Preoperative [18F]Fluorodeoxyglucose Positron Emission Tomography Standardized Uptake Value of Neck Lymph Nodes Predicts Neck Cancer Control and Survival Rates in Patients With Oral Cavity Squamous Cell Carcinoma and Pathologically Positive Lymph Nodes

DOE Office of Scientific and Technical Information (OSTI.GOV)

Liao, C.-T.; Head and Neck Oncology Group, Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan; Chang, J.T.-C.

Purpose: Survival in oral cavity squamous cell carcinoma (OSCC) depends heavily on locoregional control. In this prospective study, we sought to investigate whether preoperative maximum standardized uptake value of the neck lymph nodes (SUVnodal-max) may predict prognosis in OSCC patients. Methods and Materials: A total of 120 OSCC patients with pathologically positive lymph nodes were investigated. All subjects underwent a [18F]fluorodeoxyglucose (FDG) positron emission tomography (PET) scan within 2 weeks before radical surgery and neck dissection. All patients were followed up for at least 24 months after surgery or until death. Postoperative adjuvant therapy was performed in the presence ofmore » pathologic risk factors. Optimal cutoff values of SUVnodal-max were chosen based on 5-year disease-free survival (DFS), disease-specific survival (DSS), and overall survival (OS). Independent prognosticators were identified by Cox regression analysis. Results: The median follow-up for surviving patients was 41 months. The optimal cutoff value for SUVnodal-max was 5.7. Multivariate analyses identified the following independent predictors of poor outcome: SUVnodal-max {>=}5.7 for the 5-year neck cancer control rate, distant metastatic rate, DFS, DSS, and extracapsular spread (ECS) for the 5-year DSS and OS. Among ECS patients, the presence of a SUVnodal-max {>=}5.7 identified patients with the worst prognosis. Conclusion: A SUVnodal-max of 5.7, either alone or in combination with ECS, is an independent prognosticator for 5-year neck cancer control and survival rates in OSCC patients with pathologically positive lymph nodes.« less

Utility of up-front transoral robotic surgery in tailoring adjuvant therapy.

PubMed

Gildener-Leapman, Neil; Kim, Jeehong; Abberbock, Shira; Choby, Garret W; Mandal, Rajarsi; Duvvuri, Umamaheswar; Ferris, Robert L; Kim, Seungwon

2016-08-01

The purpose of this study was to describe how the up-front transoral robotic surgery (TORS) approach could be used to individually tailor adjuvant therapy based on surgical pathology. Between January 2009 and December 2013, 76 patients received TORS for oropharyngeal squamous cell carcinoma (OPSCC). Clinical predictors of adjuvant therapy were analyzed and comparisons were made between recommended treatment guidelines for up-front surgery versus definitive nonsurgical approaches. Advanced N classification, human papillomavirus (HPV)-positive tumor, extracapsular spread (ECS; 26 of 76), perineural invasion (PNI; 14 of 76), and positive margins (7 of 76) were significant predictors of adjuvant chemoradiotherapy (CRT) (p < .05). Up-front TORS deintensified adjuvant therapy; 76% of stage I/II and 46% of stage III/IV patients avoided CRT. Conversely, pathologic staging resulted in 33% of patients who would have received radiotherapy (RT) alone based on clinical staging, to be intensified to receive adjuvant CRT. The TORS approach deintensifies adjuvant therapy and provides valuable pathologic information to intensify treatment in select patients. TORS may be less effective in deintensification of adjuvant therapy in patients with clinically advanced N classification disease. © 2016 Wiley Periodicals, Inc. Head Neck 38:1201-1207, 2016. © 2016 Wiley Periodicals, Inc.

Treatment Outcome of Carcinoma Vulva Ten-Year Experience from a Tertiary Cancer Centre in South India.

PubMed

Jeevarajan, Sakthiushadevi; Duraipandian, Amudhan; Kottayasamy Seenivasagam, Rajkumar; Shanmugam, Subbiah; Ramamurthy, Rajaraman

2017-01-01

Carcinoma vulva is a rare disease accounting for 1.3% of all gynaecological malignancies. The present study is a 10-year retrospective review of our experience of the surgical options, morbidity, failure pattern, and survival for invasive carcinoma vulva. Retrospective analysis of case records of 39 patients who underwent surgery for invasive vulval cancer between 2004 and 2013 in the Department of Surgical Oncology at the Government Royapettah Hospital, Chennai. The median age was 55 years. Radical vulvectomy was the preferred surgery. 31 patients underwent lymphadenectomy. Seroma formation and groin skin necrosis were the most common postoperative complications. With a median follow-up of 32 months, 8 patients (20.5%) developed recurrence (systemic = 1, regional = 4, and local = 3). The estimated 5-year disease-free survival (DFS) was 65.4% and the overall survival (OS) was 85.1%. On univariate analysis, stage and lymph node involvement significantly affected OS. Nodal involvement with extracapsular spread (ECS) significantly affected both DFS and OS. The treatment of carcinoma vulva should be individualized with multidisciplinary cooperation. The paucity of data, especially from India, necessitates the need for more studies, preferably multicentric, keeping in mind the low prevalence.

A 20-Year Review of 75 Cases of Salivary Duct Carcinoma.

PubMed

Gilbert, Mark R; Sharma, Arun; Schmitt, Nicole C; Johnson, Jonas T; Ferris, Robert L; Duvvuri, Umamaheswar; Kim, Seungwon

2016-05-01

Salivary duct carcinoma is a rare, aggressive malignancy of the salivary glands. Owing to its rare nature, clinical data are limited, and only a few clinical studies comprise more than 50 patients. To review the University of Pittsburgh Medical Center's experience with salivary duct carcinoma over a 20-year period, focusing on demographics, presentation, treatment, and outcome. This investigation was a retrospective cohort study in a multihospital institution with tertiary referral. A pathology database was reviewed for all cases of histopathologically diagnosed salivary duct carcinoma from January 1, 1995, to October 20, 2014. Patients who were referrals for pathology review only and were never seen at the institution were excluded. In total, 75 study patients were identified. The electronic medical record was reviewed for details regarding demographics, presentation, treatment, and outcome, including overall survival (OS) and disease-free survival (DFS). This study was supplemented with a review of the institution's Head and Neck Oncology Database for further clinical details. Primary outcome measures consisted of OS and DFS. The study sample comprised 75 participants with a mean age at diagnosis of 66.0 years (age range, 33-93 years), and 29% (n = 22) were female. Most primary tumors were from the parotid gland (83%), with the next most frequent site being the submandibular gland (12%). Overall, 41% of the cases were carcinoma ex pleomorphic adenoma. Rates of other histologic features included the following: perineural invasion (69%), extracapsular spread (58%), ERBB2 (formerly HER2) positivity (31%) (62% of those who were tested), and vascular invasion (61%). The median OS was 3.1 years, and the median DFS was 2.7 years. Univariate Kaplan-Meier survival analyses demonstrated that facial nerve sacrifice and extracapsular spread were associated with lower OS (2.38 vs 5.11 years and 2.29 vs 6.56 years, respectively) and DFS (2.4 vs 3.88 years and 1.44 vs 4.5 years, respectively). Although underpowered, multivariable analysis demonstrated significantly worse OS in patients with N2 and N3 disease (hazard ratio [HR] 8.42, 95% CI, 1.84-38.5) but did not show significantly worse DFS or OS for facial nerve sacrifice or extracapsular spread. There was no association between ERBB2 positivity and survival and no difference in survival between patients receiving radiation therapy vs radiation therapy plus chemotherapy. No patients had recurrence or distant metastasis after 5 disease-free years. Salivary duct carcinoma is an aggressive disease. A large number of cases in this review were carcinoma ex pleomorphic adenoma and had classic negative prognostic indicators, such as perineural invasion, vascular invasion, and extracapsular spread. ERBB2 positivity was not associated with any difference in survival. Facial nerve involvement appears to indicate worse prognosis, as does nodal stage higher than N1. Recurrence and metastasis after 5 years are rare.

Treatment Outcome of Carcinoma Vulva Ten-Year Experience from a Tertiary Cancer Centre in South India

PubMed Central

Duraipandian, Amudhan; Shanmugam, Subbiah; Ramamurthy, Rajaraman

2017-01-01

Background Carcinoma vulva is a rare disease accounting for 1.3% of all gynaecological malignancies. The present study is a 10-year retrospective review of our experience of the surgical options, morbidity, failure pattern, and survival for invasive carcinoma vulva. Materials and Methods Retrospective analysis of case records of 39 patients who underwent surgery for invasive vulval cancer between 2004 and 2013 in the Department of Surgical Oncology at the Government Royapettah Hospital, Chennai. Results The median age was 55 years. Radical vulvectomy was the preferred surgery. 31 patients underwent lymphadenectomy. Seroma formation and groin skin necrosis were the most common postoperative complications. With a median follow-up of 32 months, 8 patients (20.5%) developed recurrence (systemic = 1, regional = 4, and local = 3). The estimated 5-year disease-free survival (DFS) was 65.4% and the overall survival (OS) was 85.1%. On univariate analysis, stage and lymph node involvement significantly affected OS. Nodal involvement with extracapsular spread (ECS) significantly affected both DFS and OS. Conclusion The treatment of carcinoma vulva should be individualized with multidisciplinary cooperation. The paucity of data, especially from India, necessitates the need for more studies, preferably multicentric, keeping in mind the low prevalence. PMID:29387486

Using 3 Tesla magnetic resonance imaging in the pre-operative evaluation of tongue carcinoma.

PubMed

Moreno, K F; Cornelius, R S; Lucas, F V; Meinzen-Derr, J; Patil, Y J

2017-09-01

This study aimed to evaluate the role of 3 Tesla magnetic resonance imaging in predicting tongue tumour thickness via direct and reconstructed measures, and their correlations with corresponding histological measures, nodal metastasis and extracapsular spread. A prospective study was conducted of 25 patients with histologically proven squamous cell carcinoma of the tongue and pre-operative 3 Tesla magnetic resonance imaging from 2009 to 2012. Correlations between 3 Tesla magnetic resonance imaging and histological measures of tongue tumour thickness were assessed using the Pearson correlation coefficient: r values were 0.84 (p < 0.0001) and 0.81 (p < 0.0001) for direct and reconstructed measurements, respectively. For magnetic resonance imaging, direct measures of tumour thickness (mean ± standard deviation, 18.2 ± 7.3 mm) did not significantly differ from the reconstructed measures (mean ± standard deviation, 17.9 ± 7.2 mm; r = 0.879). Moreover, 3 Tesla magnetic resonance imaging had 83 per cent sensitivity, 82 per cent specificity, 82 per cent accuracy and a 90 per cent negative predictive value for detecting cervical lymph node metastasis. In this cohort, 3 Tesla magnetic resonance imaging measures of tumour thickness correlated highly with the corresponding histological measures. Further, 3 Tesla magnetic resonance imaging was an effective method of detecting malignant adenopathy with extracapsular spread.

[Analysis of the patterns of cervical lymph node recurrence in patients with cN0 papillary thyroid carcinoma after central neck lymph node dissection].

PubMed

Huang, Hui; Xu, Zhengang; Wang, Xiaolei; Wu, Yuehuang; Liu, Shaoyan

2015-10-01

To retrospectively analyze the long-term results of prophylactic central lymph node dissection in cN0 papillary thyroid carcinoma (PTC), and investigate the treatment method of the cervical lymph nodes for cN0 PTC. One hundred and thirty-six patients with cN0 PTC were treated by surgery at the Cancer Hospital of Chinese Academy of Medical Sciences from 2000 to 2006. Their clinicopathological characteristics, surgical procedures and survival outcomes were collected and analyzed. The occult lymph node metastasis rate in central compartment was 61.0%. The average number of positive lymph nodes was 2.47 (1-13), in which 54 patients had 1-2 and 29 patients had ≥ 3 positive lymph nodes. Multiple logistic regression analysis showed that age less than 45 (P=0.001, OR 3.571, 95% CI 1.681-7.587)and extracapsular spread (ECS) (P=0.015, OR 2.99, 95% CI 1.241-7.202)were independent risk factors for lymph node metastasis in the central compartment. The ten-year cumulative overall survival rate was 98.3% and cumulative lateral neck metastasis rate was 25.2%. Multivariate analysis with Cox regression model showed that ECS (P=0.001, OR 5.211, 95% CI1.884-14.411) and positive lymph nodes in the central compartment ≥ 3 (P=0.009, OR 4.005, 95% CI 1.419-11.307) were independent risk factors for lymph node recurrence in the lateral neck region. The distribution of recurrent lymph nodes: level IV (82.4%), level III (64.7%), level II (29.4%) and level V (11.8%). Routine central lymph node dissection, at least unilateral, should be conducted for cN0 papillary thyroid carcinoma. Attention should be paid to the treatment of lateral neck region in patients with cN0 papillary thyroid carcinoma. Selective neck dissection is suggested for cN0 PTC with ECS or positive central lymph nodes ≥ 3, or both. The range of dissection should include level III and IV at least.

Prognostic impact of perineural invasion and lymphovascular invasion in advanced stage oral squamous cell carcinoma.

PubMed

Jardim, J F; Francisco, A L N; Gondak, R; Damascena, A; Kowalski, L P

2015-01-01

Perineural invasion (PNI) and lymphovascular invasion (LVI) have been associated with the risk of local recurrences and lymph node metastasis. The aim of this study was to evaluate the prognostic impact of PNI and LVI in patients with advanced stage squamous cell carcinoma of the tongue and floor of the mouth. One hundred and forty-two patients without previous treatment were selected. These patients underwent radical surgery with neck dissection and adjuvant treatment. Clinicopathological data were retrieved from the medical charts, including histopathology and surgery reports. Univariate analysis was performed to assess the impact of studied variables on survival. Overall survival was negatively influenced by six tumour-related factors: increasing T stage (P = 0.003), more than two clinically positive nodes (P = 0.002), extracapsular spread of lymph node metastasis (P < 0.001), tumour thickness (P = 0.04), PNI (P < 0.001), and LVI (P = 0.012). Disease-free survival was influenced by PNI (P = 0.04), extracapsular spread of lymph node metastasis (P = 0.008), and N stage (P = 0.006). Multivariate analysis showed PNI to be an independent predictor for overall survival (P = 0.01) and disease-free survival (P = 0.03). Thus the presence of PNI in oral carcinoma surgical specimens has a significant impact on survival outcomes in patients with advanced stage tumours submitted to radical surgery and adjuvant radiotherapy/radiochemotherapy. Copyright © 2014 International Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Predictors and Patterns of Local, Regional, and Distant Failure in Squamous Cell Carcinoma of the Vulva.

PubMed

Bogani, Giorgio; Cromi, Antonella; Serati, Maurizio; Uccella, Stefano; Donato, Violante Di; Casarin, Jvan; Naro, Edoardo Di; Ghezzi, Fabio

2017-06-01

To identify factors predicting for recurrence in vulvar cancer patients undergoing surgical treatment. We retrospectively evaluated data of consecutive patients with squamous cell vulvar cancer treated between January 1, 1990 and December 31, 2013. Basic descriptive statistics and multivariable analysis were used to design predicting models influencing outcomes. Five-year disease-free survival (DFS) and overall survival (OS) were analyzed using the Cox model. The study included 101 patients affected by vulvar cancer: 64 (63%) stage I, 12 (12%) stage II, 20 (20%) stage III, and 5 (5%) stage IV. After a mean (SD) follow-up of 37.6 (22.1) months, 21 (21%) recurrences occurred. Local, regional, and distant failures were recorded in 14 (14%), 6 (6%), and 3 (3%) patients, respectively. Five-year DFS and OS were 77% and 82%, respectively. At multivariate analysis only stromal invasion >2 mm (hazard ratio: 4.9 [95% confidence interval, 1.17-21.1]; P=0.04) and extracapsular lymph node involvement (hazard ratio: 9.0 (95% confidence interval, 1.17-69.5); P=0.03) correlated with worse DFS, although no factor independently correlated with OS. Looking at factors influencing local and regional failure, we observed that stromal invasion >2 mm was the only factor predicting for local recurrence, whereas lymph node extracapsular involvement predicted for regional recurrence. Stromal invasion >2 mm and lymph node extracapsular spread are the most important factors predicting for local and regional failure, respectively. Studies evaluating the effectiveness of adjuvant treatment in high-risk patients are warranted.

Predictive value of magnetic resonance imaging determined tumor contact length for extracapsular extension of prostate cancer.

PubMed

Baco, Eduard; Rud, Erik; Vlatkovic, Ljiljana; Svindland, Aud; Eggesbø, Heidi B; Hung, Andrew J; Matsugasumi, Toru; Bernhard, Jean-Christophe; Gill, Inderbir S; Ukimura, Osamu

2015-02-01

Tumor contact length is defined as the amount of prostate cancer in contact with the prostatic capsule. We evaluated the ability of magnetic resonance imaging determined tumor contact length to predict microscopic extracapsular extension compared to existing predictors of extracapsular extension. We retrospectively analyzed the records of 111 consecutive patients with magnetic resonance imaging/ultrasound fusion targeted, biopsy proven prostate cancer who underwent radical prostatectomy from January 2010 to July 2013. Median patient age was 64 years and median prostate specific antigen was 8.9 ng/ml. Clinical stage was cT1 in 93 cases (84%) and cT2 in 18 (16%). Postoperative pathological analysis confirmed pT2 in 71 patients (64%) and pT3 in 40 (36%). We evaluated 1) in the radical prostatectomy specimen the correlation of microscopic extracapsular extension with pathological cancer volume, pathological tumor contact length and Gleason score, 2) the correlation between microscopic extracapsular extension and magnetic resonance imaging tumor contact length, and 3) the ability of preoperative variables to predict microscopic extracapsular extension. Logistic regression analysis revealed that pathological tumor contact length correlated better with microscopic extracapsular extension than the predictive power of pathological cancer volume (0.821 vs 0.685). The Spearman correlation between pathological and magnetic resonance imaging tumor contact length was r = 0.839 (p <0.0001). ROC AUC analysis revealed that magnetic resonance imaging tumor contact length outperformed cancer core involvement on targeted biopsy and the Partin tables to predict microscopic extracapsular extension (0.88 vs 0.70 and 0.63, respectively). At a magnetic resonance imaging tumor contact length threshold of 20 mm the accuracy for diagnosing microscopic extracapsular extension was superior to that of conventional magnetic resonance imaging criteria (82% vs 67%, p = 0.015). We developed a predicted probability plot curve of extracapsular extension according to magnetic resonance imaging tumor contact length. Magnetic resonance imaging determined tumor contact length could be a promising quantitative predictor of microscopic extracapsular extension. Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Endorectal MR imaging of prostate cancer: Evaluation of tumor capsular contact length as a sign of extracapsular extension.

PubMed

Mendez, Gustavo; Foster, Bryan R; Li, Xin; Shannon, Jackilen; Garzotto, Mark; Amling, Christopher L; Coakley, Fergus V

2018-04-25

To evaluate the length of contact between dominant tumor foci and the prostatic capsule as a sign of extracapsular extension at endorectal multiparametric MR imaging. We retrospectively identified 101 patients over a three-year interval who underwent endorectal multiparametric prostate MR imaging prior to radical prostatectomy for prostate cancer. Two readers identified the presence of dominant tumor focus (largest lesion with PI-RADS version 2 score of 4 or 5), and measured the length of tumor capsular contact and likelihood of extracapsular extension by standard criteria (1-5 Likert scale). Results were analyzed using histopathological review as reference standard. Extracapsular extension was found at histopathological review in 27 patients. Reader 1 (2) identified dominant tumor in 79 (73) patients, with mean tumor capsular contact length of 18.2 (14.0) mm. The area under the receiver operating characteristic curve for identification of extracapsular extension by tumor capsular contact length was 0.76 for reader 1 and 0.77 for reader 2, with optimal discrimination at values of 18 mm and 21 mm, respectively. In the subset of patients without obvious extracapsular extension by standard criteria (Likert scores 1-3), corresponding values were 0.74 and 0.66 with optimal thresholds of 24 and 21 mm. Length of contact between the dominant tumor focus and the capsule is a moderately useful sign of extracapsular extension at endorectal multiparametric prostate MR imaging, including the subset of patients without obvious extracapsular extension by standard criteria, with optimal discrimination at threshold values of 18 to 24 mm. Copyright © 2018 Elsevier Inc. All rights reserved.

Extracapsular dissection for Warthin tumor in the tail of parotid gland.

PubMed

Lee, Dong Hoon; Yoon, Tae Mi; Lee, Joon Kyoo; Lim, Sang Chul

2017-09-01

Extracapsular dissection conferred the advantage of reduced operation time and morbidity without any recurrence, and it could be considered as the treatment of choice for Warthin tumors in the tail of the parotid gland. The purpose of this study is to confirm the appropriate surgical procedure for Warthin tumor in the tail of the parotid gland, by comparing the results of extracapsular dissection and superficial parotidectomy. The medical records of 72 patients with Warthin tumor in the tail of the parotid gland who underwent surgery between January 2006 and December 2016 were retrospectively reviewed. In the extracapsular dissection group, a total of 44 parotid gland operations were performed in 40 patients. In the superficial parotidectomy group, a total of 34 parotid gland operations were performed in 32 patients. The operation time was significantly shorter in the extracapsular dissection group than in the superficial parotidectomy group (p<.001, Table 1). One patient in the extracapsular dissection group and five patients in the superficial parotidectomy group had postoperative facial nerve palsy. Recurrence of Warthin tumor in the tail portion of the parotid gland was identified in one patient who underwent superficial parotidectomy.

Use of an extracapsular stabilization technique to repair cruciate ligament ruptures in two avian species.

PubMed

Chinnadurai, Sathya K; Spodnick, Gary; Degernes, Laurel; DeVoe, Ryan S; Marcellin-Little, Denis J

2009-12-01

An extracapsular stabilization technique was used to repair cruciate ligament ruptures in a trumpeter hornbill (Bycanistes bucinator) and an African grey parrot (Psittacus erithacus). The hornbill demonstrated cranial drawer motion and severe rotational instability of the stifle from ruptures of the cranial and caudal cruciate ligaments and stifle joint capsule. The luxation was reduced, and the fibula was cranially transposed, in relation to the tibiotarsus, and anchored with 2 positive profile threaded acrylic pins. A lateral extracapsular stabilization was then performed. The African grey parrot had a traumatic stifle luxation, and an open reduction and a lateral extracapsular stabilization were performed. Both birds regained function of the affected leg by 1 month after surgery. Extracapsular stabilization allows motion of the stifle joint to be maintained during the postoperative recovery period, an advantage over rigid stabilization. Maintaining motion in the stifle joint facilitates physical therapy and can aid in full recovery after avian stifle injuries.

Prognostic effect of isolated paraaortic nodal spread in endometrial cancer.

PubMed

Türkmen, Osman; Başaran, Derman; Karalok, Alper; Cömert Kimyon, Günsu; Taşçı, Tolga; Üreyen, Işın; Tulunay, Gökhan; Turan, Taner

2018-03-28

To evaluate the prognostic effect of isolated paraaortic lymph node metastasis in endometrial cancer (EC). This retrospective study included patients with FIGO 2009 stage IIIC2 disease due to isolated paraaortic lymph node metastasis (LNM). Patients with sarcomatous histology, synchronous gynecologic cancers and patients with concurrent pelvic lymph node metastases or patients that have intraabdominal tumor spread were excluded. Kaplan-Meier method was used for calculation of progression free survival (PFS) and overall survival. 1614 patients were operated for EC during study period.961 patients underwent lymph node dissection and 25 (2.6%) were found to have isolated LNM in paraaortic region and these constituted the study cohort.20 (80%) patients had endometrioid EC. Median number of retrieved lymph nodes from pelvic region and paraaortic region was 21.5 (range; 5-41) and 34.5 (range; 1-65), respectively. Median number of metastatic paraaortic nodes was 1 (range; 1-32).The median follow-up time was 15 months (range 5-94). 7 (28%) patients recurred after a median of 20 months (range, 3-99) from initial surgery. 3 patients recurred only in pelvis, one patient had upper abdominal spread and 3 had isolated extraabdominal recurrence.İnvolvement of uterine serosa, positive peritoneal cytology and presence of adnexal metastasis were significantly associated with diminished PFS (p<0.05). The presence of serosal involvement or adnexal involvement is as important as gross peritoneal spread and is related with poor survival in patients with isolated paraaortic nodal spread in EC. Chemotherapy should be the mainstay of treatment in this patient cohort which may eradicate systemic tumor spread.

Suggestions for Lymph Node Classification of UICC/AJCC Staging System: A Retrospective Study Based on 1197 Nasopharyngeal Carcinoma Patients Treated With Intensity-Modulated Radiation Therapy

PubMed Central

Guo, Qiaojuan; Pan, Jianji; Zong, Jingfeng; Zheng, Wei; Zhang, Chun; Tang, Linbo; Chen, Bijuan; Cui, Xiaofei; Xiao, Youping; Chen, Yunbin; Lin, Shaojun

2015-01-01

Abstract This article provides suggestions for N classification of Union for International Cancer Control/American Joint Committee on Cancer (UICC/AJCC) staging system of nasopharyngeal carcinoma (NPC), purely based on magnetic resonance imaging (MRI) in intensity-modulated radiation therapy (IMRT) era. A total of 1197 nonmetastatic NPC patients treated with IMRT were enrolled, and all were scanned by MRI at nasopharynx and neck before treatment. MRI-based nodal variables including level, laterality, maximal axial diameter (MAD), extracapsular spread (ECS), and necrosis were analyzed as potential prognostic factors. Modifications of N classification were then proposed and verified. Only nodal level and laterality were considered to be significant variables affecting the treatment outcome. N classification was thus proposed accordingly: N0, no regional lymph node (LN) metastasis; N1, retropharyngeal LNs involvement (regardless of laterality), and/or unilateral levels I, II, III, and/or Va involvement; N2, bilateral levels I, II, III, and/or Va involvement; and N3, levels IV, Vb, and Vc involvement. This proposal showed significant predicting value in multivariate analysis. N3 patients indicated relatively inferior overall survival (OS) and distant metastasis-free survival (DMFS) than N2 patients; however, the difference showed no statistical significance (P = 0.673 and 0.265 for OS and DMFS, respectively), and this was considered to be correlated with the small sample sizes of N3 patients (79 patients, 6.6%). Nodal level and laterality, but not MAD, ECS, and necrosis, were considered to be significant predicting factors for NPC. The proposed N classification was proved to be powerfully predictive in our cohort; however, treatment outcome of the proposed N2 and N3 patients could not differ significantly from each other. This insignificance may be because of the small sample sizes of N3 patients. Our results are based on a single-center data, to develop a new N classification that is universally acceptable; further verification by data from multicenter is warranted. PMID:25997052

Management of well-differentiated thyroid cancer in 2010: perspectives of a head and neck surgical oncologist.

PubMed

Urken, Mark L

2010-01-01

To review the terminology and controversy regarding the performance of prophylactic lymph node dissection for patients without evidence suggestive of pathologic adenopathy. Terminology of lymph node levels in the neck and chest, and the issues regarding lymph node dissection, are reviewed. In addition, differences between lymph nodes are reviewed and discussed. Management of lymph nodes in this disease process has become the most contentious aspect of surgical decision-making due to the ambiguity of their prognostic significance and the prevalence of nodal metastases in very early primary tumors. Performance of prophylactic central compartment node dissection is not technically any more difficult than therapeutic node dissection when clinically significant nodes are encountered. It is therefore reasonable to consider this technique as an important adjunct to a total thyroidectomy for the purpose of enhanced disease staging, prevention of nodal recurrence, and avoidance of having to re-enter the previously operated central compartment. A recent study is reviewed and discussed in detail. The literature regarding the prognostic significance of extracapsular spread in lymph nodes is also presented. Morphologic characteristics of metastatic lymph nodes in thyroid cancer vary greatly. However, the reporting of these differences is lacking. The presence of extracapsular extension in a lymph node has prognostic significance. The clinician should be aware of these variations and the impact that they may have on recurrence risk and disease-specific survival.

Traumatic Extra-capsular and Intra-capsular Floating Fat: Fat-fluid Levels of the Knee Revisited

PubMed Central

Davis, Derik L; Vachhani, Prasann

2015-01-01

Floating fat is a sign of acute bone injury at the knee following trauma. The goal of this article is to review the etiology, patterns, and mimickers of extra-capsular and intra-capsular floating fat, with the major emphasis on knee trauma in the acute setting. We will discuss the spectrum of multimodal imaging findings for rare presentations of extra-capsular floating fat, and contrast these with common and atypical forms of intra-capsular lipohemarthrosis, as an aid to the assessment of acute bone trauma at the knee. PMID:26713176

Extratropical Cyclones Leading to Extreme Weather Events over Central and Eastern North America

NASA Astrophysics Data System (ADS)

Bentley, Alicia M.

Cool-season extreme weather events (EWEs) occurring over central and eastern North America are typically associated with strong extratropical cyclones (ECs) that are governed by varying combinations of baroclinic, diabatic, and barotropic processes. This dissertation investigates the climatology, evolution, and predictability of ECs leading to EWEs over central and eastern North America, and provides a foundation on which to compare ECs leading to EWEs to ordinary ECs forming over and traversing the same regions. A climatology of ECs leading to EWEs over central and eastern North America during October-March 1979-2016 reveals that these ECs typically form 1) in the lee of the Rocky Mountains, 2) over the south central U.S., and 3) along the east coast of North America at latitudes equatorward of the typical genesis locations of ordinary ECs. ECs leading to EWEs included in the climatology form most frequently in November and March, when the seasonal alignment of baroclinic and convectively driven forcings occurs. Consistent with previous studies of North American ECs, the location and frequency of ECs leading to EWEs are partially determined by the states of the Pacific-North American pattern and the North Atlantic Oscillation. Metrics representing baroclinic, diabatic, and barotropic processes are formulated in this dissertation and are used to determine the combinations of baroclinic, diabatic, and barotropic processes associated with the formation and maintenance of ordinary ECs and ECs leading to EWEs. These metrics reveal that ECs leading to EWEs are associated with contributions from baroclinic, diabatic, and barotropic processes that are 1) similar to those associated with ordinary ECs at the time of formation (t0) and 2) considerably larger than those associated with ordinary ECs at the time of maximum intensity (tmax). Baroclinic processes typically contribute more than diabatic and barotropic processes throughout the evolution of ECs leading to EWEs. Diabatic processes typically contribute more during the intensification of ECs leading to EWEs than during their maintenance after tmax, whereas barotropic processes typically contribute more during the maintenance of ECs leading to EWEs after tmax than during their intensification. The relative contributions from baroclinic, diabatic, and barotropic processes during the evolution of ECs leading to EWEs are also shown to differ based on their genesis location. The 1.0° NOAA Global Ensemble Forecast System (GEFS) reforecast dataset is used in this dissertation to evaluate the forecast skill associated with ordinary ECs and ECs leading to EWEs at 0-192-h lead times. Ordinary ECs are consistently too slow and left of track in the GEFS, and are often too weak at longer lead times. ECs leading to EWEs are consistently too weak, fast, and right of track in the GEFS at longer lead times, and consistently too strong, slow, and left of track at shorter lead times. The positions of ordinary ECs are forecast with less skill and more spread than the positions of ECs leading to EWEs in the GEFS, whereas the intensities of ordinary ECs and ECs leading to EWEs are forecast with similar skill and spread. Locations over central and eastern North America where the positions and intensities of ordinary ECs and ECs leading to EWEs are frequently forecast with relatively low and high skill and spread in the GEFS are also identified.

Active patient decision making regarding nerve sparing during radical prostatectomy: a novel approach.

PubMed

Lavery, Hugh J; Prall, David N; Abaza, Ronney

2011-08-01

The motivation to preserve sexual function can vary widely among patients before prostatectomy. Increasing patient involvement may allow a more personalized experience and may improve satisfaction. We assessed a strategy of surgeon deference to patient choice in regard to nerve sparing to determine to what degree patients are rational actors and capable of active decision making. A total of 150 patients treated with prostatectomy participated in a standardized preoperative discussion regarding the concept of nerve sparing, extracapsular extension and the potential need for adjuvant radiation in the event of local recurrence. Each patient was given his nomogram predicted risk of extracapsular extension and then elected nerve sparing or nonnerve sparing. The corresponding procedure was performed unless grossly invasive disease was encountered. Of the 150 patients 109 chose nerve sparing (73%) and 41 chose nonnerve sparing (27%). In patients with a nomogram predicted risk of extracapsular extension less than 20%, 20% to 50% and greater than 50%, nerve sparing was elected by 88%, 41% and 25%, respectively. Patients with lower risks of extracapsular extension electing nonnerve sparing were older and had higher rates of erectile dysfunction. Empowering patients to decide on their nerve sparing status is a reasonable strategy that did not lead to a high rate of patients with a high risk of extracapsular extension electing nerve sparing. With proper counseling informed patients made reasonable decisions, and appeared to be conservative, prioritizing cancer control in the majority of instances where extracapsular extension risk was high. In addition, they may have been overly conservative in electing nonnerve sparing when the risk was low. Copyright © 2011 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Decision Making in the Management of Extracapsular Fractures of the Proximal Femur - is the Dynamic Hip Screw the Prevailing Gold Standard?

