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Sample records for facilitate multicenter association

  1. Semantic Integration of Cervical Cancer Data Repositories to Facilitate Multicenter Association Studies: The ASSIST Approach

    PubMed Central

    Agorastos, Theodoros; Koutkias, Vassilis; Falelakis, Manolis; Lekka, Irini; Mikos, Themistoklis; Delopoulos, Anastasios; Mitkas, Pericles A.; Tantsis, Antonios; Weyers, Steven; Coorevits, Pascal; Kaufmann, Andreas M.; Kurzeja, Roberto; Maglaveras, Nicos

    2009-01-01

    The current work addresses the unification of Electronic Health Records related to cervical cancer into a single medical knowledge source, in the context of the EU-funded ASSIST research project. The project aims to facilitate the research for cervical precancer and cancer through a system that virtually unifies multiple patient record repositories, physically located in different medical centers/hospitals, thus, increasing flexibility by allowing the formation of study groups “on demand” and by recycling patient records in new studies. To this end, ASSIST uses semantic technologies to translate all medical entities (such as patient examination results, history, habits, genetic profile) and represent them in a common form, encoded in the ASSIST Cervical Cancer Ontology. The current paper presents the knowledge elicitation approach followed, towards the definition and representation of the disease’s medical concepts and rules that constitute the basis for the ASSIST Cervical Cancer Ontology. The proposed approach constitutes a paradigm for semantic integration of heterogeneous clinical data that may be applicable to other biomedical application domains. PMID:19458792

  2. A Multicenter Trial Defining a Serum Protein Signature Associated with Pancreatic Ductal Adenocarcinoma

    PubMed Central

    Gerdtsson, Anna S.; Malats, Núria; Säll, Anna; Real, Francisco X.; Porta, Miquel; Skoog, Petter; Persson, Helena; Wingren, Christer; Borrebaeck, Carl A. K.

    2015-01-01

    Background. Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease with rapid tumor progression and poor prognosis. This study was motivated by the lack of sensitive and specific PDAC biomarkers and aimed to identify a diagnostic, serum protein signature for PDAC. Methods. To mimic a real life test situation, a multicenter trial comprising a serum sample cohort, including 338 patients with either PDAC or other pancreatic diseases (OPD) and controls with nonpancreatic conditions (NPC), was analyzed on 293-plex recombinant antibody microarrays targeting immunoregulatory and cancer-associated antigens. Results. Serum samples collected from different hospitals were analyzed and showed that (i) sampling from five different hospitals could not be identified as a preanalytical variable and (ii) a multiplexed biomarker signature could be identified, utilizing up to 10 serum markers that could discriminate PDAC from controls, with sensitivities and specificities in the 91–100% range. The first protein profiles associated with the location of the primary tumor in the pancreas could also be identified. Conclusions. The results demonstrate that robust enough serum signatures could be identified in a multicenter trial, potentially contributing to the development of a multiplexed biomarker immunoassay for improved PDAC diagnosis. PMID:26587286

  3. Neutrophil Gelatinase Associated Lipocalin (NGAL) in Leptospirosis Acute Kidney Injury: A Multicenter Study in Thailand

    PubMed Central

    Srisawat, Nattachai; Praditpornsilpa, Kearkiat; Patarakul, Kanitha; Techapornrung, Malee; Daraswang, Tinnapop; Sukmark, Theerapon; Khositrangsikun, Kamol; Fakthongyoo, Apinya; Oranrigsupak, Petchdee; Praderm, Laksamon; Suwattanasilpa, Ummarit; Peerapornratana, Sadudee; Loahaveeravat, Passisd; Suwachittanont, Nattachai; Wirotwan, Thaksa-on; Phonork, Chayanat; Kumpunya, Sarinya; Tiranathanagul, Khajohn; Chirathaworn, Chintana; Eiam-ong, Somchai; Tungsanga, Kriang; Sitprija, Visith; Kellum, John A.; Townamchai, Natavudh

    2015-01-01

    AKI is one of the most serious complications of leptospirosis, an important zoonosis in the tropics. Recently, NGAL, one of the novel AKI biomarkers, is extensively studied in various specific settings such as sepsis, cardiac surgery, and radiocontrast nephropathy. In this multicenter study, we aimed to study the role of NGAL as an early marker and an outcome predictor of leptospirosis associated AKI. Patients who presented with clinical suspiciousness of leptospirosis were prospectively enrolled in 9 centers from August 2012 to November 2014. The first day of enrollment was the first day of clinical suspicious leptospirosis. Blood and urine samples were serially collected on the first three days and day 7 after enrollment. We used three standard techniques (microscopic agglutination test, direct culture, and PCR technique) to confirm the diagnosis of leptospirosis. KDIGO criteria were used for AKI diagnosis. Recovery was defined as alive and not requiring dialysis during hospitalization or maintaining maximum KDIGO stage at hospital discharge. Of the 221 recruited cases, 113 cases were leptospirosis confirmed cases. Thirty seven percent developed AKI. Median uNGAL and pNGAL levels in those developing AKI were significantly higher than in patients not developing AKI [253.8 (631.4) vs 24.1 (49.6) ng/ml, p < 0.001] and [1,030 (802.5) vs 192.0 (209.0) ng/ml, p < 0.001], respectively. uNGAL and pNGAL levels associated with AKI had AUC-ROC of 0.91, and 0.92, respectively. Both of urine NGAL and pNGAL level between AKI-recovery group and AKI-non recovery were comparable. From this multicenter study, uNGAL and pNGAL provided the promising result to be a marker for leptospirosis associated AKI. However, both of them did not show the potential role to be the predictor of renal recovery in this specific setting. PMID:26629810

  4. A multicenter study confirms CD226 gene association with systemic sclerosis-related pulmonary fibrosis

    PubMed Central

    2012-01-01

    Introduction CD226 genetic variants have been associated with a number of autoimmune diseases and recently with systemic sclerosis (SSc). The aim of this study was to test the influence of CD226 loci in SSc susceptibility, clinical phenotypes and autoantibody status in a large multicenter European population. Methods A total of seven European populations of Caucasian ancestry were included, comprising 2,131 patients with SSc and 3,966 healthy controls. Three CD226 single nucleotide polymorphisms (SNPs), rs763361, rs3479968 and rs727088, were genotyped using Taqman 5'allelic discrimination assays. Results Pooled analyses showed no evidence of association of the three SNPs, neither with the global disease nor with the analyzed subphenotypes. However, haplotype block analysis revealed a significant association for the TCG haplotype (SNP order: rs763361, rs34794968, rs727088) with lung fibrosis positive patients (PBonf = 3.18E-02 OR 1.27 (1.05 to 1.54)). Conclusion Our data suggest that the tested genetic variants do not individually influence SSc susceptibility but a CD226 three-variant haplotype is related with genetic predisposition to SSc-related pulmonary fibrosis. PMID:22531499

  5. Facilitation of Play Behavior from Associative to Cooperative Play Stages.

    ERIC Educational Resources Information Center

    Lounsbury, Karen Rasmussen; Bell, Corinne Reed

    An experimental investigation of the transition from associative play to cooperative play was conducted to determine if cooperative play in young children could be facilitated by (1) presenting a toy that required cooperative responses to make it operate, and (2) instructing the children in the use of the toy prior to having them play with it. A…

  6. Association of hip and pelvic geometrywith tibiofemoral osteoarthritis: Multicenter Osteoarthritis Study (MOST)

    PubMed Central

    Boissonneault, A; Lynch, JA; Wise, BL; Segal, NA; Gross, KD; Murray, DW; Nevitt, MC; Pandit, HG

    2014-01-01

    Objective Lateral tibiofemoral osteoarthritis (OA) is overall less common than medial tibiofemoral OA, but it is more prevalent in women. This may be explained by sex differences in hip and pelvic geometry. The aim of this study is to explore sex differences in hip and pelvic geometry and determine if such parameters are associated with the presence of compartment-specific knee OA. Methods This case-control study reports on 1,328 hips/knees from 664 participants and is an ancillary to the Multicenter Osteoarthritis Study (MOST). Of the 1,328 knees, 219 had lateral OA, 260 medial OA, and 849 no OA. Hip and pelvic measurements were taken from full-limb radiographs on the ipsilateral side of the knee of interest. After adjusting for covariates, means were compared between sexes and also between knees with medial and lateral OA versus no OA using separate regression models. Results Women were shown to have a reduced femoral offset (mean 40.9 mm vs. 45.9 mm; p=0.001) and more valgus neck-shaft angle (mean 128.4° vs. 125.9°; p<0.001) compared to men. Compared to those with no OA, knees with lateral OA were associated with a reduced femoral offset (p=0.012), increased height of hip centre (p=0.003), more valgus neck-shaft angle (p=0.042), and increased abductor angle (p=0.031). Knees with medial OA were associated with a more varus neck-shaft angle (p=0.043) and a decreased abductor angle (p=0.003). Conclusion These data suggest anatomical variations at the hip and pelvis are associated with compartment-specific knee OA and may help to explain sex differences in patterns of knee OA. PMID:24971867

  7. Factors associated with prevalent human immunodeficiency virus (HIV) infection in the Multicenter AIDS Cohort Study.

    PubMed

    Chmiel, J S; Detels, R; Kaslow, R A; Van Raden, M; Kingsley, L A; Brookmeyer, R

    1987-10-01

    Interviews regarding medical history, life-style, specific drug taking and sexual activities, and physical examinations were administered to 4,955 homosexual men who volunteered for the Multicenter AIDS Cohort Study in Baltimore, Chicago, Los Angeles, and Pittsburgh. Overall, the prevalence of antibodies to human immunodeficiency virus (HIV) in these men was 38.0%. The factor most strongly associated with prevalent HIV infection according to a multiple logistic regression model was rectal trauma, a composite variable which included receptive anal fisting, enemas before sex, reporting of blood around the rectum, and the observation of scarring, fissures or fistulas on rectal examination. Receptive anal intercourse also was strongly associated with HIV infection in the model. The multivariate relative odds for HIV antibody positivity was 7.72 for the highest level of rectal trauma and 3.04 for receptive anal intercourse. Symptoms reported to occur in some persons who subsequently develop acquired immunodeficiency syndrome (AIDS) were frequent among HIV seropositive men (12.9%) but were reported in 8.4% of seronegative men as well. Generalized lymphadenopathy was observed significantly more often in seropositive men (48.8%) compared with seronegative men (11.4%). The prevalence of HIV antibodies was inversely related to the number of T-helper cells and directly related (to a lesser extent) to the number of T-suppressor cells. The results suggest that disruption of the rectal mucosa provides access by HIV to the blood stream and to specific immunologic cells. Since symptoms and generalized lymphadenopathy were often reported among seronegative men, they probably also occur among some seropositive men not currently progressing to AIDS. PMID:3651095

  8. Risk factors associated with missed colorectal flat adenoma: A multicenter retrospective tandem colonoscopy study

    PubMed Central

    Xiang, Li; Zhan, Qiang; Zhao, Xin-Hua; Wang, Ya-Dong; An, Sheng-Li; Xu, Yang-Zhi; Li, Ai-Min; Gong, Wei; Bai, Yang; Zhi, Fa-Chao; Liu, Si-De

    2014-01-01

    AIM: To determine the miss rate for colorectal flat adenomas during colonoscopy and the risk factors. METHODS: Flat adenomas are frequently missed during colonoscopy. However, the risk factors that influence their miss rates are unclear. This was a multicenter, retrospective study in which patients diagnosed with colorectal adenomas at a diagnostic colonoscopy and followed within 3 mo by a second therapeutic colonoscopy were pooled out from the established database. The “per-patient” and “per-adenoma” adenoma miss rates (AMR) for overall adenomas and flat adenomas, and patient-, adenoma-, and procedure-related risk factors potentially associated with the “per-adenoma” AMR for flat adenomas were determined. RESULTS: Chromoscopy and high-definition colonoscopy were not taken under consideration in the study. Among 2093 patients with colorectal adenomas, 691 (33.0%) were diagnosed with flat adenomas, 514 with concomitant protruding adenomas and 177 without. The “per-patient” AMR for flat adenomas was 43.3% (299/691); the rates were 54.3% and 11.3%, respectively, for those with protruding adenomas and those without (OR = 9.320, 95%CI: 5.672-15.314, χ2 = 99.084, P < 0.001). The “per-adenoma” AMR for flat adenomas was 44.3% (406/916). In multivariate analysis, older age, presence of concomitant protruding adenomas, poor bowel preparation, smaller adenoma size, location at the right colon, insufficient experience of the colonoscopist, and withdrawal time < 6 min were associated with an increased “per-adenoma” AMR for flat adenomas. The AMR for flat adenomas was moderately correlated with that for overall adenomas (r = 0.516, P < 0.0001). The AMR for flat adenomas during colonoscopy was high. CONCLUSION: Patient’s age, concomitant protruding adenomas, bowel preparation, size and location of adenomas, proficiency of the colonoscopist, and withdrawal time are factors affecting the “per-adenoma” AMR for flat adenomas. PMID:25152596

  9. Association between tumor size and Breslow's thickness in malignant melanoma: a cross-sectional, multicenter study.

    PubMed

    Moreno-Ramírez, David; Ojeda-Vila, Teresa; Ríos-Martín, Juan J; Nieto-García, Adoración; Ferrándiz, Lara

    2015-10-01

    The aim of this study was to assess the potential role of tumor diameter in explaining variations in tumoral invasion and in the initial prognosis for patients with malignant melanoma (MM). This was a multicenter, cross-sectional study that recruited between 2000 and 2009 patients with primary in-situ MM (Tis) and invasive cutaneous MM. Tis and MMs with a Breslow's thickness less than 1 mm (T1) were grouped (Tis-T1) and tumors with a Breslow's thickness 1 mm or more were also analyzed in combination (T2-T4). The tumor size was measured after routine formalin tissue fixation. Primary outcomes were the correlation between Breslow's thickness and tumor size, and the role of tumor size in explaining variations in Breslow's thickness, as assessed by the Pearson correlation test and logistic binary regression with calculation of the odds ratios. A total of 1610 MM patients were included and analyzed. The Pearson correlation between tumor size and Breslow's thickness was 0.42, with a determination coefficient of R2=0.18 (P>0.01). Correlations between tumor size and thickness were stronger in patients aged 30-60 years (r=0.42, R2=0.1764, P<0.001) and in tumors arising on the upper limbs (r=0.55, R2=0.3025). The odds ratio of identifying a T2-T4 stage MM in patients with tumors larger than 1 cm in size was 2.76 (95% confidence interval 2.25-3.39, P<0.001). Even though a direct, positive, and strong association between tumoral size and Breslow's thickness might be expected in melanoma cases, the strength of this association has been moderate. Tumor size explains a low burden of the variation observed in the Breslow's thickness. PMID:26237766

  10. Reward association facilitates distractor suppression in human visual search.

    PubMed

    Gong, Mengyuan; Yang, Feitong; Li, Sheng

    2016-04-01

    Although valuable objects are attractive in nature, people often encounter situations where they would prefer to avoid such distraction while focusing on the task goal. Contrary to the typical effect of attentional capture by a reward-associated item, we provide evidence for a facilitation effect derived from the active suppression of a high reward-associated stimulus when cuing its identity as distractor before the display of search arrays. Selection of the target is shown to be significantly faster when the distractors were in high reward-associated colour than those in low reward-associated or non-rewarded colours. This behavioural reward effect was associated with two neural signatures before the onset of the search display: the increased frontal theta oscillation and the strengthened top-down modulation from frontal to anterior temporal regions. The former suggests an enhanced working memory representation for the reward-associated stimulus and the increased need for cognitive control to override Pavlovian bias, whereas the latter indicates that the boost of inhibitory control is realized through a frontal top-down mechanism. These results suggest a mechanism in which the enhanced working memory representation of a reward-associated feature is integrated with task demands to modify attentional priority during active distractor suppression and benefit behavioural performance. PMID:26797805

  11. Associations between HIV Infection and Subclinical Coronary Atherosclerosis: The Multicenter AIDS Cohort Study (MACS)

    PubMed Central

    Post, Wendy S; Budoff, Matthew; Kingsley, Lawrence; Palella, Frank J; Witt, Mallory D; Li, Xiuhong; George, Richard T; Brown, Todd; Jacobson, Lisa P.

    2014-01-01

    Background Coronary artery disease (CAD) has been associated with HIV infection; however data are not consistent. Objective We performed cardiac CT to determine whether HIV-infected men have more coronary atherosclerosis than uninfected men. Design Cross-sectional study within the Multicenter AIDS Cohort Study(MACS). Participants HIV-infected (n=618) and –uninfected (n=383) men who have sex with men (MSM) had non-contrast and contrast enhanced cardiac CT if they were between 40–70 years, weighed <300 pounds, and had no history of coronary revascularization. Measurements Presence and extent, for those with plaque, of coronary artery calcium (CAC) on non-contrast CT, and of any plaque, non-calcified, mixed or calcified plaque and stenosis on CT angiography. Results 1001 men underwent non-contrast CT of whom 759 had coronary CT angiography. After adjusting for age, race, center, and cohort, HIV-infected men had a greater prevalence of CAC [Prevalence ratio(PR)=1.21, 95% confidence interval (CI) 1.08–1.35, p=0.001], and any plaque [PR=1.14(1.05–1.24),p=0.001], including non-calcified plaque [PR=1.28(1.13–1.45),p<0.001) and mixed plaque [PR=1.35(1.10–1.65),p=0.004] than HIV-uninfected men. Associations between HIV-infection and any plaque and non-calcified plaque remained significant (p<0.005) after CAD risk factor adjustment. HIV-infected men also had a greater extent of non-calcified plaque after CAD risk factor adjustment (p=0.026). HIV-infected men had a greater prevalence of coronary artery stenosis>50% than HIV-uninfected men [PR=1.48(1.06–2.07),p=0.020), but not after CAD risk factor adjustment. Longer duration of highly active antiretroviral therapy [PR=1.09(1.02–1.17), p=0.007,per year] and lower nadir CD4+ T-cell count [PR=0.80(0.69–0.94),p=0.005, per 100 cells] were associated with coronary stenosis>50%. Conclusions Coronary artery plaque, especially non-calcified plaque, is more prevalent and extensive in HIV-infected men, independent of

  12. Prospective multicenter assessment of perioperative and minimum 2-year postoperative complication rates associated with adult spinal deformity surgery.

    PubMed

    Smith, Justin S; Klineberg, Eric; Lafage, Virginie; Shaffrey, Christopher I; Schwab, Frank; Lafage, Renaud; Hostin, Richard; Mundis, Gregory M; Errico, Thomas J; Kim, Han Jo; Protopsaltis, Themistocles S; Hamilton, D Kojo; Scheer, Justin K; Soroceanu, Alex; Kelly, Michael P; Line, Breton; Gupta, Munish; Deviren, Vedat; Hart, Robert; Burton, Douglas C; Bess, Shay; Ames, Christopher P

    2016-07-01

    OBJECTIVE Although multiple reports have documented significant benefit from surgical treatment of adult spinal deformity (ASD), these procedures can have high complication rates. Previously reported complications rates associated with ASD surgery are limited by retrospective design, single-surgeon or single-center cohorts, lack of rigorous data on complications, and/or limited follow-up. Accurate definition of complications associated with ASD surgery is important and may serve as a resource for patient counseling and efforts to improve the safety of patient care. The authors conducted a study to prospectively assess the rates of complications associated with ASD surgery with a minimum 2-year follow-up based on a multicenter study design that incorporated standardized data-collection forms, on-site study coordinators, and regular auditing of data to help ensure complete and accurate reporting of complications. In addition, they report age stratification of complication rates and provide a general assessment of factors that may be associated with the occurrence of complications. METHODS As part of a prospective, multicenter ASD database, standardized forms were used to collect data on surgery-related complications. On-site coordinators and central auditing helped ensure complete capture of complication data. Inclusion criteria were age older than 18 years, ASD, and plan for operative treatment. Complications were classified as perioperative (within 6 weeks of surgery) or delayed (between 6 weeks after surgery and time of last follow-up), and as minor or major. The primary focus for analyses was on patients who reached a minimum follow-up of 2 years. RESULTS Of 346 patients who met the inclusion criteria, 291 (84%) had a minimum 2-year follow-up (mean 2.1 years); their mean age was 56.2 years. The vast majority (99%) had treatment including a posterior procedure, 25% had an anterior procedure, and 19% had a 3-column osteotomy. At least 1 revision was required in 82

  13. Cognitive Dysfunction is Associated with Poor Socio-Economic Status in Patients with Cirrhosis: an International Multi-Center Study

    PubMed Central

    Bajaj, Jasmohan S; Riggio, Oliviero; Allampati, Sanath; Prakash, Ravi; Gioia, Stefania; Onori, Eugenia; Piazza, Nicole; Noble, Nicole A; White, Melanie B; Mullen, Kevin D

    2013-01-01

    Background & Aims In patients with cirrhosis, cognitive dysfunction most often results from covert hepatic encephalopathy (HE). These patients are not routinely tested for cognitive dysfunction, despite single-center evidence that it could be associated with poor socio-economic status (SES). We investigated the association between SES and cognition in a multi-center study of cirrhosis. Methods In a cross-sectional study, 236 cirrhotic patients from 3 centers (84 subjects from Virginia, 102 from Ohio, and 50 from Rome, Italy; age 57.7±8.6 y; 14% with prior overt HE) were given recommended cognitive tests and a validated SES questionnaire, which included questions about employment, personal and family income, and overall financial security. Comparisons were made among centers and between subjects who were employed or not. Regression analysis was performed using employment and personal income as outcomes. Results Only 37% of subjects had been employed in the last year. Subjects had substantial financial insecurity—their yearly personal income ranged from $16,000 to $24,999 and their family income ranged from $25,000 to $49,999. They were only able to maintain a residence for 3–6 months if their income stopped, and their current liquid assets were $500–$4999 (<$500 if debt was subtracted). Cognition and SES were worst in Ohio and best in Virginia. Cognition correlated with personal and family income, within and between centers. On regression analysis, cognitive performance (digit symbol, lures, and line tracing) was associated with personal yearly income, after controlling for demographics, country, employment, and overt HE. Unemployed subjects had a higher rate of overt HE, worse cognition, and lower personal income than employed subjects. On regression analysis, performance on digit symbol, line tracing, inhibitory control test lures, and serial dotting tests remained associated with income, similar to employment. Conclusions In an international, multi-center

  14. Multi-Center Analysis of Novel and Established Variables Associated with Successful Human Islet Isolation Outcomes

    PubMed Central

    Kaddis, J.S; Danobeitia, J.S.; Niland, J.C.; Stiller, T.; Fernandez, L.A.

    2010-01-01

    Islet transplantation is a promising therapy used to achieve glycometabolic control in a select subgroup of individuals with type I diabetes. However, features that characterize human islet isolation success prior to transplantation are not standardized and lack validation. We conducted a retrospective analysis of 806 isolation records from 14 pancreas processing laboratories, considering variables from relevant studies in the last 15 years. The outcome was defined as post-purification islet equivalent count, dichotomized into yields ≥ 315,000 or ≤ 220,000. Univariate analysis showed that donor cause of death and use of hormonal medications negatively influenced outcome. Conversely, pancreata from heavier donors and those containing elevated levels of surface fat positively influence outcome, as did heavier pancreata and donors with normal amylase levels. Multivariable logistic regression analysis identified the positive impact on outcome of surgically intact pancreata and donors with normal liver function, and confirmed that younger donors, increased body mass index, shorter cold ischemia times, no administration of fluid/electrolyte medications, absence of organ edema, use of University of Wisconsin preservation solution, and a fatty pancreas improves outcome. In conclusion, this multi-center analysis highlights the importance of carefully reviewing of all donor, pancreas, and processing parameters prior to isolation and transplantation. PMID:20055802

  15. Injection-associated pain in femoral arteriography: A European multicenter study comparing safety, tolerability, and efficacy of iodixanol and iopromide

    SciTech Connect

    Justesen, Per; Downes, Mark; Grynne, Birthe Hougens; Lang, Hanne; Rasch, Wenche; Seim, Eva

    1997-07-15

    Purpose. To evaluate injection-associated pain, safety, and efficacy with the isotonic contrast medium iodixanol (Visipaque 270 mg I/ml) compared with iopromide (Ultravist 300 mg I/ml) in femoral arteriography. Methods. A multicenter, double-blind, randomized, parallel-group clinical investigation was carried out in 54 hospitals in Europe. Of the patients evaluated, 1225 received iodixanol and 1227 iopromide in conventional and/or digital subtraction angiography. Results. The iodixanol group reported statistically significantly less injection-associated pain (0.9%) than the iopromide group (9.5%) (p<0.001). Further, 4.1% in the iodixanol group experienced pain and/or severe heat sensation vs 19.8% in the iopromide group (p<0.001). In the iodixanol group, 1.8% of the patients experienced contrast-related adverse events vs 2.4% in the iopromide group (p=NS). Overall diagnostic information was optimal for 94.1% in the iodixanol group and 95.3% in the iopromide group (p=NS). Conclusions. Iodixanol 270 mg I/ml causes significantly less injection-associated pain during femoral arteriography and is as safe and efficatious as iopromide 300 mg I/ml.

  16. Post-radiosurgical edema associated with parasagittal and parafalcine meningiomas: a multicenter study.

    PubMed

    Sheehan, Jason P; Cohen-Inbar, Or; Ruangkanchanasetr, Rawee; Bulent Omay, S; Hess, Judith; Chiang, Veronica; Iorio-Morin, Christian; Alonso-Basanta, Michelle; Mathieu, David; Grills, Inga S; Lee, John Y K; Lee, Cheng-Chia; Dade Lunsford, L

    2015-11-01

    Stereotactic radiosurgery (SRS) offers a high degree of tumor control for benign meningiomas. However, radiosurgery can occasionally incite edema or exacerbate pre-existing peri-tumoral edema. The current study investigates the incidence, timing, and extent of edema around parasagittal or parafalcine meningiomas following SRS. A retrospective multicenter review was undertaken through participating centers in the International Gamma Knife Research Foundation (previously the North American Gamma Knife Consortium or NAGKC). All included patients had a parafalcine or parasagittal meningioma and a minimum of 6 months follow up. The median follow up was 19.6 months (6-158 months). Extent of new or worsening edema was quantitatively analyzed using volumetric analysis; edema indices were longitudinally computed following radiosurgery. Analysis was performed to identify prognostic factors for new or worsening edema. A cohort of 212 patients comprised of 51.9 % (n = 110) females, 40.1 % upfront SRS and 59.9 % underwent adjuvant SRS for post-surgical residual tumor. The median tumor volume at SRS was 5.2 ml. Venous sinus compression or invasion was demonstrated in 25 % (n = 53). The median marginal dose was 14 Gy (8-20 Gy). Tumor volume control was determined in 77.4 % (n = 164 out of 212 patients). Tumor edema progressed and then regressed in 33 % (n = 70), was stable or regressed in 52.8 % (n = 112), and progressively worsened in 5.2 % (n = 11). Tumor location, tumor volume, venous sinus invasion, margin, and maximal dose were found to be significantly related to post-SRS edema in multivariate analysis. SRS affords a high degree of tumor control for patients with parasagittal or parafalcine meningiomas. Nevertheless, SRS can lead to worsening peritumoral edema in a subset of patients such as those with larger tumors (>10 cc) and venous sinus invasion/compression. Long-term follow up is required to detect and appropriately manage post-SRS edema. PMID:26329323

  17. Medial Posterior Meniscal Root Tears Are Associated with Development or Worsening of Medial Tibiofemoral Cartilage Damage: The Multicenter Osteoarthritis Study

    PubMed Central

    Hayashi, Daichi; Jarraya, Mohamed; Roemer, Frank W.; Zhang, Yuqing; Niu, Jingbo; Crema, Michel D.; Englund, Martin; Lynch, John A.; Nevitt, Michael C.; Torner, James C.; Lewis, Cora E.; Felson, David T.

    2013-01-01

    Purpose: To assess the association of meniscal root tear with the development or worsening of tibiofemoral cartilage damage. Materials and Methods: Institutional review board approval and written informed consent from all subjects were obtained. A total of 596 knees with radiographically depicted osteoarthritis were randomly selected from the Multicenter Osteoarthritis study cohort. Cartilage damage was semiquantitatively assessed by using the Whole-Organ Magnetic Resonance Imaging Score (WORMS) system (grades 0–6). Subjects were separated into three groups: root tear only, meniscal tear without root tear, and neither meniscal nor root tear. A log-binomial regression model was used to calculate the relative risks for knees to develop incident or progressing cartilage damage in the root tear group and the meniscal tear group, with the no tear group serving as a reference. Results: In the medial tibiofemoral joint, there were 37 knees with isolated medial posterior root tear, 294 with meniscal tear without root tear, and 264 without meniscal or root tear. There were only two lateral posterior root tears, and no anterior root tears were found. Thus, the focus was on the medial posterior root tear. The frequency of severe cartilage damage (WORMS ≥5) was higher in the group with root tear than in the group without root or meniscal tear (76.7% vs 19.7%, P < .0001) but not in the group with meniscal but no root tear (76.7% vs 65.2%, P = .055). Longitudinal analyses included 33 knees with isolated medial posterior root tear, 270 with meniscal tear, and 245 with no tear. Adjusted relative risk of cartilage loss was 2.03 (95% confidence interval [CI]: 1.18, 3.48) for the root tear group and 1.84 (95% CI: 1.32, 2.58) for the meniscal tear group. Conclusion: Isolated medial posterior meniscal root tear is associated with incident and progressive medial tibiofemoral cartilage loss. © RSNA, 2013 PMID:23696679

  18. High protein intake is associated with low prevalence of frailty among old Japanese women: a multicenter cross-sectional study

    PubMed Central

    2013-01-01

    Background Protein intake has been inversely associated with frailty. However, no study has examined the effect of the difference of protein sources (animal or plant) or the amino acid composing the protein on frailty. Therefore, we examined the association of protein and amino acid intakes with frailty among elderly Japanese women. Methods A total of 2108 grandmothers or acquaintances of dietetic students aged 65 years and older participated in this cross-sectional multicenter study, which was conducted in 85 dietetic schools in 35 prefectures of Japan. Intakes of total, animal, and plant protein and eight selected amino acids were estimated from a validated brief-type self-administered diet history questionnaire and amino acid composition database. Frailty was defined as the presence of three or more of the following four components: slowness and weakness (two points), exhaustion, low physical activity, and unintentional weight loss. Results The number of subjects with frailty was 481 (23%). Adjusted ORs (95% CI) for frailty in the first, second, third, fourth, and fifth quintiles of total protein intake were 1.00 (reference), 1.02 (0.72, 1.45), 0.64 (0.45, 0.93), 0.62 (0.43, 0.90), and 0.66 (0.46, 0.96), respectively (P for trend = 0.001). Subjects categorized to the third, fourth, and fifth quintiles of total protein intake (>69.8 g/d) showed significantly lower ORs than those to the first quintile (all P <0.03). The intakes of animal and plant protein and all selected amino acids were also inversely associated with frailty (P for trend <0.04), with the multivariate adjusted OR in the highest compared to the lowest quintile of 0.73 for animal protein and 0.66 for plant protein, and 0.67-0.74 for amino acids, albeit that the ORs for these dietary variables were less marked than those for total protein. Conclusions Total protein intake was significantly inversely associated with frailty in elderly Japanese women. The association of total protein with

  19. Association of BDNF Polymorphisms with the Risk of Epilepsy: a Multicenter Study.

    PubMed

    Sha'ari, Hidayati Mohd; Haerian, Batoul Sadat; Baum, Larry; Tan, Hui Jan; Rafia, Mohd Hanip; Kwan, Patrick; Cherny, Stacey S; Sham, Pak Chung; Gui, Hongsheng; Raymond, Azman Ali; Lim, Kheng Seang; Mohamed, Zahurin

    2016-07-01

    Epilepsy is a common neurological disease characterized by recurrent unprovoked seizures. Evidence suggested that abnormal activity of brain-derived neurotrophic factor (BDNF) contributes to the pathogenesis of epilepsy. Some previous studies identified association between genetic variants of BDNF and risk of epilepsy. In this study, this association has been examined in the Hong Kong and Malaysian epilepsy cohorts. Genomic DNA of 6047 subjects (1640 patients with epilepsy and 4407 healthy individuals) was genotyped for rs6265, rs11030104, rs7103411, and rs7127507 polymorphisms by using Sequenom MassArray and Illumina HumanHap 610-Quad or 550-Duo BeadChip arrays techniques. Results showed significant association between rs6265 T, rs7103411 C, and rs7127507 T and cryptgenic epilepsy risk (p = 0.00003, p = 0.0002, and p = 0.002, respectively) or between rs6265 and rs7103411 and symptomatic epilepsy risk in Malaysian Indians (TT vs. CC, p = 0.004 and T vs. C, p = 0.0002, respectively) as well as between rs6265 T and risk of cryptogenic epilepsy in Malaysian Chinese (p = 0.005). The Trs6265-Crs7103411-Trs7127507 was significantly associated with cryptogenic epilepsy in Malaysian Indians (p = 0.00005). In conclusion, our results suggest that BDNF polymorphisms might contribute to the risk of epilepsy in Malaysian Indians and Chinese. PMID:25876511

  20. Acute Middle Gastrointestinal Bleeding Risk Associated with NSAIDs, Antithrombotic Drugs, and PPIs: A Multicenter Case-Control Study

    PubMed Central

    Nagata, Naoyoshi; Niikura, Ryota; Yamada, Atsuo; Sakurai, Toshiyuki; Shimbo, Takuro; Kobayashi, Yuka; Okamoto, Makoto; Mitsuno, Yuzo; Ogura, Keiji; Hirata, Yoshihiro; Fujimoto, Kazuma; Akiyama, Junichi; Uemura, Naomi; Koike, Kazuhiko

    2016-01-01

    Background Middle gastrointestinal bleeding (MGIB) risk has not been fully investigated due to its extremely rare occurrence and the need for multiple endoscopies to exclude upper and lower gastrointestinal bleeding. This study investigated whether MGIB is associated with the use of non-steroidal anti-inflammatory drugs (NSAIDs), low-dose aspirin (LDA), thienopyridines, anticoagulants, and proton-pump inhibitors (PPIs), and whether PPI use affects the interactions between MGIB and antithrombotic drugs. Methods In this multicenter, hospital-based, case-control study, 400 patients underwent upper and lower endoscopy, 80 had acute overt MGIB and 320 had no bleeding and were matched for age and sex as controls (1:4). MGIB was additionally evaluated by capsule and/or double-balloon endoscopy, after excluding upper and lower GI bleeding. Adjusted odds ratios (AOR) for MGIB risk were calculated using conditional logistic regression. To estimate the propensity score, we employed a logistic regression model for PPI use. Results In patients with MGIB, mean hemoglobin level was 9.4 g/dL, and 28 patients (35%) received blood transfusions. Factors significantly associated with MGIB were chronic kidney disease (p<0.001), liver cirrhosis (p = 0.034), NSAIDs (p<0.001), thienopyridines (p<0.001), anticoagulants (p = 0.002), and PPIs (p<0.001). After adjusting for these factors, NSAIDs (AOR, 2.5; p = 0.018), thienopyridines (AOR, 3.2; p = 0.015), anticoagulants (AOR, 4.3; p = 0.028), and PPIs (AOR; 2.0; p = 0.021) were independently associated with MGIB. After adjusting for propensity score, the use of PPIs remained an independent risk factors for MGIB (AOR, 1.94; p = 0.034). No significant interactions were observed between PPIs and NSAIDs (AOR, 0.7; p = 0.637), LDA (AOR, 0.3; p = 0.112), thienopyridine (AOR, 0.7, p = 0.671), or anticoagulants (AOR, 0.5; p = 0.545). Conclusions One-third of patients with acute small intestinal bleeding required blood transfusion. NSAIDs

  1. Barriers and Facilitators Associated with Non-Surgical Treatment Use for Osteoarthritis Patients in Orthopaedic Practice

    PubMed Central

    Hofstede, Stefanie N.; Marang-van de Mheen, Perla J.; Vliet Vlieland, Thea P. M.; van den Ende, Cornelia H. M.; Nelissen, Rob G. H. H.; van Bodegom-Vos, Leti

    2016-01-01

    Introduction International evidence-based guidelines for the management of patients with hip and knee osteoarthritis (OA) recommend to start with (a combination of) non-surgical treatments, and using surgical intervention only if a patient does not respond sufficiently to non-surgical treatment options. Despite these recommendations, there are strong indications that non-surgical treatments are not optimally used in orthopaedic practice. To improve the adoption of non-surgical treatments, more insight is needed into barriers and facilitators of these treatments. Therefore, this study assessed which barriers and facilitators are associated with the use and prescription of different non-surgical treatments before hip and knee OA in orthopaedic practice among patients and orthopaedic surgeons in the Netherlands. Materials and Methods We performed two internet-based surveys among 172 orthopaedic surgeons and 174 OA patients. Univariate association and multivariable regression techniques are used to identify barriers and facilitators associated with the use of non-surgical treatments. Results Most barriers and facilitators among patients were associated with the use of physical therapy, lifestyle advice and dietary therapy. Among orthopaedic surgeons, most were associated with prescription of acetaminophen, dietary therapy and physical therapy. Examples of barriers and facilitators among patients included “People in my environment had positive experiences with a surgery” (facilitator for education about OA), and “Advice of people in my environment to keep on moving” (facilitator for lifestyle and dietary advice). For orthopaedic surgeons, examples were “Lack of knowledge about guideline” (barrier for lifestyle advice), “Agreements/ deliberations with primary care” and “Easy communication with a dietician” (facilitators for dietary therapy). Also the belief in the efficacy of these treatments was associated with increased prescription. Conclusions

  2. Association of Insurance Status with Health Outcomes Following Traumatic Injury: Statewide Multicenter Analysis

    PubMed Central

    Chikani, Vatsal; Brophy, Maureen; Vossbrink, Anne; PhD, Khaleel Hussaini; Salvino, Chistopher; Skubic, Jeffrey; Martinez, Rogelio

    2015-01-01

    Introduction Recognizing disparities in definitive care for traumatic injuries created by insurance status may help reduce the higher risk of trauma-related mortality in this population. Our objective was to understand the relationship between patients’ insurance status and trauma outcomes. Methods We collected data on all patients involved in traumatic injury from eight Level I and 15 Level IV trauma centers, and four non-designated hospitals through Arizona State Trauma Registry between January 1, 2008 and December 31, 2011. Of 109,497 records queried, we excluded 29,062 (26.5%) due to missing data on primary payer, sex, race, zip code of residence, injury severity score (ISS), and alcohol or drug use. Of the 80,435 cases analyzed, 13.3% were self-pay, 38.8% were Medicaid, 13% were Medicare, and 35% were private insurance. We evaluated the association between survival and insurance status (private insurance, Medicare, Medicaid, and self-pay) using multiple logistic regression analyses after adjusting for race/ethnicity (White, Black/African American, Hispanic, and American Indian/Alaska Native), age, gender, income, ISS and injury type (penetrating or blunt). Results The self-pay group was more likely to suffer from penetrating trauma (18.2%) than the privately insured group (6.0%), p<0.0001. There were more non-White (53%) self-pay patients compared to the private insurance group (28.3%), p<0.0001. Additionally, the self-pay group had significantly higher mortality (4.3%) as compared to private insurance (1.9%), p<0.0001. A simple logistic regression revealed higher mortality for self-pay patients (crude OR= 2.32, 95% CI [2.07–2.67]) as well as Medicare patients (crude OR= 2.35, 95% CI [2.54–3.24]) as compared to private insurance. After adjusting for confounding, a multiple logistic regression revealed that mortality was highest for self-pay patients as compared to private insurance (adjusted OR= 2.76, 95% CI [2.30–3.32]). Conclusion These results

  3. Association of proinflammatory cytokines and chemotherapy-associated cognitive impairment in breast cancer patients: a multi-centered, prospective, cohort study†

    PubMed Central

    Cheung, Y. T.; Ng, T.; Shwe, M.; Ho, H. K.; Foo, K. M.; Cham, M. T.; Lee, J. A.; Fan, G.; Tan, Y. P.; Yong, W. S.; Madhukumar, P.; Loo, S. K.; Ang, S. F.; Wong, M.; Chay, W. Y.; Ooi, W. S.; Dent, R. A.; Yap, Y. S.; Ng, R.; Chan, A.

    2015-01-01

    Background Existing evidence suggests that proinflammatory cytokines play an intermediary role in postchemotherapy cognitive impairment. This is one of the largest multicentered, cohort studies conducted in Singapore to evaluate the prevalence and proinflammatory biomarkers associated with cognitive impairment in breast cancer patients. Patients and methods Chemotherapy-receiving breast cancer patients (stages I–III) were recruited. Proinflammatory plasma cytokines concentrations [interleukin (IL)-1β, IL-2, IL-4, IL-6, IL-8, IL-10, granulocyte–macrophage colony-stimulating factor, interferon-γ and tumor necrosis factor-α] were evaluated at 3 time points (before chemotherapy, 6 and 12 weeks after chemotherapy initiation). The FACT-Cog (version 3) was utilized to evaluate patients' self-perceived cognitive disturbances and a computerized neuropsychological assessment (Headminder™) was administered to evaluate patients' memory, attention, response speed and processing speed. Changes of cognition throughout chemotherapy treatment were compared against the baseline. Linear mixed-effects models were applied to test the relationships of clinical variables and cytokine concentrations on self-perceived cognitive disturbances and each objective cognitive domain. Results Ninety-nine patients were included (age 50.5 ± 8.4 years; 81.8% Chinese; mean duration of education = 10.8 ± 3.3 years). Higher plasma IL-1β was associated with poorer response speed performance (estimate: −0.78; 95% confidence interval (CI) −1.34 to −0.03; P = 0.023), and a higher concentration of IL-4 was associated with better response speed performance (P = 0.022). Higher concentrations of IL-1β and IL-6 were associated with more severe self-perceived cognitive disturbances (P = 0.018 and 0.001, respectively). Patients with higher concentrations of IL-4 also reported less severe cognitive disturbances (P = 0.022). Conclusions While elevated concentrations of IL-6 and IL-1β were

  4. The Use of a Sequenced Questioning Paradigm to Facilitate Associative Fluency in Preschoolers.

    ERIC Educational Resources Information Center

    Pellegrini, A. D.; Greene, Helen

    The extent to which free play versus sequenced questioning conditions facilitates preschoolers' associative fluency was investigated in this study. Twenty-four children (12 boys and 12 girls, with a mean age of 50.7 months) were randomly assigned to one of three conditions: free play, sequenced questioning, and control. In the sequenced…

  5. Prospective Multicenter Study of Community-Associated Skin and Skin Structure Infections due to Methicillin-Resistant Staphylococcus aureus in Buenos Aires, Argentina

    PubMed Central

    López Furst, María José; de Vedia, Lautaro; Fernández, Silvina; Gardella, Noella; Ganaha, María Cristina; Prieto, Sergio; Carbone, Edith; Lista, Nicolás; Rotryng, Flavio; Morera, Graciana I.; Mollerach, Marta; Stryjewski, Martín E.

    2013-01-01

    Background Community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) is now the most common cause of skin and skin structure infections (SSSI) in several world regions. In Argentina prospective, multicenter clinical studies have only been conducted in pediatric populations. Objective Primary: describe the prevalence, clinical and demographic characteristics of adult patients with community acquired SSSI due to MRSA; secondary: molecular evaluation of CA-MRSA strains. Patients with MRSA were compared to those without MRSA. Materials and Methods Prospective, observational, multicenter, epidemiologic study, with molecular analysis, conducted at 19 sites in Argentina (18 in Buenos Aires) between March 2010 and October 2011. Patients were included if they were ≥14 years, were diagnosed with SSSI, a culture was obtained, and there had no significant healthcare contact identified. A logistic regression model was used to identify factors associated with CA-MRSA. Pulse field types, SCCmec, and PVL status were also determined. Results A total of 311 patients were included. CA-MRSA was isolated in 70% (218/311) of patients. Clinical variables independently associated with CA-MRSA were: presence of purulent lesion (OR 3.29; 95%CI 1.67, 6.49) and age <50 years (OR 2.39; 95%CI 1.22, 4.70). The vast majority of CA-MRSA strains causing SSSI carried PVL genes (95%) and were SCCmec type IV. The sequence type CA-MRSA ST30 spa t019 was the predominant clone. Conclusions CA-MRSA is now the most common cause of SSSI in our adult patients without healthcare contact. ST30, SCCmec IV, PVL+, spa t019 is the predominant clone in Buenos Aires, Argentina. PMID:24324543

  6. Noninvasive electrocardiomapping facilitates previously failed ablation of right appendage diverticulum associated life-threatening accessory pathway.

    PubMed

    Hocini, Mélèze; Shah, Ashok J; Cochet, Hubert; Maury, Philippe; Denis, Arnaud; Haïssaguerre, Michel

    2013-05-01

    Combination of structural (CT-scan) and functional (3D electrocardiomapping) imaging methods helped successfully accomplish ablation of a life-threatening manifest accessory pathway in association with a complex right atrial anomaly after previous unsuccessful attempts of endo-epicardial ablation guided by the invasive electroanatomic system in an adolescent female. Such a system has a potential to facilitate the ablation procedure and impact its outcome through accurate localization of the arrhythmogenic substrate. PMID:23252769

  7. Patient associations as stakeholders: a valuable partner for facilitating access to therapy.

    PubMed

    Lobban, Trudie C A; Camm, A John

    2011-05-01

    One set of important objectives of patient associations is to provide education, support, and advice to those affected by cardiac arrhythmias to ensure that they have access to appropriate diagnosis and treatment. In this perspective it is essential to establish a balanced partnership between patients and clinicians in order to facilitate the work of the patient association. Such associations must work under the guidance of and in consultation with a medical advisory committee for the production of appropriate and validated educational and awareness materials. Patient association coalitions represent and promote partnerships between professionals, patients, government, organizations, and industry. The power of an alliance works in bringing pressure to bear, in lobbying on behalf of specific patient groups. This type of coalition may also act as a depository for relevant databases and contact information relating to all the members who participate in the coalition, and facilitate rapid and complete communication between all interested parties. When fully developed it may also serve to provide current information on the diagnosis, treatment, and management of cardiac arrhythmias to patients, paramedical staff, and physicians. The Arrhythmia Alliance, initially established in the UK but now developing on an international basis sources, collates, and reflects views and data collected from members, bringing beneficial perspectives to the fore to ensure that change is led by the people and for the people. PMID:21518744

  8. Associations between Tobacco, Alcohol, and Drug Use with Coronary Artery Plaque among HIV-Infected and Uninfected Men in the Multicenter AIDS Cohort Study

    PubMed Central

    Kelly, Sean G.; Plankey, Michael; Post, Wendy S.; Li, Xiuhong; Stall, Ronald; Jacobson, Lisa P.; Witt, Mallory D.; Kingsley, Lawrence; Cox, Christopher; Budoff, Matthew; Palella, Frank J.

    2016-01-01

    Background We characterized associations between smoking, alcohol, and recreational drug use and coronary plaque by HIV serostatus within the Multicenter AIDS Cohort Study (MACS). Methods MACS participants (N = 1005, 621 HIV+ and 384 HIV-) underwent non-contrast CT scanning to measure coronary artery calcium; 764 underwent coronary CT angiograms to evaluate plaque type and extent. Self-reported use of alcohol, tobacco, smoked/inhaled cocaine, methamphetamine, ecstasy, marijuana, inhaled nitrites, and erectile dysfunction drugs was obtained at semi-annual visits beginning 10 years prior to CT scanning. Multivariable logistic and linear regression models were performed, stratified by HIV serostatus. Results Among HIV+ men, current smoking, former smoking, and cumulative pack years of smoking were positively associated with multiple coronary plaque measures (coronary artery calcium presence and extent, total plaque presence and extent, calcified plaque presence, and stenosis >50%). Smoking was significantly associated with fewer plaque measures of comparable effect size among HIV- men; current smoking and calcified plaque extent was the only such association. Heavy alcohol use (>14 drinks/week) was associated with stenosis >50% among HIV+ men. Among HIV- men, low/moderate (1–14 drinks/week) and heavy alcohol use were inversely associated with coronary artery calcium and calcified plaque extent. Few significant associations between other recreational drug use and plaque measures were observed. Conclusion Smoking is strongly associated with coronary plaque among HIV+ men, underscoring the value of smoking cessation for HIV+ persons. Alcohol use may protect against coronary artery calcium and calcified plaque progression in HIV- (but not HIV+) men. Few positive associations were observed between recreational drug use and coronary plaque measures. PMID:26811937

  9. The Burden of Provider-Initiated Preterm Birth and Associated Factors: Evidence from the Brazilian Multicenter Study on Preterm Birth (EMIP)

    PubMed Central

    Souza, Renato T.; Cecatti, Jose G.; Passini, Renato; Tedesco, Ricardo P.; Lajos, Giuliane J.; Nomura, Marcelo L.; Rehder, Patricia M.; Dias, Tabata Z.; Haddad, Samira M.; Pacagnella, Rodolfo C.; Costa, Maria L.

