tbuckley/cabot-search huggingface dataset:
Progressive hypoglycemia's impact on driving simulation performance. Occurrence, awareness and correction.
Authors: D J Cox, L A Gonder-Frederick, B P Kovatchev, D M Julian, W L Clarke
Journal: Diabetes Care (2000)

Progressive hypoglycemia leads to cognitive-motor and driving impairments. This study evaluated the blood glucose (BG) levels at which driving was impaired, impairment was detected, and corrective action was taken by subjects, along with the mechanisms underlying these three issues.There were 37 adults with type 1 diabetes who drove a simulator during continuous euglycemia and progressive hypoglycemia. During testing, driving performance, EEG, and corrective behaviors (drinking a soda or discontinuing driving) were continually monitored, and BG, symptom perception, and judgement concerning impairment were assessed every 5 min. Mean +/- SD euglycemia performance was used to quantify z scores for performance in three hypoglycemic ranges (4.0-3.4, 3.3-2.8, and <2.8 mmol/l).During all three hypoglycemic BG ranges, driving was significantly impaired, and subjects were aware of their impaired driving. However, corrective actions did not occur until BG was <2.8 mmol/l. Driving impairment was related to increased neurogenic symptoms and increased theta-wave activity. Awareness of impaired driving was associated with neuroglycopenic symptoms. increased beta-wave activity, and awareness of hypoglycemia. High beta and low theta activity and awareness of both hypoglycemia and the need to treat low BG influenced corrective behavior.Driving performance is significantly disrupted at relatively mild hypoglycemia, yet subjects demonstrated a hesitation to take corrective action. The longer treatment is delayed, the greater the neuroglycopenia (increased theta), which precludes corrective behaviors. Patients should treat themselves while driving as soon as low BG and/or impaired driving is suspected and should not begin driving when their BG is in the 5.0-4.0 mmol/l range without prophylactic treatment.
Two decision aids for mode of delivery among women with previous caesarean section: randomised controlled trial
Authors: Alan A Montgomery, Clare L Emmett, Tom Fahey, Claire Jones, Ian Ricketts, Roshni R Patel, Tim J Peters, Deirdre J Murphy
Journal: BMJ (2007)

<b>Objectives</b> To determine the effects of two computer based decision aids on decisional conflict and mode of delivery among pregnant women with a previous caesarean section. <b>Design</b> Randomised trial, conducted from May 2004 to August 2006. <b>Setting</b> Four maternity units in south west England, and Scotland. <b>Participants</b> 742 pregnant women with one previous lower segment caesarean section and delivery expected at ≥37 weeks. Non-English speakers were excluded. <b>Interventions</b> Usual care: standard care given by obstetric and midwifery staff. Information programme: women navigated through descriptions and probabilities of clinical outcomes for mother and baby associated with planned vaginal birth, elective caesarean section, and emergency caesarean section. Decision analysis: mode of delivery was recommended based on utility assessments performed by the woman combined with probabilities of clinical outcomes within a concealed decision tree. Both interventions were delivered via a laptop computer after brief instructions from a researcher. <b>Main outcome measures</b> Total score on decisional conflict scale, and mode of delivery. <b>Results</b> Women in the information programme (adjusted difference −6.2, 95% confidence interval −8.7 to −3.7) and the decision analysis (−4.0, −6.5 to −1.5) groups had reduced decisional conflict compared with women in the usual care group. The rate of vaginal birth was higher for women in the decision analysis group compared with the usual care group (37% <i>v</i> 30%, adjusted odds ratio 1.42, 0.94 to 2.14), but the rates were similar in the information programme and usual care groups. <b>Conclusions</b> Decision aids can help women who have had a previous caesarean section to decide on mode of delivery in a subsequent pregnancy. The decision analysis approach might substantially affect national rates of caesarean section. <b>Trial Registration</b> Current Controlled Trials ISRCTN84367722.
Overall efficacy of HPV-16/18 AS04-adjuvanted vaccine against grade 3 or greater cervical intraepithelial neoplasia: 4-year end-of-study analysis of the randomised, double-blind PATRICIA trial
Authors: Matti Lehtinen, Jorma Paavonen, Cosette M Wheeler, Unnop Jaisamrarn, Suzanne M Garland, Xavier Castellsagué, S Rachel Skinner, Dan Apter, Paulo Naud, Jorge Salmerón, Song-Nan Chow, Henry Kitchener, Júlio C Teixeira, James Hedrick, Genara Limson, Anne Szarewski, Barbara Romanowski, Fred Y Aoki, Tino F Schwarz, Willy A J Poppe, Newton S De Carvalho, Maria Julieta V Germar, Klaus Peters, Adrian Mindel, Philippe De Sutter, F Xavier Bosch, Marie-Pierre David, Dominique Descamps, Frank Struyf, Gary Dubin
Journal: The Lancet Oncology (2011)
National Standards for Diabetes Self-Management Education
Authors: Martha M. Funnell, Tammy L. Brown, Belinda P. Childs, Linda B. Haas, Gwen M. Hosey, Brian Jensen, Melinda Maryniuk, Mark Peyrot, John D. Piette, Diane Reader, Linda M. Siminerio, Katie Weinger, Michael A. Weiss
Journal: Diabetes Care (2008)

