tbuckley/cabot-search huggingface dataset:
Desensitization of vascular endothelin receptors by G protein-coupled receptor kinase 2
Authors: Y.-J. Gao
Journal: Cardiovascular Research (2009)

At the heart of receptor-mediated signal transduction are two intertwined processes: translation of signals carried by stimulating agents to cells through intracellular messenger molecules and termination/restriction of signalling by cells. The latter is a critical mechanism that protects cells from overreacting to an extended or appropriate stimulus and makes cells ready to react to forthcoming stimulation. G protein-coupled receptors (GPCRs) are a family of receptors composed of seven transmembrane domains that respond to various stimuli. GPCRs usually undergo rapid desensitization after activation, in which GPCR kinases (GRKs), a family consisting of seven members (GRK 1–7), play a critical role.1

Endothelins (ETs) are a family of peptides comprising ET1, ET2, and ET3.2 ETs exert their actions through two types of receptors, ETA and ETB, which belong to the GPCR family.3 Activation of ETA receptors results in vasoconstriction through the generation of 1,4,5-inositol trisphosphate and diacylglycerol as intracellular messengers, which, in turn, trigger intracellular Ca2+ release and protein kinase C activation. Among the ET family members, ET1 is a potent vasoconstrictor that induces contraction at nanomolar concentrations in several vascular beds.3 Significant desensitization of ET1-induced cellular response was soon reported after ET was discovered in 1988,4 but the underlying mechanisms were not fully understood.

Morris … 

*Corresponding author. Tel: +1 905 525 9140 Extn 22477; Fax: +1 905 523 1224. E-mail address : gaoyu{at}mcmaster.ca
A Controlled Trial of Homocysteine Lowering and Cognitive Performance
Authors: Jennifer A. McMahon, Timothy J. Green, C. Murray Skeaff, Robert G. Knight, Jim I. Mann, Sheila M. Williams
Journal: New England Journal of Medicine (2006)

The results of observational studies suggest that plasma homocysteine concentrations are inversely related to cognitive function in older people. Our objective was to test the hypothesis that lowering the plasma homocysteine concentration improves cognitive function in healthy older people.We conducted a two-year, double-blind, placebo-controlled, randomized clinical trial involving 276 healthy participants, 65 years of age or older, with plasma homocysteine concentrations of at least 13 micromol per liter. Homocysteine-lowering treatment was a daily supplement containing folate (1000 microg) and vitamins B12 (500 microg) and B6 (10 mg). Tests of cognition were conducted at baseline and after one and two years of treatment. Treatment effects were adjusted for baseline values, sex, and education.On average, during the course of the study, the plasma homocysteine concentration was 4.36 micromol per liter (95 percent confidence interval, 3.81 to 4.91 micromol per liter) lower in the vitamin group than in the placebo group (P<0.001). Overall, there were no significant differences between the vitamin and placebo groups in the scores on tests of cognition.The results of this trial do not support the hypothesis that homocysteine lowering with B vitamins improves cognitive performance. (Australian Clinical Trials registry number, ACTR NO 12605000030673.).
The Preventive Surgical Site Infection Bundle in Colorectal Surgery
Authors: Jeffrey E. Keenan, Paul J. Speicher, Julie K. M. Thacker, Monica Walter, Maragatha Kuchibhatla, Christopher R. Mantyh
Journal: JAMA Surgery (2014)