    2016-01-01

    Background About 15 million children are born under 37 weeks of gestation worldwide. Prematurity is the leading cause of neonatal deaths and short/long term morbidities, entailing consequences not only for the individual, but also their family, health agencies, facilities and all community. The provider-initiated preterm birth is currently one of the most important obstetric conditions related to preterm births, particularly in middle and high income countries, thus decreasing the need for therapeutic preterm birth is essential to reduce global prematurity. Therefore detailed knowledge on the factors associated with provider-initiated preterm birth is essential for the efforts to reduce preterm birth rates and its consequences. In this current analysis we aimed to assess the proportion of provider-initiated (pi-PTB) among preterm births in Brazil and identify associated factors. Methods and Findings This is an analysis of a multicenter cross-sectional study with a nested case-control component called Brazilian Multicenter Study on Preterm Birth (EMIP). EMIP was conducted in 20 referral obstetric hospitals located in the three most populated of the five Brazilian regions. We analysed data of women with pi-PTB, defined as childbirth occurring at less than 37 weeks, medically indicated for maternal/fetal compromise or both; and women with term birth, childbirth at or after 37 weeks. Maternal, sociodemographic, obstetric, prenatal care, delivery, and postnatal characteristics were assessed as possible factors associated with pi-PTB, compared to term births. The overall prevalence of preterm births was 12.3%. Of these, approximately one-third of cases were initiated by the provider. Hypertensive disorders, placental abruption, and diabetes were the main maternal conditions leading to pi-PTB. Caesarean section was the most common mode of delivery. Chronic hypertension (OR 7.47; 95%CI 4.02–13.88), preeclampsia/eclampsia/HELLP syndrome (OR 15.35; 6.57–35.88), multiple

  10. No association of TGFB1 L10P genotypes and breast cancer risk in BRCA1 and BRCA2 mutation carriers: a multi-center cohort study

    PubMed Central

    Antoniou, Antonis C.; Llopis, Trinidad Caldes; Nevanlinna, Heli; Aittomäki, Kristiina; Simard, Jacques; Spurdle, Amanda B.; Couch, Fergus J.; Pereira, Lutecia H. Mateus; Greene, Mark H.; Andrulis, Irene L.; Pasche, Boris; Kaklamani, Virginia; Hamann, Ute; Szabo, Csilla; Peock, Susan; Cook, Margaret; Harrington, Patricia A.; Donaldson, Alan; Male, Allison M.; Gardiner, Carol Anne; Gregory, Helen; Side, Lucy E.; Robinson, Anne C.; Emmerson, Louise; Ellis, Ian; Peyrat, Jean-Philippe; Fournier, Joëlle; Vennin, Philippe; Adenis, Claude; Muller, Danièle; Fricker, Jean-Pierre; Longy, Michel; Sinilnikova, Olga M.; Stoppa-Lyonnet, Dominique; Schmutzler, Rita K.; Versmold, Beatrix; Engel, Christoph; Meindl, Alfons; Kast, Karin; Schaefer, Dieter; Froster, Ursula G.; Chenevix-Trench, Georgia; Easton, Douglas F.

    2008-01-01

    Background The transforming growth factor β-1 gene (TGFB1) is a plausible candidate for breast cancer susceptibility. The L10P variant of TGFB1 is associated with higher circulating levels and secretion of TGF-β, and recent large-scale studies suggest strongly that this variant is associated with breast cancer risk in the general population. Methods To evaluate whether TGFB1 L10P also modifies the risk of breast cancer in BRCA1 or BRCA2 mutation carriers, we undertook a multi-center study of 3,442 BRCA1 and 2,095 BRCA2 mutation carriers. Results We found no evidence of association between TGFB1 L10P and breast cancer risk in either BRCA1 or BRCA2 mutation carriers. The per-allele HR for the L10P variant was 1.01 (95%CI: 0.92–1.11) in BRCA1 carriers and 0.92 (95%CI: 0.81–1.04) in BRCA2 mutation carriers. Conclusions These results do not support the hypothesis that TGFB1 L10P genotypes modify the risk of breast cancer in BRCA1 or BRCA2 mutation carriers. PMID:18523885

  11. Polymicrogyria-associated epilepsy: a multi-center phenotypic study from the Epilepsy Phenome/Genome Project

    PubMed Central

    Shain, Catherine; Ramgopal, Sriram; Fallil, Zianka; Parulkar, Isha; Alongi, Richard; Knowlton, Robert; Poduri, Annapurna

    2013-01-01

    Purpose Polymicrogyria (PMG) is an epileptogenic malformation of cortical development. We describe the clinical epilepsy and imaging features of a large cohort with PMG-related epilepsy. Methods Participants were recruited through the Epilepsy Phenome/Genome Project, a multi-center collaborative effort to collect detailed phenotypic data on individuals with epilepsy. We reviewed phenotypic data from participants with epilepsy and PMG. Key Findings We identified 87 participants, 43 female and 44 male, with PMG and epilepsy. Median age of seizure onset was 3 years (range <1 month-37 years). Most presented with focal epilepsy (87.4%), some in combination with seizures generalized from onset (23.0%). Focal seizures with dyscognitive features were most common (54.3%). Of those presenting with generalized seizure types, infantile spasms were most prevalent (45.2%). The most common topographic pattern was perisylvian PMG (77.0%), of which the majority was bilateral (56.7%). Generalized PMG presented with an earlier age of seizure onset (median age of 8 months) and an increased prevalence of developmental delay prior to seizure onset (57.1%). Of the focal, unilateral and asymmetric bilateral groups where PMG was more involved in one hemisphere, the majority (71.4%) of participants had seizures that lateralized to the same hemisphere as the PMG or the hemisphere with greater involvement. Significance Participants with PMG had both focal and generalized onset of seizures. Our data confirm the involvement of known topographic patterns of PMG and suggest that more extensive distributions of PMG present with an earlier age of seizure onset and increased prevalence of developmental delay prior to seizure onset. PMID:23750890

  12. Sharing and re-use of phylogenetic trees (and associated data) to facilitate synthesis

    PubMed Central

    2012-01-01

    Background Recently, various evolution-related journals adopted policies to encourage or require archiving of phylogenetic trees and associated data. Such attention to practices that promote sharing of data reflects rapidly improving information technology, and rapidly expanding potential to use this technology to aggregate and link data from previously published research. Nevertheless, little is known about current practices, or best practices, for publishing trees and associated data so as to promote re-use. Findings Here we summarize results of an ongoing analysis of current practices for archiving phylogenetic trees and associated data, current practices of re-use, and current barriers to re-use. We find that the technical infrastructure is available to support rudimentary archiving, but the frequency of archiving is low. Currently, most phylogenetic knowledge is not easily re-used due to a lack of archiving, lack of awareness of best practices, and lack of community-wide standards for formatting data, naming entities, and annotating data. Most attempts at data re-use seem to end in disappointment. Nevertheless, we find many positive examples of data re-use, particularly those that involve customized species trees generated by grafting to, and pruning from, a much larger tree. Conclusions The technologies and practices that facilitate data re-use can catalyze synthetic and integrative research. However, success will require engagement from various stakeholders including individual scientists who produce or consume shareable data, publishers, policy-makers, technology developers and resource-providers. The critical challenges for facilitating re-use of phylogenetic trees and associated data, we suggest, include: a broader commitment to public archiving; more extensive use of globally meaningful identifiers; development of user-friendly technology for annotating, submitting, searching, and retrieving data and their metadata; and development of a minimum reporting

  13. Thyroid function modifies the association between ratio of triglyceride to high-density lipoprotein cholesterol and renal function: a multicenter cross-sectional study

    PubMed Central

    Yuan, Zhongshang; Zhao, Meng; Zhang, Bingchang; Zhang, Haiqing; Zhang, Xu; Guan, Qingbo; Ning, Guang; Gao, Ling; Xue, Fuzhong; Zhao, Jiajun

    2015-01-01

    Hypothyroidism was confirmed to be associated with both dyslipidemia and renal dysfunction. However, the impact of thyroid function on the relationship between serum lipid levels and renal function has never been given sufficient attention. In this large-scale multicenter cross-sectional study, the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL) and the prevalence of hypothyroidism in CKD subjects were significantly higher than those in non-CKD ones (P < 0.001). After adjustment for potential confounding factors, TG/HDL was shown to be significantly associated with serum Cr levels (β = 0.551; 95%CI, 0.394–0.708), and eGFR (β = −0.481; 95%CI, −0.731–−0.230). The risk for CKD was significantly increased as TG/HDL ratio was elevated (adjusted odds ratio = 1.20; 95%CI, 1.11–1.27). These significant associations were found among subjects with euthyroidism and hypothyroidism rather than hyperthyroidism. Furthermore, the associations between TG/HDL and Cr or CKD status were significantly greater in hypothyroidism than those in euthyroidism (P < 0.05). These results suggested that elevated TG/HDL ratio was associated with renal dysfunction; it exhibited a significantly stronger association with Cr and CKD in hypothyroidism than in euthyroidism. Therefore, more attention should be paid on lipid profile to prevent or delay the occurrence and progression of renal dysfunction, especially for those with hypothyroidism. PMID:26179571

  14. Thyroid function modifies the association between ratio of triglyceride to high-density lipoprotein cholesterol and renal function: a multicenter cross-sectional study.

    PubMed

    Yuan, Zhongshang; Zhao, Meng; Zhang, Bingchang; Zhang, Haiqing; Zhang, Xu; Guan, Qingbo; Ning, Guang; Gao, Ling; Xue, Fuzhong; Zhao, Jiajun

    2015-01-01

    Hypothyroidism was confirmed to be associated with both dyslipidemia and renal dysfunction. However, the impact of thyroid function on the relationship between serum lipid levels and renal function has never been given sufficient attention. In this large-scale multicenter cross-sectional study, the ratio of triglyceride to high-density lipoprotein cholesterol (TG/HDL) and the prevalence of hypothyroidism in CKD subjects were significantly higher than those in non-CKD ones (P < 0.001). After adjustment for potential confounding factors, TG/HDL was shown to be significantly associated with serum Cr levels (β = 0.551; 95%CI, 0.394-0.708), and eGFR (β = -0.481; 95%CI, -0.731--0.230). The risk for CKD was significantly increased as TG/HDL ratio was elevated (adjusted odds ratio = 1.20; 95%CI, 1.11-1.27). These significant associations were found among subjects with euthyroidism and hypothyroidism rather than hyperthyroidism. Furthermore, the associations between TG/HDL and Cr or CKD status were significantly greater in hypothyroidism than those in euthyroidism (P < 0.05). These results suggested that elevated TG/HDL ratio was associated with renal dysfunction; it exhibited a significantly stronger association with Cr and CKD in hypothyroidism than in euthyroidism. Therefore, more attention should be paid on lipid profile to prevent or delay the occurrence and progression of renal dysfunction, especially for those with hypothyroidism. PMID:26179571

  15. Implementation of Departmental Quality Strategies Is Positively Associated with Clinical Practice: Results of a Multicenter Study in 73 Hospitals in 7 European Countries

    PubMed Central

    2015-01-01

    Background Given the amount of time and resources invested in implementing quality programs in hospitals, few studies have investigated their clinical impact and what strategies could be recommended to enhance its effectiveness. Objective To assess variations in clinical practice and explore associations with hospital- and department-level quality management systems. Design Multicenter, multilevel cross-sectional study. Setting and Participants Seventy-three acute care hospitals with 276 departments managing acute myocardial infarction, deliveries, hip fracture, and stroke in seven countries. Intervention None. Measures Predictor variables included 3 hospital- and 4 department-level quality measures. Six measures were collected through direct observation by an external surveyor and one was assessed through a questionnaire completed by hospital quality managers. Dependent variables included 24 clinical practice indicators based on case note reviews covering the 4 conditions (acute myocardial infarction, deliveries, hip fracture and stroke). A directed acyclic graph was used to encode relationships between predictors, outcomes, and covariates and to guide the choice of covariates to control for confounding. Results and Limitations Data were provided on 9021 clinical records by 276 departments in 73 hospitals. There were substantial variations in compliance with the 24 clinical practice indicators. Weak associations were observed between hospital quality systems and 4 of the 24 indicators, but on analyzing department-level quality systems, strong associations were observed for 8 of the 11 indicators for acute myocardial infarction and stroke. Clinical indicators supported by higher levels of evidence were more frequently associated with quality systems and activities. Conclusions There are significant gaps between recommended standards of care and clinical practice in a large sample of hospitals. Implementation of department-level quality strategies was significantly

  16. DNA barcoding facilitates associations and diagnoses for Trichoptera larvae of the Churchill (Manitoba, Canada) area

    PubMed Central

    2013-01-01

    Background The North American Trichoptera larvae are poorly known at the species level, despite their importance in the understanding of freshwater fauna and critical use in biomonitoring. This study focused on morphological diagnoses for larvae occurring in the Churchill, Manitoba area, representing the largest larval association effort for the caddisflies at any given locality thus far. The current DNA barcode reference library of Trichoptera (available on the Barcode of Life Data Systems) was utilized to provide larval-adult associations. Results The present study collected an additional 23 new species records for the Churchill area, increasing the total Trichoptera richness to 91 species. We were able to associate 62 larval taxa, comprising 68.1% of the Churchill area Trichoptera taxa. This endeavor to identify immature life stage for the caddisflies enabled the development of morphological diagnoses, production of photographs and an appropriate taxonomic key to facilitate larval species analyses in the area. Conclusions The use of DNA for associations of unknown larvae with known adults proved rapid and successful. This method should accelerate the state-of-knowledge for North American Trichoptera larvae as well as other taxonomic lineages. The morphological analysis should be useful for determination of material from the Churchill area. PMID:23425021

  17. Competition and facilitation between the marine nitrogen-fixing cyanobacterium Cyanothece and its associated bacterial community

    PubMed Central

    Brauer, Verena S.; Stomp, Maayke; Bouvier, Thierry; Fouilland, Eric; Leboulanger, Christophe; Confurius-Guns, Veronique; Weissing, Franz J.; Stal, LucasJ.; Huisman, Jef

    2014-01-01

    N2-fixing cyanobacteria represent a major source of new nitrogen and carbon for marine microbial communities, but little is known about their ecological interactions with associated microbiota. In this study we investigated the interactions between the unicellular N2-fixing cyanobacterium Cyanothece sp. Miami BG043511 and its associated free-living chemotrophic bacteria at different concentrations of nitrate and dissolved organic carbon and different temperatures. High temperature strongly stimulated the growth of Cyanothece, but had less effect on the growth and community composition of the chemotrophic bacteria. Conversely, nitrate and carbon addition did not significantly increase the abundance of Cyanothece, but strongly affected the abundance and species composition of the associated chemotrophic bacteria. In nitrate-free medium the associated bacterial community was co-dominated by the putative diazotroph Mesorhizobium and the putative aerobic anoxygenic phototroph Erythrobacter and after addition of organic carbon also by the Flavobacterium Muricauda. Addition of nitrate shifted the composition toward co-dominance by Erythrobacter and the Gammaproteobacterium Marinobacter. Our results indicate that Cyanothece modified the species composition of its associated bacteria through a combination of competition and facilitation. Furthermore, within the bacterial community, niche differentiation appeared to play an important role, contributing to the coexistence of a variety of different functional groups. An important implication of these findings is that changes in nitrogen and carbon availability due to, e.g., eutrophication and climate change are likely to have a major impact on the species composition of the bacterial community associated with N2-fixing cyanobacteria. PMID:25642224

  18. Competition and facilitation between the marine nitrogen-fixing cyanobacterium Cyanothece and its associated bacterial community.

    PubMed

    Brauer, Verena S; Stomp, Maayke; Bouvier, Thierry; Fouilland, Eric; Leboulanger, Christophe; Confurius-Guns, Veronique; Weissing, Franz J; Stal, LucasJ; Huisman, Jef

    2014-01-01

    N2-fixing cyanobacteria represent a major source of new nitrogen and carbon for marine microbial communities, but little is known about their ecological interactions with associated microbiota. In this study we investigated the interactions between the unicellular N2-fixing cyanobacterium Cyanothece sp. Miami BG043511 and its associated free-living chemotrophic bacteria at different concentrations of nitrate and dissolved organic carbon and different temperatures. High temperature strongly stimulated the growth of Cyanothece, but had less effect on the growth and community composition of the chemotrophic bacteria. Conversely, nitrate and carbon addition did not significantly increase the abundance of Cyanothece, but strongly affected the abundance and species composition of the associated chemotrophic bacteria. In nitrate-free medium the associated bacterial community was co-dominated by the putative diazotroph Mesorhizobium and the putative aerobic anoxygenic phototroph Erythrobacter and after addition of organic carbon also by the Flavobacterium Muricauda. Addition of nitrate shifted the composition toward co-dominance by Erythrobacter and the Gammaproteobacterium Marinobacter. Our results indicate that Cyanothece modified the species composition of its associated bacteria through a combination of competition and facilitation. Furthermore, within the bacterial community, niche differentiation appeared to play an important role, contributing to the coexistence of a variety of different functional groups. An important implication of these findings is that changes in nitrogen and carbon availability due to, e.g., eutrophication and climate change are likely to have a major impact on the species composition of the bacterial community associated with N2-fixing cyanobacteria. PMID:25642224

  19. Association between moderate-to-severe diarrhea in young children in the global enteric multicenter study (GEMS) and types of handwashing materials used by caretakers in Mirzapur, Bangladesh.

    PubMed

    Baker, Kelly K; Dil Farzana, Fahmida; Ferdous, Farzana; Ahmed, Shahnawaz; Kumar Das, Sumon; Faruque, A S G; Nasrin, Dilruba; Kotloff, Karen L; Nataro, James P; Kolappaswamy, Krishnan; Levine, Myron M

    2014-07-01

    Handwashing practices among caretakers of case and control children < 5 years of age enrolled in the Global Enteric Multicenter Study in Mirzapur, Bangladesh were characterized and analyzed for association with moderate-to-severe diarrhea. Soap or detergent ownership was common, yet 48% of case and 47.7% of control caretakers also kept ashes for handwashing, including 36.8% of the wealthiest households. Soap, detergent, and ash were used for multiple hygiene purposes and were kept together at handwashing areas. Caretakers preferred soap for handwashing, but frequently relied on ash, or a detergent/ash mixture, as a low-cost alternative. Moderate-to-severe diarrhea was equally likely for children of caretakers who kept soap versus those who kept ash (matched OR = 0.91; 0.62-1.32). Contact with ash and water reduced concentrations of bacterial enteropathogens, without mechanical scrubbing. Thus, washing hands with ash is a prevalent behavior in Mirzapur and may help diminish transmission of diarrheal pathogens to children. PMID:24778193

  20. A Multicenter Phase II Study of Local Radiation Therapy for Stage IEA Mucosa-Associated Lymphoid Tissue Lymphomas: A Preliminary Report From the Japan Radiation Oncology Group (JAROG)

    SciTech Connect

    Isobe, Koichi Kagami, Yoshikazu; Higuchi, Keiko; Kodaira, Takeshi; Hasegawa, Masatoshi; Shikama, Naoto; Nakazawa, Masanori; Fukuda, Ichiro; Nihei, Keiji; Ito, Kana; Teshima, Teruki; Matsuno, Yoshihiro; Oguchi, Masahiko

    2007-11-15

    Purpose: The aim of this study was to evaluate the efficacy and toxicity of moderate dose radiation therapy (RT) for mucosa-associated lymphoid tissue (MALT) lymphoma in a prospective multicenter phase II trial. Methods and Materials: The subjects in this study were 37 patients with MALT lymphoma between April 2002 and November 2004. There were 16 male and 21 female patients, ranging in age from 24 to 82 years, with a median of 56 years. The primary tumor originated in the orbit in 24 patients, in the thyroid and salivary gland in 4 patients each, and 5 in the others. The median tumor dose was 30.6 Gy (range, 30.6-39.6 Gy), depending on the primary site and maximal tumor diameter. The median follow-up was 37.3 months. Results: Complete remission (CR) or CR/unconfirmed was achieved in 34 patients (92%). The 3-year overall survival, progression-free survival, and local control probability were 100%, 91.9%, and 97.3%, respectively. Thirteen patients experienced Grade 1 acute toxicities including dermatitis, mucositis, and conjunctivitis. One patient developed Grade 2 taste loss. Regarding late toxicities, Grade 2 reactions including hypothyroidism, and radiation pneumonitis were observed in three patients, and Grade 3 cataract was seen in three patients. Conclusions: This prospective phase II study demonstrated that moderate dose RT was highly effective in achieving local control with acceptable morbidity in 37 patients with MALT lymphoma.

  1. Association between Moderate-to-Severe Diarrhea in Young Children in the Global Enteric Multicenter Study (GEMS) and Types of Handwashing Materials Used by Caretakers in Mirzapur, Bangladesh

    PubMed Central

    Baker, Kelly K.; Dil Farzana, Fahmida; Ferdous, Farzana; Ahmed, Shahnawaz; Kumar Das, Sumon; Faruque, A. S. G.; Nasrin, Dilruba; Kotloff, Karen L.; Nataro, James P.; Kolappaswamy, Krishnan; Levine, Myron M.

    2014-01-01

    Handwashing practices among caretakers of case and control children < 5 years of age enrolled in the Global Enteric Multicenter Study in Mirzapur, Bangladesh were characterized and analyzed for association with moderate-to-severe diarrhea. Soap or detergent ownership was common, yet 48% of case and 47.7% of control caretakers also kept ashes for handwashing, including 36.8% of the wealthiest households. Soap, detergent, and ash were used for multiple hygiene purposes and were kept together at handwashing areas. Caretakers preferred soap for handwashing, but frequently relied on ash, or a detergent/ash mixture, as a low-cost alternative. Moderate-to-severe diarrhea was equally likely for children of caretakers who kept soap versus those who kept ash (matched OR = 0.91; 0.62–1.32). Contact with ash and water reduced concentrations of bacterial enteropathogens, without mechanical scrubbing. Thus, washing hands with ash is a prevalent behavior in Mirzapur and may help diminish transmission of diarrheal pathogens to children. PMID:24778193

  2. Effect of Probiotic Lactobacillus (Lacidofil® Cap) for the Prevention of Antibiotic-associated Diarrhea: A Prospective, Randomized, Double-blind, Multicenter Study

    PubMed Central

    Song, Hyun Joo; Kim, Jin-Yong; Kim, Seong-Eun; Park, Hye-Sook; Jeong, Yoolwon; Hong, Sung Pil; Cheon, Jae Hee; Kim, Won Ho; Kim, Hyo-Jong; Ye, Byong Duk; Yang, Suk-Kyun; Kim, Sang-Woo; Shin, Sung-Jae; Kim, Hyun-Soo; Sung, Jae-Kyu; Kim, Eun Young

    2010-01-01

    Antibiotic-associated diarrhea (AAD) is a common complication of antibiotic use. There is growing interest in probiotics for the treatment of AAD and Clostridium difficile infection because of the wide availability of probiotics. The aim of this multicenter, randomized, placebo-controlled, double-blind trial was to assess the efficacy of probiotic Lactobacillus (Lacidofil® cap) for the prevention of AAD in adults. From September 2008 to November 2009, a total of 214 patients with respiratory tract infection who had begun receiving antibiotics were randomized to receive Lactobacillus (Lacidofil® cap) or placebo for 14 days. Patients recorded bowel frequency and stool consistency daily for 14 days. The primary outcome was the proportion of patients who developed AAD within 14 days of enrollment. AAD developed in 4 (3.9%) of 103 patients in the Lactobacillus group and in 8 (7.2%) of 111 patients in the placebo group (P=0.44). However, the Lactobacillus group showed lower change in bowel frequency and consistency (50/103, 48.5%) than the placebo group (35/111, 31.5%) (P=0.01). Although the Lacidofil® cap does not reduce the rate of occurrence of AAD in adult patients with respiratory tract infection who have taken antibiotics, the Lactobacillus group maintains their bowel habits to a greater extent than the placebo group. PMID:21165295

  3. SEQMINER: An R-Package to Facilitate the Functional Interpretation of Sequence-Based Associations

    PubMed Central

    Zhan, Xiaowei; Liu, Dajiang J.

    2016-01-01

    Next-generation sequencing has enabled the study of a comprehensive catalogue of genetic variants for their impact on various complex diseases. Numerous consortia studies of complex traits have publically released their summary association statistics, which have become an invaluable resource for learning the underlying biology, understanding the genetic architecture, and guiding clinical translations. There is great interest in the field in developing novel statistical methods for analyzing and interpreting results from these genotype-phenotype association studies. One popular platform for method development and data analysis is R. In order to enable these analyses in R, it is necessary to develop packages that can efficiently query files of summary association statistics, explore the linkage disequilibrium structure between variants, and integrate various bioinformatics databases. The complexity and scale of sequence datasets and databases pose significant computational challenges for method developers. To address these challenges and facilitate method development, we developed the R package SEQMINER for annotating and querying files of sequence variants (e.g., VCF/BCF files) and summary association statistics (e.g., METAL/RAREMETAL files), and for integrating bioinformatics databases. SEQMINER provides an infrastructure where novel methods can be distributed and applied to analyzing sequence datasets in practice. We illustrate the performance of SEQMINER using datasets from the 1000 Genomes Project. We show that SEQMINER is highly efficient and easy to use. It will greatly accelerate the process of applying statistical innovations to analyze and interpret sequence-based associations. The R package, its source code and documentations are available from http://cran.r-project.org/web/packages/seqminer and http://seqminer.genomic.codes/. PMID:26394715

  4. SEQMINER: An R-Package to Facilitate the Functional Interpretation of Sequence-Based Associations.

    PubMed

    Zhan, Xiaowei; Liu, Dajiang J

    2015-12-01

    Next-generation sequencing has enabled the study of a comprehensive catalogue of genetic variants for their impact on various complex diseases. Numerous consortia studies of complex traits have publically released their summary association statistics, which have become an invaluable resource for learning the underlying biology, understanding the genetic architecture, and guiding clinical translations. There is great interest in the field in developing novel statistical methods for analyzing and interpreting results from these genotype-phenotype association studies. One popular platform for method development and data analysis is R. In order to enable these analyses in R, it is necessary to develop packages that can efficiently query files of summary association statistics, explore the linkage disequilibrium structure between variants, and integrate various bioinformatics databases. The complexity and scale of sequence datasets and databases pose significant computational challenges for method developers. To address these challenges and facilitate method development, we developed the R package SEQMINER for annotating and querying files of sequence variants (e.g., VCF/BCF files) and summary association statistics (e.g., METAL/RAREMETAL files), and for integrating bioinformatics databases. SEQMINER provides an infrastructure where novel methods can be distributed and applied to analyzing sequence datasets in practice. We illustrate the performance of SEQMINER using datasets from the 1000 Genomes Project. We show that SEQMINER is highly efficient and easy to use. It will greatly accelerate the process of applying statistical innovations to analyze and interpret sequence-based associations. The R package, its source code and documentations are available from http://cran.r-project.org/web/packages/seqminer and http://seqminer.genomic.codes/. PMID:26394715

  5. Randomized Multicenter Trial of the Effects of Melanoma-Associated Helper Peptides and Cyclophosphamide on the Immunogenicity of a Multipeptide Melanoma Vaccine

    PubMed Central

    Slingluff, Craig L.; Petroni, Gina R.; Chianese-Bullock, Kimberly A.; Smolkin, Mark E.; Ross, Merrick I.; Haas, Naomi B.; von Mehren, Margaret; Grosh, William W.

    2011-01-01

    Purpose This multicenter randomized trial was designed to test whether melanoma-associated helper peptides augment CD8+ T-cell responses to a melanoma vaccine and whether cyclophosphamide (CY) pretreatment augments CD4+ or CD8+ T-cell responses to that vaccine. Patients and Methods In all, 167 eligible patients with resected stage IIB to IV melanoma were randomly assigned to four vaccination study arms. Patients were vaccinated with 12 class I major histocompatibility complex–restricted melanoma peptides (12MP) to stimulate CD8+ T cells and were randomly assigned to receive a tetanus helper peptide or a mixture of six melanoma-associated helper peptides (6MHP) to stimulate CD4+ T cells. Before vaccination, patients were also randomly assigned to receive CY pretreatment or not. T-cell responses were assessed by an ex vivo interferon gamma ELISpot assay. Clinical outcomes and toxicities were recorded. Results Vaccination with 12MP plus tetanus induced CD8+ T-cell responses in 78% of patients and CD4+ T-cell responses to tetanus peptide in 93% of patients. Vaccination with 12MP plus 6MHP induced CD8+ responses in 19% of patients and CD4+ responses to 6MHP in 48% of patients. CY had no significant effect on T-cell responses. Overall 3-year survival was 79% (95% CI, 71% to 86%), with no significant differences (at this point) by study arm. Conclusion Melanoma-associated helper peptides paradoxically decreased CD8+ T-cell responses to a melanoma vaccine (P < .001), and CY pretreatment had no immunologic or clinical effect. Prior work showed immunologic and clinical activity of 6MHP alone. Possible explanations for negative effects on CD8 responses include modulation of homing receptor expression or induction of antigen-specific regulatory T cells. PMID:21690475

  6. Ant association facilitates the evolution of diet breadth in a lycaenid butterfly

    PubMed Central

    Forister, Matthew L.; Gompert, Zachariah; Nice, Chris C.; Forister, Glen W.; Fordyce, James A.

    2011-01-01

    The role of mutualistic interactions in adaptive diversification has not been thoroughly examined. Lycaenid butterflies provide excellent systems for exploring mutualistic interactions, as more than half of this family is known to use ants as a resource in interactions that range from parasitism to mutualism. We investigate the hypothesis that protection from predators offered to caterpillars by ants might facilitate host-range evolution. Specifically, experiments with the butterfly Lycaeides melissa investigated the role of ant association in the use of a novel host, alfalfa, Medicago sativa, which is a sub-optimal host for larval development. Survival on alfalfa is increased by the presence of ants, thus supporting the hypothesis that interaction with ants might be important for host-range evolution. Using a demographic model to explore ecological conditions associated with host-range expansion in L. melissa, we conclude that the presence of ants might be an essential component for populations persisting on the novel, sub-optimal host. PMID:21047856

  7. Parenteral Nutrition–Associated Hyperglycemia in Non–Critically Ill Inpatients Increases the Risk of In-Hospital Mortality (Multicenter Study)

    PubMed Central

    Olveira, Gabriel; Tapia, María José; Ocón, Julia; Cabrejas-Gómez, Carmen; Ballesteros-Pomar, María D.; Vidal-Casariego, Alfonso; Arraiza-Irigoyen, Carmen; Olivares, Josefina; Conde-García, Maria del Carmen; García-Manzanares, Álvaro; Botella-Romero, Francisco; Quílez-Toboso, Rosa P.; Cabrerizo, Lucio; Matia, Pilar; Chicharro, Luisa; Burgos, Rosa; Pujante, Pedro; Ferrer, Mercedes; Zugasti, Ana; Prieto, Javier; Diéguez, Marta; Carrera, María José; Vila-Bundo, Anna; Urgelés, Juan Ramón; Aragón-Valera, Carmen; Rovira, Adela; Bretón, Irene; García-Peris, Pilar; Muñoz-Garach, Araceli; Márquez, Efren; del Olmo, Dolores; Pereira, José Luis; Tous, María C.

    2013-01-01

    OBJECTIVE Hyperglycemia may increase mortality in patients who receive total parenteral nutrition (TPN). However, this has not been well studied in noncritically ill patients (i.e., patients in the nonintensive care unit setting). The aim of this study was to determine whether mean blood glucose level during TPN infusion is associated with increased mortality in noncritically ill hospitalized patients. RESEARCH DESIGN AND METHODS This prospective multicenter study involved 19 Spanish hospitals. Noncritically ill patients who were prescribed TPN were included prospectively, and data were collected on demographic, clinical, and laboratory variables as well as on in-hospital mortality. RESULTS The study included 605 patients (mean age 63.2 ± 15.7 years). The daily mean TPN values were 1.630 ± 323 kcal, 3.2 ± 0.7 g carbohydrates/kg, 1.26 ± 0.3 g amino acids/kg, and 0.9 ± 0.2 g lipids/kg. Multiple logistic regression analysis showed that the patients who had mean blood glucose levels >180 mg/dL during the TPN infusion had a risk of mortality that was 5.6 times greater than those with mean blood glucose levels <140 mg/dL (95% CI 1.47–21.4 mg/dL) after adjusting for age, sex, nutritional state, presence of diabetes or hyperglycemia before starting TPN, diagnosis, prior comorbidity, carbohydrates infused, use of steroid therapy, SD of blood glucose level, insulin units supplied, infectious complications, albumin, C-reactive protein, and HbA1c levels. CONCLUSIONS Hyperglycemia (mean blood glucose level >180 mg/dL) in noncritically ill patients who receive TPN is associated with a higher risk of in-hospital mortality. PMID:23223407

  8. Multicenter study of street foods in 13 towns on four continents by the food and environmental hygiene study group of the international network of pasteur and associated institutes.

    PubMed

    Garin, B; Aïdara, A; Spiegel, A; Arrive, P; Bastaraud, A; Cartel, J L; Aissa, R Ben; Duval, P; Gay, M; Gherardi, C; Gouali, M; Karou, T G; Kruy, S L; Soares, J L; Mouffok, F; Ravaonindrina, N; Rasolofonirina, N; Pham, M T; Wouafo, M; Catteau, M; Mathiot, C; Mauclere, P; Rocourt, J

    2002-01-01

    An international multicenter study of ready-to-eat foods, sandwiches, and ice creams or sorbets sold in the streets and their vendors was carried out to assess the microbiological quality of these foods and to identify characteristics of the vendors possibly associated with pathogens. Thirteen towns in Africa, America, Asia, and Oceania were involved in the study. A single protocol was used in all 13 centers: representative sampling was by random selection of vendors and a sample of foods bought from each of these vendors at a time and date selected at random. Microbiological analyses were carried out using standardized Association Française de Normalisation methods, and the use of a standardized questionnaire to collect data concerning the characteristics of the vendors. Fifteen surveys were carried out, with 3,003 food samples from 1,268 vendors. The proportion of unsatisfactory food samples was between 12.7 and 82.9% for ice creams and sorbets and between 11.3 and 92% for sandwiches. For ice creams and sorbets, the sale of a large number of units (>80 per day) increased the risk of unsatisfactory food by a factor of 2.8 (95% confidence interval [CI]: 1.5 to 5.1), lack of training in food hygiene by 6.6 (95% CI: 1.1 to 50). and by a factor of 2.8 (95% CI: 1.4 to 5.4) for mobile vendors. These risk factors were not identified for sandwiches, this difference may be due to the presence of a cooking step in their preparation. These results show that the poor microbiological quality of these street foods constitutes a potential hazard to public health, that the extent of this hazard varies between the cities studied, and that vendors' health education in food safety is a crucial factor in the prevention of foodborne infections. PMID:11808786

  9. Epicardial Fat is Associated with Duration of Antiretroviral Therapy and Coronary Atherosclerosis: The Multicenter AIDS Cohort Study

    PubMed Central

    Brener, Michael; Ketlogetswe, Kerunne; Budoff, Matthew; Jacobson, Lisa P.; Li, Xiuhong; Rezaeian, Panteha; Razipour, Aryabod; Palella, Frank J; Kingsley, Lawrence; Witt, Mallory D; George, Richard T; Post, Wendy S

    2014-01-01

    Objective Cytokines released by epicardial fat are implicated in the pathogenesis of atherosclerosis. HIV infection and anti-retroviral therapy have been associated with changes in body fat distribution and coronary artery disease. We sought to determine if HIV infection is associated with greater epicardial fat and if epicardial fat is associated with subclinical coronary atherosclerosis. Design We studied 579 HIV-infected and 353 HIV-uninfected men age 40 to 70 years with non-contrast computed tomography (CT) to measure epicardial adipose tissue volume (EAT) and coronary artery calcium (CAC). Total plaque score (TPS), and plaque subtypes (non-calcified, calcified and mixed) were measured by coronary CT angiography in 706 men. Methods We evaluated the association between EAT and HIV serostatus, and the association of EAT with subclinical atherosclerosis, adjusting for age, race and serostatus and with additional cardiovascular (CV) risk factors and tested for modifying effects of HIV serostatus. Results HIV-infected men had greater EAT than HIV-uninfected men (p=0.001). EAT was positively associated with duration of antiretroviral therapy (p=0.02), specifically AZT (p<0.05). EAT was associated with presence of any coronary artery plaque (p=0.006) and non-calcified plaque (p=0.001), adjusting for age, race, serostatus and CV risk factors. Among men with CAC, EAT was associated with CAC extent (p=0.006). HIV serostatus did not modify associations between EAT and either CAC extent or presence of plaque. Conclusions Greater epicardial fat volume in HIV-infected men and its association with coronary plaque and antiretroviral therapy duration suggest potential mechanisms that might lead to increased risk for cardiovascular disease in HIV. PMID:24809732

  10. Facilitated diffusion of 6-deoxy-D-glucose in bakers' yeast: evidence against phosphorylation-associated transport of glucose.

    PubMed Central

    Romano, A H

    1982-01-01

    6-Deoxy-D-glucose, a structural homomorph of D-glucose which lacks a hydroxyl group at carbon 6 and thus cannot be phosphorylated, is transported by Saccharomyces cerevisiae via a facilitated diffusion system with affinity equivalent to that shown with D-glucose. This finding supports the facilitated diffusion mechanism for glucose transport and contradicts theories of transport-associated phosphorylation which hold that sugar phosphorylation is necessary for high-affinity operation of the glucose carrier. PMID:6754704

  11. Graphics Processing Unit-Based Bioheat Simulation to Facilitate Rapid Decision Making Associated with Cryosurgery Training.

    PubMed

    Keelan, Robert; Zhang, Hong; Shimada, Kenji; Rabin, Yoed

    2016-04-01

    This study focuses on the implementation of an efficient numerical technique for cryosurgery simulations on a graphics processing unit as an alternative means to accelerate runtime. This study is part of an ongoing effort to develop computerized training tools for cryosurgery, with prostate cryosurgery as a developmental model. The ability to perform rapid simulations of various test cases is critical to facilitate sound decision making associated with medical training. Consistent with clinical practice, the training tool aims at correlating the frozen region contour and the corresponding temperature field with the target region shape. The current study focuses on the feasibility of graphics processing unit-based computation using C++ accelerated massive parallelism, as one possible implementation. Benchmark results on a variety of computation platforms display between 3-fold acceleration (laptop) and 13-fold acceleration (gaming computer) of cryosurgery simulation, in comparison with the more common implementation on a multicore central processing unit. While the general concept of graphics processing unit-based simulations is not new, its application to phase-change problems, combined with the unique requirements for cryosurgery optimization, represents the core contribution of the current study. PMID:25941162

  12. Multicenter cohort association study of SLC2A1 single nucleotide polymorphisms and age-related macular degeneration

    PubMed Central

    Baas, Dominique C.; Ho, Lintje; Tanck, Michael W.T.; Fritsche, Lars G.; Merriam, Joanna E.; van het Slot, Ruben; Koeleman, Bobby P.C.; Gorgels, Theo G.M.F.; van Duijn, Cornelia M.; Uitterlinden, André G.; de Jong, Paulus T.V.M.; Hofman, Albert; ten Brink, Jacoline B.; Vingerling, Johannes R.; Klaver, Caroline C.W.; Dean, Michael; Weber, Bernhard H. F.; Allikmets, Rando; Hageman, Gregory S.

    2012-01-01

    Purpose Age-related macular degeneration (AMD) is a major cause of blindness in older adults and has a genetically complex background. This study examines the potential association between single nucleotide polymorphisms (SNPs) in the glucose transporter 1 (SLC2A1) gene and AMD. SLC2A1 regulates the bioavailability of glucose in the retinal pigment epithelium (RPE), which might influence oxidative stress–mediated AMD pathology. Methods Twenty-two SNPs spanning the SLC2A1 gene were genotyped in 375 cases and 199 controls from an initial discovery cohort (the Amsterdam-Rotterdam-Netherlands study). Replication testing was performed in The Rotterdam Study (the Netherlands) and study populations from Würzburg (Germany), the Age Related Eye Disease Study (AREDS; United States), Columbia University (United States), and Iowa University (United States). Subsequently, a meta-analysis of SNP association was performed. Results In the discovery cohort, significant genotypic association between three SNPs (rs3754219, rs4660687, and rs841853) and AMD was found. Replication in five large independent (Caucasian) cohorts (4,860 cases and 4,004 controls) did not yield consistent association results. The genotype frequencies for these SNPs were significantly different for the controls and/or cases among the six individual populations. Meta-analysis revealed significant heterogeneity of effect between the studies. Conclusions No overall association between SLC2A1 SNPs and AMD was demonstrated. Since the genotype frequencies for the three SLC2A1 SNPs were significantly different for the controls and/or cases between the six cohorts, this study corroborates previous evidence that population dependent genetic risk heterogeneity in AMD exists. PMID:22509097

  13. Association of a 62 Variant Type 2 Diabetes Genetic Risk Score with Markers of Subclinical Atherosclerosis: A Transethnic, Multicenter Study

    PubMed Central

    Dauriz, Marco; Porneala, Bianca C.; Guo, Xiuqing; Bielak, Lawrence F.; Peyser, Patricia A.; Durant, Nefertiti H.; Carnethon, Mercedes R.; Bonadonna, Riccardo C.; Bonora, Enzo; Bowden, Donald W.; Florez, Jose C.; Fornage, Myriam; Hivert, Marie-France; Jacobs, David R.; Kabagambe, Edmond K.; Lewis, Cora E.; Murabito, Joanne M.; Rasmussen-Torvik, Laura J.; Rich, Stephen S.; Vassy, Jason L.; Yao, Jie; Carr, Jeffrey J.; Kardia, Sharon L.R.; Siscovick, David; O'Donnell, Christopher J.; Rotter, Jerome I.; Dupuis, Josée; Meigs, James B.

    2015-01-01

    Background Type 2 diabetes (T2D) and cardiovascular disease (CVD) share risk factors and subclinical atherosclerosis (SCA) predicts events in those with and without diabetes. T2D genetic risk may predict both T2D and SCA. We hypothesized that greater T2D genetic risk is associated with higher extent of SCA. Methods and Results In a cross-sectional analysis including up to 9,210 European Americans, 3,773 African Americans, 1,446 Hispanic Americans and 773 Chinese Americans without known CVD and enrolled in the FHS, CARDIA, MESA and GENOA studies, we tested a 62 T2D-loci genetic risk score (GRS62) for association with measures of SCA, including coronary artery (CACS) or abdominal aortic calcium score, common (CCA-IMT) and internal carotid artery intima-media thickness, and ankle-brachial index (ABI). We used ancestry-stratified linear regression models, with random effects accounting for family relatedness when appropriate, applying a genetic-only (adjusted for sex) and a full SCA risk factors adjusted model (significance = p<0.01 = 0.05/5, number of traits analyzed). An inverse association with CACS in MESA Europeans (fully-adjusted p=0.004) and with CCA-IMT in FHS (p=0.009) was not confirmed in other study cohorts, either separately or in meta-analysis. Secondary analyses showed no consistent associations with β-cell and insulin resistance sub-GRS in FHS and CARDIA. Conclusions SCA does not have a major genetic component linked to a burden of 62 T2D loci identified by large genome-wide association studies. A shared T2D-SCA genetic basis, if any, might become apparent from better functional information about both T2D and CVD risk loci. PMID:25805414

  14. THE ASSOCIATION BETWEEN PHYSIOLOGIC DEAD-SPACE FRACTION AND MORTALITY IN PATIENTS WITH THE ACUTE RESPIRATORY DISTRESS SYNDROME ENROLLED INTO A PROSPECTIVE MULTI-CENTERED CLINICAL TRIAL

    PubMed Central

    Kallet, Richard H; Zhuo, Hanjing; Liu, Kathleen D.; Calfee, Carolyn S.; Matthay, Michael A

    2014-01-01

    Objective To test the association between pulmonary dead-space fraction (VD/VT) and mortality in patients with ARDS (Berlin Definition, PaO2/FiO2 ≤ 300 mm Hg; PEEP ≥ 5 cm H2O) enrolled into a clinical trial incorporating lung-protective ventilation. Design Prospective, multi-center study. Setting Medical-surgical intensive care units in the United States. Subjects 126 ALI patients enrolled into a phase III randomized, placebo-controlled study of aerosolized albuterol. Interventions None Measurements and Main Results VD/VT and pulmonary mechanics were measured within 4 hours of enrollment and repeated daily on study days 1 and 2 in subjects requiring arterial blood gases for clinical management. At baseline, non-survivors had a trend towards higher VD/VT compared to survivors (0.62 ± 0.11 vs. 0.56 ± 0.11 respectively, p = 0.08). Differences in VD/VT between non-survivors and survivors became significant on study days 1 (0.64 ± 0.12 vs. 0.55 ± 0.11 respectively, p = 0.01) and 2 (0.67 ± 0.12 vs. 0.56 ± 0.11 respectively, p=0.004). Likewise, the association between VD/VT and mortality was significant on study day 1 (odds ratio per 0.10 change in VD/VT [95% confidence interval]: 6.84 [1.62–28.84] p = 0.01; and study day 2: 4.90 [1.28–18.73] p = 0.02) after adjusting for VD/VT, PaO2/FiO2, oxygenation index, vasopressor use and the primary risk for ARDS. Using a Cox proportional hazard model, VD/VT was associated with a trend towards higher mortality (HR = 4.37 [CI: 0.99 – 19.32]; p = 0.052) that became significant when the analysis was adjusted for daily oxygenation index (HR = 1.74 [95% CI: 1.12 – 3.35] p = 0.04). Conclusions Markedly elevated VD/VT (≥ 0.60) in early ARDS is associated with higher mortality. Measuring VD/VT may be useful in identifying ARDS patients at increased risk of death who are enrolled into a therapeutic trial. PMID:24381187

  15. Prospective multicenter surveillance identifies Staphylococcus aureus infections caused by livestock-associated strains in an agricultural state.

    PubMed

    Nair, Rajeshwari; Wu, James; Carrel, Margaret; O'Brien, Ashley; Quick, Megan; Farina, Sarah; Wardyn, Shylo; Thapaliya, Dipendra; Grenier, Dylan; Smith, Tara C

    2016-07-01

    We conducted a surveillance study to investigate the epidemiology of Staphylococcus aureus infections in Iowa, using a convenience sample. Diagnostic laboratories submitted 20 S. aureus isolates per month for a 20-month period between 2011 and 2013. Of the 2226 isolates analyzed, 73.6% were methicillin-resistant S. aureus (MRSA) and 26.4% were methicillin-susceptible S. aureus (MSSA). S. aureus infections in 25 patients (1%) were caused by ST398- and ST9-associated strain types, and appeared to be a common occurrence in areas of the state with the highest numbers of hogs and hog farms. Twenty nine (5.1%) of MSSA isolates and 10 (40.0%) livestock-associated strains were multi-drug resistant. PMID:27198741

  16. Increasing Incidence of Hospital-Acquired and Healthcare-Associated Bacteremia in Northeast Thailand: A Multicenter Surveillance Study

    PubMed Central

    Hongsuwan, Maliwan; Srisamang, Pramot; Kanoksil, Manas; Luangasanatip, Nantasit; Jatapai, Anchalee; Day, Nicholas P.; Peacock, Sharon J.; Cooper, Ben S.; Limmathurotsakul, Direk

    2014-01-01

    Background Little is known about the epidemiology of nosocomial bloodstream infections in public hospitals in developing countries. We evaluated trends in incidence of hospital-acquired bacteremia (HAB) and healthcare-associated bacteremia (HCAB) and associated mortality in a developing country using routinely available databases. Methods Information from the microbiology and hospital databases of 10 provincial hospitals in northeast Thailand was linked with the national death registry for 2004–2010. Bacteremia was considered hospital-acquired if detected after the first two days of hospital admission, and healthcare-associated if detected within two days of hospital admission with a prior inpatient episode in the preceding 30 days. Results A total of 3,424 patients out of 1,069,443 at risk developed HAB and 2,184 out of 119,286 at risk had HCAB. Of these 1,559 (45.5%) and 913 (41.8%) died within 30 days, respectively. Between 2004 and 2010, the incidence rate of HAB increased from 0.6 to 0.8 per 1,000 patient-days at risk (p<0.001), and the cumulative incidence of HCAB increased from 1.2 to 2.0 per 100 readmissions (p<0.001). The most common causes of HAB were Acinetobacter spp. (16.2%), Klebsiella pneumoniae (13.9%), and Staphylococcus aureus (13.9%), while those of HCAB were Escherichia coli (26.3%), S. aureus (14.0%), and K. pneumoniae (9.7%). There was an overall increase over time in the proportions of ESBL-producing E. coli causing HAB and HCAB. Conclusions This study demonstrates a high and increasing incidence of HAB and HCAB in provincial hospitals in northeast Thailand, increasing proportions of ESBL-producing isolates, and very high associated mortality. PMID:25310563

  17. Neutrophilic Dermatoses in Antineutrophil Cytoplasmic Antibody-Associated Vasculitis: A French Multicenter Study of 17 Cases and Literature Review.

