequently in advanced than localized melanomas (P = 0.03) and was the only factor predicting progression-free [risk ratio (RR), 2.64; 95% confidence interval (95% CI), 1.36-5.13; P = 0.004] and overall survival (RR, 2.31; 95% CI, 1.41-5.58; P = 0.003) in biochemotherapy patients. Hypermethylated ER-α is a significant factor in melanoma progression. Serum methylated ER-α is an unfavorable prognostic factor. (Cancer Res 2006; 66(13): 6692-8)
Endothelial function and inflammatory process in young patients with beta-thalassemia major
Authors: Constadina Aggeli, Christine Chrysohoou, Spyros Lambrou, Alexadra Frogoudaki, Charis Antoniadis, Dimitrios Tousoulis, Markisia Karageorga, Dimitrios Ladis, Christos Pitsavos, Christodoulos Stefanadis, Pavlos Toutouzas
Journal: Journal of the American College of Cardiology (2003)
Exercise interventions for preventing falls in older people living in the community
Authors: Marcia R Franco, Leani SM Pereira, Paulo H Ferreira
Journal: British Journal of Sports Medicine (2013)

Falls among older people are an international public health issue that requires significant attention from authorities. Around a third of people aged 65 and over experience at least one fall each year.1 Falls can lead to serious consequences, such as fractures, hospital admissions, mobility-related disability, loss of confidence and reduction in community participation. Importantly, costs related to falls are dramatically increasing worldwide.2

The previous (2009) version of this Cochrane systematic review of randomised trials3 provided evidence that the rate of falls in older people can be reduced with preventive interventions, such as exercise programmes, cataract surgery and psychoactive medication withdrawal.

This updated systematic review by Gillespie et al 4 aimed to assess the effects of interventions designed to prevent falls in older people living in the community. Different types of interventions were included, such as exercises, educational programmes, medication and surgery. The focus of this PEDro summary is on the trials evaluating exercise interventions compared to control interventions (ie, usual care and placebo intervention).

This review followed the methodology advocated by the Cochrane Collaboration. Electronic databases (the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL) and online trial registers were searched. Ongoing and unpublished trials were identified by contacting researchers …
Evidence for Multiple Genetic Factors Underlying DSM-IV Criteria for Major Depression
Authors: Kenneth S. Kendler, Steven H. Aggen, Michael C. Neale
Journal: JAMA Psychiatry (2013)

We do not know whether the clinical criteria for major depression (MD) reflect a single or multiple dimensions of genetic risk.To determine the structure of genetic and environmental risk factors for the 9 DSM-IV symptomatic MD criteria.Population-based twin registry.Virginia.Seven thousand five hundred members of adult twin pairs from the Virginia Adult Twin Study of Psychiatric and Substance Use Disorders.Symptoms of lifetime MD as assessed at personal interview.The best-fit twin model was multidimensional, requiring 3 genetic, 1 common environmental and 3 unique environmental common factors, and criterion-specific unique environmental factors. The first genetic factor was characterized by high loadings on cognitive and psychomotor depressive symptoms. The second and third genetic factors had strong loadings for mood and neurovegetative depressive symptoms, respectively. Genetic factor scores derived from these 3 factors differentially predicted patterns of comorbidity, other historical/clinical features of MD, and demographic variables. These results suggested that the first genetic factor reflected a general liability to internalizing disorders, while the third genetic factor was more specific for melancholic MD. The 3 unique environmental common factors reflected, respectively, global depressive, core mood, and cognitive depressive symptoms.The DSM-IV syndrome of MD does not reflect a single dimension of genetic liability. Rather, these criteria reflect 3 underlying dimensions that index genetic risk for cognitive/psychomotor, mood, and neurovegetative symptoms. While in need of replication, these results, validated by predictions using estimated genetic factor scores, have implications for gene-finding efforts for MD.
A Positive Family History of Premature Coronary Artery Disease Is Associated With Impaired Endothelium-Dependent Coronary Blood Flow Regulation
Authors: Volker Schächinger, Martina B. Britten, Mathias Elsner, Dirk H. Walter, Inge Scharrer, Andreas M. Zeiher
Journal: Circulation (1999)