Surgical site infections (SSIs) in colorectal surgery are associated with increased morbidity and health care costs.To determine the effect of a preventive SSI bundle (hereafter bundle) on SSI rates and costs in colorectal surgery.Retrospective study of institutional clinical and cost data. The study period was January 1, 2008, to December 31, 2012, and outcomes were assessed and compared before and after implementation of the bundle on July 1, 2011.Academic tertiary referral center among 559 patients who underwent major elective colorectal surgery.The primary outcome was the rate of superficial SSIs before and after implementation of the bundle. Secondary outcomes included deep SSIs, organ-space SSIs, wound disruption, postoperative sepsis, length of stay, 30-day readmission, and variable direct costs of the index admission.Of 559 patients in the study, 346 (61.9%) and 213 (38.1%) underwent their operation before and after implementation of the bundle, respectively. Groups were matched on their propensity to be treated with the bundle to account for significant differences in the preimplementation and postimplementation characteristics. Comparison of the matched groups revealed that implementation of the bundle was associated with reduced superficial SSIs (19.3% vs 5.7%, P < .001) and postoperative sepsis (8.5% vs 2.4%, P = .009). No significant difference was observed in deep SSIs, organ-space SSIs, wound disruption, length of stay, 30-day readmission, or variable direct costs between the matched groups. However, in a subgroup analysis of the postbundle period, superficial SSI occurrence was associated with a 35.5% increase in variable direct costs ($13,253 vs $9779, P = .001) and a 71.7% increase in length of stay (7.9 vs 4.6 days, P < .001).The preventive SSI bundle was associated with a substantial reduction in SSIs after colorectal surgery. The increased costs associated with SSIs support that the bundle represents an effective approach to reduce health care costs.
Epidemiology of microscopic colitis * Authors' response
Authors: F. Fernandez-Banares, M. Esteve, J. M. Viver, D. S Pardi, E. V Loftus, L J. Melton, A. R Zinsmeister
Journal: Gut (2007)

<h3>BACKGROUND AND PURPOSE:</h3> Bony internal auditory canal diverticula are relatively common, occurring in approximately 5% of temporal bone CTs. Internal auditory canal diverticula have historically been considered incidental; however, a recent publication reported that internal auditory canal diverticula are associated with sensorineural hearing loss. The objective of this study was to further characterize this potential association in a large cohort of patients. <h3>MATERIALS AND METHODS:</h3> A total of 1759 patients undergoing high-resolution temporal bone CT were collected during a 6-year interval, and audiometric data were obtained from those with internal auditory canal diverticula. To assess any association of isolated internal auditory canal diverticula with sensorineural hearing loss, we excluded from further analysis patients with concomitant otosclerosis and bilateral diverticula and those without audiometric data, leaving 22 index cases. Audiometric data for the ear with a diverticulum was compared with that in the contralateral ear, to serve as an internal control. <h3>RESULTS:</h3> Of 1759 patients, 82 (4.7%) had either unilateral (<i>n</i> = 33, 40%) or bilateral (<i>n</i> = 49, 60%) internal auditory canal diverticula. The co-incidence of otosclerosis and internal auditory canal diverticula was 34% (<i>n</i> = 28). There was no correlation between patient age and diverticulum size on either side. Among the index cases with isolated unilateral internal auditory canal diverticula and complete audiometric data, word recognition scores and the prevalence and severity of sensorineural hearing loss were not significantly different comparing the internal auditory canal diverticulum side to its contralateral control. <h3>CONCLUSIONS:</h3> This study did not find a statistically significant association between ears with internal auditory canal diverticula and worsening sensorineural hearing loss or word recognition. Internal auditory canal diverticula most likely represent a normal anatomic variant in ears without otosclerosis.
Novel<i>FH</i>mutation in a patient with cutaneous leiomyomatosis associated with cutis verticis gyrata, eruptive collagenoma and Charcot-Marie-Tooth disease
Authors: M. Marque, B. Gardie, B. Bressac de Paillerets, P. Rustin, B. Guillot, S. Richard, D. Bessis
Journal: British Journal of Dermatology (2010)

