tbuckley/cabot-search huggingface dataset:
Behavioral Counseling After Screening for Alcohol Misuse in Primary Care: A Systematic Review and Meta-analysis for the U.S. Preventive Services Task Force
Authors: Daniel E. Jonas, James C. Garbutt, Halle R. Amick, Janice M. Brown, Kimberly A. Brownley, Carol L. Council, Anthony J. Viera, Tania M. Wilkins, Cody J. Schwartz, Emily M. Richmond, John Yeatts, Tammeka Swinson Evans, Sally D. Wood, Russell P. Harris
Journal: Annals of Internal Medicine (2012)

Background: Alcohol misuse, which includes the full spectrum from risky drinking to alcohol dependence, is a leading cause of preventable death in the United States. Purpose: To evaluate the benefits and harms of behavioral counseling interventions for adolescents and adults who misuse alcohol. Data Sources: MEDLINE, EMBASE, the Cochrane Library, CINAHL, PsycINFO, International Pharmaceutical Abstracts, and reference lists of published literature (January 1985 through January 2012, limited to English-language articles). Study Selection: Controlled trials at least 6 months' duration that enrolled persons with alcohol misuse identified by screening in primary care settings and evaluated behavioral counseling interventions. Data Extraction: One reviewer extracted data and a second checked accuracy. Two independent reviewers assigned quality ratings and graded the strength of the evidence. Data Synthesis: The 23 included trials generally excluded persons with alcohol dependence. The best evidence was for brief (10- to 15-minute) multicontact interventions. Among adults receiving behavioral interventions, consumption decreased by 3.6 drinks per week from baseline (weighted mean difference, 3.6 drinks/wk [95% CI, 2.4 to 4.8 drinks/wk]; 10 trials; 4332 participants), 12% fewer adults reported heavy drinking episodes (risk difference, 0.12 [CI, 0.07 to 0.16]; 7 trials; 2737 participants), and 11% more adults reported drinking less than the recommended limits (risk difference, 0.11 [CI, 0.08 to 0.13]; 9 trials; 5973 participants) over 12 months compared with control participants (moderate strength of evidence). Evidence was insufficient to draw conclusions about accidents, injuries, or alcohol-related liver problems. Trials enrolling young adults or college students showed reduced consumption and fewer heavy drinking episodes (moderate strength of evidence). Little or no evidence of harms was found. Limitations: Results may be biased to the null because the behavior of control participants could have been affected by alcohol misuse assessments. In addition, evidence is probably inapplicable to persons with alcohol dependence and selective reporting may have occurred. Conclusion: Behavioral counseling interventions improve behavioral outcomes for adults with risky drinking. Primary Funding Source: Agency for Healthcare Research and Quality.
Cold acclimation recruits human brown fat and increases nonshivering thermogenesis
Authors: Anouk A.J.J. van der Lans, Joris Hoeks, Boudewijn Brans, Guy H.E.J. Vijgen, Mariëlle G.W. Visser, Maarten J. Vosselman, Jan Hansen, Johanna A. Jörgensen, Jun Wu, Felix M. Mottaghy, Patrick Schrauwen, Wouter D. van Marken Lichtenbelt
Journal: Journal of Clinical Investigation (2013)

In recent years, it has been shown that humans have active brown adipose tissue (BAT) depots, raising the question of whether activation and recruitment of BAT can be a target to counterbalance the current obesity pandemic. Here, we show that a 10-day cold acclimation protocol in humans increases BAT activity in parallel with an increase in nonshivering thermogenesis (NST). No sex differences in BAT presence and activity were found either before or after cold acclimation. Respiration measurements in permeabilized fibers and isolated mitochondria revealed no significant contribution of skeletal muscle mitochondrial uncoupling to the increased NST. Based on cell-specific markers and on uncoupling protein-1 (characteristic of both BAT and beige/brite cells), this study did not show "browning" of abdominal subcutaneous white adipose tissue upon cold acclimation. The observed physiological acclimation is in line with the subjective changes in temperature sensation; upon cold acclimation, the subjects judged the environment warmer, felt more comfortable in the cold, and reported less shivering. The combined results suggest that a variable indoor environment with frequent cold exposures might be an acceptable and economic manner to increase energy expenditure and may contribute to counteracting the current obesity epidemic.
Transgenic mice expressing a partially deleted gene for type I procollagen (COL1A1). A breeding line with a phenotype of spontaneous fractures and decreased bone collagen and mineral.
Authors: R Pereira, J S Khillan, H J Helminen, E L Hume, D J Prockop
Journal: Journal of Clinical Investigation (1993)