The aim of the study was to determine whether a positive family history of coronary artery disease is related to impaired coronary blood flow regulation.In 150 patients with angiographically normal or minimally diseased coronary vessels, risk factors for coronary artery disease, the extent of atherosclerosis and endothelium-dependent vasomotor responses to acetylcholine, and endothelium-independent blood flow regulation by papaverine or adenosine were assessed. Coronary blood flow responses to acetylcholine were reduced in a dose-dependent manner in patients with a positive family history (P=0.030). By multivariate analysis, hypercholesterolemia (P=0.001), age (P=0.002), and a positive family history (P=0.008) remained predictors of coronary blood flow increase to acetylcholine. The extent of atherosclerotic coronary artery disease was, by multivariate analysis, an additional independent predictor of acetylcholine-induced blood flow (P=0.014), but also of endothelium-independent blood flow regulation (P=0.001). A positive family history had additive effects in addition to the other risk factors, such as hypercholesterolemia or increased age. Angiotensin-converting-enzyme genotype polymorphism had no influence either on endothelium-dependent or endothelium-independent coronary blood flow responses. However, in a subset of 28 patients, homocysteine (which is, in part, genetically determined) was inversely related to maximal acetylcholine-induced blood flow regulation (r=-0.47, P=0.012).The results of this study demonstrate, for the first time, that a positive family history of coronary artery disease is an important predictor of impaired endothelium-dependent coronary blood flow regulation in humans. The influence of a positive family history is independent of other well known risk factors but instead aggravates endothelial vasodilator dysfunction associated with hypercholesterolemia and increased age, suggesting important interacting effects between genetic and environmental risk factors.
Plasma Apolipoprotein CI and CIII Levels Are Associated With Increased Plasma Triglyceride Levels and Decreased Fat Mass in Men With the Metabolic Syndrome
Authors: Rachel L.M. van der Ham, Reza Alizadeh Dehnavi, Jimmy F.P. Berbée, Hein Putter, Albert de Roos, Johannes A. Romijn, Patrick C.N. Rensen, Jouke T. Tamsma
Journal: Diabetes Care (2008)

To determine whether, in accordance with observations in mouse models, high concentrations of the lipoprotein lipase inhibitors apolipoprotein (Apo) CI and ApoCIII are associated with increased triglyceride concentrations and decreased fat mass in men with the metabolic syndrome.Plasma ApoCI, ApoCIII, and triglyceride concentrations were measured in the postabsorptive state in 98 men with the metabolic syndrome. Subcutaneous and visceral fat areas were measured by 3T-magnetic resonance imaging.Triglyceride concentrations were 49% higher, and the average visceral fat area was 26% lower (both P < 0.001), in subjects with high ApoCI and ApoCIII compared with low ApoCI and ApoCIII. Subjects with either high ApoCI or ApoCIII had 16% (P < 0.05) and 18% (P < 0.01) decreased visceral fat area, respectively.High concentrations of ApoCI and ApoCIII are associated with increased triglycerides and decreased visceral fat mass in men with the metabolic syndrome. These findings translate mouse studies into human pathophysiology.
A potential role for tiotropium bromide as an added therapy for adults with uncontrolled asthma
Authors: Y. Falah
Journal: Thorax (2011)

In this study, the addition of tiotropium bromide to an inhaled glucocorticoid was evaluated as compared with doubling the dose of the inhaled glucocorticoid (primary superiority comparison) or the addition of salmeterol (secondary non-inferiority comparison) in 210 patients with asthma.

Tiotropium use showed a superior …
Biology of Desmoplastic Melanoma: A Case-Control Comparison With Other Melanomas
Authors: Daan P. Livestro, Alona Muzikansky, Emily M. Kaine, Thomas J. Flotte, Arthur J. Sober, Martin C. Mihm, James S. Michaelson, A. Benedict Cosimi, Kenneth K. Tanabe
Journal: Journal of Clinical Oncology (2005)

