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111.
Colonoscopy bowel preparation quality improvement for patients with decompensated cirrhosis undergoing evaluation for liver transplantation 下载免费PDF全文
112.
Idiopathic subglottic stenosis is associated with activation of the inflammatory IL‐17A/IL‐23 axis 下载免费PDF全文
Alexander Gelbard MD Nicolas‐George Katsantonis MD Masanobu Mizuta MD Dawn Newcomb PhD Joseph Rotsinger MS Bernard Rousseau PhD CCC‐SLP James J. Daniero MD MS Eric S. Edell MD Dale C. Ekbom MD Jan L. Kasperbauer MD Alexander T. Hillel MD Liying Yang MD MS C. Gaelyn Garrett MD James L. Netterville MD Christopher T. Wootten MD David O. Francis MD MS Charles Stratton MD Kevin Jenkins MD Tracy L. McGregor MD Jennifer A. Gaddy PhD Timothy S. Blackwell MD Wonder P. Drake MD 《The Laryngoscope》2016,126(11):E356-E361
113.
Menzies D Nair A Meldrum KT Fleming D Barnes M Lipworth BJ 《The Journal of allergy and clinical immunology》2007,119(2):328-335
BACKGROUND: Statins lower cholesterol and also exhibit anti-inflammatory properties. In vitro and animal studies have suggested they may be useful for the treatment of a number of inflammatory conditions. OBJECTIVE: To evaluate the in vivo therapeutic potential of simvastatin as an anti-inflammatory agent in patients with asthma. METHODS: Potential signal from treatment effect was optimized by withdrawing all anti-inflammatory treatment for the duration of the study. Participants received 1 month of daily simvastatin and 1 month of daily placebo in a randomized, double-blind crossover trial. A total of 16 patients completed per protocol. Asthmatic inflammation was evaluated by measuring exhaled tidal nitric oxide, alveolar nitric oxide, sputum and peripheral eosinophil count, methacholine hyperresponsiveness, salivary eosinophilic cationic protein, and C-reactive protein. Measurements of dynamic and static lung volumes and of cholesterol were also made. RESULTS: After initial withdrawal of usual asthma medication, there was a 1.43 geometric mean fold increase (ie, 43% difference) in fraction of exhaled nitric oxide (95% CI, 1.15 to 1.78; P = .004). Compared with placebo, simvastatin led to a 0.86 geometric mean fold decrease (95% CI, 0.7 to 1.04; P = .15) in exhaled nitric oxide (ie, a 14% difference), and a -0.18 doubling dilution shift (95% CI, -1.90 to 1.55; P = 1.0) in methacholine hyperresponsiveness. There were no significant differences in other inflammatory outcomes, lung volumes, or airway resistance between simvastatin and placebo. Treatment with simvastatin led to a significant reduction (P < .005) of total and low-density lipoprotein cholesterol. CONCLUSION: There is no evidence to suggest simvastatin has anti-inflammatory activity in patients with asthma. CLINICAL IMPLICATIONS: Simvastatin is not useful for the treatment of asthma. 相似文献
114.
Giselli Scaini João Quevedo Dawn Velligan David L. Roberts Henriette Raventos Consuelo Walss-Bass 《European neuropsychopharmacology》2018,28(3):369-380
Metabolic syndrome (MetS) is seen more frequently in persons with schizophrenia than in the general population, and these metabolic abnormalities are further aggravated by second generation antipsychotic (SGA) drugs. Although the underlying mechanisms responsible for the increased prevalence of MetS among patients under SGA treatment are not well understood, alterations in mitochondria function have been implicated. We performed a comprehensive evaluation of the role of mitochondrial dysfunction in the pathophysiology of drug-induced MetS in schizophrenia. We found a downregulation in genes encoding subunits of the electron transport chain complexes (ETC), enzyme activity, and mitochondrial dynamics in peripheral blood cells from patients at high-risk for MetS. Additionally, we evaluated several markers of energy metabolism in lymphoblastoid cell lines from patients with schizophrenia and controls following exposure to antipsychotics. We found that the high-risk drugs clozapine and olanzapine induced a general down-regulation of genes involved in the ETC, as well as decreased activities of the corresponding enzymes, ATP levels and a significant decrease in all the functional parameters of mitochondrial oxygen consumption in cells from patients and controls. We also observed that the medium-risk SGA quetiapine decreased oxygen consumption and respiratory control ratio in controls and patients. Additionally, clozapine and olanzapine induced a downregulation of Drp1 and Mfn2 both in terms of mRNA and protein levels. Together, these data suggest that an intrinsic defect in multiple components of oxidative metabolism may contribute to the increased prevalence of MetS in patients under treatment with SGAs known to cause risk for MetS. 相似文献
115.