A line of transgenic mice was prepared that expressed moderate levels of an internally deleted human gene for the pro alpha 1(I) chain of type I procollagen. The gene construct was modeled after a sporadic in-frame deletion of the human gene that produced a lethal variant of osteogenesis imperfecta by causing biosynthesis of shortened pro alpha 1(I) chains. 89 transgenic mice from the line were examined. About 6% had a lethal phenotype with extensive fractures at birth, and 33% had fractures but were viable. The remaining 61% of the transgenic mice had no apparent fractures as assessed by x ray examination on the day of birth. Brother-sister matings produced eight litters in which approximately 40% of the mice had the lethal phenotype, an observation indicating that expression of the exogenous gene was more lethal in putative homozygous mice from the line. Examination of femurs from the transgenic mice indicated that the bones were significantly shorter in length and had a decrease in wet weight, mineral content, and collagen content. However, there was no statistically significant change in the mineral to collagen ratio. Biomechanical measurements on femurs from the mice at 6 wk indicated a decrease in force and energy to failure. There was also a decrease in strain to failure and an increase in Young's modulus of elasticity, observations indicating increased brittleness of bone matrix. The results suggested that the transgenic mice may be an appropriate model for testing potential therapies for osteogenesis imperfecta. They may also be a useful model for studying osteoporosis.
Increased Serum Calcium Levels and Risk of Type 2 Diabetes in Individuals at High Cardiovascular Risk
Authors: Nerea Becerra-Tomás, Ramón Estruch, Mònica Bulló, Rosa Casas, Andrés Díaz-López, Josep Basora, Montserrat Fitó, Lluis Serra-Majem, Jordi Salas-Salvadó
Journal: Diabetes Care (2014)

Insulin resistance and secretion depend on calcium homeostasis. Cross-sectional studies have associated elevated serum calcium levels with markers of impaired glucose metabolism. However, only one prospective cohort study has demonstrated an increased risk of diabetes in individuals with increased serum calcium concentrations. The aim of the current study was to prospectively investigate the association between albumin-adjusted serum calcium concentrations and type 2 diabetes in subjects at high cardiovascular risk.Prospective assessment of participants from two Spanish PREDIMED study centers where serum calcium levels were measured at baseline and yearly during follow-up. Multivariate-adjusted Cox regression models were fitted to assess associations between baseline and changes during follow-up in serum calcium levels and relative risk of diabetes incidence.After a median follow-up of 4.78 years, 77 new cases of type 2 diabetes occurred. An increase in serum calcium levels during follow-up was related to an increased risk of diabetes. In comparison with individuals in the lowest tertile (-0.78 ± 0.29 mg/dL), the hazard ratio (HR) and 95% CI for diabetes incidence in individuals in the higher tertile of change (0.52 ± 0.13 mg/dL) during follow-up was 3.48 (95% CI 1.48-8.17; P for trend = 0.01). When albumin-adjusted serum calcium was analyzed as a continuous variable, per 1 mg/dL increase, the HR of diabetes incidence was 2.87 (95% CI 1.18-6.96; P value = 0.02). These associations remained significant after individuals taking calcium supplements or having calcium levels out of normal range had been excluded.An increase in serum calcium concentrations is associated with an increased risk of type 2 diabetes in individuals at high cardiovascular risk.
Impact of Interleukin-6 on Plaque Development and Morphology in Experimental Atherosclerosis
Authors: Bernhard Schieffer, Tina Selle, Andres Hilfiker, Denise Hilfiker-Kleiner, Karsten Grote, Uwe J.F. Tietge, Christian Trautwein, Maren Luchtefeld, Christian Schmittkamp, Sylvia Heeneman, Mat J.A.P. Daemen, Helmut Drexler
Journal: Circulation (2004)