iabetes self-management education (DSME) is a critical element of care for all people with diabetes and is necessary in order to improve patient outcomes.The National Standards for DSME are designed to define quality diabetes self-management education and to assist diabetes educators in a variety of settings to provide evidence-based education.Because of the dynamic nature of health care and diabetes-related research, these Standards are reviewed and revised approximately every 5 years by key organizations and federal agencies within the diabetes education community.A Task Force was jointly convened by the American Association of Diabetes Educators and the American Diabetes Association in the summer of 2006.Additional organizations that were represented included the American Dietetic Association, the Veteran's Health Administration, the Centers for Disease Control and Prevention, the Indian Health Service, and the American Pharmaceutical Association.Members of the Task Force included a person with diabetes; several health services researchers/ behaviorists, registered nurses, and registered dietitians; and a pharmacist.The Task Force was charged with reviewing the current DSME standards for their appropriateness, relevance, and scientific basis.The Standards were then reviewed and revised based on the available evidence and expert consensus.The committee convened on 31 March
Effects of Hypertension on the Lipid Composition of Rat Aortic Intima-Media
Authors: Marie M. Daly
Journal: Circulation Research (1972)

Since hypertension intensifies the development of atherosclerosis, effects of hypertension on the lipid composition of aortic intima-media of male rats were studied. Concentrations of cholesterol, both esterified and unesterified, and of phospholipid were increased, and the concentration of triglyceride was decreased in aortas of hypertensive rats maintained on a stock diet. Changes in free cholesterol, phospholipid, and triglyceride are believed to be concomitants of medial hypertrophy, which was pronounced in aortas of hypertensive rats. Changes in esterified cholesterol, however, may be attributable to an influence of plasma lipids on aortic lipids. Cholesteryl ester, quantitatively a minor lipid component of the aorta, shows a larger increase with hypertension than other lipid classes. The resemblance between fatty acid compositions of aortic and plasma cholesteryl esters was strong, and persisted when the composition of plasma cholesteryl esters was altered by diet. These results suggest that most of the aortic esters originated in the plasma, and support the concept that hypertension intensifies the development of atherosclerosis by increasing the net transfer of lipid from plasma to vessel.
Gastric Antral Injections of Botulinum Toxin Delay Gastric Emptying but Do Not Reduce Body Weight
Authors: Mark Topazian, Michael Camilleri, Felicity T. Enders, Jonathan E. Clain, Ferga C. Gleeson, Michael J. Levy, Elizabeth Rajan, Vandana Nehra, Ross A. Dierkhising, Maria L. Collazo–Clavell, Nicholas J. Talley, Matthew M. Clark
Journal: Clinical Gastroenterology and Hepatology (2012)
Gaseotransmitters: New Frontiers for Translational Science
Authors: Csaba Szabo
Journal: Science Translational Medicine (2010)

Translational research on endogenous gaseous mediators--nitric oxide, carbon monoxide, and hydrogen sulfide--has exploded over the past decade. Drugs that modulate either the gaseous mediators themselves or their related intracellular signaling pathways are already in use in the clinics, and still more are being tested in preclinical models and clinical trials. Discussed here are the chemical and pharmacological properties that present challenges for the translation of these potentially toxic molecules.
Controlled Comparison of <scp>l</scp> -5-Methyltetrahydrofolate Versus Folic Acid for the Treatment of Hyperhomocysteinemia in Hemodialysis Patients
Authors: Andrew G. Bostom, Douglas Shemin, Pamela Bagley, Ziad A. Massy, Abdul Zanabli, Kenneth Christopher, Paul Spiegel, Paul F. Jacques, Lance Dworkin, Jacob Selhub
Journal: Circulation (2000)