PubMed

Jacob, Joshua; Desai, Ankit; Trompeter, Alex

2017-01-01

Currently, approximately half of all hip fractures are extracapsular, with an incidence as high as 50 in 100,000 in some countries. The common classification systems fail to explain the logistics of fracture classification and whether they all behave in the same manner. The Muller AO classification system is a useful platform to delineate stable and unstable fractures. The Dynamic hip screw (DHS) however, has remained the 'gold standard' implant of choice for application in all extracapsular fractures. The DHS relies on the integrity and strength of the lateral femoral wall as well as the postero-medial fragment. An analysis of several studies indicates significant improvements in design and techniques to ensure a better outcome with intramedullary nails. This article reviews the historical trends that helped to evolve the DHS implant as well as discussing if the surgeon should remain content with this implant. We suggest that the gold standard surgical management of extracapsular fractures can, and should, evolve.

Multimodality Imaging-based Evaluation of Single-Lumen Silicone Breast Implants for Rupture.

PubMed

Seiler, Stephen J; Sharma, Pooja B; Hayes, Jody C; Ganti, Ramapriya; Mootz, Ann R; Eads, Emily D; Teotia, Sumeet S; Evans, W Phil

2017-01-01

Breast implants are frequently encountered on breast imaging studies, and it is essential for any radiologist interpreting these studies to be able to correctly assess implant integrity. Ruptures of silicone gel-filled implants often occur without becoming clinically obvious and are incidentally detected at imaging. Early diagnosis of implant rupture is important because surgical removal of extracapsular silicone in the breast parenchyma and lymphatics is difficult. Conversely, misdiagnosis of rupture may prompt a patient to undergo unnecessary additional surgery to remove the implant. Mammography is the most common breast imaging examination performed and can readily depict extracapsular free silicone, although it is insensitive for detection of intracapsular implant rupture. Ultrasonography (US) can be used to assess the internal structure of the implant and may provide an economical method for initial implant assessment. Common US signs of intracapsular rupture include the "keyhole" or "noose" sign, subcapsular line sign, and "stepladder" sign; extracapsular silicone has a distinctive "snowstorm" or echogenic noise appearance. Magnetic resonance (MR) imaging is the most accurate and reliable means for assessment of implant rupture and is highly sensitive for detection of both intracapsular and extracapsular rupture. MR imaging findings of intracapsular rupture include the keyhole or noose sign, subcapsular line sign, and "linguine" sign, and silicone-selective MR imaging sequences are highly sensitive to small amounts of extracapsular silicone. © RSNA, 2017.

Computer extracted texture features on T2w MRI to predict biochemical recurrence following radiation therapy for prostate cancer

NASA Astrophysics Data System (ADS)

Ginsburg, Shoshana B.; Rusu, Mirabela; Kurhanewicz, John; Madabhushi, Anant

2014-03-01

In this study we explore the ability of a novel machine learning approach, in conjunction with computer-extracted features describing prostate cancer morphology on pre-treatment MRI, to predict whether a patient will develop biochemical recurrence within ten years of radiation therapy. Biochemical recurrence, which is characterized by a rise in serum prostate-specific antigen (PSA) of at least 2 ng/mL above the nadir PSA, is associated with increased risk of metastasis and prostate cancer-related mortality. Currently, risk of biochemical recurrence is predicted by the Kattan nomogram, which incorporates several clinical factors to predict the probability of recurrence-free survival following radiation therapy (but has limited prediction accuracy). Semantic attributes on T2w MRI, such as the presence of extracapsular extension and seminal vesicle invasion and surrogate measure- ments of tumor size, have also been shown to be predictive of biochemical recurrence risk. While the correlation between biochemical recurrence and factors like tumor stage, Gleason grade, and extracapsular spread are well- documented, it is less clear how to predict biochemical recurrence in the absence of extracapsular spread and for small tumors fully contained in the capsule. Computer{extracted texture features, which quantitatively de- scribe tumor micro-architecture and morphology on MRI, have been shown to provide clues about a tumor's aggressiveness. However, while computer{extracted features have been employed for predicting cancer presence and grade, they have not been evaluated in the context of predicting risk of biochemical recurrence. This work seeks to evaluate the role of computer-extracted texture features in predicting risk of biochemical recurrence on a cohort of sixteen patients who underwent pre{treatment 1.5 Tesla (T) T2w MRI. We extract a combination of first-order statistical, gradient, co-occurrence, and Gabor wavelet features from T2w MRI. To identify which of these T2w MRI texture features are potential independent prognostic markers of PSA failure, we implement a partial least squares (PLS) method to embed the data in a low{dimensional space and then use the variable importance in projections (VIP) method to quantify the contributions of individual features to classification on the PLS embedding. In spite of the poor resolution of the 1.5 T MRI data, we are able to identify three Gabor wavelet features that, in conjunction with a logistic regression classifier, yield an area under the receiver operating characteristic curve of 0.83 for predicting the probability of biochemical recurrence following radiation therapy. In comparison to both the Kattan nomogram and semantic MRI attributes, the ability of these three computer-extracted features to predict biochemical recurrence risk is demonstrated.

Quantifying the Sources of Intermodel Spread in Equilibrium Climate Sensitivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caldwell, Peter M.; Zelinka, Mark D.; Taylor, Karl E.

This paper clarifies the causes of intermodel differences in the global-average temperature response to doubled CO 2, commonly known as equilibrium climate sensitivity (ECS). The authors begin by noting several issues with the standard approach for decomposing ECS into a sum of forcing and feedback terms. This leads to a derivation of an alternative method based on linearizing the effect of the net feedback. Consistent with previous studies, the new method identifies shortwave cloud feedback as the dominant source of intermodel spread in ECS. This new approach also reveals that covariances between cloud feedback and forcing, between lapse rate andmore » longwave cloud feedbacks, and between albedo and shortwave cloud feedbacks play an important and previously underappreciated role in determining model differences in ECS. Finally, defining feedbacks based on fixed relative rather than specific humidity (as suggested by Held and Shell) reduces the covariances between processes and leads to more straightforward interpretations of results.« less

Quantifying the Sources of Intermodel Spread in Equilibrium Climate Sensitivity

DOE PAGES

Caldwell, Peter M.; Zelinka, Mark D.; Taylor, Karl E.; ...

2016-01-07

This paper clarifies the causes of intermodel differences in the global-average temperature response to doubled CO 2, commonly known as equilibrium climate sensitivity (ECS). The authors begin by noting several issues with the standard approach for decomposing ECS into a sum of forcing and feedback terms. This leads to a derivation of an alternative method based on linearizing the effect of the net feedback. Consistent with previous studies, the new method identifies shortwave cloud feedback as the dominant source of intermodel spread in ECS. This new approach also reveals that covariances between cloud feedback and forcing, between lapse rate andmore » longwave cloud feedbacks, and between albedo and shortwave cloud feedbacks play an important and previously underappreciated role in determining model differences in ECS. Finally, defining feedbacks based on fixed relative rather than specific humidity (as suggested by Held and Shell) reduces the covariances between processes and leads to more straightforward interpretations of results.« less

Propagation of cortical spreading depression into the hippocampus: The role of the entorhinal cortex.

PubMed

Martens-Mantai, Tanja; Speckmann, Erwin-Josef; Gorji, Ali

2014-07-22

Propagation of cortical spreading depression (CSD) to the subcortical structures could be the underlying mechanism of some neurological deficits in migraine with aura. The entorhinal cortex (EC) as a gray matter bridge between the neocortex and subcortical regions plays an important role in this propagation. In vitro combined neocortex-hippocampus brain slices were used to study the propagation pattern of CSD between the neocortex and the hippocampus. The effects of different compounds as well as tetanic electrical stimulations in the EC on propagation of CSD to the hippocampus were investigated. Repetitive induction of CSD by KCl injection in the somatosensory cortex enhanced the probability of CSD entrance to the hippocampus via EC. Local application of AMPA receptor blocker CNQX and cannabinoid receptor agonist WIN 55212-2 in EC facilitated the propagation of CSD to the hippocampus, whereas application of NMDA receptor blocker APV and GABA A receptor blocker bicuculline in this region reduced the probability of CSD penetration to the hippocampus. Application of tetanic stimulation in EC also facilitated the propagation of CSD entrance to the hippocampus. Our data suggest the importance of synaptic plasticity of EC in filtering the propagation of CSD into subcortical structures and possibly the occurrence of concomitant neurological deficits. Synapse, 2014. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Surgical Treatment for Extracapsular Condylar Fractures of the Mandible.

PubMed

Closs Ono, Maria C; de Morais, André D; Freitas, Renato da S; de Oliveira E Cruz, Gilvani A

2018-02-26

Condylar fractures are considered the most controversial mandibular fractures, regarding both the diagnosis and the treatment. With the increase in surgical indications for handling this type of fracture, it is important to discuss about the advantages and disadvantages of the several surgical approaches available. This article describes the surgical details and postoperative results of the mini-retromandibular transparotid approach for treating extracapsular condylar fractures of the mandible. In a 1-year period, 16 patients affected by extracapsular condylar fractures with surgical indication were treated with the mini-retromandibular transparotid approach. All the surgeries were executed by the same surgeon. Preoperative and postoperative details of each patient were analyzed. In the postoperatory, only 2 patients had purulent drainage in the associated fractures area and only 1 patient had paresis of the buccal branch of the facial nerve. No scar issues concerning the surgical wound were observed and reintervention was not necessary in any of the patients. The mini-retromandibular transparotid approach offers advantages and should be included as an option for the open treatment of extracapsular condylar fractures of the mandible.

Decision Making in the Management of Extracapsular Fractures of the Proximal Femur – is the Dynamic Hip Screw the Prevailing Gold Standard?

PubMed Central

Jacob, Joshua; Desai, Ankit; Trompeter, Alex

2017-01-01

Currently, approximately half of all hip fractures are extracapsular, with an incidence as high as 50 in 100,000 in some countries. The common classification systems fail to explain the logistics of fracture classification and whether they all behave in the same manner. The Muller AO classification system is a useful platform to delineate stable and unstable fractures. The Dynamic hip screw (DHS) however, has remained the ‘gold standard’ implant of choice for application in all extracapsular fractures. The DHS relies on the integrity and strength of the lateral femoral wall as well as the postero-medial fragment. An analysis of several studies indicates significant improvements in design and techniques to ensure a better outcome with intramedullary nails. This article reviews the historical trends that helped to evolve the DHS implant as well as discussing if the surgeon should remain content with this implant. We suggest that the gold standard surgical management of extracapsular fractures can, and should, evolve. PMID:29290858

Radiotherapy on hidradenocarcinoma.

PubMed

Lalya, Issam; Hadadi, Khalid; Tazi, El Mehdi; Lalya, Ilham; Bazine, Amine; Andaloussy, Khalid; Elmarjany, Mohamed; Sifat, Hassan; Hassouni, Khalid; Kebdani, Tayeb; Mansouri, Hamid; Benjaafar, Noureddine; Elgueddari, Brahim Khalil

2011-01-01

Clear cell Hidradenocarcinoma is a rare carcinoma arising from sweat glands. It is an aggressive tumor that most metastasizes to regional lymph nodes and distant viscera; surgery with safe margins is the mainstay of treatment. We report a case of 68-year-old woman who presented with an invasive clear cell hidradenocarcinoma situated in the left parotid area which recurred 5 months after surgery, this recurrence was managed successfully by high-dose irradiation of the tumor bed (66 Gy) and regional lymphatic chains (50 Gy), after a follow-up of more than 15 months, the patient is in good local control without significant toxicity. POST OPERATIVE RADIOTHERAPY ALLOWS BETTER LOCAL CONTROL AND SHOULD BE MANDATORY WHEN HISTOLOGICAL FEATURES PREDICTIVE OF RECURRENCE ARE PRESENT: positive margins, histology poorly differentiated, perineural invasion, vascular and lymphatic invasion, lymph node involvement, and extracapsular spread.

Predicted extracapsular invasion of hilar lymph node metastasis by fusion positron emission tomography/computed tomography in patients with lung cancer

PubMed Central

MAKINO, TAKASHI; HATA, YOSHINOBU; OTSUKA, HAJIME; KOEZUKA, SATOSHI; ISOBE, KAZUTOSHI; TOCHIGI, NOBUMI; SHIRAGA, NOBUYUKI; SHIBUYA, KAZUTOSHI; HOMMA, SAKAE; IYODA, AKIRA

2015-01-01

Intraoperative detection of hilar lymph node metastasis, particularly with extracapsular invasion, may affect the surgical procedure in patients with lung cancer, as the preoperative estimation of hilar lymph node metastasis is unsatisfactory. The aim of this study was to investigate whether fusion positron emission tomography/computed tomography (PET/CT) is able to predict extracapsular invasion of hilar lymph node metastasis. Between April, 2007 and April, 2013, 509 patients with primary lung cancer underwent surgical resection at our institution, among whom 28 patients exhibiting hilar lymph node metastasis (at stations 10 and 11) were enrolled in this study. A maximum lymph node standardized uptake value of >2.5 in PET scans was interpreted as positive. A total of 17 patients had positive preoperative PET/CT findings in their hilar lymph nodes, while the remaining 11 had negative findings. With regard to extracapsular nodal invasion, the PET/CT findings (P=0.0005) and the histological findings (squamous cell carcinoma, P=0.05) were found to be significant predictors in the univariate analysis. In the multivariate analysis, the PET/CT findings were the only independent predictor (P=0.0004). The requirement for extensive pulmonary resection (sleeve lobectomy, bilobectomy or pneumonectomy) was significantly more frequent in the patient group with positive compared with the group with negative PET/CT findings (76 vs. 9%, respectively, P=0.01). Therefore, the PET/CT findings in the hilar lymph nodes were useful for the prediction of extracapsular invasion and, consequently, for the estimation of possible extensive pulmonary resection. PMID:26623046

Predicted extracapsular invasion of hilar lymph node metastasis by fusion positron emission tomography/computed tomography in patients with lung cancer.

PubMed

Makino, Takashi; Hata, Yoshinobu; Otsuka, Hajime; Koezuka, Satoshi; Isobe, Kazutoshi; Tochigi, Nobumi; Shiraga, Nobuyuki; Shibuya, Kazutoshi; Homma, Sakae; Iyoda, Akira

2015-09-01

Intraoperative detection of hilar lymph node metastasis, particularly with extracapsular invasion, may affect the surgical procedure in patients with lung cancer, as the preoperative estimation of hilar lymph node metastasis is unsatisfactory. The aim of this study was to investigate whether fusion positron emission tomography/computed tomography (PET/CT) is able to predict extracapsular invasion of hilar lymph node metastasis. Between April, 2007 and April, 2013, 509 patients with primary lung cancer underwent surgical resection at our institution, among whom 28 patients exhibiting hilar lymph node metastasis (at stations 10 and 11) were enrolled in this study. A maximum lymph node standardized uptake value of >2.5 in PET scans was interpreted as positive. A total of 17 patients had positive preoperative PET/CT findings in their hilar lymph nodes, while the remaining 11 had negative findings. With regard to extracapsular nodal invasion, the PET/CT findings (P=0.0005) and the histological findings (squamous cell carcinoma, P=0.05) were found to be significant predictors in the univariate analysis. In the multivariate analysis, the PET/CT findings were the only independent predictor (P=0.0004). The requirement for extensive pulmonary resection (sleeve lobectomy, bilobectomy or pneumonectomy) was significantly more frequent in the patient group with positive compared with the group with negative PET/CT findings (76 vs. 9%, respectively, P=0.01). Therefore, the PET/CT findings in the hilar lymph nodes were useful for the prediction of extracapsular invasion and, consequently, for the estimation of possible extensive pulmonary resection.

Management of extra-capsular temporo-mandibular joint ankylosis: does conservative approach to treatment have a role?

PubMed

Anyanechi, C E; Osunde, O D; Bassey, G O

2015-06-01

The conventional management of fibrous extracapsular temporo-mandibular joint (TMJ) ankylosis, a debilitating disease, is associated with surgical complications and financial burden on the patients. To assess the outcome of conservative approach to the management of fibrous extracapsular TMJ ankylosis. This is a prospective study of patients who presented at the Dental and Maxillofacial Surgery Clinic of the University of Calabar Teaching Hospital, Nigeria, during the period from January 1999 to December 2012 with a history of inability to open the mouth diagnosed as fibrous extracapsular TMJ ankylosis. Twenty-one subjects were treated and their ages ranged from 11 to 22 years with mean at 15.0 years. There were 13 (61.9 %) males and 8 (38.1 %) females with male: female ratio of 1.6:1. The aetiological factor that predisposed to formation of extracapsular TMJ ankylosis was facial trauma. There was no facial asymmetry and the side distribution of the affliction showed that 1 (4.8 %) was bilateral while 20 (95.2 %) were unilateral. Eight cases (38.1 %) were incomplete ankylosis while the rest (n = 13, 61.9 %) were complete. The shorter the duration of fibrous ankylosis and the greater the initial inter-incisal distance before treatment, the better the treatment outcome. The outcome of treatment suggests that the conservative approach to management of this condition was beneficial to these patients because they presented early. However, randomized controlled clinical trials are needed to validate this treatment option.

Manual small incision extracapsular cataract surgery in Australia.

PubMed

van Zyl, Lourens; Kahawita, Shyalle; Goggin, Michael

2014-11-01

Examination of the results and describing the technique of manual small incision extracapsular cataract extraction on patients with advanced cataracts in urban Australia. A descriptive case series. Thirty-eight patients at three public hospitals, one tertiary and two secondary ophthalmic units in urban Australia. Forty eyes with dense mature cataracts with hand movement vision or worse underwent a planned manual small incision extracapsular cataract extraction instead of traditional phaco-emulsification. Postoperative visual aquity, surgically induced astigmatism and complications. Seventy-eight per cent of patients had an uncorrected visual acuity of 6/12 or better on the first postoperative day. Eighty-three per cent of patients had a distance corrected visual acuity of 6/9 or better 3 months postoperatively. One case was complicated by a posterior capsule rupture. No cases of endophthalmitis were reported. The summated vector mean of the surgically induced astigmatism was 0.089D at 93°. Manual small incision extracapsular cataract extraction is an efficacious cataract surgery technique with good visual outcome and is a safe alternative to phaco-emulsification in suitable cases in a first-world setting. © 2014 Royal Australian and New Zealand College of Ophthalmologists.

Treatment of medial shoulder joint instability in dogs by extracapsular stabilization with a prosthetic ligament: 39 cases (2008-2013).

PubMed

O'Donnell, Erica M; Canapp, Sherman O; Cook, James L; Pike, Fred

2017-11-01

OBJECTIVE To investigate clinical outcomes for dogs surgically treated for medial shoulder joint instability (MSI) by extracapsular stabilization with a prosthetic ligament. DESIGN Retrospective multicenter case series. ANIMALS 39 client-owned dogs. PROCEDURES Medical records of 3 veterinary medical centers were searched to identify dogs with MSI diagnosed by clinical examination and arthroscopic assessment and treated by extracapsular stabilization with a prosthetic ligament. A minimum 6-month follow-up period was required for study inclusion. Signalment, function or use of the dog, duration of clinical signs, clinical and diagnostic imaging data, MSI grade (1 [mild] to 4 [complete luxation]), follow-up duration, complications, and outcome data were recorded. RESULTS All grades of MSI were represented. Implants were placed successfully in all dogs. Complications (4 major and 2 minor) were recorded for 6 of 39 (15%) dogs; all were treated successfully. Function at the time of last follow-up (6 to 68 months) was deemed full in 30 of 39 (77%) dogs and acceptable in 9 (23%). CONCLUSIONS AND CLINICAL RELEVANCE Surgical treatment of MSI in dogs by extracapsular stabilization with a prosthetic ligament was associated with a complication rate considered acceptable for orthopedic procedures. All patient outcomes were considered successful.

Prognostic factors and relative risk for survival in N1-3 oral squamous cell carcinoma: a multivariate analysis using Cox's hazard model.

PubMed

Noguchi, M; Kido, Y; Kubota, H; Kinjo, H; Kohama, G

1999-12-01

The records of 136 patients with N1-3 oral squamous cell carcinoma treated by surgery were investigated retrospectively, with the aim of finding out which factors were predictive of survival on multivariate analysis. Four independent factors significantly influenced survival in the following order: pN stage; T stage; histological grade; and N stage. The most significant was pN stage, the five-year survival for patients with pN0 being 91% and for patients with pN1-3 41%. A further study was carried out on the 80 patients with pN1-3 to find out their prognostic factors for survival and the independent factors identified by multivariate analysis were T stage and presence or absence of extracapsular spread to metastatic lymph nodes.

Radiotherapy on hidradenocarcinoma

PubMed Central

Lalya, Issam; Hadadi, Khalid; Tazi, El Mehdi; Lalya, Ilham; Bazine, Amine; Andaloussy, Khalid; Elmarjany, Mohamed; Sifat, Hassan; Hassouni, Khalid; Kebdani, Tayeb; Mansouri, Hamid; Benjaafar, Noureddine; Elgueddari, Brahim Khalil

2011-01-01

Context: Clear cell Hidradenocarcinoma is a rare carcinoma arising from sweat glands. It is an aggressive tumor that most metastasizes to regional lymph nodes and distant viscera; surgery with safe margins is the mainstay of treatment. Case Report: We report a case of 68-year-old woman who presented with an invasive clear cell hidradenocarcinoma situated in the left parotid area which recurred 5 months after surgery, this recurrence was managed successfully by high-dose irradiation of the tumor bed (66 Gy) and regional lymphatic chains (50 Gy), after a follow-up of more than 15 months, the patient is in good local control without significant toxicity. Conclusion: Post operative radiotherapy allows better local control and should be mandatory when histological features predictive of recurrence are present: positive margins, histology poorly differentiated, perineural invasion, vascular and lymphatic invasion, lymph node involvement, and extracapsular spread. PMID:22540063

Prolonged colonisation with Escherichia coli O25:ST131 versus other extended-spectrum beta-lactamase-producing E. coli in a long-term care facility with high endemic level of rectal colonisation, the Netherlands, 2013 to 2014.

PubMed

Overdevest, Ilse; Haverkate, Manon; Veenemans, Jacobien; Hendriks, Yvonne; Verhulst, Carlo; Mulders, Ans; Couprie, Willemijn; Bootsma, Martin; Johnson, James; Kluytmans, Jan

2016-10-20

The extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli clone ST131 (ESBL-ST131) has spread in healthcare settings worldwide. The reasons for its successful spread are unknown, but might include more effective transmission and/or longer persistence. We evaluated the colonisation dynamics of ESBL-producing E. coli (ESBL-EC), including ESBL-ST131, in a long-term care facility (LTCF) with an unusually high prevalence of rectal ESBL-EC colonisation. During a 14-month period, rectal or faecal samples were obtained from 296 residents during six repetitive prevalence surveys, using ESBL-selective culture. Transmission rates, reproduction numbers, and durations of colonisation were compared for ESBL-ST131 vs other ESBL-EC. Furthermore, the likely time required for ESBL-ST131 to disappear from the LTCF was estimated. Over time, the endemic level of ESBL-ST131 remained elevated whereas other ESBL-EC returned to low-level prevalence, despite comparable transmission rates. Survival analysis showed a half-life of 13 months for ESBL-ST131 carriage, vs two to three months for other ESBL-EC (p < 0.001). Per-admission reproduction numbers were 0.66 for ESBL-ST131 vs 0.56 for other ESBL-EC, predicting a mean time of three to four years for ESBL-ST131 to disappear from the LTCF under current conditions. Transmission rates were comparable for ESBL-ST131 vs other ESBL-EC. Prolonged rectal carriage explained the persistence of ESBL-ST131 in the LTCF. This article is copyright of The Authors, 2016.

The human anterior lens capsule--an attempted chemical debridement of epithelial cells by ethylenediaminetetracetic acid (EDTA) and trypsin.

PubMed Central

Humphry, R C; Davies, E G; Jacob, T J; Thompson, G M

1988-01-01

The addition of edetic acid (EDTA) or trypsin to the infusion during a simulated extracapsular cataract extraction on cadaver eyes facilitates the removal of lens epithelial cells from the anterior capsule. Modification of the chemical composition of infusions used during extracapsular surgery may maximise lens epithelial cell removal and hence reduce the incidence of opacification of the posterior capsule after cataract extraction. Images PMID:3134044

An outbreak of endophthalmitis after extracapsular cataract surgery probably caused by endotoxin contaminated distilled water used to dissolve acetylcholine.

PubMed

Boks, T; van Dissel, J T; Teterissa, N; Ros, F; Mahmut, M H; Utama, E D; Rol, M; van Asdonk, P; Airiani, S; van Meurs, J C

2006-09-01

To study possible causes of an outbreak of severe endophthalmitis after planned extracapsular cataract surgery in Medan, Indonesia. In a 3 week period in November 2001, 17 of 43 patients developed signs of endophthalmitis after planned extracapsular cataract surgery. A search for possible causes was undertaken 4 months later. In autoclaved stored distilled water used to dissolve acetylcholine (used in 16 of 17 patients with endophthalmitis) a high amount of endotoxin was detected in a human blood essay, as well as a small number of non-typeable Pseudomonas spp. These findings suggest that distilled water used as solvent for acetylcholine was responsible for this outbreak of endophthalmitis. As a consequence, we now rely on solvents that are regularly checked for impurities such as an intravenous infusion fluid, rather than on vials with distilled water that is presumed to be sterile and kept for some time.

Pleomorphic adenoma of the accessory parotid gland: case report and reappraisal of intraoral extracapsular dissection for management.

PubMed

Tsegga, Tibebu M; Britt, Jennifer D; Ellwanger, Aragon R

2015-03-01

Pleomorphic adenoma is the most common tumor of the major and minor salivary glands. Rarely is it found evolving from an ectopic location of major salivary glandular tissue in the mid cheek. A healthy 56-year-old woman presented to our institution with a 20-year duration of a slowly growing right cheek soft tissue mass that was causing facial asymmetry. No significant functional or neurosensory dysfunction was appreciated. Radiologic examination showed a heterogeneous, hyperintense, well-delineated mass within the region of the right buccal fat pad. Fine-needle aspiration biopsy showed benign salivary gland elements consistent with pleomorphic adenoma. The decision was made to perform intraoral extracapsular dissection for removal. Discussion of the clinical assessment and magnetic resonance imaging evaluation with an emphasis on intraoral extracapsular dissection for definitive surgical therapy of longstanding benign salivary gland tumors is emphasized. Published by Elsevier Inc.

Aquaporin-4 Regulates the Velocity and Frequency of Cortical Spreading Depression in Mice

PubMed Central

Yao, Xiaoming; Smith, Alex J.; Jin, Byung-Ju; Zador, Zsolt; Manley, Geoffrey T.; Verkman, A.S.

2016-01-01

The astrocyte water channel aquaporin-4 (AQP4) regulates extracellular space (ECS) K+ concentration ([K+]e) and volume dynamics following neuronal activation. Here, we investigated how AQP4-mediated changes in [K+]e and ECS volume affect the velocity, frequency and amplitude of cortical spreading depression (CSD) depolarizations produced by surface KCl application in wild-type (AQP4+/+) and AQP4-deficient (AQP4−/−) mice. Contrary to initial expectations, both the velocity and frequency of CSD were significantly reduced in AQP4−/− mice when compared to AQP4+/+ mice, by 22% and 32%, respectively. Measurement of [K+]e with K+-selective microelectrodes demonstrated an increase to ~35 mM during spreading depolarizations in both AQP4+/+ and AQP4−/− mice, but the rates of [K+]e increase (3.5 vs. 1.5 mM/s) and reuptake (t1/2 33 vs. 61 s) were significantly reduced in AQP4−/− mice. ECS volume fraction measured by trimethylammonium iontophoresis was greatly reduced during depolarizations from 0.18 to 0.053 in AQP4+/+ mice, and 0.23 to 0.063 in AQP4−/− mice. Analysis of the experimental data using a mathematical model of CSD propagation suggested that the reduced velocity of CSD depolarizations in AQP4−/− mice was primarily a consequence of the slowed increase in [K+]e during neuronal depolarization. These results demonstrate that AQP4 effects on [K+]e and ECS volume dynamics accelerate CSD propagation. PMID:25944186

Initiation and slow propagation of epileptiform activity from ventral to dorsal medial entorhinal cortex is constrained by an inhibitory gradient.

PubMed

Ridler, Thomas; Matthews, Peter; Phillips, Keith G; Randall, Andrew D; Brown, Jonathan T

2018-06-01

The medial entorhinal cortex (mEC) has an important role in initiation and propagation of seizure activity. Several anatomical relationships exist in neurophysiological properties of mEC neurons; however, in the context of hyperexcitability, previous studies often considered it as a homogeneous structure. Using multi-site extracellular recording techniques, ictal-like activity was observed along the dorso-ventral axis of the mEC in vitro in response to various ictogenic stimuli. This originated predominantly from ventral areas, spreading to dorsal mEC with a surprisingly slow velocity. Modulation of inhibitory tone was capable of changing the slope of ictal initiation, suggesting seizure propagation behaviours are highly dependent on levels of GABAergic function in this region. A distinct disinhibition model also showed, in the absence of inhibition, a prevalence for interictal-like initiation in ventral mEC, reflecting the intrinsic differences in mEC neurons. These findings suggest the ventral mEC is more prone to hyperexcitable discharge than the dorsal mEC, which may be relevant under pathological conditions. The medial entorhinal cortex (mEC) has an important role in the generation and propagation of seizure activity. The organization of the mEC is such that a number of dorso-ventral relationships exist in neurophysiological properties of neurons. These range from intrinsic and synaptic properties to density of inhibitory connectivity. We examined the influence of these gradients on generation and propagation of epileptiform activity in the mEC. Using a 16-shank silicon probe array to record along the dorso-ventral axis of the mEC in vitro, we found 4-aminopyridine application produces ictal-like activity originating predominantly in ventral areas. This activity spreads to dorsal mEC at a surprisingly slow velocity (138 μm s -1 ), while cross-site interictal-like activity appeared relatively synchronous. We propose that ictal propagation is constrained by differential levels of GABAergic control since increasing (diazepam) or decreasing (Ro19-4603) GABA A receptor activation, respectively, reduced or increased the slope of ictal initiation. The observation that ictal activity is predominately generated in ventral mEC was replicated using a separate 0-Mg 2+ model of epileptiform activity in vitro. By using a distinct disinhibition model (co-application of kainate and picrotoxin) we show that additional physiological features (for example intrinsic properties of mEC neurons) still produce a prevalence for interictal-like initiation in ventral mEC. These findings suggest that the ventral mEC is more likely to initiate hyperexcitable discharges than the dorsal mEC, and that seizure propagation is highly dependent on levels of GABAergic expression across the mEC. © 2018 The Authors. The Journal of Physiology © 2018 The Physiological Society.

Occurrence and genetic characteristics of third-generation cephalosporin-resistant Escherichia coli in Swiss retail meat.

PubMed

Vogt, Debora; Overesch, Gudrun; Endimiani, Andrea; Collaud, Alexandra; Thomann, Andreas; Perreten, Vincent

2014-10-01

Prevalence and genetic relatedness were determined for third-generation cephalosporin-resistant Escherichia coli (3GC-R-Ec) detected in Swiss beef, veal, pork, and poultry retail meat. Samples from meat-packing plants (MPPs) processing 70% of the slaughtered animals in Switzerland were purchased at different intervals between April and June 2013 and analyzed. Sixty-nine 3GC-R-Ec isolates were obtained and characterized by microarray, PCR/DNA sequencing, Multi Locus Sequence Typing (MLST), and plasmid replicon typing. Plasmids of selected strains were transformed by electroporation into E. coli TOP10 cells and analyzed by plasmid MLST. The prevalence of 3GC-R-Ec was 73.3% in chicken and 2% in beef meat. No 3GC-R-Ec were found in pork and veal. Overall, the bla(CTX-M-1) (79.4%), bla(CMY-2) (17.6%), bla(CMY-4) (1.5%), and bla(SHV-12) (1.5%) β-lactamase genes were detected, as well as other genes conferring resistance to chloramphenicol (cmlA1-like), sulfonamides (sul), tetracycline (tet), and trimethoprim (dfrA). The 3GC-R-Ec from chicken meat often harbored virulence genes associated with avian pathogens. Plasmid incompatibility (Inc) groups IncI1, IncFIB, IncFII, and IncB/O were the most frequent. A high rate of clonality (e.g., ST1304, ST38, and ST93) among isolates from the same MPPs suggests that strains persist at the plant and spread to meat at the carcass-processing stage. Additionally, the presence of the blaCTX-M-1 gene on an IncI1 plasmid sequence type 3 (IncI1/pST3) in genetically diverse strains indicates interstrain spread of an epidemic plasmid. The bla(CMY-2) and bla(CMY-4) genes were located on IncB/O plasmids. This study represents the first comprehensive assessment of 3GC-R-Ec in meat in Switzerland. It demonstrates the need for monitoring contaminants and for the adaptation of the Hazard Analysis and Critical Control Point concept to avoid the spread of multidrug-resistant bacteria through the food chain.