Functional interaction–based nonlinear models with application to multiplatform genomics data 下载免费PDF全文
Clemontina A. Davenport Arnab Maity Veerabhadran Baladandayuthapani 《Statistics in medicine》2018,37(18):2715-2733
Functional regression allows for a scalar response to be dependent on a functional predictor; however, not much work has been done when a scalar exposure that interacts with the functional covariate is introduced. In this paper, we present 2 functional regression models that account for this interaction and propose 2 novel estimation procedures for the parameters in these models. These estimation methods allow for a noisy and/or sparsely observed functional covariate and are easily extended to generalized exponential family responses. We compute standard errors of our estimators, which allows for further statistical inference and hypothesis testing. We compare the performance of the proposed estimators to each other and to one found in the literature via simulation and demonstrate our methods using a real data example. 相似文献
116.
Kristin J. Roberts Erica Fowler R. Dawn Comstock Soledad Fernandez Mahmoud Abdel-Rasoul Leslie Mihalov Marcel J. Casavant Lara B. McKenzie 《The journal of primary prevention》2018,39(1):1-15
Although the proper installation and maintenance of carbon monoxide (CO) and smoke alarms can protect individuals from residential CO-related and fire-related injuries, these devices are underutilized. We describe characteristics associated with self-reported CO and smoke alarm use of parents recruited from a pediatric emergency department to improve CO alarm use. Parents of children ≤ 18 years (N = 299) reported socio-demographic characteristics and CO and smoke alarm ownership and practices. We assigned participants to a behavioral profile and a Precaution Adoption Process Model stage based on their self-reported CO and smoke alarm use. Most participants (71%) did not have CO alarms in their homes, but reported owning at least one working smoke alarm (98%). Participants who reported “perfect” CO alarm behavior (defined as having a working CO alarm, one near a sleeping area, with batteries replaced every 6 months; 9%) were more likely to earn a higher income, own their home, and have lived at their current residence for at least 2 years. Participants who reported “perfect” smoke alarm behavior (defined as having a working smoke alarm on every level, with batteries replaced every 6 months; 49%) were more likely to rent their home, receive federal assistance, and have lived at their current residence for at least 2 years. Interventions to increase correct CO alarm use are necessary. 相似文献
117.
Pediatric rare diseases present unique challenges in clinical trial design and in selection of clinical outcome assessments (COAs) used to support claims in medical product labeling. COAs that discriminate level of function relative to a normative sample are particularly important in the pediatric rare disease setting because the literature is often void of natural history data. Pediatric rare disease clinical trials will often include a wide age distribution. Gross and fine motor skills, communication, cognition, and independence in activities of daily living vary by age, and it may be difficult to distinguish between treatment effect and change due to developmental maturation. Asfotase alfa was granted breakthrough therapy designation and subsequently approved for the treatment of hypophosphatasia (HPP; a genetic metabolic musculoskeletal disorder) and is used in this discussion to illustrate COA selection in a pediatric rare disease. Multiple COAs with normative data in HPP clinical trials for asfotase alfa are presented. The assessment instruments included the Bayley Scales of Infant and Toddler Development-Third Edition, the Bruininks-Oseretsky Test of Motor Proficiency, Second Edition, the Childhood Health Assessment Questionnaire, the Pediatric Outcomes Data Collection Instrument, handheld dynamometry, the 6-minute walk test, and the Modified Performance-Oriented Mobility Assessment-Gait scale. Multiple end points were required to adequately capture the impact of asfotase alfa treatment on the multiple systems affected in HPP. These data illustrate the importance of using multiple COAs that provide normative data and to use COAs early in the drug development process for rare pediatric disease. 相似文献
118.
119.
Tara L. Mader Susan A. Novotny Angela S. Lin Robert E. Guldberg Dawn A. Lowe Gordon L. Warren 《Calcified tissue international》2014,95(5):457-466
Bone loss due to age and disuse contributes to osteoporosis and increases fracture risk. It has been hypothesized that such bone loss can be attenuated by modulation of the C–C chemokine receptor 2 (CCR2) and/or its ligands. The objectives of this study were to examine the effects of genetic elimination of CCR2 on cortical and trabecular bones in the mouse tibia and how bone loss was impacted following disuse and estrogen loss. Female CCR2 knockout (CCR2?/?) and wildtype mice underwent ovariectomy (OVX) or denervation of musculature adjacent to the tibia (DEN) to induce bone loss. Cortical and trabecular structural properties as well as mechanical properties (i.e., strength) of tibial bones were measured. Compared to wildtype mice, CCR2?/? mice had tibiae that were up to 9 % larger and stronger; these differences could be explained mainly by the 17 % greater body mass (P < 0.001) of CCR2?/? mice. The majority of the tibia’s structural and functional responses to OVX and DEN were similar regardless of the lack or presence of CCR2, indicating that CCR2 is not protective against bone loss per se. These findings indicate that while CCR2?/? mice do have larger and stronger bones than do wildtype mice, there is minimal evidence that CCR2 elimination provides protection against bone loss during disuse and estrogen loss. 相似文献
120.