    PubMed

    de Boysson, Hubert; Martin Silva, Nicolas; de Moreuil, Claire; Néel, Antoine; de Menthon, Mathilde; Meyer, Olivier; Launay, David; Pagnoux, Christian; Guillevin, Loïc; Puéchal, Xavier; Bienvenu, Boris; Aouba, Achille

    2016-03-01

    A few reports suggest combination of ANCA-associated vasculitis (AAV) and neutrophilic dermatoses (ND). We aimed to describe the main characteristics of patients presenting with both AAV and ND in a French cohort and through a systematic literature review, and to discuss the possible common pathogenic process involved. We conducted a retrospective study of patients with both conditions. Patients were selected via the French Internal Medicine Society (SNFMI) and the French Vasculitis Study Group (FVSG). A literature review focusing on a combination of both conditions, concentrated only on publications with well-established diagnoses and individual detailed data. Seventeen patients diagnosed with AAV and ND were identified in this cohort. Twelve patients had granulomatosis with polyangiitis (GPA), 4 had microscopic polyangiitis (MPA) and one had eosinophilic GPA (EGPA). Eight patients, all with GPA, displayed pyoderma gangrenosum (PG). Sweet's syndrome was observed in 6 patients (4 with MPA, one with GPA and one with EGPA) and erythema elevatum diutinum in the other three (2 with GPA and 1 with MPA). The literature review identified 33 additional patients with both conditions, including 26 with GPA. Altogether, of the 50 patients (17 from our study and 33 from the literature review), 33 (66%) patients presented with PG associated with GPA in 29 cases (89%). Corticosteroids were the first-line treatment in conjunction with an immunosuppressive agent in most cases. Outcomes were good and a total of 15 patients experienced a relapse. Patients who relapsed were more likely to have ear, nose and throat manifestation than patients who did not [12/15 (80%) relapsing patients vs. 15/35 (43%) non-relapsing patients; p = 0.03)]. In our stud, the most frequent association concerned GPA and PG. ND should be considered and specifically researched within the spectrum of cutaneous manifestations observed in AAV. PMID:26986103

  18. Association between levonorgestrel emergency contraception and the risk of ectopic pregnancy: a multicenter case-control study.

    PubMed

    Zhang, Jian; Li, Cheng; Zhao, Wei-Hong; Xi, Xiaowei; Cao, Shu-Jun; Ping, Hua; Qin, Guo-Juan; Cheng, Linan; Huang, He-Feng

    2015-01-01

    Cases of ectopic pregnancy (EP) following levonorgestrel emergency contraception (LNG-EC) failure have been reported continuously, but whether there is an association between EP risk and LNG-EC is unclear. We concluded a case-control study to explore this association by recruiting 2,411 EP patients as case group, and 2,416 women with intrauterine pregnancy and 2,419 non-pregnant women as control groups. Odds ratios (ORs) and their 95% confidential intervals (CIs) were calculated and adjusted for potential confounding factors. Previous use of LNG-EC was not correlated with the EP. Compared to women who did not use contraceptives, current use of LNG-EC reduced the risk for intrauterine pregnancy (Adjusted OR [AOR] = 0.20, 95%CI: 0.14-0.27), but did not increase the risk for EP (AOR2 = 1.04, 95%CI: 0.76-1.42). Furthermore, compared to women who did not have further act of intercourse, women with unprotected further act of intercourse were at a higher risk of EP (AOR1 = 2.35, 95%CI: 1.17-4.71), and women with repeated use of LNG-EC for further intercourse during the same cycle was also associated with a higher risk for EP (AOR1 = 3.08, 95%CI: 1.09-8.71; AOR2 = 2.49, 95%CI: 1.00-6.19). A better understanding of the risk of EP following LNG-EC failure can optimize LNG-EC use and thus reduce the risk of EP. PMID:25674909

  19. Enterovirus 71 Virion-Associated Galectin-1 Facilitates Viral Replication and Stability

    PubMed Central

    Lee, Pei-Huan; Liu, Chia-Ming; Ho, Tzong-Shiann; Tsai, Yi-Che; Lin, Chi-Cheng; Wang, Ya-Fang; Chen, Yuh-Ling; Yu, Chun-Keung; Wang, Shih-Min; Liu, Ching-Chuan; Shiau, Ai-Li; Lei, Huan-Yao; Chang, Chih-Peng

    2015-01-01

    Enterovirus 71 (EV71) infection causes a myriad of diseases from mild hand-foot-and-mouth disease or herpangina to fatal brain stem encephalitis complicated with pulmonary edema. Several severe EV71 endemics have occurred in Asia-Pacific region, including Taiwan, and have become a serious threat to children’s health. EV71 infection is initiated by the attachment of the virion to the target cell surface. Although this process relies primarily upon interaction between viruses and cell surface receptors, soluble factors may also influence the binding of EV71 to host cells.Galectin-1 has been reported to participate in several virus infections, but is not addressed in EV71. In this study, we found that the serum levels of galectin-1 in EV71-infected children were higher than those in non-infected people. In EV71 infected cells, galectin-1 was found to be associated with the EV71 VP1 and VP3 via carbohydrate residues and subsequently released and bound to another cell surface along with the virus. EV71 propagated from galectin-1 knockdown SK-N-SH cells exhibited lower infectivity in cultured cells and less pathogenicity in mice than the virus propagated from parental cells. In addition, this galectin-1-free EV71 virus was sensitive to high temperature and lost its viability after long-term storage, which could be restored following supplement of recombinant galectin-1. Taken together, our findings uncover a new role of galectin-1 in facilitating EV71 virus infection. PMID:25706563

  20. Enterovirus 71 virion-associated galectin-1 facilitates viral replication and stability.

    PubMed

    Lee, Pei-Huan; Liu, Chia-Ming; Ho, Tzong-Shiann; Tsai, Yi-Che; Lin, Chi-Cheng; Wang, Ya-Fang; Chen, Yuh-Ling; Yu, Chun-Keung; Wang, Shih-Min; Liu, Ching-Chuan; Shiau, Ai-Li; Lei, Huan-Yao; Chang, Chih-Peng

    2015-01-01

    Enterovirus 71 (EV71) infection causes a myriad of diseases from mild hand-foot-and-mouth disease or herpangina to fatal brain stem encephalitis complicated with pulmonary edema. Several severe EV71 endemics have occurred in Asia-Pacific region, including Taiwan, and have become a serious threat to children's health. EV71 infection is initiated by the attachment of the virion to the target cell surface. Although this process relies primarily upon interaction between viruses and cell surface receptors, soluble factors may also influence the binding of EV71 to host cells. Galectin-1 has been reported to participate in several virus infections, but is not addressed in EV71. In this study, we found that the serum levels of galectin-1 in EV71-infected children were higher than those in non-infected people. In EV71 infected cells, galectin-1 was found to be associated with the EV71 VP1 and VP3 via carbohydrate residues and subsequently released and bound to another cell surface along with the virus. EV71 propagated from galectin-1 knockdown SK-N-SH cells exhibited lower infectivity in cultured cells and less pathogenicity in mice than the virus propagated from parental cells. In addition, this galectin-1-free EV71 virus was sensitive to high temperature and lost its viability after long-term storage, which could be restored following supplement of recombinant galectin-1. Taken together, our findings uncover a new role of galectin-1 in facilitating EV71 virus infection. PMID:25706563

  1. Lack of Association Found between Helicobacter pylori Infection and Diarrhea-Predominant Irritable Bowel Syndrome: A Multicenter Retrospective Study

    PubMed Central

    Xiong, Feng; Xiong, Man; Ma, Zonghui; Huang, Senxiong; Li, Aimin

    2016-01-01

    Aims. The association between Helicobacter pylori (H. pylori) infection and diarrhea-predominant irritable bowel syndrome (IBS-D) is still controversial. Here we performed a retrospective study to explore this issue. Methods. A total of 502 inpatients with Rome III confirmed IBS-D and known H. pylori status from 8 hospitals were enrolled. H. pylori-positive patients, hospitalized in the recent year, were followed up to evaluate the effects of H. pylori eradication on IBS-D clinical course. Results. Of the 502 IBS-D patients, 206 were H. pylori-positive, with an infection rate that has no significant difference with that of the general population in Guangdong province (p = 0.348). For patients followed up, no significant differences were noted as to overall symptoms (p = 0.562), abdominal pain/discomfort (p = 0.777), bloating (p = 0.736), stool frequency (p = 0.835), or stool characteristics (p = 0.928) between the H. pylori-eradicated group and the control group. The results were the same in long-term follow-up patients except the improvement of bloating, which showed that the bloating score in the H. pylori-eradicated group was significantly lower (p = 0.047). Conclusions. No significant correlation between H. pylori infection and IBS-D was noted. Overall, IBS-D patients may not benefit from H. pylori eradication. PMID:27493660

  2. Effects of Lactobacillus gasseri OLL2716 on Helicobacter pylori-Associated Dyspepsia: A Multicenter Randomized Double-Blind Controlled Trial

    PubMed Central

    Ozawa, Hideki; Uemura, Naomi; Inoue, Kazuhiko; Kawai, Takashi; Ohtsu, Toshihiro; Koga, Yasuhiro

    2016-01-01

    Some Lactobacillus spp. suppress Helicobacter pylori in the stomach and have potential therapeutic applications for the treatment of gastrointestinal conditions. In this study, the effects of Lactobacillus strains on functional dyspepsia associated with H. pylori infection were examined. Volunteers were screened using the 13C-urea breath test (UBT) and H. pylori stool test, and 131 participants who met the selection criteria (mean age: 48.9 years) were randomly given L. gasseri OLL2716-containing yogurt or placebo yogurt once daily for 12 weeks. Gastrointestinal symptoms (epigastric pain, bloating, postprandial fullness, nausea, and heartburn) and the levels of serum pepsinogen (PG), 13C-UBT, and H. pylori stool antigen were assessed. No significant differences were observed between the groups in UBT results, H. pylori stool antigens, or the serum PGI/II ratio. In the L. gasseri group, postprandial fullness was significantly lower at the end of the trial compared to the initial level (p < 0.05) and significantly fewer patients had a VAS score of >10 for bloating compared to the placebo group (p < 0.05). Dietary supplementation with L. gasseri OLL2716-containing yogurt may effectively suppress dyspeptic symptoms in H. pylori-infected patients. This study was registered at the University Hospital Medical Network Clinical Trial Registry (UMIN000016746). PMID:27478434

  3. Treatment of ADCY5-Associated Dystonia, Chorea, and Hyperkinetic Disorders With Deep Brain Stimulation: A Multicenter Case Series.

    PubMed

    Dy, Marisela E; Chang, Florence C F; Jesus, Sol De; Anselm, Irina; Mahant, Neil; Zeilman, Pamela; Rodan, Lance H; Foote, Kelly D; Tan, Wen-Hann; Eskandar, Emad; Sharma, Nutan; Okun, Michael S; Fung, Victor S C; Waugh, Jeff L

    2016-07-01

    ADCY5 mutations have been reported as a cause of early onset hyperkinetic movements associated with delayed motor milestones, hypotonia, and exacerbation during sleep. The movement disorder may be continuous or episodic, and can vary considerably in severity within families and in individuals. The authors report a case series of 3 patients with ADCY5 mutations treated with deep brain stimulation after unsuccessful medication trials. All had extensive imaging, metabolic, and genetic testing prior to confirmation of their ADCY5 mutation. Two of the patients had the c.1252C>T; p.R418W mutation, while the youngest and most severely affected had a de novo c.2080_2088del; p.K694_M696 mutation. All had variable and incomplete, but positive responses to deep brain stimulation. The authors conclude that deep brain stimulation may provide benefit in ADCY5-related movement disorders. Long-term efficacy remains to be confirmed by longitudinal observation. ADCY5 should be considered in the differential diagnosis of early onset hyperkinetic movement disorders, and may respond to deep brain stimulation. PMID:27052971

  4. Effects of Lactobacillus gasseri OLL2716 on Helicobacter pylori-Associated Dyspepsia: A Multicenter Randomized Double-Blind Controlled Trial.

    PubMed

    Takagi, Atsushi; Yanagi, Hidetaka; Ozawa, Hideki; Uemura, Naomi; Nakajima, Shigemi; Inoue, Kazuhiko; Kawai, Takashi; Ohtsu, Toshihiro; Koga, Yasuhiro

    2016-01-01

    Some Lactobacillus spp. suppress Helicobacter pylori in the stomach and have potential therapeutic applications for the treatment of gastrointestinal conditions. In this study, the effects of Lactobacillus strains on functional dyspepsia associated with H. pylori infection were examined. Volunteers were screened using the (13)C-urea breath test (UBT) and H. pylori stool test, and 131 participants who met the selection criteria (mean age: 48.9 years) were randomly given L. gasseri OLL2716-containing yogurt or placebo yogurt once daily for 12 weeks. Gastrointestinal symptoms (epigastric pain, bloating, postprandial fullness, nausea, and heartburn) and the levels of serum pepsinogen (PG), (13)C-UBT, and H. pylori stool antigen were assessed. No significant differences were observed between the groups in UBT results, H. pylori stool antigens, or the serum PGI/II ratio. In the L. gasseri group, postprandial fullness was significantly lower at the end of the trial compared to the initial level (p < 0.05) and significantly fewer patients had a VAS score of >10 for bloating compared to the placebo group (p < 0.05). Dietary supplementation with L. gasseri OLL2716-containing yogurt may effectively suppress dyspeptic symptoms in H. pylori-infected patients. This study was registered at the University Hospital Medical Network Clinical Trial Registry (UMIN000016746). PMID:27478434

  5. Cold Hypersensitivity in the Hands and Feet May Be Associated with Functional Dyspepsia: Results of a Multicenter Survey Study

    PubMed Central

    Bae, Kwang-Ho; Lee, Ju Ah; Park, Ki-Hyun; Yoo, Jong-Hyang; Lee, Siwoo

    2016-01-01

    Aim. To investigate whether dyspepsia symptoms differ depending on the presence or absence of cold hypersensitivity in the hands and feet (CHHF). Methods. In all, 6044 patients were recruited and provided with a questionnaire about CHHF and dyspepsia. Based on their responses, subjects were divided into a CHHF group (persons who noted cold sensations; n = 1209) and a non-CHHF group (persons who noted warm or intermediate sensations; n = 1744). The groups were compared in terms of their usual digestion status, using chi-square tests and logistic regression analyses to calculate the propensity score and odds ratios (ORs). We analyzed the participants' responses to questions on dyspepsia symptoms. Results. After matching, chi-square tests indicated that the CHHF group had higher frequencies of the following symptoms: bad digestion, poor appetite, discomfort in the upper abdomen, motion sickness, epigastric burning, postprandial fullness, nausea, and bloating. Additionally, CHHF was associated with an increased OR for dyspepsia (bad digestion, vomiting, motion sickness, epigastric burning, postprandial fullness, nausea, epigastric pain, and bloating) compared with the non-CHHF group. Conclusion. This study confirmed that CHHF patients have elevated frequencies of most dyspepsia symptoms. PMID:27069497

  6. Pentraxin 3 Is Closely Associated With Tubulointerstitial Injury in Lupus Nephritis: A Large Multicenter Cross-Sectional Study.

    PubMed

    Pang, Yun; Tan, Ying; Li, Yongzhe; Zhang, Jianchun; Guo, Yongbing; Guo, Zhiling; Zhang, Chengying; Yu, Feng; Zhao, Ming-Hui

    2016-01-01

    Lupus nephritis always elicits immune inflammatory tissue damages in kidney. Pentraxin 3 (PTX3), mainly produced at inflammatory sites, is known to be involved in the regulation of the innate immunity system. The aim of this study was to investigate the serum and urine levels of PTX3, and the expression of PTX3 in renal tissues in lupus nephritis patients from a large Chinese cohort.The study used cross-sectional survey and 288 active lupus nephritis patients, including discovery cohort and validation cohort, 115 systemic lupus erythematosus (SLE) patients without clinical renal involvement and 46 healthy controls were enrolled. Serum and urine PTX3 were screened by enzyme-linked immunosorbent assay (ELISA). The renal deposition of PTX3 was detected by immunohistochemistry and immunofluorescence.The average level of serum PTX3 in the discovery cohort of lupus nephritis was significantly higher than that in nonrenal involvement SLE group and normal controls (P < 0.001, P < 0.001, respectively), which was confirmed by the validation cohort. Serum PTX3 levels of 15 lupus nephritis patients in remission decreased significantly compared with that in active phase. Serum PTX3 levels were significantly higher in patients with hematuria (P = 0.014), leucocyturia (P = 0.002), acute renal failure (P = 0.001), and nephrotic syndrome (P = 0.036). There were significant correlations between serum PTX3 levels and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) scores, serum creatinine value, renal pathological activity indices, and serum complement 3 (C3) in active lupus nephritis patients. The urinary PTX3 levels were significantly higher in active lupus nephritis patients compared with patients in remission and normal controls (P = 0.011, P = 0.008, respectively). There were significant associations between urinary PTX3 levels and multiple indices of tubulointerstitial lesions, including urinary KIM-1 (r = 0.368, P = 0

  7. The Association between Life Satisfaction and the Extent of Depression, Anxiety and Stress among Iranian Nurses: A Multicenter Survey

    PubMed Central

    Yazdanshenas Ghazwin, Manijeh; Kavian, Mohammad; Ahmadloo, Mohsen; Jarchi, Alemeh; Golchin Javadi, Shaghayegh; Latifi, Sahar; Ghajarzadeh, Mahsa

    2016-01-01

    Objective: The determinants of satisfaction of life (SWL) are poorly described among Iranian employed nurses. This study aimed to assess the effect of various factors including age, gender, marital status, depression, anxiety and stress on SWL among Iranian nurses. Method: Employed nurses in three teaching hospitals were invited to participate in this study. Ninety-four nurses (65 women and 29 men) participated in this study. Depression, anxiety, stress scale (DASS-21) was used to measure the related variables. Satisfaction with Life Scale (SWLS) was used to assess SWL. Multivariate analysis was utilized to examine the relationship between multiple variables. Results: A noticeable proportion of Iranian employed nurses were either dissatisfied or extremely dissatisfied with life (45%). Severe depression was related to lower scores of SWLS (P: 0.001, r = −0.32). The similar outcomes were detected between anxiety and stress scales, and SWLS (P: 0.023, r = −0.23 and P: 0.008, r = −0.27 for anxiety and stress, respectively). Although females were more vulnerable to depression (P: 0.010) and stress (P: 0.013), the overall effect of gender on SWL was insignificant (0.41). Satisfactions with financial power and work environment were associated with higher scores of SWLS (P: 0.030 and 0.042, respectively). Marital status was not related to severity of depression, anxiety, stress and SWLS (P: 0.39, 0.38, 0.80, and 0.61, respectively). Conclusion: This study revealed that poor satisfaction with financial status and work environment, depression, anxiety and stress are the major determinants of satisfaction with life among Iranian employed nurses. PMID:27437009

  8. Primary Mucosa-Associated Lymphoid Tissue Lymphoma of the Salivary Glands: A Multicenter Rare Cancer Network Study

    SciTech Connect

    Anacak, Yavuz; Miller, Robert C.; Constantinou, Nikos; Mamusa, Angela M.; Epelbaum, Ron; Li Yexiong; Calduch, Anna Lucas; Kowalczyk, Anna; Weber, Damien C.; Kadish, Sidney P.; Poortmans, Philip; Kamer, Serra; Ozsahin, Mahmut

    2012-01-01

    Purpose: Involvement of salivary glands with mucosa-associated lymphoid tissue (MALT) lymphoma is rare. This retrospective study was performed to assess the clinical profile, treatment outcome, and prognostic factors of MALT lymphoma of the salivary glands. Methods and Materials: Thirteen member centers of the Rare Cancer Network from 10 countries participated, providing data on 63 patients. The median age was 58 years; 47 patients were female and 16 were male. The parotid glands were involved in 49 cases, submandibular in 15, and minor glands in 3. Multiple glands were involved in 9 patients. Staging was as follows: IE in 34, IIE in 12, IIIE in 2, and IV in 15 patients. Results: Surgery (S) alone was performed in 9, radiotherapy (RT) alone in 8, and chemotherapy (CT) alone in 4 patients. Forty-one patients received combined modality treatment (S + RT in 23, S + CT in 8, RT + CT in 4, and all three modalities in 6 patients). No active treatment was given in one case. After initial treatment there was no tumor in 57 patients and residual tumor in 5. Tumor progression was observed in 23 (36.5%) (local in 1, other salivary glands in 10, lymph nodes in 11, and elsewhere in 6). Five patients died of disease progression and the other 5 of other causes. The 5-year disease-free survival, disease-specific survival, and overall survival were 54.4%, 93.2%, and 81.7%, respectively. Factors influencing disease-free survival were use of RT, stage, and residual tumor (p < 0.01). Factors influencing disease-specific survival were stage, recurrence, and residual tumor (p < 0.01). Conclusions: To our knowledge, this report represents the largest series of MALT lymphomas of the salivary glands published to date. This disease may involve all salivary glands either initially or subsequently in 30% of patients. Recurrences may occur in up to 35% of patients at 5 years; however, survival is not affected. Radiotherapy is the only treatment modality that improves disease-free survival.

  9. Association learning for emotional harbinger cues: when do previous emotional associations impair and when do they facilitate subsequent learning of new associations?

    PubMed

    Sakaki, Michiko; Ycaza-Herrera, Alexandra E; Mather, Mara

    2014-02-01

    Neutral cues that predict emotional events (emotional harbingers) acquire emotional properties and attract attention. Given the importance of emotional harbingers for future survival, it is desirable to flexibly learn new facts about emotional harbingers when needed. However, recent research revealed that it is harder to learn new associations for emotional harbingers than cues that predict non-emotional events (neutral harbingers). In the current study, we addressed whether this impaired association learning for emotional harbingers is altered by one's awareness of the contingencies between cues and emotional outcomes. Across 3 studies, we found that one's awareness of the contingencies determines subsequent association learning of emotional harbingers. Emotional harbingers produced worse association learning than neutral harbingers when people were not aware of the contingencies between cues and emotional outcomes, but produced better association learning when people were aware of the contingencies. These results suggest that emotional harbingers do not always suffer from impaired association learning and can show facilitated learning depending on one's contingency awareness. PMID:24098924

  10. A genetic contribution to cooperation: dopamine-relevant genes are associated with social facilitation.

    PubMed

    Walter, Nora T; Markett, Sebastian A; Montag, Christian; Reuter, Martin

    2011-01-01

    Social loafing and social facilitation are stable behavioral effects that describe increased or decreased motivation, as well as effort and cooperation in teamwork as opposed to individual working situations. Recent twin studies demonstrate the heritability of cooperative behavior. Brain imaging studies have shown that reciprocity, cooperativeness, and social rewards activate reward processing areas with strong dopaminergic input, such as the ventral striatum. Thus, candidate genes for social behavior are hypothesized to affect dopaminergic neurotransmission. In the present study, we investigated the dopaminergic genetic contribution to social cooperation, especially to social loafing and social facilitation. N = 106 healthy, Caucasian subjects participated in the study and were genotyped for three polymorphisms relevant to the dopaminergic system (COMTval158met, DRD2 c957t, DRD2 rs#2283265). In addition to a main effect indicating an increased performance in teamwork situations, we found a significant interaction between a haplotype block covering both DRD2 single nucleotide polymorphisms (SNPs) (rs#6277 and rs#2283265), henceforth referred to as the DRD2-haplotype block, and the COMT val158met polymorphism (rs#4680) with social facilitation. Carriers of the DRD2 CT-haplotype block and at least one Val-allele showed a greater increase in performance in teamwork settings when compared with carriers of the CT-haplotype block and the Met/Met-genotype. Our results suggest that epistasis between COMTval158met and the two DRD2 SNPs contributes to individual differences in cooperativeness in teamwork settings. PMID:21061227

  11. Multicenter breast cancer collaborative registry.

    PubMed

    Sherman, Simon; Shats, Oleg; Fleissner, Elizabeth; Bascom, George; Yiee, Kevin; Copur, Mehmet; Crow, Kate; Rooney, James; Mateen, Zubeena; Ketcham, Marsha A; Feng, Jianmin; Sherman, Alexander; Gleason, Michael; Kinarsky, Leo; Silva-Lopez, Edibaldo; Edney, James; Reed, Elizabeth; Berger, Ann; Cowan, Kenneth

    2011-01-01

    The Breast Cancer Collaborative Registry (BCCR) is a multicenter web-based system that efficiently collects and manages a variety of data on breast cancer (BC) patients and BC survivors. This registry is designed as a multi-tier web application that utilizes Java Servlet/JSP technology and has an Oracle 11g database as a back-end. The BCCR questionnaire has accommodated standards accepted in breast cancer research and healthcare. By harmonizing the controlled vocabulary with the NCI Thesaurus (NCIt) or Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT), the BCCR provides a standardized approach to data collection and reporting. The BCCR has been recently certified by the National Cancer Institute's Center for Biomedical Informatics and Information Technology (NCI CBIIT) as a cancer Biomedical Informatics Grid (caBIG(®)) Bronze Compatible product.The BCCR is aimed at facilitating rapid and uniform collection of critical information and biological samples to be used in developing diagnostic, prevention, treatment, and survivorship strategies against breast cancer. Currently, seven cancer institutions are participating in the BCCR that contains data on almost 900 subjects (BC patients and survivors, as well as individuals at high risk of getting BC). PMID:21918596

  12. Multicenter Breast Cancer Collaborative Registry

    PubMed Central

    Sherman, Simon; Shats, Oleg; Fleissner, Elizabeth; Bascom, George; Yiee, Kevin; Copur, Mehmet; Crow, Kate; Rooney, James; Mateen, Zubeena; Ketcham, Marsha A.; Feng, Jianmin; Sherman, Alexander; Gleason, Michael; Kinarsky, Leo; Silva-Lopez, Edibaldo; Edney, James; Reed, Elizabeth; Berger, Ann; Cowan, Kenneth

    2011-01-01

    The Breast Cancer Collaborative Registry (BCCR) is a multicenter web-based system that efficiently collects and manages a variety of data on breast cancer (BC) patients and BC survivors. This registry is designed as a multi-tier web application that utilizes Java Servlet/JSP technology and has an Oracle 11g database as a back-end. The BCCR questionnaire has accommodated standards accepted in breast cancer research and healthcare. By harmonizing the controlled vocabulary with the NCI Thesaurus (NCIt) or Systematized Nomenclature of Medicine-Clinical Terms (SNOMED-CT), the BCCR provides a standardized approach to data collection and reporting. The BCCR has been recently certified by the National Cancer Institute’s Center for Biomedical Informatics and Information Technology (NCI CBIIT) as a cancer Biomedical Informatics Grid (caBIG®) Bronze Compatible product. The BCCR is aimed at facilitating rapid and uniform collection of critical information and biological samples to be used in developing diagnostic, prevention, treatment, and survivorship strategies against breast cancer. Currently, seven cancer institutions are participating in the BCCR that contains data on almost 900 subjects (BC patients and survivors, as well as individuals at high risk of getting BC). PMID:21918596

  13. Cytotoxic factor secreted by Escherichia coli associated with sepsis facilitates transcytosis through human umbilical vein endothelial cell monolayers.

    PubMed

    Tibo, Luiz Henrique Soares; Bertol, Jéssica Wildgrube; Bernedo-Navarro, Robert Alvin; Yano, Tomomasa

    2016-01-01

    Culture supernatant of sepsis-associated Escherichia coli (SEPEC) isolated from patients with sepsis caused loss of intercellular junctions and elongation of human umbilical vein endothelial cells (HUVEC). The cytotoxic factor was purified from culture supernatant of SEPEC 15 (serogroup O153) by liquid chromatography process. PAGE (polyacrylamide gel electrophoresis) showed that the purified SEPEC cytotoxic factor had a molecular mass of ∼150kDa and consisted of at least two subunits. At the concentration of 1 CD50 (40μg/mL) did facilitate transcytosis through the HUVEC cells monolayer of SEPEC 15 as much as E. coli K12 within 30min without affecting cell viability. These results suggest that this cytotoxic factor, named as SPF (SEPEC's permeabilizing factor), may be an important SEPEC virulence factor that facilitates bacterial access to the bloodstream. PMID:26963151

  14. Is level of exposure to a 12-step facilitation therapy associated with treatment outcome?

    PubMed

    Wells, Elizabeth A; Donovan, Dennis M; Daley, Dennis C; Doyle, Suzanne R; Brigham, Greg; Garrett, Sharon B; Ingalsbe, Michelle H; Hatch-Maillette, Mary A; Perl, Harold I; Walker, Robrina

    2014-10-01

    This study examined whether level of exposure to Stimulant Abuser Groups to Engage in 12-Step (STAGE-12), a 12-Step facilitative therapy, is related to treatment outcome. Data were from a large National Drug Abuse Treatment Clinical Trials Network (CTN) study comparing STAGE-12 combined with treatment-as-usual (TAU) to TAU alone. These analyses include only those randomized to STAGE-12 (n=234). Assessments occurred at baseline and 30, 60, 90, and 180 days following randomization. High-exposure patients (n=158; attended at least 2 of 3 individual, and 3 of 5 group, sessions), compared to those with less exposure (n=76), demonstrated: (1) higher odds of self-reported abstinence from, and lower rates of, stimulant and non-stimulant drug use; (2) lower probabilities of stimulant-positive urines; (3) more days of attending and lower odds of not attending 12-Step meetings; (4) greater likelihood of reporting no drug problems; (5) more days of duties at meetings; and (6) more types of 12-Step activities. Many of these differences declined over time, but several were still significant by the last follow-up. Treatment and research implications are discussed. PMID:25064421

  15. Degradation of lipid droplet-associated proteins by chaperone-mediated autophagy facilitates lipolysis

    PubMed Central

    Kaushik, Susmita; Cuervo, Ana Maria

    2015-01-01

    Chaperone-mediated autophagy (CMA) selectively degrades a subset of cytosolic proteins in lysosomes. A potent physiological activator of CMA is nutrient deprivation, a condition in which intracellular triglyceride stores or lipid droplets (LD) also undergo hydrolysis (lipolysis) to generate free fatty acids for energetic purposes. Here we report that LD-associated proteins perilipin 2 (PLIN2) and perilipin 3 (PLIN3) are CMA substrates and their degradation via CMA precedes lipolysis. In vivo studies revealed that CMA degradation of PLIN2 and PLIN3 was enhanced during starvation, concurrent with elevated levels of cytosolic adipose triglyceride lipase (ATGL) and macroautophagy proteins on LD. CMA blockage both in cultured cells and mouse liver or expression of CMA-resistant PLINs lead to reduced association of ATGL and macrolipophagy-related proteins with LD and the subsequent decrease in lipid oxidation and accumulation of LD. We propose a role of CMA in LD biology and in the maintenance of lipid homeostasis. PMID:25961502

  16. SKAP2 Promotes Podosome Formation to Facilitate Tumor-Associated Macrophage Infiltration and Metastatic Progression.

    PubMed

    Tanaka, Masamitsu; Shimamura, Shintaro; Kuriyama, Sei; Maeda, Daichi; Goto, Akiteru; Aiba, Namiko

    2016-01-15

    Tumor-associated macrophages (TAM) play complex and pivotal roles during cancer progression. A subset of metastasis-associated macrophages accumulates within metastatic sites to promote the invasion and growth of tumor cells. Src kinase-associated phosphoprotein 2 (SKAP2), a substrate of Src family kinases, is highly expressed in macrophages from various tumors, but its contribution to the tumor-promoting behavior of TAMs is unknown. Here, we report that SKAP2 regulates podosome formation in macrophages to promote tumor invasion and metastasis. SKAP2 physically interacted with Wiskott-Aldrich syndrome protein (WASP) and localized to podosomes, which were rarely observed in SKAP2-null macrophages. The invasion of peritoneal macrophages derived from SKAP2-null mice was significantly reduced compared with wild-type macrophages, but could be rescued by the restoration of functional SKAP2 containing an intact tyrosine phosphorylation site and the ability to interact with WASP. Furthermore, SKAP2-null mice inoculated with lung cancer cells exhibited markedly decreased lung metastases characterized by reduced macrophage infiltration compared with wild-type mice. Moreover, intravenously injected SKAP2-null macrophages failed to efficiently infiltrate established tumors and promote their growth. Taken together, these findings reveal a novel mechanism by which macrophages assemble the appropriate motile machinery to infiltrate tumors and promote disease progression, and implicate SKAP2 as an attractive candidate for therapeutically targeting TAMs. PMID:26577701

  17. Tetraplegia is associated with enhanced peripheral chemoreflex sensitivity and ventilatory long-term facilitation

    PubMed Central

    Sankari, Abdulghani; Bascom, Amy T.; Riehani, Anas; Badr, M. Safwan

    2016-01-01

    Cardiorespiratory plasticity induced by acute intermittent hypoxia (AIH) may contribute to recovery following spinal cord injury (SCI). We hypothesized that patients with cervical SCI would demonstrate higher minute ventilation (V̇e) following AIH compared with subjects with thoracic SCI and able-bodied subjects who served as controls. Twenty-four volunteers (8 with cervical SCI, 8 with thoracic SCI, and 8 able-bodied) underwent an AIH protocol during wakefulness. Each subject experienced 15 episodes of isocapnic hypoxia using mixed gases of 100% nitrogen (N2), 8% O2, and 40% CO2 to achieve oxygen saturation ≤90% followed by room air (RA). Measurements were obtained before, during, and 40 min after AIH to obtain ventilation and heart rate variability data [R-R interval (RRI) and low-frequency/ high-frequency power (LF/HF)]. AIH results were compared with those of sham studies conducted in RA during the same time period. Individuals with cervical SCI had higher V̇e after AIH compared with able-bodied controls (117.9 ± 23.2% vs. 97.9 ± 11.2%, P < 0.05). RRI decreased during hypoxia in all individuals (those with cervical SCI, from 1,009.3 ± 65.0 ms to 750.2 ± 65.0 ms; those with thoracic SCI, from 945.2 ± 65.0 ms to 674.9 ± 65.0 ms; and those who were able-bodied, from 949 ± 75.0 to 682.2 ± 69.5 ms; P < 0.05). LH/HF increased during recovery in individuals with thoracic SCI and those who were able-bodied (0.54 ± 0.22 vs. 1.34 ± 0.22 and 0.67 ± 0.23 vs. 1.82 ± 0.23, respectively; P < 0.05) but remained unchanged in the group with cervical SCI. Our conclusion is that patients with cervical SCI demonstrate ventilatory long-term facilitation following AIH compared with able-bodied controls. Heart rate responses to hypoxia are acutely present in patients with cervical SCI but are absent during posthypoxic recovery. PMID:26272316

  18. SIPL1-facilitated PTEN ubiquitination contributes to its association with PTEN.

    PubMed

    De Melo, Jason; Lin, Xiaozeng; He, Lizhi; Wei, Fengxiang; Major, Pierre; Tang, Damu

    2014-12-01

    PTEN is post-translationally modified by ubiquitin via association with multiple E3 ubiquitin ligases, including NEDD4-1, XIAP, and WWP2. Despite the rapid progress made in researching the impact of ubiquitination on PTEN function, our understanding remains fragmented. Building on the previously observed interaction between SIPL1 and PTEN, we report here that SIPL1 promotes PTEN polyubiquitination via lysine 48 (K48)-independent polyubiquitin chains. Substitution of the K48 residue of ubiquitin with arginine (R) enhanced SIPL1-mediated PTEN polyubiquitination. In contrast, the K63R substitution significantly reduced it. The ubiquitin-like (UBL) domain is required for SIPL1-induced PTEN polyubiquitination. This post-translational modification promoted the association of SIPL1 with PTEN. Elevated amounts of the SIPL1/PTEN complex were precipitated in 293T cells co-transfected with PTEN, SIPL1, and ubiquitin compared to cells co-transfected with SIPL1 and PTEN only. Additionally, formation of the SIPL1/PTEN complex was inhibited when either lysine-less (K0) ubiquitin or K63R ubiquitin was co-transfected together with SIPL1+PTEN. The PTEN component in the SIPL1/PTEN complex contained polyubiquitin chains. The ubiquitination reaction may play a structural role, stabilizing the SIPL1/PTEN complex, as a ubiquitin binding-defective SIPL1 mutant (TFLV) is proficient in PTEN association. Collectively, we demonstrate that SIPL1 binds PTEN and enhances PTEN polyubiquitination which in turn promotes the interaction between SIPL1 and PTEN. PMID:25152374

  19. SuhB Associates with Nus Factors To Facilitate 30S Ribosome Biogenesis in Escherichia coli

    PubMed Central

    Singh, Navjot; Bubunenko, Mikhail; Smith, Carol; Abbott, David M.; Stringer, Anne M.; Shi, Ronald; Court, Donald L.

    2016-01-01

    ABSTRACT A complex of highly conserved proteins consisting of NusB, NusE, NusA, and NusG is required for robust expression of rRNA in Escherichia coli. This complex is proposed to prevent Rho-dependent transcription termination by a process known as “antitermination.” The mechanism of this antitermination in rRNA is poorly understood but requires association of NusB and NusE with a specific RNA sequence in rRNA known as BoxA. Here, we identify a novel member of the rRNA antitermination machinery: the inositol monophosphatase SuhB. We show that SuhB associates with elongating RNA polymerase (RNAP) at rRNA in a NusB-dependent manner. Although we show that SuhB is required for BoxA-mediated antitermination in a reporter system, our data indicate that the major function of the NusB/E/A/G/SuhB complex is not to prevent Rho-dependent termination of rRNA but rather to promote correct rRNA maturation. This occurs through formation of a SuhB-mediated loop between NusB/E/BoxA and RNAP/NusA/G. Thus, we have reassigned the function of these proteins at rRNA and identified another key player in this complex. PMID:26980831

  20. The Ubiquitin-associated Domain of Cellular Inhibitor of Apoptosis Proteins Facilitates Ubiquitylation*

    PubMed Central

    Budhidarmo, Rhesa; Day, Catherine L.

    2014-01-01

    The cellular inhibitor of apoptosis (cIAP) proteins are essential RING E3 ubiquitin ligases that regulate apoptosis and inflammatory responses. cIAPs contain a ubiquitin-associated (UBA) domain that binds ubiquitin and is implicated in the regulation of cell survival and proteasomal degradation. Here we show that mutation of the MGF and LL motifs in the UBA domain of cIAP1 caused unfolding and increased cIAP1 multimonoubiquitylation. By developing a UBA mutant that disrupted ubiquitin binding but not the structure of the UBA domain, we found that the UBA domain enhances cIAP1 and cIAP2 ubiquitylation. We demonstrate that the UBA domain binds to the UbcH5b∼Ub conjugate, and this promotes RING domain-dependent monoubiquitylation. This study establishes ubiquitin-binding modules, such as the UBA domain, as important regulatory modules that can fine tune the activity of E3 ligases. PMID:25065467

  1. Ultrasound Targeted Microbubble Destruction Stimulates Cellular Endocytosis in Facilitation of Adeno-Associated Virus Delivery

    PubMed Central

    Jin, Li-Fang; Li, Fan; Wang, Hui-Ping; Wei, Fang; Qin, Peng; Du, Lian-Fang

    2013-01-01

    The generally accepted mechanism for ultrasound targeted microbubble destruction (UTMD) to enhance drug and gene delivery is through sonoporation. However, passive uptake of adeno-associated virus (AAV) into cells following sonoporation does not adequately explain observations of enhanced transduction by UTMD. This study investigated alternative mechanisms of UTMD enhancement in AAV delivery. UTMD significantly enhanced transduction efficiency of AAV in a dose-dependent manner. UTMD stimulated a persistent uptake of AAV into the cytoplasm and nucleus. This phenomenon occurred over several hours, suggesting that some viral particles are endocytosed by cells rather than exclusively passing through pores created by sonoporation. Additionally, UTMD enhanced clathrin expression and accumulation at the plasma membrane suggesting greater clathrin-mediated endocytosis following UTMD. Transmission electron microscopy (TEM) revealed that UTMD stimulated formation of clathrin-coated pits (CPs) and uncoated pits (nCPs). Furthermore, inhibition of clathrin-mediated endocytosis partially blocked the enhancement of AAV uptake following UTMD. The results of this study implicate endocytosis as a mechanism that contributes to UTMD-enhanced AAV delivery. PMID:23652832

  2. Tyrosine kinase 2 promotes sepsis-associated lethality by facilitating production of interleukin-27.

    PubMed

    Bosmann, Markus; Strobl, Birgit; Kichler, Nadia; Rigler, Doris; Grailer, Jamison J; Pache, Florence; Murray, Peter J; Müller, Mathias; Ward, Peter A

    2014-07-01

    The aim of this study was to test the hypothesis that gene expression and release of IL-27 may be modulated by Tyk2. Macrophages derived from the peritoneum or bone marrow of C57BL/10SnJ (WT) mice produced abundant amounts of IL-27(p28) following TLR4 activation by LPS. In contrast, production of IL-27(p28), but not EBI3, was reduced by ∼50% in TLR4-activated macrophages derived from mice with genetic deficiency of Tyk2 compared with WT macrophages. Frequencies of IL-27(p28)+F4/80+CD11b+ cells were lower in TLR4-activated macrophages derived from Tyk2-/- mice. Mechanistically, Tyk2-/- resulted in disruption of a type I IFN-dependent mechanism for production of IL-27(p28), which was induced by type I IFNs, and release of IL-27 was defective in macrophages from IFN-β-/- and IFNAR1-/- mice. In contrast, Tyk2 was not required to mediate the effects of IL-27 on target gene expression in CD4(+) T cells. In vivo, we observed that Tyk2-/- mice have improved survival following endotoxic shock or polymicrobial sepsis induced by CLP. Plasma levels of IL-27(p28) during endotoxic shock or polymicrobial sepsis were markedly reduced in Tyk2-/- mice compared with WT mice. Disruption of IL-27 signaling using IL-27RA-/- mice was protective against sepsis-associated mortality. These data suggest that Tyk2 may mediate adverse outcomes of SIRS by promoting the production of IL-27. In conclusion, this report identifies Tyk2 as a prerequisite factor in the molecular networks that are involved in generation of IL-27. PMID:24604832

  3. HIV-Associated Disruption of Tight and Adherens Junctions of Oral Epithelial Cells Facilitates HSV-1 Infection and Spread

    PubMed Central

    Sufiawati, Irna; Tugizov, Sharof M.

    2014-01-01

    Herpes simplex virus (HSV) types 1 and 2 are the most common opportunistic infections in HIV/AIDS. In these immunocompromised individuals, HSV-1 reactivates and replicates in oral epithelium, leading to oral disorders such as ulcers, gingivitis, and necrotic lesions. Although the increased risk of HSV infection may be mediated in part by HIV-induced immune dysfunction, direct or indirect interactions of HIV and HSV at the molecular level may also play a role. In this report we show that prolonged interaction of the HIV proteins tat and gp120 and cell-free HIV virions with polarized oral epithelial cells leads to disruption of tight and adherens junctions of epithelial cells through the mitogen-activated protein kinase signaling pathway. HIV-induced disruption of oral epithelial junctions facilitates HSV-1 paracellular spread between the epithelial cells. Furthermore, HIV-associated disruption of adherens junctions exposes sequestered nectin-1, an adhesion protein and critical receptor for HSV envelope glycoprotein D (gD). Exposure of nectin-1 facilitates binding of HSV-1 gD, which substantially increases HSV-1 infection of epithelial cells with disrupted junctions over that of cells with intact junctions. Exposed nectin-1 from disrupted adherens junctions also increases the cell-to-cell spread of HSV-1 from infected to uninfected oral epithelial cells. Antibodies to nectin-1 and HSV-1 gD substantially reduce HSV-1 infection and cell-to-cell spread, indicating that HIV-promoted HSV infection and spread are mediated by the interaction of HSV gD with HIV-exposed nectin-1. Our data suggest that HIV-associated disruption of oral epithelial junctions may potentiate HSV-1 infection and its paracellular and cell-to-cell spread within the oral mucosal epithelium. This could be one of the possible mechanisms of rapid development of HSV-associated oral lesions in HIV-infected individuals. PMID:24586397

  4. HIV-associated disruption of tight and adherens junctions of oral epithelial cells facilitates HSV-1 infection and spread.

    PubMed

    Sufiawati, Irna; Tugizov, Sharof M

    2014-01-01

    Herpes simplex virus (HSV) types 1 and 2 are the most common opportunistic infections in HIV/AIDS. In these immunocompromised individuals, HSV-1 reactivates and replicates in oral epithelium, leading to oral disorders such as ulcers, gingivitis, and necrotic lesions. Although the increased risk of HSV infection may be mediated in part by HIV-induced immune dysfunction, direct or indirect interactions of HIV and HSV at the molecular level may also play a role. In this report we show that prolonged interaction of the HIV proteins tat and gp120 and cell-free HIV virions with polarized oral epithelial cells leads to disruption of tight and adherens junctions of epithelial cells through the mitogen-activated protein kinase signaling pathway. HIV-induced disruption of oral epithelial junctions facilitates HSV-1 paracellular spread between the epithelial cells. Furthermore, HIV-associated disruption of adherens junctions exposes sequestered nectin-1, an adhesion protein and critical receptor for HSV envelope glycoprotein D (gD). Exposure of nectin-1 facilitates binding of HSV-1 gD, which substantially increases HSV-1 infection of epithelial cells with disrupted junctions over that of cells with intact junctions. Exposed nectin-1 from disrupted adherens junctions also increases the cell-to-cell spread of HSV-1 from infected to uninfected oral epithelial cells. Antibodies to nectin-1 and HSV-1 gD substantially reduce HSV-1 infection and cell-to-cell spread, indicating that HIV-promoted HSV infection and spread are mediated by the interaction of HSV gD with HIV-exposed nectin-1. Our data suggest that HIV-associated disruption of oral epithelial junctions may potentiate HSV-1 infection and its paracellular and cell-to-cell spread within the oral mucosal epithelium. This could be one of the possible mechanisms of rapid development of HSV-associated oral lesions in HIV-infected individuals. PMID:24586397

  5. Phospholipases and arachidonic acid contribute independently to sensory transduction and associative neuronal facilitation in Hermissenda type B photoreceptors.

    PubMed

    Talk, A C; Muzzio, I A; Matzel, L D

    1997-03-21

    During contiguous pairings of light and rotation, B photoreceptors in the Hermissenda eye undergo an increase in excitability that contributes to a modification of several light-elicited behaviors. This excitability increase requires a light-induced rise in intracellular Ca2+ in the photoreceptor concomitant with transmitter binding to G protein-coupled receptors as a result of presynaptic vestibular hair cell stimulation. Phospholipases and arachidonic acid (ArA) are here reported to be involved in independent signal transduction pathways that underlie both receptor function and activity-dependent facilitation of the B photoreceptor. 4-Bromophenacyl bromide (BPB), an inhibitor of phospholipases A2 (PLA2) and C (PLC), blocked the generation of light-induced depolarizing generator potentials, but had no affect on the inhibitory postsynaptic potential (IPSP) in the B cell that results from hair cell stimulation. Quinacrine, which predominantly blocks the activity of PLA2 in neurons, had no affect on either the light response or the IPSP, but did block increases in excitability (i.e. increased input resistance and elicited spike rate) of the B cell that results from pairings of light and presynaptic vestibular stimulation (i.e., in vitro associative conditioning). Neither nordihydroquararetic acid (NDGA), which inhibits metabolism of ArA by cyclooxygenase, nor indomethacin, which inhibits lipoxygenase metabolism of ArA, affected the light response or IPSP, but both blocked the increases in excitability in the B cell that accompanied in vitro conditioning. In combination with earlier results, these data suggest that ArA activates PKC in a synergistic fashion with Ca2+ and diacylglycerol in the B cell, and suggest that PLA2-induced ArA release, though not necessary for transduction of light or the hair cell-induced IPSP in the B cell, is a critical component of the convergence of signals that precipitates associative facilitation in this system. PMID:9099806

  6. The Comparative Toxicogenomics Database facilitates identification and understanding of chemical-gene-disease associations: arsenic as a case study

    PubMed Central

    Davis, Allan P; Murphy, Cynthia G; Rosenstein, Michael C; Wiegers, Thomas C; Mattingly, Carolyn J

    2008-01-01

    integrates these data with additional curated data sets that facilitate construction of chemical-gene-disease networks and provide the groundwork for investigating the molecular basis of arsenic-associated diseases or toxicity. The analysis reported here is extensible to any environmental chemical or therapeutic drug. PMID:18845002

  7. TGFβ3-mediated induction of Periostin facilitates head and neck cancer growth and is associated with metastasis.

    PubMed

    Qin, Xing; Yan, Ming; Zhang, Jianjun; Wang, Xu; Shen, Zongze; Lv, Zhongjing; Li, Zhihui; Wei, Wenyi; Chen, Wantao

    2016-01-01

    The matrix-specific protein periostin (POSTN) is up-regulated in human cancers and associated with cancer growth, metastasis and angiogenesis. Although the stroma of cancer tissues is the main source of POSTN, it is still unclear how POSTN plays a role to facilitate the interplay between cancer cells and cancer-associated fibroblasts (CAFs) in head and neck cancer (HNC), thereby promoting tumorigenesis via modifying the tumor microenvironment. Herein, we have performed studies to investigate POSTN and its role in HNC microenvironment. Our results indicated that POSTN was significantly up-regulated in HNCs, especially in the tissues with lymph node metastasis. Moreover, POSTN was highly enriched in the stroma of cancer tissues and produced mainly by CAFs. More importantly, we have pinpointed TGF-β3 as the major upstream molecular that triggers the induction of POSTN in CAFs. As such, during the interaction between fibroblasts and cancer cells, the increased stromal POSTN induced by TGF-β3 directly accelerated the growth, migration and invasion of cancer cells. Hence, our study has provided a novel modulative role for POSTN on HNC progression and further reveals POSTN as an effective biomarker to predict metastasis as well as a potential cancer therapeutic target. PMID:26857387

  8. Inhibition of histone deacetylase in the basolateral amygdala facilitates morphine context-associated memory formation in rats.

