tbuckley/cabot-search huggingface dataset:
The Use of Insulin Pumps With Meal Bolus Alarms in Children With Type 1 Diabetes to Improve Glycemic Control
Authors: H. Peter Chase, Brian Horner, Kim McFann, Hannah Yetzer, Jana Gaston, Carolyn Banion, Rosanna Fiallo-Scharer, Robert Slover, Georgeanna Klingensmith
Journal: Diabetes Care (2006)

OBJECTIVE—The aim of this study was to determine whether the use of meal bolus alarms would result in fewer missed meal boluses per week in youth with type 1 diabetes using continuous subcutaneous insulin infusion (CSII) therapy. RESEARCH DESIGN AND METHODS—This was a randomized trial of 48 youth using CSII, who were in suboptimal glycemic control with HbA1c (A1C) values ≥8.0%. Twenty-four subjects were randomized to use a Deltec Cozmo insulin pump with meal bolus alarms (experimental group), while the other 24 subjects continued use of their current insulin pumps (control group) without meal bolus alarms. RESULTS—After 3 months of study, the number of missed meal boluses per week was significantly lower in the experimental group (from 4.9 ± 3.7 to 2.5 ± 2.5; P = 0.0005) but not significantly lower in the control group (from 4.3 ± 2.7 to 4.2 ± 3.9; P = 0.7610). Also after 3 months, the mean A1C value of the experimental group declined significantly (from 9.32 ± 1.12 to 8.86 ± 1.10; P = 0.0430). No significant decline in A1C was present for the control group (from 8.93 ± 1.04 to 8.67 ± 1.17; P = 0.1940). After 6 months of study, the significant decline in A1C from baseline in the experimental group was no longer present. Pooling of all available data from the control and experimental groups showed that at baseline and 3 and 6 months, the number of missed meal boluses per week was significantly correlated with A1C values. CONCLUSIONS—While meal bolus alarms may have the potential to improve suboptimal glycemic control in youth using CSII, our results demonstrated that these alarms had only a transient, modest effect in doing so.
Protease-activated receptor-2 activation: a major actor in intestinal inflammation
Authors: E Hyun, P Andrade-Gordon, M Steinhoff, N Vergnolle
Journal: Gut (2008)

<h3>Background and aims:</h3> The role of protease-activated receptor-2 (PAR<sub>2</sub>) during intestinal inflammation is still unclear due to the fact that PAR<sub>2</sub>-activating peptide has both pro- and anti-inflammatory properties. The aim of this study was to investigate the effects of PAR<sub>2</sub> deficiency (using PAR<sub>2</sub>-deficient mice, PAR<sub>2</sub><sup>−/−</sup>) in models of colitis, in order to elucidate the role of endogenous PAR<sub>2</sub> in the process of inflammation in the gut. <h3>Methods:</h3> Colonic inflammation in wild-type and PAR<sub>2</sub><sup>−/−</sup> mice was induced by dextran sodium sulfate, trinitrobenzene sulfonic acid (TNBS), a T helper-1 predominant model, or oxazolone, a T helper-2 predominant model. Leukocyte recruitment, assessed by intravital microscopy, and inflammatory parameters (myeloperoxidase (MPO), macroscopic and microscopic damage) were assessed during the development of colitis. Lastly, the protein levels of cyclooxygenases (COXs) and adhesion molecules (ICAM-1, VCAM-1, alpha-M, alpha-4) were assessed by using western blot analysis. <h3>Results:</h3> In all three models of colitis, MPO activity, macroscopic damage score and bowel thickness were significantly lower in PAR<sub>2</sub><sup>−/−</sup> mice. Changes in vessel leukocyte recruitment parameters (rolling and adhesion) were also significantly reduced in PAR<sub>2</sub><sup>−/−</sup> mice compared to wild-type mice after the induction of colitis. The protein expression of ICAM-1, VCAM-1 and alpha-4 was significantly attenuated, whereas the expression of COX-1 was significantly increased in PAR<sub>2</sub><sup>−/−</sup> mice challenged with TNBS-induced colitis. <h3>Conclusions:</h3> The role of endogenous PAR<sub>2</sub> in the gut is pro-inflammatory and independent of the T helper-1 or -2 cytokine profile. Endogenous PAR<sub>2</sub> activation controls leukocyte recruitment in the colon and thus appears as a new potential therapeutic target for the treatment of inflammatory bowel disease.
What is immoral about eugenics?
Authors: A. L Caplan, G. McGee, D. Magnus
Journal: BMJ (1999)