Extracapsular cataract extraction with and without intra-ocular lenses in black patients.

PubMed

Welsh, N H

1992-04-04

Cataracts are the commonest cause of blindness in Third-World countries and cataract extraction is the commonest eye operation performed anywhere. Patients require optical correction after surgery either in the form of an intra-ocular lens (IOL) or bifocal aphakic glasses. The standard operative procedure in First-World countries is an extracapsular cataract extraction with an IOL. This type of operation has been thought to be contraindicated in black patients because of the complications and lack of adequate postoperative follow-up. During 1987-1989 3,144 cataract extractions, of which 2,157 were simple extracapsular extractions and 987 had IOLs inserted, were performed at the above hospitals. The two groups were compared for complications and visual results. The complications were similar in both groups and were acceptable, therefore posterior lens implantation confers no additional risk on routine extracapsular cataract extraction. The visual results in the IOL group with and without additional glasses were compared with those patients who had correcting aphakic glasses. In the corrected IOL group, 98% of patients saw better than 6/24, whereas in the aphakic spectacle group, 87.5% saw 6/24 or better. Since the majority of black patients cannot afford costly prescribed spectacles, it was important to analyse the visual acuity in patients who had IOLs and were uncorrected; 81.6% saw 6/24 or better. IOLs in black patients are therefore indicated but the disadvantage is the cost.

Correlation between obesity and prognostic/predictive parameters with emphasis on the importance of lymph node metastases in patients with invasive breast carcinoma.

PubMed

Hankó-Bauer, Orsolya; Georgescu, Rares; Coros, Marius F; Boros, Monica; Barsan, Iulia; Stolnicu, Simona

We aimed to evaluate whether obese women experience more advanced invasive breast carcinoma (IBC) with a higher number of involved lymph nodes, higher range of axillary lymph node ratio (LNR) and presence and size of extracapsular extension as it may have an impact on prognosis and management. 245 patients diagnosed with IBC were divided into normal weight (NW), overweight (OW) and obese (OB) groups. Patients were divided into high range of LNR (LNR over or equal to 0.2) and low LNR (LNR less than 0.2). The extracapsular extension dimensions were measured on the original slides of each case and grouped into ≤ 1 mm and > 1 mm. 84 patients (33.07%) were OW, 72 (29.38%) OB and 91 (37.14%) NW. 45.7% of cases had macrometastasis in the axillary lymph nodes. NW patients had significantly fewer metastatic lymph nodes (p = 0.05) than in the OW/OB groups. There was no statistically significant difference between BMI groups according to the LNR (p = 0.66). Out of 111 cases with macrometastasis, 58 cases (52.25%) had extracapsular extension (ECE) (11.7% NW, 24.32% OW and 16.22% OB). Significantly more OW patients presented extranodal invasion (p = 0.04). We found no statistically significant relationship between the extracapsular extension diameter and BMI groups (p = 0.1).

Can Prostate-Specific Antigen Kinetics before Prostate Biopsy Predict the Malignant Potential of Prostate Cancer?

PubMed

Kim, Sang Jin; Jeong, Tae Yoong; Yoo, Dae Seon; Park, Jinsung; Cho, Seok; Kang, Seok Ho; Lee, Sang Hyub; Jeon, Seung Hyun; Lee, Tchun Yong; Park, Sung Yul

2015-11-01

To predict the malignant potential of prostate cancer (PCa) according to prostate-specific antigen velocity (PSAV), PSA density (PSAD), free/total PSA ratio (%fPSA), and digital rectal examination (DRE). From January 2009 to December 2012, 548 adult male patients were diagnosed with PCa by prostate biopsy at four hospitals in Korea. We retrospectively analyzed 155 adult male patients with an initial PSA level≤10 ng/mL and whose PSA levels had been checked more than two times at least 6 months before they had been diagnosed with PCa, with test intervals of more than 3 months. Patients with a urinary tract infection, and patients who had previously undergone cystoscopy or surgery of the prostate were excluded. We separated patients into two groups according to Gleason sum [Gleason sum≤7 (n=134) or Gleason sum≥8 (n=21)] and the presence of extracapsular invasion [organ confined (n=129) or extracapsular invasion (n=26)]. Differences between the groups were compared. The group with a Gleason sum≥8 or extracapsular invasion of PCa showed high PSAV and significantly lower %fPSA. There were no significant differences in PSAD and the presence of an abnormality on DRE between two groups. In PCa patients treated with other therapies besides prostatectomy, a high PSA velocity and a low %fPSA may predict high grade PCa with a Gleason sum≥8 or the presence of extracapsular invasion.

An outbreak of endophthalmitis after extracapsular cataract surgery probably caused by endotoxin contaminated distilled water used to dissolve acetylcholine

PubMed Central

Boks, T; van Dissel, J T; Teterissa, N; Ros, F; Mahmut, M H; Utama, E D; Rol, M; van Asdonk, P; Airiani, S; van Meurs, J C

2006-01-01

Aim To study possible causes of an outbreak of severe endophthalmitis after planned extracapsular cataract surgery in Medan, Indonesia. Methods In a 3 week period in November 2001, 17 of 43 patients developed signs of endophthalmitis after planned extracapsular cataract surgery. A search for possible causes was undertaken 4 months later. Results In autoclaved stored distilled water used to dissolve acetylcholine (used in 16 of 17 patients with endophthalmitis) a high amount of endotoxin was detected in a human blood essay, as well as a small number of non‐typeable Pseudomonas spp. Conclusions These findings suggest that distilled water used as solvent for acetylcholine was responsible for this outbreak of endophthalmitis. As a consequence, we now rely on solvents that are regularly checked for impurities such as an intravenous infusion fluid, rather than on vials with distilled water that is presumed to be sterile and kept for some time. PMID:16687451

In vitro activity of tafenoquine alone and in combination with artemisinin against Plasmodium falciparum.

PubMed

Ramharter, Michael; Noedl, Harald; Thimasarn, Krongthong; Wiedermann, Gerhard; Wernsdorfer, Gunther; Wernsdorfer, Walther H

2002-07-01

Emergence and spread of drug-resistant falciparum malaria has created an urgent demand for alternative therapeutic agents. This study was conducted to assess the in vitro blood schizontocidal activity of tafenoquine, the most advanced candidate drug of the 8-aminoquinolines, and of its 1:1 combination with artemisinin in fresh isolates of Plasmodium falciparum in an area with multi-drug resistance, measuring the inhibition of schizont maturation. In 43 successfully tested parasite isolates, the mean effective concentrations (ECs) of tafenoquine were 209 nmol/L for the EC50, and 1,414 nmol/L for the EC90. Tafenoquine showed no significant activity relationships with mefloquine, artemisinin, and chloroquine. With quinine, a highly significant activity relationship was observed at the EC50, but not at the EC90. The EC50, and EC90 of the tafenoquine-artemisinin combination were 15.9 nmol/L and 84.3 nmol/L. The combination was synergistic. Tafenoquine appears to be a promising candidate for treating multidrug-resistant falciparum malaria, especially in combination with artemisinin derivatives.

The Anti-Inflammatory Cytokine Interleukin-19 Is Expressed in and Angiogenic for Human Endothelial Cells

PubMed Central

Jain, Surbhi; Gabunia, Khatuna; Kelemen, Sheri E.; Panetti, Tracee S.; Autieri, Michael V.

2010-01-01

OBJECTIVE The expression and effects of anti-inflammatory interleukins on endothelial cell (EC) activation and development of angiogenesis is uncharacterized. The purpose of this study is to characterize the expression and function of Interleukin-19 (IL-19), a recently described Th2 anti-inflammatory interleukin on EC pathophysiology. METHODS and RESULTS We demonstrate by immunohistochemistry and immunoblot that IL-19 is expressed in inflamed, but not normal human coronary endothelium, and can be induced in cultured human EC by serum and bFGF. IL-19 is mitogenic, chemotactic, and promotes cell EC spreading. IL-19 activates the signaling proteins STAT3, p44/42, and Rac1. In functional ex vivo studies, IL-19 promotes cord-like structure formation of cultured EC and also enhances microvessel sprouting in the mouse aortic ring assay. IL-19 induces tube formation in matrigel plugs in vivo. CONCLUSIONS These data are the first to report expression of the anti-inflammatory interleukin IL-19 in EC, and the first to indicate that IL-19 is mitogenic and chemotactic for EC, and can induce the angiogenic potential of EC. PMID:20966397

On the Emergent Constraints of Climate Sensitivity [On proposed emergent constraints of climate sensitivity

DOE PAGES

Qu, Xin; Hall, Alex; DeAngelis, Anthony M.; ...

2018-01-11

Differences among climate models in equilibrium climate sensitivity (ECS; the equilibrium surface temperature response to a doubling of atmospheric CO2) remain a significant barrier to the accurate assessment of societally important impacts of climate change. Relationships between ECS and observable metrics of the current climate in model ensembles, so-called emergent constraints, have been used to constrain ECS. Here a statistical method (including a backward selection process) is employed to achieve a better statistical understanding of the connections between four recently proposed emergent constraint metrics and individual feedbacks influencing ECS. The relationship between each metric and ECS is largely attributable tomore » a statistical connection with shortwave low cloud feedback, the leading cause of intermodel ECS spread. This result bolsters confidence in some of the metrics, which had assumed such a connection in the first place. Additional analysis is conducted with a few thousand artificial metrics that are randomly generated but are well correlated with ECS. The relationships between the contrived metrics and ECS can also be linked statistically to shortwave cloud feedback. Thus, any proposed or forthcoming ECS constraint based on the current generation of climate models should be viewed as a potential constraint on shortwave cloud feedback, and physical links with that feedback should be investigated to verify that the constraint is real. Additionally, any proposed ECS constraint should not be taken at face value since other factors influencing ECS besides shortwave cloud feedback could be systematically biased in the models.« less

On the Emergent Constraints of Climate Sensitivity [On proposed emergent constraints of climate sensitivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Qu, Xin; Hall, Alex; DeAngelis, Anthony M.

Differences among climate models in equilibrium climate sensitivity (ECS; the equilibrium surface temperature response to a doubling of atmospheric CO2) remain a significant barrier to the accurate assessment of societally important impacts of climate change. Relationships between ECS and observable metrics of the current climate in model ensembles, so-called emergent constraints, have been used to constrain ECS. Here a statistical method (including a backward selection process) is employed to achieve a better statistical understanding of the connections between four recently proposed emergent constraint metrics and individual feedbacks influencing ECS. The relationship between each metric and ECS is largely attributable tomore » a statistical connection with shortwave low cloud feedback, the leading cause of intermodel ECS spread. This result bolsters confidence in some of the metrics, which had assumed such a connection in the first place. Additional analysis is conducted with a few thousand artificial metrics that are randomly generated but are well correlated with ECS. The relationships between the contrived metrics and ECS can also be linked statistically to shortwave cloud feedback. Thus, any proposed or forthcoming ECS constraint based on the current generation of climate models should be viewed as a potential constraint on shortwave cloud feedback, and physical links with that feedback should be investigated to verify that the constraint is real. Additionally, any proposed ECS constraint should not be taken at face value since other factors influencing ECS besides shortwave cloud feedback could be systematically biased in the models.« less

A new technique of extracapsular restoration with a tie made of ethylene tetrafluoroethylene (ETFE) for rupture of the cranial cruciate ligament in dogs.

PubMed

Yamada, E; Imayama, Y; Katano, S; Nagashima, F; Shibata, T

1996-06-01

A new extracapsular technique for repair of canine cranial cruciate ligament rupture using an ethylene tetrafluoroethylene (ETFE) tie was presented. Eighteen dogs (body weight: 6.0-46 kg) with this problem were used for this study. The advantages of this method were 1) the operation was easily performed. 2) Joint could be stabilized by proper fixation with microadjustment during operation. 3) This method presented less surgical invasion than the intracapsular one, since wide incision was not conducted over peripheral tissue of the stifle joint.

Extracapsular dissection for warthin tumors despite the risk of ipsilateral metachronous occurrence.

PubMed

Mantsopoulos, Konstantinos; Goncalves, Miguel; Koch, Michael; Iro, Heinrich

2018-03-24

The ideal extent of surgical intervention for cystadenolymphomas of the parotid gland remains a matter of controversy. The aim of our study was to assess the surgical outcome after extracapsular dissection for cystadenolymphomas of the parotid gland. A further purpose of this study was to examine how the number of primary cystadenolymphomas or the size of the primary lesion influences the possibility of an ipsilateral metachronous tumor occurrence. Retrospective clinical study. A retrospective evaluation of the records was carried out for all patients treated for cystadenolymphomas of the parotid gland by means of extracapsular dissection at a tertiary referral center between 2000 and 2012. Three hundred twenty-seven patients were included in the study. Our analysis detected an overall occurrence rate of ipsilateral metachronous tumors of 3.1% (10/327) with a mean follow-up of 108.4 months. A significant difference in the rate of metachronous lesions between unilocular (1.7%) and multilocular (11.6%) tumors could be detected (χ 2 (1) = 7.342, P < .001). Our analysis was not able to find any significant influence of the maximal tumor size on the rate of metachronous tumors (χ 2 (1) = 0.634, P = .426). One of the most controversial issues in the treatment of cystadenolymphomas of the parotid gland concerns the question of which is the best therapeutic approach to be taken in such patients. Our analysis was able to demonstrate the benefits of extracapsular dissection in the management of solitary as well as carefully selected multicentric cystadenolymphomas with a consistently acceptable surgical outcome. 4. Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

Predicting extracapsular involvement in prostate cancer through the tumor contact length and the apparent diffusion coefficient.

PubMed

Granja, M F; Pedraza, C M; Flórez, D C; Romero, J A; Palau, M A; Aguirre, D A

To evaluate the diagnostic performance of the length of the tumor contact with the capsule (LTC) and the apparent diffusion coefficient (ADC) map in the prediction of microscopic extracapsular extension in patients with prostate cancer who are candidates for radical prostatectomy. We used receiver operating curves to retrospectively study the diagnostic performance of the ADC map and the LTC as predictors of microscopic extracapsular extension in 92 patients with prostate cancer and moderate to high risk who were examined between May 2011 and December 2013. The optimal cutoff for the ADC map was 0.87× 10 -3 mm 2 /s, which yielded an area under the ROC curve of 72% (95% CI: 57%-86%), corresponding to a sensitivity of 83% and a specificity of 61%. The optimal cutoff for the LTC was 17.5mm, which yielded an area under the ROC curve of 74% (95% CI: 61%-87%), corresponding to a sensitivity of 91% and a specificity of 57%. Combining the two criteria improved the diagnostic performance, yielding an area under the ROC curve of 77% (95% CI: 62%-92%), corresponding to a sensitivity of 77% and a specificity of 61%. We elaborated a logistic regression model, obtaining an area under the ROC curve of 82% (95% CI: 73%-93%). Using quantitative measures improves the diagnostic accuracy of multiparametric magnetic resonance imaging in the staging of prostate cancer. The values of the ADC and LTC were predictors of microscopic extracapsular extension, and the best results were obtained when both values were used in combination. Copyright © 2017 SERAM. Publicado por Elsevier España, S.L.U. All rights reserved.

Ability of preoperative 3.0-Tesla magnetic resonance imaging to predict the absence of side-specific extracapsular extension of prostate cancer.

PubMed

Hara, Tomohiko; Nakanishi, Hiroyuki; Nakagawa, Tohru; Komiyama, Motokiyo; Kawahara, Takashi; Manabe, Tomoko; Miyake, Mototaka; Arai, Eri; Kanai, Yae; Fujimoto, Hiroyuki

2013-10-01

Recent studies have shown an improvement in prostate cancer diagnosis with the use of 3.0-Tesla magnetic resonance imaging. We retrospectively assessed the ability of this imaging technique to predict side-specific extracapsular extension of prostate cancer. From October 2007 to August 2011, prostatectomy was carried out in 396 patients after preoperative 3.0-Tesla magnetic resonance imaging. Among these, 132 (primary sample) and 134 patients (validation sample) underwent 12-core prostate biopsy at the National Cancer Center Hospital of Tokyo, Japan, and at other institutions, respectively. In the primary dataset, univariate and multivariate analyses were carried out to predict side-specific extracapsular extension using variables determined preoperatively, including 3.0-Tesla magnetic resonance imaging findings (T2-weighted and diffusion-weighted imaging). A prediction model was then constructed and applied to the validation study sample. Multivariate analysis identified four significant independent predictors (P < 0.05), including a biopsy Gleason score of ≥8, positive 3.0-Tesla diffusion-weighted magnetic resonance imaging findings, ≥2 positive biopsy cores on each side and a maximum percentage of positive cores ≥31% on each side. The negative predictive value was 93.9% in the combination model with these four predictors, meanwhile the positive predictive value was 33.8%. Good reproducibility of these four significant predictors and the combination model was observed in the validation study sample. The side-specific extracapsular extension prediction by the biopsy Gleason score and factors associated with tumor location, including a positive 3.0-Tesla diffusion-weighted magnetic resonance imaging finding, have a high negative predictive value, but a low positive predictive value. © 2013 The Japanese Urological Association.

Immunocompromised patients with metastatic cutaneous nodal squamous cell carcinoma of the head and neck: Poor outcome unrelated to the index lesion.

PubMed

Lam, Johnson K S; Sundaresan, Puma; Gebski, Val; Veness, Michael J

2018-05-01

Immunocompromised patients with metastatic cutaneous nodal head and neck squamous cell carcinoma (HNSCC) have worse outcomes compared to the immunocompetent. The purpose of this study was to investigate the characteristics of the primary cutaneous squamous cell carcinoma (SCC), nodal pathology, and outcome between these 2 groups. Analysis of a prospective database was performed. A 2:1 pooled analysis selected 46 immunocompetent patients matched with 23 immunocompromised patients. Overall survival (OS) and relapse-free survival (RFS) were calculated using the Kaplan-Meier method. No significant difference was found in the primary tumor characteristics between the 2 groups. In the immunocompromised group, RFS (hazard ratio [HR] 2.70; P = .01) and OS (HR 2.32; P = .04) were significantly worse. Extracapsular spread was present in 100% of the immunocompromised patients. No significant difference was identified in the primary cutaneous SCC between the immunocompetent and immunocompromised patients. Immunosuppression predicted worse outcome. © 2018 Wiley Periodicals, Inc.

Invasive infection caused by Klebsiella pneumoniae is a disease affecting patients with high comorbidity and associated with high long-term mortality

PubMed Central

Nauclér, P.; Kalin, M.; Giske, C. G.

2018-01-01

Klebsiella pneumoniae (KP) is after Escherichia coli (EC) the most common gram-negative species causing invasive infections. Herein, we analyzed risk factors and prognosis in invasive infections caused by KP versus EC, in an area with low antimicrobial resistance. Moreover, we compared antimicrobial resistance and relative prevalence of KP and EC (KP/EC-ratio) in different European countries, using EARS-Net data. Adult patients admitted to Karolinska University Hospital 2006–2012 with invasive infection caused by KP (n = 599) were matched regarding sex and age with patients infected by EC. The medical records were retrospectively reviewed. Comorbidity was adjusted for with multivariable analysis. European data were retrieved from the EARS-Net database. No differences were observed in 7- and 30-day mortality between the groups. The 90-day mortality was significantly higher in the KP cohort (26% versus 17%, p<0.001), but not after adjusting for comorbidity. Malignancy was seen in 53% of the patients with KP versus 38% with EC, OR 1.86 (1.34–2.58). A significant increase in the rate of ESBL-production was observed in EC, but not in KP. The KP/EC-ratio remained stable. In contrast, European data showed increasing percentages of isolates non-susceptible to third-generation cephalosporins in EC and KP, and increasing KP/EC-ratio. Invasive infection caused by KP is a disease affecting patients with high comorbidity and associated with high 90-d mortality. The stable KP/EC-ratio and low occurrence of antimicrobial resistance in data from Karolinska University Hospital compared to aggregate data from 20 EARS-Net countries could be related to absence of clonal spread of multidrug-resistant KP. PMID:29624618

Linguine sign in musculoskeletal imaging: calf silicone implant rupture.

PubMed

Duryea, Dennis; Petscavage-Thomas, Jonelle; Frauenhoffer, Elizabeth E; Walker, Eric A

2015-08-01

Imaging findings of breast silicone implant rupture are well described in the literature. On MRI, the linguine sign indicates intracapsular rupture, while the presence of silicone particles outside the fibrous capsule indicates extracapsular rupture. The linguine sign is described as the thin, wavy hypodense wall of the implant within the hyperintense silicone on T2-weighted images indicative of rupture of the implant within the naturally formed fibrous capsule. Hyperintense T2 signal outside of the fibrous capsule is indicative of an extracapsular rupture with silicone granuloma formation. We present a rare case of a patient with a silicone calf implant rupture and discuss the MRI findings associated with this condition.

Risk factors and molecular epidemiology of community-onset, multidrug resistance extended-spectrum β-lactamase-producing Escherichia coli infections.

PubMed

Park, So Yeon; Kang, Cheol-In; Wi, Yu Mi; Chung, Doo Ryeon; Peck, Kyong Ran; Lee, Nam-Yong; Song, Jae-Hoon

2017-01-01

Although multidrug resistance (MDR) among extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) poses significant therapeutic challenges, little is known regarding the risk factors and epidemiology of community-onset MDR-ESBL-EC infections. We performed this study to investigate risk factors and the molecular epidemiology of community-onset MDR-ESBL-EC infections. We conducted a case-control-control study of community-onset infections. MDR-ESBL-EC was defined as ESBL-EC that demonstrated in vitro resistance to trimethoprim-sulfamethoxazole, fluoroquinolones (FQs), and gentamicin. Patients with MDR-ESBL-EC infections were designated as case patients. A control group I (CG I) patient was defined as a person whose clinical sample yielded ESBL-EC that did not meet the criteria for MDR. A control group II (CG II) patient was defined as a patient with a non-ESBL-EC infection. Of 108 patients with ESBL-EC infections, 30 cases (27.8%) were due to MDR-ESBL-EC. Compared with CG I, prior use of FQs (odds ratio [OR], 3.16; 95% confidence interval [CI], 1.11 to 8.98) and immunosuppressant use (OR, 10.47; 95% CI, 1.07 to 102.57) were significantly associated with MDR-ESBL-EC. Compared with CG II, prior use of FQs (OR, 15.53; 95% CI, 2.86 to 84.27) and healthcare-associated infection (OR, 5.98; 95% CI, 2.26 to 15.86) were significantly associated with MDR-ESBL-EC. CTX-M-15 was the most common in MDR-ESBL-EC infections (59.1% [13/22]), while CTX-M-14 was the most common in non-MDR-ESBL-EC infections (41.6% [32/77]). CTX-M-15 was significantly associated with MDR-ESBL-EC (59.1% vs. 32.5%, p = 0.028). Pulsed-field gel electrophoresis showed clonal diversity of MDR-ESBL-EC isolates. The emergence of strains of MDR-ESBL-EC in the community poses an important new public health threat. More information on the emergence and transmission of these strains will be necessary in order to prevent their spread.

PTP1B inhibitor promotes endothelial cell motility by activating the DOCK180/Rac1 pathway.

PubMed

Wang, Yuan; Yan, Feng; Ye, Qing; Wu, Xiao; Jiang, Fan

2016-04-07

Promoting endothelial cell (EC) migration is important not only for therapeutic angiogenesis, but also for accelerating re-endothelialization after vessel injury. Several recent studies have shown that inhibition of protein tyrosine phosphatase 1B (PTP1B) may promote EC migration and angiogenesis by enhancing the vascular endothelial growth factor receptor-2 (VEGFR2) signalling. In the present study, we demonstrated that PTP1B inhibitor could promote EC adhesion, spreading and migration, which were abolished by the inhibitor of Rac1 but not RhoA GTPase. PTP1B inhibitor significantly increased phosphorylation of p130Cas, and the interactions among p130Cas, Crk and DOCK180; whereas the phosphorylation levels of focal adhesion kinase, Src, paxillin, or Vav2 were unchanged. Gene silencing of DOCK180, but not Vav2, abrogated the effects of PTP1B inhibitor on EC motility. The effects of PTP1B inhibitor on EC motility and p130Cas/DOCK180 activation persisted in the presence of the VEGFR2 antagonist. In conclusion, we suggest that stimulation of the DOCK180 pathway represents an alternative mechanism of PTP1B inhibitor-stimulated EC motility, which does not require concomitant VEGFR2 activation as a prerequisite. Therefore, PTP1B inhibitor may be a useful therapeutic strategy for promoting EC migration in cardiovascular patients in which the VEGF/VEGFR functions are compromised.

Perspectives on How Human Simultaneous Multi-Modal Imaging Adds Directionality to Spread Models of Alzheimer’s Disease

PubMed Central

Neitzel, Julia; Nuttall, Rachel; Sorg, Christian

2018-01-01

Previous animal research suggests that the spread of pathological agents in Alzheimer’s disease (AD) follows the direction of signaling pathways. Specifically, tau pathology has been suggested to propagate in an infection-like mode along axons, from transentorhinal cortices to medial temporal lobe cortices and consequently to other cortical regions, while amyloid-beta (Aβ) pathology seems to spread in an activity-dependent manner among and from isocortical regions into limbic and then subcortical regions. These directed connectivity-based spread models, however, have not been tested directly in AD patients due to the lack of an in vivo method to identify directed connectivity in humans. Recently, a new method—metabolic connectivity mapping (MCM)—has been developed and validated in healthy participants that uses simultaneous FDG-PET and resting-state fMRI data acquisition to identify directed intrinsic effective connectivity (EC). To this end, postsynaptic energy consumption (FDG-PET) is used to identify regions with afferent input from other functionally connected brain regions (resting-state fMRI). Here, we discuss how this multi-modal imaging approach allows quantitative, whole-brain mapping of signaling direction in AD patients, thereby pointing out some of the advantages it offers compared to other EC methods (i.e., Granger causality, dynamic causal modeling, Bayesian networks). Most importantly, MCM provides the basis on which models of pathology spread, derived from animal studies, can be tested in AD patients. In particular, future work should investigate whether tau and Aβ in humans propagate along the trajectories of directed connectivity in order to advance our understanding of the neuropathological mechanisms causing disease progression. PMID:29434570

[Imaging and quantitative measurement of brain extracellular space using MRI Gd-DTPA tracer method].

PubMed

He, Qing-yuan; Han, Hong-bin; Xu, Fang-jing-wei; Yan, Jun-hao; Zeng, Jin-jin; Li, Xiao-gang; Fu, Yu; Peng, Yun; Chen, He; Hou, Chao; Xu, Xiao-juan

2010-04-18

To observe the diffusion of Gd-DTPA in brain extracellular space (ECS) by magnetic resonance imaging(MRI) and investigate the feasibility of ECS measurement by using MRI tracer method in vivo. 2 microL Gd-DTPA was introduced into ECS by caudate nucleus according to stereotaxic atlas in 8 Sprague Dawley(SD) rats (male, 280-320 g). The MRI scans were performed at 1 h, 3 h, 6 h, 9 h and 12 h respectively after administration. MRI appearances of Gd-DTPA diffusion and distribution was observed and compared. The MRI signal enhancement was measured at each time point. The neuroethology assessment was performed after MRI scanning at 12 h. The injection was accurate at the center of the caudate nucleus in 6 rats, while, at the capsula externa in other 2 rats. Gd-DTPA diffused isotropically after it was introduced into caudate nucleus, which spread into lateral cortex at 3 h. The MRI signal enhancement distributed mainly in the middle cerebral artery territory. A significant difference was found between the signal enhancement ratio at 1 h and that at 3 h in the original point of caudate nucleus (t=95.63, P<0.01), and the signal enhancement attenuated following the exponential power function y=1.7886x(-0.1776) (R2=0.94). In 2 rats with the injection point at capsula externa, Gd-DTPA diffused anisotropically along the fiber track of white matter during 1 h to 3 h, and spread into the lateral cortex at 6 h. The diffusion and clearance of Gd-DTPA in brain ECS could be monitored and measured quantitatively in vivo by MRI tracer method.

Squamous Cell Carcinoma Antigen-encoding Genes SERPINB3/B4 as Potentially Useful Markers for the Stratification of HNSCC Tumours.

PubMed

Saidak, Zuzana; Morisse, Mony Chenda; Chatelain, Denis; Sauzay, Chloé; Houessinon, Aline; Guilain, Nelly; Soyez, Marion; Chauffert, Bruno; Dakpé, Stéphanie; Galmiche, Antoine

2018-03-01

The squamous cell carcinoma antigen (SCCA), encoded by the genes SERPINB3/B4, is a tumour marker produced by head and neck squamous cell carcinoma (HNSCC). We aimed to examine SERPINB3/B4 mRNA levels and its clinical significance in the therapeutic context. We retrieved mRNA expression levels, clinical, pathological and genomic data for 520 HNSCC from The Cancer Genome Atlas (TCGA). HNSCC tumours express high levels of SERPINB3/B4 mRNA. SERPINB3 expression differs depending on Human papillomavirus (HPV) infection status, primary tumour location, grade and differentiation, extension to lymph nodes and extracapsular spread. Interestingly, we observed an association between SERPINB3/B4 and the presence of tumour immune infiltrate as well as the expression of the immune checkpoint regulators PD-L1/PD-L2 that depended on HPV status. Our findings point to potential interest of SERPINB3/B4 for the stratification of HNSCC patients in the therapeutic context. Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Modified Weekly Cisplatin-Based Chemotherapy Is Acceptable in Postoperative Concurrent Chemoradiotherapy for Locally Advanced Head and Neck Cancer

PubMed Central

Lu, Hsueh-Ju; Yang, Chao-Chun; Wang, Ling-Wei; Chu, Pen-Yuan; Tai, Shyh-Kuan; Chen, Ming-Huang; Yang, Muh-Hwa; Chang, Peter Mu-Hsin

2015-01-01

Background. Triweekly cisplatin-based postoperative concurrent chemoradiotherapy (CCRT) has high intolerance and toxicities in locally advanced head and neck cancer (LAHNC). We evaluated the effect of a modified weekly cisplatin-based chemotherapy in postoperative CCRT. Methods. A total of 117 patients with LAHNC were enrolled between December 2007 and December 2012. Survival, compliance/adverse events, and independent prognostic factors were analyzed. Results. Median follow-up time was 30.0 (3.1–73.0) months. Most patients completed the entire course of postoperative CCRT (radiotherapy ≥ 60 Gy, 94.9%; ≥6 times weekly chemotherapy, 75.2%). Only 17.1% patients required hospital admission. The most common adverse effect was grade 3/4 mucositis (28.2%). No patient died due to protocol-related adverse effects. Multivariate analysis revealed the following independent prognostic factors: oropharyngeal cancer, extracapsular spread, and total radiation dose. Two-year progression-free survival and overall survival rates were 70.9% and 79.5%, respectively. Conclusion. Modified weekly cisplatin-based chemotherapy is an acceptable regimen in postoperative CCRT for LAHNC. PMID:25793192

A new method to model electroconvulsive therapy in rats with increased construct validity and enhanced translational value.

PubMed

Theilmann, Wiebke; Löscher, Wolfgang; Socala, Katarzyna; Frieling, Helge; Bleich, Stefan; Brandt, Claudia

2014-06-01

Electroconvulsive therapy is the most effective therapy for major depressive disorder (MDD). The remission rate is above 50% in previously pharmacoresistant patients but the mechanisms of action are not fully understood. Electroconvulsive stimulation (ECS) in rodents mimics antidepressant electroconvulsive therapy (ECT) in humans and is widely used to investigate the underlying mechanisms of ECT. For the translational value of findings in animal models it is essential to establish models with the highest construct, face and predictive validity possible. The commonly used model for ECT in rodents does not meet the demand for high construct validity. For ECT, cortical surface electrodes are used to induce therapeutic seizures whereas ECS in rodents is exclusively performed by auricular or corneal electrodes. However, the stimulation site has a major impact on the type and spread of the induced seizure activity and its antidepressant effect. We propose a method in which ECS is performed by screw electrodes placed above the motor cortex of rats to closely simulate the clinical situation and thereby increase the construct validity of the model. Cortical ECS in rats induced reliably seizures comparable to human ECT. Cortical ECS was more effective than auricular ECS to reduce immobility in the forced swim test. Importantly, auricular stimulation had a negative influence on the general health condition of the rats with signs of fear during the stimulation sessions. These results suggest that auricular ECS in rats is not a suitable ECT model. Cortical ECS in rats promises to be a valid method to mimic ECT. Copyright © 2014 Elsevier Ltd. All rights reserved.

