bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical practice patterns among native and immigrant doctors doing out-of-hours work in Norway: a registry-based observational study
Authors: Sandvik Hogne , Hunskaar Steinar , Diaz Esperanza 
Published: July 2012

ObjectivesTo evaluate whether immigrant and native Norwegian doctors differ in their practice patterns.DesignObservational study.SettingOut-of-hours (OOH) emergency primary healthcare in Norway, 2008.ParticipantsAll primary care physicians doing OOH work, altogether 4165 physicians.Main outcome measuresNumber of patient contacts per doctor. Use of laboratory tests, minor surgery, sickness certification and length of consultations. Use of diagnoses related to psychiatric and sexual health. Choice of management strategy with psychiatric patients (psychotherapy or hospitalisation).Results21.4% of the physicians were immigrants, and they had 30.6% of the patient contacts. Immigrant doctors from Asia, Africa and Latin America had most patient contacts, 633 (95% CI 549 to 716), while native Norwegian doctors had 306 (95% CI 288 to 325). In multivariate analyses, immigrant physicians did not differ significantly from native Norwegians regarding use of laboratory tests, minor surgery or length of consultations, but immigrant doctors wrote more sickness certificates, OR 1.75 (95% CI 1.24 to 2.47) for immigrant doctors from Europe, North America and Oceania versus native Norwegian doctors and OR 1.56 (95% CI 1.15 to 2.11) for immigrant doctors from Asia, Africa and Latin America versus native Norwegians. Immigrant physicians from Europe, North America and Oceania used more diagnoses related to pregnancy, family planning and female genitals, OR 1.55 (95% CI 1.11 to 2.16), versus native Norwegian physicians. Immigrant doctors from Asia, Africa and Latin America used less psychiatric diagnoses, OR 0.71 (95% CI 0.53 to 0.95), versus native Norwegian doctors but did not differ significantly in their management of recognised psychiatric illness.ConclusionsImmigrant doctors make an important contribution to OOH emergency primary healthcare in Norway. The authors found only modest evidence that their clinical practice patterns are different from that of native Norwegian doctors.
Campylobacterepidemiology: a descriptive study reviewing 1 million cases in England and Wales between 1989 and 2011
Authors: Nichols Gordon L , Richardson Judith F , Sheppard Samuel K , Lane Chris , Sarran Christophe 
Published: July 2012

ObjectivesTo reviewCampylobactercases in England and Wales over 2 decades and examine the main factors/mechanisms driving the changing epidemiology.DesignA descriptive study ofCampylobacterpatients between 1989 and 2011. Cases over 3 years were linked anonymously to postcode, population density, deprivation indices and census data. Cases over 5 years were anonymously linked to local weather exposure estimates.SettingPatients were from general practice, hospital and environmental health investigations through primary diagnostic laboratories across England and Wales.ParticipantsThere were 1 109 406 cases.Outcome measuresDescription of changes inCampylobacterepidemiology over 23 years and how the main drivers may influence these.ResultsThere was an increase inCampylobactercases over the past 23 years, with the largest increase in people over 50 years. Changes in the underlying population have contributed to this, including the impacts of population increases after World War I, World War II and the ‘baby boom’ of the 1960s. A recent increase in risk or ascertainment within this population has caused an increase in cases in all age groups from 2004 to 2011. The seasonal increase in cases between weeks 18 (Early May) and 22 (Early June) was consistent across ages, years and regions and was most marked in children and in more rural regions.Campylobacterprevalence by week in each region correlated with temperature 2 weeks before. There were higher prevalences in areas with a low population density, low deprivation and lower percentage of people of ethnic origin. Data from sero–phage and multilocus sequence typing show a few common types and many uncommon types.ConclusionsThe drivers/mechanisms influencing seasonality, age distribution, population density, socioeconomic and long-term differences are diverse and their relative contributions remain to be established. Surveillance and typing provide insights intoCampylobacterepidemiology and sources of infection, providing a sound basis for targeted interventions.
Gastrointestinal surgery in adult patients with cystic fibrosis
Authors: Sharma Abhiram , Morton Alison , Peckham Daniel , Jayne David 
Published: July 2012