It is a “given” in discussions of genetic engineering that no sensible person can be in favour of eugenics. The main reason for this presumption is that so much horror, misery, and mayhem have been carried out in the name of eugenics in the 20th century that no person with any moral sense could think otherwise.1–3 In fact, the abysmal history of murder and sterilisation undertaken in the name of race hygiene and the “improvement” of the human species again and again in this century is so overpowering that the risk of reoccurrence, sliding down what has proved time and time again to be an extremely slick, slippery slope, does seem enough to bring all ethical argument in favour of eugenics to an end. 

However, before dismissing any favourable stance towards eugenics it is important to distinguish what has happened in the past under the banner of eugenics and what might happen in the future. It is important to distinguish between genetic changes undertaken with respect to improving a group or population and genetic change that takes a single individual as its focus.

#### Summary points

The horrible abuses committed in the name of eugenics through coercive policies imposed by governments have obscured the fact that eugenic goals can be the subject of choice as well as coercion

In the rush to map the human genome and reap the benefits of new genetic knowledge it has become commonplace to argue that eugenic goals will play no part in how new genetic knowledge is used

The moral case against voluntary choices to advance eugenic goals by individuals or couples has not been persuasively made

Given the power and authority granted to parents to seek to improve or better their children by environmental interventions, at least some forms of genetic selection or …
Metabolism and Anticancer Activity of the Curcumin Analogue, Dimethoxycurcumin
Authors: Constantin Tamvakopoulos, Konstantinos Dimas, Zacharias D. Sofianos, Sophia Hatziantoniou, Zhiyong Han, Zhong-Li Liu, James H. Wyche, Panayotis Pantazis
Journal: Clinical Cancer Research (2007)

Abstract Purpose: The plant-derived compound curcumin has shown promising abilities as a cancer chemoprevention and chemotherapy agent in vitro and in vivo but exhibits poor bioavailability. Therefore, there is a need to investigate modified curcumin congeners for improved anticancer activity and pharmacokinetic properties. Experimental Design: The synthetic curcumin analogue dimethoxycurcumin was compared with curcumin for ability to inhibit proliferation and apoptosis of human HCT116 colon cancer cells in vitro by estimating the GI50 and LC50 values and detecting the extent of apoptosis by flow cytometry analysis of the cell cycle. Metabolic stability and/or identification of metabolites were evaluated by recently developed mass spectrometric approaches after incubation with mouse and human liver microsomes and cancer cells in vitro. Additionally, circulating levels of dimethoxycurcumin and curcumin were determined in mice following i.p. administration. Results: Dimethoxycurcumin is significantly more potent than curcumin in inhibiting proliferation and inducing apoptosis in HCT116 cells treated for 48 h. Nearly 100% of curcumin but &amp;lt;30% of dimethoxycurcumin was degraded in cells treated for 48 h, and incubation with liver microsomes confirmed the limited metabolism of dimethoxycurcumin. Both compounds were rapidly degraded in vivo but dimethoxycurcumin was more stable. Conclusions: Compared with curcumin, dimethoxycurcumin is (a) more stable in cultured cells, (b) more potent in the ability to kill cancer cells by apoptosis, (c) less extensively metabolized in microsomal systems, and (d) more stable in vivo. It is likely that the differential extent of apoptosis induced by curcumin and dimethoxycurcumin in vitro is associated with the metabolite profiling and/or the extent of stability.
World class commissioning in the NHS is achievable, say officials
Authors: A. O'Dowd
Journal: BMJ (2009)

Government officials have denied claims that the move by the NHS to world class commissioning is “ludicrous,” calling it instead an aspiration for the service.