Journal Article Novel FH mutation in a patient with cutaneous leiomyomatosis associated with cutis verticis gyrata, eruptive collagenoma and Charcot‐Marie‐Tooth disease Get access M. Marque, M. Marque Service de Dermatologie, Université de Montpellier 1, CHU Montpellier, Montpellier, France Correspondence: Myriam Marque. E‐mail: myriammarque@yahoo.fr Search for other works by this author on: Oxford Academic Google Scholar B. Gardie, B. Gardie Génétique Oncologique EPHE, INSERM U753, Institut de Cancérologie Gustave Roussy, Villejuif, and Faculté de Médecine Paris‐Sud, Le Kremlin‐Bicêtre, France Search for other works by this author on: Oxford Academic Google Scholar B. Bressac de Paillerets, B. Bressac de Paillerets Service de Génétique et FRE2939 CNRS, Institut de Cancérologie Gustave Roussy, Villejuif, FranceCentre de Référence PREDIR et Réseau National 'Maladie de VHL et Prédispositions Héréditaires au Cancer Rénal' INCa/AP‐HP, Service d'Urologie, CHU de Bicêtre, Le Kremlin‐Bicêtre, France Search for other works by this author on: Oxford Academic Google Scholar P. Rustin, P. Rustin INSERM U676, Hôpital Robert Debré, Paris, France Search for other works by this author on: Oxford Academic Google Scholar B. Guillot, B. Guillot Service de Dermatologie, Université de Montpellier 1, CHU Montpellier, Montpellier, France Search for other works by this author on: Oxford Academic Google Scholar S. Richard, S. Richard Génétique Oncologique EPHE, INSERM U753, Institut de Cancérologie Gustave Roussy, Villejuif, and Faculté de Médecine Paris‐Sud, Le Kremlin‐Bicêtre, FranceCentre de Référence PREDIR et Réseau National 'Maladie de VHL et Prédispositions Héréditaires au Cancer Rénal' INCa/AP‐HP, Service d'Urologie, CHU de Bicêtre, Le Kremlin‐Bicêtre, France Search for other works by this author on: Oxford Academic Google Scholar D. Bessis D. Bessis Service de Dermatologie, Université de Montpellier 1, CHU Montpellier, Montpellier, FranceCentre de Référence PREDIR et Réseau National 'Maladie de VHL et Prédispositions Héréditaires au Cancer Rénal' INCa/AP‐HP, Service d'Urologie, CHU de Bicêtre, Le Kremlin‐Bicêtre, France Search for other works by this author on: Oxford Academic Google Scholar British Journal of Dermatology, Volume 163, Issue 6, 1 December 2010, Pages 1337–1339, https://doi.org/10.1111/j.1365-2133.2010.09912.x Published: 01 December 2010
Medical Ethics: Some Uses, Abuses, and Limitations
Authors: K. Danner Clouser
Journal: New England Journal of Medicine (1975)

Abstract A backlash against medical ethics may be developing because of a misunderstanding of its purpose and limitations. A primary role of medical ethics is to "structure" the disputed issues — i.e., by detailing the relevant principles and implications, analyzing the pivotal concepts, and focusing on the relevant facts. Medical ethics is limited by being unable to discriminate finely, so that a single line of action can seldom be determined by moral criteria alone. Underlying many criticisms of medical ethics is the failure to realize that medical ethics as such is not a reform movement or an effort to inspire moral behavior, that it is not and cannot be a specialist's body of esoteric knowledge, that it requires facts and conceptual analyses from other fields to do its work, and that value arguments can be carried farther than one generally expects. (N Engl J Med 293:384–387 1975)
Inhibition of casein kinase 1-epsilon induces cancer-cell-selective, PERIOD2-dependent growth arrest
Authors: Wan Seok Yang, Brent R Stockwell
Journal: Genome biology (2008)

Kinases are under extensive investigation as targets for drug development. Discovering novel kinases whose inhibition induces cancer-cell-selective lethality would be of value. Recent advances in RNA interference have enabled the realization of this goal. We screened 5,760 short hairpin RNA clones targeting the human kinome to detect human kinases on which cancer cells are more dependent than normal cells. We employed a two-step screening strategy using human sarcoma cell lines and human fibroblast-derived isogenic cell lines, and found that short hairpin RNAs targeting CSNK1E, a clock gene that regulates circadian rhythms, can induce selective growth inhibition in engineered tumor cells. Analysis of gene-expression data revealed that CSNK1E is overexpressed in several cancer tissue samples examined compared to non-tumorigenic normal tissue, suggesting a positive role of CSNK1E in neogenesis or maintenance. Treatment with IC261, a kinase domain inhibitor of casein kinase 1-epsilon (CK1ε), a protein product of CSNK1E, showed a similar degree of cancer-cell-selective growth inhibition. In a search for substrates of CK1ε that mediate IC261-induced growth inhibition, we discovered that knocking down PER2, another clock gene involved in circadian rhythm control, rescues IC261-induced growth inhibition. We identified CK1ε as a potential target for developing anticancer reagents with a high therapeutic index. These data support the hypothesis that circadian clock genes can control the cell cycle and cell survival signaling, and emphasize a central role of CK1ε and PERIOD2 in linking these systems.
Beliefs of People With Diabetes About Skin Prick During Ramadan Fasting
Authors: Shabeen Naz Masood, Muhammad Adil Sheikh, Yasir Masood, Rubina Hakeem, A. Samad Shera
Journal: Diabetes Care (2014)

A large number of adult Muslims choose to fast during the month of Ramadan. The Ramadan fasting lasts 29–30 days, depending on the sighting of the moon. The duration of the fast can be 12–19 h, depending on the regional equatorial position. People with serious illness and long-distance travelers are exempted from fasting, but they have to fast after Ramadan to complete the missed days, except for those with serious disease (1). Most of the people with chronic diseases such as diabetes do not like to quit fasting. Studies show that individuals are exposed to risks if they do not modify their lifestyle and monitor their blood glucose during the Ramadan fasting (2–4).