    PubMed

    Wang, Yunpeng; Lai, Jianghua; Cui, Haimin; Zhu, Yongsheng; Zhao, Bin; Wang, Wei; Wei, Shuguang

    2015-01-01

    Histone acetylation/deacetylation is a crucial mechanism in memory formation and drug addiction. There is evidence suggesting that histone H3 acetylation may contribute to the long-term neural and behavioral responses to addictive drugs. In addition, the basolateral amygdala (BLA) is critically involved in the formation of cue-associated memories. However, the behavioral effect of histone deacetylase (HDAC) inhibition in the BLA and the underlying molecular alterations at different phases of morphine-induced conditioned place preference (CPP) has not been investigated. In this study, we measured the expression, extinction, and reinstatement of morphine-induced place preference in rats pretreated with trichostatin A (TSA), an HDAC inhibitor. Intra-BLA pretreatment with TSA significantly enhanced morphine-induced CPP acquisition and expression, facilitated extinction, and reduced reinstatement of morphine-induced CPP. These behavioral changes were associated with a general increase in histone H3 lysine14 (H3K14) acetylation in the BLA together with upregulation of the brain-derived neurophic factor (BDNF) and ΔFosB and CREB activation. Collectively, our findings imply that HDAC inhibition in the BLA promotes some aspects of the memory that develops during conditioning and extinction training. Furthermore, histone H3 acetylation may play a role in learning and memory for morphine addiction in the BLA. PMID:24829091

  9. A virally encoded small peptide regulates RTA stability and facilitates Kaposi's sarcoma-associated herpesvirus lytic replication.

    PubMed

    Jaber, Tareq; Yuan, Yan

    2013-03-01

    In both mammalian and viral genomes, a large proportion of sequences are transcribed and annotated as noncoding RNAs. A polyadenylated RNA of 3.0 kb (T3.0) is transcribed from the opposite strand of the open reading frame 50 (ORF50) DNA template in the genome of Kaposi's sarcoma-associated herpesvirus (KSHV) and has been annotated previously as a noncoding RNA. ORF50 encodes the replication and transcription activator (RTA), which controls the switch of the virus between the latent and lytic phases of the life cycle. Here we show that T3.0 encodes a small peptide of 48 amino acids (designated viral small peptide 1 [vSP-1]). vSP-1 interacts with RTA at the protein abundance regulatory signal (PARS) motifs, and the association prevents RTA from being subjected to degradation through the ubiquitin-proteasome pathway. As a consequence, vSP-1 facilitates KSHV gene expression and lytic replication. This finding reveals a novel mechanism of gene regulation in the viral life cycle. PMID:23302891

  10. TGFβ3-mediated induction of Periostin facilitates head and neck cancer growth and is associated with metastasis

    PubMed Central

    Qin, Xing; Yan, Ming; Zhang, Jianjun; Wang, Xu; Shen, Zongze; Lv, Zhongjing; Li, Zhihui; Wei, Wenyi; Chen, Wantao

    2016-01-01

    The matrix-specific protein periostin (POSTN) is up-regulated in human cancers and associated with cancer growth, metastasis and angiogenesis. Although the stroma of cancer tissues is the main source of POSTN, it is still unclear how POSTN plays a role to facilitate the interplay between cancer cells and cancer-associated fibroblasts (CAFs) in head and neck cancer (HNC), thereby promoting tumorigenesis via modifying the tumor microenvironment. Herein, we have performed studies to investigate POSTN and its role in HNC microenvironment. Our results indicated that POSTN was significantly up-regulated in HNCs, especially in the tissues with lymph node metastasis. Moreover, POSTN was highly enriched in the stroma of cancer tissues and produced mainly by CAFs. More importantly, we have pinpointed TGF-β3 as the major upstream molecular that triggers the induction of POSTN in CAFs. As such, during the interaction between fibroblasts and cancer cells, the increased stromal POSTN induced by TGF-β3 directly accelerated the growth, migration and invasion of cancer cells. Hence, our study has provided a novel modulative role for POSTN on HNC progression and further reveals POSTN as an effective biomarker to predict metastasis as well as a potential cancer therapeutic target. PMID:26857387

  11. Does Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2) Use in Adult Spinal Deformity (ASD) Increase Complications and Are Complications Associated With Location of rhBMP-2 Use?: A Prospective, Multicenter Study of 279 Consecutive Patients.

    PubMed

    Bess, Shay; Line, Breton G; Lafarge, Virginie; Schwab, Frank; Shaffrey, Christopher I; Hart, Robert A; Boachie-Adjei, Oheneba; Akbarnia, Behrooz A; Ames, Christopher P; Burton, Douglas C; Deverin, Vedat; Fu, Kai-Ming G; Gupta, Munish; Hostin, Richard; Kebaish, Khaled; Klineberg, Eric; Mundis, Gregory; O'Brien, Michael; Shelokov, Alexis; Smith, Justin S

    2013-11-18

    Study Design. Multi-center, prospective analysis of consecutive ASD patients.Objective. Evaluate complications associated with rhBMP-2 use in ASDSummary of Background Data. Off-label rhBMP-2 use is common, however under-reporting of rhBMP-2 associated complications has been recently scrutinized.Methods. ASD patients consecutively enrolled into a prospective, multicenter database, were evaluated for type and timing of acute perioperative complications. Inclusion criteria: age ≥ 18 years, ASD, spinal arthrodesis >4 levels, and ≥3 months follow-up. Patients divided into those receiving rhBMP-2 (BMP) or no rhBMP-2 (NOBMP). BMP divided into location of use: posterior (PBMP), interbody (IBMP), and interbody + posterior spine (I+PBMP). Correlations between acute perioperative complications and rhBMP-2 use including total dose, dose/level and location of use were evaluated.Results. 279 patients (mean age 57 years, mean spinal levels fused 12.0, mean follow-up 28.8 months) met inclusion criteria. BMP (n = 172; average posterior dose = 2.5 mg/level, average interbody dose = 5 mg/level) had similar age, smoking history, previous spine surgery, total spinal levels fused, estimated blood loss, and duration of hospital stay as NOBMP (n = 107; p>0.05). BMP had greater Charlson Comorbidity Index (1.9 vs. 1.2), greater scoliosis (43° vs. 38°), longer operative time (488.2 vs. 414.6 minutes), more osteotomies/patient (4.0 vs. 1.6) and greater percentage of anteroposterior fusion (APSF; 20.9% vs. 8.4%) than NOBMP, respectively (p<0.05). BMP had more total complications/patient (1.4 vs.0.6) and more minor complications/patient (0.9 vs. 0.2) than NOBMP, respectively (p<0.05). NOBMP had more complications requiring surgery/patient than BMP (0.3 vs. 0.2; p<0.05). Major, neurological, wound, and infection complications were similar for NOBMP, BMP, PBMP, IBMP, and I+PBMP (p>0.05). Multivariate analysis demonstrated small to non-existent correlations between rhBMP-2 use and

  12. Noninvasive, neuron-specific gene therapy can be facilitated by focused ultrasound and recombinant adeno-associated virus.

    PubMed

    Wang, S; Olumolade, O O; Sun, T; Samiotaki, G; Konofagou, E E

    2015-01-01

    Recombinant adeno-associated virus (rAAV) has shown great promise as a potential cure for neurodegenerative diseases. The existence of the blood-brain barrier (BBB), however, hinders efficient delivery of the viral vectors. Direct infusion through craniotomy is the most commonly used approach to achieve rAAV delivery, which carries increased risks of infection and other complications. Here, we report a focused ultrasound (FUS)-facilitated noninvasive rAAV delivery paradigm that is capable of producing targeted and neuron-specific transductions. Oscillating ultrasound contrast agents (microbubbles), driven by FUS waves, temporarily 'unlock' the BBB, allowing the systemically administrated rAAVs to enter the brain parenchyma, while maintaining their bioactivity and selectivity. Taking the advantage of the neuron-specific promoter synapsin, rAAV gene expression was triggered almost exclusively (95%) in neurons of the targeted caudate-putamen region. Both behavioral assessment and histological examination revealed no significant long-term adverse effects (in the brain and several other critical organs) for this combined treatment paradigm. Results from this study demonstrated the feasibility and safety for the noninvasive, targeted rAAV delivery, which might have open a new avenue in gene therapy in both preclinical and clinical settings. PMID:25354683

  13. Non-invasive, neuron-specific gene therapy can be facilitated by focused ultrasound and recombinant adeno-associated virus

    PubMed Central

    Wang, Shutao; Olumolade, Oluyemi O.; Sun, Tao; Samiotaki, Gesthimani; Konofagou, Elisa E.

    2015-01-01

    Recombinant adeno-associated virus (rAAV) has shown great promise as a potential cure for neurodegenerative diseases. The existence of the blood-brain barrier (BBB), however, hinders efficient delivery of the viral vectors. Direct infusion through craniotomy is the most commonly used approach to achieve rAAV delivery, which carries increased risks of infection and other complications. Here we report a focused ultrasound (FUS) facilitated, non-invasive rAAV delivery paradigm that is capable of producing targeted and neuron-specific transductions. Oscillating ultrasound contrast agents (i.e. microbubbles), driven by focused ultrasound waves, temporarily “unlocking” the BBB, allowing the systemically administrated rAAVs to enter the brain parenchyma, while maintaining their bioactivity and selectivity. Taking the advantage of the neuron-specific promoter-synapsin, rAAV gene expression was triggered almost exclusively (95%) in neurons of the targeted (i.e. caudate-putamen) region. Both behavioral assessment and histological examination revealed no significant long term adverse effects (in the brain and several other critical organs) for this combined treatment paradigm. Results from this study demonstrated the feasibility and safety for the non-invasive, targeted rAAV delivery technique, which might have provided a new arena for gene therapy in both pre-clinical and clinical settings. PMID:25354683

  14. A 348-base-pair region in the latency-associated transcript facilitates herpes simplex virus type 1 reactivation.

    PubMed Central

    Bloom, D C; Hill, J M; Devi-Rao, G; Wagner, E K; Feldman, L T; Stevens, J G

    1996-01-01

    Latency-associated transcript (LAT) promoter deletion mutants of herpes simplex virus type 1 have a reduced capacity to reactivate following adrenergic induction in the rabbit eye model. We have mapped a reactivation phenotype within LAT and describe the construction of recombinants in which poly(A) addition sites have been placed at intervals within the LAT region to form truncated LAT transcripts. These mutants localize the induced reactivation phenotype to the 5' end of LAT. To further define this region, we constructed a recombinant containing a 348-bp deletion located 217 bp downstream of the transcription start site of the 8.5-kb LAT. This virus, 17delta348, expresses LAT but exhibits a significantly reduced ability to reactivate following epinephrine iontophoresis into the cornea. Quantitative DNA PCR analysis reveals that 17delta 348 establishes a latent infection within rabbit trigeminal ganglia with the same efficiency as does either the rescuant or wild-type virus. The region deleted in 17delta348 encodes three potential translational initiators (ATGs) which we have mutated and demonstrated to be dispensable for epinephrine-induced reactivation. In addition, three smaller deletions within this region have been constructed and were shown to reactivate at wild-type (parent) frequencies. These studies indicate that an undefined portion of the 348-bp region is required to facilitate induced reactivation. Sequence analysis of this 348-bp region revealed a CpG island which extends into the LAT promoter and which possesses homology to conserved elements within the mouse and human XIST transcript encoded on the X chromosome. Possible implications of these elements in the regulation of LAT expression are discussed. PMID:8642650

  15. Cardiac Resynchronization Therapy Delivered Via a Multipolar Left Ventricular Lead is Associated with Reduced Mortality and Elimination of Phrenic Nerve Stimulation: Long‐Term Follow‐Up from a Multicenter Registry

    PubMed Central

    BEHAR, JONATHAN M.; BOSTOCK, JULIAN; ZHU LI, ADRIAN PO; CHIN, HUI MEN SELINA; JUBB, STEPHEN; LENT, EDWARD; GAMBLE, JAMES; FOLEY, PAUL W.X.; BETTS, TIM R.; RINALDI, CHRISTOPHER ALDO

    2015-01-01

    Lower Mortality and Eliminated PNS Associated with Quadripolar Leads Introduction Cardiac resynchronization therapy (CRT) using quadripolar left ventricular (LV) leads provides more pacing vectors compared to bipolar leads. This may avoid phrenic nerve stimulation (PNS) and allow optimal lead placement to maximize biventricular pacing. However, a long‐term improvement in patient outcome has yet to be demonstrated. Methods A total of 721 consecutive patients with conventional CRTD criteria implanted with quadripolar (n = 357) or bipolar (n = 364) LV leads were enrolled into a registry at 3 UK centers. Lead performance and mortality was analyzed over a 5‐year period. Results Patients receiving a quadripolar lead were of similar age and sex to those receiving a bipolar lead, although a lower proportion had ischemic heart disease (62.6% vs. 54.1%, P = 0.02). Both groups had similar rates of procedural success, although lead threshold, impedance, and procedural radiation dose were significantly lower in those receiving a quadripolar lead. PNS was more common in those with quadripolar leads (16.0% vs. 11.6%, P = 0.08), but was eliminated by switching pacing vector in all cases compared with 60% in the bipolar group (P < 0.001). Furthermore, LV lead displacement (1.7% vs. 4.6%, P = 0.03) and repositioning (2.0% vs. 5.2%, P = 0.03) occurred significantly less often in those with a quadripolar lead. All‐cause mortality was also significantly lower in the quadripolar compared to bipolar lead group in univariate and multivariate analysis (13.2% vs. 22.5%, P < 0.001). Conclusions In a large, multicenter experience, the use of quadripolar LV leads for CRT was associated with elimination of PNS and lower overall mortality. This has important implications for LV pacing lead choice. PMID:25631303

  16. Association between barriers and facilitators to meeting the Dietary Guidelines for Americans and body weight status of caregiver-child dyads: The HEALTH study

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Few Americans meet the Dietary Guidelines for Americans (DGA) yet, a large percentage are overweight. The goal of this research was to examine the association between barriers and facilitators to meeting the DGA and weight in a multi-site study. In a cross-sectional study, a total of 836 caregiver-c...

  17. Validation of Single Nucleotide Polymorphisms (SNPs) Associated with Acute Rejection in Kidney Transplant Recipients Using a Large Multi-Center Cohort

    PubMed Central

    Oetting, William S.; Schladt, David P.; Leduc, Robert E.; Jacobson, Pamala A.; Guan, Weihua; Matas, Arthur J.; Israni, Ajay

    2011-01-01

    There have been numerous reports proposing a statistically significant association between a genetic variant, usually in the form of a single nucleotide polymorphism (SNP), and acute rejection (AR). Unfortunately, there are additional publications reporting a lack of association with AR when a different cohort of recipients was analyzed for the same SNP. The objective of this report was to attempt replication of these published finding in our own kidney allograft recipient cohort. We analyzed 23 genetic variants, previously reported to have a significant association with AR, using a cohort of 969 clinically well defined kidney transplant recipients. Only one SNP, rs6025 (Leiden mutation), within the coagulation factor V gene, showed a significant association with a p-value of 0.011 in a race adjusted analysis and 0.0003 in multiple variable analysis. An additional SNP, rs11706052 in IMPDH2, gave a modest p-value of 0.044 using multiple variable analysis which is not significant when multiple testing is taken into consideration. Our results suggest that careful validation of previously reported associations with AR is necessary and different strategies other than candidate gene studies can help to identify causative genetic variants associated with AR. PMID:21955043

  18. Risk-Reducing Salpingo-Oophorectomy for the Prevention of BRCA1- and BRCA2-Associated Breast and Gynecologic Cancer: A Multicenter, Prospective Study

    PubMed Central

    Kauff, Noah D.; Domchek, Susan M.; Friebel, Tara M.; Robson, Mark E.; Lee, Johanna; Garber, Judy E.; Isaacs, Claudine; Evans, D. Gareth; Lynch, Henry; Eeles, Rosalind A.; Neuhausen, Susan L.; Daly, Mary B.; Matloff, Ellen; Blum, Joanne L.; Sabbatini, Paul; Barakat, Richard R.; Hudis, Clifford; Norton, Larry; Offit, Kenneth; Rebbeck, Timothy R.

    2011-01-01

    Purpose Risk-reducing salpingo-oophorectomy (RRSO) has been widely adopted as a key component of breast and gynecologic cancer risk-reduction for women with BRCA1 and BRCA2 mutations. Despite 17% to 39% of all BRCA mutation carriers having a mutation in BRCA2, no prospective study to date has evaluated the efficacy of RRSO for the prevention of breast and BRCA-associated gynecologic (ovarian, fallopian tube or primary peritoneal) cancer when BRCA2 mutation carriers are analyzed separately from BRCA1 mutation carriers. Patients and Methods A total of 1,079 women 30 years of age and older with ovaries in situ and a deleterious BRCA1 or BRCA2 mutation were enrolled onto prospective follow-up studies at one of 11 centers from November 1, 1994 to December 1, 2004. Women self-selected RRSO or observation. Follow-up information through November 30, 2005, was collected by questionnaire and medical record review. The effect of RRSO on time to diagnosis of breast or BRCA-associated gynecologic cancer was analyzed using a Cox proportional-hazards model. Results During 3-year follow-up, RRSO was associated with an 85% reduction in BRCA1-associated gynecologic cancer risk (hazard ratio [HR] = 0.15; 95% CI, 0.04 to 0.56) and a 72% reduction in BRCA2-associated breast cancer risk (HR = 0.28; 95% CI, 0.08 to 0.92). While protection against BRCA1-associated breast cancer (HR = 0.61; 95% CI, 0.30 to 1.22) and BRCA2-associated gynecologic cancer (HR = 0.00; 95% CI, not estimable) was suggested, neither effect reached statistical significance. Conclusion The protection conferred by RRSO against breast and gynecologic cancers may differ between carriers of BRCA1 and BRCA2 mutations. Further studies evaluating the efficacy of risk-reduction strategies in BRCA mutation carriers should stratify by the specific gene mutated. PMID:18268356

  19. A Multicenter Blinded Analysis Indicates No Association between Chronic Fatigue Syndrome/Myalgic Encephalomyelitis and either Xenotropic Murine Leukemia Virus-Related Virus or Polytropic Murine Leukemia Virus

    PubMed Central

    Alter, Harvey J.; Mikovits, Judy A.; Switzer, William M.; Ruscetti, Francis W.; Lo, Shyh-Ching; Klimas, Nancy; Komaroff, Anthony L.; Montoya, Jose G.; Bateman, Lucinda; Levine, Susan; Peterson, Daniel; Levin, Bruce; Hanson, Maureen R.; Genfi, Afia; Bhat, Meera; Zheng, HaoQiang; Wang, Richard; Li, Bingjie; Hung, Guo-Chiuan; Lee, Li Ling; Sameroff, Stephen; Heneine, Walid; Coffin, John; Hornig, Mady; Lipkin, W. Ian

    2012-01-01

    ABSTRACT The disabling disorder known as chronic fatigue syndrome or myalgic encephalomyelitis (CFS/ME) has been linked in two independent studies to infection with xenotropic murine leukemia virus-related virus (XMRV) and polytropic murine leukemia virus (pMLV). Although the associations were not confirmed in subsequent studies by other investigators, patients continue to question the consensus of the scientific community in rejecting the validity of the association. Here we report blinded analysis of peripheral blood from a rigorously characterized, geographically diverse population of 147 patients with CFS/ME and 146 healthy subjects by the investigators describing the original association. This analysis reveals no evidence of either XMRV or pMLV infection. PMID:22991430

  20. Six sequence variants on chromosome 9p21.3 are associated with a positive family history of myocardial infarction: a multicenter registry

    PubMed Central

    2011-01-01

    Background Recent genome-wide association studies have identified several genetic loci linked to coronary artery disease (CAD) and myocardial infarction (MI). The 9p21.3 locus was verified by numerous replication studies to be the first common locus for CAD and MI. In the present study, we investigated whether six single nucleotide polymorphisms (SNP) rs1333049, rs1333040, rs10757274, rs2383206, rs10757278, and rs2383207 representing the 9p21.3 locus were associated with the incidence of an acute MI in patients with the main focus on the familial aggregation of the disease. Methods The overall cohort consisted of 976 unrelated male patients presenting with an acute coronary syndrome (ACS) with ST-elevated (STEMI) as well as non-ST-elevated myocardial infarction (NSTEMI). Genotyping data of the investigated SNPs were generated and statistically analyzed in comparison to previously published findings of matchable control cohorts. Results Statistical evaluation confirmed a highly significant association of all analyzed SNP's with the occurrence of MI (p < 0.0001; OR: 1.621-2.039). When only MI patients with a positive family disposition were comprised in the analysis a much stronger association of the accordant risk alleles with incident disease was found with odds ratios up to 2.769. Conclusions The findings in the present study confirmed a strong association of the 9p21.3 locus with MI particularly in patients with a positive family history thereby, emphasizing the pathogenic relevance of this locus as a common genetic cardiovascular risk factor. PMID:21385355

  1. Epidemiology, Seasonality and Factors Associated with Rotavirus Infection among Children with Moderate-to-Severe Diarrhea in Rural Western Kenya, 2008–2012: The Global Enteric Multicenter Study (GEMS)

    PubMed Central

    Omore, Richard; Tate, Jacqueline E.; O’Reilly, Ciara E.; Ayers, Tracy; Williamson, John; Moke, Feny; Schilling, Katie A.; Awuor, Alex O.; Jaron, Peter; Ochieng, John B.; Oundo, Joseph; Parashar, Umesh D.; Parsons, Michele B.; Bopp, Cheryl C.; Nasrin, Dilruba; Farag, Tamer H.; Kotloff, Karen L.; Nataro, James P.; Panchalingam, Sandra; Levine, Myron M.; Laserson, Kayla F.; Nuorti, J. Pekka; Mintz, Eric D.; Breiman, Robert F.

    2016-01-01

    Objective To evaluate factors associated with rotavirus diarrhea and to describe severity of illness among children <5 years old with non-dysenteric, moderate-to-severe diarrhea (MSD) in rural western Kenya. Methods We analyzed data from children <5 years old with non-dysenteric MSD enrolled as cases in the Global Enteric Multicenter Study (GEMS) in Kenya. A non-dysenteric MSD case was defined as a child with ≥3 loose stools in 24 hrs. and one or more of the following: sunken eyes, skin tenting, intravenous rehydration, or hospitalization, who sought care at a sentinel health center within 7 days of illness onset. Rotavirus antigens in stool samples were detected by ELISA. Demographic and clinical information was collected at enrollment and during a single follow-up home visit at approximately 60 days. We analyzed diarrhea severity using a GEMS 17 point numerical scoring system adapted from the Vesikari score. We used logistic regression to evaluate factors associated with rotavirus infection. Results From January 31, 2008 to September 30, 2012, among 1,637 (92%) non-dysenteric MSD cases, rotavirus was detected in stools of 245 (15.0%). Rotavirus-positive compared with negative cases were: younger (median age, 8 vs. 13 months; p<0.0001), had more severe illness (median severity score, 9 vs 8; p<0.0001) and had to be hospitalized more frequently (37/245 [15.1%] vs. 134/1,392 [9.6%]), p <0.013). Independent factors associated with rotavirus infection included age 0–11 months old (aOR = 5.29, 95% CI 3.14–8.89) and presenting with vomiting ≥3 times/24hrs (aOR = 2.58, 95% CI [1.91–3.48]). Rotavirus was detected more commonly in warm and dry months than in the cool and rainy months (142/691 [20%] vs 70/673 [10%]) p<0.0001). Conclusions Diarrhea caused by rotavirus is associated with severe symptoms leading to hospitalization. Consistent with other settings, infants had the greatest burden of disease. PMID:27494517

  2. Defining Competencies for Associate Degree Nursing Education and Practice. Proceedings of the Midwest Regional Conference on "The Associate Degree Nursing--Facilitating Competency Development" Project (Chicago, Illinois, March 10-11, 1983).

    ERIC Educational Resources Information Center

    Minckley, Barbara B., Ed.; Walters, Mary Dale, Ed.

    Focusing on "Associate Degree Nursing--Facilitating Competency Development," a 3-year project sponsored by the Midwest Alliance in Nursing (MAIN) to explore and recommend ways of strengthening Associate Degree Nursing (ADN) education and service, these proceedings contain papers by individuals involved with the development of the project and those…

  3. Maternal and Infant Factors Associated With Failure to Thrive in Children With Vertically Transmitted Human Immunodeficiency Virus-1 Infection: The Prospective, P2C2 Human Immunodeficiency Virus Multicenter Study

    PubMed Central

    Miller, Tracie L.; Easley, Kirk A.; Zhang, Weihong; Orav, E. John; Bier, Dennis M.; Luder, Elisabeth; Ting, Andrew; Shearer, William T.; Vargas, Jorge Humberto; Lipshultz, Steven E.

    2015-01-01

    Objective Many children with human immunodeficiency virus-1 (HIV-1) have chronic problems with growth and nutrition, yet limited information is available to identify infected children at high risk for growth abnormalities. Using data from the prospective, multicenter P2C2 HIV study, we evaluated the relationships between maternal and infant clinical and laboratory factors and impaired growth in this cohort. Methods Children of HIV-1–infected women were enrolled prenatally or within the first 28 days of life. Failure to thrive (FTT) was defined as an age- and sex-adjusted weight z score ≤−2.0 SD. Maternal baseline covariates included age, race, illicit drug use, zidovudine use, CD4+ T-cell count, and smoking. Infant baseline predictors included sex, race, CD4+ T-cell count, Centers for Disease Control stage, HIV-1 RNA, antiretroviral therapy, pneumonia, heart rate, cytomegalovirus, and Epstein–Barr virus infection status. Results The study cohort included 92 HIV-1–infected and 439 uninfected children. Infected children had a lower mean gestational age, but birth weights, lengths, and head circumferences in the 2 groups were similar. Mothers of growth-delayed infants were more likely to have smoked tobacco and used illicit drugs during pregnancy. In repeated-measures analyses of weight and length or height z scores, the means of the HIV-1–infected group were significantly lower at 6 months of age (P < .001) and remained lower throughout the first 5 years of life. In a multivariable Cox regression analysis, FTT was associated with a history of pneumonia (relative risk [RR] = 8.78; 95% confidence interval [CI]: 3.59–21.44), maternal use of cocaine, crack, or heroin during pregnancy (RR = 3.17; 95% CI: 1.51–6.66), infant CD4+ T-cell count z score (RR = 2.13 per 1 SD decrease; 95% CI: 1.25–3.57), and any antiretroviral therapy by 3 months of age (RR = 2.77; 95% CI: 1.16–6.65). After adjustment for pneumonia and antiretroviral therapy, HIV-1 RNA load

  4. An open-label multicenter study to assess the safety of dextromethorphan/quinidine in patients with pseudobulbar affect associated with a range of underlying neurological conditions

    PubMed Central

    Pattee, Gary L.; Wymer, James P.; Lomen-Hoerth, Catherine; Appel, Stanley H.; Formella, Andrea E.; Pope, Laura E.

    2014-01-01

    Abstract Background: Pseudobulbar affect (PBA) is associated with neurological disorders or injury affecting the brain, and characterized by frequent, uncontrollable episodes of crying and/or laughing that are exaggerated or unrelated to the patient’s emotional state. Clinical trials establishing dextromethorphan and quinidine (DM/Q) as PBA treatment were conducted in patients with amyotrophic lateral sclerosis (ALS) or multiple sclerosis (MS). This trial evaluated DM/Q safety in patients with PBA secondary to any neurological condition affecting the brain. Objective: To evaluate the safety and tolerability of DM/Q during long-term administration to patients with PBA associated with multiple neurological conditions. Methods: Fifty-two-week open-label study of DM/Q 30/30 mg twice daily. Safety measures included adverse events (AEs), laboratory tests, electrocardiograms (ECGs), vital signs, and physical examinations. Clinical trial registration: #NCT00056524. Results: A total of 553 PBA patients with >30 different neurological conditions enrolled; 296 (53.5%) completed. The most frequently reported treatment-related AEs (TRAEs) were nausea (11.8%), dizziness (10.5%), headache (9.9%), somnolence (7.2%), fatigue (7.1%), diarrhea (6.5%), and dry mouth (5.1%). TRAEs were mostly mild/moderate, generally transient, and consistent with previous controlled trials. Serious AEs (SAEs) were reported in 126 patients (22.8%), including 47 deaths, mostly due to ALS progression and respiratory failure. No SAEs were deemed related to DM/Q treatment by investigators. ECG results suggested no clinically meaningful effect of DM/Q on myocardial repolarization. Differences in AEs across neurological disease groups appeared consistent with the known morbidity of the primary neurological conditions. Study interpretation is limited by the small size of some disease groups, the lack of a specific efficacy measure and the use of a DM/Q dose higher than the eventually approved dose

  5. Association of Alcohol Consumption with Markers of Prostate Health and Reproductive Hormone Profiles: A Multi-Center Study of 4535 Men in China

    PubMed Central

    Fang, Fang; Martin, Kuete; Zheng, Yi; Zhang, Hui-Ping; Li, Hong-Gang; Zhu, Chang-Hong; Xiong, Cheng-Liang; Guan, Huang-Tao

    2015-01-01

    Background The effect of alcohol consumption on prostate health and reproductive hormone profiles has long been investigated and currently, no consensus has been reached. Additionally, large studies focusing on this topic are relatively rare in China. Purpose To investigate the association of alcohol consumption with prostate measurements and reproductive hormone profiles in Chinese population; and to examine the relationship between hormone levels and prostate measurements. Methods This cross-sectional study included 4535 men from four representative provinces of China. Demographic details, family history of prostate disease, tobacco and alcohol consumption, as well as International Prostate Symptom Score (I-PSS) were collected through a questionnaire. Total prostate specific antingen (total PSA), free PSA, free PSA/total PSA ratio (f/tPSA), and reproductive hormones were measured in serum. Multi-variable regression models were used to test for association of alcohol consumption with markers of prostate health, used to test for association of alcohol consumption with reproductive hormones, and reproductive hormones with markers of prostate health. Results Alcohol consumption had no obvious impact on total PSA concentration and I-PSS. Current drinkers had lower level of free PSA (β = -0.11, p = 0.02) and f/tPSA (β = -0.03, p = 0.005), former drinkers also had lower level of free PSA (β = -0.19, p = 0.02) when compared with never drinkers. Lower Luteinizing hormone (LH) (β = -1.05, p = 0.01), sex hormone-binding globulin (SHBG) (β = -4.71, p = 0.01) and higher estradiol (β = 7.81, p = 0.01) was found in current drinkers than never drinkers, whereas higher LH (β = 1.04, p = 0.04) and free testosterone (FT) (β = 0.03, p = 0.02) was detected in former drinkers than never drinkers. Furthermore, LH was positively associated with f/tPSA (β = 0.002, p = 0.006), SHBG was also positively related with free PSA (β = 0.003, p = 0.003) and f/tPSA (β = 0.0004, p = 0

  6. Associations among Visual Acuity and Vision- and Health-Related Quality of Life among Patients in the Multicenter Uveitis Steroid Treatment Trial

    PubMed Central

    Drye, Lea T.; Kempen, John H.; Dunn, James P.; Holland, Gary N.; Latkany, Paul; Rao, Narsing A.; Sen, H. Nida; Sugar, Elizabeth A.; Thorne, Jennifer E.; Wang, Robert C.; Holbrook, Janet T.

    2012-01-01

    Purpose. To evaluate the associations between visual acuity and self-reported visual function; visual acuity and health-related quality of life (QoL) metrics; a summary measure of self-reported visual function and health-related QoL; and individual domains of self-reported visual function and health-related QoL in patients with uveitis. Methods. Best-corrected visual acuity, vision-related functioning as assessed by the NEI VFQ-25, and health-related QoL as assessed by the SF-36 and EuroQoL EQ-5D questionnaires were obtained at enrollment in a clinical trial of uveitis treatments. Multivariate regression and Spearman correlations were used to evaluate associations between visual acuity, vision-related function, and health-related QoL. Results. Among the 255 patients, median visual acuity in the better-seeing eyes was 20/25, the vision-related function score indicated impairment (median, 60), and health-related QoL scores were within the normal population range. Better visual acuity was predictive of higher visual function scores (P ≤ 0.001), a higher SF-36 physical component score, and a higher EQ-5D health utility score (P < 0.001). The vision-specific function score was predictive of all general health-related QoL (P < 0.001). The correlations between visual function score and general quality of life measures were moderate (ρ = 0.29–0.52). Conclusions. The vision-related function score correlated positively with visual acuity and moderately positively with general QoL measures. Cost–utility analyses relying on changes in generic healthy utility measures will be more likely to detect changes when there are clinically meaningful changes in vision-related function, rather than when there are only changes in visual acuity. (ClinicalTrials.gov number, NCT00132691.) PMID:22247489

  7. Association of HER2 status with prognosis in gastric cancer patients undergoing R0 resection: A large-scale multicenter study in China

    PubMed Central

    Shen, Guo-Shuang; Zhao, Jiu-Da; Zhao, Jun-Hui; Ma, Xin-Fu; Du, Feng; Kan, Jie; Ji, Fa-Xiang; Ma, Fei; Zheng, Fang-Chao; Wang, Zi-Yi; Xu, Bing-He

    2016-01-01

    AIM: To determine whether the positive status of human epidermal growth receptor 2 (HER2) can be regarded as an effective prognostic factor for patients with gastric cancer (GC) undergoing R0 resection. METHODS: A total of 1562 GC patients treated by R0 resection were recruited. HER2 status was evaluated in surgically resected samples of all the patients using immunohistochemical (IHC) staining. Correlations between HER2 status and clinicopathological characteristics were retrospective analyzed. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox proportional hazard model, stratified by age, gender, tumor location and tumor-node-metastasis (TNM) stage, with additional adjustment for potential prognostic factors. RESULTS: Among 1562 patients, 548 (positive rate = 35.08%, 95%CI: 32.72%-37.45%) were HER2 positive. Positive status of HER2 was significantly correlated with gender (P = 0.004), minority (P < 0.001), tumor location (P = 0.001), pathological grade (P < 0.001), TNM stage (P < 0.001) and adjuvant radiotherapy (74.67% vs 23.53%, P = 0.011). No significant associations were observed between HER2 status and disease free survival (HR = 0.19, 95%CI: 0.96-1.46, P = 0.105) or overall survival (HR = 1.19, 95%CI: 0.96-1.48, P = 0.118) using multivariate analysis, although stratified analyses showed marginally statistically significant associations both in disease free survival and overall survival, especially among patients aged < 60 years or with early TNM stages (I and II). Categorical age, TNM stage, neural invasion, and adjuvant chemotherapy were, as expected, independent prognostic factors for both disease free survival and overall survival. CONCLUSION: The positive status of HER2 based on IHC staining was not related to the survival in patients with GC among the Chinese population. PMID:27340357

  8. Genetic Association for P2X7R rs3751142 and CARD8 rs2043211 Polymorphisms for Susceptibility of Gout in Korean Men: Multi-Center Study.

    PubMed

    Lee, Sung Won; Lee, Shin Seok; Oh, Dong Ho; Park, Dong Jin; Kim, Hyun Sook; Choi, Jung Ran; Chae, Soo Cheon; Yun, Ki Jung; Chung, Won Tae; Choe, Jung Yoon; Kim, Seong Kyu

    2016-10-01

    The aim of this study was to determine the association between P2X7R rs3751142 and CARD8 rs2043211 polymorphisms and gout susceptibility in male Korean subjects. This study enrolled a total of 242 male patients with gout and 280 healthy controls. The polymorphisms of two individual genes including rs3751142(C>A) in the P2X7R gene and rs2043211(A>T) in the CARD8 gene were assessed using Taq-Man analysis. Statistical analyses were performed using the Chi-square test, Kruskal-Wallis test, and logistic regression analyses. A difference in genotypic frequency of the P2X7R rs3751142 and CARD8 rs2043211 genes was not detected between gout and control patients. Clinical parameters including age, onset age, disease duration, body mass index, and serum uric acid levels were not different among the three genotypes for either P2X7R or CARD8 (P > 0.05 for all). A pair-wise comparison of P2X7R rs3751142 and CARD8 rs2043211 genotype combinations revealed that subjects with the CA P2X7R rs3751142 genotype and the TT CARD8 rs2043211 genotype had a trend toward a higher risk of gout compared to the CC/AA combination (P = 0.056, OR = 2.618, 95% CI 0.975 - 7.031). In conclusion, this study revealed that genetic variability of the P2X7R rs3751142 and CARD8 rs2043211 genes might, in part, be associated with susceptibility for gout. PMID:27550484

  9. Operative treatment of 733 patients with acute thoracolumbar spinal injuries: comprehensive results from the second, prospective, internet-based multicenter study of the Spine Study Group of the German Association of Trauma Surgery

    PubMed Central

    Knop, C.; Beisse, R.; Audigé, L.; Kandziora, F.; Pizanis, A.; Pranzl, R.; Gercek, E.; Schultheiss, M.; Weckbach, A.; Bühren, V.; Blauth, M.

    2010-01-01

    The second, internet-based multicenter study (MCSII) of the Spine Study Group of the German Association of Trauma Surgery (Deutsche Gesellschaft für Unfallchirurgie) is a representative patient collection of acute traumatic thoracolumbar (T1–L5) injuries. The MCSII results are an update of those obtained with the first multicenter study (MCSI) more than a decade ago. The aim of the study was to assess and bring into focus: the (1) epidemiologic data, (2) surgical and radiological outcome, and (3) 2-year follow-up (FU) results of these injuries. According to the Magerl/AO classification, there were 424 (57.8%) compression fractures (A type), 178 (24.3%) distractions injuries (B type), and 131 (17.9%) rotational injuries (C type). B and C type injuries carried a higher risk for neurological deficits, concomitant injuries, and multiple vertebral fractures. The level of injury was located at the thoracolumbar junction (T11–L2) in 67.0% of the case. 380 (51.8%) patients were operated on by posterior stabilization and instrumentation alone (POSTERIOR), 34 (4.6%) had an anterior procedure (ANTERIOR), and 319 (43.5%) patients were treated with combined posteroanterior surgery (COMBINED). 65% of patients with thoracic (T1–T10) and 57% with lumbar spinal (L3–L5) injuries were treated with a single posterior approach (POSTERIOR). 47% of the patients with thoracolumbar junction (T11–L2) injuries were either operated from posterior or with a combined posterior–anterior surgery (COMBINED) each. Short angular stable implant systems have replaced conventional non-angular stable instrumentation systems to a large extent. The posttraumatic deformity was restored best with COMBINED surgery. T-spine injuries were accompanied by a higher number and more severe neurologic deficits than TL junction or L-spine injuries. At the same time T-spine injuries showed less potential for neurologic recovery especially in paraplegic (Frankel/AISA A) patients. 5% of all patients

  10. Multicenter study of trimethoprim/sulfamethoxazole-related hepatotoxicity: incidence and associated factors among HIV-infected patients treated for Pneumocystis jirovecii pneumonia.

    PubMed

    Yang, Jen-Jia; Huang, Chung-Hao; Liu, Chun-Eng; Tang, Hung-Jen; Yang, Chia-Jui; Lee, Yi-Chien; Lee, Kuan-Yeh; Tsai, Mao-Song; Lin, Shu-Wen; Chen, Yen-Hsu; Lu, Po-Liang; Hung, Chien-Ching

    2014-01-01

    The incidence of hepatotoxicity related to trimethoprim/sulfamethoxazole (TMP/SMX) administered at a therapeutic dose may vary among study populations of different ethnicities and hepatotoxic metabolites of TMP/SMX may be decreased by drug-drug interaction with fluconazole. We aimed to investigate the incidence of hepatotoxicity and the role of concomitant use of fluconazole in HIV-infected patients receiving TMP/SMX for Pneumocystis jirovecii pneumonia. We reviewed medical records to collect clinical characteristics and laboratory data of HIV-infected patients who received TMP/SMX for treatment of P. jirovecii pneumonia at 6 hospitals around Taiwan between September 2009 and February 2013. Hepatotoxicity was defined as 2-fold or greater increase of aminotransferase or total bilirubin level from baselines. Roussel UCLAF Causality Assessment Method (RUCAM) was used to analyze the causality of drug-induced liver injuries. NAT1 and NAT2 acetylator types were determined with the use of polymerase-chain-reaction (PCR) restriction fragment length polymorphism to differentiate common single-nucleotide polymorphisms (SNPs) predictive of the acetylator phenotypes in a subgroup of patients. During the study period, 286 courses of TMP/SMX treatment administered to 284 patients were analyzed. One hundred and fifty-two patients (53.1%) developed hepatotoxicity, and TMP/SMX was considered causative in 47 (16.4%) who had a RUCAM score of 6 or greater. In multivariate analysis, concomitant use of fluconazole for candidiasis was the only factor associated with reduced risk for hepatotoxicity (adjusted odds ratio, 0.372; 95% confidence interval, 0.145-0.957), while serostatus of hepatitis B or C virus, NAT1 and NAT2 acetylator types, or receipt of combination antiretroviral therapy was not. The incidence of hepatotoxicity decreased with an increasing daily dose of fluconazole up to 4.0 mg/kg. We conclude that the incidence of TMP/SMX-related hepatotoxicity was 16.4% in HIV

  11. Multicenter Study of Trimethoprim/Sulfamethoxazole-Related Hepatotoxicity: Incidence and Associated Factors among HIV-Infected Patients Treated for Pneumocystis jirovecii Pneumonia

    PubMed Central

    Yang, Jen-Jia; Huang, Chung-Hao; Liu, Chun-Eng; Tang, Hung-Jen; Yang, Chia-Jui; Lee, Yi-Chien; Lee, Kuan-Yeh; Tsai, Mao-Song; Lin, Shu-Wen; Chen, Yen-Hsu; Lu, Po-Liang; Hung, Chien-Ching

    2014-01-01

    The incidence of hepatotoxicity related to trimethoprim/sulfamethoxazole (TMP/SMX) administered at a therapeutic dose may vary among study populations of different ethnicities and hepatotoxic metabolites of TMP/SMX may be decreased by drug-drug interaction with fluconazole. We aimed to investigate the incidence of hepatotoxicity and the role of concomitant use of fluconazole in HIV-infected patients receiving TMP/SMX for Pneumocystis jirovecii pneumonia. We reviewed medical records to collect clinical characteristics and laboratory data of HIV-infected patients who received TMP/SMX for treatment of P. jirovecii pneumonia at 6 hospitals around Taiwan between September 2009 and February 2013. Hepatotoxicity was defined as 2-fold or greater increase of aminotransferase or total bilirubin level from baselines. Roussel UCLAF Causality Assessment Method (RUCAM) was used to analyze the causality of drug-induced liver injuries. NAT1 and NAT2 acetylator types were determined with the use of polymerase-chain-reaction (PCR) restriction fragment length polymorphism to differentiate common single-nucleotide polymorphisms (SNPs) predictive of the acetylator phenotypes in a subgroup of patients. During the study period, 286 courses of TMP/SMX treatment administered to 284 patients were analyzed. One hundred and fifty-two patients (53.1%) developed hepatotoxicity, and TMP/SMX was considered causative in 47 (16.4%) who had a RUCAM score of 6 or greater. In multivariate analysis, concomitant use of fluconazole for candidiasis was the only factor associated with reduced risk for hepatotoxicity (adjusted odds ratio, 0.372; 95% confidence interval, 0.145–0.957), while serostatus of hepatitis B or C virus, NAT1 and NAT2 acetylator types, or receipt of combination antiretroviral therapy was not. The incidence of hepatotoxicity decreased with an increasing daily dose of fluconazole up to 4.0 mg/kg. We conclude that the incidence of TMP/SMX-related hepatotoxicity was 16.4% in HIV

  12. Association of Relapse with Renal Outcomes under the Current Therapy Regimen for IgA Nephropathy: A Multi-Center Study

    PubMed Central

    Ni, Zhaohui; Zhong, Yifei; Qi, Yinghui; Shao, Xinghua; Wang, Qin; Cao, Liou; Zhang, Minfang; Xie, Yuanyuan; Qi, Chaojun; Tian, Lei; Mou, Shan

    2015-01-01

    Background and Objectives Renal relapse is a very common manifestation of IgA nephropathy (IgAN). The clinical characteristics and long-term outcomes of this condition have not yet been carefully explored. Design and Patients Patients with biopsy-proven IgAN between January 2005 and December 2010 from three medical centers in China was a primary cohort of patients. From January 2010 to April 2012, data of an independent cohort of IgAN patients from Ren Ji Hospital, Shanghai, China was collected using the same inclusion and exclusion criteria. These patients formed the validation cohort of this study. Results Of the patients with biopsy-proven IgAN from three medical centers, 489 patients achieved remission within 6 months following the therapy. Additionally, 76 (15.5%) of these patients experienced a relapse after achieving remission. During the median follow-up period of 66 months, 6 patients (1.4%) in the non-relapse group experienced renal deterioration, compared with 22 patients (29.6%) in the relapse group. Our study indicated that each 1-mmHg increase in the baseline diastolic blood pressure (DBP) was associated with a 4.5% increase in the risk of renal relapse; additionally, the male patients had a 3.324-fold greater risk of relapse compared with the female patients according to the adjusted multivariate Cox analysis. The nomogram was based on 489 patients achieved remission. The predictive accuracy and discriminative ability of the nomogram were determined by concordance index (C-index) and calibration curve. The results were validated using bootstrap resampling on the validation cohort. Conclusions This study demonstrated that renal relapse is a potential predictor of prognostic outcomes in patients under the current therapeutic regimens for IgAN. And male patients with higher diastolic blood pressure had a greater risk of experiencing relapse. PMID:26371477

  13. Standard versus extended lymphadenectomy associated with pancreatoduodenectomy in the surgical treatment of adenocarcinoma of the head of the pancreas: a multicenter, prospective, randomized study. Lymphadenectomy Study Group.