Differential neurophysiological effects of magnetic seizure therapy (MST) and electroconvulsive shock (ECS) in non-human primates.

PubMed

Cycowicz, Yael M; Luber, Bruce; Spellman, Timothy; Lisanby, Sarah H

2008-07-01

Magnetic seizure therapy (MST) is under development as a means of reducing the side effects of electroconvulsive therapy (ECT) through enhanced control over patterns of seizure induction and spread. We previously reported that chronic treatment with MST resulted in less impairment in cognitive function than electroconvulsive shock (ECS) in a non-human primate model of convulsive therapy. Here we present quantitative analyses of ictal expression and post-ictal suppression following ECS, MST, and anesthesia-alone sham in the same model to test whether differential neurophysiological characteristics of the seizures could be identified. Rhesus monkeys received 4 weeks of daily treatment with ECS, MST, and anesthesia-alone sham in a counterbalanced order separated by a recovery period. Both ECS and MST were given bilaterally at 2.5 x seizure threshold. Neurophysiological characteristics were derived from two scalp EEG electrode recording sites during and immediately following the ictal period, and were compared to sham treatment. EEG power within four frequencies (delta, theta, alpha and beta) was calculated. Our results support earlier findings from intracerebral electrode recordings demonstrating that MST- and ECS- induced seizures elicit differential patterns of EEG activation. Specifically, we found that ECS shows significantly more marked ictal expression, and more intense post-ictal suppression than MST in the theta, alpha, and beta frequency bands (Ps < .05). However, the ECS and MST were indistinguishable in the delta frequency band during both ictal and post-ictal periods. These results demonstrate that magnetic seizure induction can result in seizures that differ in some neurophysiological respects compared with ECS, but that these modalities share some aspects of seizure expression. The clinical significance of these similarities and differences awaits clinical correlation.

Increased plasmatic soluble HLA-G levels in endometrial cancer.

PubMed

Ben Yahia, Hamza; Babay, Wafa; Bortolotti, Daria; Boujelbene, Nadia; Laaribi, Ahmed Baligh; Zidi, Nour; Kehila, Mehdi; Chelbi, Hanène; Boudabous, Abdellatif; Mrad, Karima; Mezlini, Amel; Di Luca, Dario; Ouzari, Hadda-Imene; Rizzo, Roberta; Zidi, Inès

2018-05-03

Human Leukocyte Antigen-G (HLA-G) is known as an immune suppressive molecule; it interacts with several immune cells and inhibits their functions. HLA-G molecule is highly represented in pathological conditions including malignant transformation. To the best of our knowledge this is the first study that focuses on the expression of soluble HLA-G (sHLA-G) in endometrial cancer (EC). We aimed at exploring sHLA-G plasma levels and its prognostic value in EC. We examined total sHLA-G expression as well as the sHLA-G1 and HLA-G5 isoforms expression in plasma samples from 40 patients with EC and 45 healthy controls by a specific sandwich ELISA. Immunoprecipitation and Coomassie blue staining were performed to explore the presence of plasmatic sHLA-G monomers and dimers. sHLA-G plasma level was significantly enhanced in patients with EC compared to healthy controls (p = 0.028). Additionally, HLA-G5 molecules were highly represented than sHLA-G1 molecules in EC, at the borderline of significance (p = 0.061). Interestingly, sHLA-G has been shown to be increased in early stages (Stages I and II) as well as in high grade EC (Grade 3) that is associated with rapid spread of the disease (p = 0.057). sHLA-G positive EC plasma were majorly in monomeric form (75%). Clinically, all the HLA-G dimers were detected in early stages and in high grade of EC. Our data strengthen the implication of HLA-G molecules in EC etiology and especially in progression. Copyright © 2018 Elsevier Ltd. All rights reserved.

Electrical conduction along endothelial cell tubes from mouse feed arteries: confounding actions of glycyrrhetinic acid derivatives

PubMed Central

Behringer, Erik J; Socha, Matthew J; Polo-Parada, Luis; Segal, Steven S

2012-01-01

BACKGROUND AND PURPOSE Electrical conduction along endothelium of resistance vessels has not been determined independently of the influence of smooth muscle, surrounding tissue or blood. Two interrelated hypotheses were tested: (i) Intercellular conduction of electrical signals is manifest in endothelial cell (EC) tubes; and (ii) Inhibitors of gap junction channels (GJCs) have confounding actions on EC electrical and Ca2+ signalling. EXPERIMENTAL APPROACH Intact EC tubes were isolated from abdominal muscle feed (superior epigastric) arteries of C57BL/6 mice. Hyperpolarization was initiated with indirect (ACh) and direct (NS309) stimulation of intermediate- and small-conductance Ca2+-activated K+ channels (IKCa/SKCa). Remote membrane potential (Vm) responses to intracellular current injection defined the length constant (λ) for electrical conduction. Dye coupling was evaluated following intracellular microinjection of propidium iodide. Intracellular Ca2+ dynamics were determined using Fura-2 photometry. Carbenoxolone (CBX) or β-glycyrrhetinic acid (βGA) was used to investigate the role of GJCs. KEY RESULTS Steady-state Vm of ECs was −25 mV. ACh and NS309 hyperpolarized ECs by −40 and −60 mV respectively. Electrical conduction decayed monoexponentially with distance (λ∼1.4 mm). Propidium iodide injected into one EC spread into surrounding ECs. CBX or βGA inhibited dye transfer, electrical conduction and EC hyperpolarization reversibly. Both agents elevated resting Ca2+ while βGA inhibited responses to ACh. CONCLUSIONS AND IMPLICATIONS Individual cells were effectively coupled to each other within EC tubes. Inhibiting GJCs with glycyrrhetinic acid derivatives blocked hyperpolarization mediated by IKCa/SKCa channels, regardless of Ca2+ signalling, obviating use of these agents in distinguishing key determinants of electrical conduction along the endothelium. PMID:22168386

Extraoral approach to mandibular condylar fractures: our experience with 100 cases.

PubMed

Colletti, Giacomo; Battista, Valeria Marinella Augusta; Allevi, Fabiana; Giovanditto, Federica; Rabbiosi, Dimitri; Biglioli, Federico

2014-07-01

Mandibular condylar fractures are very common. The current literature contains many indications and methods of treatment. Extraoral approaches are complicated by the need to avoid injury to the facial nerve. On the other hand intraoral approaches can make fracture reduction and/or fixation difficult. The mini-retromandibular approach provides an excellent view of the surgical field, minimises the risk of injury to the facial nerve, and allows rapid and easy management of condylar fractures. We have collected and reviewed our first 100 condylar fractures treated by means of a mini-retromandibular approach. Between June 2006 and June 2012, Eighty-seven patients with extracapsular condylar fractures underwent open reduction and rigid fixation for 100 extracapsular condylar fractures via a mini-retromandibular approach. Dental occlusion and anatomic reduction were restored in all 100 condylar fractures. Postoperative infection developed in three patients. There was one sialocele and one case of plate fracture. Four patients experienced transient palsy of the buccal branch of the facial nerve. No permanent deficit of any facial nerve branch was observed. No patient showed condylar head resorption. Our experience with the treatment of the first 100 condylar fractures using the mini-retromandibular approach has demonstrated that this technique has allowed the Authors to safely manage extracapsular condylar fractures at all levels. Copyright © 2013 European Association for Cranio-Maxillo-Facial Surgery. Published by Elsevier Ltd. All rights reserved.

The effect of extracapsular injuries on growth and development of the mandible condyle: an experimental study in growing dogs.

PubMed

Liu, Siying; Tian, Lei; Ding, Mingchao; Liu, Yanpu; Li, Guiyu; Chen, Jinwu; Ding, Yin

2016-11-01

To investigate the effects of condylar extracapsular injuries on the development of the mandibular condyle and try to find a way to treat condylar hyperplasia by electively using such injuries to restrict the overdeveloped mandibular condyle. Sixty 6-month-old beagle puppies were divided randomly into five groups: blank control; unilateral fracture to the condylar neck; unilateral fracture to the condylar neck treated with rigid internal fixation; unilateral periosteum injury; unilateral decortication of the condylar neck. Computed tomography, 99 m Tc single-photon emission computed tomography, and tetracycline-calcein double-labeling were performed after surgery. The puppies were sacrificed 12 and 24 weeks after surgery. Morphologic analyses and examination of growth activity were done. Unilateral fracture of the condylar neck without fixation caused local morphologic changes during the early postoperative period, but compensatory growth of the condyle altered such changes after healing. The other types of injury failed to inhibit the growth of the condyle and the mandible, whereas functional deviation of the chin was found after unilateral fracture of the condylar neck with or without fixation. The four types of extracapsular injury described here failed to inhibit the growth of the mandibular condyle and could not be selected as alternatives to treat condylar hyperplasia. Copyright © 2016 Elsevier Inc. All rights reserved.

Femoral neck-shaft angle in extra-capsular proximal femoral fracture fixation; does it make a TAD of difference?

PubMed

Walton, N P; Wynn-Jones, H; Ward, M S; Wimhurst, J A

2005-11-01

The effect of femoral neck-shaft angle and implant type on the accuracy of lag screw placement in extra-capsular proximal femoral fracture fixation was investigated. Radiographs of all extra-capsular proximal femoral fractures seen in one unit over 18 months were reviewed. Of 399 cases, 307 (237 female, 70 male) were included in the study as they had no contra-lateral proximal femoral metal work. Femoral neck-shaft angle (NSA) of the uninjured hip and magnification adjusted tip-apex distance (TAD) of femoral head lag screw were measured. Type of fixation implant was 135 degrees classic hip screw (CHS) (n=144) or 130 degrees intra-medullary hip screw (IMHS) (n=163). Mean contra-lateral NSA was 130.2 degrees (112.9--148 degrees ) and 64 patients (58 female, 6 male) had a NSA <125 degrees . Mean adjusted TAD was 18.7 mm (5.8--43.8mm) and 88.9% of cases had a TAD of less than 25 mm. TAD values were significantly greater using an IMHS if NSA was <125 degrees than if NSA was >125 degrees (p=0.028). This was not the case with the CHS. The use of the 130 degrees -IMHS in patients with a NSA <125 degrees leads to poorer lag screw placement than if NSA >125 degrees and caution is advocated when using this device in such cases.

Patterning of Endothelial Cells and Mesenchymal Stem Cells by Laser-Assisted Bioprinting to Study Cell Migration.

PubMed

Bourget, Jean-Michel; Kérourédan, Olivia; Medina, Manuela; Rémy, Murielle; Thébaud, Noélie Brunehilde; Bareille, Reine; Chassande, Olivier; Amédée, Joëlle; Catros, Sylvain; Devillard, Raphaël

2016-01-01

Tissue engineering of large organs is currently limited by the lack of potent vascularization in vitro . Tissue-engineered bone grafts can be prevascularized in vitro using endothelial cells (ECs). The microvascular network architecture could be controlled by printing ECs following a specific pattern. Using laser-assisted bioprinting, we investigated the effect of distance between printed cell islets and the influence of coprinted mesenchymal cells on migration. When printed alone, ECs spread out evenly on the collagen hydrogel, regardless of the distance between cell islets. However, when printed in coculture with mesenchymal cells by laser-assisted bioprinting, they remained in the printed area. Therefore, the presence of mesenchymal cell is mandatory in order to create a pattern that will be conserved over time. This work describes an interesting approach to study cell migration that could be reproduced to study the effect of trophic factors.

Patterning of Endothelial Cells and Mesenchymal Stem Cells by Laser-Assisted Bioprinting to Study Cell Migration

PubMed Central

Medina, Manuela; Rémy, Murielle; Thébaud, Noélie Brunehilde; Bareille, Reine; Chassande, Olivier; Amédée, Joëlle; Catros, Sylvain

2016-01-01

Tissue engineering of large organs is currently limited by the lack of potent vascularization in vitro. Tissue-engineered bone grafts can be prevascularized in vitro using endothelial cells (ECs). The microvascular network architecture could be controlled by printing ECs following a specific pattern. Using laser-assisted bioprinting, we investigated the effect of distance between printed cell islets and the influence of coprinted mesenchymal cells on migration. When printed alone, ECs spread out evenly on the collagen hydrogel, regardless of the distance between cell islets. However, when printed in coculture with mesenchymal cells by laser-assisted bioprinting, they remained in the printed area. Therefore, the presence of mesenchymal cell is mandatory in order to create a pattern that will be conserved over time. This work describes an interesting approach to study cell migration that could be reproduced to study the effect of trophic factors. PMID:27833916

Safety evaluation of phytosterol-esters. Part 9: Results of a European post-launch monitoring programme.

PubMed

Lea, L J; Hepburn, P A

2006-08-01

Phytosterol-esters were developed by Unilever as a cholesterol lowering novel food ingredient for use initially in vegetable oil spreads. In addition to an extensive package of safety studies and clinical studies a programme of post-launch monitoring (PLM) was developed. PLM was used to address the following questions: (a) Is the product use as predicted/recommended? (b) Are the known effects as predicted? (c) Does the product cause unexpected health effects? The overall conclusions from the PLM programme were: the product is being bought by the target population but intakes are less than the original assumptions made in the risk assessment; long-term use of phytosterol-ester enriched spreads results in a reduction in the serum levels of the most lipophilic carotenoids but at current levels of intake this is unlikely to result in reductions in carotenoids that are of biological significance; evaluation of health related consumer complaints have not indicated any unexpected health effects associated with the use of the product in the marketplace. As part of the European approval under Regulation (EC) No. 258/97 on Novel Foods and Food Ingredients the results of the PLM programme had to be submitted to the European Commission (EC) and reviewed by the Scientific Committee on Food (SCF). They concluded that the study provided valuable information, which complemented the pre-market safety evaluation studies, and that the EC mandatory requirement had been met.

Evaluating Emergent Constraints for Equilibrium Climate Sensitivity

DOE PAGES

Caldwell, Peter M.; Zelinka, Mark D.; Klein, Stephen A.

2018-04-23

Emergent constraints are quantities that are observable from current measurements and have skill predicting future climate. Here, this study explores 19 previously proposed emergent constraints related to equilibrium climate sensitivity (ECS; the global-average equilibrium surface temperature response to CO 2 doubling). Several constraints are shown to be closely related, emphasizing the importance for careful understanding of proposed constraints. A new method is presented for decomposing correlation between an emergent constraint and ECS into terms related to physical processes and geographical regions. Using this decomposition, one can determine whether the processes and regions explaining correlation with ECS correspond to the physicalmore » explanation offered for the constraint. Shortwave cloud feedback is generally found to be the dominant contributor to correlations with ECS because it is the largest source of intermodel spread in ECS. In all cases, correlation results from interaction between a variety of terms, reflecting the complex nature of ECS and the fact that feedback terms and forcing are themselves correlated with each other. For 4 of the 19 constraints, the originally proposed explanation for correlation is borne out by our analysis. These four constraints all predict relatively high climate sensitivity. The credibility of six other constraints is called into question owing to correlation with ECS coming mainly from unexpected sources and/or lack of robustness to changes in ensembles. Another six constraints lack a testable explanation and hence cannot be confirmed. Lastly, the fact that this study casts doubt upon more constraints than it confirms highlights the need for caution when identifying emergent constraints from small ensembles.« less

Evaluating Emergent Constraints for Equilibrium Climate Sensitivity

DOE Office of Scientific and Technical Information (OSTI.GOV)

Caldwell, Peter M.; Zelinka, Mark D.; Klein, Stephen A.

Emergent constraints are quantities that are observable from current measurements and have skill predicting future climate. Here, this study explores 19 previously proposed emergent constraints related to equilibrium climate sensitivity (ECS; the global-average equilibrium surface temperature response to CO 2 doubling). Several constraints are shown to be closely related, emphasizing the importance for careful understanding of proposed constraints. A new method is presented for decomposing correlation between an emergent constraint and ECS into terms related to physical processes and geographical regions. Using this decomposition, one can determine whether the processes and regions explaining correlation with ECS correspond to the physicalmore » explanation offered for the constraint. Shortwave cloud feedback is generally found to be the dominant contributor to correlations with ECS because it is the largest source of intermodel spread in ECS. In all cases, correlation results from interaction between a variety of terms, reflecting the complex nature of ECS and the fact that feedback terms and forcing are themselves correlated with each other. For 4 of the 19 constraints, the originally proposed explanation for correlation is borne out by our analysis. These four constraints all predict relatively high climate sensitivity. The credibility of six other constraints is called into question owing to correlation with ECS coming mainly from unexpected sources and/or lack of robustness to changes in ensembles. Another six constraints lack a testable explanation and hence cannot be confirmed. Lastly, the fact that this study casts doubt upon more constraints than it confirms highlights the need for caution when identifying emergent constraints from small ensembles.« less

Management of endometrial cancer: issues and controversies.

PubMed

Bogani, G; Dowdy, S C; Cliby, W A; Ghezzi, F; Rossetti, D; Frigerio, L; Mariani, A

2016-01-01

Although endometrial cancer (EC) is the most common gynecologic cancer in developed countries, several aspects of its management are still controversial. In particular, the need to perform lymphadenectomy represents an important matter of discussion. Because of the discordant results in the literature, it is still not possible to draft any definitive conclusions regarding the therapeutic value of lymph node dissection. The present review discusses the role of lymphadenectomy in the setting of EC, risk factors for lymphatic spread, identification of patients at risk for lymph node dissemination, and the current evidence for adjuvant therapies in patients with positive nodes. Reasons for the difficulty in demonstrating any therapeutic value of pelvic and para-aortic lymphadenectomy are also discussed.

Status of Phytophthora ramorum and P. kernoviae in Europe

Treesearch

Joan F. Webber

2008-01-01

Following the recognition that Phytophthora ramorum (the cause of sudden oak death in the U.S.) was present in Europe as well as America, emergency European Community (EC) phytosanitary measures were put in place in September 2002 to prevent spread of P. ramorum, and also to stop introductions of the pathogen from elsewhere. A 3...

Selective alterations of neurons and circuits related to early memory loss in Alzheimer’s disease

PubMed Central

Llorens-Martín, Maria; Blazquez-Llorca, Lidia; Benavides-Piccione, Ruth; Rabano, Alberto; Hernandez, Felix; Avila, Jesus; DeFelipe, Javier

2014-01-01

A progressive loss of episodic memory is a well-known clinical symptom that characterizes Alzheimer’s disease (AD). The beginning of this loss of memory has been associated with the very early, pathological accumulation of tau and neuronal degeneration observed in the entorhinal cortex (EC). Tau-related pathology is thought to then spread progressively to the hippocampal formation and other brain areas as the disease progresses. The major cortical afferent source of the hippocampus and dentate gyrus is the EC through the perforant pathway. At least two main circuits participate in the connection between EC and the hippocampus; one originating in layer II and the other in layer III of the EC giving rise to the classical trisynaptic (ECII → dentate gyrus → CA3 → CA1) and monosynaptic (ECIII → CA1) circuits. Thus, the study of the early pathological changes in these circuits is of great interest. In this review, we will discuss mainly the alterations of the granule cell neurons of the dentate gyrus and the atrophy of CA1 pyramidal neurons that occur in AD in relation to the possible differential alterations of these two main circuits. PMID:24904307

Selective alterations of neurons and circuits related to early memory loss in Alzheimer's disease.

PubMed

Llorens-Martín, Maria; Blazquez-Llorca, Lidia; Benavides-Piccione, Ruth; Rabano, Alberto; Hernandez, Felix; Avila, Jesus; DeFelipe, Javier

2014-01-01

A progressive loss of episodic memory is a well-known clinical symptom that characterizes Alzheimer's disease (AD). The beginning of this loss of memory has been associated with the very early, pathological accumulation of tau and neuronal degeneration observed in the entorhinal cortex (EC). Tau-related pathology is thought to then spread progressively to the hippocampal formation and other brain areas as the disease progresses. The major cortical afferent source of the hippocampus and dentate gyrus is the EC through the perforant pathway. At least two main circuits participate in the connection between EC and the hippocampus; one originating in layer II and the other in layer III of the EC giving rise to the classical trisynaptic (ECII → dentate gyrus → CA3 → CA1) and monosynaptic (ECIII → CA1) circuits. Thus, the study of the early pathological changes in these circuits is of great interest. In this review, we will discuss mainly the alterations of the granule cell neurons of the dentate gyrus and the atrophy of CA1 pyramidal neurons that occur in AD in relation to the possible differential alterations of these two main circuits.

Differences in Seizure Expression Between Magnetic Seizure Therapy and Electroconvulsive Shock.

PubMed

Cycowicz, Yael M; Rowny, Stefan B; Luber, Bruce; Lisanby, Sarah H

2018-06-01

Evidence suggests that magnetic seizure therapy (MST) results in fewer side effects than electroconvulsive treatment, both in humans treated with electroconvulsive therapy (ECT) as well as in the animal preclinical model that uses electroconvulsive shock (ECS). Evidence suggests that MST results in fewer cognitive side effects than ECT. Although MST offers enhanced control over seizure induction and spread, little is known about how MST and ECT seizures differ. Seizure characteristics are associated with treatment effect. This study presents quantitative analyses of electroencephalogram (EEG) power after electrical and magnetic seizure induction and anesthesia-alone sham in an animal model. The aim was to test whether differential neurophysiological characteristics of the seizures could be identified that support earlier observations that the powers of theta, alpha, and beta but not delta frequency bands were lower after MST when compared with those after ECS. In a randomized, sham-controlled trial, 24 macaca mulatte received 6 weeks of daily sessions while scalp EEG was recorded. Electroencephalogram power was quantified within delta, theta, alpha, and beta frequency bands. Magnetic seizure therapy induced lower ictal expression in the theta, alpha and beta frequencies than ECS, but MST and ECS were indistinguishable in the delta band. Magnetic seizure therapy showed less postictal suppression than ECS. Increasing electrical dosage increased ictal power, whereas increasing MST dosage had no effect on EEG expression. Magnetic seizure therapy seizures have less robust electrophysiological expression than ECS, and these differences are largest in the alpha and beta bands. The relevance of these differences in higher frequency bands to clinical outcomes deserves further exploration. Contrasting EEG in ECS and MST may lead to insights on the physiological underpinnings of seizure-induced amnesia and to finding ways to reduce cognitive side effects.

Reasons for requesting emergency contraception: a survey of 506 Italian women.

PubMed

Bastianelli, C; Farris, M; Benagiano, G

2005-09-01

To evaluate the reason for requesting emergency contraception (EC), previous use of contraceptive methods and provision route in a Family Planning Clinic in Italy. Women requesting EC were interviewed, through a questionnaire containing questions on demographic characteristics, about their reasons for requesting EC, their prior contraceptive use, their reasons for not using an effective contraceptive method (or possible reasons for its failure) and specifically about the so-called 'provision route' (i.e. whether and where they had previously requested EC receiving a negative response). Almost 70% of all women requesting EC were aged between 18 and 25 years. Some 80% of all women were in a stable relationship with their partner, with fewer than 20% having had an occasional intercourse. The vast majority of women (83%) reported prior use of a modern contraceptive method, i.e. 64% with a condom, 27% for combined oral contraceptives and 1.1% for the intrauterine device (IUD). In addition, 15% of the women had used more than one method (oral pills and condoms). Concerning the reasons for requesting EC, condom breakage or slipping was the most frequently cited (64%), followed by totally unprotected intercourse (28%), failed withdrawal (5%) and forgetting one or more pill (only 1.1%). More than one-third of the women interviewed had previously used an emergency contraceptive modality; although no one did so more than four times. Therefore, it can be inferred that-at least in the present series-EC had not been used as a routine contraceptive method. Finally, it seems clear that in Italy, even in large cities, information about the availability, proper usage and mechanism of action is lacking. This seems due to information being spread by word of mouth between peers and friends, with more formal communication channels lagging behind.

[Economic assessment of the routine use of Oncotype DX® assay for early breast cancer in Franche-Comte region].

PubMed

Nerich, Virginie; Curtit, Elsa; Bazan, Fernando; Montcuquet, Philippe; Villanueva, Cristian; Chaigneau, Loïc; Cals, Laurent; Méneveau, Nathalie; Dobi, Erion; Altmotlak, Hamadi; Algros, Marie-Paule; Choulot, Marie-Jeanne; Nallet, Gilles; Limat, Samuel; Mansion, Sylvie; Pivot, Xavier

2014-01-01

Oncotype DX® has been validated as quantifying the likelihood of distant recurrence at 10 years and overall chemotherapy benefit in patients with estrogen-receptor-positive and HER-2-negative early breast cancer. In 2012, this genomic signature was routinely available for patients in Franche-Comté, France. Patients eligible for Oncotype DX(®) testing had a ER-positive, HER-2-négative early breast cancer with a nodal involvement limited to 0 or 1 positive-node without extracapsular spread; an adjuvant chemotherapy was indicated based on usual prognostic factors. The aim was to assess the economic impact of Oncotype DX(®) testing in a French region. A cost-minimisation analysis from the French Public Healthcare System perspective was performed. The availability of Oncotype DX(®) in Franche-Comté, France, and its use in clinical routine allowed a decrease of 73 % of adjuvant chemotherapy without increase of the cost of the patients' management and with a potential reduction of the cost for the French Public Healthcare System. This strategy was successful and may allow the reimbursement of this test in France for patients with early breast cancer.

Arthroscopy of the Nondistractable Hip: A Novel Extracapsular Approach

PubMed Central

Doron, Ran; Amar, Eyal; Rath, Ehud; Sampson, Thomas; Ochiai, Derek; Matsuda, Dean K.

2014-01-01

Adequate traction to achieve hip joint distraction is essential for avoiding iatrogenic injury to the joint during hip arthroscopy. An inability to distract the joint is a relative contraindication for hip arthroscopy. This report describes a novel technique involving an extracapsular approach to gain safe access to a hip joint that fails a trial of traction during positioning for hip arthroscopy. The anterolateral portal is established under fluoroscopic guidance. The arthroscope is positioned on the lateral rim of the acetabulum. A shaver, introduced through a modified anterior portal, is used to facilitate capsular exposure. An arthroscopic capsular incision is made proximal to the lateral acetabular rim and extended anteriorly with a radiofrequency probe. Osteoplasty of the anterolateral acetabular rim is carried out with a burr while protecting the labrum. Distraction of the hip is then possible, allowing safe central-compartment access and subsequent chondrolabral procedures. PMID:25685682

Increasing Type 1 Poliovirus Capsid Stability by Thermal Selection

PubMed Central

Adeyemi, Oluwapelumi O.; Nicol, Clare

2016-01-01

ABSTRACT Poliomyelitis is a highly infectious disease caused by poliovirus (PV). It can result in paralysis and may be fatal. Integrated global immunization programs using live-attenuated oral (OPV) and/or inactivated (IPV) PV vaccines have systematically reduced its spread and paved the way for eradication. Immunization will continue posteradication to ensure against reintroduction of the disease, but there are biosafety concerns for both OPV and IPV. They could be addressed by the production and use of virus-free virus-like particle (VLP) vaccines that mimic the “empty” capsids (ECs) normally produced in viral infection. Although ECs are antigenically indistinguishable from mature virus particles, they are less stable and readily convert into an alternative conformation unsuitable for vaccine purposes. Stabilized ECs, expressed recombinantly as VLPs, could be ideal candidate vaccines for a polio-free world. However, although genome-free PV ECs have been expressed as VLPs in a variety of systems, their inherent antigenic instability has proved a barrier to further development. In this study, we selected thermally stable ECs of type 1 PV (PV-1). The ECs are antigenically stable at temperatures above the conversion temperature of wild-type (wt) virions. We have identified mutations on the capsid surface and in internal networks that are responsible for EC stability. With reference to the capsid structure, we speculate on the roles of these residues in capsid stability and postulate that such stabilized VLPs could be used as novel vaccines. IMPORTANCE Poliomyelitis is a highly infectious disease caused by PV and is on the verge of eradication. There are biosafety concerns about reintroduction of the disease from current vaccines that require live virus for production. Recombinantly expressed virus-like particles (VLPs) could address these inherent problems. However, the genome-free capsids (ECs) of wt PV are unstable and readily change antigenicity to a form not suitable as a vaccine. Here, we demonstrate that the ECs of type 1 PV can be stabilized by selecting heat-resistant viruses. Our data show that some capsid mutations stabilize the ECs and could be applied as candidates to synthesize stable VLPs as future genome-free poliovirus vaccines. PMID:27928008

Extracapsular local infiltration analgesia in hip arthroscopy: a retrospective study

PubMed Central

Kahn, Timothy L; Adeyemi, Temitope F; Maak, Travis G

2018-01-01

ABSTRACT Many hip arthroscopy patients experience significant pain in the immediate postoperative period. Although peripheral nerve blocks have demonstrated efficacy in alleviating some of this pain, they come with significant costs. Local infiltration analgesia (LIA) may be a significantly cheaper and efficacious treatment modality. Although LIA has been well studied in hip and knee arthroplasty, its efficacy in hip arthroscopy is unclear. The purpose of this retrospective study is to determine the efficacy of a single extracapsular injection of bupivacaine–epinephrine during hip arthroscopy in reducing the rate of elective postoperative femoral nerve blocks. A retrospective review of 100 consecutive patients who underwent primary hip arthroscopy at a single medical center was performed. The control group consisted of 50 patients before the implementation of the current LIA protocol, whereas another 50 patients received a 20-ml extracapsular injection of 0.25% bupivacaine–epinephrine under direct arthroscopic visualization after capsular closure. In the post-anesthesia care unit (PACU), patients were offered a femoral nerve block for uncontrolled pain. The rate of femoral nerve block, and total opioid consumption, was compared between groups. The proportion of patients receiving elective femoral nerve blocks was significantly less in the LIA group (34%) as compared with the control group (56%; P = 0.027). There was no significant difference in total PACU opioid consumption between groups (P = 0.740). The decreased utilization of postoperative nerve blocks observed in the LIA group suggests that LIA may improve postoperative pain management and should be considered as a potentially cost-effective tool in pain management in hip arthroscopy patients. Level of Evidence: III PMID:29423252

A prospective study about the preoperative total blood loss in older people with hip fracture.

PubMed

Wu, Jie-Zhou; Liu, Peng-Cheng; Ge, Wei; Cai, Ming

2016-01-01

Our study is to confirm that hemoglobin (Hb) level is significantly reduced before operation in elderly patients with hip fracture and to specify potential amounts of bleeding and Hb decline in different types of fractures. A prospective analysis was made on the clinical data of 349 patients with both a diagnosis of hip fracture and an operative delay of greater than 72 hours between April 2014 and February 2016. Hb concentration was measured on a daily basis before the surgery. Patients were grouped according to the type of fracture (intracapsular and extracapsular) for calculation of the total blood loss (TBL). All data analyses were done by SPSS version 21 software. There was a significant decrease preoperatively in the Hb concentration of nearly 21.55 g/L (standard error of the mean [SEM] 7.67) in patients with extracapsular hip fractures and nearly 15.63 g/L (SEM 6.01) in patients with intracapsular hip fractures. The preoperative TBL in patients with extracapsular fracture was significantly larger compared to that in patients with intracapsular fracture (790.3 mL and 581.7 mL, respectively, P <0.05 using Student's t -test). We found no significant difference in the preoperative TBL between the male and female groups. Hip fracture patients have an obvious blood loss after the injury, yet prior to the surgery the Hb levels were found to be normal. Anesthetic and orthopedic staff should pay additional attention to the problem of low preoperative Hb concentration, even if the initial Hb level was apparently normal.

A multicenter study shows PTEN deletion is strongly associated with seminal vesicle involvement and extracapsular extension in localized prostate cancer.

