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《The American journal of drug and alcohol abuse》2013,39(5):392-399
Background: Multisite trials, the gold standard for conducting studies in community-based settings, can mask variability across sites resulting in misrepresentation of effects in specific sites. In a placebo-controlled trial of osmotic-release oral system methylphenidate (OROS-MPH) as augmentation treatment for smokers with attention deficit hyperactivity/impulsivity disorder (ADHD), three types of sites were selected according to their clinical research specialty (ADHD, smoking cessation, and general mental health). Objective: Analysis was conducted to determine if clinical outcomes, that is, reduction in ADHD symptoms and smoking cessation rates, and the effect of treatment on these outcomes would differ by type of site. Method: A total of 255 adult smokers diagnosed with ADHD were enrolled in three clinic types: 72 in ADHD, 79 in tobacco dependence, and 104 in the mental health clinics. Results: The three site-types were similar in demographic characteristics, smoking history, baseline level of ADHD symptoms, and history of psychiatric illness. Site-type but not a site-type by treatment interaction predicted prolonged smoking abstinence. A significant three-way interaction of site-type, treatment, and time-predicted improvement in ADHD symptoms. Moderate to strong effects of OROS-MPH relative to placebo were observed in the mental health and the ADHD clinics; a weak effect was observed in the tobacco dependence clinics. Conclusion: OROS-MPH benefit varied by site for reducing ADHD symptoms but not for improving smoking abstinence. Scientific Significance: Assessment of site-type effects can indicate the generalizability of findings from multisite trials and should be routinely incorporated in the design of multisite trials. 相似文献
103.
《Journal of consumer health on the Internet》2013,17(2):1-2
Abstract Consumer empowerment through authoritative health information is a positive force in today's health care environment. As the nation's lead agency for protecting the health and safety of people, the Centers for Disease Control and Prevention (CDC) has as part of its mission the responsibility of providing credible information to enhance health decisions. CDC health communications are provided through many venues, and particularly its Web site. This article identifies CDC consumer health sites, giving particular attention to two new initiatives, the CDC Kids Page and CDC en Espãol, which have been developed for specialized consumer health audiences. 相似文献
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《Journal of neurogenetics》2013,27(4):134-139
Abstract: Voltage-gated sodium channels (VGSC) contribute to the initiation and propagation of action potentials within the nervous system. These channels are important targets for inhibition by several classes of drugs, including antiarrhythmics and local anesthetics. Structural and pharmacological studies have localized the binding of these drugs to a common site near the channel's intracellular pore region. Point mutations within this region disrupt local anesthetic inhibition of cardiac, CNS, and skeletal muscle VGSC subtypes. This study was designed to test whether a similar structural requirement for drug binding exists on the peripheral neuronal VGSC subtype; Nav1.7. In support of this hypothesis, an alanine substitution for phenylalanine at position 1737 (F1737A) in the pore lining S6 segment of domain IV in human Nav1.7 reduced both use- and state- dependent inhibition of the local anesthetics, lidocaine and tetracaine, by 8–21-fold. We also saw a 2–3-fold reduction in tonic inhibition with the F1737A mutant. The voltage dependence of both activation and inactivation were unaffected by the F1737A mutation, however, fast inactivation kinetics were impaired, such that a significant portion of inward current remained at the end of a 20-ms depolarization. These data suggest that F1737 forms a part of the high affinity binding of local anesthetics as well as mediating inactivation processes of neuronal Nav1.7 channels. 相似文献
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《Journal of minimally invasive gynecology》2014,21(6):1015-1021
Study ObjectiveTo determine if injection of local anesthetic into trocar insertion sites after laparoscopy improves postoperative pain.DesignA prospective, 2-arm, randomized, double-blind, stratified, and controlled trial (Canadian Task Force classification I).SettingA university-based teaching hospital.PatientsThis study was performed on women who had a laparoscopic gynecologic procedure for benign indications from March 2013 to June 2013. One hundred thirty-five subjects were stratified by chronic pelvic pain or no chronic pelvic pain. Chronic pelvic pain was defined as pelvic pain occurring for 6 months or more in duration. Randomization was performed for this trial, with 68 receiving a bupivacaine block and 67 receiving no bupivacaine block. Of the 71 patients with chronic pelvic pain, 35 patients were in group 1 (i.e., bupivacaine block) and 36 patients were in group 2 (i.e., no bupivacaine block).InterventionsAfter the laparoscopic surgery was completed, the trocar incision sites were closed. For subjects randomized to receive a local anesthesia block, bupivacaine (0.25%) was injected. Incisions 8 mm or greater were injected with 10 mL 0.25% bupivacaine. Incisions 5 mm or less were infiltrated with 5 mL. Injecting the local anesthetic through all preperitoneal layers provided a full-thickness local injection. Group 2 did not receive a local injection.Measurements and Main ResultsAt the preoperative suite, the nurses gauged the patient's pain using the Numeric Rating Scale. This score was used as the baseline pain level with which the postoperative pain scores were compared. The primary objective was to measure changes in pain scores, from preoperative to postoperative time frames of 2 to 4 hours, 6 to 8 hours, 18 to 24 hours, and 3 to 7 days postoperatively. These score changes were measured as the main objective. Secondary objectives include estimated blood loss, operating time, length of hospital stay, and histopathologic diagnosis. The hospital personnel caring for the patient during the preoperative and postoperative course were given standard pain evaluation protocols. All study pain evaluators and patients were blinded to treatment assignments throughout the pain assessment process. There were no statistically significant differences in patient characteristics between the 2 treatment groups. No significant difference was found in secondary outcomes including estimated blood loss, length of hospital stay, and histopathologic diagnosis. In general, Numeric Rating Scale pain scores were lower (i.e., less pain) in the “bupivacaine block” group compared with the “no bupivacaine” block group at the following postsurgery time assessments: 2 to 4 hours, 6 to 8 hours, 18 to 24 hours, and 3 to 7 days after surgery. However, the effect was not large enough (<1 point) to show a statistical difference between the treatment groups at any of these postsurgery assessments.ConclusionThe postoperative injection of bupivacaine in trocar port sites did not significantly improve pain scores after laparoscopic gynecologic surgery. 相似文献
106.
