tbuckley/cabot-search huggingface dataset:
Host-Symbiont Conflicts: Positive Selection on an Outer Membrane Protein of Parasitic but not Mutualistic Rickettsiaceae
Authors: Francis M. Jiggins, Gregory D. D. Hurst, Ziheng Yang
Journal: Molecular Biology and Evolution (2002)

The Rickettsiaceae is a family of intracellular bacterial symbionts that includes both vertically transmitted parasites that spread by manipulating the reproduction of their host (Wolbachia in arthropods) and horizontally transmitted parasites (represented by Cowdria ruminantium), and mutualists (Wolbachia pipientis in nematode worms). We have investigated the nature of natural selection acting on an outer membrane protein, the wsp gene in Wolbachia and its homologue map1 in Cowdria, thought likely to be involved in host-parasite interactions in these bacteria. The ratio of nonsynonymous to synonymous substitution rates (dN/dS) at individual amino acid sites or at lineages within the gene's phylogeny was estimated using maximum likelihood models of codon substitution. The first hypothesis we tested was that this protein is under positive selection in the parasitic but not in the mutualistic Rickettsiaceae. This hypothesis was supported as positive selection and was detected in Cowdria and arthropod Wolbachia sequence evolution but not in the evolution of Wolbachia sequences from nematodes. Furthermore, this selection was concentrated outside the transmembrane region of the protein and, therefore, in the regions of the protein that may interact with the host. The second hypothesis tested was that positive selection would be stronger in the strains of arthropod Wolbachia that distort the host sex ratio than in those that induce cytoplasmic incompatibility. However, we found no support for this hypothesis. In conclusion, our results are consistent with the hypothesis that antagonistic coevolution causes faster evolution of surface protein sequences in parasites than in mutualists. Confirmation of this conclusion awaits the replication of these results both in additional genes and across more bacterial taxa. The regions of the wsp and map1 genes we identified as likely to be involved in host-parasite arms races should be examined in future studies of parasite virulence and host immune responses, and during the design of vaccines.
Effects of oral glucosamine sulphate on serum glucose and insulin during an oral glucose tolerance test of subjects with osteoarthritis
Authors: B A Biggee, C M Blinn, M Nuite, J E Silbert, T E McAlindon
Journal: Annals of the Rheumatic Diseases (2006)

and objective: Glucosamine is suggested to affect glucose transport and insulin resistance. The effects of oral glucosamine on serum glucose and insulin levels at the initiation and throughout the duration of a 3-h oral glucose tolerance test were examined.Sera from 16 patients with osteoarthritis, but with no other diagnosed medical condition who had fasted overnight, were obtained every 15-30 min during the 3 h of continued fasting and during the 3 h after ingestion of 75 g of glucose with or without ingestion of 1500 mg of glucosamine sulphate. Glucose was analysed by high-performance liquid chromatography using a Metrohm-Peak 817 Bioscan, and the area under the curve (AUC) for glucose was calculated. Insulin was measured by radioimmunoassay every 30 min for 2 h.Three participants who were found to have previously undiagnosed abnormalities of glucose tolerance demonstrated significant (p = 0.04) incremental elevations in glucose levels after ingestion of glucosamine sulphate. The other 13 participants also had mean incremental elevations that were not significant (p = 0.20). Glucosamine sulphate ingestion had no effect on insulin levels.The results suggest that glucosamine ingestion may affect glucose levels and consequent glucose uptake in patients who have untreated diabetes or glucose intolerance.
Bay K 8644 Increases Resting Ca <sup>2+</sup> Spark Frequency in Ferret Ventricular Myocytes Independent of Ca Influx
Authors: Hiroshi Satoh, Hideki Katoh, Patricio Velez, Michael Fill, Donald M. Bers
Journal: Circulation Research (1998)