ObjectiveGastrointestinal conditions requiring surgical intervention are becoming increasingly frequent in adults with cystic fibrosis (CF) as life expectancy increases. In addition, patients with CF are at risk of specific gastrointestinal complications associated with their disease. This includes distal intestinal obstruction syndrome (DIOS), which may affect up to 15% of patients, and can present diagnostic and therapeutic challenges. The aim of this study was to determine the nature and frequency of general surgical procedures undertaken in a large cohort of adult CF patients so as to guide future care.DesignThe medical records of all surviving adult CF patients followed at a large tertiary referral centre in the UK were scrutinised and details retrieved on those who had undergone abdominal surgery after the age of 16 years.ResultsA total of 377 patients with CF were identified from the prospectively held database. Thirty-three patients had undergone 43 abdominal operations. The median age at surgery was 22.7 years (range 16–58 years). The three most commonly performed operations were: surgery for DIOS (n=9); cholecystectomy (n=8) and fundoplication (n=6). A past history of surgically treated meconium ileus at birth was a significant risk factor for requiring surgery for DIOS as an adult.ConclusionsThe treatment of DIOS-related complications is one of the main reasons for abdominal surgery in the adult CF population. The general surgical community needs to be increasingly aware of the existence of disease-related gastrointestinal conditions in adult CF patients so that treatment can be optimised.
Responsiveness of prehaemolytic copper poisoning in sheep from a specific pathogen‐free environment to a relatively high dose of tetrathiomolybdate
Authors: Suttle N. F. 
Published: July 2012

Efficacy of ammonium tetrathiomolybdate (3.4 mg/kg LW, TTM3.4) was monitored in nine, specific pathogen‐free sheep with mild‐to‐severe, prehaemolytic copper poisoning (pre‐HCP). Five sheep were given three subcutaneous injections over seven days and four began a shorter, five‐day course four days later. Plasma bile acid (BA) and glutamate dehydrogenase (GDH) had fallen significantly after six days but BA briefly rose again between days 10 to 18. Aspartate aminotransferase (AST), δ‐glutamyl transferase (GGT) were later to decline but presented little evidence of hepatotoxicity by day 45. Erythrocyte superoxide dismutase (ESOD) was rapidly inhibited, activities falling by 65 per cent within three days and taking 25 days to recover. Trichloroacetic (TCA)‐insoluble copper increased by 6 to 8 μmol/l after three days but had largely disappeared by day 18. Six lambs had become hypercupraemic by day 18 due to a rise in TCA‐soluble Cu. ESOD activity fell again by 188±29.5 U/gHb between days 25 and 45 but had largely recovered by day 62. TTM3.4 gave better control of hepatotoxicity than TTM1.7 had done in more severely affects cohorts but at the expense of greater inhibition of ESOD. Treatment of pre‐HCuP should rely more on reducing copper absorption until more is known of the side effects of TTM on cuproenzymes.
Monthly application of 10 per cent moxidectin and 2·5 per cent imidacloprid spot‐on to prevent relapses in generalised demodicosis: a pilot study
Authors: Colombo S. , Leone F. , Vercelli A. , Cornegliani L. 
Published: July 2012

Canine generalised demodicosis (GD) can be difficult to cure, with some dogs requiring life‐long treatment. The aim of this pilot study was to evaluate the effectiveness of monthly 10 per cent moxidectin/2·5 per cent imidacloprid spot‐on in maintaining long‐term (12 months) clinical and parasitological remission in dogs with relapsing GD. Fourteen dogs were included: 10 with juvenile‐onset GD (JOGD) and four with adult‐onset GD (AOGD). All dogs had been treated previously and relapsed (1–4 times). Each dog was treated again with either milbemycin oxime 2 mg/kg or ivermectin 400μg/kg orally once daily, until two consecutive negative skin scrapings at one‐month intervals (total 4–7 months of treatment). After treatment discontinuation, 10 per cent moxidectin/2·5 per cent imidacloprid spot‐on was applied monthly for 12 months. Dogs were rechecked after 1, 2, 3, 6 and 12 months, and multiple skin scrapings were taken. Twelve dogs completed the study and were clinically normal and parasitologically negative at each recheck (four dogs with AOGD and eight with JOGD). One dog died suddenly for unrelated reasons, and one dog relapsed. Results of this pilot study suggest that monthly application of 10 per cent moxidectin/2·5 per cent imidacloprid spot‐on may be effective as maintenance therapy in relapsing cases of GD.
BRAF
L597 Mutations in Melanoma Are Associated with Sensitivity to MEK Inhibitors
Authors: Dahlman Kimberly Brown , Xia Junfeng , Hutchinson Katherine , Ng Charles , Hucks Donald , Jia Peilin , Atefi Mohammad , Su Zengliu , Branch Suzanne , Lyle Pamela L. , Hicks Donna J. , Bozon Viviana , Glaspy John A. , Rosen Neal , Solit David B. , Netterville James L. , Vnencak-Jones Cindy L. , Sosman Jeffrey A. , Ribas Antoni , Zhao Zhongming , Pao William 
Published: July 2012