Vascular lipid accumulation and inflammation are hallmarks of atherosclerosis and perpetuate atherosclerotic plaque development. Mediators of inflammation, ie, interleukin (IL)-6, are elevated in patients with acute coronary syndromes and may contribute to the exacerbation of atherosclerosis.To assess the role of IL-6 in atherosclerosis, ApoE-/--IL-6-/- double-knockout mice were generated, fed a normal chow diet, and housed for 53+/-4 weeks. Mortality and blood pressure were unaltered. However, serum cholesterol levels and subsequent atherosclerotic lesion formation (oil red O stain) were significantly increased in ApoE-/--IL-6-/- mice compared with ApoE-/-, wild-type (WT), and IL-6-/- mice. Plaques of ApoE-/--IL-6-/- mice showed significantly reduced transcript and protein levels of matrix metalloproteinase-9, tissue inhibitor of metalloproteinase-1, collagen I and V, and lysyl oxidase (by reverse transcriptase-polymerase chain reaction and immunohistochemistry). Recruitment of macrophages and leukocytes (Mac3- and CD45-positive staining) into the atherosclerotic lesion was significantly reduced in ApoE-/--IL-6-/- mice. The transcript and serum protein (ELISA) levels of IL-10 were significantly reduced.Thus, a lifetime IL-6 deficiency enhances atherosclerotic plaque formation in ApoEK-/--IL-6-/- mice and leads to maladaptive vascular developmental processes. These observations are consistent with the notion that baseline levels of IL-6 are required to modulate lipid homeostasis, vascular remodeling, and plaque inflammation in atherosclerosis.
Modernizing Eligibility Criteria for Molecularly Driven Trials
Authors: Edward S. Kim, David Bernstein, Susan G. Hilsenbeck, Christine H. Chung, Adam P. Dicker, Jennifer L. Ersek, Steven Stein, Fadlo R. Khuri, Earle Burgess, Kelly Hunt, Percy Ivy, Suanna S. Bruinooge, Neal Meropol, Richard L. Schilsky
Journal: Journal of Clinical Oncology (2015)

As more clinical trials of molecularly targeted agents evolve, the number of eligibility criteria seems to be increasing. The importance and utility of eligibility criteria must be considered in the context of the fundamental goal of a clinical trial: to understand the risks and benefits of a treatment in the intended-use patient population. Although eligibility criteria are necessary to define the population under study and conduct trials safely, excessive requirements may severely restrict the population available for study, and often, this population is not reflective of the general population for which the drug would be prescribed. The American Society of Clinical Oncology Cancer Research Committee, which comprises academic faculty, industry representatives, and patient advocates, evaluated this issue. Evaluation results were mixed. Most physicians agreed that excessive eligibility criterias slow study enrollment rates and prolong the duration of enrollment; however, this hypothesis was difficult to validate with the data examined. We propose the organization of a public workshop, with input from regulatory bodies and key stakeholders, with the goal of developing an algorithmic approach to determining eligibility criteria for individual study protocols, which may help guide future investigators and companies in streamlining eligibility criteria in the era of molecularly driven therapy.
Nerve growth factor levels and localisation in human asthmatic bronchi
Authors: C. Olgart Höglund, F. de Blay, J-P. Oster, C. Duvernelle, O. Kassel, G. Pauli, N. Frossard
Journal: European Respiratory Journal (2002)

Nerve growth factor (NGF) has recently been suggested to be an important mediator of inflammation. In support of this, serum levels of NGF have been shown to be enhanced in asthmatics. However, it has not yet been shown whether the levels of NGF are also altered locally in asthmatic airways, when compared with healthy subjects, and the localisation of potential sources of NGF in the human bronchus have not yet been described. The aim of the present study was to assess NGF levels in bronchoalveolar lavage fluid (BALF) from asthmatics and to compare them to those of control subjects. Furthermore, the authors wanted to localise potential sources of NGF in bronchial tissue, and to number NGF-immunopositive infiltrating cells in the bronchial submucosa. BALF and bronchial biopsies were obtained from seven control subjects and seven asthmatic patients by fibreoptic bronchoscopy. NGF protein levels were quantified by enzyme-linked immunosorbent assay in BALF. NGF localisation was examined by immunohistochemistry on bronchial biopsy sections. The asthmatics exhibited significantly enhanced NGF levels in BALF. Intense NGF-immunoreactivity was observed in bronchial epithelium, smooth muscle cells and infiltrating inflammatory cells in the submucosa, and to a lesser extent in the connective tissue. The asthmatics exhibited a higher number of NGF-immunoreactive infiltrating cells in the bronchial submucosa than control subjects. This study provides evidence that nerve growth factor is locally produced in the airways, and shows that this production is enhanced in asthmatics. These findings suggest that nerve growth factor is produced by both structural cells and infiltrating inflammatory cells in human bronchus in vivo , and the authors suggest that the increase in nerve growth factor protein in bronchoalveolar lavage fluid observed in asthmatic patients may originate both from structural cells, producing increased nerve growth factor levels in inflammatory conditons, and from the increase in nerve growth factor-immunopositive cells determined in the bronchial submucosa.
THE INFECTION BY PLASMODIUM LOPHURAE OF DUCK ERYTHROCYTES IN THE CHICKEN EMBRYO
Authors: R. Barclay McGhee
Journal: The Journal of Experimental Medicine (1953)