Background —The hyperhomocysteinemia regularly found in hemodialysis patients is largely refractory to combined oral B-vitamin supplementation featuring supraphysiological doses of folic acid. We evaluated whether a high-dose l -5-methyltetrahydrofolate–based regimen provided improved total homocysteine (tHcy)–lowering efficacy in chronic hemodialysis patients. Methods and Results —We block-randomized 50 chronic, stable hemodialysis patients on the basis of their screening predialysis tHcy levels, sex, and dialysis center into 2 groups of 25 subjects treated for 12 weeks with oral folic acid at 15 mg/d (FA group) or an equimolar amount (17 mg/d) of oral l -5-methyltetrahydrofolate (MTHF group). All 50 subjects also received 50 mg/d of oral vitamin B 6 and 1.0 mg/d of oral vitamin B 12 . The mean percent reductions (±95% CIs) in predialysis tHcy were not significantly different: MTHF, 17.0% (12.0% to 22.0%); FA, 14.8% (9.6% to 20.1%); P =0.444 by matched ANCOVA adjusted for pretreatment tHcy. Final on-treatment values (mean with 95% CI) were MTHF, 20.0 μmol/L (18.8 to 21.2 μmol/L); FA, 19.5 μmol/L (18.3 to 20.7 μmol/L). Moreover, neither treatment resulted in “normalization” of tHcy levels (ie, final on-treatment values &lt;12 μmol/L) among a significantly different or clinically meaningful number of patients: MTHF, 2 of 25 (8%); FA, 0 of 25 (0%); Fisher’s exact test of between-groups difference, P =0.490. Conclusions —Relative to high-dose folic acid, high-dose oral l -5-methyltetrahydrofolate–based supplementation does not afford improved tHcy-lowering efficacy in hemodialysis patients. The preponderance of hemodialysis patients (ie, &gt;90%) exhibit mild hyperhomocysteinemia refractory to treatment with either regimen. This treatment refractoriness is not related to defects in folate absorption or circulating plasma and tissue distribution.
The influence of intracellular levels of cyclic nucleotides on cell proliferation and the induction of antibody synthesis.
Authors: J Watson
Journal: The Journal of Experimental Medicine (1975)

The intracellular ratio of adenosine 3',5'-cyclic monophosphate (cyclic AMP) to guanosine 3',5'-cyclic monophosphate (cyclic GMP) may control the developmental pathway followed by antibody-forming cell (AFC) precursors. The evidence for this is derived from several different types of experiments. First lipopolysaccharide (LPS) which is mitogenic for B lymphocytes, stimulates rapid, transient changes in intracellular levels of cyclic GMP but not cyclic AMP when added to mouse spleen cultures. Cyclic GMP itself stimulates DNA synthesis in these cultures, suggesting that the intracellular changes in cyclic GMP levels are involved in the mitogenic signal delivered by LPS to cells. The absolute amounts of cyclic nucleotides may vary widely in different cells under various conditions, however, the intracellular ratio of cyclic AMP to cyclic GMP is always high in nondividing cells and low in dividing cells. AFC precursors appear to respond to antigen in the absence of T-cell activity by inactivation (1-7). In the response to antigen in the presence of specific T cells, precursor cells proliferate and mature to AFC. Raising intracellular levels of cyclic AMP inhibits cell proliferation and leads to precursor cell inactivation (14, 15). It is suggested that the interaction of antigen with immunoglobulin receptors on the surface of precursors cells leads to the stimulation of adenylate cyclase activity and initiates the inactivation pathway. Since cyclic GMP stimulates immune responses in T-cell-depleted cultures (14, 15) and increasing cyclic GMP levels appear to be involved in the delivery of a mitogenic signal to cells, it is suggested that T-helper cells deliver a signal to precursor cells via the stimulation of guanylate cyclase to initiate the inductive pathway. It is suggested that it is the intracellular ratio of cyclic AMP to cyclic GMP that regulates the fate of precursor cells, not the absolute level of one cyclic nucleotide.
Successful treatment of asymptomatic endometriosis: does it benefit infertile women?
Authors: E J Thomas, I D Cooke
Journal: BMJ (1987)

The relation between asymptomatic endometriosis and infertility was investigated in a randomised double blind placebo controlled trial of the impact of treating the endometriosis with gestrinone. The 12 month cumulative conception rate in those patients treated with gestrinone was 25% (5/20) and in those given placebo 24% (4/17). These same patients were divided into those in whom no visible endometriosis was present at the second laparoscopy and those in whom residual disease was present and the 12 month cumulative conception rates were 25% (4/16) and 30% (6/20) respectively. None of these rates differed significantly, and they compared with a rate of 23% (6/26) in a control group of patients with unexplained infertility. Those patients in whom the disease was eliminated did not return to normal fertility, though all other causes of infertility were excluded. This study failed to show any impact of treatment or the absence or presence of asymptomatic endometriosis on future fertility compared with patients with unexplained infertility. The findings therefore question any causal role of the disease in infertility.
Mutation patterns of amino acid tandem repeats in the human proteome.
Authors: Loris Mularoni, Roderic Guigó, M Mar Albà
Journal: Genome biology (2006)