PubMed

Troyer, Dean A; Jamaspishvili, Tamara; Wei, Wei; Feng, Ziding; Good, Jennifer; Hawley, Sarah; Fazli, Ladan; McKenney, Jesse K; Simko, Jeff; Hurtado-Coll, Antonio; Carroll, Peter R; Gleave, Martin; Lance, Raymond; Lin, Daniel W; Nelson, Peter S; Thompson, Ian M; True, Lawrence D; Brooks, James D; Squire, Jeremy A

2015-08-01

Loss of the phosphatase and tensin homolog (PTEN) tumor suppressor gene is a promising marker of aggressive prostate cancer. Active surveillance and watchful waiting are increasingly recommended to patients with small tumors felt to be low risk, highlighting the difficulties of Gleason scoring in this setting. There is an urgent need for predictive biomarkers that can be rapidly deployed to aid in clinical decision-making. Our objectives were to assess the incidence and ability of PTEN alterations to predict aggressive disease in a multicenter study. We used recently developed probes optimized for sensitivity and specificity in a four-color FISH deletion assay to study the Canary Retrospective multicenter Prostate Cancer Tissue Microarray (TMA). This TMA was constructed specifically for biomarker validation from radical prostatectomy specimens, and is accompanied by detailed clinical information with long-term follow-up. In 612 prostate cancers, the overall rate of PTEN deletion was 112 (18.3%). Hemizygous PTEN losses were present in 55/612 (9.0%) of cancers, whereas homozygous PTEN deletion was observed in 57/612 (9.3%) of tumors. Significant associations were found between PTEN status and pathologic stage (P < 0.0001), seminal vesicle invasion (P = 0.0008), extracapsular extension (P < 0.0001), and Gleason score (P = 0.0002). In logistic regression analysis of clinical and pathological variables, PTEN deletion was significantly associated with extracapsular extension, seminal vesicle involvement, and higher Gleason score. In the 406 patients in which clinical information was available, PTEN homozygous (P = 0.009) deletion was associated with worse post-operative recurrence-free survival (number of events = 189), pre-operative prostate specific antigen (PSA) (P < 0.001), and pathologic stage (P = 0.03). PTEN status assessed by FISH is an independent predictor for recurrence-free survival in multivariate models, as were seminal vesicle invasion, extracapsular extension, and Gleason score, and preoperative PSA. Furthermore, these data demonstrate that the assay can be readily introduced at first diagnosis in a cost effective manner analogous to the use of FISH for analysis of HER2/neu status in breast cancer. Combined with published research beginning 17 years ago, both the data and tools now exist to implement a PTEN assay in the clinic. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc.

Positive Margins by Oropharyngeal Subsite in Transoral Robotic Surgery for T1/T2 Squamous Cell Carcinoma.

PubMed

Persky, Michael J; Albergotti, William G; Rath, Tanya J; Kubik, Mark W; Abberbock, Shira; Geltzeiler, Mathew; Kim, Seungwon; Duvvuri, Umamaheswar; Ferris, Robert L

2018-04-01

Objective To compare positive margin rates between the 2 most common subsites of oropharyngeal transoral robotic surgery (TORS), the base of tongue (BOT) and the tonsil, as well as identify preoperative imaging characteristics that predispose toward positive margins. Study Design Case series with chart review. Setting Tertiary care referral center. Subjects and Methods We compared the final and intraoperative positive margin rate between TORS resections for tonsil and BOT oropharyngeal squamous cell carcinoma (OPSCC), as well as the effect of margins on treatment. A blinded neuroradiologist examined the preoperative imaging of BOT tumors to measure their dimensions and patterns of spread and provided a prediction of final margin results. Results Between January 2010 and May 2016, a total of 254 patients underwent TORS for OPSCC. A total of 140 patients who underwent TORS for T1/T2 OPSCC met inclusion criteria. A final positive margin is significantly more likely for BOT tumors than tonsil tumors (19.6% vs 4.5%, respectively, P = .004) and likewise for intraoperative margins of BOT and tonsil tumors (35.3% vs 12.4%, respectively; P = .002). A positive final margin is 10 times more likely to receive chemoradiation compared to a negative margin, controlling for extracapsular spread and nodal status (odds ratio, 9.6; 95% confidence interval, 1.6-59.6; P = .02). Preoperative imaging characteristics and subjective radiologic examination of BOT tumors did not correlate with final margin status. Conclusion Positive margins are significantly more likely during TORS BOT resections compared to tonsil resections. More research is needed to help surgeons predict which T1/T2 tumors will be difficult to completely extirpate.

Prevalence, prognosis, and treatment implications of retropharyngeal nodes in unknown primary head and neck carcinoma.

PubMed

Horowitz, Gilad; Hosni, Ali; Yu, Eugene; Xu, Wei; Lu, Lin; Au, Michael; Dixon, Peter R; Brown, Dale; Chepeha, Douglas B; Gilbert, Ralph W; Goldstein, David P; Gullane, Patrick J; Irish, Jonathan C; Bayley, Andrew; Cho, John; Giuliani, Meredith; Huang, Shao Hui; Hope, Andrew; Kim, John; O'Sullivan, Brian; Ringash, Jolie; Waldron, John; Weinreb, Ilan; Perez-Ordonez, Bayardo; Bratman, Scott V; de Almeida, John R

2018-07-01

(1) To estimate the prevalence of radiographically positive Retro-Pharyngeal Lymph Nodes (RPLN) in unknown primary carcinoma of the head and neck and (2) to determine the prognostic implications of radiographically positive RPLN and other radiographic features (3) to identify patients at low risk for retropharyngeal metastasis. The medical records of all 68 eligible patients treated at the Princess Margaret Cancer Centre between 2000 and 2014 were retrospectively reviewed for demographic, clinical, pathologic, and radiologic data. Radiologic data included: RPLN, extra capsular spread (ECS), neck staging and cystic/necrotic or matted neck nodes. LRR, DR, DFS and OS were estimated using the competing risk methods and the Kaplan-Meier method. Seven patients had concerning RPLN (10.3%). Forty-four patients were p16 positive (65%). RPLN status did not have any effect on LRR, DFS, DR and OS. Radiological ECS and p16 (neg.) status were found to be significant predictors of LRR (p = 0.023; p = 0.014). Matted nodes, radiological ECS and p16 (neg.) status were found to be significant predictors of DFS (p = 0.012; p < 0.001; p = 0.014). Matted nodes and radiological ECS were found to be significant predictors of OS (p = 0.017; p = 0.0036). Only radiological ECS was found to be a significant predictor of distant recurrence (p = 0.0066). 10% of CUP patients will harbor radiological positive RPLN. A large proportion of CUP patients are positive for p16. Radiologic features such as ECS and matted nodes can predict worse outcomes. Copyright © 2018. Published by Elsevier Ltd.

Magnitude of benefit for adjuvant radiotherapy following minimally invasive surgery in intermediate to high risk HPV-positive oropharyngeal squamous cell carcinoma.

PubMed

Pasalic, Dario; Funk, Ryan K; García, Joaquín J; Price, Daniel L; Price, Katharine A; Harmsen, William S; Patel, Samir H; Young, Geoffrey D; Foote, Robert L; Moore, Eric J; Ma, Daniel J

2018-07-01

To determine the outcomes and toxicities of minimally-invasive surgery with adjuvant intensity-modulated radiotherapy +/- chemotherapy (AT) compared to definitive surgical therapy (ST) in a contemporary cohort of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC). From 2005 to 2013, a consecutive cohort of 190 HPV-positive OPSCC patients was retrospectively reviewed from multi-institutional databases maintained by the Departments of Otorhinolaryngology and Radiation Oncology. A total of 116 AT patients and 42 ST patients with intermediate or high risk pathologic features were included in the final analysis. All patients received minimally invasive surgery. Time to recurrence and time to death from the onset of surgery were evaluated. Toxicity data collected included dysphagia or xerostomia requiring feeding tube placement >6 months, or mandibular osteonecrosis requiring surgery or hyperbaric oxygen. All AT patients received IMRT to a median dose of 60 Gy. Chemotherapy delivered to 67.2% of AT patients. AT group included more high-risk patients given higher nodal classification (p = 0.005) and extracapsular extension (p = 0.0005). AT improved disease-free survival (HR 2.77, CI 1.22-6.28; p = 0.02) and local-regional control (HR 14.83, CI 3.240-67.839; p = 0.001). Disease-free survival with AT and tumor extracapsular extension was improved when compared to ST (HR of 4.34, CI 1.540-12.213; p = 0.006). Dysphagia or mandibular osteonecrosis toxicity after AT vs. ST of 19.0% vs. 2.4%. AT improved local-regional control and disease-free survival but was associated with greater toxicity. The recurrence benefit was most pronounced in tumors with extracapsular extension. Copyright © 2018 Elsevier Ltd. All rights reserved.

Disabled infectious single animal (DISA) vaccine against Bluetongue by deletion of viroporin-like NS3/NS3a expression is effective, safe, and enables differentiation of infected from vaccinated animals (DIVA)

USDA-ARS?s Scientific Manuscript database

The prototype virus species of the genus Orbivirus (family Reoviridae) is bluetongue virus (BTV) consisting of at least 27 serotypes. Bluetongue is a noncontagious haemorrhagic disease of ruminants spread by competent species of Culicoides biting midges in large parts of the world leading to huge ec...

Pulsed and oscillating gradient MRI for assessment of cell size and Extracellular space (POMACE) in mouse gliomas

PubMed Central

Reynaud, Olivier; Winters, Kerryanne Veronica; Hoang, Dung Minh; Wadghiri, Youssef Zaim; Novikov, Dmitry S.; Kim, Sungheon Gene

2016-01-01

Solid tumor microstructure is related to aggressiveness of tumor, interstitial pressure and drug delivery pathways that are closely associated with treatment response, metastatic spread and prognosis. In this study, we introduce a novel diffusion MRI data analysis framework, Pulsed and Oscillating gradient MRI for Assessment of Cell size and Extracellular space (POMACE), and demonstrate its feasibility in a mouse tumor model. In vivo and ex vivo POMACE experiments were performed on mice bearing the GL261 murine glioma model (n=8). Since the complete diffusion time-dependence is in general non-analytical, the tumor microstructure was modeled in an appropriate time/frequency regime by impermeable spheres (radius Rcell, intracellular diffusivity Dics) surrounded by extracellular space (approximated by constant apparent diffusivity Decs in volume fraction ECS). POMACE parametric maps (ECS, Rcell, Dics, Decs) were compared with conventional diffusion weighted imaging metrics, electron microscopy (EM), alternative ECS determination based on effective medium theory (EMT), and optical microscopy performed on the same samples. It was shown that Decs can be approximated by its long-time tortuosity limit in the range [1/(88 Hz) - 31 ms]. ECS estimations (44±7% in vivo and 54±11% ex vivo) were in agreement with EMT-based ECS and literature on brain gliomas. Ex vivo, ECS maps correlated well with optical microscopy. Cell sizes (Rcell=4.8±1.3 in vivo and 4.3±1.4 μm ex vivo) were consistent with EM measurements (4.7±1.8 μm). In conclusion, Rcell and ECS can be quantified and mapped in vivo and ex vivo in brain tumors using the proposed POMACE method. Our experimental results support that POMACE provides a way to interpret the frequency- or time-dependence of the diffusion coefficient in tumors in terms of objective biophysical parameters of neuronal tissue, which can be used for non-invasive monitoring of preclinical cancer studies and treatment efficacy. PMID:27448059

A multicenter study shows PTEN deletion is strongly associated with seminal vesicle involvement and extracapsular extension in localized prostate cancer

PubMed Central

Troyer, Dean A; Jamaspishvili, Tamara; Wei, Wei; Feng, Ziding; Good, Jennifer; Hawley, Sarah; Fazli, Ladan; McKenney, Jesse K; Simko, Jeff; Hurtado-Coll, Antonio; Carroll, Peter R; Gleave, Martin; Lance, Raymond; Lin, Daniel W; Nelson, Peter S; Thompson, Ian M; True, Lawrence D; Brooks, James D; Squire, Jeremy A

2015-01-01

BACKGROUND Loss of the phosphatase and tensin homolog (PTEN) tumor suppressor gene is a promising marker of aggressive prostate cancer. Active surveillance and watchful waiting are increasingly recommended to patients with small tumors felt to be low risk, highlighting the difficulties of Gleason scoring in this setting. There is an urgent need for predictive biomarkers that can be rapidly deployed to aid in clinical decision-making. Our objectives were to assess the incidence and ability of PTEN alterations to predict aggressive disease in a multicenter study. METHODS We used recently developed probes optimized for sensitivity and specificity in a four-color FISH deletion assay to study the Canary Retrospective multicenter Prostate Cancer Tissue Microarray (TMA). This TMA was constructed specifically for biomarker validation from radical prostatectomy specimens, and is accompanied by detailed clinical information with long-term follow-up. RESULTS In 612 prostate cancers, the overall rate of PTEN deletion was 112 (18.3%). Hemizygous PTEN losses were present in 55/612 (9.0%) of cancers, whereas homozygous PTEN deletion was observed in 57/612 (9.3%) of tumors. Significant associations were found between PTEN status and pathologic stage (P < 0.0001), seminal vesicle invasion (P = 0.0008), extracapsular extension (P < 0.0001), and Gleason score (P = 0.0002). In logistic regression analysis of clinical and pathological variables, PTEN deletion was significantly associated with extracapsular extension, seminal vesicle involvement, and higher Gleason score. In the 406 patients in which clinical information was available, PTEN homozygous (P = 0.009) deletion was associated with worse post-operative recurrence-free survival (number of events = 189), pre-operative prostate specific antigen (PSA) (P < 0.001), and pathologic stage (P = 0.03). CONCLUSION PTEN status assessed by FISH is an independent predictor for recurrence-free survival in multivariate models, as were seminal vesicle invasion, extracapsular extension, and Gleason score, and preoperative PSA. Furthermore, these data demonstrate that the assay can be readily introduced at first diagnosis in a cost effective manner analogous to the use of FISH for analysis of HER2/neu status in breast cancer. Combined with published research beginning 17 years ago, both the data and tools now exist to implement a PTEN assay in the clinic. Prostate 75: 1206–1215, 2015. © 2015 The Authors. The Prostate, published by Wiley Periodicals, Inc. PMID:25939393

Long-term survival outcomes in patients with surgically treated oropharyngeal cancer and defined human papilloma virus status.

PubMed

Dale, O T; Sood, S; Shah, K A; Han, C; Rapozo, D; Mehanna, H; Winter, S C

2016-11-01

This study investigated long-term survival outcomes in surgically treated oropharyngeal cancer patients with known human papilloma virus status. A case note review was performed of all patients undergoing primary surgery for oropharyngeal cancer in a single centre over a 10-year period. Human papilloma virus status was determined via dual modality testing. Associations between clinicopathological variables and survival were identified using a log-rank test. Of the 107 cases in the study, 40 per cent (n = 41) were human papilloma virus positive. The positive and negative predictive values of p16 immunohistochemistry for human papilloma virus status were 57 per cent and 100 per cent, respectively. At a mean follow up of 59.5 months, 5-year overall and disease-specific survival estimates were 78 per cent and 69 per cent, respectively. Human papilloma virus status (p = 0.014), smoking status (p = 0.021) and tumour stage (p = 0.03) were significant prognostic indicators. The long-term survival rates in surgically treated oropharyngeal cancer patients were comparable to other studies. Variables including human papilloma virus status and tumour stage were associated with survival in patients treated with primary surgery; however, nodal stage and presence of extracapsular spread were non-prognostic.

Zika Virus Persistently Infects and Is Basolaterally Released from Primary Human Brain Microvascular Endothelial Cells.

PubMed

Mladinich, Megan C; Schwedes, John; Mackow, Erich R

2017-07-11

Zika virus (ZIKV) is a mosquito-borne Flavivirus that has emerged as the cause of encephalitis and fetal microencephaly in the Americas. ZIKV uniquely persists in human bodily fluids for up to 6 months, is sexually transmitted, and traverses the placenta and the blood-brain barrier (BBB) to damage neurons. Cells that support persistent ZIKV replication and mechanisms by which ZIKV establishes persistence remain enigmatic but central to ZIKV entry into protected neuronal compartments. The endothelial cell (EC) lining of capillaries normally constrains transplacental transmission and forms the BBB, which selectively restricts access of blood constituents to neurons. We found that ZIKV (strain PRVABC59) persistently infects and continuously replicates in primary human brain microvascular ECs (hBMECs), without cytopathology, for >9 days and following hBMEC passage. ZIKV did not permeabilize hBMECs but was released basolaterally from polarized hBMECs, suggesting a direct mechanism for ZIKV to cross the BBB. ZIKV-infected hBMECs were rapidly resistant to alpha interferon (IFN-α) and transiently induced, but failed to secrete, IFN-β and IFN-λ. Global transcriptome analysis determined that ZIKV constitutively induced IFN regulatory factor 7 (IRF7), IRF9, and IFN-stimulated genes (ISGs) 1 to 9 days postinfection, despite persistently replicating in hBMECs. ZIKV constitutively induced ISG15, HERC5, and USP18, which are linked to hepatitis C virus (HCV) persistence and IFN regulation, chemokine CCL5, which is associated with immunopathogenesis, as well as cell survival factors. Our results reveal that hBMECs act as a reservoir of persistent ZIKV replication, suggest routes for ZIKV to cross hBMECs into neuronal compartments, and define novel mechanisms of ZIKV persistence that can be targeted to restrict ZIKV spread. IMPORTANCE ZIKV persists in patients, crossing placental and neuronal barriers, damaging neurons, and causing fetal microencephaly. We found that ZIKV persistently infects brain endothelial cells that normally protect neurons from viral exposure. hBMECs are not damaged by ZIKV infection and, analogous to persistent HCV infection, ZIKV constitutively induces and evades antiviral ISG and IFN responses to continuously replicate in hBMECs. As a result, hBMECs provide a protective niche for systemic ZIKV spread and a viral reservoir localized in the normally protective blood-brain barrier. Consistent with the spread of ZIKV into neuronal compartments, ZIKV was released basolaterally from hBMECs. Our findings define hBMEC responses that contribute to persistent ZIKV infection and potential targets for clearing ZIKV infections from hBMECs. These results further suggest roles for additional ZIKV-infected ECs to facilitate viral spread and persistence in the protected placental, retinal, and testicular compartments. Copyright © 2017 Mladinich et al.

Proteases induce secretion of collagenase and plasminogen activator by fibroblasts

DOE Office of Scientific and Technical Information (OSTI.GOV)

Werb, Z.; Aggeler, J.

1978-04-01

We have observed that treatment of rabbit synovial fibroblasts with proteolytic enzymes can induce secretion of collagenase (EC 3.4.24.7) and plasminogen activator (EC 3.4.21.-). Cells treated for 2 to 24 hr with plasmin, trypsin, chymotrypsin, pancreatic elastase, papain, bromelain, thermolysin, or ..cap alpha..-protease but not with thrombin or neuraminidase secreted detectable amounts of collagenase within 16 to 48 hr. Treatment of fibroblasts with trypsin also induced secretion of plasminogen activator. Proteases initiated secretion of collagenase (up to 20 units per 10/sup 6/ cells per 24 hr) only when treatment produced decreased cell adhesion. Collagenase production did not depend on continuedmore » presence of proteolytic activity or on subsequent cell adhesion, spreading, or proliferation. Routine subculturing with crude trypsin also induced collagenase secretion by cells. Secretion of collagenase was prevented and normal spreading was obtained if the trypsinized cells were placed into medium containing fetal calf serum. Soybean trypsin inhibitor, ..cap alpha../sub 1/-antitrypsin, bovine serum albumin, collagen, and fibronectin did not inhibit collagenase production. Although proteases that induced collagenase secretion also removed surface glycoprotein, the kinetics of induction of cell protease secretion were different from those for removal of fibronectin. Physiological inducers of secretion of collagenase and plasminogen activator by cells have not been identified. These results suggest that extracellular proteases in conjunction with plasma proteins may govern protease secretion by cells.« less

The influence of internal variability on Earth's energy balance framework and implications for estimating climate sensitivity

NASA Astrophysics Data System (ADS)

Dessler, Andrew E.; Mauritsen, Thorsten; Stevens, Bjorn

2018-04-01

Our climate is constrained by the balance between solar energy absorbed by the Earth and terrestrial energy radiated to space. This energy balance has been widely used to infer equilibrium climate sensitivity (ECS) from observations of 20th-century warming. Such estimates yield lower values than other methods, and these have been influential in pushing down the consensus ECS range in recent assessments. Here we test the method using a 100-member ensemble of the Max Planck Institute Earth System Model (MPI-ESM1.1) simulations of the period 1850-2005 with known forcing. We calculate ECS in each ensemble member using energy balance, yielding values ranging from 2.1 to 3.9 K. The spread in the ensemble is related to the central assumption in the energy budget framework: that global average surface temperature anomalies are indicative of anomalies in outgoing energy (either of terrestrial origin or reflected solar energy). We find that this assumption is not well supported over the historical temperature record in the model ensemble or more recent satellite observations. We find that framing energy balance in terms of 500 hPa tropical temperature better describes the planet's energy balance.

A Simple Model to Rank Shellfish Farming Areas Based on the Risk of Disease Introduction and Spread.

PubMed

Thrush, M A; Pearce, F M; Gubbins, M J; Oidtmann, B C; Peeler, E J

2017-08-01

The European Union Council Directive 2006/88/EC requires that risk-based surveillance (RBS) for listed aquatic animal diseases is applied to all aquaculture production businesses. The principle behind this is the efficient use of resources directed towards high-risk farm categories, animal types and geographic areas. To achieve this requirement, fish and shellfish farms must be ranked according to their risk of disease introduction and spread. We present a method to risk rank shellfish farming areas based on the risk of disease introduction and spread and demonstrate how the approach was applied in 45 shellfish farming areas in England and Wales. Ten parameters were used to inform the risk model, which were grouped into four risk themes based on related pathways for transmission of pathogens: (i) live animal movement, (ii) transmission via water, (iii) short distance mechanical spread (birds) and (iv) long distance mechanical spread (vessels). Weights (informed by expert knowledge) were applied both to individual parameters and to risk themes for introduction and spread to reflect their relative importance. A spreadsheet model was developed to determine quantitative scores for the risk of pathogen introduction and risk of pathogen spread for each shellfish farming area. These scores were used to independently rank areas for risk of introduction and for risk of spread. Thresholds were set to establish risk categories (low, medium and high) for introduction and spread based on risk scores. Risk categories for introduction and spread for each area were combined to provide overall risk categories to inform a risk-based surveillance programme directed at the area level. Applying the combined risk category designation framework for risk of introduction and spread suggested by European Commission guidance for risk-based surveillance, 4, 10 and 31 areas were classified as high, medium and low risk, respectively. © 2016 Crown copyright.

[Trabeculotomy ab interno combined with extracapsular cataract extraction and IOL implantation].

PubMed

Alekseev, B N; Ermolaev, A P

2003-01-01

We made a total of 96 surgeries of extracapsular cataract extraction and IOL implantation combined with trabeculotomy ab interno during a period of 7 years. Patients with both open-angle and narrow-angle glaucoma of stages I and II and with the intraocular pressure (IOP) below or equal to 23 mm Hg according to Goldman under the conditions of hypotensive medicamental regimen were selected for surgery. After IOL was implanted into the lens bag, trabeculotomy ab interno was implemented as stage 2. A special mirror, introduced through the cataract incision, was used for direct gonioscopic monitoring. The trabecula was incised by the edge of a curved surgical knife under direct visual control. We regarded bleeding from the opened sinus as a favorable sign indicative of that the intrascleral collectors were intact. Only minor hyphemas were registered as postoperative complications; there was not a single case of ciliary-and-choroidal detachment. IOP was compensated for, in 6 months after surgery, in 94% of patients--69.8% of them did not use any hypotensive drops.

Intrahippocampal Pathways Involved in Learning/Memory Mechanisms are Affected by Intracerebral Infusions of Amyloid-β25-35 Peptide and Hydrated Fullerene C60 in Rats.

PubMed

Gordon, Rita; Podolski, Igor; Makarova, Ekaterina; Deev, Alexander; Mugantseva, Ekaterina; Khutsyan, Sergey; Sengpiel, Frank; Murashev, Arkady; Vorobyov, Vasily

2017-01-01

Primary memory impairments associated with increased level of amyloid-β (Aβ) in the brain have been shown to be linked, partially, with early pathological changes in the entorhinal cortex (EC) which spread on the whole limbic system. While the hippocampus is known to play a key role in learning and memory mechanisms, it is as yet unclear how its structures are involved in the EC pathology. In this study, changes in memory and neuronal morphology in male Wistar rats intrahippocampally injected with Aβ25-35 were correlated on days 14 and 45 after the injection to reveal specific cognitive-structural associations. The main focus was on the dentate gyrus (DG) and hippocampal areas of CA1 and CA3 because of their involvement in afferent flows from EC to the hippocampus through tri-synaptic (EC → DG → CA3 → CA1) and/or mono-synaptic (EC → CA1) pathways. Evident memory impairments were observed at both time points after Aβ25-35 injection. However, on day 14, populations of morphological intact neurons were decreased in CA3 and, drastically, in CA1, and the DG supramedial bundle was significantly damaged. On day 45, this bundle largely and CA1 neurons partially recovered, whereas CA3 neurons remained damaged. We suggest that Aβ25-35 primarily affects the tri-synaptic pathway, destroying the granular cells in the DG supramedial area and neurons in CA3 and, through the Schaffer collaterals, in CA1. Intrahippocampal pretreatment with hydrated fullerene C60 allows the neurons and their connections to survive the amyloidosis, thus supporting the memory mechanisms.

Micropatterned coculture of vascular endothelial and smooth muscle cells on layered electrospun fibrous mats toward blood vessel engineering.

PubMed

Li, Huinan; Liu, Yaowen; Lu, Jinfu; Wei, Jiaojun; Li, Xiaohong

2015-06-01

A major challenge in vascular engineering is the establishment of proper microenvironment to guide the spatial organization, growth, and extracellular matrix (ECM) productions of cells found in blood vessels. In the current study, micropatterned fibrous mats with distinct ridges and grooves of different width were created to load smooth muscle cells (SMCs), which were assembled by stacking on vascular endothelial cell (EC)-loaded flat fibrous mats to mimic the in vivo-like organized structure of blood vessels. SMCs were mainly distributed in the ridges, and aligned fibers in the patterned regions led to the formation of elongated cell bodies, intense actin filaments, and expressions of collagen I and α-smooth muscle actin in a parallel direction with fibers. ECs spread over the flat fibrous mats and expressed collagen IV and laminin with a cobblestone-like feature. A z-stack scanning of fluorescently stained fibrous mats indicated that SMCs effectively infiltrated into fibrous scaffolds at the depth of around 200 μm. Compared with SMCs cultured alone, the coculture with ECs enhanced the proliferation, infiltration, and cytoskeleton elongation of SMCs on patterned fibrous mats. Although the coculture of SMCs made no significant difference in the EC growth, the coculture system on patterned fibrous scaffolds promoted ECM productions of both ECs and SMCs. Thus, this patterned fibrous configuration not only offers a promising technology in the design of tissue engineering scaffolds to construct blood vessels with durable mechanical properties, but also provides a platform for patterned coculture to investigate cell-matrix and cell-cell interactions in highly organized tissues. © 2014 Wiley Periodicals, Inc.

Clinical risk scoring system for predicting extended-spectrum β-lactamase-producing Escherichia coli infection in hospitalized patients.

PubMed

Kengkla, K; Charoensuk, N; Chaichana, M; Puangjan, S; Rattanapornsompong, T; Choorassamee, J; Wilairat, P; Saokaew, S

2016-05-01

Extended spectrum β-lactamase-producing Escherichia coli (ESBL-EC) has important implications for infection control and empiric antibiotic prescribing. This study aims to develop a risk scoring system for predicting ESBL-EC infection based on local epidemiology. The study retrospectively collected eligible patients with a positive culture for E. coli during 2011 to 2014. The risk scoring system was developed using variables independently associated with ESBL-EC infection through logistic regression-based prediction. Area under the receiver-operator characteristic curve (AuROC) was determined to confirm the prediction power of the model. Predictors for ESBL-EC infection were male gender [odds ratio (OR): 1.53], age ≥55 years (OR: 1.50), healthcare-associated infection (OR: 3.21), hospital-acquired infection (OR: 2.28), sepsis (OR: 1.79), prolonged hospitalization (OR: 1.88), history of ESBL infection within one year (OR: 7.88), prior use of broad-spectrum cephalosporins within three months (OR: 12.92), and prior use of other antibiotics within three months (OR: 2.14). Points scored ranged from 0 to 47, and were divided into three groups based on diagnostic performance parameters: low risk (score: 0-8; 44.57%), moderate risk (score: 9-11; 21.85%) and high risk (score: ≥12; 33.58%). The model displayed moderate power of prediction (AuROC: 0.773; 95% confidence interval: 0.742-0.805) and good calibration (Hosmer-Lemeshow χ(2) = 13.29; P = 0.065). This tool may optimize the prescribing of empirical antibiotic therapy, minimize time to identify patients, and prevent spreading of ESBL-EC. Prior to adoption into routine clinical practice, further validation study of the tool is needed. Copyright © 2016 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

Molecular characteristics of extended-spectrum β-lactamase-producing Escherichia coli in Riyadh: emergence of CTX-M-15-producing E. coli ST131.

PubMed

Al-Agamy, Mohamed H; Shibl, Atef M; Hafez, Mohamed M; Al-Ahdal, Mohammad N; Memish, Ziad A; Khubnani, Harish

2014-01-07

The prevalence of extended-spectrum β-lactamase-producing Escherichia coli (ESBL-EC) has increased recently. The aim of this study was to further characterise and to assess the occurrence of ESBL-EC in Riyadh, to use pulsed field gel electrophoresis (PFGE) typing to investigate the epidemiology of ESBL-EC and to determine the prevalence of ST131 in ESBL-EC. A total of 152 E. coli isolates were collected at a tertiary hospital in Riyadh from September 2010 to June 2011. Genotypic and phenotypic methods were used to characterise ESBLs. PFGE was used to determine genetic relatedness. Detection of ST131 and CTX-M-like ESBLs was performed using real-time PCR. Of 152 strains, 31 were positive for ESBLs by phenotypic methods. The blaCTX-M-15 gene was highly prevalent (30/31 strains, 96.77%) among the 31 ESBL-positive E. coli strains. The blaCTX-M-27 gene was detected in one strain. Twenty (64.5%) out of 31 of ESBL-EC were ST131. PFGE revealed 29 different pulsotypes. Our study documented the high prevalence of ESBLs in E. coli isolates, with CTX-M-15 as the predominant ESBL gene. ST131 clone producing CTX-M-15 has a major presence in our hospital. The high prevalence of CTX-M producers was not due to the spread of a single clone. To the best of our knowledge, this study represents the first report of CTX-M-15 and CTX-M-27 β-lactamases and the detection of the ST131 clone in Saudi E. coli isolates.

Pericyte contractility controls endothelial cell cycle progression and sprouting: insights into angiogenic switch mechanics.

PubMed

Durham, Jennifer T; Surks, Howard K; Dulmovits, Brian M; Herman, Ira M

2014-11-01

Microvascular stability and regulation of capillary tonus are regulated by pericytes and their interactions with endothelial cells (EC). While the RhoA/Rho kinase (ROCK) pathway has been implicated in modulation of pericyte contractility, in part via regulation of the myosin light chain phosphatase (MLCP), the mechanisms linking Rho GTPase activity with actomyosin-based contraction and the cytoskeleton are equivocal. Recently, the myosin phosphatase-RhoA-interacting protein (MRIP) was shown to mediate the RhoA/ROCK-directed MLCP inactivation in vascular smooth muscle. Here we report that MRIP directly interacts with the β-actin-specific capping protein βcap73. Furthermore, manipulation of MRIP expression influences pericyte contractility, with MRIP silencing inducing cytoskeletal remodeling and cellular hypertrophy. MRIP knockdown induces a repositioning of βcap73 from the leading edge to stress fibers; thus MRIP-silenced pericytes increase F-actin-driven cell spreading twofold. These hypertrophied and cytoskeleton-enriched pericytes demonstrate a 2.2-fold increase in contractility upon MRIP knockdown when cells are plated on a deformable substrate. In turn, silencing pericyte MRIP significantly affects EC cycle progression and angiogenic activation. When MRIP-silenced pericytes are cocultured with capillary EC, there is a 2.0-fold increase in EC cycle entry. Furthermore, in three-dimensional models of injury and repair, silencing pericyte MRIP results in a 1.6-fold elevation of total tube area due to EC network formation and increased angiogenic sprouting. The pivotal role of MRIP expression in governing pericyte contractile phenotype and endothelial growth should lend important new insights into how chemomechanical signaling pathways control the "angiogenic switch" and pathological angiogenic induction. Copyright © 2014 the American Physiological Society.