MPs on the parliamentary health select committee quizzed Department of Health officials on 22 October as part of their first evidence session of an inquiry into commissioning. They asked whether the claim that England was now moving to world class commissioning was not a “ludicrous” one.

Gary Belfield, acting director general for commissioning and system management at the Department of Health, said, “We are one of the largest organisations in the world and we’ve got 60 million people in England …
Low vitamin D serum concentration is associated with high levels of hepatitis B virus replication in chronically infected patients
Authors: Harald Farnik, Jörg Bojunga, Annemarie Berger, Regina Allwinn, Oliver Waidmann, Bernd Kronenberger, Oliver T. Keppler, Stefan Zeuzem, Christoph Sarrazin, Christian M. Lange
Journal: Hepatology (2013)

Vitamin D is an important immune modulator that plays an emerging role in inflammatory and metabolic liver diseases, including infection with hepatitis C virus (HCV). In contrast, the relationship between vitamin D metabolism and chronic hepatitis B (CHB) is less well characterized. Therefore, we quantified 25(OH)D3 serum levels in a cohort of 203 treatment-naïve patients with chronic hepatitis B virus (HBV) infection and tested for their association with clinical parameters of CHB. Of 203 patients, 69 (34%), 95 (47%), and 39 (19%) had severe vitamin D deficiency (25(OH)D3 &lt;10 ng/mL), vitamin D insufficiency (25(OH)D3 ≥10 and &lt;20 ng/mL), or adequate vitamin D serum levels (25(OH)D3 ≥20 ng/mL), respectively. In both uni- and multivariate analyses, HBV DNA viral load (log10 IU/mL) was a strong predictor of low 25(OH)D3 serum levels ( P = 0.0007 and P = 0.000048, respectively) and vice versa. Mean 25(OH)D3 serum concentrations in patients with HBV DNA &lt;2,000 versus ≥2,000 IU/mL were 17 versus 11 ng/mL, respectively ( P &lt; 0.00001). In addition, hepatitis B early antigen (HBeAg)-positive patients had lower 25(OH)D3 serum levels than HBeAg-negative patients ( P = 0.0013). Finally, 25(OH)D3 and HBV DNA serum levels showed inverse seasonal fluctuations. Conclusion : Low 25(OH)D3 serum levels are associated with high levels of HBV replication in patients with CHB. This represents a major difference from chronic hepatitis C, where numerous previous studies have shown a lack of correlation between HCV viral load and vitamin D serum levels. Inverse seasonal fluctuations of 25(OH)D3 and HBV DNA serum levels are suggestive of a functional relationship between both variables. (Hepatology 2013;58:1270–1276)
Localized Mucosa-Associated Lymphoid Tissue Lymphoma Treated With Radiation Therapy Has Excellent Clinical Outcome
Authors: Richard W. Tsang, Mary K. Gospodarowicz, Melania Pintilie, Woodrow Wells, David C. Hodgson, Alexander Sun, Michael Crump, Bruce J. Patterson
Journal: Journal of Clinical Oncology (2003)

Extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is a distinct lymphoma with unique clinicopathologic features. We report the clinical outcome of stage I and II MALT lymphoma treated with involved field radiation therapy (RT).From 1989 to 2000, 103 patients with stage IE and IIE disease were referred. Their median age was 60 years, with a 2:1 female predominance. Presenting sites were stomach (17 patients), orbital adnexa (31 patients), salivary glands (24 patients), thyroid gland (13 patients), and other sites (18 patients). Ninety-three patients received RT--85 received RT alone, and eight received chemotherapy and RT--with a median dose of 30 Gy. The median follow-up time was 5.1 years.A complete response (CR) to RT alone was achieved in 84 of 85 patients. Among CR patients, 14 experienced relapse. Relapse sites were mostly contralateral paired-organ or distant MALT locations and, infrequently, lymph nodes. The crude local control rate with RT was 95.3% (81 of 85 patients). No relapses were observed in patients with stomach or thyroid lymphoma, whereas 14 of 63 patients (22%) experienced relapse in the other sites. The overall 5-year survival rate was 98%, and the disease-free survival rate was 77%. Transformed lymphoma was observed in 14% of patients (two of 14) experiencing relapse.Moderate-dose RT achieved excellent local control in localized MALT lymphomas and had curative potential for three fourths of the patients. Gastric and thyroid MALT lymphomas had better outcome, whereas distant failures were common for other sites. Despite relapse, the disease often maintained an indolent course.
Integrating Genetic, Transcriptional, and Functional Analyses to Identify 5 Novel Genes for Atrial Fibrillation
Authors: Moritz F. Sinner, Nathan R. Tucker, Kathryn L. Lunetta, Kouichi Ozaki, J. Gustav Smith, Stella Trompet, Joshua C. Bis, Honghuang Lin, Mina K. Chung, Jonas B. Nielsen, Steven A. Lubitz, Bouwe P. Krijthe, Jared W. Magnani, Jiangchuan Ye, Michael H. Gollob, Tatsuhiko Tsunoda, Martina Müller-Nurasyid, Peter Lichtner, Annette Peters, Elena Dolmatova, Michiaki Kubo, Jonathan D. Smith, Bruce M. Psaty, Nicholas L. Smith, J. Wouter Jukema, Daniel I. Chasman, Christine M. Albert, Yusuke Ebana, Tetsushi Furukawa, Peter W. Macfarlane, Tamara B. Harris, Dawood Darbar, Marcus Dörr, Anders G. Holst, Jesper H. Svendsen, Albert Hofman, Andre G. Uitterlinden, Vilmundur Gudnason, Mitsuaki Isobe, Rainer Malik, Martin Dichgans, Jonathan Rosand, David R. Van Wagoner, Emelia J. Benjamin, David J. Milan, Olle Melander, Susan R. Heckbert, Ian Ford, Yongmei Liu, John Barnard, Morten S. Olesen, Bruno H.C. Stricker, Toshihiro Tanaka, Stefan Kääb, Patrick T. Ellinor
Journal: Circulation (2014)

Atrial fibrillation (AF) affects >30 million individuals worldwide and is associated with an increased risk of stroke, heart failure, and death. AF is highly heritable, yet the genetic basis for the arrhythmia remains incompletely understood.
Immunopathology of subcutaneous rheumatoid nodules.
Authors: O J Mellbye, O Forre, T E Mollnes, L Kvarnes
Journal: Annals of the Rheumatic Diseases (1991)

Nodules obtained from five patients with classical seropositive rheumatoid arthritis were studied by an immunofluorescence technique using polyclonal antibodies to IgG, IgA, IgM, C3c, and fibrin, and monoclonal antibodies to the terminal (C5b-9) complement complex (reaction with a neoantigen in C9 revealed during activation), DR antigens, T cells, macrophages, and interdigitating cells. In all instances the central necrotic areas stained strongly for fibrin and more weakly for IgG, IgA, IgM, C3, and terminal complement complex. The surrounding palisading cells reacted with antibodies to DR and macrophages. In the peripheral granulomatous tissue most of the lymphocytes reacted with the antibodies to T cells, whereas various amounts of the larger mononuclear cells were stained by antibodies to DR antigens, macrophages, and interdigitating cells. In all instances the walls of some of the smaller vessels in the granulomatous tissue stained for fibrin, C3, and terminal complement complex. Plasma cells were not seen except for scattered IgM cells in one nodule. These results support the view that the palisading cells are derived from macrophages, and indicate that there is vasculitis with activation of C3 and the terminal complement pathway in the granulomatous tissue.
The diagnosis of cutaneous T-cell lymphoma by morphometric evaluation of the cellular infiltrate, using semithin sections
Authors: M. LESSANA-LEIBOWITCH, A. PRADO, A. PALANGIE, F. LAMY, G. FLANDRIN
Journal: British Journal of Dermatology (2006)