    PubMed Central

    Pedrazzoli, S; DiCarlo, V; Dionigi, R; Mosca, F; Pederzoli, P; Pasquali, C; Klöppel, G; Dhaene, K; Michelassi, F

    1998-01-01

    OBJECTIVE: The study was conducted to determine whether the performance of an extended lymphadenectomy and retroperitoneal soft-tissue clearance in association with a pancreatoduodenal resection improves the long-term survival of patients with a potentially curable adenocarcinoma of the head of the pancreas. SUMMARY BACKGROUND DATA: The usefulness of performing an extended lymphadenectomy and retroperitoneal soft-tissue clearance in conjunction with a pancreatoduodenal resection in the treatment of ductal adenocarcinoma of the head of the pancreas is still unknown. Published studies suggest a benefit for the procedure in terms of better long-term survival rates; however, these studies were retrospective or did not prospectively evaluate large series of patients. MATERIALS AND METHODS: Eighty-one patients undergoing a pancreatoduodenal resection for a potentially curable ductal adenocarcinoma of the head of the pancreas were randomized to a standard (n = 40) or extended (n = 41) lymphadenectomy and retroperitoneal soft-tissue clearance in a prospective, multicentric study. The standard lymphadenectomy included removal of the anterior and posterior pancreatoduodenal, pyloric, and biliary duct, superior and inferior pancreatic head, and body lymph node stations. In addition to the above, the extended lymphadenectomy included removal of lymph nodes from the hepatic hilum and along the aorta from the diaphragmatic hiatus to the inferior mesenteric artery and laterally to both renal hila, with circumferential clearance of the origin of the celiac trunk and superior mesenteric artery. Patients did not receive any postoperative adjuvant therapy. RESULTS: Demographic (age, gender) and histopathologic (tumor size, stage, differentiation, oncologic clearance) characteristics were similar in the two patient groups. Performance of the extended lymphadenectomy added time to the procedure, although the difference did not reach statistical significance (397 +/- 50 minutes vs. 372

  14. MSX1 Modulates RLR-Mediated Innate Antiviral Signaling by Facilitating Assembly of TBK1-Associated Complexes.

    PubMed

    Chen, Liu-Ting; Hu, Ming-Ming; Xu, Zhi-Sheng; Liu, Yu; Shu, Hong-Bing

    2016-07-01

    Recognition of viral dsRNA by the retinoic acid-inducible gene-1-like receptors (RLRs) triggers signaling cascades that lead to activation of the TBK1 kinase and transcription factor IFN regulatory factor 3, induction of downstream antiviral genes, and innate antiviral responses. In this study, we identified muscle segment homeobox1 (MSX1) as an important modulator of RLR-mediated signaling pathways. Knockdown or knockout of MSX1 significantly impaired Sendai virus-triggered activation of TBK1 and IFN regulatory factor 3, induction of downstream antiviral genes, and cellular antiviral responses. Interestingly, MSX1 was translocated from the nucleus to cytoplasm, particularly mitochondria upon infection of Sendai virus. Biochemcially, MSX1 was important for assembly of TBK1/IKK-related kinase-associated protein 1/TNFR-associated factor-associated NF-κB activator complexes. Our results suggest that MSX1 is an important component of RLR-mediated signaling and reveal mechanisms on innate immune responses against RNA viruses. PMID:27194789

  15. A Heart and A Mind: Self-distancing Facilitates the Association Between Heart Rate Variability, and Wise Reasoning.

    PubMed

    Grossmann, Igor; Sahdra, Baljinder K; Ciarrochi, Joseph

    2016-01-01

    Cardiac vagal tone (indexed via resting heart rate variability [HRV]) has been previously associated with superior executive functioning. Is HRV related to wiser reasoning and less biased judgments? Here we hypothesize that this will be the case when adopting a self-distanced (as opposed to a self-immersed) perspective, with self-distancing enabling individuals with higher HRV to overcome bias-promoting egocentric impulses and to reason wisely. However, higher HRV may not be associated with greater wisdom when adopting a self-immersed perspective. Participants were randomly assigned to reflect on societal issues from a self-distanced- or self-immersed perspective, with responses coded for reasoning quality. In a separate task, participants read about and evaluated a person performing morally ambiguous actions, with responses coded for dispositional vs. situational attributions. We simultaneously assessed resting cardiac recordings, obtaining six HRV indicators. As hypothesized, in the self-distanced condition, each HRV indicator was positively related to prevalence of wisdom-related reasoning (e.g., prevalence of recognition of limits of one's knowledge, recognition that the world is in flux/change, consideration of others' opinions and search for an integration of these opinions) and to balanced vs. biased attributions (recognition of situational and dispositional factors vs. focus on dispositional factors alone). In contrast, there was no relationship between these variables in the self-immersed condition. We discuss implications for research on psychophysiology, cognition, and wisdom. PMID:27092066

  16. A Heart and A Mind: Self-distancing Facilitates the Association Between Heart Rate Variability, and Wise Reasoning

    PubMed Central

    Grossmann, Igor; Sahdra, Baljinder K.; Ciarrochi, Joseph

    2016-01-01

    Cardiac vagal tone (indexed via resting heart rate variability [HRV]) has been previously associated with superior executive functioning. Is HRV related to wiser reasoning and less biased judgments? Here we hypothesize that this will be the case when adopting a self-distanced (as opposed to a self-immersed) perspective, with self-distancing enabling individuals with higher HRV to overcome bias-promoting egocentric impulses and to reason wisely. However, higher HRV may not be associated with greater wisdom when adopting a self-immersed perspective. Participants were randomly assigned to reflect on societal issues from a self-distanced- or self-immersed perspective, with responses coded for reasoning quality. In a separate task, participants read about and evaluated a person performing morally ambiguous actions, with responses coded for dispositional vs. situational attributions. We simultaneously assessed resting cardiac recordings, obtaining six HRV indicators. As hypothesized, in the self-distanced condition, each HRV indicator was positively related to prevalence of wisdom-related reasoning (e.g., prevalence of recognition of limits of one’s knowledge, recognition that the world is in flux/change, consideration of others’ opinions and search for an integration of these opinions) and to balanced vs. biased attributions (recognition of situational and dispositional factors vs. focus on dispositional factors alone). In contrast, there was no relationship between these variables in the self-immersed condition. We discuss implications for research on psychophysiology, cognition, and wisdom. PMID:27092066

  17. Reductions in native grass biomass associated with drought facilitates the invasion of an exotic grass into a model grassland system.

    PubMed

    Manea, Anthony; Sloane, Daniel R; Leishman, Michelle R

    2016-05-01

    The invasion success of exotic plant species is often dependent on resource availability. Aspects of climate change such as rising atmospheric CO2 concentration and extreme climatic events will directly and indirectly alter resource availability in ecological communities. Understanding how these climate change-associated changes in resource availability will interact with one another to influence the invasion success of exotic plant species is complex. The aim of the study was to assess the establishment success of an invasive exotic species in response to climate change-associated changes in resource availability (CO2 levels and soil water availability) as a result of extreme drought. We grew grassland mesocosms consisting of four co-occurring native grass species common to the Cumberland Plain Woodland of western Sydney, Australia, under ambient and elevated CO2 levels and subjected them to an extreme drought treatment. We then added seeds of a highly invasive C3 grass, Ehrharta erecta, and assessed its establishment success (biomass production and reproductive output). We found that reduced biomass production of the native grasses in response to the extreme drought treatment enhanced the establishment success of E. erecta by creating resource pulses in light and space. Surprisingly, CO2 level did not affect the establishment success of E. erecta. Our results suggest that the invasion risk of grasslands in the future may be coupled to soil water availability and the subsequent response of resident native vegetation therefore making it strongly context- dependent. PMID:26780256

  18. Facilitated c-Fos Induction in Mice Deficient for the AMPA Receptor-Associated Protein Ckamp44.

    PubMed

    Yang, Boyi; Dormann, Christof; Vogt, Miriam A; Sprengel, Rolf; Gass, Peter; Inta, Dragos

    2016-10-01

    The recently identified Cystine-knot containing AMPAR-associated protein (Ckamp44) represents a novel AMPAR-related protein that critically controls AMPAR-mediated currents and short-term plasticity. However, the effects of the lack of this protein at network level are not entirely understood. Here we used c-Fos brain mapping to analyse whether the excitatory/inhibitory balance is altered in the absence of the Ckamp44. We found that Ckamp44(-/-) mice treated with an NMDAR antagonist exhibited a very robust c-Fos expression pattern, similar with that seen in mice lacking the GluN2A subunit of NMDAR treated with the same compound. This finding is unexpected, in particular, since Ckamp44 expression is strongest in dentate gyrus granule cells and less abundant in the rest of the brain. PMID:26645823

  19. Physical Association of Saccharomyces cerevisiae Polo-like Kinase Cdc5 with Chromosomal Cohesin Facilitates DNA Damage Response*

    PubMed Central

    Pakchuen, Sujiraporn; Ishibashi, Mai; Takakusagi, Emi; Shirahige, Katsuhiko; Sutani, Takashi

    2016-01-01

    At the onset of anaphase, a protease called separase breaks the link between sister chromatids by cleaving the cohesin subunit Scc1. This irreversible step in the cell cycle is promoted by degradation of the separase inhibitor, securin, and polo-like kinase (Plk) 1-dependent phosphorylation of the Scc1 subunit. Plk could recognize substrates through interaction between its phosphopeptide interaction domain, the polo-box domain, and a phosphorylated priming site in the substrate, which has been generated by a priming kinase beforehand. However, the physiological relevance of this targeting mechanism remains to be addressed for many of the Plk1 substrates. Here, we show that budding yeast Plk1, Cdc5, is pre-deposited onto cohesin engaged in cohesion on chromosome arms in G2/M phase cells. The Cdc5-cohesin association is mediated by direct interaction between the polo-box domain of Cdc5 and Scc1 phosphorylated at multiple sites in its middle region. Alanine substitutions of the possible priming phosphorylation sites (scc1-15A) impair Cdc5 association with chromosomal cohesin, but they make only a moderate impact on mitotic cell growth even in securin-deleted cells (pds1Δ), where Scc1 phosphorylation by Cdc5 is indispensable. The same scc1-15A pds1Δ double mutant, however, exhibits marked sensitivity to the DNA-damaging agent phleomycin, suggesting that the priming phosphorylation of Scc1 poses an additional layer of regulation that enables yeast cells to adapt to genotoxic environments. PMID:27325700

  20. Lansoprazole Upregulates Polyubiquitination of the TNF Receptor-Associated Factor 6 and Facilitates Runx2-mediated Osteoblastogenesis

    PubMed Central

    Mishima, Kenichi; Kitoh, Hiroshi; Ohkawara, Bisei; Okuno, Tatsuya; Ito, Mikako; Masuda, Akio; Ishiguro, Naoki; Ohno, Kinji

    2015-01-01

    The transcription factor, runt-related transcription factor 2 (Runx2), plays a pivotal role in the differentiation of the mesenchymal stem cells to the osteochondroblast lineages. We found by the drug repositioning strategy that a proton pump inhibitor, lansoprazole, enhances nuclear accumulation of Runx2 and induces osteoblastogenesis of human mesenchymal stromal cells. Systemic administration of lansoprazole to a rat femoral fracture model increased osteoblastogenesis. Dissection of signaling pathways revealed that lansoprazole activates a noncanonical bone morphogenic protein (BMP)-transforming growth factor-beta (TGF-β) activated kinase-1 (TAK1)–p38 mitogen-activated protein kinase (MAPK) pathway. We found by in cellulo ubiquitination studies that lansoprazole enhances polyubiquitination of the TNF receptor-associated factor 6 (TRAF6) and by in vitro ubiquitination studies that the enhanced polyubiquitination of TRAF6 is attributed to the blocking of a deubiquitination enzyme, cylindromatosis (CYLD). Structural modeling and site-directed mutagenesis of CYLD demonstrated that lansoprazole tightly fits in a pocket of CYLD where the C-terminal tail of ubiquitin lies. Lansoprazole is a potential therapeutic agent for enhancing osteoblastic differentiation. PMID:26844285

  1. SHANK3 Gene Mutations Associated with Autism Facilitate Ligand Binding to the Shank3 Ankyrin Repeat Region*

    PubMed Central

    Mameza, Marie Germaine; Dvoretskova, Elena; Bamann, Margarete; Hönck, Hans-Hinrich; Güler, Türkan; Boeckers, Tobias M.; Schoen, Michael; Verpelli, Chiara; Sala, Carlo; Barsukov, Igor; Dityatev, Alexander; Kreienkamp, Hans-Jürgen

    2013-01-01

    Shank/ProSAP proteins are major scaffold proteins of the postsynaptic density; mutations in the human SHANK3 gene are associated with intellectual disability or autism spectrum disorders. We have analyzed the functional relevance of several SHANK3 missense mutations affecting the N-terminal portion of the protein by expression of wild-type and mutant Shank3 in cultured neurons and by binding assays in heterologous cells. Postsynaptic targeting of recombinant Shank3 was unaltered. In electrophysiological experiments, both wild-type and L68P mutant forms of Shank3 were equally effective in restoring synaptic function after knockdown of endogenous Shank3. We observed that several mutations affected binding to interaction partners of the Shank3 ankyrin repeat region. One of these mutations, L68P, improved binding to both ligands. Leu-68 is located N-terminal to the ankyrin repeats, in a highly conserved region that we identify here as a novel domain termed the Shank/ProSAP N-terminal (SPN) domain. We show that the SPN domain interacts with the ankyrin repeats in an intramolecular manner, thereby restricting access of either Sharpin or α-fodrin. The L68P mutation disrupts this blockade, thus exposing the Shank3 ankyrin repeat region to its ligands. Our data identify a new type of regulation of Shank proteins and suggest that mutations in the SHANK3 gene do not necessarily induce a loss of function, but may represent a gain of function with respect to specific interaction partners. PMID:23897824

  2. Sequestration of RNA by grass carp Ctenopharyngodon idella TIA1 is associated with its positive role in facilitating grass carp reovirus infection.

    PubMed

    Song, Lang; Wang, Hao; Wang, Tu; Lu, Liqun

    2015-10-01

    Previous report demonstrated that grass carp reovirus (GCRV) infection resulted in unlinking cellular stress granule formation from aggregation of grass carp Ctenopharyngodon idella TIA1 (CiTIA1). Here, we provided evidence to show that CiTIA1 bound to synthesized ssRNA and dsRNA in vitro. Both GST-pull down assay and RNA immunoprecipitation analysis confirmed the association between GCRV-specific RNA and GST-tagged CiTIA1 in C. idella kidney (CIK) cells. Furthermore, CiTIA1 was shown to protect dsRNA of virus-origin from degradation in CIK cells through Northern blot analysis. Finally, transient overexpression of CiTIA1 enhanced the replication efficiency of GCRV in CIK cells. Taken together, our results suggested that cellular CiTIA1 might facilitate GCRV replication through sequestrating and protecting viral RNA from degradation. PMID:26208752

  3. The Multicenter Pediatric and Adult Congenital EP Quality (MAP-IT) Initiative-rationale and design: report from the pediatric and congenital electrophysiology society's MAP-IT taskforce.

    PubMed

    Seslar, Stephen P; Kugler, John; Batra, Anjan S; Collins, Kathryn K; Crosson, Jane; Dubin, Anne M; Etheridge, Susan; Kanter, Ronald; Papez, Andrew; Radbill, Andrew E; Serwer, Gerald A; Tanel, Ronn E; Tsao, Sabrina; Webster, Gregory; Saarel, Elizabeth V

    2013-01-01

    Multicenter clinical registries are increasingly recognized as valuable tools for establishing benchmarks, facilitating patient-centered quality improvement and research. In 2010, the Pediatric and Congenital Electrophysiology Society convened a taskforce of its members to design, construct, and implement a clinical registry known as the Multicenter Pediatric and Adult Congenital EP Quality (MAP-IT) Initiative. The present aim of the MAP-IT Initiative is to create an infrastructure by which we can measurably improve patient-centered outcomes and reduce complications associated with electrophysiology studies and catheter ablation in pediatric and congenital heart disease patients. The purpose of this writing is to report the progress to date from three of the four subcommittees of the MAP-IT taskforce. Specifically, we present our initial set of key data elements and definitions, recommended database table structure, and considerations regarding wide-scale implementation of the registry. Development of a risk/complexity score for use in the MAP-IT registry is presented in a separate companion manuscript. It is our intent that these manuscripts will serve to introduce the electrophysiology and pediatric cardiology community to the MAP-IT initiative and provide a rationale for its design and recommended implementation strategy. PMID:23663492

  4. The G protein-coupled receptor T-cell death-associated gene 8 (TDAG8) facilitates tumor development by serving as an extracellular pH sensor.

    PubMed

    Ihara, Yuichiro; Kihara, Yasuyuki; Hamano, Fumie; Yanagida, Keisuke; Morishita, Yasuyuki; Kunita, Akiko; Yamori, Takao; Fukayama, Masashi; Aburatani, Hiroyuki; Shimizu, Takao; Ishii, Satoshi

    2010-10-01

    Tumors often are associated with a low extracellular pH, which induces a variety of cellular events. However, the mechanisms by which tumor cells recognize and react to the acidic environment have not been fully elucidated. T-cell death-associated gene 8 (TDAG8) is an extracellular pH-sensing G protein-coupled receptor that is overexpressed in various tumors and tumor cell lines. In this report, we show that TDAG8 on the surface of tumor cells facilitates tumor development by sensing the acidic environment. Overexpression of TDAG8 in mouse Lewis lung carcinoma (LLC) cells enhanced tumor development in animal models and rendered LLC cells resistant to acidic culture conditions by increasing activation of protein kinase A and extracellular signal-regulated kinase in vitro. Moreover, shRNA-mediated knockdown of endogenous TDAG8 in NCI-H460 human non-small cell lung cancer cells reduced cell survival in an acidic environment in vitro as well as tumor development in vivo. Microarray analyses of tumor-containing lung tissues of mice injected with TDAG8-expressing LLC cells revealed up-regulation of genes related to cell growth and glycolysis. These results support the hypothesis that TDAG8 enhances tumor development by promoting adaptation to the acidic environment to enhance cell survival/proliferation. TDAG8 may represent a therapeutic target for arresting tumor growth. PMID:20855608

  5. The Essential Elements of Facilitation.

    ERIC Educational Resources Information Center

    Priest, Simon; Gass, Michael; Gillis, Lee

    Most organizations find it difficult to implement change, and only about 10 percent of learning from training and development experiences is actually applied in the workplace. This book advocates facilitation as a means of enhancing change and increasing productivity. Facilitation engages employees by enhancing the processes associated with their…

  6. Multicenter Guidelines | Division of Cancer Prevention

    Cancer.gov

    A Lead Organization conducting multi-institutional studies in the consortium has specific responsibilities in order to comply with the DCP Multicenter Guidelines. The Lead Organization is responsible for the following at all Participating Organizations as well as the Lead Organization: |

  7. Serum metabolomic profiling facilitates the non-invasive identification of metabolic biomarkers associated with the onset and progression of non-small cell lung cancer.

    PubMed

    Puchades-Carrasco, Leonor; Jantus-Lewintre, Eloisa; Pérez-Rambla, Clara; García-García, Francisco; Lucas, Rut; Calabuig, Silvia; Blasco, Ana; Dopazo, Joaquín; Camps, Carlos; Pineda-Lucena, Antonio

    2016-03-15

    Lung cancer (LC) is responsible for most cancer deaths. One of the main factors contributing to the lethality of this disease is the fact that a large proportion of patients are diagnosed at advanced stages when a clinical intervention is unlikely to succeed. In this study, we evaluated the potential of metabolomics by 1H-NMR to facilitate the identification of accurate and reliable biomarkers to support the early diagnosis and prognosis of non-small cell lung cancer (NSCLC).We found that the metabolic profile of NSCLC patients, compared with healthy individuals, is characterized by statistically significant changes in the concentration of 18 metabolites representing different amino acids, organic acids and alcohols, as well as different lipids and molecules involved in lipid metabolism. Furthermore, the analysis of the differences between the metabolic profiles of NSCLC patients at different stages of the disease revealed the existence of 17 metabolites involved in metabolic changes associated with disease progression.Our results underscore the potential of metabolomics profiling to uncover pathophysiological mechanisms that could be useful to objectively discriminate NSCLC patients from healthy individuals, as well as between different stages of the disease. PMID:26883203

  8. Serum metabolomic profiling facilitates the non-invasive identification of metabolic biomarkers associated with the onset and progression of non-small cell lung cancer

    PubMed Central

    Puchades-Carrasco, Leonor; Jantus-Lewintre, Eloisa; Pérez-Rambla, Clara; García-García, Francisco; Lucas, Rut; Calabuig, Silvia; Blasco, Ana; Dopazo, Joaquín; Camps, Carlos; Pineda-Lucena, Antonio

    2016-01-01

    Lung cancer (LC) is responsible for most cancer deaths. One of the main factors contributing to the lethality of this disease is the fact that a large proportion of patients are diagnosed at advanced stages when a clinical intervention is unlikely to succeed. In this study, we evaluated the potential of metabolomics by 1H-NMR to facilitate the identification of accurate and reliable biomarkers to support the early diagnosis and prognosis of non-small cell lung cancer (NSCLC). We found that the metabolic profile of NSCLC patients, compared with healthy individuals, is characterized by statistically significant changes in the concentration of 18 metabolites representing different amino acids, organic acids and alcohols, as well as different lipids and molecules involved in lipid metabolism. Furthermore, the analysis of the differences between the metabolic profiles of NSCLC patients at different stages of the disease revealed the existence of 17 metabolites involved in metabolic changes associated with disease progression. Our results underscore the potential of metabolomics profiling to uncover pathophysiological mechanisms that could be useful to objectively discriminate NSCLC patients from healthy individuals, as well as between different stages of the disease. PMID:26883203

  9. The collagen triple helix repeat containing 1 facilitates hepatitis B virus-associated hepatocellular carcinoma progression by regulating multiple cellular factors and signal cascades.

    PubMed

    Zhang, Rui; Cao, Yanhua; Bai, Lan; Zhu, Chengliang; Li, Rui; He, Hui; Liu, Yingle; Wu, Kailang; Liu, Fang; Wu, Jianguo

    2015-12-01

    Hepatitis B virus (HBV) infection is one of the major causes of acute and chronic liver diseases, fulminant hepatitis, cirrhosis, and hepatocellular carcinoma (HCC). HCC accounts for more than 85% of primary liver cancers and is the seventh most common cancer and the third leading cause of cancer-related deaths. However, the mechanism by which HBV induces HCC is largely unknown. Collagen triple helixes repeat containing 1 (CTHRC1) is a secreted protein and has characteristics of a circulating hormone with potentially broad implications for cell metabolism and physiology. CTHRC1 is associated with human cancers, but its effect on HCC is unknown. Here, we revealed that CTHRC1 expression is highly correlated with HCC progression in HBV-infected patients, and demonstrated that HBV stimulates CTHRC1 expression by activating nuclear factor-kappa B (NF-κB) and cAMP response element binding protein (CREB), through extracellular signal-regulated kinase/c-Jun N-terminal kinase (ERK/c-JNK) pathway. In addition, CTHRC1 activates hypoxia-inducible factor 1α (HIF-1α) and vascular endothelial growth factor (VEGF) through regulating phosphoinosmde-3-kinase/protein kinase B/mammalian target of rapamycin (PI-3K/AKT/mTOR) pathway. More interestingly, CTHRC1 enhances colony formation, migration, and invasion of hepatoma cells by regulating p53 and stimulating matrix metalloproteinase-9 (MMP-9) expression. In addition, knock-down of CTHRC1 results in the repression of HBV-associated carcinogenesis in nude mice. Thus, we revealed a novel mechanism by which HBV facilitates HCC development through activating the oncoprotein CTHRC1, which in turn enhances HBV-related HCC progression by stimulates colony formation, migration, and invasion of hepatoma cells through regulating multiple cellular factors and signal cascades. PMID:25263696

  10. Ethanol and drug findings in women consulting a Sexual Assault Center--associations with clinical characteristics and suspicions of drug-facilitated sexual assault.

    PubMed

    Hagemann, Cecilie T; Helland, Arne; Spigset, Olav; Espnes, Ketil A; Ormstad, Kari; Schei, Berit

    2013-08-01

    The purpose of the study was to describe toxicological findings among women seeking health care after sexual assault, and to assess the relationship with so-called proactive DFSA (drug facilitated sexual assault). We also explored associations between ethanol in blood/urine and background data, assault characteristics, and clinical findings. We conducted a retrospective, descriptive study of female patients ≥ 12 years of age consulting the Sexual Assault Center at St. Olavs University Hospital, Trondheim, Norway. They were examined between July 1, 2003 and December 31, 2010, and urine and/or blood were analyzed for ethanol and selected medicinal/recreational drugs. Among the 264 patients included, ethanol and/or drugs were detected in 155 (59%). Of the 50 patients (19%) testing positive for drugs other than ethanol, benzodiazepines/benzodiazepine-like drugs were found in 31, central stimulants in 14, cannabinoids in 13 and opioids in nine. None tested positive for gamma-hydroxybutyrate (GHB). In total, 57 patients (22%) suspected proactive DFSA, but only five had findings of sedative drugs that were not accounted for by self-reported voluntary intake. No cases could unequivocally be attributed to proactive DFSA. Among the 120 patients tested for ethanol within 12 h after the assault, 102 were positive. The median estimated blood alcohol concentration (BAC) at the time of assault was 1.87 g/L. Patients testing positive for ethanol more often reported a public place of assault and a stranger assailant. Higher estimated BAC at the time of assault was associated with higher frequency of suspecting proactive DFSA. Ethanol was the most prevalent toxicological finding in urine/blood from victims of sexual assault, and high ethanol concentrations were often detected. Among the patients suspecting proactive DFSA, very few had sedative drug findings not explained by voluntary intake. It seems like opportunistic DFSA, rather than proactive DFSA dominate among the sexually

  11. Predictors of survival and effect of short (40 Gy) or standard-course (60 Gy) irradiation plus concomitant temozolomide in elderly patients with glioblastoma: a multicenter retrospective study of AINO (Italian Association of Neuro-Oncology).

    PubMed

    Lombardi, Giuseppe; Pace, Andrea; Pasqualetti, Francesco; Rizzato, Simona; Faedi, Marina; Anghileri, Elena; Nicolotto, Elisa; Bazzoli, Elena; Bellu, Luisa; Villani, Veronica; Fabi, Alessandra; Ferrazza, Patrizia; Gurrieri, Lorena; Dall'Agata, Monia; Eoli, Marica; Della Puppa, Alessandro; Pambuku, Ardi; D'Avella, Domenico; Berti, Franco; Rudà, Roberta; Zagonel, Vittorina

    2015-11-01

    The efficacy of temozolomide (TMZ) plus radiation therapy (RT) in elderly patients with glioblastoma is unclear. We performed a large multicenter retrospective study to analyze prognostic factors and clinical outcome in these patients. Inclusion criteria were age ≥65 years, newly histologically confirmed glioblastoma, ECOG PS 0-2, adjuvant treatment with RT plus TMZ. We enrolled 237 patients; the average age was 71 and ECOG PS was 0-1 in 196 patients; gross total resection was performed in 174 cases. MGMT was analyzed in 151 persons and was methylated in 56 %. IDH1 was assessed in 100 patients and was mutated in 6 %. Seventy-one patients were treated with RT 40 Gy and 166 with RT 60 Gy. Progression-free survival and overall survival (OS) were 11.3 and 17.3 months, respectively. Overall survival was 19.4 vs 13.8 months for patients treated with RT 60 Gy and 40 Gy (p = 0.02); OS was 17.7 versus 16.1 months for patients treated with gross total resection vs partial surgery (p = 0.02); OS was 21.2 versus 13.6 months for methylated and unmethylated MGMT (p < 0.001). On multivariate analysis, gross total resection, RT 60 Gy, methylated MGMT and ECOG PS 0-1 were independent predictors of longer survival. Twenty-five patients (10 %) had grade 3-4 haematological toxicity during the concomitant treatment. We showed that, in elderly patients in good clinical condition treated with concomitant treatment, standard-course irradiation might be more effective than short-course irradiation. Methylated MGMT remains the most important prognostic factor. PMID:26423801

  12. Expression and Association of the Yersinia pestis Translocon Proteins, YopB and YopD, Are Facilitated by Nanolipoprotein Particles

    DOE PAGESBeta

    Coleman, Matthew A.; Cappuccio, Jenny A.; Blanchette, Craig D.; Gao, Tingjuan; Arroyo, Erin S.; Hinz, Angela K.; Bourguet, Feliza A.; Segelke, Brent; Hoeprich, Paul D.; Huser, Thomas; et al

    2016-03-25

    Yersinia pestis enters host cells and evades host defenses, in part, through interactions between Yersinia pestis proteins and host membranes. One such interaction is through the type III secretion system, which uses a highly conserved and ordered complex for Yersinia pestis outer membrane effector protein translocation called the injectisome. The portion of the injectisome that interacts directly with host cell membranes is referred to as the translocon. The translocon is believed to form a pore allowing effector molecules to enter host cells. To facilitate mechanistic studies of the translocon, we have developed a cell-free approach for expressing translocon pore proteinsmore » as a complex supported in a bilayer membrane mimetic nano-scaffold known as a nanolipoprotein particle (NLP) Initial results show cell-free expression of Yersinia pestis outer membrane proteins YopB and YopD was enhanced in the presence of liposomes. However, these complexes tended to aggregate and precipitate. With the addition of co-expressed (NLP) forming components, the YopB and/or YopD complex was rendered soluble, increasing the yield of protein for biophysical studies. Biophysical methods such as Atomic Force Microscopy and Fluorescence Correlation Spectroscopy were used to confirm that the soluble YopB/D complex was associated with NLPs. An interaction between the YopB/D complex and NLP was validated by immunoprecipitation. The YopB/D translocon complex embedded in a NLP provides a platform for protein interaction studies between pathogen and host proteins. Ultimately, these studies will help elucidate the poorly understood mechanism which enables this pathogen to inject effector proteins into host cells, thus evading host defenses.« less

  13. Expression and Association of the Yersinia pestis Translocon Proteins, YopB and YopD, Are Facilitated by Nanolipoprotein Particles.

    PubMed

    Coleman, Matthew A; Cappuccio, Jenny A; Blanchette, Craig D; Gao, Tingjuan; Arroyo, Erin S; Hinz, Angela K; Bourguet, Feliza A; Segelke, Brent; Hoeprich, Paul D; Huser, Thomas; Laurence, Ted A; Motin, Vladimir L; Chromy, Brett A

    2016-01-01

    Yersinia pestis enters host cells and evades host defenses, in part, through interactions between Yersinia pestis proteins and host membranes. One such interaction is through the type III secretion system, which uses a highly conserved and ordered complex for Yersinia pestis outer membrane effector protein translocation called the injectisome. The portion of the injectisome that interacts directly with host cell membranes is referred to as the translocon. The translocon is believed to form a pore allowing effector molecules to enter host cells. To facilitate mechanistic studies of the translocon, we have developed a cell-free approach for expressing translocon pore proteins as a complex supported in a bilayer membrane mimetic nano-scaffold known as a nanolipoprotein particle (NLP) Initial results show cell-free expression of Yersinia pestis outer membrane proteins YopB and YopD was enhanced in the presence of liposomes. However, these complexes tended to aggregate and precipitate. With the addition of co-expressed (NLP) forming components, the YopB and/or YopD complex was rendered soluble, increasing the yield of protein for biophysical studies. Biophysical methods such as Atomic Force Microscopy and Fluorescence Correlation Spectroscopy were used to confirm that the soluble YopB/D complex was associated with NLPs. An interaction between the YopB/D complex and NLP was validated by immunoprecipitation. The YopB/D translocon complex embedded in a NLP provides a platform for protein interaction studies between pathogen and host proteins. These studies will help elucidate the poorly understood mechanism which enables this pathogen to inject effector proteins into host cells, thus evading host defenses. PMID:27015536

  14. Expression and Association of the Yersinia pestis Translocon Proteins, YopB and YopD, Are Facilitated by Nanolipoprotein Particles

    PubMed Central

    Blanchette, Craig D.; Gao, Tingjuan; Arroyo, Erin S.; Hinz, Angela K.; Bourguet, Feliza A.; Segelke, Brent; Hoeprich, Paul D.; Huser, Thomas; Laurence, Ted A.; Motin, Vladimir L.; Chromy, Brett A.

    2016-01-01

    Yersinia pestis enters host cells and evades host defenses, in part, through interactions between Yersinia pestis proteins and host membranes. One such interaction is through the type III secretion system, which uses a highly conserved and ordered complex for Yersinia pestis outer membrane effector protein translocation called the injectisome. The portion of the injectisome that interacts directly with host cell membranes is referred to as the translocon. The translocon is believed to form a pore allowing effector molecules to enter host cells. To facilitate mechanistic studies of the translocon, we have developed a cell-free approach for expressing translocon pore proteins as a complex supported in a bilayer membrane mimetic nano-scaffold known as a nanolipoprotein particle (NLP) Initial results show cell-free expression of Yersinia pestis outer membrane proteins YopB and YopD was enhanced in the presence of liposomes. However, these complexes tended to aggregate and precipitate. With the addition of co-expressed (NLP) forming components, the YopB and/or YopD complex was rendered soluble, increasing the yield of protein for biophysical studies. Biophysical methods such as Atomic Force Microscopy and Fluorescence Correlation Spectroscopy were used to confirm that the soluble YopB/D complex was associated with NLPs. An interaction between the YopB/D complex and NLP was validated by immunoprecipitation. The YopB/D translocon complex embedded in a NLP provides a platform for protein interaction studies between pathogen and host proteins. These studies will help elucidate the poorly understood mechanism which enables this pathogen to inject effector proteins into host cells, thus evading host defenses. PMID:27015536

  15. Facilitating Facilitators: Enhancing PBL through a Structured Facilitator Development Program

    ERIC Educational Resources Information Center

    Salinitri, Francine D.; Wilhelm, Sheila M.; Crabtree, Brian L.

    2015-01-01

    With increasing adoption of the problem-based learning (PBL) model, creative approaches to enhancing facilitator training and optimizing resources to maintain effective learning in small groups is essential. We describe a theoretical framework for the development of a PBL facilitator training program that uses the constructivist approach as the…

  16. The Zen of Facilitation.

    ERIC Educational Resources Information Center

    Killion, Joellen P.; Simmons, Lynn A.

    1992-01-01

    Distinguishes between training and facilitation, examines the belief system of a facilitator, and shares a process for moving from the familiar mind-set of the trainer to the zen (the practice of seeking the truth) of facilitation. (GLR)

  17. Expanding the Use of Time-Based Metering: Multi-Center Traffic Management Advisor

    NASA Technical Reports Server (NTRS)

    Landry, Steven J.; Farley, Todd; Hoang, Ty

    2005-01-01

    Time-based metering is an efficient air traffic management alternative to the more common practice of distance-based metering (or "miles-in-trail spacing"). Despite having demonstrated significant operational benefit to airspace users and service providers, time-based metering is used in the United States for arrivals to just nine airports and is not used at all for non-arrival traffic flows. The Multi-Center Traffic Management Advisor promises to bring time-based metering into the mainstream of air traffic management techniques. Not constrained to operate solely on arrival traffic, Multi-Center Traffic Management Advisor is flexible enough to work in highly congested or heavily partitioned airspace for any and all traffic flows in a region. This broader and more general application of time-based metering is expected to bring the operational benefits of time-based metering to a much wider pool of beneficiaries than is possible with existing technology. It also promises to facilitate more collaborative traffic management on a regional basis. This paper focuses on the operational concept of the Multi-Center Traffic Management Advisor, touching also on its system architecture, field test results, and prospects for near-term deployment to the United States National Airspace System.

  18. Elliptic genera from multi-centers

    NASA Astrophysics Data System (ADS)

    Gaddam, Nava

    2016-05-01

    I show how elliptic genera for various Calabi-Yau threefolds may be understood from supergravity localization using the quantization of the phase space of certain multi-center configurations. I present a simple procedure that allows for the enumeration of all multi-center configurations contributing to the polar sector of the elliptic genera — explicitly verifying this in the cases of the quintic in {P} 4, the sextic in {W}{P} (2,1,1,1,1), the octic in {W}{P} (4,1,1,1,1) and the dectic in {W}{P} (5,2,1,1,1). With an input of the corresponding `single-center' indices (Donaldson-Thomas invariants), the polar terms have been known to determine the elliptic genera completely. I argue that this multi-center approach to the low-lying spectrum of the elliptic genera is a stepping stone towards an understanding of the exact microscopic states that contribute to supersymmetric single center black hole entropy in {N} = 2 supergravity.

  19. Renal cell carcinoma in South Korea: a multicenter study.

    PubMed

    Kim, Haeryoung; Cho, Nam Hoon; Kim, Dong-Sug; Kwon, Young-Mi; Kim, Eun Kyung; Rha, Seo Hee; Park, Yong Wook; Shim, Jung Weon; Lee, Sang Sook; Lee, Shi Nae; Lee, Juhie; Lee, Jin Sook; Lee, Tae-Jin; Jung, Soo Jin; Jung, Soon-Hee; Chung, Jin Haeng; Cho, Hyun Yee; Joo, Hee Jae; Choi, Yeong-Jin; Choi, Chan; Han, Woon Sup; Hur, Bang; Ro, Jae Y

    2004-12-01

    The incidence of renal cell carcinoma (RCC) in South Korea is steadily becoming similar to that in Western countries. This study summarizes the results of a 3-year multicenter survey of RCC in South Korea, conducted by the Korean Genitourinary Pathology Study Group. A total of 795 cases of RCC were collected from 20 institutes between 1995 and 1997, including 686 clear cell RCCs (86.3%), 58 papillary RCCS (7.30%), 49 chromphobe RCCs (6.16%), and 2 collecting duct RCCs (0.25%). At least 5 years of follow-up was available for 627 clear cell, 54 papillary, and 49 chromophobe RCCs. All subtypes presented most frequently with stage T3aN0M0 at the time of operation, and papillary RCCs demonstrated more frequent lymph node metastasis. Overall survival was not significantly related to the histological subtype (clear cell vs papillary, P = 0.8651; clear cell vs chromophobe, P = 0.0584; papillary vs chromophobe, P = 0.0743). For clear cell RCCs, statistically significant associations were found between overall survival and sex (P = 0.0153), multiplicity (P = 0.0461), necrosis (P = 0.0191), age, sarcomatoid change, TNM stage, nuclear grade, and modality of treatment (all P <0.0001). Overall survival was significantly associated with tumor size (P = 0.0307), nuclear grade (P = 0.0235), multiplicity, sarcomatoid change, and TNM stage (all P <0.0001) for papillary RCCs and with the presence of sarcomatoid change (P = 0.0281), nuclear grade (P = 0.0015), treatment modality (P = 0.0328), and TNM stage (P <0.0001) for chromophobe RCCs. Age (P = 0.0125), nodal stage (P = 0.0010), and treatment modality (P = 0.0001) were significant independent prognostic indicators for clear cell RCC on multivariate analysis. This is the first multicenter study of RCC in South Korea, demonstrating the general patterns and prognostic factors of Korean RCCs. PMID:15619217

  20. Alcohol Consumption among University Students in North Rhine-Westphalia, Germany--Results from a Multicenter Cross-Sectional Study

    ERIC Educational Resources Information Center

    Akmatov, Manas K.; Mikolajczyk, Rafael T.; Meier, Sabine; Kramer, Alexander

    2011-01-01

    Objective: To assess alcohol use and problem drinking among university students in the German Federal State of North Rhine-Westphalia (NRW) and to examine the associated factors. Method: A multicenter cross-sectional study was conducted in 16 universities in 2006-2007 in NRW by a standardized questionnaire and 3,306 students provided information…

  1. Implementation of evidence-based stroke care: enablers, barriers, and the role of facilitators

    PubMed Central

    Purvis, Tara; Moss, Karen; Denisenko, Sonia; Bladin, Chris; Cadilhac, Dominique A

    2014-01-01

    A stroke care strategy was developed in 2007 to improve stroke services in Victoria, Australia. Eight stroke network facilitators (SNFs) were appointed in selected hospitals to enable the establishment of stroke units, develop thrombolysis services, and implement protocols. We aimed to explain the main issues being faced by clinicians in providing evidence-based stroke care, and to determine if the appointment of an SNF was perceived as an acceptable strategy to improve stroke care. Face-to-face semistructured interviews were used in a qualitative research design. Interview transcripts were verified by respondents prior to coding. Two researchers conducted thematic analysis of major themes and subthemes. Overall, 84 hospital staff participated in 33 interviews during 2008. The common factors found to impact on stroke care included staff and equipment availability, location of care, inconsistent use of clinical pathways, and professional beliefs. Other barriers included limited access to specialist clinicians and workload demands. The establishment of dedicated stroke units was considered essential to improve the quality of care. The SNF role was valued for identifying gaps in care and providing capacity to change clinical processes. This is the first large, qualitative multicenter study to describe issues associated with delivering high-quality stroke care and the potential benefits of SNFs to facilitate these improvements. PMID:25246799

  2. Prospective Evaluation of Ultrasonic Surgical Dissectors in Hepatic Resection: A Cooperative Multicenter Study

    PubMed Central

    Millat, Bertrand; Hay, Jean-Marie; Descottes, Bernard; Fagniez, Pierre-Louis

    1992-01-01

    Blood loss is the major cause of postoperative mortality and morbidity associated with hepatic resection. A prospective multicenter study was conducted to determine if ultrasonic dissectors (USD) were useful in hepatic resection and could reduce this hemorrhagic risk. Forty-seven hepatic resections were performed in 42 consecutive patients during a two month period in 11 public, surgical centers. Twenty-one patients had primary or secondary malignancies, six had benign tumors, two had biliary cysts, one had cholangiocarcinoma, one had Caroli’s disease, and 11 had hydatid cysts of the liver. Two different USD devices were evaluated (CUSA System-Lasersonics and NIIC-DX 101 T). The hepatic resections tested included a wide range of procedures. Each surgeon had the possibility of choosing between the USD and his own usual technique for each operative step and according to local conditions. The average volume of blood infused, irrespective of the underlying pathology or the procedure performed, was 1.0 L (range 0-4.8 L). Fourteen patients required no transfusions. No operative or immediate postoperative deaths were recorded. Five major complications, all unrelated to the use of the USD, developed in three patients. Access to intra and extraparenchymal arterial and venous tributaries and particularly the control of the hepatic veins were facilitated by USD. While transection of hepatic parenchyma was neither easier nor faster than with conventional techniques, it was found to be less hemorrhagic. Overall appraisal was expressed on an analog scale; the USD was found to be helpful or very helpful in 75 percent of all resections. With regard to the pathology being treated, total or partial excision of hydatid cysts was greatly enhanced by the use of the USD while this benefit was not found for wedge resections of other hepatic lesions. With regard to user friendliness and maintenance, the NIIC-DX 101 T device was preferred. We conclude that the USD facilitates formal

  3. The ESCRT-Associated Protein Alix Recruits the Ubiquitin Ligase Nedd4-1 To Facilitate HIV-1 Release through the LYPXnL L Domain Motif▿

    PubMed Central

    Sette, Paola; Jadwin, Joshua A.; Dussupt, Vincent; Bello, Nana F.; Bouamr, Fadila

    2010-01-01

    The p6 region of HIV-1 Gag contains two late (L) domains, PTAP and LYPXnL, that bind Tsg101 and Alix, respectively. Interactions with these two cellular proteins recruit members of the host's fission machinery (ESCRT) to facilitate HIV-1 release. Other retroviruses gain access to the host ESCRT components by utilizing a PPXY-type L domain that interacts with cellular Nedd4-like ubiquitin ligases. Despite the absence of a PPXY motif in HIV-1 Gag, interaction with the ubiquitin ligase Nedd4-2 was recently shown to stimulate HIV-1 release. We show here that another Nedd4-like ubiquitin ligase, Nedd4-1, corrected release defects resulting from the disruption of PTAP (PTAP−), suggesting that HIV-1 Gag also recruits Nedd4-1 to facilitate virus release. Notably, Nedd4-1 remediation of HIV-1 PTAP− budding defects is independent of cellular Tsg101, implying that Nedd4-1's function in HIV-1 release does not involve ESCRT-I components and is therefore distinct from that of Nedd4-2. Consistent with this finding, deletion of the p6 region decreased Nedd4-1-Gag interaction, and disruption of the LYPXnL motif eliminated Nedd4-1-mediated restoration of HIV-1 PTAP−. This result indicated that both Nedd4-1 interaction with Gag and function in virus release occur through the Alix-binding LYPXnL motif. Mutations of basic residues located in the NC domain of Gag that are critical for Alix's facilitation of HIV-1 release, also disrupted release mediated by Nedd4-1, further confirming a Nedd4-1-Alix functional interdependence. In fact we found that Nedd4-1 binds Alix in both immunoprecipitation and yeast-two-hybrid assays. In addition, Nedd4-1 requires its catalytic activity to promote virus release. Remarkably, RNAi knockdown of cellular Nedd4-1 eliminated Alix ubiquitination in the cell and impeded its ability to function in HIV-1 release. Together our data support a model in which Alix recruits Nedd4-1 to facilitate HIV-1 release mediated through the LYPXnL/Alix budding pathway

  4. MiDas: Automatic Extraction of a Common Domain of Discourse in Sleep Medicine for Multi-center Data Integration

    PubMed Central

    Sahoo, Satya S.; Ogbuji, Chimezie; Luo, Lingyun; Dong, Xiao; Cui, Licong; Redline, Susan S.; Zhang, Guo-Qiang

    2011-01-01

    Clinical studies often use data dictionaries with controlled sets of terms to facilitate data collection, limited interoperability and sharing at a local site. Multi-center retrospective clinical studies require that these data dictionaries, originating from individual participating centers, be harmonized in preparation for the integration of the corresponding clinical research data. Domain ontologies are often used to facilitate multi-center data integration by modeling terms from data dictionaries in a logic-based language, but interoperability among domain ontologies (using automated techniques) is an unresolved issue. Although many upper-level reference ontologies have been proposed to address this challenge, our experience in integrating multi-center sleep medicine data highlights the need for an upper level ontology that models a common set of terms at multiple-levels of abstraction, which is not covered by the existing upper-level ontologies. We introduce a methodology underpinned by a Minimal Domain of Discourse (MiDas) algorithm to automatically extract a minimal common domain of discourse (upper-domain ontology) from an existing domain ontology. Using the Multi-Modality, Multi-Resource Environment for Physiological and Clinical Research (Physio-MIMI) multi-center project in sleep medicine as a use case, we demonstrate the use of MiDas in extracting a minimal domain of discourse for sleep medicine, from Physio-MIMI’s Sleep Domain Ontology (SDO). We then extend the resulting domain of discourse with terms from the data dictionary of the Sleep Heart and Health Study (SHHS) to validate MiDas. To illustrate the wider applicability of MiDas, we automatically extract the respective domains of discourse from 6 sample domain ontologies from the National Center for Biomedical Ontologies (NCBO) and the OBO Foundry. PMID:22195180

  5. MiDas: automatic extraction of a common domain of discourse in sleep medicine for multi-center data integration.

    PubMed

    Sahoo, Satya S; Ogbuji, Chimezie; Luo, Lingyun; Dong, Xiao; Cui, Licong; Redline, Susan S; Zhang, Guo-Qiang

    2011-01-01

    Clinical studies often use data dictionaries with controlled sets of terms to facilitate data collection, limited interoperability and sharing at a local site. Multi-center retrospective clinical studies require that these data dictionaries, originating from individual participating centers, be harmonized in preparation for the integration of the corresponding clinical research data. Domain ontologies are often used to facilitate multi-center data integration by modeling terms from data dictionaries in a logic-based language, but interoperability among domain ontologies (using automated techniques) is an unresolved issue. Although many upper-level reference ontologies have been proposed to address this challenge, our experience in integrating multi-center sleep medicine data highlights the need for an upper level ontology that models a common set of terms at multiple-levels of abstraction, which is not covered by the existing upper-level ontologies. We introduce a methodology underpinned by a Minimal Domain of Discourse (MiDas) algorithm to automatically extract a minimal common domain of discourse (upper-domain ontology) from an existing domain ontology. Using the Multi-Modality, Multi-Resource Environment for Physiological and Clinical Research (Physio-MIMI) multi-center project in sleep medicine as a use case, we demonstrate the use of MiDas in extracting a minimal domain of discourse for sleep medicine, from Physio-MIMI's Sleep Domain Ontology (SDO). We then extend the resulting domain of discourse with terms from the data dictionary of the Sleep Heart and Health Study (SHHS) to validate MiDas. To illustrate the wider applicability of MiDas, we automatically extract the respective domains of discourse from 6 sample domain ontologies from the National Center for Biomedical Ontologies (NCBO) and the OBO Foundry. PMID:22195180

  6. Association of PHB 1630 C>T and MTHFR 677 C>T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study

    PubMed Central

    Jakubowska, A; Rozkrut, D; Antoniou, A; Hamann, U; Scott, R J; McGuffog, L; Healy, S; Sinilnikova, O M; Rennert, G; Lejbkowicz, F; Flugelman, A; Andrulis, I L; Glendon, G; Ozcelik, H; Thomassen, M; Paligo, M; Aretini, P; Kantala, J; Aroer, B; von Wachenfeldt, A; Liljegren, A; Loman, N; Herbst, K; Kristoffersson, U; Rosenquist, R; Karlsson, P; Stenmark-Askmalm, M; Melin, B; Nathanson, K L; Domchek, S M; Byrski, T; Huzarski, T; Gronwald, J; Menkiszak, J; Cybulski, C; Serrano, P; Osorio, A; Cajal, T R; Tsitlaidou, M; Benítez, J; Gilbert, M; Rookus, M; Aalfs, C M; Kluijt, I; Boessenkool-Pape, J L; Meijers-Heijboer, H E J; Oosterwijk, J C; van Asperen, C J; Blok, M J; Nelen, M R; van den Ouweland, A M W; Seynaeve, C; van der Luijt, R B; Devilee, P; Easton, D F; Peock, S; Frost, D; Platte, R; Ellis, S D; Fineberg, E; Evans, D G; Lalloo, F; Eeles, R; Jacobs, C; Adlard, J; Davidson, R; Eccles, D; Cole, T; Cook, J; Godwin, A; Bove, B; Stoppa-Lyonnet, D; Caux-Moncoutier, V; Belotti, M; Tirapo, C; Mazoyer, S; Barjhoux, L; Boutry-Kryza, N; Pujol, P; Coupier, I; Peyrat, J-P; Vennin, P; Muller, D; Fricker, J-P; Venat-Bouvet, L; Johannsson, O Th; Isaacs, C; Schmutzler, R; Wappenschmidt, B; Meindl, A; Arnold, N; Varon-Mateeva, R; Niederacher, D; Sutter, C; Deissler, H; Preisler-Adams, S; Simard, J; Soucy, P; Durocher, F; Chenevix-Trench, G; Beesley, J; Chen, X; Rebbeck, T; Couch, F; Wang, X; Lindor, N; Fredericksen, Z; Pankratz, V S; Peterlongo, P; Bonanni, B; Fortuzzi, S; Peissel, B; Szabo, C; Mai, P L; Loud, J T; Lubinski, J

    2012-01-01

    Background: The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity. Methods: To evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 C>T (rs6917) polymorphism and the MTHFR 677 C>T (rs1801133) polymorphism, respectively. Results: There was no evidence of association between the PHB 1630 C>T and MTHFR 677 C>T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 C>T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95%CI 1.10–2.04 and HR 2.16, 95%CI 1.24–3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele. Conclusion: The PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers. PMID:22669161

  7. The Leu33Pro polymorphism in the ITGB3 gene does not modify BRCA1/2-associated breast or ovarian cancer risks: results from a multicenter study among 15,542 BRCA1 and BRCA2 mutation carriers

    PubMed Central

    Jakubowska, Anna; Rozkrut, Dominik; Antoniou, Antonis; Hamann, Ute; Lubinski, Jan

    2011-01-01

    Integrins containing the β3 subunit are key players in tumor growth and metastasis. A functional Leu33Pro polymorphism (rs5918) in the β3 subunit of the integrin gene (ITGB3) has previously been suggested to act as a modifier of ovarian cancer risk in Polish BRCA1 mutation carriers. To investigate the association further, we genotyped 9,998 BRCA1 and 5,544 BRCA2 mutation carriers from 34 studies from the Consortium of Investigators of Modifiers of BRCA1/2 for the ITGB3 Leu33Pro polymorphism. Data were analysed within a Cox-proportional hazards framework using a retrospective likelihood approach. There was marginal evidence that the ITGB3 polymorphism was associated with an increased risk of ovarian cancer for BRCA1 mutation carriers (per-allele Hazard Ratio (HR) 1.11, 95% CI 1.00–1.23, p-trend 0.05). However, when the original Polish study was excluded from the analysis, the polymorphism was no longer significantly associated with ovarian cancer risk (HR 1.07, 95% CI 0.96–1.19, p-trend 0.25). There was no evidence of an association with ovarian cancer risk for BRCA2 mutation carriers (HR 1.09, 95% CI 0.89–1.32). The polymorphism was not associated with breast cancer risk for either BRCA1 or BRCA2 mutation carriers. The ITGB3 Leu33Pro polymorphism does not modify breast or ovarian cancer risk in BRCA1 or BRCA2 mutation carriers. PMID:19876733

  8. Fungal phylogenetic diversity drives plant facilitation.

    PubMed

    Montesinos-Navarro, Alicia; Segarra-Moragues, J G; Valiente-Banuet, A; Verdú, M

    2016-06-01

    Plant-plant facilitation is a crucial ecological process, as many plant species (facilitated) require the presence of an established individual (nurse) to recruit. Some plant facilitative interactions disappear during the ontogenetic development of the facilitated plant but others persist, even when the two plants are adults. We test whether the persistence of plant facilitative interactions is explained by the phylogenetic diversity of mutualistic and non-mutualistic fungi that the nurse and the facilitated species add to the shared rhizosphere. We classify plant facilitative interactions as persistent and non-persistent interactions and quantify the phylogenetic diversity of mutualistic and non-mutualistic fungi added by the plant species to the shared rhizosphere. Our results show that the facilitated species add less phylogenetic diversity of non-mutualistic fungi when plant facilitative interactions persist than when they do not persist. However, persistent and non-persistent facilitative interactions did not differ in the phylogenetic diversity of mutualistic fungi added by the facilitated species to the shared rhizosphere. Finally, the fungal phylogenetic diversity added by the nurse to the shared rhizosphere did not differ between persistent and non-persistent interactions. This study suggests that considering the fungal associates of the plant species involved in facilitative interactions can shed light on the mechanisms of persistence for plant-plant interactions. PMID:26915080

  9. Mass Spectrometry Imaging of Biological Tissue: An Approach for Multicenter Studies

    SciTech Connect

    Rompp, Andreas; Both, Jean-Pierre; Brunelle, Alain; Heeren, Ronald M.; Laprevote, Olivier; Prideaux, Brendan; Seyer, Alexandre; Spengler, Bernhard; Stoeckli, Markus; Smith, Donald F.