Abstract —Bay K 8644, an L-type Ca 2+ channel agonist, was shown previously to increase resting sarcoplasmic reticulum (SR) Ca 2+ loss and convert post-rest potentiation to decay in dog and ferret ventricular muscle. Here, the effects of Bay K 8644 on local SR Ca 2+ release events (Ca 2+ sparks) were measured in isolated ferret ventricular myocytes, using laser scanning confocal microscopy and the fluorescent Ca 2+ indicator fluo-3. The spark frequency under control conditions was fairly constant during 20 s of rest after interruption of electrical stimulation. Bay K 8644 (100 nmol/L) increased the spark frequency by 466±90% of control at constant SR Ca 2+ load but did not change the spatial and temporal characteristics of individual sparks. The increase in spark frequency was maintained throughout the period of rest. The increase in Ca 2+ spark frequency induced by Bay K 8644 was not affected by superfusion with Ca 2+ -free solution (with 10 mmol/L EGTA) but was suppressed by the addition of 10 μmol/L nifedipine (which by itself did not alter resting Ca 2+ spark frequency). This suggests that the effect of Bay K 8644 on Ca 2+ sparks is mediated by the sarcolemmal dihydropyridine receptor but is also independent of Ca 2+ influx. Low concentrations of caffeine (0.5 mmol/L) increased both the average frequency and duration of sparks. Ryanodine (50 nmol/L) increased the spark frequency and also induced long-lasting Ca 2+ signals. This may indicate long-lasting openings of SR Ca 2+ release channels and a lack of local SR Ca 2+ depletion. In lipid bilayers, Bay K 8644 had no effect on either single-channel current amplitude or open probability of the cardiac ryanodine receptor. It is concluded that Bay K 8644 activates SR Ca 2+ release at rest, independent of Ca 2+ influx and perhaps through a functional linkage between the sarcolemmal dihydropyridine receptor and the SR ryanodine receptor. In contrast, caffeine and ryanodine modulate Ca 2+ sparks by a direct action on the SR Ca 2+ release channels.
Mortality Rates Among Early-Stage Hormone Receptor-Positive Breast Cancer Patients: A Population-Based Cohort Study in Denmark
Authors: P. Christiansen, K. Bjerre, B. Ejlertsen, M.-B. Jensen, B. B. Rasmussen, A.-V. Laenkholm, N. Kroman, M. Ewertz, B. Offersen, D. B. Toftdahl, S. Moller, H. T. Mouridsen
Journal: JNCI Journal of the National Cancer Institute (2011)

Indications for adjuvant endocrine treatment of breast cancer have gradually increased over the past several years. We aimed to define subgroups of patients who may or may not benefit from adjuvant endocrine therapy. A population-based cohort of systemically untreated breast cancer patients (N = 3197) were identified within the registry of the Danish Breast Cancer Cooperative Group (DBCG). The patients were node negative and had estrogen receptor–positive and/or progesterone receptor–positive tumors (except medullary tumors) and were further characterized by the following risk factors: aged 35–74 years (grouped into 5-year categories) at surgery, tumor size (≤20 mm), and histopathology (grade 1 ductal carcinoma, grade 1 or 2 invasive lobular carcinoma, other or unknown histopathology). Standardized mortality ratios (SMRs) were calculated based on the mortality rate (observed number of deaths per 100 000 person-years) among patients relative to the mortality rate in the general population of women (expected number of deaths per 100 000 person-years). The association between standardized mortality ratio and risk factors were analyzed in univariate and multivariable Poisson regression models. All findings were validated in a subsequent DBCG cohort of breast cancer patients (N = 2710). The median follow-up after surgery was 14.8 years. In the study population there were 970 deaths compared with expected death of 737 women, which was an excess mortality of 233 deaths (SMR = 1.32, 95% CI = 1.24 to 1.40). Mortality rates were 2356 per 100 000 person-years in the study population and 1790 per 100 000 person-years in the general population of women. The mortality rate was associated with larger tumor size (11–20 mm tumors vs 1–10 mm tumors, SMR = 1.42, 95% confidence interval [CI] = 1.31 to 1.53 vs SMR = 1.12, 95% CI = 1.00 to 1.26). The mortality rate was also associated with age (35–59 years, SMR > 1) compared with that in the general population of age-matched women, except for a small subgroup of patients (aged 60–74 years, tumors ≤10 mm, grade 1 ductal carcinoma, and grade 1 or 2 lobular carcinoma: adjusted relative risk = 1.02, 95% CI = 0.89 to 1.16.). A small subgroup of breast cancer patients who were 60 years or older and had hormone-responsive early-stage tumors up to 10 mm, and received no systemic adjuvant therapy, were not at increased risk of mortality compared with women in this age-group in the general population.
Structured Self-Monitoring of Blood Glucose Significantly Reduces A1C Levels in Poorly Controlled, Noninsulin-Treated Type 2 Diabetes
Authors: William H. Polonsky, Lawrence Fisher, Charles H. Schikman, Deborah A. Hinnen, Christopher G. Parkin, Zhihong Jelsovsky, Bettina Petersen, Matthias Schweitzer, Robin S. Wagner
Journal: Diabetes Care (2011)