In order to improve the cytological criteria for the diagnosis of cutaneous T-cell lymphomas (CTCL), a number of morphometric assessments in semithin sections have been performed on the dermal infiltrates of twenty-one cases of overt CTCL (group I) and twenty-two cases of well-defined benign dermatoses (group II). In each biopsy, an average of 250 cells were measured for perimeter (P), surface area (S), 'nuclear shape index' (NSI), mean surface and mean NSI. We also determined the percentage of typical 'highly cerebriform lymphocytes' (HCL). Cells of group I patients were found to have mean S and mean NSI that differed significantly from those of group II. HCL were found to have a mean NSI value of less than 0.40. The diagnostic value of these measurements was confirmed in the group I patients. Nineteen of them had a mean NSI value of less than 0.61, together with a mean S greater than 14 sq. micron. None of the twenty-two patients of group II had such values. The discriminating power of these criteria was then tested retrospectively on another group of initially controversial patients who presented with suspected CTCL (group III patients). Nine have since evolved into overt CTCL (group III M) while the other ten have remained benign (group III B). All group III B patients and five patients of group III M were correctly assigned using the above morphometric criteria. This method could improve the diagnosis of the early stage of cutaneous T-cell lymphoma.
ACE inhibitors, cough, and genetics
Authors: Carmen Kreft-Jais, Laurent Laforest, Alain Bonnardeaux, Cécile Dumont, Pierre-François Plouin, Xavier Jeunemaitre, I.G. Chadwick, W.W. Yeo, K.S. Higgins, P.R. Jackson, L.E. Ramsay, A.H. Morice
Journal: The Lancet (1994)
High-Density Lipoprotein Maintains Skeletal Muscle Function by Modulating Cellular Respiration in Mice
Authors: Maarit Lehti, Elizabeth Donelan, William Abplanalp, Omar Al-Massadi, Kirk M. Habegger, Jon Weber, Chandler Ress, Johannes Mansfeld, Sonal Somvanshi, Chitrang Trivedi, Michaela Keuper, Teja Ograjsek, Cynthia Striese, Sebastian Cucuruz, Paul T. Pfluger, Radhakrishna Krishna, Scott M. Gordon, R.A. Gangani D. Silva, Serge Luquet, Julien Castel, Sarah Martinez, David D’Alessio, W. Sean Davidson, Susanna M. Hofmann
Journal: Circulation (2013)

Abnormal glucose metabolism is a central feature of disorders with increased rates of cardiovascular disease. Low levels of high-density lipoprotein (HDL) are a key predictor for cardiovascular disease. We used genetic mouse models with increased HDL levels (apolipoprotein A-I transgenic [apoA-I tg]) and reduced HDL levels (apoA-I-deficient [apoA-I ko]) to investigate whether HDL modulates mitochondrial bioenergetics in skeletal muscle.
Low T cell production of TNFalpha and IFNgamma in ankylosing spondylitis: its relation to HLA-B27 and influence of the TNF-308 gene polymorphism
Authors: M Rudwaleit, S Siegert, Z Yin, J Eick, A Thiel, A Radbruch, J Sieper, J Braun
Journal: Annals of the Rheumatic Diseases (2001)