    2015-03-01

    Mass spectrometry imaging has become a popular tool for probing the chemical complexity of biological surfaces. This led to the development of a wide range of instrumentation and preparation protocols. It is thus desirable to evaluate and compare the data output from different methodologies and mass spectrometers. Here, we present an approach for the comparison of mass spectrometry imaging data from different laboratories (often referred to as multicenter studies). This is exemplified by the analysis of mouse brain sections in five laboratories in Europe and the USA. The instrumentation includes matrix-assisted laser desorption/ionization (MALDI)-time-of-flight (TOF), MALDI-QTOF, MALDIFourier transform ion cyclotron resonance (FTICR), atmospheric-pressure (AP)-MALDI-Orbitrap, and cluster TOF-secondary ion mass spectrometry (SIMS). Experimental parameters such as measurement speed, imaging bin width, and mass spectrometric parameters are discussed. All datasets were converted to the standard data format imzML and displayed in a common open-source software with identical parameters for visualization, which facilitates direct comparison of MS images. The imzML conversion also allowed exchange of fully functional MS imaging datasets between the different laboratories. The experiments ranged from overview measurements of the full mouse brain to detailed analysis of smaller features (depending on spatial resolution settings), but common histological features such as the corpus callosum were visible in all measurements. High spatial resolution measurements of AP-MALDI-Orbitrap and TOF-SIMS showed comparable structures in the low-micrometer range. We discuss general considerations for planning and performing multicenter studies in mass spectrometry imaging. This includes details on the selection, distribution, and preparation of tissue samples as well as on data handling. Such multicenter studies in combination with ongoing activities for reporting guidelines, a common

  10. Virion-associated cofactor high-mobility group DNA-binding protein-1 facilitates transposition from the herpes simplex virus/Sleeping Beauty amplicon vector platform.

    PubMed

    de Silva, Suresh; Lotta, Louis T; Burris, Clark A; Bowers, William J

    2010-11-01

    The development of the integration-competent, herpes simplex virus/Sleeping Beauty (HSV/SB) amplicon vector platform has created a means to efficiently and stably deliver therapeutic transcription units (termed "transgenons") to neurons within the mammalian brain. Furthermore, an investigation into the transposition capacity of the HSV/SB vector system revealed that the amplicon genome provides an optimal substrate for the transposition of transgenons at least 12 kb in length [de Silva, S., Mastrangelo, M.A., Lotta, L.T., Jr., Burris, C.A., Federoff, H.J., and Bowers, W.J. ( 2010 ). Gene Ther. 17, 424-431]. These results prompted an investigation into the factors that may contribute toward efficient transposition from the HSV/SB amplicon. One of the cellular cofactors known to play a key role during SB-mediated transposition is the high-mobility group DNA-binding protein-1 (HMGB1). Our present investigation into the role of HMGB1 during amplicon-based transposition revealed that transposition is not strictly dependent on the presence of cellular HMGB1, contrary to what had been previously demonstrated with plasmid-based SB transposition. We have shown for the first time that during amplicon preparation, biologically active HMGB1 derived from the packaging cell line is copackaged into amplicon vector particles. As a result, HSV/SB amplicon virions arrive prearmed with HMGB1 protein at levels sufficient for facilitating SB-mediated transposition in the transduced mammalian cell. PMID:20568967

  11. Canine genome assembly correction facilitates identification of a MAP9 deletion as a potential age of onset modifier for RPGRIP1-associated canine retinal degeneration.

    PubMed

    Forman, Oliver P; Hitti, Rebekkah J; Boursnell, Mike; Miyadera, Keiko; Sargan, David; Mellersh, Cathryn

    2016-06-01

    Retinal degeneration (RD) in the Miniature Long Haired Dachshund (MLHD) is a cone-rod dystrophy resulting in eventual blindness in affected individuals. In a previous study, a 44-nucleotide insertion (ins44) in exon 2 of RPGRIP1 was associated with RD. However, results on an extended population of MLHD revealed a variable RD onset age for ins44 homozygous dogs. Further investigations using a genome-wide association study comparing early onset and late onset RD cases identified an age of onset modifying locus for RD, approximately 30 Mb upstream of RPGRIP1 on chr15. In this investigation, target enriched sequencing identified a MAP9 deletion spanning approximately 22 kb associated with early RD onset. Identification of the deletion required correction to the CanFam3.1 genome build as canine MAP9 is part of a historic tandem duplication, resulting in incomplete assembly of this genome region. The deletion breakpoints were identified in MAP9 intron 10 and in a downstream partial MAP9 pseudogene. The fusion of these two genes, which we have called MAP9 EORD (microtubule-associated protein, early onset retinal degeneration), is in frame and is expressed at the RNA level, with the 3' region containing several predicted deleterious variants. We speculate that MAP9 associates with α-tubulin in the basal body of the cilium. RPGRIP1 is also known to locate to the cilium, where it is closely associated with RPGR. RPGRIP1 mutations also cause redistribution of α-tubulin away from the ciliary region in photoreceptors. Hence, a MAP9 partial deficit is a particularly attractive candidate to synergise with a partial RPGRIP1 deficit to cause a more serious disease. PMID:27017229

  12. A Facilitation Performance Aid.

    ERIC Educational Resources Information Center

    Chevalier, Roger

    1997-01-01

    Presents a guide, derived from the Situational Leadership model, which describes the process that should be used in facilitating a group discussion. The process includes preparation, assessment, diagnosis, prescription, development, reinforcement, and follow-up. Three figures depict the Situational Leadership model, the facilitation process, and…

  13. Economic Impact of Dengue: Multicenter Study across Four Brazilian Regions

    PubMed Central

    Martelli, Celina Maria Turchi; Siqueira, Joao Bosco; Parente, Mirian Perpetua Palha Dias; Zara, Ana Laura de Sene Amancio; Oliveira, Consuelo Silva; Braga, Cynthia; Pimenta, Fabiano Geraldo; Cortes, Fanny; Lopez, Juan Guillermo; Bahia, Luciana Ribeiro; Mendes, Marcia Costa Ooteman; da Rosa, Michelle Quarti Machado; de Siqueira Filha, Noemia Teixeira; Constenla, Dagna; de Souza, Wayner Vieira

    2015-01-01

    Background Dengue is an increasing public health concern in Brazil. There is a need for an updated evaluation of the economic impact of dengue within the country. We undertook this multicenter study to evaluate the economic burden of dengue in Brazil. Methods We estimated the economic burden of dengue in Brazil for the years 2009 to 2013 and for the epidemic season of August 2012- September 2013. We conducted a multicenter cohort study across four endemic regions: Midwest, Goiania; Southeast, Belo Horizonte and Rio de Janeiro; Northeast: Teresina and Recife; and the North, Belem. Ambulatory or hospitalized cases with suspected or laboratory-confirmed dengue treated in both the private and public sectors were recruited. Interviews were scheduled for the convalescent period to ascertain characteristics of the dengue episode, date of first symptoms/signs and recovery, use of medical services, work/school absence, household spending (out-of-pocket expense) and income lost using a questionnaire developed for a previous cost study. We also extracted data from the patients’ medical records for hospitalized cases. Overall costs per case and cumulative costs were calculated from the public payer and societal perspectives. National cost estimations took into account cases reported in the official notification system (SINAN) with adjustment for underreporting of cases. We applied a probabilistic sensitivity analysis using Monte Carlo simulations with 90% certainty levels (CL). Results We screened 2,223 cases, of which 2,035 (91.5%) symptomatic dengue cases were included in our study. The estimated cost for dengue for the epidemic season (2012–2013) in the societal perspective was US$ 468 million (90% CL: 349–590) or US$ 1,212 million (90% CL: 904–1,526) after adjusting for under-reporting. Considering the time series of dengue (2009–2013) the estimated cost of dengue varied from US$ 371 million (2009) to US$ 1,228 million (2013). Conclusions The economic burden

  14. Mycobacterium tuberculosis Pyrazinamide Resistance Determinants: a Multicenter Study

    PubMed Central

    Cabibbe, Andrea M.; Feuerriegel, Silke; Casali, Nicola; Drobniewski, Francis; Rodionova, Yulia; Bakonyte, Daiva; Stakenas, Petras; Pimkina, Edita; Augustynowicz-Kopeć, Ewa; Degano, Massimo; Ambrosi, Alessandro; Hoffner, Sven; Mansjö, Mikael; Werngren, Jim; Rüsch-Gerdes, Sabine; Niemann, Stefan; Cirillo, Daniela M.

    2014-01-01

    ABSTRACT Pyrazinamide (PZA) is a prodrug that is converted to pyrazinoic acid by the enzyme pyrazinamidase, encoded by the pncA gene in Mycobacterium tuberculosis. Molecular identification of mutations in pncA offers the potential for rapid detection of pyrazinamide resistance (PZAr). However, the genetic variants are highly variable and scattered over the full length of pncA, complicating the development of a molecular test. We performed a large multicenter study assessing pncA sequence variations in 1,950 clinical isolates, including 1,142 multidrug-resistant (MDR) strains and 483 fully susceptible strains. The results of pncA sequencing were correlated with phenotype, enzymatic activity, and structural and phylogenetic data. We identified 280 genetic variants which were divided into four classes: (i) very high confidence resistance mutations that were found only in PZAr strains (85%), (ii) high-confidence resistance mutations found in more than 70% of PZAr strains, (iii) mutations with an unclear role found in less than 70% of PZAr strains, and (iv) mutations not associated with phenotypic resistance (10%). Any future molecular diagnostic assay should be able to target and identify at least the very high and high-confidence genetic variant markers of PZAr; the diagnostic accuracy of such an assay would be in the range of 89.5 to 98.8%. PMID:25336456

  15. LZAP Inhibits p38 MAPK (p38) Phosphorylation and Activity by Facilitating p38 Association with the Wild-Type p53 Induced Phosphatase 1 (WIP1)

    PubMed Central

    An, Hanbing; Lu, Xinyuan; Liu, Dan; Yarbrough, Wendell G.

    2011-01-01

    LZAP (Cdk5rap3, C53) is a putative tumor suppressor that inhibits RelA, Chk1 and Chk2 and activates p53. LZAP is lost in a portion of human head and neck squamous cell carcinoma and experimental loss of LZAP expression is associated with enhanced invasion, xenograft tumor growth and angiogenesis. p38 MAPK can increase or decrease proliferation and cell death depending on cellular context. LZAP has no known enzymatic activity, implying that its biological functions are likely mediated by its protein-protein interactions. To gain further insight into LZAP activities, we searched for LZAP-associated proteins (LAPs). Here we show that the LZAP binds p38, alters p38 cellular localization, and inhibits basal and cytokine-stimulated p38 activity. Expression of LZAP inhibits p38 phosphorylation in a dose-dependent fashion while loss of LZAP enhances phosphorylation and activation with resultant phosphorylation of p38 downstream targets. Mechanistically, the ability of LZAP to alter p38 phosphorylation depended, at least partially, on the p38 phosphatase, Wip1. Expression of LZAP increased both LZAP and Wip1 binding to p38. Taken together, these data suggest that LZAP activity includes inhibition of p38 phosphorylation and activation. PMID:21283629

  16. Pharmacotherapy of elderly patients in everyday anthroposophic medical practice: a prospective, multicenter observational study

    PubMed Central

    2010-01-01

    Background Pharmacotherapy in the older adult is a complex field involving several different medical professionals. The evidence base for pharmacotherapy in elderly patients in primary care relies on only a few clinical trials, thus documentation must be improved, particularly in the field of complementary and alternative medicine (CAM) like phytotherapy, homoeopathy, and anthroposophic medicine. This study describes diagnoses and therapies observed in elderly patients treated with anthroposophic medicine in usual care. Methods Twenty-nine primary care physicians in Germany participated in this prospective, multicenter observational study on prescribing patterns. Prescriptions and diagnoses were reported for each consecutive patient. Data were included if patients were at least 60 years of age. Multiple logistic regression analysis was used to determine factors associated with anthroposophic prescriptions. Results In 2005, a total of 12 314 prescriptions for 3076 patients (68.1% female) were included. The most frequent diagnoses were hypertension (11.1%), breast cancer (3.5%), and heart failure (3.0%). In total, 30.5% of the prescriptions were classified as CAM remedies alone, 54.4% as conventional pharmaceuticals alone, and 15.1% as a combination of both. CAM remedies accounted for 41.7% of all medications prescribed (35.5% anthroposophic). The adjusted odds ratio (AOR) for receiving an anthroposophic remedy was significantly higher for the first consultation (AOR = 1.65; CI: 1.52-1.79), treatment by an internist (AOR = 1.49; CI: 1.40-1.58), female patients (AOR = 1.35; CI: 1.27-1.43), cancer (AOR = 4.54; CI: 4.12-4.99), arthropathies (AOR = 1.36; CI: 1.19-1.55), or dorsopathies (AOR = 1.34; CI: 1.16-1.55) and it decreased with patient age (AOR = 0.97; CI: 0.97-0.98). The likelihood of being prescribed an anthroposophic remedy was especially low for patients with hypertensive diseases (AOR = 0.36; CI: 0.32-0.39), diabetes mellitus (AOR = 0.17; CI: 0.14-0.22), or

  17. Lessons from Korean Capsule Endoscopy Multicenter Studies

    PubMed Central

    Kim, Kyeong Ok

    2012-01-01

    Since its development, video capsule endoscopy (VCE) introduced a new area in the study of small bowel disease. We reviewed and discussed current issues from Korean capsule endoscopy multicenter studies. Main results are as follows: First, there was no significant difference in diagnostic yield according to the method of bowel preparation. Second, VCE represents a reliable and influential screening measure in patients with chronic unexplained abdominal pain and this technique could successfully alter the clinical course especially for patients with small bowel tumor. Third, the inter-observer variation in the expert group was lower than that in trainee group. Fourth, studies about the spontaneous capsule passage after retention showed 2.5% of retention rate and the size of lumen was an important factor of spontaneous passage. We need larger scale studies on the effect of bowel preparation methods on the diagnostic yield and further studies about the learning curve or unique capsule endoscopic findings for small intestinal diseases in Korean patients. PMID:22977821

  18. Multicenter study of nursing role complexity on environmental stressors and emotional exhaustion.

    PubMed

    Solomon, Deborah; Singleton, Kathleen A; Sun, Zhiyuan; Zell, Katrina; Vriezen, Kathryn; Albert, Nancy M

    2016-05-01

    Among nurses, work and cognitive complexity patterns of care were previously associated with environmental stressors, but it is unknown if complexity patterns are also associated with emotional exhaustion. A multicenter sample of hospital nurses (N=281) completed valid, reliable questionnaires. Data were analyzed using multivariable modeling. Registered nurse characteristics did not vary by work setting. Overall mean (standard deviation [SD]) standardized complexity of care score was 45.82 (13.73), reflecting moderate complexity during 3-hour work periods. Nurses experienced greater cognitive complexity patterns than work complexity patterns (p<0.001). In multivariable analyses, overall complexity of care and work and cognitive complexity patterns were not associated with high emotional exhaustion. Higher work complexity pattern score was associated with more environmental stressors (p=0.009), but there was no association between overall complexity of care or cognitive complexity pattern and environmental stressors. Interventions that reduce environmental stressors might reduce work complexity of care. PMID:27091253

  19. Microtubule-Associated Protein SBgLR Facilitates Storage Protein Deposition and Its Expression Leads to Lysine Content Increase in Transgenic Maize Endosperm.

    PubMed

    Liu, Chen; Li, Shixue; Yue, Jing; Xiao, Wenhan; Zhao, Qian; Zhu, Dengyun; Yu, Jingjuan

    2015-01-01

    Maize (Zea mays) seed is deficient in protein and lysine content. Many studies have been made to improve the nutritional quality of maize seeds. Previously, we reported the role of a natural lysine-rich protein gene SBgLR in increasing protein and lysine content. However, how the SBgLR improves lysine and protein content remains unclear. Here, the reasons and possible mechanism for SBgLR in protein and lysine improvement have been analyzed and discussed. Through seed-specific expression of SBgLR, we obtained transgenic maize with the simultaneously increased lysine and protein contents. High-protein and high-lysine characters were stably inherited across generations. The expression of SBgLR in maize kernels increased the accumulation of both zeins and non-zein proteins. Transmission electron microscopy showed that the number of protein bodies (PBs) was increased obviously in SBgLR transgenic immature endosperms with the morphology and structure of PBs unchanged. The proteinaceous matrix was more abundant in transgenic mature endosperms under scanning electron microscopy. The stabilities of zein and lysine-rich non-zein genes were also increased in transgenic endosperms. Finally, the potential application of SBgLR in maize nutrient improvement was evaluated. This study shows that a cytoskeleton-associated protein has potential applicable value in crop nutrient improving, and provided a feasible strategy for improvement of maize grain quality. PMID:26703573

  20. Phosphatidic acid and phosphoinositides facilitate liposome association of Yas3p and potentiate derepression of ARE1 (alkane-responsive element one)-mediated transcription control.

    PubMed

    Kobayashi, Satoshi; Hirakawa, Kiyoshi; Horiuchi, Hiroyuki; Fukuda, Ryouichi; Ohta, Akinori

    2013-12-01

    In the n-alkane assimilating yeast Yarrowia lipolytica, the expression of ALK1, encoding a cytochrome P450 that catalyzes terminal mono-oxygenation of n-alkanes, is induced by n-alkanes. The transcription of ALK1 is regulated by a heterocomplex that comprises the basic helix-loop-helix transcription activators, Yas1p and Yas2p, and binds to alkane-responsive element 1 (ARE1) in the ALK1 promoter. An Opi1 family transcription repressor, Yas3p, represses transcription by binding to Yas2p. Yas3p localizes in the nucleus when Y. lipolytica is grown on glucose but localizes to the endoplasmic reticulum (ER) upon the addition of n-alkanes. In this study, we showed that recombinant Yas3p binds to the acidic phospholipids, phosphatidic acid (PA) and phosphoinositides (PIPs), in vitro. The ARE1-mediated transcription was enhanced in vivo in mutants defective in an ortholog of the Saccharomyces cerevisiae gene PAH1, encoding PA phosphatase, and in an ortholog of SAC1, encoding PIP phosphatase in the ER. Truncation mutation analyses for Yas3p revealed two regions that bound to PA and PIPs. These results suggest that the interaction with acidic phospholipids is important for the n-alkane-induced association of Yas3p with the ER membrane. PMID:24120453

  1. Microtubule-Associated Protein SBgLR Facilitates Storage Protein Deposition and Its Expression Leads to Lysine Content Increase in Transgenic Maize Endosperm

    PubMed Central

    Liu, Chen; Li, Shixue; Yue, Jing; Xiao, Wenhan; Zhao, Qian; Zhu, Dengyun; Yu, Jingjuan

    2015-01-01

    Maize (Zea mays) seed is deficient in protein and lysine content. Many studies have been made to improve the nutritional quality of maize seeds. Previously, we reported the role of a natural lysine-rich protein gene SBgLR in increasing protein and lysine content. However, how the SBgLR improves lysine and protein content remains unclear. Here, the reasons and possible mechanism for SBgLR in protein and lysine improvement have been analyzed and discussed. Through seed-specific expression of SBgLR, we obtained transgenic maize with the simultaneously increased lysine and protein contents. High-protein and high-lysine characters were stably inherited across generations. The expression of SBgLR in maize kernels increased the accumulation of both zeins and non-zein proteins. Transmission electron microscopy showed that the number of protein bodies (PBs) was increased obviously in SBgLR transgenic immature endosperms with the morphology and structure of PBs unchanged. The proteinaceous matrix was more abundant in transgenic mature endosperms under scanning electron microscopy. The stabilities of zein and lysine-rich non-zein genes were also increased in transgenic endosperms. Finally, the potential application of SBgLR in maize nutrient improvement was evaluated. This study shows that a cytoskeleton-associated protein has potential applicable value in crop nutrient improving, and provided a feasible strategy for improvement of maize grain quality. PMID:26703573

  2. Cell surface-associated aggregation-promoting factor from Lactobacillus gasseri SBT2055 facilitates host colonization and competitive exclusion of Campylobacter jejuni.

    PubMed

    Nishiyama, Keita; Nakazato, Akiko; Ueno, Shintaro; Seto, Yasuyuki; Kakuda, Tsutomu; Takai, Shinji; Yamamoto, Yuji; Mukai, Takao

    2015-11-01

    Campylobacter jejuni, one of the most common causes of gastroenteritis worldwide, is transmitted to humans through poultry. We previously reported that Lactobacillus gasseri SBT2055 (LG2055) reduced C. jejuni infection in human epithelial cells in vitro and inhibited pathogen colonization of chickens in vivo. This suggested that the LG2055 adhesion and/or co-aggregation phenotype mediated by cell-surface aggregation-promoting factors (APFs) may be important for the competitive exclusion of C. jejuni. Here, we show that cell surface-associated APF1 promoted LG2055 self-aggregation and adhesion to human epithelial cells and exhibited high affinity for the extracellular matrix component fibronectin. These effects were absent in the apf1 knockout mutant, indicating the role of APF1 in LG2055-mediated inhibition of C. jejuni in epithelial cells and chicken colonization. Similar to APF1, APF2 promoted the co-aggregation of LG2055 and C. jejuni but did not inhibit C. jejuni infection. Our data suggest a pivotal role for APF1 in mediating the interaction of LG2055 with human intestinal cells and in inhibiting C. jejuni colonization of the gastrointestinal tract. We thus provide new insight into the health-promoting effects of probiotics and mechanisms of competitive exclusion in poultry. Further research is needed to determine whether the probiotic strains reach the epithelial surface. PMID:26239091

  3. SecDF as Part of the Sec-Translocase Facilitates Efficient Secretion of Bacillus cereus Toxins and Cell Wall-Associated Proteins

    PubMed Central

    Vörös, Aniko; Simm, Roger; Slamti, Leyla; McKay, Matthew J.; Hegna, Ida K.; Nielsen-LeRoux, Christina; Hassan, Karl A.; Paulsen, Ian T.; Lereclus, Didier; Økstad, Ole Andreas; Molloy, Mark P.; Kolstø, Anne-Brit

    2014-01-01

    The aim of this study was to explore the role of SecDF in protein secretion in Bacillus cereus ATCC 14579 by in-depth characterization of a markerless secDF knock out mutant. Deletion of secDF resulted in pleiotropic effects characterized by a moderately slower growth rate, aberrant cell morphology, enhanced susceptibility to xenobiotics, reduced virulence and motility. Most toxins, including food poisoning-associated enterotoxins Nhe, Hbl, and cytotoxin K, as well as phospholipase C were less abundant in the secretome of the ΔsecDF mutant as determined by label-free mass spectrometry. Global transcriptome studies revealed profound transcriptional changes upon deletion of secDF indicating cell envelope stress. Interestingly, the addition of glucose enhanced the described phenotypes. This study shows that SecDF is an important part of the Sec-translocase mediating efficient secretion of virulence factors in the Gram-positive opportunistic pathogen B. cereus, and further supports the notion that B. cereus enterotoxins are secreted by the Sec-system. PMID:25083861

  4. Race, Ethnicity, Psychosocial Factors, and Telomere Length in a Multicenter Setting

    PubMed Central

    Mitra, Nandita; Ravichandran, Krithika; Branas, Charles; Spangler, Elaine; Zhou, Wenting; Paskett, Electra D.; Gehlert, Sarah; DeGraffinreid, Cecilia

    2016-01-01

    Background Leukocyte telomere length(LTL) has been associated with age, self-reported race/ethnicity, gender, education, and psychosocial factors, including perceived stress, and depression. However, inconsistencies in associations of LTL with disease and other phenotypes exist across studies. Population characteristics, including race/ethnicity, laboratory methods, and statistical approaches in LTL have not been comprehensively studied and could explain inconsistent LTL associations. Methods LTL was measured using Southern Blot in 1510 participants from a multi-ethnic, multi-center study combining data from 3 centers with different population characteristics and laboratory processing methods. Main associations between LTL and psychosocial factors and LTL and race/ethnicity were evaluated and then compared across generalized estimating equations(GEE) and linear regression models. Statistical models were adjusted for factors typically associated with LTL(age, gender, cancer status) and also accounted for factors related to center differences, including laboratory methods(i.e., DNA extraction). Associations between LTL and psychosocial factors were also evaluated within race/ethnicity subgroups (Non-hispanic Whites, African Americans, and Hispanics). Results Beyond adjustment for age, gender, and cancer status, additional adjustments for DNA extraction and clustering by center were needed given their effects on LTL measurements. In adjusted GEE models, longer LTL was associated with African American race (Beta(β)(standard error(SE)) = 0.09(0.04), p-value = 0.04) and Hispanic ethnicity (β(SE) = 0.06(0.01), p-value = 0.02) compared to Non-Hispanic Whites. Longer LTL was also associated with less than a high school education compared to having greater than a high school education (β(SE) = 0.06(0.02), p-value = 0.04). LTL was inversely related to perceived stress (β(SE) = -0.02(0.003), p<0.001). In subgroup analyses, there was a negative association with LTL in

  5. A single bout of high-intensity aerobic exercise facilitates response to paired associative stimulation and promotes sequence-specific implicit motor learning.

    PubMed

    Mang, Cameron S; Snow, Nicholas J; Campbell, Kristin L; Ross, Colin J D; Boyd, Lara A

    2014-12-01

    The objectives of the present study were to evaluate the impact of a single bout of high-intensity aerobic exercise on 1) long-term potentiation (LTP)-like neuroplasticity via response to paired associative stimulation (PAS) and 2) the temporal and spatial components of sequence-specific implicit motor learning. Additionally, relationships between exercise-induced increases in systemic brain-derived neurotrophic factor (BDNF) and response to PAS and motor learning were evaluated. Sixteen young healthy participants completed six experimental sessions, including the following: 1) rest followed by PAS; 2) aerobic exercise followed by PAS; 3) rest followed by practice of a continuous tracking (CT) task and 4) a no-exercise 24-h retention test; and 5) aerobic exercise followed by CT task practice and 6) a no-exercise 24-h retention test. The CT task included an embedded repeated sequence allowing for evaluation of sequence-specific implicit learning. Slope of motor-evoked potential recruitment curves generated with transcranial magnetic stimulation showed larger increases when PAS was preceded by aerobic exercise (59.8% increase) compared with rest (14.2% increase, P = 0.02). Time lag of CT task performance on the repeated sequence improved under the aerobic exercise condition from early (-100.8 ms) to late practice (-75.2 ms, P < 0.001) and was maintained at retention (-79.2 ms, P = 0.004) but did not change under the rest condition (P > 0.16). Systemic BDNF increased on average by 3.4-fold following aerobic exercise (P = 0.003), but the changes did not relate to neurophysiological or behavioral measures (P > 0.42). These results indicate that a single bout of high-intensity aerobic exercise can prime LTP-like neuroplasticity and promote sequence-specific implicit motor learning. PMID:25257866

  6. Multicenter pediatric emergency medicine research and Rhode Island.

    PubMed

    Chun, Thomas H

    2014-01-01

    Multicenter clinical research studies are often needed to address issues of generalizability, conditions with low incidence, adequate statistical power, and potential study bias. While pediatric research networks began work in the 1950s, and Rhode Island physicians have contributed to many of these studies, pediatric emergency medicine (PEM) collaboratives are relative newcomers. Since the mid-1990s, Rhode Island pediatricians have contributed to multicenter studies of diabetic ketoacidosis, bronchiolitis, asthma, quality of PEM care, meningitis, brief interventions for substance use disorders, point-of-care ultrasound, and pre-hospital triage protocols. In 2011, Rhode Island Hospital joined the Pediatric Emergency Care Applied Research Network, the first federally funded pediatric emergency medicine network of its kind. Its mission is to perform high quality, high impact PEM research. Since joining the network, Rhode Island Hospital has quickly become a productive and valued member of the network, portending a bright future for multicenter PEM research in the Ocean State. PMID:24400311

  7. Understanding Facilitation: Theory and Principles.

    ERIC Educational Resources Information Center

    Hogan, Christine

    This book introduces newcomers to the concept of facilitation, and it presents a critical analysis of established and current theory on facilitation for existing practitioners. The following are among the topics discussed: (1) emergence of the field of facilitation; (2) development of facilitation in management; (3) development of facilitation in…

  8. Binding of HTm4 to cyclin-dependent kinase (Cdk)-associated phosphatase (KAP).Cdk2.cyclin A complex enhances the phosphatase activity of KAP, dissociates cyclin A, and facilitates KAP dephosphorylation of Cdk2.

    PubMed

    Chinami, Masanobu; Yano, Yoshihiko; Yang, Xing; Salahuddin, Saira; Moriyama, Kosei; Shiroishi, Mitsunori; Turner, Helen; Shirakawa, Taro; Adra, Chaker N

    2005-04-29

    Cyclin-dependent kinase 2 (cdk2) activation requires phosphorylation of Thr160 and dissociation from cyclin A. The T-loop of cdk2 contains a regulatory phosphorylation site at Thr160. An interaction between cdc-associated phosphatase (KAP) and cdk2 compromises the interaction between cdk2 and cyclin A, which permits access of KAP, a Thr160-directed phosphatase, to its substrate, cdk2. We have reported that KAP is bound and activated by a nuclear membrane protein, HTm4. Here, we present in vitro data showing the direct interaction between the HTm4 C terminus and KAP Tyr141. We show that this interaction not only facilitates access of KAP to Thr160 and accelerates KAP kinetics, but also forces exclusion of cyclin A from the KAP.cdk2 complex. PMID:15671017

  9. Intracluster correlation coefficients for the Brazilian Multicenter Study on Preterm Birth (EMIP): methodological and practical implications

    PubMed Central

    2014-01-01

    Background Cluster-based studies in health research are increasing. An important characteristic of such studies is the presence of intracluster correlation, typically quantified by the intracluster correlation coefficient (ICC), that indicate the proportion of data variability that is explained by the way of clustering. The purpose of this manuscript was to evaluate ICC of variables studied in the Brazilian Multicenter Study on Preterm Birth. Methods This was a multicenter cross-sectional study on preterm births involving 20 referral hospitals in different regions of Brazil plus a nested case–control study to assess associated factors with spontaneous preterm births. Estimated prevalence rates or means, ICC with 95% confidence intervals, design effects and mean cluster sizes were presented for more than 250 maternal and newborn variables. Results Overall, 5296 cases were included in the study (4,150 preterm births and 1,146 term births). ICC ranged from <0.001 to 0.965, with a median of 0.028. For descriptive characteristics (socio-demographic, obstetric history and perinatal outcomes) the median ICC was 0.014, for newborn outcomes the median ICC was 0.041 and for process variables (clinical management and delivery), it was 0.102. ICC was <0.1 in 78.4% of the variables and <0.3 for approximately 95% of them. Most of ICC >0.3 was found in some clinical management aspects well defined in literature such as use of corticosteroids, indicating there was homogeneity in clusters for these variables. Conclusions Clusters selected for Brazilian Multicenter Study on Preterm Birth had mainly heterogeneous findings and these results can help researchers estimate the required sample size for future studies on maternal and perinatal health. PMID:24755392

  10. Formation of Freirian Facilitators.

    ERIC Educational Resources Information Center

    Noble, Phyllis

    This paper is written for people who are already familiar with the philosophy and methodology of Paulo Freire's liberatory education and are interested in creating a formation program for adult education facilitators using his ideas. The author describes the paper as "a collection of thoughts, of things to consider," when organizing such a…

  11. The Inclusion Facilitator's Guide

    ERIC Educational Resources Information Center

    Jorgensen, Cheryl M.; Schuh, Mary C.; Nisbet, Jan

    2005-01-01

    Inclusion facilitators are educators who do more than teach children with disabilities--they advocate for change in schools and communities, sparking a passion for inclusion in teachers, administrators, and families and giving them the practical guidance they need to make it work. This is an essential new role in today's schools, and this guide…

  12. Action Research Facilitator's Handbook.

    ERIC Educational Resources Information Center

    Caro-Bruce, Cathy

    This handbook is a roadmap for action research facilitators to help groups as they work through the research process. It offers quotations, handouts, strategies, resources, and insights from actual experiences. The sections of the handbook follow the action research cycle, focusing on: "What is Action Research?"; "What is the Action Research…

  13. Facilitative Strategies in Action.

    ERIC Educational Resources Information Center

    Fuller, Thara M. A.; Haugabrook, Adrian K.

    2001-01-01

    Describes campus-based strategies to facilitate collaboration by examining the process of restructuring a division of student affairs as an educational partner with academic affairs. Describes three collaborative efforts at the University of Massachusetts Boston: the Beacon Leadership Project, the Diversity Research Initiative, and the Beacon…

  14. Facilitation of Adult Development

    ERIC Educational Resources Information Center

    Boydell, Tom

    2016-01-01

    Taking an autobiographical approach, I tell the story of my experiences facilitating adult development, in a polytechnic and as a management consultant. I relate these to a developmental framework of Modes of Being and Learning that I created and elaborated with colleagues. I connect this picture with a number of related models, theories,…

  15. Methodological Issues on Planning and Running the Brazilian Multicenter Study on Preterm Birth

    PubMed Central

    Lajos, Giuliane J.; Tedesco, Ricardo P.; Passini, Renato; Dias, Tabata Z.; Nomura, Marcelo L.; Rehder, Patrícia M.; Haddad, Samira M.; Sousa, Maria H.; Cecatti, Jose G.; Brazilian Multicenter Study on Preterm Birth Study Group

    2015-01-01

    Objectives. Assuming that the occurrence of preterm births and their maternal and neonatal associated conditions in Brazil are not completely known, a multicenter study was proposed. The purpose of this paper is to describe the methods used, its processes, achievements, and challenges. Study Design. A multicenter cross-sectional study on preterm births in Brazilian facilities plus a nested case-control study to assess their associated factors. A description of all steps of planning and implementing such a nationwide study, including strategies for dealing with problems arising during the process, is presented. Results. 20 referral hospitals in different regions of Brazil participated in the study. A detailed questionnaire for data collection, an electronic platform for data transcription and monitoring, research materials, and specific monitoring tools were developed; then data management and analyses were performed. Finally, we got information on 4,150 preterm births and 1,146 term births. Conclusions. This study represented the first step of a planned comprehensive assessment of preterm birth in Brazil, with detailed information that will lead to several analyses and further studies, bringing the knowledge to improve screening, diagnosis, and treatment practices in maternal and perinatal health with the final purpose of reducing the burden of this condition in the country. PMID:25759862

  16. Implementation of the Exception from Informed Consent Regulations in a Large Multicenter Emergency Clinical Trials Network; the RAMPART Experience

    PubMed Central

    Silbergleit, Robert; Biros, Michelle H.; Harney, Deneil; Dickert, Neal; Baren, Jill

    2012-01-01

    Clinical trials investigating therapies for acutely and critically ill and injured patients in the earliest phases of treatment often can only be performed under regulations allowing for exception from informed consent (EFIC) for emergency research. Implementation of these regulations in multicenter clinical trials involves special challenges and opportunities. The Rapid Anticonvulsant Medication Prior to Arrival Trial (RAMPART), the first EFIC trial conducted by the Neurological Emergencies Treatment Trials (NETT) network, combined centralized resources and coordination with retention of local control and flexibility to facilitate compliance with the EFIC regulations. Specific methods used by the NETT included common tools for community consultation and public disclosure, sharing of experiences and knowledge, and reporting of aggregate results. Tracking of community consultation and public disclosure activities and feedback facilitates empirical research on EFIC methods in the network and supports quality improvements for future NETT trials. The NETT model used in RAMPART demonstrates how EFIC may be effectively performed in established clinical trial networks. PMID:22506949

  17. Infliximab-induced autoantibodies: a multicenter study.

    PubMed

    Vaz, João Luiz Pereira; Fernandes, Vander; Nogueira, Felipe; Arnóbio, Adriano; Levy, Roger A

    2016-02-01

    The purpose of this study was to assess autoantibody incidence in patients treated with infliximab for various diseases, and the development of autoimmune diseases using a multicenter, longitudinal, open-label, phase IV observational study. All patients received anti-tumor necrosis factor (anti-TNF) according to local treatment guidelines. The autoantibodies assessed before and after infliximab treatment were ANA, anti-Sm, anti-dsDNA, anticardiolipin IgM/IgG, anti-Scl70, anti-centromere B, anti-chromatin, anti-ribosomal P, anti-Sm-RNP, anti-RNP A, anti-RNP 68 kD, anti-La/SSB, anti-Ro/SSA 52 kD and 60 kD, and anti-Jo1. ANA was determined by indirect immunofluorescence on HEp-2 cells (INOVA); the remaining was assessed using BioPlexTM 2200. The Fisher exact test, Wilcoxon test, and the McNemar were used when appropriate.Two hundred eighty-six patients were included (139 with rheumatoid arthritis, 77 with ankylosing spondylitis, 29 with inflammatory bowel disease, 27 with psoriatic arthritis, and 14 with psoriasis), 167 females and 119 males, with mean age of 46.3 years. Subjects received at least five infusions of infliximab (6-month treatment). A significant difference was observed in antinuclear antibody (ANA) detection between samplings (p = 0.001). Among patients that had ANA before treatment (n = 92), six became ANA-negative, 48 had increased titers, 29 maintained, and nine decreased titers after treatment; a total of 186 patients had a positive ANA after treatment. Fine speckled nuclear pattern was most commonly observed (both before and after infliximab treatment). The number of patients with anti-dsDNA had a statistically significant increase (p = 0.003). No significant differences were noted for anticardiolipin and the remaining autoantibodies tested. Among the 286 patients included in the study, only one (0.35 %) showed clinical signs of drug-induced lupus, presenting elevated ANA and anti-dsDNA titers that normalized once treatment was

  18. Prospective multicenter international surveillance of azole resistance in Aspergillus fumigatus.

    PubMed

    van der Linden, J W M; Arendrup, M C; Warris, A; Lagrou, K; Pelloux, H; Hauser, P M; Chryssanthou, E; Mellado, E; Kidd, S E; Tortorano, A M; Dannaoui, E; Gaustad, P; Baddley, J W; Uekötter, A; Lass-Flörl, C; Klimko, N; Moore, C B; Denning, D W; Pasqualotto, A C; Kibbler, C; Arikan-Akdagli, S; Andes, D; Meletiadis, J; Naumiuk, L; Nucci, M; Melchers, W J G; Verweij, P E

    2015-06-01

    To investigate azole resistance in clinical Aspergillus isolates, we conducted prospective multicenter international surveillance. A total of 3,788 Aspergillus isolates were screened in 22 centers from 19 countries. Azole-resistant A. fumigatus was more frequently found (3.2% prevalence) than previously acknowledged, causing resistant invasive and noninvasive aspergillosis and severely compromising clinical use of azoles. PMID:25988348

  19. Multicenter historical cohort study of the relationship between shift work and blood pressure

    PubMed Central

    Gholami-Fesharaki, Mohammad; Kazemnejad, Anoshirvan; Zayeri, Farid; Rowzati, Mohsen; Sanati, Javad; Akbari, Hamed

    2014-01-01

    BACKGROUND Regarding the relationship between blood pressure (BP) and shift work (SW), previous studies have reported contradictory results. In the present study, we used Bayesian multilevel modeling to evaluate the association of SW and BP after controlling some confounding factors. METHODS Data of this multicenter historical study were extracted from annual observations of the male workers of Isfahan’s Mobarakeh Steel Company (IMSC) and Polyacryl Iran Corporation (PIC) in Isfahan, Iran, between 2003 and 2011. In this research, we assessed the effect of SW on systolic BP (SBP) and diastolic BP (DPB) with controlling body mass index, age, work experience, marriage, and education status. RESULTS A total of 8613 (IMSC, n = 5314 and PIC, n = 3299) workers participated in this study with a mean [standard deviation (SD)] age of 41.60 (8.30) and mean (SD) work experience of 16.17 (7.89) years. In this study, after controlling confounding factors, we found no significant relationship between SW and SBP and DBP. CONCLUSION In general, the results of this multicenter cohort study did not support a relationship between SW and BP. We suggest prospective studies with controlling more confounding factors in this area. PMID:25815017

  20. Technical success from endovascular aneurysm repair in the post-marketing era: a multicenter prospective trial.

    PubMed

    Naslund, Thomas C; Becker, Stacey Y

    2003-01-01

    Evaluation of post-marketing success with the Ancure Endovascular Graft (AEG) was accomplished by review of a multicenter, prospective trial involving 46 centers and 163 patients. A second cohort of patients (n = 350) treated with the AEG under a controlled-use interval prior to the prospective trial was simultaneously evaluated. Technical success in both groups of patients (96.9% and 97.4%, respectively) was similar to what was reported in pre-market clinical trials. Operative implantation complications unique to the AEG included graft limb stenosis/occlusion in 35.6 and 31.4%, contralateral pull wire being caught on hooks in 33.7 and 28%, failure to seal (type I endoleak) in 17.2 and 18.3%, jacket guard being stuck in 12.9 and 11%, contralateral wire being stuck in 6.8 and 7.1%, high jacket retraction force in 16 and 8.5%, and inability to retract jacket in 1.8 and 0.5% of patients involved in the multicenter trial and controlled-use interval, respectively. One of four patients undergoing conversion in the prospective trial had graft misdeployment as a mode of failure. Three were converted for access failure. The 30-day mortality rate in the prospective trial was 3.7%. Interventions to resolve implantation-related events included stenting, guide catheter manipulations, wire exchanges, and delivery catheter disassembly. These interventions were successful in virtually every case. Open surgical procedures were not needed to correct these operative problems. Results from this study demonstrate excellent technical success with the AEG in the post-market era. Interventions to resolve implantation complications, when utilized, are highly successful in facilitating AEG implantation and providing technical success. PMID:12522699

  1. Positive Emotion Facilitates Audiovisual Binding

    PubMed Central

    Kitamura, Miho S.; Watanabe, Katsumi; Kitagawa, Norimichi

    2016-01-01

    It has been shown that positive emotions can facilitate integrative and associative information processing in cognitive functions. The present study examined whether emotions in observers can also enhance perceptual integrative processes. We tested 125 participants in total for revealing the effects of emotional states and traits in observers on the multisensory binding between auditory and visual signals. Participants in Experiment 1 observed two identical visual disks moving toward each other, coinciding, and moving away, presented with a brief sound. We found that for participants with lower depressive tendency, induced happy moods increased the width of the temporal binding window of the sound-induced bounce percept in the stream/bounce display, while no effect was found for the participants with higher depressive tendency. In contrast, no effect of mood was observed for a simple audiovisual simultaneity discrimination task in Experiment 2. These results provide the first empirical evidence of a dependency of multisensory binding upon emotional states and traits, revealing that positive emotions can facilitate the multisensory binding processes at a perceptual level. PMID:26834585

  2. Propofol sedation versus no sedation in detection of pharyngeal and upper gastrointestinal superficial squamous cell carcinoma using endoscopic narrow band imaging: a multicenter prospective trial

    PubMed Central

    He, Yuqi; Zhao, Yuqing; Fu, Kuangi; Du, Yongqiang; Yu, Jin; Wang, Jianxun; Jin, Peng; Zhao, Xiaojun; Li, Na; Guo, Hua; Li, Jiandong; Zhao, Fayun; Sheng, Jianqiu

    2015-01-01

    Intravenous propofol can provide a superior quality of sedation compared to standard sedation for upper gastrointestinal endoscopy. However, the utility of propofol sedation for the endoscopic early detection of superficial pharyngeal and esophageal squamous cell carcinoma has not been investigated. In a multicenter, prospective trial, 255 patients with esophageal squamous cell carcinomas (ESCCs) were assigned to receive propofol sedation or no sedation according to their own willingness. The primary aim was to compare the detection rates of superficial cancer in the pharyngeal region and the esophagus between two groups. The secondary aim was to evaluate factors associated with technical adequacy. The detection rate was higher in the propofol sedation vs. no sedation group for H&N region (6.06% vs. 2.40%), but not significantly (P=0.22). However, the small lesion (less than 10 mm in diameter) detection rate was higher in sedation vs. no sedation group for H&N region (88.89% vs. 33.33%; P=0.048). The median time for pharyngeal observation in the sedation group was faster than in the no sedation group (20.6 s vs. 44.3 s; P<0.001). Ninety-five percent of H&N region evaluations were totally complete in sedation compared with sixty percent in the no sedation group (P<0.001). The overall p value indicated that only smoking habit was associated with incomplete pharyngeal observation (P<0.05), and it was more difficult to accomplish a complete pharyngeal observation in patients who smoked more than 10 packs per day. Intravenous propofol sedation compared to no intravenous sedation during conventional upper gastrointestinal endoscopy can facilitate a more complete pharyngeal examination and increase the detection rate of superficial H&N squamous cell carcinoma in high risk patients. PMID:26770478

  3. Propofol sedation versus no sedation in detection of pharyngeal and upper gastrointestinal superficial squamous cell carcinoma using endoscopic narrow band imaging: a multicenter prospective trial.