To assess the effectiveness of structured blood glucose testing in poorly controlled, noninsulin-treated type 2 diabetes.
A Randomized Trial of Two Weight-Based Doses of Insulin Glargine and Glulisine in Hospitalized Subjects With Type 2 Diabetes and Renal Insufficiency
Authors: David Baldwin, Jennifer Zander, Christina Munoz, Preeya Raghu, Susan DeLange-Hudec, Hong Lee, Mary Ann Emanuele, Valerie Glossop, Kimberly Smallwood, Mark Molitch
Journal: Diabetes Care (2012)

Renal insufficiency may increase the risk of hypoglycemia in hospitalized patients with diabetes who are treated with insulin. We randomized inpatients with type 2 diabetes and chronic renal failure to treatment with two different dose levels of insulin glargine and glulisine and studied control of hyperglycemia and the frequency of hypoglycemia.We conducted a multicenter, prospective, randomized trial to compare the efficacy of once-daily glargine and three-times daily glulisine at 0.5 vs. 0.25 units/kg/day. A total of 107 subjects had type 2 diabetes for >1 year, had a glomerular filtration rate <45 mL/min but did not require dialysis, and had an initial blood glucose (BG) >180 mg/dL. Doses were adjusted based on four-times daily BG measurements for 6 days.Mean BG on the first day was 196 ± 71 mg/dL in the group receiving 0.5 units/kg (0.5 group) and 197 ± 55 mg/dL in the group receiving 0.25 units/kg (0.25 group; P = 0.94). On days 2 to 6, mean BG was 174 ± 52 mg/dL in the 0.5 group and 174 ± 46 mg/dL in the 0.25 group (P = 0.96). There were no significant differences between groups in the percentage of BG values within the target range of 100 to 180 mg/dL on any of the 6 study days. In the 0.5 group, 30% experienced hypoglycemia (BG <70 mg/dL) compared with 15.8% of the 0.25 group (P = 0.08).Reduction of initial glargine/glulisine insulin weight-based dosing in hospitalized patients with diabetes and renal insufficiency reduced the frequency of hypoglycemia by 50% without compromising the control of hyperglycemia.
Loci Identified by Genome-wide Association Studies Influence Different Disease-related Phenotypes in Chronic Obstructive Pulmonary Disease
Authors: Sreekumar G. Pillai, Xiangyang Kong, Lisa D. Edwards, Michael H. Cho, Wayne H. Anderson, Harvey O. Coxson, David A. Lomas, Edwin K. Silverman
Journal: American Journal of Respiratory and Critical Care Medicine (2010)