Abstract
Kinase inhibitors are accepted treatment for metastatic melanomas that harbor specific driver mutations in BRAF or KIT, but only 40% to 50% of cases are positive. To uncover other potential targetable mutations, we conducted whole-genome sequencing of a highly aggressive BRAF (V600) and KIT (W557, V559, L576, K642, and D816) wild-type melanoma. Surprisingly, we found a somatic BRAFL597R mutation in exon 15. Analysis of BRAF exon 15 in 49 tumors negative for BRAFV600 mutations as well as driver mutations in KIT, NRAS, GNAQ, and GNA11, showed that two (4%) harbored L597 mutations and another two involved BRAF D594 and K601 mutations. In vitro signaling induced by L597R/S/Q mutants was suppressed by mitogen-activated protein (MAP)/extracellular signal–regulated kinase (ERK) kinase (MEK) inhibition. A patient with BRAFL597S mutant metastatic melanoma responded significantly to treatment with the MEK inhibitor, TAK-733. Collectively, these data show clinical significance to BRAFL597 mutations in melanoma.
Significance: This study shows that cells harboring BRAFL597 mutants are sensitive to MEK inhibitor treatment, providing a rationale for routine screening and therapy of BRAFL597-mutant melanoma. Cancer Discov; 2(9); 791–7. ©2012 AACR.
Read the Commentary on this article by Garraway and Baselga, p. 766.
This article is highlighted in the In This Issue feature, p. 753.
Simvastatin Reduces Myocardial Injury Undergoing Noncoronary Artery Cardiac Surgery
Authors: Almansob Mohammed Ahmed Saad , Xu Bo , Zhou Li , Hu Xiao-Xia , Chen Wen , Chang Feng-Jun , Ci Hong-Bo , Yao Jian-Ping , Xu Ying-Qi , Yao Feng-Juan , Liu Dong-Hong , Zhang Wen-Bo , Tang Bai-Yun , Wang Zhi-Ping , Ou Jing-Song 
Published: July 2012

Objective—
Myocardial injury during cardiac surgery is a major cause of perioperative morbidity and mortality. We determined whether perioperative statin therapy is cardioprotective in patients undergoing noncoronary artery cardiac surgery and the potential mechanisms.

Methods and Results—
One hundred fifty-one patients undergoing noncoronary artery cardiac surgery were randomly assigned to either a statin group (n=77) or a control group (n=74). Simvastatin (20 mg) was administered preoperatively and postoperatively. Plasma were analyzed for troponin T, isoenzyme of creatine kinase, C-reaction protein, interleukin-6, interleukin-8, creatinine, and blood urea nitrogen. Cardiac echocardiography was performed. Endothelial nitric oxide synthase (eNOS), Akt, p38, heat shock protein 90, caveolin-1, and nitric oxide (NO) in the heart were detected. Simvastatin significantly reduced plasma troponin T, isoenzyme of creatine kinase, C-reaction protein, blood urea nitrogen , creatinine, interleukin-6, interleukin-8, and the requirement of inotropic postoperatively. Simvastatin increased NO production, the expression of eNOS and phosphorylation at serine1177, phosphorylation of Akt, expression of heat shock protein 90, heat shock protein 90 association with eNOS and decreased eNOS phosphorylation at threonine 495, phosphorylation of p38, and expression of caveolin-1. Simvastatin also improved cardiac function postoperatively.

Conclusion—
Perioperative statin therapy can improve cardiac function and renal function by reducing myocardial injury and inflammatory response through activating Akt-eNOS and attenuating p38 signaling pathways in patients undergoing noncoronary artery cardiac surgery.