A retrospective observational study was planned to assess the existing beliefs and practices of people with diabetes about skin prick …
Prospective multicentre study on antibiotic resistance of Helicobacter pylori strains obtained from children living in Europe
Authors: S Koletzko, F Richy, P Bontems, J Crone, N Kalach, M L Monteiro, F Gottrand, D Celinska-Cedro, E Roma-Giannikou, G Orderda, S Kolacek, P Urruzuno, M J Martinez-Gomez, T Casswall, M Ashorn, H Bodanszky, F Megraud
Journal: Gut (2006)

<b>Aim:</b> To prospectively assess the antibacterial resistance rate in <i>Helicobacter pylori</i> strains obtained from symptomatic children in Europe. <b>Methods:</b> During a 4-year period, 17 paediatric centres from 14 European countries reported prospectively on patients infected with <i>H pylori</i>, for whom antibiotic susceptibility was tested. <b>Results:</b> A total of 1233 patients were reported from Northern (3%), Western (70%), Eastern (9%) and Southern Europe (18%); 41% originated from outside Europe as indicated by mother's birth-country; 13% were &lt;6 years of age, 43% 6–11 years of age and 44% &gt;11 years of age. Testing was carried out before the first treatment (group A, n = 1037), and after treatment failure (group B, n = 196). Overall resistance to clarithromycin was detected in 24% (mean, A: 20%, B: 42%). The primary clarithromycin resistance rate was higher in boys (odds ratio (OR) 1.58; 1.12 to 2.24, p = 0.01), in children &lt;6 years compared with &gt;12 years (OR 1.82, 1.10 to 3.03, p = 0.020) and in patients living in Southern Europe compared with those living in Northern Europe (OR 2.25; 1.52 to 3.30, p&lt;0.001). Overall resistance rate to metronidazole was 25% (A: 23%, B: 35%) and higher in children born outside Europe (A: adjusted. OR 2.42, 95% CI: 1.61 to 3.66, p&lt;0.001). Resistance to both antibiotics occurred in 6.9% (A: 5.3%, B: 15.3%). Resistance to amoxicillin was exceptional (0.6%). Children with peptic ulcer disease (80/1180, 6.8%) were older than patients without ulcer (p = 0.001). <b>Conclusion:</b> The primary resistance rate of <i>H pylori</i> strains obtained from unselected children in Europe is high. The use of antibiotics for other indications seems to be the major risk factor for development of primary resistance.
Culture in whales and dolphins
Authors: Luke Rendell, Hal Whitehead
Journal: Behavioral and Brain Sciences (2001)

Studies of animal culture have not normally included a consideration of cetaceans. However, with several long-term field studies now maturing, this situation should change. Animal culture is generally studied by either investigating transmission mechanisms experimentally, or observing patterns of behavioural variation in wild populations that cannot be explained by either genetic or environmental factors. Taking this second, ethnographic, approach, there is good evidence for cultural transmission in several cetacean species. However, only the bottlenose dolphin (Tursiops) has been shown experimentally to possess sophisticated social learning abilities, including vocal and motor imitation; other species have not been studied. There is observational evidence for imitation and teaching in killer whales. For cetaceans and other large, wide-ranging animals, excessive reliance on experimental data for evidence of culture is not productive; we favour the ethnographic approach. The complex and stable vocal and behavioural cultures of sympatric groups of killer whales (Orcinus orca) appear to have no parallel outside humans, and represent an independent evolution of cultural faculties. The wide movements of cetaceans, the greater variability of the marine environment over large temporal scales relative to that on land, and the stable matrilineal social groups of some species are potentially important factors in the evolution of cetacean culture. There have been suggestions of gene-culture coevolution in cetaceans, and culture may be implicated in some unusual behavioural and life-history traits of whales and dolphins. We hope to stimulate discussion and research on culture in these animals.
Helicobacter pylori stimulates antral mucosal reactive oxygen metabolite production in vivo.
Authors: G R Davies, N J Simmonds, T R Stevens, M T Sheaff, N Banatvala, I F Laurenson, D R Blake, D S Rampton
Journal: Gut (1994)