Identification of Differentially Expressed Proteins in Direct Expressed Prostatic Secretions of Men with Organ-confined Versus Extracapsular Prostate Cancer*

PubMed Central

Kim, Yunee; Ignatchenko, Vladimir; Yao, Cindy Q.; Kalatskaya, Irina; Nyalwidhe, Julius O.; Lance, Raymond S.; Gramolini, Anthony O.; Troyer, Dean A.; Stein, Lincoln D.; Boutros, Paul C.; Medin, Jeffrey A.; Semmes, O. John; Drake, Richard R.; Kislinger, Thomas

2012-01-01

Current protocols for the screening of prostate cancer cannot accurately discriminate clinically indolent tumors from more aggressive ones. One reliable indicator of outcome has been the determination of organ-confined versus nonorgan-confined disease but even this determination is often only made following prostatectomy. This underscores the need to explore alternate avenues to enhance outcome prediction of prostate cancer patients. Fluids that are proximal to the prostate, such as expressed prostatic secretions (EPS), are attractive sources of potential prostate cancer biomarkers as these fluids likely bathe the tumor. Direct-EPS samples from 16 individuals with extracapsular (n = 8) or organ-confined (n = 8) prostate cancer were used as a discovery cohort, and were analyzed in duplicate by a nine-step MudPIT on a LTQ-Orbitrap XL mass spectrometer. A total of 624 unique proteins were identified by at least two unique peptides with a 0.2% false discovery rate. A semiquantitative spectral counting algorithm identified 133 significantly differentially expressed proteins in the discovery cohort. Integrative data mining prioritized 14 candidates, including two known prostate cancer biomarkers: prostate-specific antigen and prostatic acid phosphatase, which were significantly elevated in the direct-EPS from the organ-confined cancer group. These and five other candidates (SFN, MME, PARK7, TIMP1, and TGM4) were verified by Western blotting in an independent set of direct-EPS from patients with biochemically recurrent disease (n = 5) versus patients with no evidence of recurrence upon follow-up (n = 10). Lastly, we performed proof-of-concept SRM-MS-based relative quantification of the five candidates using unpurified heavy isotope-labeled synthetic peptides spiked into pools of EPS-urines from men with extracapsular and organ-confined prostate tumors. This study represents the first efforts to define the direct-EPS proteome from two major subclasses of prostate cancer using shotgun proteomics and verification in EPS-urine by SRM-MS. PMID:22986220

PIP breast implants: rupture rate and correlation with breast cancer

PubMed Central

MOSCHETTA, M.; TELEGRAFO, M.; CORNACCHIA, I.; VINCENTI, L.; RANIERI, V.; CIRILLI, A.; RELLA, L.; IANORA, A.A. STABILE; ANGELELLI, G.

2014-01-01

Aim To evaluate the incidence of Poly Implant Prosthése (PIP) rupture as assessed by magnetic resonance imaging (MRI), the prevalence of the detected signs and the potential correlation with breast carcinoma. Patients and methods 67 patients with silicone breast implants and clinical indications for breast MRI were evaluated for a total of 125 implants: 40 (32%) PIP in 21 patients and 85 non-PIP in 46 patients (68%), the latest considered as control group. A 1.5-T MR imaging device was used in order to assess implant integrity with dedicated sequences and in 6 cases a dynamic study was performed for characterizing breast lesions. Two radiologists with more than 5 years’ experience in the field of MRI evaluated in consensus all MR images searching for the presence of clear signs of intra or extra-capsular implant rupture. Results 20/40 (50%) PIP implants presented signs of intra-capsular rupture: linguine sign in 20 cases (100%), tear-drop sign in 6 (30%). In 12/20 cases (60%), MRI signs of extra-capsular rupture were detected. In the control group, an intra-capsular rupture was diagnosed in 12/85 cases (14%) associated with extra-capsular one in 5/12 cases (42%). Among the six cases with suspected breast lesions, in 2/21 patients with PIP implants (10%) a breast carcinoma was diagnosed (mucinous carcinoma, n=1; invasive ductal carcinoma, n=1). In 4/46 patients (9%) with non-PIP implants, an invasive ductal carcinoma was diagnosed. Conclusion The rupture rate of PIP breast implants is significantly higher than non-PIP (50% vs 14%). MRI represents the most accurate imaging tool for evaluating breast prostheses and the linguine sign is the most common MRI sign to be searched. The incidence of breast carcinoma does not significantly differ between the PIP and non-PIP implants and a direct correlation with breast cancer can not been demonstrated. PMID:25644728

PIP breast implants: rupture rate and correlation with breast cancer.

PubMed

Moschetta, M; Telegrafo, M; Cornacchia, I; Vincenti, L; Ranieri, V; Cirili, A; Rella, L; Stabile Ianora, A A; Angelelli, G

2014-01-01

To evaluate the incidence of Poly Implant Prosthése (PIP) rupture as assessed by magnetic resonance imaging (MRI), the prevalence of the detected signs and the potential correlation with breast carcinoma. 67 patients with silicone breast implants and clinical indications for breast MRI were evaluated for a total of 125 implants: 40 (32%) PIP in 21 patients and 85 non-PIP in 46 patients (68%), the latest considered as control group. A 1.5-T MR imaging device was used in order to assess implant integrity with dedicated sequences and in 6 cases a dynamic study was performed for characterizing breast lesions. Two radiologists with more than 5 years' experience in the field of MRI evaluated in consensus all MR images searching for the presence of clear signs of intra or extra-capsular implant rupture. 20/40 (50%) PIP implants presented signs of intra-capsular rupture: linguine sign in 20 cases (100%), tear-drop sign in 6 (30%). In 12/20 cases (60%), MRI signs of extra-capsular rupture were detected. In the control group, an intra-capsular rupture was diagnosed in 12/85 cases (14%) associated with extra-capsular one in 5/12 cases (42%). Among the six cases with suspected breast lesions, in 2/21 patients with PIP implants (10%) a breast carcinoma was diagnosed (mucinous carcinoma, n=1; invasive ductal carcinoma, n=1). In 4/46 patients (9%) with non-PIP implants, an invasive ductal carcinoma was diagnosed. The rupture rate of PIP breast implants is significantly higher than non-PIP (50% vs 14%). MRI represents the most accurate imaging tool for evaluating breast prostheses and the linguine sign is the most common MRI sign to be searched. The incidence of breast carcinoma does not significantly differ between the PIP and non-PIP implants and a direct correlation with breast cancer can not been demonstrated.

Risk Factors for Central Neck Lymph Node Metastases in Micro- Versus Macro- Clinically Node Negative Papillary Thyroid Carcinoma.

PubMed

Sessa, Luca; Lombardi, Celestino Pio; De Crea, Carmela; Tempera, Serena Elisa; Bellantone, Rocco; Raffaelli, Marco

2018-03-01

Tumor size has been advocated as possible risk factors for occult central lymph node metastases (CNM) in papillary thyroid carcinoma (PTC) patients. This prospective study evaluated factors that could identify patients at higher risk of occult CNM, especially comparing micro-PTC and macro-PTC. One hundred and eighty-six patients were recruited. All the patients had cN0 clinically unifocal PTC and underwent total thyroidectomy and bilateral prophylactic central neck dissection. Risk factors for occult CNM in micro- and macro-PTC patients were evaluated. Eighty-two patients showed CNM. The rate of CNM did not differ among different sizes cut off (≤20 mm, ≤10 mm, ≤5 mm P = NS). Significantly more pN1a than pN0 patients had pT3 tumors (35/82 vs. 26/104) (P < 0.05), extracapsular invasion (35/82 vs. 22/104) (P < 0.01) and microscopic multifocal disease (50/82 vs. 47/104) (P < 0.05). Independent risk factors for CNM were extracapsular invasion and multifocality at multivariate analysis. Risk factors for CNM in 77 micro-PTC were extracapsular invasion (16/31 pN1 vs. 10/46 pN0, P < 0.05) and multifocality (21/31 pN1 vs. 16/46 pN0, P < 0.01). Among 109 macro-PTC, risk factors for CNM were angioinvasion (15/51 pN1 vs. 7/58 pN0, P < 0.05) and classic PTC at the final histology (PTC vs. tall cell variant vs. follicular variant PTC) (P < 0.05). Risk factors for CNM can differ between micro- and macro-PTC, but no preoperatively known clinical parameter is predictor of CNM in cN0 clinically unifocal PTC.

Infracentimetric cervical lymph node metastasis in head and neck squamous cell carcinoma: Incidence and prognostic value.

PubMed

Pauzie, A; Gavid, M; Dumollard, J-M; Timoshenko, A; Peoc'h, M; Prades, J-M

2016-11-01

Supracentimetric cervical lymph node metastasis is classically a poor prognostic factor for locoregional recurrence and survival in head and neck cancer. Causality, however, is more controversial for infracentimetric cervical lymph node metastases. The objective of this study was to evaluate the incidence and prognostic value of infracentimetric lymph node metastasis. Two hundred and forty-three neck dissections from 150 head and neck cancer patients were analyzed. A single pathologist exhaustively inventoried the number and size of all adenopathies in the surgical specimen. Cervical lymph node metastases were infracentimetric in 38% of cases, with 72% extracapsular spread (versus 91% for supracentimetric adenopathies; P<0.01). Infracentimetric metastases were more often associated with other cervical lymph node metastases (mean 5.3 versus 3.9; P=0.14). Fifty three percent of specimens showed only supracentimetric metastases (versus 13% infracentimetric metastases; P<0.01). Disease-specific and failure-free survival were lower in case of infracentimetric metastasis, associated with supracentimetric metastasis or not, than in case of macrometastasis only. Infracentimetric cervical lymph node metastasis is a factor of poor prognosis, and may represent a different, more aggressive lymphatic process. We suggest complete neck dissection by the surgeon and meticulous analysis by the pathologist, the results of which guide complementary therapy. Close surveillance of recurrence is also recommended. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Esophageal Cancer Metastases to Unexpected Sites: A Systematic Review

PubMed Central

2017-01-01

The most common pattern of esophageal cancer metastases (ECM) is to the lymph nodes, lung, liver, bones, adrenal glands, and brain. On the other hand, unexpected metastasis (UM) spread to uncommon sites has increasingly reported and consequently affected the pathway of diagnosis, staging, and management. Using the PubMed database, a systematic search of the following headings “Esophageal” and “Metastasis” or “Metastases” was performed, 10049 articles were identified, and the articles were included if they demonstrated unexpected ECM. 84% of cases were men with an average age of 60.7 years. EC was located in the lower third in 65%. Two-thirds of the UM originated from the lower esophagus, and the two major histological types were adenocarcinoma 40% and squamous cell carcinoma 60%. Metastases were disseminated toward five main anatomical sites: the head and neck (42%), thoracic (17%), abdomen and pelvis (25%), extremities (9%), and multiple skin and muscle metastases (7%). The EC metastases were found to be synchronous 42% and metachronous 58%, isolated in 53.5% and multiple in 46.5%. The overall survival rate was 10.2 months. Since distant metastases are responsible for most EC-related deaths, understanding of ECM dissemination patterns needs more extensive studies. These critical data are the cornerstone of optimal cancer approach and treatment. PMID:28659974

Comparison of pelvic phased-array versus endorectal coil magnetic resonance imaging at 3 Tesla for local staging of prostate cancer.

PubMed

Kim, Bum Soo; Kim, Tae-Hwan; Kwon, Tae Gyun; Yoo, Eun Sang

2012-05-01

Several studies have demonstrated the superiority of endorectal coil magnetic resonance imaging (MRI) over pelvic phased-array coil MRI at 1.5 Tesla for local staging of prostate cancer. However, few have studied which evaluation is more accurate at 3 Tesla MRI. In this study, we compared the accuracy of local staging of prostate cancer using pelvic phased-array coil or endorectal coil MRI at 3 Tesla. Between January 2005 and May 2010, 151 patients underwent radical prostatectomy. All patients were evaluated with either pelvic phased-array coil or endorectal coil prostate MRI prior to surgery (63 endorectal coils and 88 pelvic phased-array coils). Tumor stage based on MRI was compared with pathologic stage. We calculated the specificity, sensitivity and accuracy of each group in the evaluation of extracapsular extension and seminal vesicle invasion. Both endorectal coil and pelvic phased-array coil MRI achieved high specificity, low sensitivity and moderate accuracy for the detection of extracapsular extension and seminal vesicle invasion. There were statistically no differences in specificity, sensitivity and accuracy between the two groups. Overall staging accuracy, sensitivity and specificity were not significantly different between endorectal coil and pelvic phased-array coil MRI.

Single- and double- lumen silicone breast implant integrity: prospective evaluation of MR and US criteria.

PubMed

Berg, W A; Caskey, C I; Hamper, U M; Kuhlman, J E; Anderson, N D; Chang, B W; Sheth, S; Zerhouni, E A

1995-10-01

To evaluate the accuracy of magnetic resonance (MR) and ultrasound (US) criteria for breast implant integrity. One hundred twenty-two single-lumen silicone breast implants and 22 bilumen implants were evaluated with surface coil MR imaging and US and surgically removed. MR criteria for implant failure were a collapsed implant shell ("linguine sign"), foci of silicone outside the shell ("noose sign"), and extracapsular gel, US criteria were collapsed shell, low-level echoes within the gel, and "snowstorm" echoes of extracapsular silicone. Among single-lumen implants, MR imaging depicted 39 of 40 ruptures, 14 of 28 with minimal leakage; 49 of 54 intact implants were correctly interpreted. US depicted 26 of 40 ruptured implants, four of 28 with minimal leakage, and 30 of 54 intact implants. Among bilumen implants, MR imaging depicted four of five implants with rupture of both lumina and nine of 10 as intact; US depicted one rupture and helped identify two of 10 as intact. Mammography accurately depicted the status of 29 of 30 bilumen implants with MR imaging correlation. MR imaging depicts implant integrity more accurately than US; neither method reliably depicts minimal leakage with shell collapse. Mammography is useful in screening bilumen implant integrity.

A comparison of six different ballast water treatment systems based on UV radiation, electrochlorination and chlorine dioxide.

PubMed

Stehouwer, Peter Paul; Buma, Anita; Peperzak, Louis

2015-01-01

The spread of aquatic invasive species through ballast water is a major ecological and economical threat. Because of this, the International Maritime Organization (IMO) set limits to the concentrations of organisms allowed in ballast water. To meet these limits, ballast water treatment systems (BWTSs) were developed. The main techniques used for ballast water treatment are ultraviolet (UV) radiation and electrochlorination (EC). In this study, phytoplankton regrowth after treatment was followed for six BWTSs. Natural plankton communities were treated and incubated for 20 days. Growth, photosystem II efficiency and species composition were followed. The three UV systems all showed similar patterns of decrease in phytoplankton concentrations followed by regrowth. The two EC and the chlorine dioxide systems showed comparable results. However, UV- and chlorine-based treatment systems showed significantly different responses. Overall, all BWTSs reduced phytoplankton concentrations to below the IMO limits, which represents a reduced risk of aquatic invasions through ballast water.

The Complete Sequence and Comparative Analysis of a Multidrug-Resistance and Virulence Multireplicon IncFII Plasmid pEC302/04 from an Extraintestinal Pathogenic Escherichia coli EC302/04 Indicate Extensive Diversity of IncFII Plasmids.

PubMed

Ho, Wing Sze; Yap, Kien-Pong; Yeo, Chew Chieng; Rajasekaram, Ganeswrie; Thong, Kwai Lin

2015-01-01

Extraintestinal pathogenic Escherichia coli (ExPEC) that causes extraintestinal infections often harbor plasmids encoding fitness traits such as resistance and virulence determinants that are of clinical importance. We determined the complete nucleotide sequence of plasmid pEC302/04 from a multidrug-resistant E. coli EC302/04 which was isolated from the tracheal aspirate of a patient in Malaysia. In addition, we also performed comparative sequence analyses of 18 related IncFIIA plasmids to determine the phylogenetic relationship and diversity of these plasmids. The 140,232 bp pEC302/04 is a multireplicon plasmid that bears three replication systems (FII, FIA, and FIB) with subtype of F2:A1:B1. The plasmid is self-transmissible with a complete transfer region. pEC302/04 also carries antibiotic resistance genes such as bla TEM-1 and a class I integron containing sul1, cml and aadA resistance genes, conferring multidrug resistance (MDR) to its host, E. coli EC302/04. Besides, two iron acquisition systems (SitABCD and IutA-IucABCD) which are the conserved virulence determinants of ExPEC-colicin V or B and M (ColV/ColBM)-producing plasmids were identified in pEC302/04. Multiple toxin-antitoxin (TA)-based addiction systems (i.e., PemI/PemK, VagC/VagD, CcdA/CcdB, and Hok/Sok) and a plasmid partitioning system, ParAB, and PsiAB, which are important for plasmid maintenance were also found. Comparative plasmid analysis revealed only one conserved gene, the repA1 as the core genome, showing that there is an extensive diversity among the IncFIIA plasmids. The phylogenetic relationship of 18 IncF plasmids based on the core regions revealed that ColV/ColBM-plasmids and non-ColV/ColBM plasmids were separated into two distinct groups. These plasmids, which carry highly diverse genetic contents, are also mosaic in nature. The atypical combination of genetic materials, i.e., the MDR- and ColV/ColBM-plasmid-virulence encoding regions in a single ExPEC plasmid is rare but of clinical importance. Such phenomenon is bothersome when the plasmids are transmissible, facilitating the spread of virulence and resistance plasmids among pathogenic bacteria. Notably, certain TA systems are more commonly found in particular ExPEC plasmid types, indicating the possible relationships between certain TA systems and ExPEC pathogenesis.

Enhanced Re-Endothelialization of Decellularized Rat Lungs

PubMed Central

Stabler, Collin T.; Caires, Luiz C.; Mondrinos, Mark J.; Marcinkiewicz, Cezary; Lazarovici, Philip; Wolfson, Marla R.

2016-01-01

Decellularized lung tissue has been recognized as a potential platform to engineer whole lung organs suitable for transplantation or for modeling a variety of lung diseases. However, many technical hurdles remain before this potential may be fully realized. Inability to efficiently re-endothelialize the pulmonary vasculature with a functional endothelium appears to be the primary cause of failure of recellularized lung scaffolds in early transplant studies. Here, we present an optimized approach for enhanced re-endothelialization of decellularized rodent lung scaffolds with rat lung microvascular endothelial cells (ECs). This was achieved by adjusting the posture of the lung to a supine position during cell seeding through the pulmonary artery. The supine position allowed for significantly more homogeneous seeding and better cell retention in the apex regions of all lobes than the traditional upright position, especially in the right upper and left lobes. Additionally, the supine position allowed for greater cell retention within large diameter vessels (proximal 100–5000 μm) than the upright position, with little to no difference in the small diameter distal vessels. EC adhesion in the proximal regions of the pulmonary vasculature in the decellularized lung was dependent on the binding of EC integrins, specifically α1β1, α2β1, and α5β1 integrins to, respectively, collagen type-I, type-IV, and fibronectin in the residual extracellular matrix. Following in vitro maturation of the seeded constructs under perfusion culture, the seeded ECs spread along the vascular wall, leading to a partial reestablishment of endothelial barrier function as inferred from a custom-designed leakage assay. Our results suggest that attention to cellular distribution within the whole organ is of paramount importance for restoring proper vascular function. PMID:26935764

Expression of Tau Pathology-Related Proteins in Different Brain Regions: A Molecular Basis of Tau Pathogenesis.

PubMed

Hu, Wen; Wu, Feng; Zhang, Yanchong; Gong, Cheng-Xin; Iqbal, Khalid; Liu, Fei

2017-01-01

Microtubule-associated protein tau is hyperphosphorylated and aggregated in affected neurons in Alzheimer disease (AD) brains. The tau pathology starts from the entorhinal cortex (EC), spreads to the hippocampus and frontal and temporal cortices, and finally to all isocortex areas, but the cerebellum is spared from tau lesions. The molecular basis of differential vulnerability of different brain regions to tau pathology is not understood. In the present study, we analyzed brain regional expressions of tau and tau pathology-related proteins. We found that tau was hyperphosphorylated at multiple sites in the frontal cortex (FC), but not in the cerebellum, from AD brain. The level of tau expression in the cerebellum was about 1/4 of that seen in the frontal and temporal cortices in human brain. In the rat brain, the expression level of tau with three microtubule-binding repeats (3R-tau) was comparable in the hippocampus, EC, FC, parietal-temporal cortex (PTC), occipital-temporal cortex (OTC), striatum, thalamus, olfactory bulb (OB) and cerebellum. However, the expression level of 4R-tau was the highest in the EC and the lowest in the cerebellum. Tau phosphatases, kinases, microtubule-related proteins and other tau pathology-related proteins were also expressed in a region-specific manner in the rat brain. These results suggest that higher levels of tau and tau kinases in the EC and low levels of these proteins in the cerebellum may accounts for the vulnerability and resistance of these representative brain regions to the development of tau pathology, respectively. The present study provides the regional expression profiles of tau and tau pathology-related proteins in the brain, which may help understand the brain regional vulnerability to tau pathology in neurodegenerative tauopathies.

Evaluation of an interlaced triple procedure: penetrating keratoplasty, extracapsular cataract extraction, and nonopen-sky intraocular lens implantation.

PubMed

Yang, Shuo; Wang, Bin; Zhang, Yangyang; Zhai, Hualei; Wang, Junyi; Wang, Shuang; Xie, Lixin

2017-09-01

To evaluate an interlaced triple procedure that involved penetrating keratoplasty (PKP), extracapsular cataract extraction (ECCE) using diathermy capsulotomy, and nonopen-sky intraocular lens (IOL) implantation.This retrospective study involved data from 34 patients who were diagnosed with severe corneal opacities and cataracts. These patients were divided into an interlaced procedure group (21 patients) and a traditional procedure group (13 patients). In the interlaced group, the method of continuous curvilinear capsulorhexis (CCC) was completed via diathermy capsulotomy. The donor corneal button was sutured at 8 positions (at equal intervals) using 10-0 nylon sutures, and the IOL was inserted into the capsular bag using a closed anterior chamber approach at the 10:30 to 12 o'clock positions between the sutures. In the traditional group, CCC was completed using side-port capsular forceps, and the IOL was implanted using an open anterior chamber approach.In the interlaced group, the CCC, open-sky, and total operation times were significantly shorter than in the traditional group (P < .05). Neither the best-corrected visual acuity (BCVA) nor corneal endothelial cell density was significantly different between the groups at 1 and 6 months after the operation.This interlaced triple procedure for the treatment of corneal diseases with cataracts appears to be feasible and practical.

Germline PRKACA amplification leads to Cushing syndrome caused by 3 adrenocortical pathologic phenotypes.

PubMed

Carney, J Aidan; Lyssikatos, Charalampos; Lodish, Maya B; Stratakis, Constantine A

2015-01-01

We describe the pathology of 5 patients with germline PRKACA copy number gain and Cushing syndrome: 4 males and 1 female, aged 2 to 43 years, including a mother and son. Imaging showed normal or slightly enlarged adrenal glands in 4 patients and a unilateral mass in the fifth. Biochemically, the patients had corticotropin-independent hypercortisolism. Four underwent bilateral adrenalectomy; unilateral adrenalectomy was performed in the patient with the adrenal mass. Pathologically, 3 patients, including the 1 with the tumor (adenoma), had primary pigmented nodular adrenocortical disease with extranodular cortical atrophy and mild intracapsular and extracapsular extension of cortical cells. The other 2 patients had cortical hyperplasia and prominent capsular and extracapsular micronodular cortical hyperplasia. Immunoperoxidase staining revealed differences for synaptophysin, inhibin-A, and Ki-67 (nuclei) in the atrophic cortices (patients 1, 2, and 3) and hyperplastic cortices (patients 4 and 5) and for Ki-67 (nuclei) and vimentin in the extracortical nodules in the 2 groups of patients. β-Catenin stained the cell membrane, cytoplasm, and nuclei of the adenoma. The patients were well at follow-up (1-23 years); 24-hour urinary cortisol excretion was elevated in the patient who had unilateral adrenalectomy. Copyright © 2014 Elsevier Inc. All rights reserved.

Comparison of Pelvic Phased-Array versus Endorectal Coil Magnetic Resonance Imaging at 3 Tesla for Local Staging of Prostate Cancer

PubMed Central

Kim, Bum Soo; Kim, Tae-Hwan; Kwon, Tae Gyun

2012-01-01

Purpose Several studies have demonstrated the superiority of endorectal coil magnetic resonance imaging (MRI) over pelvic phased-array coil MRI at 1.5 Tesla for local staging of prostate cancer. However, few have studied which evaluation is more accurate at 3 Tesla MRI. In this study, we compared the accuracy of local staging of prostate cancer using pelvic phased-array coil or endorectal coil MRI at 3 Tesla. Materials and Methods Between January 2005 and May 2010, 151 patients underwent radical prostatectomy. All patients were evaluated with either pelvic phased-array coil or endorectal coil prostate MRI prior to surgery (63 endorectal coils and 88 pelvic phased-array coils). Tumor stage based on MRI was compared with pathologic stage. We calculated the specificity, sensitivity and accuracy of each group in the evaluation of extracapsular extension and seminal vesicle invasion. Results Both endorectal coil and pelvic phased-array coil MRI achieved high specificity, low sensitivity and moderate accuracy for the detection of extracapsular extension and seminal vesicle invasion. There were statistically no differences in specificity, sensitivity and accuracy between the two groups. Conclusion Overall staging accuracy, sensitivity and specificity were not significantly different between endorectal coil and pelvic phased-array coil MRI. PMID:22476999

Complications of hip fractures: A review

PubMed Central

Carpintero, Pedro; Caeiro, Jose Ramón; Carpintero, Rocío; Morales, Angela; Silva, Samuel; Mesa, Manuel

2014-01-01

Nowadays, fracture surgery represents a big part of the orthopedic surgeon workload, and usually has associated major clinical and social cost implications. These fractures have several complications. Some of these are medical, and other related to the surgical treatment itself. Medical complications may affect around 20% of patients with hip fracture. Cognitive and neurological alterations, cardiopulmonary affections (alone or combined), venous thromboembolism, gastrointestinal tract bleeding, urinary tract complications, perioperative anemia, electrolytic and metabolic disorders, and pressure scars are the most important medical complications after hip surgery in terms of frequency, increase of length of stay and perioperative mortality. Complications arising from hip fracture surgery are fairly common, and vary depending on whether the fracture is intracapsular or extracapsular. The main problems in intracapsular fractures are biological: vascularization of the femoral head, and lack of periosteum -a major contributor to fracture healing- in the femoral neck. In extracapsular fractures, by contrast, the problem is mechanical, and relates to load-bearing. Early surgical fixation, the role of anti-thromboembolic and anti-infective prophylaxis, good pain control at the perioperative, detection and management of delirium, correct urinary tract management, avoidance of malnutrition, vitamin D supplementation, osteoporosis treatment and advancement of early mobilization to improve functional recovery and falls prevention are basic recommendations for an optimal maintenance of hip fractured patients. PMID:25232517

Investigation of the feasibility of elective irradiation to neck level Ib using intensity-modulated radiotherapy for patients with nasopharyngeal carcinoma: a retrospective analysis.

PubMed

Zhang, Fan; Cheng, Yi-Kan; Li, Wen-Fei; Guo, Rui; Chen, Lei; Sun, Ying; Mao, Yan-Ping; Zhou, Guan-Qun; Liu, Xu; Liu, Li-Zhi; Lin, Ai-Hua; Tang, Ling-Long; Ma, Jun

2015-10-15

To assess the feasibility of elective neck irradiation to level Ib in nasopharyngeal carcinoma (NPC) using intensity-modulated radiation therapy (IMRT). We retrospectively analyzed 1438 patients with newly-diagnosed, non-metastatic and biopsy-proven NPC treated with IMRT. Greatest dimension of level IIa LNs (DLN-IIa) ≥ 20 mm and/or level IIa LNs with extracapsular spread (ES), oropharynx involvement and positive bilateral cervical lymph nodes (CLNs) were independently significantly associated with metastasis to level Ib LN at diagnosis. No recurrence at level Ib was observed in the 904 patients without these characteristics (median follow-up, 38.7 months; range, 1.3-57.8 months), these patients were classified as low risk. Level Ib irradiation was not an independent risk factor for locoregional failure-free survival, distant failure-free survival, failure-free survival or overall survival in low risk patients. The frequency of grade ≥ 2 subjective xerostomia at 12 months after radiotherapy was not significantly different between low risk patients who received level Ib-sparing, unilateral level Ib-covering or bilateral level Ib-covering IMRT. Level Ib-sparing IMRT should be safe and feasible for patients without a DLN-IIa ≥ 20 mm and/or level IIa LNs with ES, positive bilateral CLNs or oropharynx involvement at diagnosis. Further investigations based on specific criteria for dose constraints for the submandibular glands are warranted to confirm the benefit of elective level Ib irradiation.

Role of chronic lymphocytic thyroiditis in central node metastasis of papillary thyroid carcinoma.

PubMed

Paulson, Lorien M; Shindo, Maisie L; Schuff, Kathryn G

2012-09-01

(1) To investigate the role of chronic lymphocytic thyroiditis (CLT) in central node metastasis of papillary thyroid carcinoma (PTC) and (2) to evaluate the presence of chronic lymphocytic thyroiditis according to PTC-specific molecular markers. Historical cohort study. Academic medical center. All patients who underwent total thyroidectomy with central neck dissection for PTC at Oregon Health & Science University between 2005 and 2010 were screened for the presence of CLT and reviewed for clinical prognostic factors. Patients with inadequate central neck dissections were excluded. Molecular markers for PTC were analyzed on archived tumor samples. A total of 139 patients met selection criteria. The rate of CLT was 43.8%. The rate of central node positivity was 63%. Presence of CLT was associated with a significantly lower proportion of central node metastases (49% vs 74%, P = .003) and angiolymphatic invasion (31% vs 15%, P = .03). There was no significant difference in mean age, tumor size, and extracapsular extension. Molecular genotyping did not reveal a significant difference in the types of mutations found in both groups. The data indicate a lower incidence of central compartment lymph node metastasis in those with CLT in this patient population, suggesting a potential protective role in tumor spread. The equal distribution of tumor mutations between the carcinomas with and without evidence of CLT argues against a mutation-specific antigen as the immunologic stimulus. Further research is needed to characterize the role of autoimmunity in thyroid cancer.

Amtyr1: characterization of a gene from honeybee (Apis mellifera) brain encoding a functional tyramine receptor.

PubMed

Blenau, W; Balfanz, S; Baumann, A

2000-03-01

Biogenic amine receptors are involved in the regulation and modulation of various physiological and behavioral processes in both vertebrates and invertebrates. We have cloned a member of this gene family from the CNS of the honeybee, Apis mellifera. The deduced amino acid sequence is homologous to tyramine receptors cloned from Locusta migratoria and Drosophila melanogaster as well as to an octopamine receptor cloned from Heliothis virescens. Functional properties of the honeybee receptor were studied in stably transfected human embryonic kidney 293 cells. Tyramine reduced forskolin-induced cyclic AMP production in a dose-dependent manner with an EC50 of approximately 130 nM. A similar effect of tyramine was observed in membrane homogenates of honeybee brains. Octopamine also reduced cyclic AMP production in the transfected cell line but was both less potent (EC50 of approximately 3 microM) and less efficacious than tyramine. Receptor-encoding mRNA has a wide-spread distribution in the brain and subesophageal ganglion of the honeybee, suggesting that this tyramine receptor is involved in sensory signal processing as well as in higher-order brain functions.

Characterization of UC781-Tenofovir Combination Gel Products for HIV-1 Infection Prevention in an Ex Vivo Ectocervical Model

PubMed Central

Cost, Marilyn; Dezzutti, Charlene S.; Clark, Meredith R.; Friend, David R.; Akil, Ayman

2012-01-01

HIV continues to be a problem worldwide. Topical vaginal microbicides represent one option being evaluated to stop the spread of HIV. With drug candidates that have a specific action against HIV now being studied, it is important that, when appropriate and based on the mechanism of action, the drug permeates the tissue so that it can be delivered to specific targets which reside there. Novel formulations of the nucleotide reverse transcriptase inhibitor tenofovir (TFV) and the nonnucleoside reverse transcriptase inhibitor UC781 have been developed and evaluated here. Gels with three distinct rheological properties were prepared. The three gels released both UC781 and TFV under in vitro conditions at concentrations equal to or above the reported 50% effective concentrations (EC50s). The drug concentrations in ectocervical tissues were well in excess of the reported EC50s. The gels maintain ectocervical viability and prevent infection of ectocervical explants after a HIV-1 challenge. This study successfully demonstrates the feasibility of using this novel combination of antiretroviral agents in an aqueous gel as an HIV infection preventative. PMID:22430977

[The value of methods for morphofunctional analysis of cornea in cataract surgery].

PubMed

Borodina, N B; Kobzova, M V; Musaeva, G M

2011-01-01

The characteristics of morphofunctional status of cornea after extracapsular cataract extraction and phakoemulsification with IOL implantation (30 and 58 operations respectively) were analyzed in detail using up-to-date diagnostic techniques. The results of examination using developed algorithm including study of light transmission, refraction and protective function of cornea show advantage of microinvasive ultrasound technique of cataract surgery in terms of minimal impact on corneal structure, optical and biomechanical characteristics.

Encoding Hydrogel Mechanics via Network Cross-Linking Structure.