Abstract Background Amino acid tandem repeats are found in nearly one-fifth of human proteins. Abnormal expansion of these regions is associated with several human disorders. To gain further insight into the mutational mechanisms that operate in this type of sequence, we have analyzed a large number of mutation variants derived from human expressed sequence tags (ESTs). Results We identified 137 polymorphic variants in 115 different amino acid tandem repeats. Of these, 77 contained amino acid substitutions and 60 contained gaps (expansions or contractions of the repeat unit). The analysis showed that at least about 21% of the repeats might be polymorphic in humans. We compared the mutations found in different types of amino acid repeats and in adjacent regions. Overall, repeats showed a five-fold increase in the number of gap mutations compared to adjacent regions, reflecting the action of slippage within the repetitive structures. Gap and substitution mutations were very differently distributed between different amino acid repeat types. Among repeats containing gap variants we identified several disease and candidate disease genes. Conclusion This is the first report at a genome-wide scale of the types of mutations occurring in the amino acid repeat component of the human proteome. We show that the mutational dynamics of different amino acid repeat types are very diverse. We provide a list of loci with highly variable repeat structures, some of which may be potentially involved in disease.
CD4+ T cell responses to epitopes of self-heat shock protein 70 in patients with juvenile dermatomyositis
Authors: E. Koffeman, E. Elst, F. van Wijk, B. Prakken, A. van Royen-Kerkhof
Journal: Annals of the Rheumatic Diseases (2011)

<h3>Background and objectives</h3> Juvenile dermatomyositis (JDM) is a childhood disease characterised by inflammation in the muscle and the skin. In several human chronic inflammatory diseases CD4 T cell responses to epitopes of heat shock proteins (hsp) have been found to play a role, both pathogenic and regulatory. In JDM hsp70 is highly up regulated in the inflamed muscle. Therefore, hsp70 could be a target in the inflammatory process in JDM. Responses to hsp70 epitopes in JDM have not yet been characterised. In HLA elution studies it has become clear that epitopes from self-hsp70 are abundantly bound to HLA. In this study the authors tested whether peripheral blood CD4 T cell responses to hsp70-epitopes can be detected and whether they are different in JDM patients compared to healthy controls (HC). <h3>Materials and methods</h3> Hsp70-epitopes were selected based on (1) literature on HLA-elution studies, (2) HLA-class II binding capacity tested with computer models and (3) in vitro responses by CD4 T cells from healthy donors. Proliferation of PBMC from healthy controls (HC, age 2–18) and JDM patients and juvenile idiopathic arthritis patients as disease controls was tested using 3H-thymidine assays and CFSE-staining. Cytokine production was tested by Luminex analysis, flow cytometry and PCR. <h3>Results</h3> The following epitopes were selected: aa 38–52, aa 161–175, aa 290–304 and aa 443–457. These peptides were immunogenic in humans, inducing proliferation or cytokine production. The proliferation of CD4 T cells towards aa 443–457 is increased in JDM. <h3>Conclusion</h3> The authors identified novel epitopes of hsp70 that are immunogenic in healthy donors and JDM and they found indications that the CD4 T cell response towards H443 is increased in JDM.
Induction of Interleukin-6 by Hepatitis C Virus Core Protein in Hepatitis C–Associated Mixed Cryoglobulinemia and B-Cell Non–Hodgkin's Lymphoma
Authors: Georg Feldmann, Hans Dieter Nischalke, Jacob Nattermann, Brigitte Banas, Thomas Berg, Christian Teschendorf, Wolff Schmiegel, Ulrich Dührsen, Juliane Halangk, Agathe Iwan, Tilman Sauerbruch, Wolfgang H. Caselmann, Ulrich Spengler
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Chronic hepatitis C carries the risk to develop mixed cryoglobulinemia (MC) and B-cell non–Hodgkin's lymphoma (B-NHL), possibly because viral antigens stimulate the host's inflammatory response via extracellular pattern recognition receptors (PRR). To clarify this issue, we studied whether recognition of hepatitis C virus (HCV) proteins by PRR is involved in the pathogenesis of HCV-associated MC or B-NHL. Experimental Design: Peripheral blood mononuclear cells of patients with HCV-associated B-NHL (n = 12), MC (n = 14), uncomplicated hepatitis C (n = 12), and healthy volunteers (n = 12) were incubated with the recombinant HCV proteins E2, core, and NS3 to study induction of cytokine production, stimulation of B-cell proliferation, and immunoglobulin secretion. In addition, serum levels of interleukin-6 (IL-6) were measured by ELISA. Results: HCV core was the only studied protein, which induced production of IL-6 and IL-8 in CD14+ cells. IL-6 induction was mediated via Toll-like receptor 2 (TLR2) and lead to increased B-cell proliferation in vitro. TLR2 expression on monocytes and IL-6 serum concentrations were increased in all groups of HCV-infected patients compared with healthy controls and were highest in MC (P &amp;lt; 0.05). Conclusions: Increased secretion of IL-6 via stimulation of TLR2 by HCV core protein may play a role in the pathogenesis of hepatitis C–associated MC and B-NHL.
Favorable Neuroblastoma Genes and Molecular Therapeutics of Neuroblastoma
Authors: Xao X. Tang, Marjorie E. Robinson, Justin S. Riceberg, David Y. Kim, Bing Kung, Tracy B. Titus, Satoshi Hayashi, Alan W. Flake, David Carpentieri, Naohiko Ikegaki
Journal: Clinical Cancer Research (2004)