Genome-wide association studies have shown significant associations between variants near hedgehog interacting protein HHIP, FAM13A, and cholinergic nicotinic acetylcholine receptor CHRNA3/5 with increased risk of chronic obstructive pulmonary disease (COPD) in smokers; however, the disease mechanisms behind these associations are not well understood.To identify the association between replicated loci and COPD-related phenotypes in well-characterized patient populations.The relationship between these three loci and COPD-related phenotypes was assessed in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-point (ECLIPSE) cohort. The results were validated in the family-based International COPD Genetics Network (ICGN).The CHRNA3/5 locus was significantly associated with pack-years of smoking (P = 0.002 and 3 × 10⁻⁴), emphysema assessed by a radiologist using high-resolution computed tomography (P = 2 × 10⁻⁴ and 4.8 × 10⁻⁵), and airflow obstruction (P = 0.004 and 1.8 × 10⁻⁵) in the ECLIPSE and ICGN populations, respectively. However, variants in the IREB2 gene were only significantly associated with FEV₁. The HHIP locus was not associated with smoking intensity but was associated with FEV₁/FVC (P = 1.9 × 10⁻⁴ and 0.004 in the ECLIPSE and ICGN populations). The HHIP locus was also associated with fat-free body mass (P = 0.007) and with both retrospectively (P = 0.015) and prospectively (P = 0.024) collected COPD exacerbations in the ECLIPSE cohort. Single-nucleotide polymorphisms in the FAM13A locus were associated with lung function.The CHRNA3/5 locus was associated with increased smoking intensity and emphysema in individuals with COPD, whereas the HHIP and FAM13A loci were not associated with smoking intensity. The HHIP locus was associated with the systemic components of COPD and with the frequency of COPD exacerbations. FAM13A locus was associated with lung function.
Parathyroid Hormone 7-84 Induces Hypocalcemia and Inhibits the Parathyroid Hormone 1-84 Secretory Response to Hypocalcemia in Rats with Intact Parathyroid Glands
Authors: Jinxing Huan, Klaus Olgaard, Lars Bo Nielsen, Ewa Lewin
Journal: Journal of the American Society of Nephrology (2006)

Biologic effects of large C-terminal parathyroid hormone (PTH) fragments, opposite to those of N-terminal PTH, have been demonstrated. C-terminal PTH fragments are co-secreted with N-terminal PTH from the parathyroids. The aim of our study was to examine whether C-terminal PTH 7-84 regulates secretion of PTH 1-84 and affects the expression of genes of relevance for parathyroid function, PTH, calcium-sensing receptor (CaR), PTH type 1 receptor (PTHR1), and PTH-related peptide (PTHrP) genes in rat parathyroid glands. PTH 7-84 induced a significant decrease in plasma Ca2+ in rats with intact parathyroid glands. Despite the reduction of plasma Ca2+, no stimulation of PTH 1-84 secretion took place. Furthermore, the PTH 1-84 secretory response to EGTA-induced acute and severe hypocalcemia was significantly inhibited by PTH 7-84. During recovery from hypocalcemia, plasma Ca2+ levels were significantly lower in the PTH 7-84–treated group, as compared with the vehicle group, and at the same time plasma PTH 1-84 levels were significantly suppressed. The expression of PTH, CaR, PTHR1, and PTHrP genes in the rat parathyroid glands was not affected by PTH 7-84. The peripheral metabolism of PTH 1-84 was not affected by PTH 7-84. PTH 7-84 did not cross-react with the rat bioactive PTH 1-84 assay. In normal rats with intact parathyroid glands, PTH 7-84 inhibited the PTH 1-84 secretory response to hypocalcemia and induced a significant decrease in plasma Ca2+. These effects of PTH 7-84 on PTH 1-84 secretion and on plasma Ca2+ levels were not associated with significant changes in PTH, PTHR1, CaR, and PTHrP gene expressions in the rat parathyroid glands. It is hypothesized that PTH 7-84 regulates PTH secretion via an autocrine/paracrine regulatory mechanism.
Update in Chronic Obstructive Pulmonary Disease 2007
Authors: William MacNee
Journal: American Journal of Respiratory and Critical Care Medicine (2008)