Previous studies have established that patients with desmoplastic melanoma (DM) have thicker primary tumors. Consequently, comparisons with other forms of melanoma have been strongly biased by differences in Breslow stage. This is the first case-matched control study comparing DM with other forms of melanoma.From a database of 3,202 melanoma patients treated at one institution, 89 patients with DM and 178 case-matched control patients (2:1) were identified by matching for tumor thickness, age, sex, and year of diagnosis. Clinical, pathologic, and outcome information was obtained from chart review.Controls were matched successfully to patients for tumor thickness, age, sex, and year of diagnosis. Presentation with American Joint Committee on Cancer stage III or IV disease is less common in patients with DM compared to case-matched control patients (5% v 21%; P < .001). Re-excisions to obtain clear surgical margins are required more often in patients with DM compared to case-matched control patients (21% v 6%; P < .001). Risk of positive sentinel nodes is lower in patients with DM compared to case-matched control patients (8% v 34%; P = .013). Despite these differences, survival rates of patients with DM are the same as case-matched control patients.Use of case-matched control patients matched for tumor thickness avoids biases introduced by the advanced Breslow stage of DMs. DMs are more locally aggressive than thickness-matched controls, and positive sentinel nodes are limited to patients with thick primary tumors. Importantly, patients with DM have survival rates similar to patients with other melanomas of similar thickness.
Observations on the Pathogenesis of Spontaneous Inherited Hypertension and Constricted Renal-Artery Hypertension in Rats
Authors: RICHARD LAVERTY, F. HORACE SMIRK
Journal: Circulation Research (1961)

A preparation is described in which blood is taken alternately from a pair of donor rats and perfused at constant rate through the same vascularly isolated, denervated recipient rat hind limb. The preparation, though sensitive to the vasoconstrictor agent released in acute renal hypertension, fails to detect any vasoconstrictor substance either in the blood of rats bred to develop hyper-tension spontaneously or in the blood of rats with chronic renal hypertension. To study nervous tone in limb blood vessels, an innervated rat hind limb was perfused through a femoral artery with blood taken from the opposite femoral artery. After administration of hexamethonium, weight-corrected hind-limb perfusion pressures of spontaneous hypertensive (B), chronic renal hypertensive (CR), and control (C) rats (all series included) fall to the same average level. Hence, the component of the hind-limb peripheral resistance which is not neurogenically maintained must be of the same order of magnitude in all three groups. In B, CR, and C rats, the perfusion pressure falls after hexamethonium ; all have the same relationship to the height of the blood pressure at the time the perfusion pressure is measured, high blood pressures being associated with high perfusion pressures and low blood pressures with low perfusion pressures. Therefore, since the differences between the hind-limb peripheral resistances of B, CR, and C rats, as measured by the perfusion pressure, are removed by administration of hexamethonium, it follows that they depend upon differences in the neurogenically maintained component of the peripheral resistance. After hexamethonium the blood pressures of B and C rats fall to the same average level.
Individualising the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) function subscale: incorporating patient priorities for improvement to measure functional impairment in hip or knee osteoarthritis
Authors: R Seror, F Tubach, G Baron, B Falissard, I Logeart, M Dougados, P Ravaud
Journal: Annals of the Rheumatic Diseases (2007)

Objective: Recommended outcome measures in osteoarthritis are standardised scales identical for each patient. As patient-specific scales are of increasing interest when considering patient priorities in outcome assessment, this study aims to validate individualised forms of the Western Ontario and McMaster Universities osteoarthritis index (WOMAC) function subscale. Patients and Methods: WOMAC function subscale data were prospectively obtained from 1218 outpatients with hip or knee osteoarthritis requiring non-steroidal anti-inflammatory drugs. Patients also rated the importance to remove disability in each activity of the WOMAC function subscale, and selected the five activities they considered the most important to be improved upon. After treatment, patients again completed the WOMAC function subscale. Several individualisation methods were evaluated: methods whereby the score of each item is multiplied by, or added to, its importance, and methods based on the five most important activities (WOMAC top 5). Psychometric properties of individualised scales were compared to those of the WOMAC function subscale. Results: The missing data rate was 11%, 13% and 2% for the WOMAC function, its individualised forms and the WOMAC top 5, respectively. Combining severity and importance of each item did not improve the properties of the scales. The WOMAC top 5 was the most responsive scale (standardised response mean: 0.96 vs 0.80, p&lt;0.001). Conclusion: Because of its better responsiveness, ease of use, low missing data rate and ability to highlight patient priorities, the WOMAC top 5 could be an interesting tool in therapeutic evaluation in hip or knee osteoarthritis.