Abstract Purpose and Experimental Design: Neuroblastoma (NB) is a common pediatric solid tumor that exhibits a striking clinical bipolarity: favorable and unfavorable. Favorable NB genes (EPHB6, EFNB2, EFNB3, NTRK1, and CD44) are genes whose high-level expression predicts favorable NB outcome, and forced expression of these genes inhibits growth of unfavorable NB cells. In this study, we investigated whether favorable NB gene expression could be augmented in unfavorable NB cells by chemical compounds and whether an increased expression of these genes was associated with suppression of NB growth and metastasis. Results: We found that inhibitors of DNA methylation [5-aza-2′-deoxycytidine (5AdC)], histone deacetylase (HDAC) [4-phenylbutyrate (4PB)], and proteasome (MG262) enhanced the expression of favorable NB genes in NB cell lines and inhibited the growth of these cells in vitro (P &amp;lt; 0.0005). The growth-inhibitory effects of 5AdC and 4PB in vitro were in part due to caspase-dependent cell death and inhibition of DNA synthesis. Administration of 5AdC and/or 4PB also suppressed growth of subcutaneous NB xenografts in nude mice (P &amp;lt; 0.001), which was accompanied by enhanced favorable NB gene expression and an increase in apoptosis. Moreover, 4PB suppressed bone marrow and liver metastases of NB cells in severe combined immunodeficient/Beige mice (P = 0.007 and P = 0.008, respectively). The growth-suppressive activity of HDAC inhibitors on NB was further confirmed by the efficacy of trichostatin A, a potent and specific HDAC inhibitor. Conclusions: Collectively, these observations further emphasize the link between the elevated favorable NB gene expression and a benign phenotype of NB.
Acquired carbapenemases in Gram-negative bacterial pathogens: detection and surveillance issues
Authors: V. Miriagou, G. Cornaglia, M. Edelstein, I. Galani, C.G. Giske, M. Gniadkowski, E. Malamou-Lada, L. Martinez-Martinez, F. Navarro, P. Nordmann, L. Peixe, S. Pournaras, G.M. Rossolini, A. Tsakris, A. Vatopoulos, R. Cantón
Journal: Clinical Microbiology and Infection (2010)
PROTECTION AGAINST FATAL RENAL INJURY DUE TO CHOLINE DEFICIENCY BY RENAL DECAPSULATION
Authors: James H. Baxter
Journal: The Journal of Experimental Medicine (1952)

Decapsulation of the left kidney through a lumbar incision immediately prior to placing young rats on a choline-deficient diet afforded a significant degree of protection against animal mortality, compared with that which occurred as a result of the deficiency in the control groups. Decapsulation also was effective in reducing greatly the renal injury which developed in the decapsulated kidneys, as judged by a comparison of the decapsulated kidneys with the contralateral undecapsulated kidneys of the same animals. Decapsulation through an abdominal incision also was efficacious. Decapsulation after 4 or 5 days on the deficient diet, at which time relatively early renal lesions were present in most of the animals, afforded little if any protection. Experiments in which the usual adhesions between the decapsulated kidneys and surrounding tissues were prevented by covering the decapsulated kidneys with artificial capsules demonstrated that protection due to decapsulation could occur in the absence of adhesions. Renal denervation without removal of the renal capsule was not associated with a decrease in renal damage or animal mortality. Possible mechanisms of the protective effect of renal decapsulation in choline deficiency are discussed.