There is intense scientific and clinical interest in chronic obstructive pulmonary disease (COPD), which is reflected in the increasing number of articles in scientific journals on this topic. There have been advances in our understanding of the pathogenesis, diagnosis, and assessment and in the applications of current treatments in COPD, but not in the development of new treatments for COPD, particularly those that might retard or reverse its progression.
Assessment of methodological quality of primary studies by systematic reviews: results of the metaquality cross sectional study
Authors: Lorenzo P Moja, Elena Telaro, Roberto D'Amico, Ivan Moschetti, Laura Coe, Alessandro Liberati
Journal: BMJ (2005)

<h3>Abstract</h3> <b>Objectives</b> To describe how the methodological quality of primary studies is assessed in systematic reviews and whether the quality assessment is taken into account in the interpretation of results. <b>Data sources</b> Cochrane systematic reviews and systematic reviews in paper based journals. <b>Study selection</b> 965 systematic reviews (809 Cochrane reviews and 156 paper based reviews) published between 1995 and 2002. <b>Data synthesis</b> The methodological quality of primary studies was assessed in 854 of the 965 systematic reviews (88.5%). This occurred more often in Cochrane reviews than in paper based reviews (93.9% <i>v</i> 60.3%, P &lt; 0.0001). Overall, only 496 (51.4%) used the quality assessment in the analysis and interpretation of the results or in their discussion, with no significant differences between Cochrane reviews and paper based reviews (52% <i>v</i> 49%, P = 0.58). The tools and methods used for quality assessment varied widely. <b>Conclusions</b> Cochrane reviews fared better than systematic reviews published in paper based journals in terms of assessment of methodological quality of primary studies, although they both largely failed to take it into account in the interpretation of results. Methods for assessment of methodological quality by systematic reviews are still in their infancy and there is substantial room for improvement.
The survival time of chocolates on hospital wards: covert observational study
Authors: P. R. Gajendragadkar, D. J. Moualed, P. L. R. Nicolson, F. D. Adjei, H. E. Cakebread, R. M. Duehmke, C. A. Martin
Journal: BMJ (2013)

<b>Objective</b> To quantify the consumption of chocolates in a hospital ward environment. <b>Design</b> Multicentre, prospective, covert observational study. <b>Setting</b> Four wards at three hospitals (where the authors worked) within the United Kingdom. <b>Participants</b> Boxes of Quality Street (Nestlé) and Roses (Cadbury) on the ward and anyone eating these chocolates. <b>Intervention</b> Observers covertly placed two 350 g boxes of Quality Street and Roses chocolates on each ward (eight boxes were used in the study containing a total of 258 individual chocolates). These boxes were kept under continuous covert surveillance, with the time recorded when each chocolate was eaten. <b>Main outcome measure</b> Median survival time of a chocolate. <b>Results</b> 191 out of 258 (74%) chocolates were observed being eaten. The mean total observation period was 254 minutes (95% confidence interval 179 to 329). The median survival time of a chocolate was 51 minutes (39 to 63). The model of chocolate consumption was non-linear, with an initial rapid rate of consumption that slowed with time. An exponential decay model best fitted these findings (model R<sup>2</sup>=0.844, P&lt;0.001), with a survival half life (time taken for 50% of the chocolates to be eaten) of 99 minutes. The mean time taken to open a box of chocolates from first appearance on the ward was 12 minutes (95% confidence interval 0 to 24). Quality Street chocolates survived longer than Roses chocolates (hazard ratio for survival of Roses <i>v</i> Quality Street 0.70, 95% confidence interval 0.53 to 0.93, P=0.014). The highest percentages of chocolates were consumed by healthcare assistants (28%) and nurses (28%), followed by doctors (15%). <b>Conclusions</b> From our observational study, chocolate survival in a hospital ward was relatively short, and was modelled well by an exponential decay model. Roses chocolates were preferentially consumed to Quality Street chocolates in a ward setting. Chocolates were consumed primarily by healthcare assistants and nurses, followed by doctors. Further practical studies are needed.
Treatment of post-partum haemorrhage with sublingual misoprostol versus oxytocin in women receiving prophylactic oxytocin: a double-blind, randomised, non-inferiority trial
Authors: Jennifer Blum, Beverly Winikoff, Sheila Raghavan, Rasha Dabash, Mohamed Cherine Ramadan, Berna Dilbaz, Blami Dao, Jill Durocher, Serdar Yalvac, Ayisha Diop, Ilana G Dzuba, Nguyen Thi Nhu Ngoc
Journal: The Lancet (2010)
Elevated Plasma Glucose-Dependent Insulinotropic Polypeptide Associates With Hyperinsulinemia in Impaired Glucose Tolerance
Authors: Michael J. Theodorakis, Olga Carlson, Denis C. Muller, Josephine M. Egan
Journal: Diabetes Care (2004)