To test the hypothesis that ankylosing spondylitis (AS) is a T helper cell type 2 polarised disease by quantifying the T cell cytokines interferon gamma (IFNgamma), interleukin 4 (IL4), tumour necrosis factor alpha (TNFalpha), and IL10 at the single cell level in patients with AS in comparison with healthy HLA-B27 negative and HLA-B27 positive controls.Peripheral blood mononuclear cells from 65 subjects (25 HLA-B27 positive patients with active AS, 18 healthy HLA-B27 positive controls, and 22 healthy HLA-B27 negative controls) were stimulated with phorbol myristate acetate/ionomycin for six hours, surface stained for CD3 and CD8, intracellularly stained for the cytokines IFNgamma, TNFalpha, IL4, and IL10, and analysed by flow cytometry. TNFalpha production was related to the genotype of the TNFalpha promoter at the -308 and -238 polymorphisms.In peripheral blood the percentage of TNFalpha+ T cells was significantly lower in HLA-B27 positive patients with AS (median 5.1% for CD4+ T cells) than in healthy HLA-B27 negative controls (median 9.5%; p=0.008). Surprisingly, the percentage of TNFalpha+ T cells was also significantly lower in healthy HLA-B27 positive controls (median 7.48%) than in healthy HLA-B27 negative controls (p=0.034). Furthermore, the percentage of IFNgamma+ T cells was lower in patients with AS and in healthy HLA-B27 positive controls than in healthy HLA-B27 negative controls (p=0.005 and p=0.003, respectively). The percentage of IL10+/CD8+ T cells was higher in patients with AS than in both control groups. In HLA-B27 positive subjects, TNF1/2 heterozygosity at -308 (n=6) was associated with a higher percentage of TNFalpha+ T cells than TNF1/1 homozygosity (n=25; median 9.97% v 5.11% for CD4+ T cells; p=0.017). In contrast, in HLA-B27 negative controls (n=18) there was no such genotype/phenotype correlation (median 9.4% v 10.6%).The lower T cell production of TNFalpha and IFNgamma shown at the single cell level in HLA-B27 positive patients with AS and healthy HLA-B27 positive controls may contribute to the increased susceptibility of HLA-B27 positive subjects to develop AS. Preliminary genotype-phenotype correlations suggest that in HLA-B27 positive subjects TNF2 at -308 or a linked gene results in higher TNFalpha production and, therefore, might be a marker for a protective haplotype.
Improvement in precision of counting actinic keratoses
Authors: K.C. Lee, R. Lew, M.A. Weinstock
Journal: British Journal of Dermatology (2013)

Actinic keratoses (AKs) often serve as a primary endpoint for clinical studies. However, reliability of counting these lesions is poor, even among expert dermatologists. To investigate the reliability of counting AKs before and after a yearly consensus meeting, held annually for 4 years. As part of the Veterans Affairs (VA) Keratinocyte Carcinoma Chemoprevention Trial, board-certified dermatologists convened annually for 4 years to individually count the number of actinic keratoses on three to five test subjects. The dermatologists then met as a group for a consensus discussion on what constituted an AK lesion on each subject. Afterwards, each dermatologist repeated the independent counting exercise on three to five new subjects. The intraclass correlation coefficient (ICC) was used to analyze the reliability of counting AKs among the dermatologists. Eight dermatologists participated in this exercise for 4 consecutive years. Pre-consensus discussion ICCs over 4 years were 0.18, 0.34, 0.38, 0.75, respectively, showing sustained improvement with each consensus discussion. The greatest improvement in reliability of AK counts was shown during the first year of consensus discussions, when the ICC improved from 0.18 to 0.67. There was no improvement by the fourth year of consensus discussion, with pre- and post-consensus ICCs of 0.75 and 0.75, respectively. Annual consensus discussions can lead to improvement in reliability of AK counts. This improvement was sustained over 4 years. By the fourth year, the discussion meeting had no effect on improvement in reliability. A consensus meeting discussion may be helpful for improving reliability in other trials.
Effect of binge drinking on the liver: an alarming public health issue?
Authors: P. Mathurin, P. Deltenre
Journal: Gut (2009)

<h3>Abstract</h3> Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is caused by mutations in <i>SACS</i>, which manifest as a childhood-onset cerebellar ataxia. Cellular ARSACS phenotypes include mitochondrial dysfunction, intermediate filament (IF) disorganization, and loss of Purkinje neurons. It is unclear how the loss of SACS causes these deficits, or why they manifest as cerebellar ataxia. We employed a multi-omics approach to characterize molecular and cellular deficiencies in <i>SACS</i> knockout (KO) cells. We identified alterations in microtubule structure and dynamics, protein trafficking, and mislocalization of synaptic and focal adhesion proteins. Targeting <i>PTEN</i>, a negative regulator of focal adhesions, rescued several cellular phenotypes in <i>SACS</i> KO cells. We found sacsin interacts with proteins implicated in vesicle transport, including HSP proteins, and interactions between structural and cell adhesion proteins were diminished in <i>SACS</i> KO cells. In all, this study suggests that trafficking and localization of synaptic adhesion proteins is a causal molecular deficiency in ARSACS.