Clinical Trial Registration—

URL:

http://www.clinicaltrials.gov

. Unique identifier: NCT01178710.
Lufaxin, a Novel Factor Xa Inhibitor From the Salivary Gland of the Sand Fly
Lutzomyia longipalpis
Blocks Protease-Activated Receptor 2 Activation and Inhibits Inflammation and Thrombosis In Vivo
Authors: Collin Nicolas , Assumpção Teresa C.F. , Mizurini Daniella M. , Gilmore Dana C. , Dutra-Oliveira Angélica , Kotsyfakis Michalis , Sá-Nunes Anderson , Teixeira Clarissa , Ribeiro José M.C. , Monteiro Robson Q. , Valenzuela Jesus G. , Francischetti Ivo M.B. 
Published: July 2012

Objective—

Blood-sucking arthropods’ salivary glands contain a remarkable diversity of antihemostatics. The aim of the present study was to identify the unique salivary anticoagulant of the sand fly
Lutzomyia longipalpis
, which remained elusive for decades.

Methods and Results—

Several
L. longipalpis
salivary proteins were expressed in human embryonic kidney 293 cells and screened for inhibition of blood coagulation. A novel 32.4-kDa molecule, named Lufaxin, was identified as a slow, tight, noncompetitive, and reversible inhibitor of factor Xa (FXa). Notably, Lufaxin’s primary sequence does not share similarity to any physiological or salivary inhibitors of coagulation reported to date. Lufaxin is specific for FXa and does not interact with FX, Dansyl-Glu-Gly-Arg-FXa, or 15 other enzymes. In addition, Lufaxin blocks prothrombinase and increases both prothrombin time and activated partial thromboplastin time. Surface plasmon resonance experiments revealed that FXa binds Lufaxin with an equilibrium constant ≈3 nM, and isothermal titration calorimetry determined a stoichiometry of 1:1. Lufaxin also prevents protease-activated receptor 2 activation by FXa in the MDA-MB-231 cell line and abrogates edema formation triggered by injection of FXa in the paw of mice. Moreover, Lufaxin prevents FeCl
3
-induced carotid artery thrombus formation and prolongs activated partial thromboplastin time ex vivo, implying that it works as an anticoagulant in vivo. Finally, salivary gland of sand flies was found to inhibit FXa and to interact with the enzyme.

Conclusion—
Lufaxin belongs to a novel family of slow-tight FXa inhibitors, which display antithrombotic and anti-inflammatory activities. It is a useful tool to understand FXa structural features and its role in prohemostatic and proinflammatory events.
The Chemokine Decoy Receptor D6 Prevents Excessive Inflammation and Adverse Ventricular Remodeling After Myocardial Infarction
Authors: Cochain Clément , Auvynet Constance , Poupel Lucie , Vilar José , Dumeau Edouard , Richart Adèle , Récalde Alice , Zouggari Yasmine , Yin Kiave Yune Ho Wang , Bruneval Patrick , Renault Gilles , Marchiol Carmen , Bonnin Philippe , Lévy Bernard , Bonecchi Raffaella , Locati Massimo , Combadière Christophe , Silvestre Jean-Sébastien 
Published: July 2012

Objective—
Leukocyte infiltration in ischemic areas is a hallmark of myocardial infarction, and overwhelming infiltration of innate immune cells has been shown to promote adverse remodeling and cardiac rupture. Recruitment of inflammatory cells in the ischemic heart depends highly on the family of CC-chemokines and their receptors. Here, we hypothesized that the chemokine decoy receptor D6, which specifically binds and scavenges inflammatory CC-chemokines, might limit inflammation and adverse cardiac remodeling after infarction.

Methods and Results—

D6 was expressed in human and murine infarcted myocardium. In a murine model of myocardial infarction, D6 deficiency led to increased chemokine (C-C motif) ligand 2 and chemokine (C-C motif) ligand 3 levels in the ischemic heart. D6-deficient (D6
−/−)
infarcts displayed increased infiltration of pathogenic neutrophils and Ly6Chi monocytes, associated with strong matrix metalloproteinase-9 and matrix metalloproteinase-2 activities in the ischemic heart. D6
−/−
mice were cardiac rupture prone after myocardial infarction, and functional analysis revealed that D6
−/−
hearts had features of adverse remodeling with left ventricle dilation and reduced ejection fraction. Bone marrow chimera experiments showed that leukocyte-borne D6 had no role in this setting, and that leukocyte-specific chemokine (C-C motif) receptor 2 deficiency rescued the adverse phenotype observed in D6
−/−
mice.