PubMed

Schweller, Ryan M; West, Jennifer L

2015-05-11

The effects of mechanical cues on cell behaviors in 3D remain difficult to characterize as the ability to tune hydrogel mechanics often requires changes in the polymer density, potentially altering the material's biochemical and physical characteristics. Additionally, with most PEG diacrylate (PEGDA) hydrogels, forming materials with compressive moduli less than ∼10 kPa has been virtually impossible. Here, we present a new method of controlling the mechanical properties of PEGDA hydrogels independent of polymer chain density through the incorporation of additional vinyl group moieties that interfere with the cross-linking of the network. This modification can tune hydrogel mechanics in a concentration dependent manner from <1 to 17 kPa, a more physiologically relevant range than previously possible with PEG-based hydrogels, without altering the hydrogel's degradation and permeability. Across this range of mechanical properties, endothelial cells (ECs) encapsulated within MMP-2/MMP-9 degradable hydrogels with RGDS adhesive peptides revealed increased cell spreading as hydrogel stiffness decreased in contrast to behavior typically observed for cells on 2D surfaces. EC-pericyte cocultures exhibited vessel-like networks within 3 days in highly compliant hydrogels as compared to a week in stiffer hydrogels. These vessel networks persisted for at least 4 weeks and deposited laminin and collagen IV perivascularly. These results indicate that EC morphogenesis can be regulated using mechanical cues in 3D. Furthermore, controlling hydrogel compliance independent of density allows for the attainment of highly compliant mechanical regimes in materials that can act as customizable cell microenvironments.

Pathogenesis of Crimean-Congo hemorrhagic fever.

PubMed

Akıncı, Esragül; Bodur, Hürrem; Leblebicioglu, Hakan

2013-07-01

Although Crimean-Congo hemorrhagic fever (CCHF) is a widespread tick-borne disease, little is known about its pathogenesis. The interaction of the virus with host cells is most likely responsible for the pathogenesis of CCHF. The main contributors are endothelial cells (ECs) and immune cells. There are 2 theories underlying the CCHF pathogenesis: One is that the virus interacts with the ECs directly and the other that it interacts indirectly via immune cells with subsequent release of soluble mediators. ECs are activated upon infection by the upregulation of soluble molecules and proinflammatory cytokines. Probably, in severe cases, deregulation and excessive release of the cytokines accompanied by endothelial activation have toxic effects, leading to increased vascular permeability, vasodilatation, and subsequently hypotension, multiple organ failure, shock, and death. Studies indicate that CCHF virus (CCHFV) also can impair the innate immune system and cause a delay in adaptive immune response, which is critical for the clearance of CCHFV. The virus has many different ways to block the immune response, leading to uncontrolled viral replication followed by systemic spread of the virus throughout the body. Partial activation of dendritic cells and macrophages, delayed induction of interferons, weak antibody response, apoptosis of lymphocytes, and hemophagocytosis are some of these tactics. However, there are many points waiting for clarification about the pathogenesis of CCHF. Although the high risk of contagiousness limits research, we need more studies to understand the CCHF pathogenesis better. Here we review the main characteristics of the pathogenesis of CCHF.

Is arthroplasty preferable to internal fixation for the treatment of extracapsular fracture of the upper femur in the elderly?

PubMed

Duriez, P; Devaux, T; Chantelot, C; Baudrier, N; Hery, J-Y; Mainard, D; Favier, T; Massin, P

2016-10-01

Although internal fixation is the reference treatment for extracapsular fracture of the upper femur, indications for arthroplasty are broadening, especially in unstable comminutive fracture in fragile bone. The present study hypothesis was that arthroplasty reduces early mortality and morbidity and provides better recovery of autonomy in over-80 year-old patients than does internal fixation. A prospective multicenter study was conducted on 8 sites. Internal fixation was systematically used in 5 centers; arthroplasty was used systematically in 1 center, and reserved for unstable fracture in 2 centers. A total of 697 patients aged over 80 years (mean age, 85±5 years), presenting with extracapsular fracture, were included; 521 were treated by internal fixation and 176 by arthroplasty. Results were studied on multivariate analysis of ASA score, blood loss, transfusion, and also of treatment modality as an independent factor for early (first 6 months) mortality and morbidity (mechanical, general and nutritional complications) and functional outcome (autonomy and dependence). Overall mortality was 19.2%. Autonomy deteriorated in 56% of patients alive at 6 months and dependence worsened in 44%. Two percent of those managed by internal fixation underwent revision for disassembly (n=8) or infection (n=1). Eight percent of those managed by arthroplasty underwent revision for dislocation (n=4), implant loosening (n=3) or infection (n=7). On univariate analysis, mortality was higher in the arthroplasty group (25%) than with internal fixation (17%; P=0.002), as were blood loss (425±286mL versus 333±223mL; P<0.0001), transfusion rate (61% versus 32%; P<0.0001) and infection (4% versus 0.2%; P<0.001). On multivariate analysis, however, treatment modality no longer showed impact on mortality or on morbidity and autonomy at 6 months. Nutritional status was better conserved at 6 months following arthroplasty, but dependence worsened. Poor preoperative autonomy, ASA score, and nutritional status and time to treatment were independent factors for mortality. Transfusion, associated with onset of mechanical complications, significantly increased dependence. Type of treatment had little impact on mortality, morbidity or functional outcome. Differences seemed more related to preoperative functional and nutritional status. III, prospective case-control study. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Mitochondrial assembly receptor expression is an independent prognosticator for patients with oral tongue squamous cell carcinoma.

PubMed

Su, Yan-Ye; Chen, Chang-Han; Chien, Chih-Yen; Lin, Wei-Che; Huang, Wan-Ting; Li, Shau-Hsuan

2017-01-01

Recent evidence suggests that the local renin-angiotensin system has been implicated in various malignancies. The mitochondrial assembly receptor is a newly identified receptor for angiotensin peptides, angiotensin-(1-7), and has an important role in the renin-angiotensin system. However, the role of the mitochondrial assembly receptor in the prognosis of cancer patients remains unclear. The aim of this study was to evaluate the significance of mitochondrial assembly receptor signaling in the prognosis of oral tongue squamous cell carcinoma. Mitochondrial assembly receptor immunohistochemistry was examined in 151 oral tongue squamous cell carcinoma patients and was correlated with treatment outcome. The functional relevance of the mitochondrial assembly receptor in oral tongue squamous cell carcinoma cell lines was evaluated by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide reduction and bromodeoxyuridine incorporation assays. Mitochondrial assembly receptor overexpression was significantly correlated with early pathological T classification ( p=0.029) and the absence of extracapsular spread ( p=0.039). Univariate analyses demonstrated that mitochondrial assembly receptor overexpression was significantly associated with superior overall survival ( p=0.012). In multivariate comparison, mitochondrial assembly receptor overexpression remained independently associated with superior overall survival ( p=0.008, hazard ratio=1.862). In vitro, angiotensin-(1-7) suppressed the cell growth in oral tongue squamous cell carcinoma cells, and this response was reversed by the mitochondrial assembly receptor antagonist, A779. Mitochondrial assembly receptor expression is independently associated with the prognosis of oral tongue squamous cell carcinoma patients. These findings suggest that mitochondrial assembly receptor signaling may be a promising novel target for oral tongue squamous cell carcinoma.

Combined Magnetic Resonance Imaging and Spectroscopic Imaging Approach to Molecular Imaging of Prostate Cancer

PubMed Central

Kurhanewicz, John; Swanson, Mark G.; Nelson, Sarah J.; Vigneron, Daniel B.

2005-01-01

Magnetic resonance spectroscopic imaging (MRSI) provides a noninvasive method of detecting small molecular markers (historically the metabolites choline and citrate) within the cytosol and extracellular spaces of the prostate, and is performed in conjunction with high-resolution anatomic imaging. Recent studies in pre-prostatectomy patients have indicated that the metabolic information provided by MRSI combined with the anatomical information provided by MRI can significantly improve the assessment of cancer location and extent within the prostate, extracapsular spread, and cancer aggressiveness. Additionally, pre- and post-therapy studies have demonstrated the potential of MRI/MRSI to provide a direct measure of the presence and spatial extent of prostate cancer after therapy, a measure of the time course of response, and information concerning the mechanism of therapeutic response. In addition to detecting metabolic biomarkers of disease behavior and therapeutic response, MRI/MRSI guidance can improve tissue selection for ex vivo analysis. High-resolution magic angle spinning (1H HR-MAS) spectroscopy provides a full chemical analysis of MRI/MRSI-targeted tissues prior to pathologic and immunohistochemical analyses of the same tissue. Preliminary 1H HR-MAS spectroscopy studies have already identified unique spectral patterns for healthy glandular and stromal tissues and prostate cancer, determined the composition of the composite in vivo choline peak, and identified the polyamine spermine as a new metabolic marker of prostate cancer. The addition of imaging sequences that provide other functional information within the same exam (dynamic contrast uptake imaging and diffusion-weighted imaging) have also demonstrated the potential to further increase the accuracy of prostate cancer detection and characterization. PMID:12353259

Randomized controlled trial of piperacillin-tazobactam, cefepime and ertapenem for the treatment of urinary tract infection caused by extended-spectrum beta-lactamase-producing Escherichia coli.

PubMed

Seo, Yu Bin; Lee, Jacob; Kim, Young Keun; Lee, Seung Soon; Lee, Jeong-A; Kim, Hyo Youl; Uh, Young; Kim, Han-Sung; Song, Wonkeun

2017-06-07

Due to limited therapeutic options, the spread of extended-spectrum beta-lactamases (ESBLs) have become a major public health concern. We conducted a prospective, randomized, open-label comparison of the therapeutic efficacy of piperacillin-tazobactam (PTZ), cefepime, and ertapenem in febrile nosocomial urinary tract infection with ESBL-producing Escherichia coli (ESBL-EC). This study was conducted at three university hospitals between January 2013 and August 2015. Hospitalized adult patients presenting with fever were screened for healthcare-associated urinary tract infection (HA-UTI). When ESBL-EC was solely detected and susceptible to a randomized antibiotic in vitro, the case was included in the final analysis. Participants were treated for 10-14 days with PTZ, cefepime, or ertapenem. A total of 66 participants were evenly assigned to the PTZ and ertapenem treatment groups. After the recruitment of six participants, assignment to the cefepime treatment group was stopped because of an unexpectedly high treatment failure rate. The baseline characteristics of these participants did not differ from participants in other treatment groups. The clinical and microbiological response to PTZ treatment was estimated to be 94% and was similar to the response to ertapenem treatment. The efficacy of cefepime was 33.3%. In the cefepime group, age, Charlson comorbidity index, genotype, and minimal inhibitory concentration (MIC) did not significantly affect the success of treatment. Similarly, genotype seemed to be irrelevant with respect to clinical outcome in the PTZ group. Expired cases tended to involve septic shock with a high Charlson comorbidity index and high MIC. Results from this study suggest that PTZ is effective in the treatment of urinary tract infection caused by ESBL-EC when the in vitro test indicates susceptibility. In addition, cefepime should not be used as an alternative treatment for urinary tract infection caused by ESBL-EC. The trial was registered with the Clinical Research Information Service of Korea Centers for Disease Control and Prevention. (KCT0001895).

Changes in corneal shape after suture cutting using the argon laser for postoperative astigmatism following cataract extraction.

PubMed

Hayashi, K; Nakao, F; Hayashi, F

1993-03-01

We studied the changes in corneal shape after suture cutting with an argon laser to reduce corneal astigmatism following cataract extraction. Sixty-two patients who exhibited high with-the-rule astigmatism (> 3 diopters [D]) following extracapsular lens extraction had argon laser suture cutting. The patients were classified into three groups: Group A comprised 30 patients whose sutures were cut two to three months after planned extracapsular cataract extraction (p-ECCE); Group B consisted of eight patients who had the same treatment five to nine months after p-ECCE; Group C comprised 24 patients who had the treatment one to two months after phacoemulsification (PE). The dioptric reduction of corneal astigmatism (the percent reduction of astigmatism) was 1.83 +/- 0.98 D (37.4 +/- 18.3%) in Group A, 3.20 +/- 2.35 D (55.6 +/- 34.4%) in Group B, and 2.08 +/- 1.20 D (41.4 +/- 20.4%) in Group C. There was no statistical significance in the dioptric reduction and the percent reduction among Groups A, B, and C. This suggests that the wound size and time of cutting are not directly correlated to the effect of argon laser suture cutting. To examine the relationship between the effect and changes in corneal shape from suture cutting, we divided the patients into two subgroups; one was Subgroup (+) in which the percent reduction of astigmatism was above 25%; the other was Subgroup (-) in which the percent reduction was below 25%.(ABSTRACT TRUNCATED AT 250 WORDS)

Electrical coupling and release of K+ from endothelial cells co-mediate ACh-induced smooth muscle hyperpolarization in guinea-pig inner ear artery

PubMed Central

Jiang, Zhi-Gen; Nuttall, Alfred L; Zhao, Hui; Dai, Chun-Fu; Guan, Bing-Cai; Si, Jun-Qiang; Yang, Yu-Qin

2005-01-01

The physiological basis of ACh-elicited hyperpolarization in guinea-pig in vitro cochlear spiral modiolar artery (SMA) was investigated by intracellular recording combined with dye labelling of recorded cells and immunocytochemistry. We found the following. (1) The ACh-hyperpolarization was prominent only in cells that had a low resting potential (less negative than −60 mV). ACh-hyperpolarization was reversibly blocked by 4-DAMP, charybdotoxin or BAPTA-AM, but not by Nω-nitro-l-arginine methyl ester, glipizide, indomethacin or 17-octadecynoic acid. (2) Ba2+ (100 μm) and ouabain (1 μm) each attenuated ACh-hyperpolarization by ∼ 30% in smooth muscle cells (SMCs) but had only slight or no inhibition in endothelial cells (ECs). A combination of Ba2+ and 18β-glycyrrhetinic acid near completely blocked the ACh-hyperpolarization in SMCs. (3) High K+ (10 mm) induced a smaller hyperpolarization in ECs than in SMCs, with an amplitude ratio of 0.49: 1. Ba2+ blocked the K+-induced hyperpolarization by ∼ 85% in both cell types, whereas ouabain inhibited K+-hyperpolarization differently in SMCs (19%) and ECs (35%) and increased input resistance. 18β-Glycyrrhetinic acid blocked the high K+-hyperpolarization in ECs only. (4) Weak myoendothelial dye coupling was detected by confocal microscopy in cells recorded with a propidium iodide-containing electrode for longer than 30 min. A sparse plexus of choline acetyltransferase-immunoreactive (ChAT) fibres was observed around the SMA and its up-stream arteries. (5) Evoked excitatory junction potentials (EJP) were partially blocked by 4-DAMP in half of the cells tested. We conclude that ACh-induced hyperpolarization originates from ECs via activation of Ca2+-activated potassium channels, and is independent of the release of NO, cyclo-oxygenase or cytochrome P450 products. ACh-induced hyperpolarization in smooth muscle cells involves two mechanisms: (a) electrical spread of the hyperpolarization from the endothelium, and (b) activation of inward rectifier K+ channels (Kir) and Na+–K+ pump current by elevated interstitial K+ released from the endothelial cells, these being responsible for about 60% and 40% of the hyperpolarization, respectively. The role ratio of Kir and pump current activation is at 8 : 1 or less. PMID:15731195

Electrical coupling and release of K+ from endothelial cells co-mediate ACh-induced smooth muscle hyperpolarization in guinea-pig inner ear artery.

PubMed

Jiang, Zhi-Gen; Nuttall, Alfred L; Zhao, Hui; Dai, Chun-Fu; Guan, Bing-Cai; Si, Jun-Qiang; Yang, Yu-Qin

2005-04-15

The physiological basis of ACh-elicited hyperpolarization in guinea-pig in vitro cochlear spiral modiolar artery (SMA) was investigated by intracellular recording combined with dye labelling of recorded cells and immunocytochemistry. We found the following. (1) The ACh-hyperpolarization was prominent only in cells that had a low resting potential (less negative than -60 mV). ACh-hyperpolarization was reversibly blocked by 4-DAMP, charybdotoxin or BAPTA-AM, but not by N(omega)-nitro-L-arginine methyl ester, glipizide, indomethacin or 17-octadecynoic acid. (2) Ba(2)(+) (100 microm) and ouabain (1 microm) each attenuated ACh-hyperpolarization by approximately 30% in smooth muscle cells (SMCs) but had only slight or no inhibition in endothelial cells (ECs). A combination of Ba(2)(+) and 18beta-glycyrrhetinic acid near completely blocked the ACh-hyperpolarization in SMCs. (3) High K(+) (10 mm) induced a smaller hyperpolarization in ECs than in SMCs, with an amplitude ratio of 0.49 : 1. Ba(2)(+) blocked the K(+)-induced hyperpolarization by approximately 85% in both cell types, whereas ouabain inhibited K(+)-hyperpolarization differently in SMCs (19%) and ECs (35%) and increased input resistance. 18beta-Glycyrrhetinic acid blocked the high K(+)-hyperpolarization in ECs only. (4) Weak myoendothelial dye coupling was detected by confocal microscopy in cells recorded with a propidium iodide-containing electrode for longer than 30 min. A sparse plexus of choline acetyltransferase-immunoreactive (ChAT) fibres was observed around the SMA and its up-stream arteries. (5) Evoked excitatory junction potentials (EJP) were partially blocked by 4-DAMP in half of the cells tested. We conclude that ACh-induced hyperpolarization originates from ECs via activation of Ca(2)(+)-activated potassium channels, and is independent of the release of NO, cyclo-oxygenase or cytochrome P450 products. ACh-induced hyperpolarization in smooth muscle cells involves two mechanisms: (a) electrical spread of the hyperpolarization from the endothelium, and (b) activation of inward rectifier K(+) channels (K(ir)) and Na(+)-K(+) pump current by elevated interstitial K(+) released from the endothelial cells, these being responsible for about 60% and 40% of the hyperpolarization, respectively. The role ratio of K(ir) and pump current activation is at 8 : 1 or less.

Hippocampal α-Synuclein in Dementia with Lewy Bodies Contributes to Memory Impairment and Is Consistent with Spread of Pathology

PubMed Central

Roy, Subhojit; Galasko, Douglas R.; Hansen, Lawrence A.; Masliah, Eliezer

2017-01-01

Despite considerable research to uncover them, the anatomic and neuropathologic correlates of memory impairment in dementia with Lewy bodies (DLB) remain unclear. While some studies have implicated Lewy bodies in the neocortex, others have pointed to α-synuclein pathology in the hippocampus. We systematically examined hippocampal Lewy pathology and its distribution in hippocampal subfields in 95 clinically and neuropathologically characterized human cases of DLB, finding that α-synuclein pathology was highest in two hippocampal-related subregions: the CA2 subfield and the entorhinal cortex (EC). While the EC had numerous classic somatic Lewy bodies, CA2 contained mainly Lewy neurites in presumed axon terminals, suggesting the involvement of the EC → CA2 circuitry in the pathogenesis of DLB symptoms. Clinicopathological correlations with measures of verbal and visual memory supported a role for EC Lewy pathology, but not CA2, in causing these memory deficits. Lewy pathology in CA1—the main output region for CA2—correlated best with results from memory testing despite a milder pathology. This result indicates that CA1 may be more functionally relevant than CA2 in the context of memory impairment in DLB. These correlations remained significant after controlling for several factors, including concurrent Alzheimer's pathology (neuritic plaques and neurofibrillary tangles) and the interval between time of testing and time of death. Our data suggest that although hippocampal Lewy pathology in DLB is predominant in CA2 and EC, memory performance correlates most strongly with CA1 burden. SIGNIFICANCE STATEMENT This study provides a detailed neuropathologic analysis of hippocampal Lewy pathology in human patients with autopsy-confirmed dementia with Lewy bodies. The approach—informed by regional molecular markers, concurrent Alzheimer's pathology analysis, and relevant clinical data—helps tease out the relative contribution of Lewy pathology to memory dysfunction in the disease. Levels of Lewy pathology were found to be highest in the hippocampal CA2 subregion and entorhinal cortex, implicating a potentially overlooked circuit in disease pathogenesis. However, correlation with memory performance was strongest with CA1. This unexpected finding suggests that Lewy pathology must reach a critical burden across hippocampal circuitry to contribute to memory dysfunction beyond that related to other factors, notably coexisting Alzheimer's disease tau pathology. PMID:28039370

Source and migration of short-chain chlorinated paraffins in the coastal East China Sea using multiproxies of marine organic geochemistry.

PubMed

Zhao, Zongshan; Li, Huijuan; Wang, Yawei; Li, Guoliang; Cao, Yali; Zeng, Lixi; Lan, Jing; Wang, Thanh; Jiang, Guibin

2013-05-21

Multiple proxies of terrestrial organic matters (TOM) were introduced to study the migration behaviors of short-chain chlorinated paraffins (SCCPs) in the coastal East China Sea (ECS). The contents of SCCPs in the surface sediment collected from Changjiang (Yangtze) River Delta (CRD) and along the Zhejiang-Fujian coastline ranged from 9.0 to 37.2 ng/g (dry weight, d.w.), displaying a "band-style" distribution trend. Spatial distribution patterns of SCCP congeners presented an increasing trend seaward and southward along the coastline for shorter carbon length (C₁₀ + C₁₁) and lower chlorinated (Cl₅ + Cl₆ + Cl₇) congeners, suggesting a spreading tendency seaward and southward from the CRD and the north of the inner shelf. The significant relationship between ΣSCCPs and total organic carbons (TOC) (r(2) = 0.402, p < 0.05) indicated that the migration of SCCPs in sediments was markedly affected by TOC. The spatial patterns of the TOM proxies of TOC δ(13)C, the contents of ΣC₂₇ + C₂₉ + C₃₁ n-alkanes, terrestrial marine biomarker ratio (TMBR), and terrestrial TOC (T-TOC) were all similar to that of ΣSCCPs. Linear relationships between SCCP contents and both the contents of ΣC₂₇ + C₂₉ + C₃₁ n-alkanes (r(2) = 0.537, p < 0.05) and T-TOC (r(2) = 0.495, p < 0.05) were also observed. The consistence demonstrated that a major portion of sedimentary SCCPs in the coastal ECS should be from the river input of Changjiang River and deposited in the CRD and along the inner shelf of the ECS, but only a minor fraction was transported to the offshore areas.

Elevation-dependent warming in global climate model simulations at high spatial resolution

NASA Astrophysics Data System (ADS)

Palazzi, Elisa; Mortarini, Luca; Terzago, Silvia; von Hardenberg, Jost

2018-06-01

The enhancement of warming rates with elevation, so-called elevation-dependent warming (EDW), is one of the regional, still not completely understood, expressions of global warming. Sentinels of climate and environmental changes, mountains have experienced more rapid and intense warming trends in the recent decades, leading to serious impacts on mountain ecosystems and downstream. In this paper we use a state-of-the-art Global Climate Model (EC-Earth) to investigate the impact of model spatial resolution on the representation of this phenomenon and to highlight possible differences in EDW and its causes in different mountain regions of the Northern Hemisphere. To this end we use EC-Earth climate simulations at five different spatial resolutions, from ˜ 125 to ˜ 16 km, to explore the existence and the driving mechanisms of EDW in the Colorado Rocky Mountains, the Greater Alpine Region and the Tibetan Plateau-Himalayas. Our results show that the more frequent EDW drivers in all regions and seasons are the changes in albedo and in downward thermal radiation and this is reflected in both daytime and nighttime warming. In the Tibetan Plateau-Himalayas and in the Greater Alpine Region, an additional driver is the change in specific humidity. We also find that, while generally the model shows no clear resolution dependence in its ability to simulate the existence of EDW in the different regions, specific EDW characteristics such as its intensity and the relative role of different driving mechanisms may be different in simulations performed at different spatial resolutions. Moreover, we find that the role of internal climate variability can be significant in modulating the EDW signal, as suggested by the spread found in the multi-member ensemble of the EC-Earth experiments which we use.

Structure–function analyses of a pertussis-like toxin from pathogenic Escherichia coli reveal a distinct mechanism of inhibition of trimeric G-proteins

PubMed Central

Littler, Dene R.; Ang, Sheng Y.; Moriel, Danilo G.; Kocan, Martina; Kleifeld, Oded; Johnson, Matthew D.; Tran, Mai T.; Paton, Adrienne W.; Paton, James C.; Summers, Roger J.; Schembri, Mark A.; Rossjohn, Jamie; Beddoe, Travis

2017-01-01

Pertussis-like toxins are secreted by several bacterial pathogens during infection. They belong to the AB5 virulence factors, which bind to glycans on host cell membranes for internalization. Host cell recognition and internalization are mediated by toxin B subunits sharing a unique pentameric ring-like assembly. Although the role of pertussis toxin in whooping cough is well-established, pertussis-like toxins produced by other bacteria are less studied, and their mechanisms of action are unclear. Here, we report that some extra-intestinal Escherichia coli pathogens (i.e. those that reside in the gut but can spread to other bodily locations) encode a pertussis-like toxin that inhibits mammalian cell growth in vitro. We found that this protein, EcPlt, is related to toxins produced by both nontyphoidal and typhoidal Salmonella serovars. Pertussis-like toxins are secreted as disulfide-bonded heterohexamers in which the catalytic ADP-ribosyltransferase subunit is activated when exposed to the reducing environment in mammalian cells. We found here that the reduced EcPlt exhibits large structural rearrangements associated with its activation. We noted that inhibitory residues tethered within the NAD+-binding site by an intramolecular disulfide in the oxidized state dissociate upon the reduction and enable loop restructuring to form the nucleotide-binding site. Surprisingly, although pertussis toxin targets a cysteine residue within the α subunit of inhibitory trimeric G-proteins, we observed that activated EcPlt toxin modifies a proximal lysine/asparagine residue instead. In conclusion, our results reveal the molecular mechanism underpinning activation of pertussis-like toxins, and we also identified differences in host target specificity. PMID:28663369

Role of Radiotherapy in the Treatment of Cervical Lymph Node Metastases From an Unknown Primary Site: Retrospective Analysis of 113 Patients

DOE Office of Scientific and Technical Information (OSTI.GOV)

Beldi, Debora; Jereczek-Fossa, Barbara A.; University of Milan, Milan

2007-11-15

Purpose: The management of patients with cervical lymph-node metastases from unknown primary site (UPS) remains a matter of discussion. This study aimed to analyze the results and prognostic factors in a series of patients treated with radiotherapy. Methods and Materials: Data from 113 patients who presented with cervical lymph nodes metastases from UPS treated from 1980 to 2004 were reviewed. Eighty-seven patients (77.0%) were squamous cell carcinoma (SCC). Ninety-one patients were treated with curative and 22 with palliative intent. Fifty-nine of 113 patients (52.2%) received surgery followed by radiotherapy and 54 of 113 (47.8%) received radiotherapy alone. Radiotherapy was deliveredmore » to the neck and pharyngeal mucosa in 67 patients and to the ipsilateral or bilateral neck in 45 patients. Twenty-one patients (18.5%) also received chemotherapy. Results: The 5-year overall survival rates were 40.7% for the entire group and 46.6% for the SCC subgroup. The occurrence of the occult primary was observed in 23 of 113 patients (20.3%), 19 (82.6%) within the head and neck region. At multivariate analysis, treatment with curative intent and extensive irradiation of bilateral neck and pharyngeal mucosa were favorable prognostic factors for the whole series, and treatment with curative intent, extensive irradiation of bilateral neck and pharyngeal mucosa, and absence of extracapsular spread were favorable prognostic factors for the SCC subgroup. Conclusions: Patients with cervical lymph node metastases from UPS have a similar prognosis to those affected by other head and neck malignancies. Curative treatment strategies including neck dissection and extensive irradiation by three-dimensional conformal radiation therapy resulted in significantly better outcomes.« less

Treatment Results of Postoperative Radiotherapy on Squamous Cell Carcinoma of the Oral Cavity: Coexistence of Multiple Minor Risk Factors Results in Higher Recurrence Rates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fan, Kang-Hsing; Taipei Chang Gung Head and Neck Oncology Group, Chang Gung Memorial Hospital, Taiwan; Graduate Institute of Clinical Medical Sciences, Taiwan

2010-07-15

Purpose: The aim of this study was to investigate the treatment results of postoperative radiotherapy (PORT) on squamous cell carcinoma of the oral cavity (OSCC). Materials and Methods: This study included 302 OSCC patients who were treated by radical surgery and PORT. Indications for PORT include Stage III or IV OSCC according to the 2002 criteria of the American Joint Committee on Cancer, the presence of perineural invasion or lymphatic invasion, the depth of tumor invasion, or a close surgical margin. Patients with major risk factors, such as multiple nodal metastases, a positive surgical margin, or extracapsular spreading, were excluded.more » The prescribed dose of PORT ranged from 59.4 to 66.6Gy (median, 63Gy). Results: The 3-year overall and recurrence-free survival rates were 73% and 70%, respectively. Univariate analysis revealed that differentiation, perineural invasion, lymphatic invasion, bone invasion, location (hard palate and retromolar trigone), invasion depths {>=}10mm, and margin distances {<=}4mm were significant prognostic factors. The presence of multiple significant factors of univariate analysis correlated with disease recurrence. The 3-year recurrence-free survival rates were 82%, 76%, and 45% for patients with no risk factors, one or two risk factors, and three or more risk factors, respectively. After multivariate analysis, the number of risk factors and lymphatic invasion were significant prognostic factors. Conclusion: PORT may be an adequate adjuvant therapy for OSCC patients with one or two risk factors of recurrence. The presence of multiple risk factors and lymphatic invasion correlated with poor prognosis, and more aggressive treatment may need to be considered.« less

Tumor infiltrating lymphocytes (TIL) and prognosis in oral cavity squamous carcinoma: a preliminary study.

PubMed

Wolf, Gregory T; Chepeha, Douglas B; Bellile, Emily; Nguyen, Ariane; Thomas, Daffyd; McHugh, Jonathan

2015-01-01

Tumor infiltrating lymphocytes (TILs) in the microenvironment reflect may tumor biology and predict outcome. We previously demonstrated that infiltrates of CD4, CD8, and FoxP3 positive lymphocytes were associated with HPV-status and survival in oropharyngeal cancers. To determine if TILs were of prognostic importance in oral cancer, TIL levels were evaluated retrospectively in 52 oral cancer patients treated with surgery and correlations with outcome determined. Complete TIL and clinical data were available for 39 patients. Levels of CD4, CD8, FoxP3 (Treg), CD68 and NK cells were assessed by immunohistochemistry in tumor cores on a tissue microarray. Associations with clinical variables, tobacco and alcohol use and histologic features were assessed using Spearman correlation coefficient and the non-parametric Kruskal-Wallis testing. Time-to-event outcomes were determined using univariate and multivariate Cox models. Median follow up was 60 months. The ratio of CD4/CD8 (p=.01) and CD8 infiltrates (p=.05) were associated with tumor recurrence but not overall survival. Lower CD4 infiltrates were associated with alcohol use (p=.005) and poor tumor differentiation (p=.02). Interestingly, higher levels of CD68+ macrophages were found associated with positive nodes (p=.06) and poorer overall survival (p=.07). Overall and DSS survival were significantly shorter for patients with positive nodes, extracapsular spread, or perineural invasion. Infiltrating immune cell levels in oral cavity cancer appear influenced by health behaviors and tumor characteristics. In contrast to oropharynx cancer, infiltrates of CD68 positive tumor associated macrophages may contribute to metastatic behavior and outcome in advanced oral cavity carcinoma. Copyright © 2014 Elsevier Ltd. All rights reserved.

Tumor Infiltrating Lymphocytes (TIL) and Prognosis in Oral Cavity Squamous Carcinoma: A Preliminary Study

PubMed Central

Wolf, Gregory T.; Chepeha, Douglas B.; Bellile, Emily; Nguyen, Ariane; Thomas, Daffyd; McHugh, Jonathan

2014-01-01

Objectives Tumor infiltrating lymphocytes (TILs) in the microenvironment reflect may tumor biology and predict outcome. We previously demonstrated that infiltrates of CD4, CD8, and FoxP3 positive lymphocytes were associated with HPV-status and survival in oropharyngeal cancers. To determine if TILs were of prognostic importance in oral cancer, TIL levels were evaluated retrospectively in 52 oral cancer patients treated with surgery and correlations with outcome determined. Methods Complete TIL and clinical data were available for 39 patients. Levels of CD4, CD8, FoxP3 (Treg), CD68 and NK cells were assessed by immunohistochemistry in tumor cores on a tissue microarray. Associations with clinical variables, tobacco and alcohol use and histologic features were assessed using Spearman correlation coefficient and the non-parametric Kruskal-Wallis testing. Timeto-event outcomes were determined using univariate and multivariate Cox models. Median follow up was 60 months. Results The ratio of CD4/CD8 (p=.01) and CD8 infiltrates (p=.05) were associated with tumor recurrence but not overall survival. Lower CD4 infiltrates were associated with alcohol use (p=.005) and poor tumor differentiation (p=.02). Interestingly, there higher levels of CD68+ macrophages were found associated with positive nodes (p=.06) and poorer overall survival (p=.07). Overall and DSS survival were significantly shorter for patients with positive nodes, extracapsular spread , or perineural invasion. Conclusions Infiltrating immune cell levels in oral cavity cancer appear influenced by health behaviors and tumor characteristics. In contrast to oropharynx cancer, infiltrates of CD68 positive tumor associated macrophages may contribute to metastatic behavior and outcome in advanced oral cavity carcinoma. PMID:25283344

Institutional pathology consultation.