    PubMed

    He, Yuqi; Zhao, Yuqing; Fu, Kuangi; Du, Yongqiang; Yu, Jin; Wang, Jianxun; Jin, Peng; Zhao, Xiaojun; Li, Na; Guo, Hua; Li, Jiandong; Zhao, Fayun; Sheng, Jianqiu

    2015-01-01

    Intravenous propofol can provide a superior quality of sedation compared to standard sedation for upper gastrointestinal endoscopy. However, the utility of propofol sedation for the endoscopic early detection of superficial pharyngeal and esophageal squamous cell carcinoma has not been investigated. In a multicenter, prospective trial, 255 patients with esophageal squamous cell carcinomas (ESCCs) were assigned to receive propofol sedation or no sedation according to their own willingness. The primary aim was to compare the detection rates of superficial cancer in the pharyngeal region and the esophagus between two groups. The secondary aim was to evaluate factors associated with technical adequacy. The detection rate was higher in the propofol sedation vs. no sedation group for H&N region (6.06% vs. 2.40%), but not significantly (P=0.22). However, the small lesion (less than 10 mm in diameter) detection rate was higher in sedation vs. no sedation group for H&N region (88.89% vs. 33.33%; P=0.048). The median time for pharyngeal observation in the sedation group was faster than in the no sedation group (20.6 s vs. 44.3 s; P<0.001). Ninety-five percent of H&N region evaluations were totally complete in sedation compared with sixty percent in the no sedation group (P<0.001). The overall p value indicated that only smoking habit was associated with incomplete pharyngeal observation (P<0.05), and it was more difficult to accomplish a complete pharyngeal observation in patients who smoked more than 10 packs per day. Intravenous propofol sedation compared to no intravenous sedation during conventional upper gastrointestinal endoscopy can facilitate a more complete pharyngeal examination and increase the detection rate of superficial H&N squamous cell carcinoma in high risk patients. PMID:26770478

  4. The oxidation capacity of Mn3O4 nanoparticles is significantly enhanced by anchoring them onto reduced graphene oxide to facilitate regeneration of surface-associated Mn(III).

    PubMed

    Duan, Lin; Wang, Zhongyuan; Hou, Yan; Wang, Zepeng; Gao, Guandao; Chen, Wei; Alvarez, Pedro J J

    2016-10-15

    Metal oxides are often anchored to graphene materials to achieve greater contaminant removal efficiency. To date, the enhanced performance has mainly been attributed to the role of graphene materials as a conductor for electron transfer. Herein, we report a new mechanism via which graphene materials enhance oxidation of organic contaminants by metal oxides. Specifically, Mn3O4-rGO nanocomposites (Mn3O4 nanoparticles anchored to reduced graphene oxide (rGO) nanosheets) enhanced oxidation of 1-naphthylamine (used here as a reaction probe) compared to bare Mn3O4. Spectroscopic analyses (X-ray photoelectron spectroscopy and Fourier transform infrared spectroscopy) show that the rGO component of Mn3O4-rGO was further reduced during the oxidation of 1-naphthylamine, although rGO reduction was not the result of direct interaction with 1-naphthylamine. We postulate that rGO improved the oxidation efficiency of anchored Mn3O4 by re-oxidizing Mn(II) formed from the reaction between Mn3O4 and 1-naphthylamine, thereby regenerating the surface-associated oxidant Mn(III). The proposed role of rGO was verified by separate experiments demonstrating its ability to oxidize dissolved Mn(II) to Mn(III), which subsequently can oxidize 1-naphthylamine. The role of dissolved oxygen in re-oxidizing Mn(II) was ruled out by anoxic (N2-purged) control experiments showing similar results as O2-sparged tests. Opposite pH effects on the oxidation efficiency of Mn3O4-rGO versus bare Mn3O4 were also observed, corroborating the proposed mechanism because higher pH facilitates oxidation of surface-associated Mn(II) even though it lowers the oxidation potential of Mn3O4. Overall, these findings may guide the development of novel metal oxide-graphene nanocomposites for contaminant removal. PMID:27448035

  5. A pragmatic discussion on establishing a multicenter digital imaging network.

    PubMed

    Ingeholm, Mary Lou; Levine, Betty A; Fatemi, Seyed Ali; Moser, And Hugo W

    2002-01-01

    Multicenter clinical trials for therapy evaluation of rare diseases are necessary. A digital imaging network improves the ability to share information between collaborating institutions for adrenoleukodystrophy. The DICOM 3.0 standard is used to move images over the Internet from contributing sites to the central clinical database and on to the reviewing physicians' workstations. Patient confidentiality and data integrity are ensured during transmission using virtual private network technology. Fifteen sites are participating in the network. Of these sites, 6 use the proposed protocol. The other 9 sites have either security policy issues or technical considerations that dictate alternative protocols. Network infrastructure, Internet access, image management practices, and security policies vary significantly between sites. Successful implementation of a multicenter digital imaging network requires flexibility in the implementation of network connectivity. Flexibility increases participation as well as complexity of the network. PMID:12105723

  6. Multi-Center Traffic Management Advisor Operational Field Test Results

    NASA Technical Reports Server (NTRS)

    Farley, Todd; Landry, Steven J.; Hoang, Ty; Nickelson, Monicarol; Levin, Kerry M.; Rowe, Dennis W.

    2005-01-01

    The Multi-Center Traffic Management Advisor (McTMA) is a research prototype system which seeks to bring time-based metering into the mainstream of air traffic control (ATC) operations. Time-based metering is an efficient alternative to traditional air traffic management techniques such as distance-based spacing (miles-in-trail spacing) and managed arrival reservoirs (airborne holding). While time-based metering has demonstrated significant benefit in terms of arrival throughput and arrival delay, its use to date has been limited to arrival operations at just nine airports nationally. Wide-scale adoption of time-based metering has been hampered, in part, by the limited scalability of metering automation. In order to realize the full spectrum of efficiency benefits possible with time-based metering, a much more modular, scalable time-based metering capability is required. With its distributed metering architecture, multi-center TMA offers such a capability.

  7. The Emergence of Career Development Facilitators.

    ERIC Educational Resources Information Center

    Splete, Howard H.; Hoppin, Judith M.

    2000-01-01

    Describes the collaborative efforts of the National Career Development Association, National Occupational Information Coordinating Committee, and Career Development Training Institute at Oakland University, which resulted in the emergence and recognition of the important role of career development facilitators (CDFs). Summarizes the development of…

  8. Gradualness facilitates knowledge refinement.

    PubMed

    Rada, R

    1985-05-01

    To facilitate knowledge refinement, a system should be designed so that small changes in the knowledge correspond to small changes in the function or performance of the system. Two sets of experiments show the value of small, heuristically guided changes in a weighted rule base. In the first set, the ordering among numbers (reflecting certainties) makes their manipulation more straightforward than the manipulation of relationships. A simple credit assignment and weight adjustment strategy for improving numbers in a weighted, rule-based expert system is presented. In the second set, the rearrangement of predicates benefits from additional knowledge about the ``ordering'' among predicates. A third set of experiments indicates the importance of the proper level of granularity when augmenting a knowledge base. Augmentation of one knowledge base by analogical reasoning from another knowledge base did not work with only binary relationships, but did succeed with ternary relationships. To obtain a small improvement in the knowledge base, a substantial amount of structure had to be treated as a unit. PMID:21869290

  9. Facilitating post traumatic growth

    PubMed Central

    Turner, de Sales; Cox, Helen

    2004-01-01

    Background Whilst negative responses to traumatic injury have been well documented in the literature, there is a small but growing body of work that identifies posttraumatic growth as a salient feature of this experience. We contribute to this discourse by reporting on the experiences of 13 individuals who were traumatically injured, had undergone extensive rehabilitation and were discharged from formal care. All participants were injured through involvement in a motor vehicle accident, with the exception of one, who was injured through falling off the roof of a house. Methods In this qualitative study, we used an audio-taped in-depth interview with each participant as the means of data collection. Interviews were transcribed verbatim and analysed thematically to determine the participants' unique perspectives on the experience of recovery from traumatic injury. In reporting the findings, all participants' were given a pseudonym to assure their anonymity. Results Most participants indicated that their involvement in a traumatic occurrence was a springboard for growth that enabled them to develop new perspectives on life and living. Conclusion There are a number of contributions that health providers may make to the recovery of individuals who have been traumatically injured to assist them to develop new views of vulnerability and strength, make changes in relationships, and facilitate philosophical, physical and spiritual growth. PMID:15248894

  10. Process Evaluation in the Multicenter Child and Adolescent Trial for Cardiovascular Health (CATCH).

    ERIC Educational Resources Information Center

    McGraw, Sarah A.; And Others

    1994-01-01

    Includes "Design of Process Evaluation (PE) within the Child and Adolescent Trial for Cardiovascular Health,""Classroom PE in a Multicenter Trial,""Food Service Program PE,""Physical Activity PE,""Family PE,""PE of Environmental Factors and Programs,""Challenges of Conducting PE in a Multicenter Trial." (SK)

  11. Oligonucleotide facilitators may inhibit or activate a hammerhead ribozyme.

    PubMed Central

    Jankowsky, E; Schwenzer, B

    1996-01-01

    Facilitators are oligonucleotides capable of affecting hammerhead ribozyme activity by interacting with the substrate at the termini of the ribozyme. Facilitator effects were determined in vitro using a system consisting of a ribozyme with 7 nucleotides in every stem sequence and two substrates with inverted facilitator binding sequences. The effects of 9mer and 12mer RNA as well as DNA facilitators which bind either adjacent to the 3'- or 5'-end of the ribozyme were investigated. A kinetic model was developed which allows determination of the apparent dissociation constant of the ribozyme-substrate complex from single turnover reactions. We observed a decreased dissociation constant of the ribozyme-substrate complex due to facilitator addition corresponding to an additional stabilization energy of delta delta G=-1.7 kcal/mol with 3'-end facilitators. The cleavage rate constant was increased by 3'-end facilitators and decreased by 5'-end facilitators. Values for Km were slightly lowered by all facilitators and kcat was increased by 3'-end facilitators and decreased by 5'-end facilitators in our system. Generally the facilitator effects increased with the length of the facilitators and RNA provided greater effects than DNA of the same sequence. Results suggest facilitator influences on several steps of the hammerhead reaction, substrate association, cleavage and dissociation of products. Moreover, these effects are dependent in different manners on ribozyme and substrate concentration. This leads to the conclusion that there is a concentration dependence whether activation or inhibition is caused by facilitators. Conclusions are drawn with regard to the design of hammerhead ribozyme facilitator systems. PMID:8602353

  12. Calculations of fast ion collisions with multi-center molecular targets

    NASA Astrophysics Data System (ADS)

    Kirchner, Tom

    2011-05-01

    The theoretical treatment of ion-molecule collisions is challenging for several reasons: the systems have many degrees of freedom, a rather complex geometry, and the electron dynamics might be nonperturbative and involve electron-electron interaction effects. However, the interest in accurate calculations has been growing recently. An important reason for this development is the relevance of ion-molecule collisions for a number of fields, such as atmospheric science, and the understanding of radiation damage of biological tissue. We have developed a new approach to meet these challenges. It disregards rovibrational motion, but it does address the multi-center geometry of the system and the generally nonperturbative nature of the electron dynamics. The key ingredients are an expansion of the initially populated molecular orbitals in terms of a single-center basis and a spectral representation of the molecular Hamiltonian. This facilitates a separation of molecular geometry and collision dynamics and makes it possible to use well-established ion-atom methods with relatively minor modifications. We have extended our basis generator method to deal with the collision dynamics and report on results for ionization and fragmentation of water molecules by proton and He+ ion impact over wide ranges of collision energies. For the case of He+ impact this will include a discussion of effects due to the presence of the projectile electron. This work has been supported by the Natural Sciences and Engineering Research Council of Canada.

  13. Multicenter Analysis of Long-Term Oncologic Impact of Anastomotic Leakage After Laparoscopic Total Mesorectal Excision

    PubMed Central

    Kang, Jeonghyun; Choi, Gyu-Seog; Oh, Jae Hwan; Kim, Nam Kyu; Park, Jun Seok; Kim, Min Jung; Lee, Kang Young; Baik, Seung Hyuk

    2015-01-01

    Abstract This study aims to validate the oncologic outcomes of anastomotic leakage (AL) after laparoscopic total mesorectal excision (TME) in a large multicenter cohort. The impact of AL after laparoscopic TME for rectal cancer surgery has not yet been clearly described. This was a multicenter retrospective study of 1083 patients who underwent laparoscopic TME for nonmetastatic rectal cancer (stage 0–III). AL was defined as an anastomotic complication within 30 days of surgery irrespective of requiring a reoperation or interventional radiology. Estimated local recurrence (LR), disease-free survival (DFS), and overall survival (OS) were compared between the leakage group and the no leakage group using the log-rank method. Multivariate Cox-regression analysis was used to adjust confounding for survival. The incidence of AL was 6.4%. Mortality within 30 days of surgery occurred in 1 patient (1.4%) in the leakage group and 2 patients (0.2%) in the no leakage group. The leakage group showed a higher LR rate (6.4% vs 1.8%, P = 0.011). Five-year DFS and OS were significantly lower in the leakage group than the no leakage group (DFS 71.7% vs 82.1%, P = 0.016, OS 81.8% vs 93.5%, P = 0.007). Multivariate analysis showed that AL was an independent poor prognostic factor for DFS and OS (hazard ratio [HR] = 1.6; 95% confidence intervals [CI]: 1.0–2.6; P = 0.042, HR = 2.1; 95% CI: 1.0–4.2; P = 0.028, respectively). AL after laparoscopic TME was significantly associated with an increased rate of LR, systemic recurrence and poor OS. PMID:26200636

  14. Split liver transplantation: Report of right and left graft outcomes from a multicenter Argentinean group.

    PubMed

    Halac, Esteban; Dip, Marcelo; Quiñonez, Emilio; Alvarez, Fernando; Espinoza, Johana Leiva; Romero, Pablo; Nievas, Franco; Maurette, Rafael; Luque, Carlos; Matus, Daniel; Surraco, Paz; Fauda, Martin; McCormack, Lucas; Mattera, Francisco J; Gondolesi, Gabriel; Imventarza, Oscar

    2016-01-01

    Grafts from split livers (SLs) constitute an accepted approach to expand the donor pool. Over the last 5 years, most Argentinean centers have shown significant interest in increasing the use of this technique. The purpose of this article is to describe and analyze the outcomes of right-side grafts (RSGs) and left-side grafts (LSGs) from a multicenter study. The multicenter retrospective study included data from 111 recipients of SL grafts from between January 1, 2009 and December 31, 2013. Incidence of surgical complications, patient and graft survival, and factors that affected RSG and LSG survival were analyzed. Grafts types were 57 LSG and 54 RSG. Median follow-up times for LSG and RSG were 46 and 42 months, respectively. The 36-month patient and graft survivals for LSG were 83% and 79%, respectively, and for RSG were 78% and 69%, respectively. Retransplantation rates for LSG and RSG were 3.5% and 11%, respectively. Arterial complications were the most common cause of early retransplantation (less than 12 months). Cold ischemia time (CIT) longer than 10 hours and the use of high-risk donors (age ≥ 40 years or body mass index ≥ 30 kg/m2 or ≥ 5 days intensive care unit stay) were independent factors for diminished graft survival in RSG. None of the analyzed variables were associated with worse graft survival in LSG. Biliary complications were the most frequent complications in both groups (57% in LSG and 33% in RSG). Partial grafts obtained from liver splitting are an excellent option for patients in need of liver transplantation and have the potential to alleviate the organ shortage. Adequate donor selection and reducing CIT are crucial for optimizing results. PMID:26369269

  15. Automated Telecommunication to Obtain Longitudinal Follow-up in a Multicenter Cross-sectional COPD Study

    PubMed Central

    Stewart, Jeffrey I.; Moyle, Sarah; Criner, Gerard J.; Wilson, Carla; Tanner, Ron; Bowler, Russell P.; Crapo, James D.; Zeldin, Robert K.; Make, Barry J.; Regan, Elizabeth A.

    2013-01-01

    Background It can be challenging to maintain longitudinal follow-up of subjects in clinical studies. COPDGene is a multicenter, observational study designed to identify genetic factors associated with COPD and to characterize COPD-related phenotypes. To obtain follow-up data on patient's vital status and outcomes, the COPDGene Longitudinal Follow-up (LFU) Program was developed to supplement its parent study. Methods/Results We used a telecommunication system that employed automated telephone contact or web-based questions to obtain longitudinal follow-up data in our subjects. A branching questionnaire asked about exacerbations, new therapies, smoking status, development of co-morbid conditions, and general health status. Study coordinators contacted subjects who did not respond to one of the automated methods. We enrolled 10,383 subjects in the COPDGene study. As of August 29, 2011, 7,959 subjects completed 19,955 surveys. On the first survey, 68.8% of subjects who completed their survey did so by electronic means, while 31.3% required coordinator phone follow-up. On each subsequent survey the number of subjects who completed their survey by electronic means increased, while the number of subjects who required coordinator follow-up decreased. Despite many of the patients in the cohort being chronically ill and elderly, there was broad acceptance of the system with over half the cohort using electronic response methods. Conclusions The COPDGene LFU Study demonstrated that telecommunications was an effective way to obtain longitudinal follow-up of subjects in a large multicenter study. Web-based and automated phone contacts are accepted by research subjects and could serve as a model for LFU in future studies. PMID:22676387

  16. Structural MRI correlates of cognitive impairment in patients with multiple sclerosis: A Multicenter Study.

    PubMed

    Preziosa, Paolo; Rocca, Maria A; Pagani, Elisabetta; Stromillo, Maria Laura; Enzinger, Christian; Gallo, Antonio; Hulst, Hanneke E; Atzori, Matteo; Pareto, Deborah; Riccitelli, Gianna C; Copetti, Massimiliano; De Stefano, Nicola; Fazekas, Franz; Bisecco, Alvino; Barkhof, Frederik; Yousry, Tarek A; Arévalo, Maria J; Filippi, Massimo

    2016-04-01

    In a multicenter setting, we applied voxel-based methods to different structural MR imaging modalities to define the relative contributions of focal lesions, normal-appearing white matter (NAWM), and gray matter (GM) damage and their regional distribution to cognitive deficits as well as impairment of specific cognitive domains in multiple sclerosis (MS) patients. Approval of the institutional review boards was obtained, together with written informed consent from all participants. Standardized neuropsychological assessment and conventional, diffusion tensor and volumetric brain MRI sequences were collected from 61 relapsing-remitting MS patients and 61 healthy controls (HC) from seven centers. Patients with ≥2 abnormal tests were considered cognitively impaired (CI). The distribution of focal lesions, GM and WM atrophy, and microstructural WM damage were assessed using voxel-wise approaches. A random forest analysis identified the best imaging predictors of global cognitive impairment and deficits of specific cognitive domains. Twenty-three (38%) MS patients were CI. Compared with cognitively preserved (CP), CI MS patients had GM atrophy of the left thalamus, right hippocampus and parietal regions. They also showed atrophy of several WM tracts, mainly located in posterior brain regions and widespread WM diffusivity abnormalities. WM diffusivity abnormalities in cognitive-relevant WM tracts followed by atrophy of cognitive-relevant GM regions explained global cognitive impairment. Variable patterns of NAWM and GM damage were associated with deficits in selected cognitive domains. Structural, multiparametric, voxel-wise MRI approaches are feasible in a multicenter setting. The combination of different imaging modalities is needed to assess and monitor cognitive impairment in MS. PMID:26833969

  17. Multicenter Evaluation of a Nonweekend Reading Schedule for Radiometric Pyrazinamide Susceptibility Testing of Mycobacterium tuberculosis

    PubMed Central

    Madison, B.; Gross, W.; George, I.; Sloutsky, A.; Washabaugh, G.; Robinson-Dunn, B.; Lipman, H.; Metchock, B.; Mazurek, G.; Ridderhof, J.

    2002-01-01

    Pyrazinamide (PZA) is an integral component of the short-course chemotherapy regimen for tuberculosis. The BACTEC 460TB PZA susceptibility test for Mycobacterium tuberculosis with a daily (D) reading schedule has been available for more than 10 years, but weekend laboratory staffing is necessary. A nonweekend (NW) reading schedule has not been validated in a multicenter study. This prospective multicenter study compares the interlaboratory reproducibility of PZA susceptibility results by following both the D and NW schedules. A total of 181 cultures were shared among four laboratories. Isolates were selected based on resistance or borderline resistance to at least one streptomycin-isoniazid-rifampin-ethambutol drug or PZA. One laboratory used a D reading schedule, and three laboratories used a NW schedule. Both reading schedules are based on the standard BACTEC 460TB PZA protocol. With the NW schedule, the growth index (GI) is not available for test interpretation on Saturday, Sunday, and Monday. Of the 181 shared cultures, 154 were found to be susceptible by all laboratories, 19 were found to be resistant, and 8 had discordant results. The overall pairwise interlaboratory agreement was 97.7%. The discrepancies were not associated with the type of reading schedule used. However, the median control GI was significantly higher for the NW schedule (321) than for the D schedule (259) (P < 0.0001) although results were available on average in about 7 days from setup for both schedules. These results show that the NW schedule is a suitable alternative for laboratories that do not read and interpret PZA susceptibility tests on weekends. PMID:12354876

  18. Splice-variant changes of the CaV3.2 T-type calcium channel mediate voltage-dependent facilitation and associate with cardiac hypertrophy and development

    PubMed Central

    David, Laurence S; Garcia, Esperanza; Cain, Stuart M; Thau, Elana M; Tyson, John R

    2010-01-01

    Low voltage-activated T-type calcium (Ca) channels contribute to the normal development of the heart and are also implicated in pathophysiological states such as cardiac hypertrophy. Functionally distinct T-type Ca channel isoforms can be generated by alternative splicing from each of three different T-type genes (CaV3.1, CaV3.2, CaV3.3), although it remains to be described whether specific splice variants are associated with developmental states and pathological conditions. We aimed to identify and functionally characterize CaV3.2 T-type Ca channel alternatively spliced variants from newborn animals and to compare with adult normotensive and spontaneously hypertensive rats (SHR). DNA sequence analysis of full-length CaV3.2 cDNA generated from newborn heart tissue identified ten major regions of alternative splicing, the more common variants of which were analyzed by quantitative real-time PCR (qRT-PCR) and also subject to functional examination by whole-cell patch clamp. The main findings are that: (1) cardiac CaV3.2 T-type Ca channels are subject to considerable alternative splicing, (2) there is preferential expression of CaV3.2(−25) splice variant channels in newborn rat heart with a developmental shift in adult heart that results in approximately equal levels of expression of both (+25) and (−25) exon variants, (3) in the adult stage of hypertensive rats there is both an increase in overall CaV3.2 expression and a shift towards expression of CaV3.2(+25) containing channels as the predominant form and (4) alternative splicing confers a variant-specific voltage-dependent facilitation of CaV3.2 channels. We conclude that CaV3.2 alternative splicing generates significant T-type Ca channel structural and functional diversity with potential implications relevant to cardiac developmental and pathophysiological states. PMID:20699644

  19. Facilitating Dialogues about Racial Realities

    ERIC Educational Resources Information Center

    Quaye, Stephen John

    2014-01-01

    Background/Context: Facilitating dialogues about racial issues in higher education classroom settings continues to be a vexing problem facing postsecondary educators. In order for students to discuss race with their peers, they need skilled facilitators who are knowledgeable about racial issues and able to support students in these difficult…

  20. ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS): The study methodology, recruitment, and baseline demographic and disease characteristics

    PubMed Central

    Mitsumoto, Hiroshi; Factor-Litvak, Pam; Andrews, Howard; Goetz, Raymond R.; Andrews, Leslie; Rabkin, Judith G.; McElhiney, Martin; Nieves, Jeri; Santella, Regina M.; Murphy, Jennifer; Hupf, Jonathan; Singleton, Jess; Merle, David; Kilty, Mary; Heitzman, Daragh; Bedlack, Richard S.; Miller, Robert G; Katz, Jonathan S.; Forshew, Dallas; Barohn, Richard J.; Sorenson, Eric J.; Oskarsson, Bjorn; Filho, J Americo M. Fernandes; Kasarskis, Edward J.; Lomen-Hoerth, Catherine; Mozaffar, Tahseen; Rollins, Yvonne D.; Nations, Sharon P.; Swenson, Andrea J.; Shefner, Jeremy M.; Andrews, Jinsy A.; Koczon-Jaremko, Boguslawa A.

    2015-01-01

    Objective In a multicenter study of newly diagnosed ALS patients without a reported family history of ALS, we are prospectively investigating whether markers of oxidative stress (OS) are associated with disease progression. Methods An extensive structured telephone interview ascertained environmental, lifestyle, dietary and psychological risk factors associated with OS. Detailed assessments were performed at baseline and at 3 to 6 month intervals during the ensuing 30 months. Our biorepository includes DNA, plasma, urine, and skin. Results 355 patients were recruited. Subjects were enrolled over a 36 month-period at 16 sites. To meet the target number of subjects, the recruitment period was prolonged and additional sites were included. Demographic and disease characteristics were similar between 477 eligible/non-enrolled and enrolled patients, with the only difference being type of health insurance among enrolled patients. Sites were divided into 3 groups by the number of enrolled subjects. Comparing these 3 groups, the Columbia site had fewer “definite ALS” diagnoses. Conclusion This is the first prospective, interdisciplinary, in-depth, multicenter epidemiological investigation of OS related to ALS progression and was accomplished by an aggressive recruitment process. The baseline demographic and disease features of the study sample are now fully characterized. PMID:24564738

  1. [Multidrug resistance in Klebsiella pneumoniae: multicenter study].

    PubMed

    Boutiba-Ben Boubaker, Ilhem; Ben Salah, Dorra; Besbes, Makram; Mahjoubi, Faouzia; Ghozzi, Rafiaa; Ben Redjeb, Saida; Ben Hassen, Assia; Hammami, Adnène

    2002-01-01

    The extensive use of broad spectrum antibiotics, especially the third generation cephalosporins (C3G), was followed by the emergence of newer plasmid mediated betalactamases called extended spectrum betalactamases (ESBLs). To assess the impact of K. pneumoniae resistant to 3GC in Tunisia, this study was conducted in 3 teaching hospitals. A total of 1110 strains of K pneumoniae was collected. The antibiotics susceptibilities were tested by diffusion method using Mueller-Hinton agar. The quality control was regularly performed. I ESBLs producing solates were detected using the double-disc synergy test. Data analysis was done using the Whonet 4 software. 23.6% K. pneumoniae isolates showed phenotype pattern of ESBLs producers. The double-disc synergy test was positive in 75% of the cases. These isolates were recovered from hospitalized patients in different wards but mainly from pediatrics (23.6%), medicine (23.2%), surgery (22.9%), intensive care units (11%) and neonatology (11%). 54% were isolated from urines, 22% from blood cultures. These isolates remained susceptible to imipenem (100%) and most of them to cefoxitin (96.4%) but all had associated resistance to aminoglycosides, quinolones and trimethoprim-sulfamethoxazole. The prevalence of multidrug resistant K. pneumoniae is high. This resistance can be minimized by the implementation of infection control measures including handwashing and isolation procedures. PMID:12071040

  2. Multicentered black holes with a negative cosmological constant

    NASA Astrophysics Data System (ADS)

    Chimento, Samuele; Klemm, Dietmar

    2014-01-01

    We present a recipe that allows us to construct multicentered black holes embedded in an arbitrary Friedmann-Lemaître-Robertson-Walker (FLRW) universe. These solutions are completely determined by a function satisfying the conformal Laplace equation on the spatial slices E3, S3, or H3. Since anti-de Sitter (AdS) space can be written in FLRW coordinates, this includes as a special case multicentered black holes in AdS, in the sense that, far away from the black holes, the energy density and the pressure approach the values given by a negative cosmological constant. We study in some detail the physical properties of the single-centered asymptotically AdS case, which does not coincide with the usual Reissner-Nordström-AdS black hole, but is highly dynamical. In particular, we determine the curvature singularities and trapping horizons of this solution, compute the surface gravity of the trapping horizons, and show that the generalized first law of black hole dynamics proposed by Hayward holds in this case. It turns out that the spurious big bang/big crunch singularities that appear when one writes AdS in FLRW form become real in the presence of these dynamical black holes. This implies that actually only one point of the usual conformal boundary of AdS survives in the solutions that we construct. Finally, a generalization to arbitrary dimension is also presented.

  3. Review of rank-based procedures for multicenter clinical trials.

    PubMed

    Rashid, M Mushfiqur; McKean, Joseph W; Kloke, John D

    2013-01-01

    This article reviews nonparametric alternatives to the mixed model normal theory analysis for the analyses of multicenter clinical trials. Under a mixed model, the traditional analysis is based on maximum likelihood theory under normal errors. This analysis, though, is not robust to outliers. Robust, rank-based, Wilcoxon-type procedures are reviewed for a multicenter clinical trial for the mixed model but without the assumption of normality. These procedures retain the high efficiency of Wilcoxon methods for simple location problems and are based on a fitting criterion which is robust to outliers in response space. A simple weighting scheme can be employed so that the procedures are robust to outliers in factor (design) space as well as response space. These rank-based analyses offer a complete analysis, including estimation of fixed effects and their standard errors, and tests of linear hypotheses. Both rank-based estimates of contrasts and individual treatment effects are reviewed. We illustrate the analyses using real data from a clinical trial. PMID:24138428

  4. Subregional Basal Forebrain Atrophy in Alzheimer's Disease: A Multicenter Study

    PubMed Central

    Kilimann, Ingo; Grothe, Michel; Heinsen, Helmut; Alho, Eduardo Joaquim Lopez; Grinberg, Lea; Amaro, Edson; dos Santos, Gláucia Aparecida Bento; da Silva, Rafael Emídio; Mitchell, Alex J.; Frisoni, Giovanni B.; Bokde, Arun L.W.; Fellgiebel, Andreas; Filippi, Massimo; Hampel, Harald; Klöppel, Stefan; Teipel, Stefan J.

    2014-01-01

    Histopathological studies in Alzheimer's disease (AD) suggest severe and region-specific neurodegeneration of the basal forebrain cholinergic system (BFCS). Here, we studied the between-center reliability and diagnostic accuracy of MRI-based BFCS volumetry in a large multicenter data set, including participants with prodromal (n = 41) or clinically manifest AD (n = 134) and 148 cognitively healthy controls. Atrophy was determined using voxel-based and region-of-interest based analyses of high-dimensionally normalized MRI scans using a newly created map of the BFCS based on postmortem in cranio MRI and histology. The AD group showed significant volume reductions of all subregions of the BFCS, which were most pronounced in the posterior nucleus basalis Meynert (NbM). The mild cognitive impairment-AD group showed pronounced volume reductions in the posterior NbM, but preserved volumes of anterior-medial regions. Diagnostic accuracy of posterior NbM volume was superior to hippocampus volume in both groups, despite higher multicenter variability of the BFCS measurements. The data of our study suggest that BFCS morphometry may provide an emerging biomarker in AD. PMID:24503619

  5. Chest radiographic data acquisition and quality assurance in multicenter studies

    PubMed Central

    Schluchter, Mark; Wood, Beverly P.; Berdon, Walter E.; Boechat, M. Ines; Easley, Kirk A.; Meziane, Moulay; Mellins, Robert B.; Norton, Karen I.; Singleton, Edward; Trautwein, Lynn

    2015-01-01

    Background Multicenter studies rely on data derived from different institutions. Forms can be designed to standardize the reporting process allowing reliable comparison of data. Objective The purpose of the report is to provide a standardized method, developed as a part of a multicenter study of vertically transmitted HIV, for assessing chest radiographic results. Materials and methods Eight hundred and five infants and children were studied at five centers; 3057 chest radiographs were scored. Data were entered using a forced-choice, graded response for 12 findings. Quality assurance measures and inter- rater agreement statistics are reported. Results The form used for reporting chest radiographic results is presented. Inter-rater agreement was moderate to high for most findings, with the best correlation reported for the presence of bronchovascular markings and/or reticular densities addressed as a composite question (kappa = 0.71). The presence of nodular densities (kappa = 0.56) and parenchymal consolidation (kappa = 0.57) had moderate agreement. Agreement for lung volume was low. Conclusion The current tool, developed for use in the pediatric population, is applicable to any study involving the assessment of pediatric chest radiographs for a large population, whether at one or many centers. PMID:9361051

  6. Effects of Short-Term Facilitation Training on Attitudes.

    ERIC Educational Resources Information Center

    Meadows, Mark E.; And Others

    This study investigated the effects of facilitation training upon the attitude of administrators and lead teachers toward their professional associates. The project consisted of a 3-day workshop in facilitative communication involving 25 participants and four trainers. Exercises designed to improve ability to respond with empathy, positive regard,…

  7. Prospective study of attitudinal and relationship predictors of sexual risk in the multicenter AIDS cohort study.

    PubMed

    Ostrow, David G; Silverberg, Michael J; Cook, Robert L; Chmiel, Joan S; Johnson, Lisette; Li, Xiuhong; Jacobson, Lisa P

    2008-01-01

    We examined the influence of attitudes concerning HIV transmission, safe sex, and sexual sensation seeking, as well as negotiated risk reduction with primary partners, on the proportion of unprotected sexual partners (%UASP) among men who have sex with men (MSM). Participants were 263 HIV-seropositive and 238 HIV-seronegative MSM in the Multicenter AIDS Cohort Study between 1999 and 2003 who completed a 20-item attitude survey twice. Behavioral data were collected concurrently and 6-12 months after each survey. Among seropositives, decreased HIV concern and increased safer sex fatigue were associated with higher %UASP at 6 and 12 months. Among seronegatives, increased %UASP at 12 months was associated with safer sex fatigue. At 6 months and 12 months, risk reduction agreements were associated with increased %UASP among seronegatives in seroconcordant monogamous relationships, reflecting their abandonment of condoms in such partnerships. We conclude that HIV prevention efforts should target modifiable attitudes (reduced concern about HIV and safer sex fatigue) and increases in sexual risk-taking of MSM, particularly among HIV+ men having sex with serodiscordant partners. PMID:17410419

  8. Collinear facilitation in color vision.

    PubMed

    Huang, Pi-Chun; Mullen, Kathy T; Hess, Robert F

    2007-01-01

    The detection of a luminance-defined Gabor is improved by two high contrast, aligned, flanking Gabors, an effect termed collinear facilitation. We investigate whether this facilitation also occurs for isoluminant chromatic stimuli, and whether it can occur for chromatic targets with luminance flanks and vice versa. We measured collinear facilitation for Gabor stimuli (0.75 cpd, 1 octave bandwidth) of three different contrast types: achromatic, red-green that isolates the L/M-cone opponent mechanism, and blue-yellow that isolates the S-cone opponent mechanism. Three conditions were investigated: (1) target and flanks all of the same contrast type and spatial phase; (2) target and flanks of the same contrast type but opposite phases (0 degrees and 180 degrees ); and (3) target and flanks of different contrast types (chromatic with achromatic contrast) and two opposite phase combinations. We find that a similar degree of collinear facilitation occurs for the isoluminant chromatic stimuli as for the achromatic stimuli, and all exhibit phase dependency. Facilitation did not occur, however, between chromatic and achromatic target and flanking stimuli. This suggests that at the level of collinear facilitation, the chromatic and the achromatic postreceptoral mechanisms have their own spatial interactions that are segregated from one another. PMID:17997661

  9. ICA-based artifact removal diminishes scan site differences in multi-center resting-state fMRI

    PubMed Central

    Feis, Rogier A.; Smith, Stephen M.; Filippini, Nicola; Douaud, Gwenaëlle; Dopper, Elise G. P.; Heise, Verena; Trachtenberg, Aaron J.; van Swieten, John C.; van Buchem, Mark A.; Rombouts, Serge A. R. B.; Mackay, Clare E.

    2015-01-01

    Resting-state fMRI (R-fMRI) has shown considerable promise in providing potential biomarkers for diagnosis, prognosis and drug response across a range of diseases. Incorporating R-fMRI into multi-center studies is becoming increasingly popular, imposing technical challenges on data acquisition and analysis, as fMRI data is particularly sensitive to structured noise resulting from hardware, software, and environmental differences. Here, we investigated whether a novel clean up tool for structured noise was capable of reducing center-related R-fMRI differences between healthy subjects. We analyzed three Tesla R-fMRI data from 72 subjects, half of whom were scanned with eyes closed in a Philips Achieva system in The Netherlands, and half of whom were scanned with eyes open in a Siemens Trio system in the UK. After pre-statistical processing and individual Independent Component Analysis (ICA), FMRIB's ICA-based X-noiseifier (FIX) was used to remove noise components from the data. GICA and dual regression were run and non-parametric statistics were used to compare spatial maps between groups before and after applying FIX. Large significant differences were found in all resting-state networks between study sites before using FIX, most of which were reduced to non-significant after applying FIX. The between-center difference in the medial/primary visual network, presumably reflecting a between-center difference in protocol, remained statistically significant. FIX helps facilitate multi-center R-fMRI research by diminishing structured noise from R-fMRI data. In doing so, it improves combination of existing data from different centers in new settings and comparison of rare diseases and risk genes for which adequate sample size remains a challenge. PMID:26578859

  10. Fluoxetine Facilitates Fear Extinction Through Amygdala Endocannabinoids

    PubMed Central

    Gunduz-Cinar, Ozge; Flynn, Shaun; Brockway, Emma; Kaugars, Katherine; Baldi, Rita; Ramikie, Teniel S; Cinar, Resat; Kunos, George; Patel, Sachin; Holmes, Andrew

    2016-01-01

    Pharmacologically elevating brain endocannabinoids (eCBs) share anxiolytic and fear extinction-facilitating properties with classical therapeutics, including the selective serotonin reuptake inhibitor, fluoxetine. There are also known functional interactions between the eCB and serotonin systems and preliminary evidence that antidepressants cause alterations in brain eCBs. However, the potential role of eCBs in mediating the facilitatory effects of fluoxetine on fear extinction has not been established. Here, to test for a possible mechanistic contribution of eCBs to fluoxetine's proextinction effects, we integrated biochemical, electrophysiological, pharmacological, and behavioral techniques, using the extinction-impaired 129S1/Sv1mJ mouse strain. Chronic fluoxetine treatment produced a significant and selective increase in levels of anandamide in the BLA, and an associated decrease in activity of the anandamide-catabolizing enzyme, fatty acid amide hydrolase. Slice electrophysiological recordings showed that fluoxetine-induced increases in anandamide were associated with the amplification of eCB-mediated tonic constraint of inhibitory, but not excitatory, transmission in the BLA. Behaviorally, chronic fluoxetine facilitated extinction retrieval in a manner that was prevented by systemic or BLA-specific blockade of CB1 receptors. In contrast to fluoxetine, citalopram treatment did not increase BLA eCBs or facilitate extinction. Taken together, these findings reveal a novel, obligatory role for amygdala eCBs in the proextinction effects of a major pharmacotherapy for trauma- and stressor-related disorders and anxiety disorders. PMID:26514583

  11. Fluoxetine Facilitates Fear Extinction Through Amygdala Endocannabinoids.

    PubMed

    Gunduz-Cinar, Ozge; Flynn, Shaun; Brockway, Emma; Kaugars, Katherine; Baldi, Rita; Ramikie, Teniel S; Cinar, Resat; Kunos, George; Patel, Sachin; Holmes, Andrew

    2016-05-01

    Pharmacologically elevating brain endocannabinoids (eCBs) share anxiolytic and fear extinction-facilitating properties with classical therapeutics, including the selective serotonin reuptake inhibitor, fluoxetine. There are also known functional interactions between the eCB and serotonin systems and preliminary evidence that antidepressants cause alterations in brain eCBs. However, the potential role of eCBs in mediating the facilitatory effects of fluoxetine on fear extinction has not been established. Here, to test for a possible mechanistic contribution of eCBs to fluoxetine's proextinction effects, we integrated biochemical, electrophysiological, pharmacological, and behavioral techniques, using the extinction-impaired 129S1/Sv1mJ mouse strain. Chronic fluoxetine treatment produced a significant and selective increase in levels of anandamide in the BLA, and an associated decrease in activity of the anandamide-catabolizing enzyme, fatty acid amide hydrolase. Slice electrophysiological recordings showed that fluoxetine-induced increases in anandamide were associated with the amplification of eCB-mediated tonic constraint of inhibitory, but not excitatory, transmission in the BLA. Behaviorally, chronic fluoxetine facilitated extinction retrieval in a manner that was prevented by systemic or BLA-specific blockade of CB1 receptors. In contrast to fluoxetine, citalopram treatment did not increase BLA eCBs or facilitate extinction. Taken together, these findings reveal a novel, obligatory role for amygdala eCBs in the proextinction effects of a major pharmacotherapy for trauma- and stressor-related disorders and anxiety disorders. PMID:26514583

  12. Lateralization in cluster headache: a Nordic multicenter study.

    PubMed

    Meyer, Eva Laudon; Laurell, Katarina; Artto, Ville; Bendtsen, Lars; Linde, Mattias; Kallela, Mikko; Tronvik, Erling; Zwart, John-Anker; Jensen, Rikke M; Hagen, Knut

    2009-08-01

    A slight predominance of cluster pain on the right side has been reported in several studies. The aim of this large retrospective Nordic multicenter study was to estimate the prevalence of right- and left-sided pain in cluster headache (CH) patients with side-locked pain, the prevalence of side shifts in episodic and chronic CH patients, and the occurrence of cranial autonomic symptoms related to pain side. Among 383 cluster patients, 55 (14%) had experienced pain side shift. Of the remaining 328 individuals without side shift, there was no significant difference between the occurrence of right-sided and left-sided pain (54 vs. 46%). The prevalence of side shift was similar for episodic and chronic CH and the occurrence of cranial autonomic symptoms was not influenced by the pain side. In conclusion, previous reports of a side difference in location of cluster pain could not be confirmed in this large Nordic sample. PMID:19495933

  13. Thromboembolism after foot and ankle surgery. A multicenter study.

    PubMed

    Mizel, M S; Temple, H T; Michelson, J D; Alvarez, R G; Clanton, T O; Frey, C C; Gegenheimer, A P; Hurwitz, S R; Lutter, L D; Mankey, M G; Mann, R A; Miller, R A; Richardson, E G; Schon, L C; Thompson, F M; Yodlowski, M L

    1998-03-01

    Thromboembolic disease presents a potentially fatal complication to patients undergoing orthopaedic surgery. Although the incidence after hip and knee surgery has been studied and documented, its incidence after surgery of the foot and ankle is unknown. For this reason, a prospective multicenter study was undertaken to identify patients with clinically evident thromboembolic disease to evaluate potential risk factors. Two thousand seven hundred thirty-three patients were evaluated for preoperative risk factors and postoperative thromboembolic events. There were six clinically significant thromboembolic events, including four nonfatal pulmonary emboli, after foot and ankle surgery. The incidence of deep vein thrombosis was six of 2733 (0.22%) and that of nonfatal pulmonary emboli was four of 2733 (0.15%). Factors found to correlate with an increased incidence of deep vein thrombosis were nonweightbearing status and immobilization after surgery. On the basis of these results, routine prophylaxis for thromboembolic disease after foot and ankle surgery probably is not warranted. PMID:9553551

  14. Forming a Research Question from a Multi-Center Database

    PubMed Central

    Likosky, Donald S.

    2009-01-01

    Abstract: It is not uncommon for individuals to ask biostatisiticians and epidemiologists to assist them with a research project. Often the request is in the shape of statistical analyses. However, most of these requests are nothing more than missed opportunities. This manuscript focuses on the reasons underlying such a statement. Most individuals might say that the most important aspect of a study is its conclusion. Many who would disagree with this sentiment and would feel that the most important aspect of a study rather is the question it intends to address. If this question is not articulated sufficiently, any additional information stemming from the study will most likely be irrelevant. Herein, some principles for formulating (successfully) a question from a multi-center database will be described. PMID:19361039

  15. Early sedation and clinical outcomes of mechanically ventilated patients: a prospective multicenter cohort study

    PubMed Central

    2014-01-01

    Introduction Sedation overuse is frequent and possibly associated with poor outcomes in the intensive care unit (ICU) patients. However, the association of early oversedation with clinical outcomes has not been thoroughly evaluated. The aim of this study was to assess the association of early sedation strategies with outcomes of critically ill adult patients under mechanical ventilation (MV). Methods A secondary analysis of a multicenter prospective cohort conducted in 45 Brazilian ICUs, including adult patients requiring ventilatory support and sedation in the first 48 hours of ICU admissions, was performed. Sedation depth was evaluated after 48 hours of MV. Multivariate analysis was used to identify variables associated with hospital mortality. Results A total of 322 patients were evaluated. Overall, ICU and hospital mortality rates were 30.4% and 38.8%, respectively. Deep sedation was observed in 113 patients (35.1%). Longer duration of ventilatory support was observed (7 (4 to 10) versus 5 (3 to 9) days, P = 0.041) and more tracheostomies were performed in the deep sedation group (38.9% versus 22%, P = 0.001) despite similar PaO2/FiO2 ratios and acute respiratory distress syndrome (ARDS) severity. In a multivariate analysis, age (Odds Ratio (OR) 1.02; 95% confidence interval (CI) 1.00 to 1.03), Charlson Comorbidity Index >2 (OR 2.06; 95% CI, 1.44 to 2.94), Simplified Acute Physiology Score 3 (SAPS 3) score (OR 1.02; CI 95%, 1.00 to 1.04), severe ARDS (OR 1.44; CI 95%, 1.09 to 1.91) and deep sedation (OR 2.36; CI 95%, 1.31 to 4.25) were independently associated with increased hospital mortality. Conclusions Early deep sedation is associated with adverse outcomes and constitutes an independent predictor of hospital mortality in mechanically ventilated patients. PMID:25047960

  16. Singing can facilitate foreign language learning.

    PubMed

    Ludke, Karen M; Ferreira, Fernanda; Overy, Katie

    2014-01-01

    This study presents the first experimental evidence that singing can facilitate short-term paired-associate phrase learning in an unfamiliar language (Hungarian). Sixty adult participants were randomly assigned to one of three "listen-and-repeat" learning conditions: speaking, rhythmic speaking, or singing. Participants in the singing condition showed superior overall performance on a collection of Hungarian language tests after a 15-min learning period, as compared with participants in the speaking and rhythmic speaking conditions. This superior performance was statistically significant (p < .05) for the two tests that required participants to recall and produce spoken Hungarian phrases. The differences in performance were not explained by potentially influencing factors such as age, gender, mood, phonological working memory ability, or musical ability and training. These results suggest that a "listen-and-sing" learning method can facilitate verbatim memory for spoken foreign language phrases. PMID:23860945

  17. Factors influencing the quality of postoperative epidural analgesia: an observational multicenter study

    PubMed Central

    Wranicz, Piotr; Andersen, Hege; Nordbø, Arve; Kongsgaard, Ulf E

    2014-01-01

    Background Epidural analgesia (EDA) is used widely for postoperative pain treatment. However, studies have reported a failure rate of EDA of up to 30%. We aimed to evaluate the quality of postoperative EDA in patients undergoing a laparotomy in five Norwegian hospitals. Methods This was a multicenter observational study in patients undergoing a laparotomy with epidural-based postoperative analgesia. Data were registered at three time points. Technical aspects, infusion rates, pain intensity, assessment procedures, side effects, and satisfaction of patients and health personnel were recorded. The use of other pain medications and coanalgesics was registered. Results Three hundred and seventeen patients were included. Pain control at rest was satisfactory in 89% of patients at 24 hours and in 91% at 48 hours. Pain control when coughing was satisfactory in 62% at 24 hours and in 59% at 48 hours. The spread of hypoesthesia was consistent for each individual patient but varied between patients. The hypoesthetic area was not associated with pain intensity, and the precision of the EDA insertion point was not associated with the pain score. Few side effects were reported. EDA was regarded as effective and functioning well by 64% of health personnel. Conclusion EDA was an effective method for postoperative pain relief at rest but did not give sufficient pain relief during mobilization. The use of cold stimulation to assess the spread of EDA had limited value as a clinical indicator of the efficacy of postoperative pain control. Validated tools for the control of EDA quality are needed. PMID:25206312

  18. Incidence of Malignancy after Living Kidney Transplantation: A Multicenter Study from Iran

    PubMed Central

    Einollahi, Behzad; Rostami, Zohreh; Nourbala, Mohammad Hossein; Lessan-Pezeshki, Mahboob; Simforoosh, Naser; Nemati, Eghlim; Pourfarziani, Vahid; Beiraghdar, Fatemeh; Nafar, Mohsen; Pour-Reza-Gholi, Fatemeh; Mazdeh, Mitra Mahdavi; Amini, Manochehr; Ahmadpour, Pedram; Makhdoomi, Khadijeh; Ghafari, Ali; Ardalan, Mohammad Reza; Khosroshahi, Hamid Taebi; Oliaei, Farshid; Shahidi, Shahrzad; Abbaszadeh, Shahin; Fatahi, Mohammad Reza; Hiedari, Fatemeh; Makhlogh, Atehieh; Azmandian, Jalal; Samimagham, Hamid Reza; Shahbazian, Heshmatollah; Nazemian, Fatemeh; Naghibi, Massih; Khosravi, Masoud; Monfared, Ali; Mosavi, Seyed Majid; Ahmadi, Javad; Jalalzadeh, Mojgan

    2012-01-01

    Malignancy is a common complication after renal transplantation. However, limited data are available on post-transplant malignancy in living kidney transplantation. Therefore, we made a plan to evaluate the incidence and types of malignancies, association with the main risk factors and patient survival in a large population of living kidney transplantation. We conducted a large retrospective multicenter study on 12525 renal recipients, accounting for up to 59% of all kidney transplantation in Iran during 22 years follow up period. All information was collected from observation of individual notes or computerized records for transplant patients. Two hundred and sixty-six biopsy-proven malignancies were collected from 16 Transplant Centers in Iran; 26 different type of malignancy categorized in 5 groups were detected. The mean age of patients was 46.2±12.9 years, mean age at tumor diagnosis was 50.8±13.2 years and average time between transplantation and detection of malignancy was 50.0±48.4 months. Overall tumor incidence in recipients was 2%. Kaposis' sarcoma was the most common type of tumor. The overall mean survival time was 117.1 months (95% CI: 104.9-129.3). In multivariate analysis, the only independent risk factor associated with mortality was type of malignancy. This study revealed the lowest malignancy incidence in living unrelated kidney transplantation. PMID:22712025

  19. Reducing Contrast-Induced Acute Kidney Injury Using a Regional Multicenter Quality Improvement Intervention

    PubMed Central

    Brown, Jeremiah R.; Solomon, Richard J.; Sarnak, Mark J.; McCullough, Peter A.; Splaine, Mark E.; Davies, Louise; Ross, Cathy S.; Dauerman, Harold L.; Stender, Janette L.; Conley, Sheila M.; Robb, John F.; Chaisson, Kristine; Boss, Richard; Lambert, Peggy; Goldberg, David J.; Lucier, Deborah; Fedele, Frank A.; Kellett, Mirle A.; Horton, Susan; Phillips, William J.; Downs, Cynthia; Wiseman, Alan; MacKenzie, Todd A.; Malenka, David J.