Conclusion—
We show for the first time that the chemokine decoy receptor D6 limits CC-chemokine–dependent pathogenic inflammation and is required for adequate cardiac remodeling after myocardial infarction.
Predictors for Neoatherosclerosis
Authors: Yonetsu Taishi , Kato Koji , Kim Soo-Joong , Xing Lei , Jia Haibo , McNulty Iris , Lee Hang , Zhang Shaosong , Uemura Shiro , Jang Yangsoo , Kang Soo-Jin , Park Seung-Jung , Lee Stephen , Yu Bo , Kakuta Tsunekazu , Jang Ik-Kyung 
Published: July 2012

Background—
Recent studies have reported development of neoatherosclerosis (NA) inside the stents several years after stent implantation. The aim of this study was to determine the predictors for NA using optical coherence tomography.

Methods and Results—

From a total of 1080 patients who underwent optical coherence tomography, we identified 179 stents in 151 patients in which the mean neointimal thickness was >100 µm. The presence of lipid-laden neointima or calcification inside the stents was defined as NA in the present study. Patient characteristics, stent type, and time since stent implantation (stent age) were compared between stents with or without NA. Univariable and multivariable logistic regression analyses were used to assess the independent predictors. In univariate analysis, stent age ≥48 months (Odds ratio [OR], 4.48; [95% CI 2.68-9.65];
P
<0.001), drug-eluting stents (OR, 2.66; [95% CI, 1.38–5.16];
P
=0.004), age ≥65 years (OR, 1.91; [95% CI, 1.05–3.44];
P
=0.032), current smoking (OR, 2.30; [95% CI, 1.10–4.82];
P
=0.024), chronic kidney disease (OR, 4.17; [95% CI, 1.42–12.23];
P
=0.009), and angiotensin-converting enzyme inhibitors or angiotensin II receptor blockade use (OR, 0.42; [95% CI, 0.22–0.80];
P
=0.008) were significant predictors. In multivariate analysis, stent age ≥48 months, all subtypes of drug-eluting stent, current smoking, chronic kidney disease, and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockade use remained independent predictors for NA.

Conclusions—
In addition to the stent type and the stent age, patient characteristics, including current smoking, chronic kidney disease, and angiotensin-converting enzyme inhibitors/angiotensin II receptor blockade, were associated with the presence of NA. This result may support the importance of secondary prevention after stent implantation.
Pharmacological Stabilization of Intracranial Aneurysms in Mice
Authors: Makino Hiroshi , Tada Yoshiteru , Wada Kosuke , Liang Elena I. , Chang Mayland , Mobashery Shahriar , Kanematsu Yasuhisa , Kurihara Chie , Palova Emma , Kanematsu Miyuki , Kitazato Keiko , Hashimoto Tomoki 
Published: July 2012

Background and Purpose—
An increasing number of unruptured intracranial aneurysms are being detected, partly due to the increased use of brain imaging techniques. Pharmacological stabilization of aneurysms for the prevention of aneurysmal rupture could potentially be an attractive alternative approach to clipping or coiling in patients with unruptured intracranial aneurysms. We have developed a mouse model of intracranial aneurysm that recapitulates key features of intracranial aneurysms. In this model, subarachnoid hemorrhage from aneurysmal rupture causes neurological symptoms that can be easily detected by a simple neurological examination. Using this model, we tested whether anti-inflammatory agents such as tetracycline derivatives, or a selective inhibitor of matrix metalloproteinases-2 and -9 (SB-3CT), can prevent the rupture of intracranial aneurysms.

Methods—
Aneurysms were induced by a combination of induced hypertension and a single injection of elastase into the cerebrospinal fluid in mice. Treatment with minocycline, doxycycline, or SB-3CT was started 6 days after aneurysm induction. Aneurysmal rupture was detected by neurological symptoms and confirmed by the presence of intracranial aneurysms with subarachnoid hemorrhage.

Results—

Minocycline and doxycycline significantly reduced rupture rates (vehicle versus doxycycline=80% versus 35%,
P
<0.05; vehicle versus minocycline=73% versus 24%,
P
<0.05) without affecting the overall incidence of aneurysms. However, SB-3CT did not affect the rupture rate (62% versus 55%,
P
=0.53).

Conclusions—
Our data established the feasibility of using a mouse model of intracranial aneurysm to test pharmacological stabilization of aneurysms. Tetracycline derivatives could be potentially effective in preventing aneurysmal rupture.