The prognostic value of polycomb group protein B‐cell‐specific moloney murine leukemia virus insertion site 1 in stage II colon cancer patients
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Maiken L. M. Espersen Dorte Linnemann Ib J. Christensen Mahdi Alamili Jesper T. Troelsen Estrid Høgdall 《APMIS : acta pathologica, microbiologica, et immunologica Scandinavica》2016,124(7):541-546
The aim of this study was to investigate the prognostic value of B‐cell‐specific moloney murine leukemia virus insertion site 1 (BMI1) protein expression in primary tumors of stage II colon cancer patients. BMI1 protein expression was assessed by immunohistochemistry in a retrospective patient cohort consisting of 144 stage II colon cancer patients. BMI1 expression at the invasive front of the primary tumors correlated with mismatch repair status of the tumors. Furthermore, BMI1 expression at the luminal surface correlated with T‐stage, tumor location, and the histological subtypes of the tumors. In a univariate Cox proportional hazard analysis, no statistical significant association between risk of relapse and BMI1 protein expression at the invasive front (HR: 1.12; 95% CI 0.78–1.60; p = 0.53) or at the luminal surface of the tumor (HR: 1.06; 95% CI 0.75–1.48; p = 0.70) was found. Likewise, there was no association between 5‐year overall survival and BMI1 expression at the invasive front (HR: 1.12; 95% CI 0.80–1.56; p = 0.46) or at the luminal surface of the tumor (HR: 1.16; 95% CI 0.86–1.60; p = 0.33). In conclusion, BMI1 expression in primary tumors of stage II colon cancer patients could not predict relapse or overall survival of the patients, thus having a limited prognostic value in stage II colon cancer patients. 相似文献
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B. Wrzesińska A. Czerwoniec P. Wieczorek P. Węgorek J. Zamojska A. Obrępalska‐Stęplowska 《Insect molecular biology》2014,23(5):682-693
The pollen beetle (Meligethes aeneus F.) is the most devastating pest of oilseed rape (Brassica napus) and is controlled by pyrethroid insecticides. However, resistance to pyrethroids in Europe is becoming widespread and predominant. Pyrethroids target the voltage‐sensitive sodium channel (VSSC), and mutations in VSSC may be responsible for pyrethroid insensitivity. Here, we analysed individual beetles that were resistant to esfenvalerate, a pyrethroid, from 14 populations that were collected from oilseed rape fields in Poland. We screened the VSSC domains that were presumed to directly interact with pyrethroids. We identified 18 heterozygous nucleic acid substitutions, amongst which six caused an amino acid change: N912S, G926S, I936V, R957G, F1538L and E1553G. Our analysis of the three‐dimensional structure of these domains in VSSC revealed that some of these changes may slightly influence the protein structure and hence the docking efficiency of esfenvalerate. Therefore, these mutations may impact the susceptibility of the sodium channel to the action of this insecticide. 相似文献
110.
《Acta oto-laryngologica》2012,132(6):688-693
Branchio-oto-renal (BOR) and branchio-oto (BO) syndromes are autosomal dominant hereditary disorders characterized by the presence of hearing loss and branchial fistulae and cysts, with (BOR syndrome) or without (BO syndrome) renal malformations of varying degrees of severity. Mutations in the human homologous of the Drosophila eyes absent (EYA1) gene are frequently the cause of BOR/BO syndrome. Here we describe a Korean family with BO syndrome; the proband had preauricular pit, cup-shaped auricles, branchial fistula, and hearing loss, without renal involvement. Molecular genetic study revealed a novel mutation occurring in the consensus acceptor splice site of intron 8 (c.868-2A > G) in the EYA1 gene. To the best of our knowledge, this is the first report of a splice site mutation in a family with BO syndrome without renal involvement, further extending the phenotypic-genotypic heterogeneity of BOR/BO syndrome. 相似文献