To determine if reactive oxygen metabolites have a pathogenic role in Helicobacter pylori (H pylori) related gastroduodenal disease, this study measured their production in antral mucosal biopsy specimens. Two related chemiluminescence techniques were used comparing H pylori positive (n = 105) and negative patients (n = 64) with a similar spectrum of macroscopic disease. After chemiluminescence assays, biopsy specimens were graded histologically. Increased luminol dependent chemiluminescence (detecting reactive oxygen metabolites through peroxidase catalysed reactions) was found in H pylori positive patients (median photon emission = 6.4 x 10(3)/min/mg wet weight (95% confidence intervals 3.6 to 9.9)) but not H pylori negative cases (-0.9 (-1.3 to -0.6)) (p = 0.0001). Similar results were found using lucigenin (which reacts directly with oxygen metabolites, particularly superoxide): (H pylori positive 0.9 (0.1 to 3.2); H pylori negative -1.2 (-3.4 to -0.6)) (p = 0.0003). Chemiluminescence was greater in H pylori positive compared with negative tissue when samples were grouped by equivalent macroscopic or microscopic damage. This difference was in part accounted for by a greater neutrophil infiltration in the H pylori positive mucosa, but when biopsy specimens with equivalent neutrophil infiltration could be compared directly, positive specimens gave greater chemiluminescence than negative. Smoking, drugs, and alcohol consumption had no independent effect. It is concluded that excess mucosal reactive oxygen metabolite production is associated with H pylori gastric antral infection and may be an important pathogenic mechanism. There is no evidence for reactive oxygen metabolite participation in the pathogenesis of gastric mucosal injury in cases unrelated to H pylori infection.
Thrombelastographic Studies with a Twenty-Four-Hour Schedule for Subcutaneous Heparin
Authors: ROBERT S. ELIOT, KURT N. VON KAULLA, S. GILBERT BLOUNT
Journal: Circulation (1961)

In 55 patients 430 thrombelastographic studies after 305 heparin injections revealed that a more complete and more rapid reduction of the over-all coagulability of the blood is obtained by a subcutaneous injection of 40 per cent heparin once every 24 hours than that obtained with prothrombin-depressing agents. The individual dose, by the thrombelastographic technic, is between 3.5 and 4.5 mg./Kg. Further clinical studies are indicated with use of simple laboratory control technics, such as recalcification time.
Application of a new mass-spectrometric platform for determination of lipid mediators in urine reveals increased oxidative stress during allergen bronchoprovocation of subjects with atopic asthma
Authors: David Balgoma, Kameran Daham, Johan Larsson, Agneta Lindeberg, Barbro Dahlén, Joshua Rokach, Craig Wheelock, Sven-Erik Dahlén
Journal: European Respiratory Journal (2012)

Background: Traditionally, mechanisms in allergen-induced bronchoconstriction have been investigated by measurement of a few metabolites of lipid mediators (LMs) in urine. Mass spectrometry enables quantification of a wider panel of compounds per analysis. We applied a new platform that included isoprostanes (IPs), markers of oxidative stress.

Aim: To assess the levels of IPs in urine before and after allergen provocation in asthma patients.

Methods: Eighteen subjects with mild atopic asthma and airway hyperresponsiveness to methacholine were challenged with allergen to produce at least a 20% drop in FEV1. Urine was collected before and after the provocation. Metabolites were extracted and analyzed by a new mass spectrometry platform. Data were normalized per mmol of creatinine.

Results(Fig 1): As expected, metabolites of prostaglandin D2, thromboxane A2, and leukotriene E4 increased after the provocation. However, two IPs (2,3-dinor-8-isoPGF2α and 8,12-iPF2α-VI) also increased significantly. Multivariate analysis showed gender differences in basal levels, potentially due to higher excretion of creatinine by males.

![Figure][1] 



![Figure][1] 



Conclusions: We discovered that allergen provocation of atopic asthmatics increased the level of oxidative stress, suggesting that IPs might represent a new target for therapeutic intervention.

 [1]: pending:yes