    2016-01-01

    Background Contrast-induced acute kidney injury (CI-AKI) is associated with increased morbidity and mortality following percutaneous coronary interventions (PCI) and is a patient safety objective of the National Quality Forum. However, no formal quality improvement program to prevent CI-AKI has been conducted. Therefore, we sought to determine if a six-year regional multi-center quality improvement intervention could reduce CI-AKI following PCI. Methods and Results We conducted a prospective multi-center quality improvement study to prevent CI-AKI (serum creatinine increase ≥0.3 mg/dL within 48 hours or ≥50% during hospitalization) among 21,067 non-emergent patients undergoing PCI at ten hospitals between 2007 and 2012. Six ‘intervention’ hospitals participated in the quality improvement intervention. Two hospitals with significantly lower baseline rates of CI-AKI, which served as “benchmark” sites and were used to develop the intervention and two hospitals not receiving the intervention were used as controls. Using time series analysis and multilevel poisson regression clustering to the hospital-level we calculated adjusted risk ratios (RR) for CI-AKI comparing the intervention period to baseline. Adjusted rates of CI-AKI were significantly reduced in hospitals receiving the intervention by 21% (RR 0.79; 95%CI: 0.67 to 0.93; p=0.005) for all patients and by 28% in patients with baseline eGFR<60 ml/min/1.73 m2 (RR 0.72; 95%CI: 0.56 to 0.91; p=0.007). Benchmark hospitals had no significant changes in CI-AKI. Key qualitative system factors associated with improvement included: multidisciplinary teams, limiting contrast volume, standardized fluid orders, intravenous fluid bolus, and patient education about oral hydration. Conclusions Simple cost-effective quality improvement interventions can prevent up to one in five CI-AKI events in patients with undergoing non-emergent PCI. PMID:25074372

  20. Oral Lymphoma Prevalence in Iranian Population: A Multicenter Retrospective Study

    PubMed Central

    Akbari, Mohammad Esmaeil; Bastani, Zahra; Mokhtari, Sepideh; Atarbashi Moghadam, Saede

    2015-01-01

    Background: Oral lymphoma is the second most common malignancy of the head and neck region after malignant epithelial tumors. Objectives: Considering the lack of a multicenter study on the frequency of oral lymphoma in Iran, this study aimed to assess the relative frequency of oral lymphomas in Iran during a 6-year period. Materials and Methods: This multicenter, retrospective, cross-sectional study was conducted in two phases. In the first phase, cases of oral lymphoma registered in the cancer research center (CRC) of Shahid Beheshti university of medical sciences were extracted. The patient records and pathology reports of these patients were retrieved from the archives and age, sex and microscopic type site of the lesions were evaluated. Results: Oral lymphoma accounts for 1% of head and neck malignancies and 8% of all lymphomas. From 2003 to 2008, a total of 437 new cases of oral lymphomas had been registered in the CRC. Diffuse large B-cell lymphoma was found to be the most common form of oral lymphoma in the 6-year period with 240 (54.9%) registered cases. The majority of detected cases were in the 6th and 7th decades of life with a male to female ratio of 1:84. Tonsils were the most common site of occurrence of lymphoma in the oral cavity (77.8%). Conclusions: The age of onset, site of involvement, sex of patients, and histopathological subtype of oral lymphomas in the Iranian population were found to be similar to those of most other countries. PMID:26855724

  1. Descriptive Epidemiology of the Multicenter ACL Revision Study (MARS) Cohort

    PubMed Central

    2013-01-01

    Background Revision anterior cruciate ligament (ACL) reconstruction has worse outcomes than primary reconstructions. Predictors for these worse outcomes are not known. The Multicenter ACL Revision Study (MARS) Group was developed to perform a multisurgeon, multicenter prospective longitudinal study to obtain sufficient subjects to allow multivariable analysis to determine predictors of clinical outcome. Purpose To describe the formation of MARS and provide descriptive analysis of patient demographics and clinical features for the initial 460 enrolled patients to date in this prospective cohort. Study Design Cross-sectional study; Level of evidence, 2. Methods After training and institutional review board approval, surgeons began enrolling patients undergoing revision ACL reconstruction, recording patient demographics, previous ACL reconstruction methods, intra-articular injuries, and current revision techniques. Enrolled subjects completed a questionnaire consisting of validated patient-based outcome measures. Results As of April 1, 2009, 87 surgeons have enrolled a total of 460 patients (57% men; median age, 26 years). For 89%, the reconstruction was the first revision. Mode of failure as deemed by the revising surgeon was traumatic (32%), technical (24%), biologic (7%), combination (37%), infection (<1%), and no response (<1%). Previous graft present at the time of injury was 70% autograft, 27% allograft, 2% combination, and 1% unknown. Sixty-two percent were more than 2 years removed from their last reconstruction. Graft choice for revision ACL reconstruction was 45% autograft, 54% allograft, and more than 1% both allograft and autograft. Meniscus and/or chondral damage was found in 90% of patients. Conclusion The MARS Group has been able to quickly accumulate the largest revision ACL reconstruction cohort reported to date. Traumatic reinjury is deemed by surgeons to be the most common single mode of failure, but a combination of factors represents the most

  2. Multi-Center Electronic Structure Calculations for Plasma Equation of State

    SciTech Connect

    Wilson, B G; Johnson, D D; Alam, A

    2010-12-14

    We report on an approach for computing electronic structure utilizing solid-state multi-center scattering techniques, but generalized to finite temperatures to model plasmas. This approach has the advantage of handling mixtures at a fundamental level without the imposition of ad hoc continuum lowering models, and incorporates bonding and charge exchange, as well as multi-center effects in the calculation of the continuum density of states.

  3. Family Presence during Resuscitation: A Qualitative Analysis from a National Multicenter Randomized Clinical Trial

    PubMed Central

    De Stefano, Carla; Normand, Domitille; Jabre, Patricia; Azoulay, Elie; Kentish-Barnes, Nancy; Lapostolle, Frederic; Baubet, Thierry; Reuter, Paul-Georges; Javaud, Nicolas; Borron, Stephen W.; Vicaut, Eric; Adnet, Frederic

    2016-01-01

    Background The themes of qualitative assessments that characterize the experience of family members offered the choice of observing cardiopulmonary resuscitation (CPR) of a loved one have not been formally identified. Methods and Findings In the context of a multicenter randomized clinical trial offering family members the choice of observing CPR of a patient with sudden cardiac arrest, a qualitative analysis, with a sequential explanatory design, was conducted. The aim of the study was to understand family members’ experience during CPR. All participants were interviewed by phone at home three months after cardiac arrest. Saturation was reached after analysis of 30 interviews of a randomly selected sample of 75 family members included in the trial. Four themes were identified: 1- choosing to be actively involved in the resuscitation; 2- communication between the relative and the emergency care team; 3- perception of the reality of the death, promoting acceptance of the loss; 4- experience and reactions of the relatives who did or did not witness the CPR, describing their feelings. Twelve sub-themes further defining these four themes were identified. Transferability of our findings should take into account the country-specific medical system. Conclusions Family presence can help to ameliorate the pain of the death, through the feeling of having helped to support the patient during the passage from life to death and of having participated in this important moment. Our results showed the central role of communication between the family and the emergency care team in facilitating the acceptance of the reality of death. PMID:27253993

  4. Rationale and design of the Multicenter Medication Reconciliation Quality Improvement Study (MARQUIS)

    PubMed Central

    2013-01-01

    Background Unresolved medication discrepancies during hospitalization can contribute to adverse drug events, resulting in patient harm. Discrepancies can be reduced by performing medication reconciliation; however, effective implementation of medication reconciliation has proven to be challenging. The goals of the Multi-Center Medication Reconciliation Quality Improvement Study (MARQUIS) are to operationalize best practices for inpatient medication reconciliation, test their effect on potentially harmful unintentional medication discrepancies, and understand barriers and facilitators of successful implementation. Methods Six U.S. hospitals are participating in this quality improvement mentored implementation study. Each hospital has collected baseline data on the primary outcome: the number of potentially harmful unintentional medication discrepancies per patient, as determined by a trained on-site pharmacist taking a “gold standard” medication history. With the guidance of their mentors, each site has also begun to implement one or more of 11 best practices to improve medication reconciliation. To understand the effect of the implemented interventions on hospital staff and culture, we are performing mixed methods program evaluation including surveys, interviews, and focus groups of front line staff and hospital leaders. Discussion At baseline the number of unintentional medication discrepancies in admission and discharge orders per patient varies by site from 2.35 to 4.67 (mean=3.35). Most discrepancies are due to history errors (mean 2.12 per patient) as opposed to reconciliation errors (mean 1.23 per patient). Potentially harmful medication discrepancies averages 0.45 per patient and varies by site from 0.13 to 0.82 per patient. We discuss several barriers to implementation encountered thus far. In the end, we anticipate that MARQUIS tools and lessons learned have the potential to decrease medication discrepancies and improve patient outcomes. Trial

  5. Facilitation of learning: part 1.

    PubMed

    Warburton, Tyler; Trish, Houghton; Barry, Debbie

    2016-04-01

    This article, the fourth in a series of 11, discusses the context for the facilitation of learning. It outlines the main principles and theories for understanding the process of learning, including examples which link these concepts to practice. The practical aspects of using these theories in a practice setting will be discussed in the fifth article of this series. Together, these two articles will provide mentors and practice teachers with knowledge of the learning process, which will enable them to meet the second domain of the Nursing and Midwifery Council's Standards to Support Learning and Assessment in Practice on facilitation of learning. PMID:27050014

  6. Clinical features and outcomes of gastric variceal bleeding: retrospective Korean multicenter data

    PubMed Central

    Kim, Moon Young; Baik, Soon Koo; Seo, Yeon Seok; Park, Soo Young; Lee, Jung Il; Lee, Jin Woo; Cheon, Gab Jin; Sohn, Joo Hyun; Kim, Tae Yeob; Lim, Young Suk; Kim, Tae Hyo; Lee, Tae Hee; Park, Sung Jae; Park, Seung Ha; Kim, Jin Dong; Han, Sang Young; Choi, Chang Soo; Cho, Eun Young; Kim, Dong Joon; Hwang, Jae Seok; Jang, Byoung Kuk; Lee, June Sung; Kim, Sang Gyune; Kim, Young Seok; Kwon, So Young; Choe, Won Hyeok; Lee, Chang Hyeong; Kim, Byung Seok; Jang, Jae Young; Jeong, Soung Won; Kim, Byung Ho; Shim, Jae Jun; Cho, Yong Kyun; Koh, Moon Soo; Lee, Hyun Woong

    2013-01-01

    Background/Aims While gastric variceal bleeding (GVB) is not as prevalent as esophageal variceal bleeding, it is reportedly more serious, with high failure rates of the initial hemostasis (>30%), and has a worse prognosis than esophageal variceal bleeding. However, there is limited information regarding hemostasis and the prognosis for GVB. The aim of this study was to determine retrospectively the clinical outcomes of GVB in a multicenter study in Korea. Methods The data of 1,308 episodes of GVB (males:females=1062:246, age=55.0±11.0 years, mean±SD) were collected from 24 referral hospital centers in South Korea between March 2003 and December 2008. The rates of initial hemostasis failure, rebleeding, and mortality within 5 days and 6 weeks of the index bleed were evaluated. Results The initial hemostasis failed in 6.1% of the patients, and this was associated with the Child-Pugh score [odds ratio (OR)=1.619; P<0.001] and the treatment modality: endoscopic variceal ligation, endoscopic variceal obturation, and balloon-occluded retrograde transvenous obliteration vs. endoscopic sclerotherapy, transjugular intrahepatic portosystemic shunt, and balloon tamponade (OR=0.221, P<0.001). Rebleeding developed in 11.5% of the patients, and was significantly associated with Child-Pugh score (OR=1.159, P<0.001) and treatment modality (OR=0.619, P=0.026). The GVB-associated mortality was 10.3%; mortality in these cases was associated with Child-Pugh score (OR=1.795, P<0.001) and the treatment modality for the initial hemostasis (OR=0.467, P=0.001). Conclusions The clinical outcome for GVB was better for the present cohort than in previous reports. Initial hemostasis failure, rebleeding, and mortality due to GVB were universally associated with the severity of liver cirrhosis. PMID:23593608

  7. The DNA Methyltransferase Dnmt1 Directly Interacts with the SET and RING Finger-associated (SRA) Domain of the Multifunctional Protein Uhrf1 to Facilitate Accession of the Catalytic Center to Hemi-methylated DNA*

    PubMed Central

    Berkyurek, Ahmet Can; Suetake, Isao; Arita, Kyohei; Takeshita, Kohei; Nakagawa, Atsushi; Shirakawa, Masahiro; Tajima, Shoji

    2014-01-01

    Dnmt1 is responsible for the maintenance DNA methylation during replication to propagate methylation patterns to the next generation. The replication foci targeting sequence (RFTS), which plugs the catalytic pocket, is necessary for recruitment of Dnmt1 to the replication site. In the present study we found that the DNA methylation activity of Dnmt1 was DNA length-dependent and scarcely methylated 12-bp short hemi-methylated DNA. Contrarily, the RFTS-deleted Dnmt1 and Dnmt1 mutants that destroyed the hydrogen bonds between the RFTS and catalytic domain showed significant DNA methylation activity even toward 12-bp hemi-methylated DNA. The DNA methylation activity of the RFTS-deleted Dnmt1 toward 12-bp hemi-methylated DNA was strongly inhibited on the addition of RFTS, but to a lesser extent by Dnmt1 harboring the mutations that impair the hydrogen bond formation. The SRA domain of Uhrf1, which is a prerequisite factor for maintenance methylation and selectively binds to hemi-methylated DNA, stimulated the DNA methylation activity of Dnmt1. The SRA to Dnmt1 concentration ratio was the determinant for the maximum stimulation. In addition, a mutant SRA, which had lost the DNA binding activity but was able to bind to Dnmt1, stimulated the DNA methylation activity of Dnmt1. The results indicate that the DNA methylation activity of Dnmt1 was stimulated on the direct interaction of the SRA and Dnmt1. The SRA facilitated acceptance of the 12-bp fluorocytosine-containing DNA by the catalytic center. We propose that the SRA removes the RFTS plug from the catalytic pocket to facilitate DNA acceptance by the catalytic center. PMID:24253042

  8. Code stroke: multicenter experience with in-hospital stroke alerts.

    PubMed

    Cumbler, Ethan; Simpson, Jennifer

    2015-03-01

    Between 2.2% and 17% of all strokes have symptom onset during hospitalization in a patient originally admitted for another diagnosis or procedure. A response system to rapidly evaluate inpatients with acute neurologic symptoms facilitates evaluation and treatment of stroke developing during hospitalization. The National Stroke Association implemented an in-hospital stroke quality-improvement initiative from July 2010 to June 2011 in 6 certified stroke centers from Michigan, South Carolina, Pennsylvania, Colorado, Washington, and North Carolina. Three hundred ninety-three in-hospital stroke alerts were examined over a 1-year period. Of the alerts, 42.5% were for ischemic stroke, 8.7% probable or possible TIA, 2.8% intracranial hemorrhage, and 46.1% were stroke mimics. The most common stroke mimics were seizure, hypotension, and delirium. Participating hospitals had an alarm rate for diagnoses other than acute cerebrovascular events ranging from 28.0% to 66.7%. Of 194 in-hospital stroke/transient ischemic attack cases, 8.2% received intravenous thrombolysis alone, 10.3% received intra-arterial/mechanical thrombolysis alone, and 1% received both. No patient with a stroke mimic received thrombolysis. Our findings suggest that in-hospital response teams need to be prepared to respond to a range of acute medical conditions other than ischemic stroke. PMID:25537887

  9. SUPERFUND GROUNDWATER ISSUE - FACILITATED TRANSPORT

    EPA Science Inventory

    The Regional Superfund Ground Water Forum is a group of ground-water scientists representing EPA's Regional Superfund Offices, organized to exchange up to date information related to ground-water remediation at Superfund sites. Facilitated transport is an issue identified by the ...

  10. Facilitation of Mourning During Childhood.

    ERIC Educational Resources Information Center

    Kliman, Gilbert; And Others

    This paper discusses case studies of children psychologically disturbed by the death of parents or siblings. Illustrations of mourning facilitation were mainly gathered from 16 orphaned children, ages 3-14. Some techniques used in helping children mourn include: discussing physical details of the illness, discussing previous deaths of animals and…

  11. Facilitating Conditions for School Motivation.

    ERIC Educational Resources Information Center

    Yeung, Alexander Seeshing; McInerney, Dennis M.

    Primary and high school students (277 in grades 5-6; 615 in grades 7-12) in the United States (47 percent boys) responded to 26 items of the Facilitating Conditions Questionnaire (FCQ). Results indicate 7 distinct FCQ factors: perceived value of schooling; affect toward schooling; peer positive academic climate (Peer Positive); encouragement from…

  12. Producing gestures facilitates route learning.

    PubMed

    So, Wing Chee; Ching, Terence Han-Wei; Lim, Phoebe Elizabeth; Cheng, Xiaoqin; Ip, Kit Yee

    2014-01-01

    The present study investigates whether producing gestures would facilitate route learning in a navigation task and whether its facilitation effect is comparable to that of hand movements that leave physical visible traces. In two experiments, we focused on gestures produced without accompanying speech, i.e., co-thought gestures (e.g., an index finger traces the spatial sequence of a route in the air). Adult participants were asked to study routes shown in four diagrams, one at a time. Participants reproduced the routes (verbally in Experiment 1 and non-verbally in Experiment 2) without rehearsal or after rehearsal by mentally simulating the route, by drawing it, or by gesturing (either in the air or on paper). Participants who moved their hands (either in the form of gestures or drawing) recalled better than those who mentally simulated the routes and those who did not rehearse, suggesting that hand movements produced during rehearsal facilitate route learning. Interestingly, participants who gestured the routes in the air or on paper recalled better than those who drew them on paper in both experiments, suggesting that the facilitation effect of co-thought gesture holds for both verbal and nonverbal recall modalities. It is possibly because, co-thought gesture, as a kind of representational action, consolidates spatial sequence better than drawing and thus exerting more powerful influence on spatial representation. PMID:25426624

  13. Casebook of Selected State Facilitators.

    ERIC Educational Resources Information Center

    Network of Innovative Schools, Inc., Andover, MA.

    The U.S. Office of Education's National Diffusion Network is designed to transport and systematically promote the adoption of validated innovative programs throughout the nation. The 13 case studies in this publication are intended to provide a comprehensive overview of the state facilitator effort and accurately represent the range and diversity…

  14. Twelve tips for facilitating team-based learning

    PubMed Central

    Gullo, Charles; Ha, Tam Cam; Cook, Sandy

    2015-01-01

    Abstract Background: Team-based learning (TBL) has become a more commonly recognized and implemented pedagogical approach in curricula of numerous disciplines. The desire to place more autonomy on the student and spend less in-class time delivering content has resulted in complete or partial adoption of this style of learning in many educational settings. Aim: Provide faculty with tools that foster a well facilitated and interactive TBL learning environment. Methods: We examined the published literature in the area of facilitation – specifically in TBL environments, and explored learning theories associated with team learning and our own experiences to create these facilitation tips. Results: We created 12 tips for TBL facilitation designed to assist faculty to achieve an effective and engaging TBL learning environment. Conclusions: Applying these twelve tips while facilitating a TBL classroom session will help to ensure maximal participation and optimal learning in a safe yet stimulating environment. PMID:25665624

  15. EFFECTS OF SYNDEMICS ON HIV VIRAL LOAD AND MEDICATION ADHERENCE IN THE MULTICENTER AIDS COHORT STUDY

    PubMed Central

    FRIEDMAN, M. Reuel; STALL, Ron; PLANKEY, Michael; WEI, Chongyi; SHOPTAW, Steve; HERRICK, Amy; SURKAN, Pamela J.; TEPLIN, Linda; SILVESTRE, Anthony J.

    2015-01-01

    OBJECTIVES To determine associations between intertwining epidemics (syndemics) and HIV medication adherence and viral load levels among HIV-positive men who have sex with men (MSM); and to test whether adherence mediates the relationship between syndemics and viral load. DESIGN We analyzed participant data collected between 2003—2009 from the Multicenter AIDS Cohort Study, a prospective HIV/AIDS cohort study in four U.S. cities. METHODS We conducted longitudinal analyses (repeated measures mixed models) to assess if differences in viral load levels, undetectable viral load, and self-reported HIV medication adherence were associated with count of syndemic conditions (substance use, depression symptoms, and sexual risk behavior, range 0 to 3), adjusting for race/ethnicity, age, and income. Mediation analyses were conducted using structural equation modeling and the SAS %mediate macro. RESULTS Syndemics count was associated with higher viral loads (p<.0001) and lower adherence (p<.0001). Increased counts of concomitant syndemics were associated with viral load (p <.01), detectable viral load (p <.05), and adherence (p <.001). Black MSM experienced worse outcomes across domains than White MSM (p <.0001) and experienced higher overall rates of syndemics (p<.01). Adherence significantly mediated the relationship between syndemics and viral load, accounting for an estimated 32.3% of the effect (p<.05). CONCLUSIONS Effectively lowering viral load levels among MSM has implications for both HIV/AIDS prevention and care. Our findings suggest that integrating substance use interventions, mental health care, and sexual risk prevention into standard HIV care may be necessary to optimize treatment and Treatment as Prevention (TasP) models. PMID:25870981

  16. Subclinical coronary atherosclerosis, HIV infection and antiretroviral therapy: Multicenter AIDS Cohort Study

    PubMed Central

    Kingsley, Lawrence A.; Cuervo-Rojas, Juliana; Muñoz, Alvaro; Palella, Frank J.; Post, Wendy; Witt, Mallory D.; Budoff, Matthew; Kuller, Lewis

    2010-01-01

    Objective To evaluate the association of HIV infection and cumulative exposure to highly active antiretroviral therapy (HAART) with the presence and extent of coronary artery calcification (CAC). Design A cross-sectional study of 947 male participants (332 HIV-seronegative, 84 HAART-naive and 531 HAART-experienced HIV-infected) from the Multicenter AIDS Cohort Study. Methods The main outcome was CAC score calculated as the geometric mean of the Agatston scores of two computed tomography replicates. Presence of CAC was defined as calcification score above 10, and extent of CAC by the score for those with CAC present. Multivariable regression was used to evaluate the association between HIV infection and HAART and presence and extent of calcification. Results Increasing age was most strongly associated with both prevalence and extent of CAC for all study groups. After adjustment for age, race, family history, smoking, high-density lipoprotein-C, low-density lipoprotein-C and hypertension, HIV infection (odds ratio, 1.35; 95% confidence interval, 0.70, 2.61) and long-term HAART use (odds ratio, 1.33; 95% confidence interval, 0.87, 2.05) increased the odds for presence of CAC. In contrast, after adjustment for these covariates, the extent of CAC was lower among HAART users. Among those not taking lipid-lowering therapy, HAART usage of at least 8 years was associated with significantly reduced CAC scores (relative CAC score, 0.43; 95% confidence interval, 0.24, 0.79). Conclusion HAART use may have different effects on the presence and extent of coronary calcification. Although prevalence of calcification was marginally increased among long-term HAART users, the extent of calcification was significantly reduced among HAART users compared with HIV-seronegative controls. PMID:18670218

  17. Developmental outcomes of children with congenital diaphragmatic hernia: a multicenter prospective study

    PubMed Central

    Wynn, Julia; Aspelund, Gudrun; Zygmunt, Annette; Stolar, Charles JH.; Mychaliska, George; Butcher, Jennifer; Lim, Foong-Yen; Gratton, Teresa; Potoka, Douglas; Brennan, Kate; Azarow, Ken; Jackson, Barbara; Needelman, Howard; Crombleholme, Timothy; Zhang, Yuan; Duong, Jimmy; Arkovitz, Marc S.; Chung, Wendy K.; Farkouh, Christiana

    2013-01-01

    Purpose To determine developmental outcomes and associated factors in patients with congenital diaphragmatic hernia (CDH) at two years of age. Methods This is a multicenter prospective study of a CDH birth cohort. Clinical and socioeconomic data were collected. Bayley Scales of Infant Development (BSID-III) and Vineland Adaptive Behavior Scales (VABS-II) were performed at two years of age. Results BSID-III and VABS-II assessments were completed on 48 and 49 children, respectively. The BSID-III mean cognitive, language, and motor scores were significantly below the norm mean with average scores of 93 +/− 15, 95 +/−16, and 95 +/− 11. Ten percent (5/47) scored more than two standard deviations below the norm on one or more domains. VABS-II scores were similar to BSID-III scores with mean communication, daily living skills, social, motor, adaptive behavior scores of 97 +/−14, 94+/−16, 93 +/− 13, 97+/− 10, and 94 +/− 14. For the BSID-III, supplemental oxygen at 28 days, a prenatal diagnosis, need for extracorporeal membrane oxygenation (ECMO) and exclusive tube feeds at time of discharge were associated with lower scores. At two years of age, history of hospital readmission and need for tube feeds were associated with lower scores. Lower socioeconomic status correlated with lower developmental scores when adjusted for significant health factors. Conclusion CDH patients on average have lower developmental scores at two years of age compared to the norm. A need for ECMO, oxygen at 28 days of life, ongoing health issues and lower socioeconomic status are factors associated with developmental delays. PMID:24094947

  18. Predictors of Enteral Autonomy in Children with Intestinal Failure: A Multicenter Cohort Study

    PubMed Central

    Khan, Faraz A.; Squires, Robert H.; Litman, Heather J.; Balint, Jane; Carter, Beth A.; Fisher, Jeremy G.; Horslen, Simon P.; Jaksic, Tom; Kocoshis, Samuel; Martinez, J. Andres; Mercer, David; Rhee, Susan; Rudolph, Jeffrey A.; Soden, Jason; Sudan, Debra; Superina, Riccardo A.; Teitelbaum, Daniel H.; Venick, Robert; Wales, Paul W.; Duggan, Christopher

    2015-01-01

    Objectives In a large cohort of children with intestinal failure (IF), we sought to determine the cumulative incidence of achieving enteral autonomy and identify patient and institutional characteristics associated with enteral autonomy. Study design A multicenter retrospective cohort analysis from the Pediatric Intestinal Failure Consortium (PIFCon) was performed. IF was defined as severe congenital or acquired gastrointestinal diseases during infancy with PN dependence >60 days. Enteral autonomy was defined as PN discontinuation >3 months. Results 272 infants were followed for a median (IQR) of 33.5(16.2, 51.5) months. Enteral autonomy was achieved in 118(43%); 36(13%) remained PN dependent and 118 (43%) patients died or underwent transplantation. Multivariable analysis identified NEC [OR 95% CI: 2.42 (1.33, 4.47)], care at an IF site without an associated intestinal transplant (ITx) program [OR 2.73 (1.56, 4.78)] and an intact ileocecal valve (ICV) [OR 2.80 (1.63, 4.83)] as independent risk factors for enteral autonomy. A second model (n=144) including only patients with intra-operatively measured residual small bowel length (RSB) found NEC [OR 3.44 (1.36, 8.71)], care at a non-ITx center [OR 6.56 (2.53, 16.98)] and RSB (cm) [OR 1.04 (1.02, 1.06)] to be independently associated with enteral autonomy. Conclusions A substantial proportion of infants with IF can achieve enteral autonomy. Underlying NEC, preserved ICV and longer bowel length are associated with achieving enteral autonomy. It is likely that variations in institutional practices and referral patterns also affect outcomes in children with IF. PMID:25917765

  19. Proteinuria as a Therapeutic Target in Advanced Chronic Kidney Disease: a Retrospective Multicenter Cohort Study

    PubMed Central

    Chen, Chang-Hsu; Wu, Hon-Yen; Wang, Chieh-Li; Yang, Feng-Jung; Wu, Pei-Chen; Hung, Szu-Chun; Kan, Wei-Chih; Yang, Chung-Wei; Chiang, Chih-Kang; Huang, Jenq-Wen; Hung, Kuan-Yu

    2016-01-01

    Current evidence of proteinuria reduction as a surrogate target in advanced chronic kidney disease (CKD) is incomplete due to lack of patient-pooled database. We retrospectively studied a multicenter cohort of 1891 patients who were enrolled in the nationwide multidisciplinary pre-end stage renal disease care program with a baseline glomerular filtration rate (GFR) <45 mL/min/1.73 m2 and followed longitudinally to investigate the effect of the change in proteinuria on renal death (defined as composite of dialysis and death occurring before initiation of dialysis). The group with a change in proteinuria ≤0.30 g/g (n = 1261) had lower cumulative probabilities of renal death (p < 0.001). In a linear regression model, a higher baseline proteinuria and a greater increase in proteinuria were associated with faster annual GFR decline. Cox’s analysis showed that every 1 unit increase in natural log(baseline proteinuria, 10 g/g) and every 0.1 g/g increase in the change in proteinuria resulted in 67% (HR = 1.67, 95% CI: 1.46–1.91) and 1% (HR = 1.01, 95% CI: 1.01–1.01) greater risk of renal death respectively after adjusting for the effects of the other covariates. Our study provided a patient-based evidence to support proteinuria as a therapeutic target in advanced CKD. PMID:27198863

  20. Changing etiology of community-acquired bacterial meningitis in adults: a nationwide multicenter study in Korea.

    PubMed

    Moon, S-Y; Chung, D R; Kim, S-W; Chang, H H; Lee, H; Jung, D S; Kim, Y-S; Jung, S I; Ryu, S Y; Heo, S T; Moon, C; Ki, H K; Son, J S; Kwon, K T; Shin, S Y; Lee, J S; Lee, S S; Rhee, J-Y; Lee, J-A; Joung, M K; Cheong, H S; Peck, K R; Song, J-H

    2010-07-01

    Epidemiologic data on the etiologic organisms is important for appropriate empirical antibiotic treatment of bacterial meningitis. We identified the etiologies of community-acquired bacterial meningitis in Korean adults and the associated epidemiological factors. A retrospective, multicenter nationwide study was carried out. Patients 18 years of age or older with community-acquired bacterial meningitis with a confirmed pathogen were enrolled. Demographic, clinical, and microbiological data were collected. One hundred and ninety-five cases were collected. Streptococcus pneumoniae was the most common pathogen (50.8%), followed by Staphylococcus aureus (10.3%), Klebsiella pneumoniae (7.7%), Listeria monocytogenes (6.7%), and group B Streptococcus (3.1%). The penicillin resistance rate of the S. pneumoniae was 60.3%; 40.0% of the organisms were not susceptible to third-generation cephalosporins. The combination of third-generation cephalosporin with vancomycin was used in 76.3% of cases. Steroids were given before or with the first dose of antibiotics in 37.4% of patients. The 30-day mortality rate was 20.5% and neurological sequelae developed in 15.6% of cases. S. pneumoniae was the most common organism identified in community-acquired bacterial meningitis among Korean adults. S. aureus, K. pneumoniae, L. monocytogenes, and group B Streptococcus were also common. S. pneumoniae had high rates of resistance to penicillin and third-generation cephalosporins. PMID:20432052

  1. Photorejuvenation with intense pulsed light: results of a multi-center study.

    PubMed

    Sadick, Neil S; Weiss, Robert; Kilmer, Suzanne; Bitter, Patrick

    2004-01-01

    This multi-center study evaluating the role of Intense Pulsed Light (IPL) in the non-ablative rejuvenation of Type I and Type II photoaged skin study was conducted in order to evaluate the clinical efficacy and safety of using IPL in treating clinical indications associated with photoaged skin. Ninety-three patients of Fitzpatrick skin phenotypes I-III, Fitzpatrick Wrinkle Classes I-II, and Elastosis Scores 1-6 were enrolled in the study. Up to five treatments were performed at 4-week intervals with follow-up visits at 4 and 6 months after the last treatment. Patients received full-face treatments using the recommended parameters of the Quantum SR/HR (Lumenis Ltd.) with the 560 or 640 nm cutoff filter. Parameters of elastometry, physicians' evaluation of the Elastosis Score ('W/ES'), and global improvement as well as patient satisfaction were analyzed. Results showed that the average Fitzpatrick W/ES improved significantly (p<0.001) by 1.39 and 1.32 units at the 4 and 6 months follow-ups, respectively; an improved W/ES evaluation was recorded for 82% and 75% of the patients at each of these time points. In conclusion, IPL treatment is an effective non-invasive, non-ablative method for rejuvenating photoaged skin with minimal adverse events, no downtime, excellent long-term results, and a very high measure of patient satisfaction. PMID:14964745

  2. Incidence and epidemiology of anal cancer in the Multicenter AIDS Cohort Study (MACS)

    PubMed Central

    D’Souza, Gypsyamber; Wiley, Dorothy J.; Li, Xiuhong; Chmiel, Joan S.; Margolick, Joseph B.; Cranston, Ross D.; Jacobson, Lisa P.

    2014-01-01

    Objective To examine the incidence and risk factors for anal cancer in a multicenter cohort of HIV-positive and negative men who have sex with men followed between 1984 and 2006 (MACS). Methods Prospective analysis using Poisson regression and Cox proportional hazard models, and a nested case-control study using conditional logistic regression. Results There were 28 cases of anal cancer among the 6,972 men who were evaluated. The incidence rate was significantly higher in HIV-positive men than in HIV-negative men (IR= 69 vs. 14 per 100,000 person-years). Among HIV-positive men, anal cancer incidence was higher in the HAART era than the pre-HAART era (IR=137 vs. 30 per 100,000 person-years). In multivariate analysis restricted to the HAART era, anal cancer risk increased significantly with HIV infection (RH=4.7, 95%CI=1.3–17), and increasing number of unprotected receptive anal sex partners at the first three study visits (p-trend=0.03). Among HIV-positive men, current HAART use did not decrease anal cancer risk. Conclusion HIV-positive men had increased risk of anal cancer. Improved survival of HIV-positive individuals following HAART initiation may allow for sufficient time for human papillomavirus (HPV) associated anal dysplasias to develop into malignancies, thus explaining the increased incidence of anal cancer in the HAART era. PMID:18614927

  3. [Education programs on atopic eczema. Design and first results of the German Randomized Intervention Multicenter Study].

    PubMed

    Diepgen, T L; Fartasch, M; Ring, J; Scheewe, S; Staab, D; Szcepanski, R; Werfel, T; Wahn, U; Gieler, U

    2003-10-01

    Atopic eczema (AE) is a common, chronically relapsing, inflammatory skin disease with an early onset during infancy associated with a high loss of quality of life and socioeconomic burden. In the past few years, an Atopic Eczema Prevention Program was established to improve disease management and the quality of life of patients with atopic eczema. In Germany, the Task Force on Education Programs for Atopic Eczema (AGNES = Arbeitsgemeinschaft Neurodermitis Schulung) for children, youths, and parents was founded as well as the Task Force on Dermatological Prevention (ADP) for adults. These groups ensure structure and process quality of the prevention programs and organize train-the-trainer workshops. In a randomized prospective controlled trial (the German Randomized Intervention Multicenter Study = GRIMS), we are currently comparing the effectiveness of an atopic eczema group intervention program in (1) parents of atopic eczema children aged 0-7 years, (2) parents and children 7-12 years old, and (3) youths with AE aged between 13 and 18 years. The groups were randomized and compared with a waiting control group. The design and first results will be reported. PMID:14513241

  4. Multicenter Study of Antimicrobial Susceptibility of Anaerobic Bacteria in Korea in 2012

    PubMed Central

    Lee, Yangsoon; Park, Yeon-Joon; Kim, Mi-Na; Uh, Young; Kim, Myung Sook

    2015-01-01

    Background Periodic monitoring of regional or institutional resistance trends of clinically important anaerobic bacteria is recommended, because the resistance of anaerobic pathogens to antimicrobial drugs and inappropriate therapy are associated with poor clinical outcomes. There has been no multicenter study of clinical anaerobic isolates in Korea. We aimed to determine the antimicrobial resistance patterns of clinically important anaerobes at multiple centers in Korea. Methods A total of 268 non-duplicated clinical isolates of anaerobic bacteria were collected from four large medical centers in Korea in 2012. Antimicrobial susceptibility was tested by the agar dilution method according to the CLSI guidelines. The following antimicrobials were tested: piperacillin, piperacillin-tazobactam, cefoxitin, cefotetan, imipenem, meropenem, clindamycin, moxifloxacin, chloramphenicol, metronidazole, and tigecycline. Results Organisms of the Bacteroides fragilis group were highly susceptible to piperacillin-tazobactam, imipenem, and meropenem, as their resistance rates to these three antimicrobials were lower than 6%. For B. fragilis group isolates and anaerobic gram-positive cocci, the resistance rates to moxifloxacin were 12-25% and 11-13%, respectively. Among B. fragilis group organisms, the resistance rates to tigecycline were 16-17%. Two isolates of Finegoldia magna were non-susceptible to chloramphenicol (minimum inhibitory concentrations of 16-32 mg/L). Resistance patterns were different among the different hospitals. Conclusions Piperacillin-tazobactam, cefoxitin, and carbapemems are highly active β-lactam agents against most of the anaerobes. The resistance rates to moxifloxacin and tigecycline are slightly higher than those in the previous study. PMID:26206683

  5. Proteinuria as a Therapeutic Target in Advanced Chronic Kidney Disease: a Retrospective Multicenter Cohort Study.

    PubMed

    Chen, Chang-Hsu; Wu, Hon-Yen; Wang, Chieh-Li; Yang, Feng-Jung; Wu, Pei-Chen; Hung, Szu-Chun; Kan, Wei-Chih; Yang, Chung-Wei; Chiang, Chih-Kang; Huang, Jenq-Wen; Hung, Kuan-Yu

    2016-01-01

    Current evidence of proteinuria reduction as a surrogate target in advanced chronic kidney disease (CKD) is incomplete due to lack of patient-pooled database. We retrospectively studied a multicenter cohort of 1891 patients who were enrolled in the nationwide multidisciplinary pre-end stage renal disease care program with a baseline glomerular filtration rate (GFR) <45 mL/min/1.73 m(2) and followed longitudinally to investigate the effect of the change in proteinuria on renal death (defined as composite of dialysis and death occurring before initiation of dialysis). The group with a change in proteinuria ≤0.30 g/g (n = 1261) had lower cumulative probabilities of renal death (p < 0.001). In a linear regression model, a higher baseline proteinuria and a greater increase in proteinuria were associated with faster annual GFR decline. Cox's analysis showed that every 1 unit increase in natural log(baseline proteinuria, 10 g/g) and every 0.1 g/g increase in the change in proteinuria resulted in 67% (HR = 1.67, 95% CI: 1.46-1.91) and 1% (HR = 1.01, 95% CI: 1.01-1.01) greater risk of renal death respectively after adjusting for the effects of the other covariates. Our study provided a patient-based evidence to support proteinuria as a therapeutic target in advanced CKD. PMID:27198863

  6. Hypotony in Patients with Uveitis: The Multicenter Uveitis Steroid Treatment (MUST) Trial

    PubMed Central

    Sen, H. Nida; Drye, Lea T.; Goldstein, Debra A.; Larson, Theresa A.; Merrill, Pauline T.; Pavan, Peter R.; Sheppard, John D.; Burke, Alyce; Srivastava, Sunil K.; Jabs, Douglas A.

    2013-01-01

    Purpose To assess the prevalence of hypotony in patients with severe forms of uveitis. Methods The Multicenter Uveitis Steroid Treatment (MUST) Trial, a randomized study, enrolled 255 patients. Patients with hypotony at the baseline visit were identified. Results Twenty (8.3%) of 240 patients with sufficient data had hypotony. Hypotony was more common in patients with uveitis ≥5 years duration (odds ratio [OR] = 5.0; p < .01), and in eyes with a history of ocular surgery (vitrectomy vs. none, OR = 3.1; p = .03). Hypotony was less in patients with older age of uveitis onset (>51 years vs. <51 years, OR = 0.1; p = .02), in Caucasian patients (OR = 0.1; p < .01) compared to African American patients. Hypotonous eyes were more likely to have visual impairment (OR = 22.9; p < .01). Conclusions Hypotony is an important complication of uveitis and more commonly affects African-American patients, those with uveitis onset at a younger age, and those with longer disease duration. It is associated with visual impairment. PMID:22409563

  7. Multicenter Study of Prevalence of Nontuberculous Mycobacteria in Patients with Cystic Fibrosis in France ▿

    PubMed Central

    Roux, Anne-Laure; Catherinot, Emilie; Ripoll, Fabienne; Soismier, Nathalie; Macheras, Edouard; Ravilly, Sophie; Bellis, Gil; Vibet, Marie-Anne; Le Roux, Evelyne; Lemonnier, Lydie; Gutierrez, Cristina; Vincent, Véronique; Fauroux, Brigitte; Rottman, Martin; Guillemot, Didier; Gaillard, Jean-Louis

    2009-01-01

    We performed a multicenter prevalence study of nontuberculous mycobacteria (NTM) involving 1,582 patients (mean age, 18.9 years; male/female ratio, 1.06) with cystic fibrosis in France. The overall NTM prevalence (percentage of patients with at least one positive culture) was 6.6% (104/1,582 patients), with prevalences ranging from 3.7% (in the east of France) to 9.6% (in the greater Paris area). Mycobacterium abscessus complex (MABSC; 50 patients) and Mycobacterium avium complex (MAC; 23 patients) species were the most common NTM, and the only ones associated with fulfillment of the American Thoracic Society bacteriological criteria for NTM lung disease. The “new” species, Mycobacterium bolletii and Mycobacterium massiliense, accounted for 40% of MABSC isolates. MABSC species were isolated at all ages, with a prevalence peak between 11 and 15 years of age (5.8%), while MAC species reached their highest prevalence value among patients over 25 years of age (2.2%). PMID:19846643

  8. Multicenter study of prevalence of nontuberculous mycobacteria in patients with cystic fibrosis in france.

    PubMed

    Roux, Anne-Laure; Catherinot, Emilie; Ripoll, Fabienne; Soismier, Nathalie; Macheras, Edouard; Ravilly, Sophie; Bellis, Gil; Vibet, Marie-Anne; Le Roux, Evelyne; Lemonnier, Lydie; Gutierrez, Cristina; Vincent, Véronique; Fauroux, Brigitte; Rottman, Martin; Guillemot, Didier; Gaillard, Jean-Louis

    2009-12-01

    We performed a multicenter prevalence study of nontuberculous mycobacteria (NTM) involving 1,582 patients (mean age, 18.9 years; male/female ratio, 1.06) with cystic fibrosis in France. The overall NTM prevalence (percentage of patients with at least one positive culture) was 6.6% (104/1,582 patients), with prevalences ranging from 3.7% (in the east of France) to 9.6% (in the greater Paris area). Mycobacterium abscessus complex (MABSC; 50 patients) and Mycobacterium avium complex (MAC; 23 patients) species were the most common NTM, and the only ones associated with fulfillment of the American Thoracic Society bacteriological criteria for NTM lung disease. The "new" species, Mycobacterium bolletii and Mycobacterium massiliense, accounted for 40% of MABSC isolates. MABSC species were isolated at all ages, with a prevalence peak between 11 and 15 years of age (5.8%), while MAC species reached their highest prevalence value among patients over 25 years of age (2.2%). PMID:19846643

  9. Undernutrition, risk of malnutrition and obesity in gastroenterological patients: A multicenter study

    PubMed Central

    Rizzi, Massimiliano; Mazzuoli, Silvia; Regano, Nunzia; Inguaggiato, Rosa; Bianco, Margherita; Leandro, Gioacchino; Bugianesi, Elisabetta; Noè, Donatella; Orzes, Nicoletta; Pallini, Paolo; Petroni, Maria Letizia; Testino, Gianni; Guglielmi, Francesco William

    2016-01-01

    AIM: To investigate the prevalence of undernutrition, risk of malnutrition and obesity in the Italian gastroenterological population. METHODS: The Italian Hospital Gastroenterology Association conducted an observational, cross-sectional multicenter study. Weight, weight loss, and body mass index were evaluated. Undernutrition was defined as unintentional weight loss > 10% in the last three-six months. Values of Malnutrition Universal Screening Tool (MUST) > 2, NRS-2002 > 3, and Mini Nutritional Assessment (MNA) from 17 to 25 identified risk of malnutrition in outpatients, inpatients and elderly patients, respectively. A body mass index ≥ 30 indicated obesity. Gastrointestinal pathologies were categorized into acute, chronic and neoplastic diseases. RESULTS: A total of 513 patients participated in the study. The prevalence of undernutrition was 4.6% in outpatients and 19.6% in inpatients. Moreover, undernutrition was present in 4.3% of the gastrointestinal patients with chronic disease, 11.0% of those with acute disease, and 17.6% of those with cancer. The risk of malnutrition increased progressively and significantly in chronic, acute and neoplastic gastrointestinal diseases in inpatients and the elderly population. Logistical regression analysis confirmed that cancer was a risk factor for undernutrition (OR = 2.7; 95%CI: 1.2-6.44, P = 0.02). Obesity and overweight were more frequent in outpatients. CONCLUSION: More than 63% of outpatients and 80% of inpatients in gastroenterological centers suffered from significant changes in body composition and required specific nutritional competence and treatment. PMID:27559436

  10. Cohort Profile: Recruitment cohorts in the neuropsychological substudy of the Multicenter AIDS Cohort Study.

    PubMed

    Becker, James T; Kingsley, Lawrence A; Molsberry, Samantha; Reynolds, Sandra; Aronow, Aaron; Levine, Andrew J; Martin, Eileen; Miller, Eric N; Munro, Cynthia A; Ragin, Ann; Sacktor, Ned; Selnes, Ola A

    2015-10-01

    The Multicenter AIDS Cohort Study (MACS) is one of the largest and longest running studies of the natural and treated history of HIV disease. The Neuropsychological (NP) substudy was begun in 1988 following reports of significant adverse neurological consequences of HIV disease, including dementia. The goal was to characterize the neuropsychological deficits among individuals with HIV disease, and track the natural history of the neurological complications over time. There were three distinct MACS recruitment stages that focused on different groups of HIV-infected men, or men at risk for infection. Initially, a subcohort was evaluated semi-annually with NP tests but, beginning in 2005, the entire group of MACS participants have had NP examinations biannually, unless closer follow-up was warranted. The participants complete a battery of NP tests, and are classified as either normal, mildly or severely impaired using the Antinori criteria for HIV-Associated Neurocognitive Disorder (HAND). Additional behavioural data, including mood state and psychoactive substance use, are recorded as part of the main MACS data collection. The MACS public data set (PDS) has been available since 1994 and includes baseline and 6-monthly follow-up data. Beginning in October 1995, the PDS has been released annually with new releases superseding previous versions. PMID:24771276