OBJECTIVE—The role of gut-derived incretin, glucose-dependent insulinotropic polypeptide (also known as gastric inhibitory peptide [GIP]), in compensatory β-cell hypersecretion during insulin-resistant states and in transition to β-cell failure in type 2 diabetes is unknown. RESEARCH DESIGN AND METHODS—We carried out oral glucose tolerance testing followed by blood sampling 10 times for 2 h on 68 age- and BMI-matched participants of the Baltimore Longitudinal Study on Aging (BLSA) with normal glucose tolerance (34 subjects), impaired glucose tolerance (IGT) (18 subjects with both impaired fasting and 2-h plasma glucose levels), and type 2 diabetes (16 subjects with both diabetic fasting and 2-h plasma glucose levels). We assayed plasma glucose, insulin, C-peptide, glucagon, and intact and total GIP levels and quantitated glucose and hormone responses to the oral glucose tolerance test. We also compared GIP and insulin release and sensitivity indexes between groups. RESULTS—After glucose ingestion, subjects with IGT had both hyperinsulinemia and hyperemia, while subjects with type 2 diabetes had both β- and GIP-cell deficiency. In the former group, there was also a significant positive correlation between the augmented plasma intact and total GIP levels and both fasting and post-oral glucose load plasma insulin levels. CONCLUSIONS— Elevated plasma GIP levels are correlated with hyperinsulinemia in the impaired glucose-tolerant state, whereas type 2 diabetes is associated with a failure to secrete adequate amounts of both GIP and insulin, indicating a common pathway of resistance to and eventually failure of glucose responsiveness in β- and GIP-cells.
Fast foods – are they a risk factor for asthma?
Authors: K. Wickens, D. Barry, A. Friezema, R. Rhodius, N. Bone, G. Purdie, J. Crane
Journal: Allergy (2005)

Lifestyle changes over the last 30 years are the most likely explanation for the increase in allergic disease over this period.This study tests the hypothesis that the consumption of fast food is related to the prevalence of asthma and allergy.As part of the International Study of Asthma and Allergies in Childhood (ISAAC) a cross-sectional prevalence study of 1321 children (mean age = 11.4 years, range: 10.1-12.5) was conducted in Hastings, New Zealand. Using standard questions we collected data on the prevalence of asthma and asthma symptoms, as well as food frequency data. Skin prick tests were performed to common environmental allergens and exercise-induced bronchial hyperresponsiveness (BHR) was assessed according to a standard protocol. Body mass index (BMI) was calculated as weight/height2 (kg/m2) and classified into overweight and obese according to a standard international definition.After adjusting for lifestyle factors, including other diet and BMI variables, compared with children who never ate hamburgers, we found an independent risk of hamburger consumption on having a history of wheeze [consumption less than once a week (OR = 1.44, 95% CI: 1.06-1.96) and 1+ times a week (OR = 1.65, 95% CI: 1.07-2.52)] and on current wheeze [consumption less than once a week (OR = 1.17, 95% CI: 0.80-1.70) and 1+ times a week (OR = 1.81, 95% CI: 1.10-2.98)]. Takeaway consumption 1+ times a week was marginally significantly related to BHR (OR = 2.41, 95% CI: 0.99-5.91). There was no effect on atopy.Frequent consumption of hamburgers showed a dose-dependent association with asthma symptoms, and frequent takeaway consumption showed a similar association with BHR.