Certain morphological differences render it possible to recognize duck erythrocytes after introduction into the circulating blood of chick embryos infected with P. lophurae. 4 hours afterward, considerable numbers of merozoites have entered duck erythrocytes, while the parasitemia of the chick itself remains essentially unchanged in degree. By estimating the numbers of potentially invading merozoites from blood films made at the time of introduction of duck cells, it was learned that a relatively constant rate of invasion into duck cells by merozoites was maintained. In counter-distinction there was an ever increasing merozoite death rate in embryos not receiving duck cells concurrent with the increase in numbers of parasites. After the injection into parasitized embryos of duck erythrocytes showing but few parasites, no difference was apparent in the rate of merozoite invasion into the introduced cells and the host cells, respectively; but when the percentage of duck cells was greater, the rate of merozoite penetration diminished to zero. The selective penetration of duck erythrocytes which, under the experimental conditions obtaining, constituted only 30 per cent of the total cell numbers of most, and the inability of the merozoites to move independently, taken together, suggest that the greater susceptibility of the duck erythrocyte may be due to greater numbers of accessible areas on its surface. The decreased susceptibility following parasitization indicates that the presence of the parasite alters the cell in such wise that entry of additional parasites is rendered more difficult.
Antagonism of the cannabinoid CB-1 receptor protects rat liver against ischaemia-reperfusion injury complicated by endotoxaemia
Authors: P. Caraceni, A. M. Pertosa, F. Giannone, M. Domenicali, I. Grattagliano, A. Principe, C. Mastroleo, M. G. Perrelli, J. Cutrin, F. Trevisani, T. Croci, M. Bernardi
Journal: Gut (2009)

<h3>Background/aim:</h3> Endotoxaemia can complicate hepatic ischaemia–reperfusion (IR) injury. Endocannabinoids appear to modulate the haemodynamic alterations and cytokine response induced by lipopolysaccharide (LPS). Thus, we aimed to determine the effect of the endocannabinoid CB1-receptor antagonist Rimonabant in a model of hepatic IR injury complicated by endotoxaemia. <h3>Methods:</h3> Sprague–Dawley rats pre-treated with Rimonabant 3 or 10 mg/kg or vehicle underwent partial hepatic IR and lipopolysaccharide (LPS) injection at reperfusion. Liver injury was evaluated by serum alanine aminotransferase (ALT) and necrotic-cell count. The inflammatory response was investigated by assessing hepatic neutrophil infiltration, tumour necrosis factor α (TNFα), interferon γ (IFNγ), interleukin 6 (IL6), and suppressor of cytokine signalling (SOCS) 1 and SOCS3 gene expression by real-time polymerase chain reaction (RT-PCR). Systolic blood pressure and hepatic blood flow were measured as haemodynamic parameters. Finally, lipid peroxidation, glutathione status, and immunoreactive CB1 receptor expression in the liver were also determined. <h3>Results:</h3> Liver injury and neutrophil infiltration occurring in the late-phase of LPS-enhanced IR were significantly reduced by CB1-receptor antagonism. Rimonabant-treated rats showed significantly higher gene expression of IFNγ, IL6, SOCS1 and SOCS3 in "early" reperfusion, while that of TNFα was reduced. These findings were associated with increased STAT3 phosphorylation. Furthermore, CB1-receptor antagonism significantly improved the oxidative injury and haemodynamic alterations occurring during reperfusion in untreated rats. Finally, CB1-receptor immunoreactivity was upregulated early after reperfusion. <h3>Conclusions:</h3> This study demonstrates that CB1-receptor antagonism protects the liver against LPS-enhanced IR injury by interfering with the inflammatory response that causes the late, neutrophil-dependent phase of reperfusion injury, although the prevention of the transient endotoxin-related hypotension occurring early during reperfusion may be also involved.
Association between Traffic-Related Air Pollution in Schools and Cognitive Development in Primary School Children: A Prospective Cohort Study
Authors: Jordi Sunyer, Mikel Esnaola, Mar Alvarez-Pedrerol, Joan Forns, Ioar Rivas, Mònica López-Vicente, Elisabet Suades-González, Maria Foraster, Raquel Garcia-Esteban, Xavier Basagaña, Mar Viana, Marta Cirach, Teresa Moreno, Andrés Alastuey, Núria Sebastian-Galles, Mark Nieuwenhuijsen, Xavier Querol
Journal: PLoS Medicine (2015)

Air pollution is a suspected developmental neurotoxicant. Many schools are located in close proximity to busy roads, and traffic air pollution peaks when children are at school. We aimed to assess whether exposure of children in primary school to traffic-related air pollutants is associated with impaired cognitive development.We conducted a prospective study of children (n = 2,715, aged 7 to 10 y) from 39 schools in Barcelona (Catalonia, Spain) exposed to high and low traffic-related air pollution, paired by school socioeconomic index; children were tested four times (i.e., to assess the 12-mo developmental trajectories) via computerized tests (n = 10,112). Chronic traffic air pollution (elemental carbon [EC], nitrogen dioxide [NO2], and ultrafine particle number [UFP; 10-700 nm]) was measured twice during 1-wk campaigns both in the courtyard (outdoor) and inside the classroom (indoor) simultaneously in each school pair. Cognitive development was assessed with the n-back and the attentional network tests, in particular, working memory (two-back detectability), superior working memory (three-back detectability), and inattentiveness (hit reaction time standard error). Linear mixed effects models were adjusted for age, sex, maternal education, socioeconomic status, and air pollution exposure at home. Children from highly polluted schools had a smaller growth in cognitive development than children from the paired lowly polluted schools, both in crude and adjusted models (e.g., 7.4% [95% CI 5.6%-8.8%] versus 11.5% [95% CI 8.9%-12.5%] improvement in working memory, p = 0.0024). Cogently, children attending schools with higher levels of EC, NO2, and UFP both indoors and outdoors experienced substantially smaller growth in all the cognitive measurements; for example, a change from the first to the fourth quartile in indoor EC reduced the gain in working memory by 13.0% (95% CI 4.2%-23.1%). Residual confounding for social class could not be discarded completely; however, the associations remained in stratified analyses (e.g., for type of school or high-/low-polluted area) and after additional adjustments (e.g., for commuting, educational quality, or smoking at home), contradicting a potential residual confounding explanation.Children attending schools with higher traffic-related air pollution had a smaller improvement in cognitive development.
The prone position in acute respiratory distress syndrome
Authors: D. Ryan, P Pelosi
Journal: BMJ (1996)

treatment with DHEA.Treatment was also associated with an increase in insulin binding and degradation by T lymphocytes, and this was thought to reflect increased insulin sensitivity.No adverse effects were reported.In the third study eight men and eight women aged 50-65 were given 100 mg of DHEA or placebo for six months.13The investigators confirmed their previous observation10 that the intake of DHEA was associated with an increase in insulin like growth factor.Treatment at the higher dose led to an increase in lean body mass that reached statistical significance when both men and women were analysed together.Muscle strength at the knee was increased in men but not in women.Because the 100 mg dose of DHEA stimulated a greater increase in serum androgens in women than had been observed with a dose of 50 mg, the authors concluded that this amount "may induce undesirable androgenic effects with time."The effect of DHEA on well being was not discussed.Writing in the Lancet, Herbert concluded: "Enough is known or suspected to warrant investigation of DHEA as an effective, worthwhile, and relatively risk-free replacement therapy in advancing age.This can only be done by a controlled prospective trial of DHEA treatment."8This recommendation may be scientifically sound but it will be dif- ficult to follow.The pharmaceutical industry may hesitate to support studies with DHEA, a molecule that cannot be patented.Similarly, it may not be easy to attract research funds from government agencies or private philanthropies at a time when support is shifting from clinical trials to fundamental research.Further research studies confirming or rejecting the reported results of DHEA replacement treatment seem unlikely to appear in the near future.What advice should a doctor give when asked about the treatment?In my opinion there is not at present sufficient evi- dence for routinely recommending replacement treatment with DHEA to middle aged and elderly people.Furthermore, patients with a family or personal history of a tumour respon- sive to hormones-for example, breast cancer or prostate cancer-should be dissuaded from taking DHEA.Treatment should be restricted to patients with low serum levels of DHEA and normal levels of prostate antigen.This means that patients who say that they want to take DHEA should have their serum DHEA and prostate antigen levels determined before treatment.All patients receiving DHEA should be asked to attend their doctor for regular clinical review and monitoring of their serum levels of DHEA and prostate specific antigen.