PubMed

Tsung, Jeffrey S H

2004-03-01

Sun Yat-Sen Cancer Center is the only cancer center in Taiwan. The hospital maintains a policy, and the division of oncology makes a concerted effort to obtain and review pertinent pathologic specimens in all patients who had pathologic diagnosis performed at other institution before rendering therapy. A 1-year retrospective study was undertaken to assess the frequency of discordant diagnosis of our second-opinion pathology slide review and determine its impact on patient care. Discrepancies were classified into four basic categories: A) no diagnostic disagreement; B) no diagnostic disagreement but pertinent information not included, such as tumor size, lymphovascular invasion, perineural invasion, histologic grading, margin status, extracapsular spread in metastatic lymph nodes; and C) major diagnostic disagreement, which was defined as follows; 1) change from benign to malignant, 2) change from malignant to benign, 3) a different type of neoplasm, and 4) change in N and M classification in TMN staging framework. Of 715 cases, a total of 673 (94%) showed no discrepancy. However, 35 of 673 (5.2%) cases failed to offer pertinent information (category B). Major disagreement was found in 42 16%) cases (category C). This study illustrated the fact that second pathology slide review prior to therapy can identify a small group of cases that result in a major change in their therapeutic plan. Admittedly, the review of pathology slides involves additional time and effort for both consulting and referring institutions. It can ensure quality medical care and limit medicolegal liability. As the Association of Directors of Anatomic and Surgical Pathology recommended, second pathology review should be standard practice. It is necessary that our major Pathology Association and Societies adopt a strong position on this matter to influence government or insurance company to pay for this service rendered by pathologists.

Effects of omitting elective neck irradiation to nodal Level IB in nasopharyngeal carcinoma patients with negative Level IB lymph nodes treated by intensity-modulated radiotherapy: a Phase 2 study.

PubMed

Li, Mei; Huang, Xiao-Guang; Yang, Zhi-Ning; Lu, Jia-Yang; Zhan, Yi-Zhou; Xie, Wen-Jia; Zhou, Dong-Jie; Wang, Li; Zhu, Di-Xia; Lin, Zhi-Xiong

2016-09-01

To investigate the need for elective neck irradiation (ENI) to nodal Level IB in patients with nasopharyngeal carcinoma (NPC) with negative Level IB lymph nodes (IB-negative) treated by intensity-modulated radiotherapy (IMRT). We conducted a Phase 2 prospective study in 123 newly diagnosed IB-negative patients with NPC treated by IMRT, who met at least 1 of the following criteria: (1) unilateral or bilateral Level II involvement with 1 of the following: Level IIA involvement or any Level II node ≥2 cm/with extracapsular spread; (2) ≥2 unilateral node-positive regions. Bilateral Level IB nodes were not contoured as part of the treatment target and treated electively. Level IB regional recurrence rate; pattern of treatment failure; 3-year overall survival (3y-OS), 3-year local control (3y-LC) and 3-year regional control (3y-RC) rates; toxicities; and dosimetric data for planning target volumes, organs at risk, Level IB and submandibular glands (SMGs) were evaluated. Two patients developed failures at Level IB (1.6%). The 3y-LC, 3y-RC and 3y-OS rates were 93.5%, 93.5% and 78.0%, respectively. Bilateral Level IB received unplanned high-dose irradiation with a mean dose (Dmean) ≥50 Gy in 60% of patients. The average Dmean of bilateral SMGs was approximately 53 Gy. ENI to Level IB may be unnecessary in IB-negative patients with NPC treated by IMRT. A further Phase 3 study is warranted. Based on the results of this first Phase 2 study, we suggest omitting ENI to Level IB in Ib-negative patients with NPC with extensive nodal disease treated by IMRT.

Decreased staging of differentiated thyroid cancer in patients with chronic lymphocytic thyroiditis.

PubMed

Borowczyk, M; Janicki, A; Dworacki, G; Szczepanek-Parulska, E; Danieluk, M; Barnett, J; Antonik, M; Kałużna, M; Bromińska, B; Czepczyński, R; Bączyk, M; Ziemnicka, K; Ruchała, M

2018-04-04

The biological association between chronic lymphocytic thyroiditis (CLT) and differentiated thyroid cancer (DTC) has not been elucidated yet. The aim of the study was to assess whether the presence of CLT exerts any influence on clinical or histological presentation of DTC. Nine hundred and seven consecutive patients with DTC treated in the years 1998-2016 were divided into two groups according to the presence or absence of concomitant CLT. The statistical differences were analysed. Out of 907 patients included in the study, 331 were diagnosed with DTC and CLT (studied group), while 576 patients with DTC but without CLT constituted a control group. The distribution of papillary and follicular thyroid cancer did not differ. In CLT group, the prevalence of pT1 was greater than for pT2-pT4 DTC (P = 0.0003; OR = 1.69, 95% CI 1.27-2.24) compared to controls (68.3 vs. 56.1%, respectively). The presence of multifocal lesions was similar. The thyroid capsule infiltration without extrathyroidal invasion (P < 0.0001; OR = 0.21, 95% CI 0.14-0.31) was more frequent in the studied group, unlike extracapsular invasion, which was significantly more often present in patients with DTC but without CLT (P = 0.004; OR = 1.66; 95% CI 1.17-2.34) as well as nodal involvement (P = 0.048; OR = 0.65, 95% CI 0.42-0.99). The collected data indicate a protective role of CLT in preventing the spread of the DTC. The presence of CLT might limit tumour growth to the primary site.

Qualitative risk assessment in a data-scarce environment: a model to assess the impact of control measures on spread of African Swine Fever.

PubMed

Wieland, Barbara; Dhollander, Sofie; Salman, Mo; Koenen, Frank

2011-04-01

In the absence of data, qualitative risk assessment frameworks have proved useful to assess risks associated with animal health diseases. As part of a scientific opinion for the European Commission (EC) on African Swine Fever (ASF), a working group of the European Food Safety Authority (EFSA) assessed the risk of ASF remaining endemic in Trans Caucasus Countries (TCC) and the Russian Federation (RF) and the risk of ASF becoming endemic in the EU if disease were introduced. The aim was to develop a tool to evaluate how current control or preventive measures mitigate the risk of spread and giving decision makers the means to review how strengthening of surveillance and control measures would mitigate the risk of disease spread. Based on a generic model outlining disease introduction, spread and endemicity in a region, the impact of risk mitigation measures on spread of disease was assessed for specific risk questions. The resulting hierarchical models consisted of key steps containing several sub-steps. For each step of the risk pathways risk estimates were determined by the expert group based on existing data or through expert opinion elicitation. Risk estimates were combined using two different combination matrices, one to combine estimates of independent steps and one to combine conditional probabilities. The qualitative risk assessment indicated a moderate risk that ASF will remain endemic in current affected areas in the TCC and RF and a high risk of spread to currently unaffected areas. If introduced into the EU, ASF is likely to be controlled effectively in the production sector with high or limited biosecurity. In the free range production sector, however, there is a moderate risk of ASF becoming endemic due to wild boar contact, non-compliance with animal movement bans, and difficult access to all individual pigs upon implementation of control measures. This study demonstrated the advantages of a systematic framework to assist an expert panel to carry out a risk assessment as it helped experts to disassociate steps in the risk pathway and to overcome preconceived notions of final risk estimates. The approach presented here shows how a qualitative risk assessment framework can address animal diseases with complexity in their spread and control measures and how transparency of the resulting estimates was achieved. Copyright © 2011 Elsevier B.V. All rights reserved.

Integration of electromagnetic induction sensor data in soil sampling scheme optimization using simulated annealing.

PubMed

Barca, E; Castrignanò, A; Buttafuoco, G; De Benedetto, D; Passarella, G

2015-07-01

Soil survey is generally time-consuming, labor-intensive, and costly. Optimization of sampling scheme allows one to reduce the number of sampling points without decreasing or even increasing the accuracy of investigated attribute. Maps of bulk soil electrical conductivity (EC a ) recorded with electromagnetic induction (EMI) sensors could be effectively used to direct soil sampling design for assessing spatial variability of soil moisture. A protocol, using a field-scale bulk EC a survey, has been applied in an agricultural field in Apulia region (southeastern Italy). Spatial simulated annealing was used as a method to optimize spatial soil sampling scheme taking into account sampling constraints, field boundaries, and preliminary observations. Three optimization criteria were used. the first criterion (minimization of mean of the shortest distances, MMSD) optimizes the spreading of the point observations over the entire field by minimizing the expectation of the distance between an arbitrarily chosen point and its nearest observation; the second criterion (minimization of weighted mean of the shortest distances, MWMSD) is a weighted version of the MMSD, which uses the digital gradient of the grid EC a data as weighting function; and the third criterion (mean of average ordinary kriging variance, MAOKV) minimizes mean kriging estimation variance of the target variable. The last criterion utilizes the variogram model of soil water content estimated in a previous trial. The procedures, or a combination of them, were tested and compared in a real case. Simulated annealing was implemented by the software MSANOS able to define or redesign any sampling scheme by increasing or decreasing the original sampling locations. The output consists of the computed sampling scheme, the convergence time, and the cooling law, which can be an invaluable support to the process of sampling design. The proposed approach has found the optimal solution in a reasonable computation time. The use of bulk EC a gradient as an exhaustive variable, known at any node of an interpolation grid, has allowed the optimization of the sampling scheme, distinguishing among areas with different priority levels.

Two-Phase Helical Computed Tomography Study of Salivary Gland Warthin Tumors: A Radiologic Findings and Surgical Applications

PubMed Central

Joo, Yeon Hee; Kim, Jin Pyeong; Park, Jung Je

2014-01-01

Objectives The goal of this study was to define the radiologic characteristics of two-phase computed tomography (CT) of salivary gland Warthin tumors and to compare them to pleomorphic adenomas. We also aimed to provide a foundation for selecting a surgical method on the basis of radiologic findings. Methods We prospectively enrolled 116 patients with parotid gland tumors, who underwent two-phase CT preoperatively. Early and delayed phase scans were obtained, with scanning delays of 30 and 120 seconds, respectively. The attenuation changes and enhancement patterns were analyzed. In cases when the attenuation changes were decreased, we presumed Warthin tumor preoperatively and performed extracapsular dissection. When the attenuation changes were increased, superficial parotidectomy was performed on the parotid gland tumors. We analyzed the operation times, incision sizes, complications, and recurrence rates. Results Attenuation of Warthin tumors was decreased from early to delayed scans. The ratio of CT numbers in Warthin tumors was also significantly different from other tumors. Warthin tumors were diagnosed with a sensitivity of 96.1% and specificity of 97% using two-phase CT. The mean operation time was 38 minutes and the mean incision size was 36.2 mm for Warthin tumors. However, for the other parotid tumors, the average operation time was 122 minutes and the average incision size was 91.8 mm (P<0.05). Conclusion Salivary Warthin tumor has a distinct pattern of contrast enhancement on two-phase CT, which can guide treatment decisions. The preoperative diagnosis of Warthin tumor made extracapsular dissection possible instead of superficial parotidectomy. PMID:25177439

Two-phase helical computed tomography study of salivary gland warthin tumors: a radiologic findings and surgical applications.

PubMed

Joo, Yeon Hee; Kim, Jin Pyeong; Park, Jung Je; Woo, Seung Hoon

2014-09-01

The goal of this study was to define the radiologic characteristics of two-phase computed tomography (CT) of salivary gland Warthin tumors and to compare them to pleomorphic adenomas. We also aimed to provide a foundation for selecting a surgical method on the basis of radiologic findings. We prospectively enrolled 116 patients with parotid gland tumors, who underwent two-phase CT preoperatively. Early and delayed phase scans were obtained, with scanning delays of 30 and 120 seconds, respectively. The attenuation changes and enhancement patterns were analyzed. In cases when the attenuation changes were decreased, we presumed Warthin tumor preoperatively and performed extracapsular dissection. When the attenuation changes were increased, superficial parotidectomy was performed on the parotid gland tumors. We analyzed the operation times, incision sizes, complications, and recurrence rates. Attenuation of Warthin tumors was decreased from early to delayed scans. The ratio of CT numbers in Warthin tumors was also significantly different from other tumors. Warthin tumors were diagnosed with a sensitivity of 96.1% and specificity of 97% using two-phase CT. The mean operation time was 38 minutes and the mean incision size was 36.2 mm for Warthin tumors. However, for the other parotid tumors, the average operation time was 122 minutes and the average incision size was 91.8 mm (P<0.05). Salivary Warthin tumor has a distinct pattern of contrast enhancement on two-phase CT, which can guide treatment decisions. The preoperative diagnosis of Warthin tumor made extracapsular dissection possible instead of superficial parotidectomy.

[Extracapsular hepatic adenoma. Case report and literature review].

PubMed

Vargas-Flores, Edgar; Pérez-Aguilar, Francisco; Valdez-Mendieta, Yanet

Hepatic adenomas are uncommon epithelial tumours. They usually appear in women between 20 and 44 years old. They are commonly located in the right hepatic lobe and are typically solitary masses. Multiple adenomas can present in patients with prolonged use of oral contraceptive pills, glycogen storage diseases and hepatic adenomatosis. A 35 year-old woman without any significant past medical history, with a chief complaint that started in December 2012 with oppressive, mild intensity abdominal pain located in right upper quadrant in the abdomen on deep palpation. With an abdominal ultrasound showing a mass of 91×82×65cm located in the right flank, isoechogenic with internal vascularity. Contrast computed tomography scan showing an ovoid tumour with circumscribed borders, with heterogenic intense reinforcement and displacement of adjacent structures with dimensions of 88×71×80cm. In laparotomy, excision of the tumour and cholecystectomy with the trans surgical findings of an 8cm tumour with a pedicle containing one artery and one vein coming from the hepatic free border with strong adhesions to the gallbladder. Pathologic diagnosis: Extracapsular hepatic adenoma. Incidence of hepatic adenomas has increased in the last decades, in a parallel fashion with the introduction of oral contraceptive pills, showing association with glycogen storage diseases and to a lesser degree with diabetes and pregnancy. Diagnosis is clinical with the aid of imaging studies. Prognosis of hepatic adenomas is not well established, therefore, management depends on symptoms, size, number, location and certainty of diagnosis. Copyright © 2015 Academia Mexicana de Cirugía A.C. Publicado por Masson Doyma México S.A. All rights reserved.

External validation of a nomogram for prediction of side-specific extracapsular extension at robotic radical prostatectomy.

PubMed

Zorn, Kevin C; Gallina, Andrea; Hutterer, Georg C; Walz, Jochen; Shalhav, Arieh L; Zagaja, Gregory P; Valiquette, Luc; Gofrit, Ofer N; Orvieto, Marcelo A; Taxy, Jerome B; Karakiewicz, Pierre I

2007-11-01

Several staging tools have been developed for open radical prostatectomy (ORP) patients. However, the validity of these tools has never been formally tested in patients treated with robot-assisted laparoscopic radical prostatectomy (RALP). We tested the accuracy of an ORP-derived nomogram in predicting the rate of extracapsular extension (ECE) in a large RALP cohort. Serum prostate specific antigen (PSA) and side-specific clinical stage and biopsy Gleason sum information were used in a previously validated nomogram predicting side-specific ECE. The nomogram-derived predictions were compared with the observed rate of ECE, and the accuracy of the predictions was quantified. Each prostate lobe was analyzed independently. As complete data were available for 576 patients, the analyses targeted 1152 prostate lobes. Median age and serum PSA concentration at radical prostatectomy were 60 years and 5.4 ng/mL, respectively. The majority of side-specific clinical stages were T(1c) (993; 86.2%). Most side-specific biopsy Gleason sums were 6 (572; 49.7%). The median side-specific percentages of positive cores and of cancer were, respectively, 20.0% and 5.0%. At final pathologic review, 107 patients (18.6%) had ECE, and side-specific ECE was present in 117 patients (20.3%). The nomogram was 89% accurate in the RALP cohort v 84% in the previously reported ORP validation. The ORP side-specific ECE nomogram is highly accurate in the RALP population, suggesting that predictive and possibly prognostic tools developed in ORP patients may be equally accurate in their RALP counterparts.

Accuracy of high resolution (1.5 tesla) pelvic phased array magnetic resonance imaging (MRI) in staging prostate cancer in candidates for radical prostatectomy: results from a prospective study.

PubMed

Renard-Penna, Raphaële; Rouprêt, Morgan; Comperat, Eva; Ayed, Amine; Coudert, Mathieu; Mozer, Pierre; Xylinas, Evanguelos; Bitker, Marc-Olivier; Grenier, Philippe

2013-05-01

To evaluate the role of pelvic phased array MRI in staging prostate cancer (CaP). We prospectively collected data over 12 months on CaP patients who underwent preoperative MR imaging with a pelvic phased array before radical prostatectomy. MR images were analyzed prospectively by 2 radiologists. MR imaging findings were then correlated with pathologic findings. Overall, 101 patients were included with a mean PSA level of 8 (range 1.8-30). Reader 1 (AUC 0.895, 95% CI 0.791-0.999) had a higher performance than reader 2 (AUC 0.687, 95% CI, 0.555-0.819) and than DRE (AUC 0.728, 95% CI, 0.599-0.857) in discriminating T2 from T3 CaP (P = 0.01). The κ-index of inter-observer agreement was 0.56. A model that combines MRI findings, DRE, PSA, and Gleason score was the most competitive for staging (AUC 0.895, 95% CI, 0.791-0.999). For the multivariate analysis, 3 criteria were significantly associated with extracapsular extension: asymmetry of the neuro-vascular bundles (P = 0.001), asymmetric enhancement of neurovascular bundles (P = 0.02), and bulging of the capsule (P = 0.0003). Pelvic phased array MRI presented satisfying results in its ability to adequately stage CaP and notably in detecting the extracapsular extension of tumors. It is likely to provide reliable information but rather in the hands of an experienced radiologist. Copyright © 2013 Elsevier Inc. All rights reserved.

Pathological upgrading in prostate cancer patients eligible for active surveillance: Does prostate-specific antigen density matter?

PubMed

Jin, Byung-Soo; Kang, Seok-Hyun; Kim, Duk-Yoon; Oh, Hoon-Gyu; Kim, Chun-Il; Moon, Gi-Hak; Kwon, Tae-Gyun; Park, Jae-Shin

2015-09-01

To evaluate prospectively the role of prostate-specific antigen (PSA) density in predicting Gleason score upgrading in prostate cancer patients eligible for active surveillance (T1/T2, biopsy Gleason score≤6, PSA≤10 ng/mL, and ≤2 positive biopsy cores). Between January 2010 and November 2013, among patients who underwent greater than 10-core transrectal ultrasound-guided biopsy, 60 patients eligible for active surveillance underwent radical prostatectomy. By use of the modified Gleason criteria, the tumor grade of the surgical specimens was examined and compared with the biopsy results. Tumor upgrading occurred in 24 patients (40.0%). Extracapsular disease and positive surgical margins were found in 6 patients (10.0%) and 8 patients (17.30%), respectively. A statistically significant correlation between PSA density and postoperative upgrading was found (p=0.030); this was in contrast with the other studied parameters, which failed to reach significance, including PSA, prostate volume, number of biopsy cores, and number of positive cores. Tumor upgrading was also highly associated with extracapsular cancer extension (p=0.000). The estimated optimal cutoff value of PSA density was 0.13 ng/mL(2), obtained by receiver operating characteristic analysis (area under the curve=0.66; p=0.020; 95% confidence interval, 0.53-0.78). PSA density is a strong predictor of Gleason score upgrading after radical prostatectomy in patients eligible for active surveillance. Because tumor upgrading increases the potential for postoperative pathological adverse findings and prognosis, PSA density should be considered when treating and consulting patients eligible for active surveillance.

Long Term Functional Outcome of Tibial Tuberosity Advancement vs. Tibial Plateau Leveling Osteotomy and Extracapsular Repair in a Heterogeneous Population of Dogs.

PubMed

Krotscheck, Ursula; Nelson, Samantha A; Todhunter, Rory J; Stone, Marisa; Zhang, Zhiwu

2016-02-01

To determine a long term function of tibial tuberosity advancement (TTA) for treatment of ruptured cranial cruciate ligament (CCL) in dogs, and to compare this to the long term function of previously reported tibial plateau leveling osteotomy (TPLO), extracapsular reconstruction (ECR), and a population of normal dogs. Prospective clinical trial. Dogs with unilateral ruptured CCL treated with TTA (n = 14), TPLO (n = 15), and ECR (n = 23), and normal adult dogs (control, n = 80). Force plate gait analysis was performed at 1 time point for the normal control group and preoperatively, and at 2 and 8 weeks and 6 and 12 months postoperatively for the treatment groups. Using serial force plates, symmetry indices (SI) were calculated between the operated and unoperated pelvic limbs for peak vertical force (PVF), contact time (CT), and vertical impulse (VI). Ground reaction forces (GRF) of the treatment and control group were compared using a general linear model. Walk SI for dogs with TTA were not significantly different from the control group at 12 months postoperatively. At the trot, neither TTA nor ECR achieved normal GRF. SI of the TPLO group were not different from the normal control group by 6-12 months postoperatively. At the walk, TTA achieves normal function by 12 months; however, at the trot TTA is indistinguishable from ECR. TPLO resulted in operated limb function that was similar to the control population by 6-12 months postoperatively at the walk and the trot. © Copyright 2016 by The American College of Veterinary Surgeons.

Initial contact guidance during cell spreading is contractility-independent.

PubMed

Sales, Adrià; Holle, Andrew W; Kemkemer, Ralf

2017-08-02

A wide variety of cell types exhibit substrate topography-based behavior, also known as contact guidance. However, the precise cellular mechanisms underlying this process are still unknown. In this study, we investigated contact guidance by studying the reaction of human endothelial cells (ECs) to well-defined microgroove topographies, both during and after initial cell spreading. As the cytoskeleton plays a major role in cellular adaptation to topographical features, two methods were used to perturb cytoskeletal structures. Inhibition of actomyosin contractility with the chemical inhibitor blebbistatatin demonstrated that initial contact guidance events are independent of traction force generation. However, cell alignment to the grooved substrate was altered at later time points, suggesting an initial 'passive' phase of contact guidance, followed by a contractility-dependent 'active' phase that relies on mechanosensitive feedback. The actin cytoskeleton was also perturbed in an indirect manner by culturing cells upside down, resulting in decreased levels of contact guidance and suggesting that a possible loss of contact between the actin cytoskeleton and the substrate could lead to cytoskeleton impairment. The process of contact guidance at the microscale was found to be primarily lamellipodia driven, as no bias in filopodia extension was observed on micron-scale grooves.

Predicting Likelihood of Having Four or More Positive Nodes in Patient With Sentinel Lymph Node-Positive Breast Cancer: A Nomogram Validation Study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Unal, Bulent; Gur, Akif Serhat; Beriwal, Sushil

2009-11-15

Purpose: Katz suggested a nomogram for predicting having four or more positive nodes in sentinel lymph node (SLN)-positive breast cancer patients. The findings from this formula might influence adjuvant radiotherapy decisions. Our goal was to validate the accuracy of the Katz nomogram. Methods and Materials: We reviewed the records of 309 patients with breast cancer who had undergone completion axillary lymph node dissection. The factors associated with the likelihood of having four or more positive axillary nodes were evaluated in patients with one to three positive SLNs. The nomogram developed by Katz was applied to our data set. The areamore » under the curve of the corresponding receiver operating characteristics curve was calculated for the nomogram. Results: Of the 309 patients, 80 (25.9%) had four or more positive axillary lymph nodes. On multivariate analysis, the number of positive SLNs (p < .0001), overall metastasis size (p = .019), primary tumor size (p = .0001), and extracapsular extension (p = .01) were significant factors predicting for four or more positive nodes. For patients with <5% probability, 90.3% had fewer than four positive nodes and 9.7% had four or more positive nodes. The negative predictive value was 91.7%, and sensitivity was 80%. The nomogram was accurate and discriminating (area under the curve, .801). Conclusion: The probability of four or more involved nodes is significantly greater in patients who have an increased number of positive SLNs, increased overall metastasis size, increased tumor size, and extracapsular extension. The Katz nomogram was validated in our patients. This nomogram will be helpful to clinicians making adjuvant treatment recommendations to their patients.« less

Determining Which Patients Require Irradiation of the Supraclavicular Nodal Area After Surgery for N1 Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yu, Jeong Il; Park, Won, E-mail: wonp68@skku.ed; Huh, Seung Jae

2010-11-15

Purpose: We designed this study to determine which patients have a high risk of supraclavicular node recurrence in N1 breast cancer previously treated with surgery but not having received supraclavicular radiation therapy (SCRT) and to identify which patients needed SCRT. Methods and Materials: We performed a retrospective review of 448 pathologic N1 breast cancer patients treated with mastectomy or breast-conserving treatment, but without SCRT, between 1994 and 2003. Mastectomy was performed in 302 patients (67.4%). The median number of axillary nodes dissected was 17 (range, 5-53). Systemic chemotherapy was administered in 443 patients (98.9%), and 144 patients received radiation aftermore » breast-conserving surgery. The median follow-up was 88 months (range, 15-170 months). Results: At follow-up, the treatment failed in 101 patients (22.5%), and 39 patients (8.7%) had supraclavicular node recurrence. Prognostic factors in supraclavicular node recurrence included lymphovascular invasion (p < 0.0001), extracapsular extension (p < 0.0001), the number of involved axillary nodes (p = 0.0003), and the level of involved axillary nodes (p = 0.012) in univariate and multivariate analyses. The total number of prognostic factors correlated well with supraclavicular node recurrence. In the analysis of 5-year supraclavicular node recurrence-free survival, patients with two or more factors showed a significantly higher recurrence rate than did patients with fewer than two factors (96.8% and 72.9%, respectively; p < 0.0001). Conclusions: The prognostic factors associated with supraclavicular node recurrence were lymphovascular invasion, extracapsular extension, and the number and level of involved axillary nodes. Patients with two or more prognostic factors might benefit from SCRT.« less

Evolution of the patient characteristics of candidates for radical prostatectomy and the results obtained with the technique.

PubMed

Sanchís-Bonet, A; Arribas-Gómez, I; Sánchez-Rodríguez, C; Sánchez-Chapado, M

2015-03-01

To evaluate the oncological profile and risk of biochemical recurrence of patients with prostate cancer who underwent radical prostatectomy based on the time period in which the patients were operated. To evaluate the differences in prostate-specific antigen (PSA) at diagnosis of patients with or without biochemical recurrence based on these time periods. Observation carried forward study of a cohort of 972 radical prostatectomies performed during 3 time periods (1994-2000, 2001-2006, 2007-2011). The importance of PSA at diagnosis on the time periods and on biochemical recurrence was assessed using a generalized linear model. The independent predictive behavior of biochemical recurrence was analyzed using Cox regression. The median follow-up was 38 (16-76) months. PSA levels at diagnosis were higher in the period 1994-2000 (12.97ng/mL, P<.001). Seventy-two percent of the patients from the period 2007-2011 were diagnosed as clinical stage T1c (P<.001), compared with 55% from the period 1994-2000. The percentage of extracapsular extension in the specimen decreased from 27% to 18% from the period 1994-2000 to the period 2007-2011 (p<.001). The percentage of patients with biochemical recurrence went from 38% to 14% from the first to the third period (P>.001). The difference between PSA levels at diagnosis for the patients with or without biochemical recurrence was independent of the period (P=.84). The period during which surgery was performed was not an independent predictive factor for biochemical recurrence (P=.09). Patients from the 2007-2011 period had less extracapsular disease in the radical prostatectomy. The period was not an independent predictive factor for biochemical recurrence. Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.

MUC1 Expression by Immunohistochemistry Is Associated with Adverse Pathologic Features in Prostate Cancer: A Multi-Institutional Study.

PubMed

Eminaga, Okyaz; Wei, Wei; Hawley, Sarah J; Auman, Heidi; Newcomb, Lisa F; Simko, Jeff; Hurtado-Coll, Antonio; Troyer, Dean A; Carroll, Peter R; Gleave, Martin E; Lin, Daniel W; Nelson, Peter S; Thompson, Ian M; True, Lawrence D; McKenney, Jesse K; Feng, Ziding; Fazli, Ladan; Brooks, James D

2016-01-01

The uncertainties inherent in clinical measures of prostate cancer (CaP) aggressiveness endorse the investigation of clinically validated tissue biomarkers. MUC1 expression has been previously reported to independently predict aggressive localized prostate cancer. We used a large cohort to validate whether MUC1 protein levels measured by immunohistochemistry (IHC) predict aggressive cancer, recurrence and survival outcomes after radical prostatectomy independent of clinical and pathological parameters. MUC1 IHC was performed on a multi-institutional tissue microarray (TMA) resource including 1,326 men with a median follow-up of 5 years. Associations with clinical and pathological parameters were tested by the Chi-square test and the Wilcoxon rank sum test. Relationships with outcome were assessed with univariable and multivariable Cox proportional hazard models and the Log-rank test. The presence of MUC1 expression was significantly associated with extracapsular extension and higher Gleason score, but not with seminal vesicle invasion, age, positive surgical margins or pre-operative serum PSA levels. In univariable analyses, positive MUC1 staining was significantly associated with a worse recurrence free survival (RFS) (HR: 1.24, CI 1.03-1.49, P = 0.02), although not with disease specific survival (DSS, P>0.5). On multivariable analyses, the presence of positive surgical margins, extracapsular extension, seminal vesicle invasion, as well as higher pre-operative PSA and increasing Gleason score were independently associated with RFS, while MUC1 expression was not. Positive MUC1 expression was not independently associated with disease specific survival (DSS), but was weakly associated with overall survival (OS). In our large, rigorously designed validation cohort, MUC1 protein expression was associated with adverse pathological features, although it was not an independent predictor of outcome after radical prostatectomy.

Tumor cell anaplasia and multinucleation are predictors of disease recurrence in oropharyngeal squamous cell carcinoma, including among just the human papillomavirus-related cancers.

PubMed

Lewis, James S; Scantlebury, Juliette B; Luo, Jingqin; Thorstad, Wade L

2012-07-01

Oropharyngeal squamous cell carcinoma (SCC) is frequently related to high risk human papillomavirus. This tumor expresses p16, frequently has a nonkeratinizing morphology, and has improved outcomes. Despite having a good prognosis, tumors can have focal or diffuse nuclear anaplasia or multinucleation, the significance of which is unknown. From a database of 270 oropharyngeal SCCs with known histologic typing (using our established system) and p16 immunohistochemistry, all surgically resected cases (149) were reviewed. Anaplasia was defined as any × 40 field with ≥ 3 tumor nuclei with diameters ≥ 5 lymphocyte nuclei (~25 μm), and multinucleation was defined as any × 40 field with ≥ 3 tumor cells with multiple nuclei. p16 was positive in 128 cases (85.9%), 64 cases (43.0%) showed anaplasia, and 71 (47.7%) showed multinucleation. Anaplasia and multinucleation were highly related (P<0.001), and both also correlated with histologic type (P<0.001 and P=0.01, respectively), p16 status (P=0.09 and 0.03, respectively), and partially with nodal extracapsular extension. There was no correlation with any of the other variables. In univariate analysis, cases showing anaplasia or multinucleation had worse overall, disease-specific, and disease-free survival (P<0.006 for all). Higher T-stage, keratinizing histologic type, extracapsular extension, and smoking also all correlated with worse survival. In multivariate analysis, anaplasia and multinucleation both predicted worse disease-specific survival (hazard ratio 9.9, P=0.04; and hazard ratio 11.9, P=0.02, respectively) independent of the other variables. In summary, among surgically resectable oropharyngeal SCC (including among just the p16-positive cohort), tumor cell anaplasia and multinucleation independently correlated with disease recurrence and poorer survival.

Tumor Cell Anaplasia and Multinucleation Are Predictors of Disease Recurrence in Oropharyngeal Squamous Cell Carcinoma, Including Among Just the Human Papillomavirus-Related Cancers

PubMed Central

Lewis, James S.; Scantlebury, Juliette B.; Luo, Jingqin; Thorstad, Wade L.

2013-01-01

Oropharyngeal squamous cell carcinoma (SCC) is frequently related to high risk human papillomavirus. This tumor expresses p16, frequently has a nonkeratinizing morphology, and has improved outcomes. Despite having a good prognosis, tumors can have focal or diffuse nuclear anaplasia or multinucleation, the significance of which is unknown. From a database of 270 oropharyngeal SCCs with known histologic typing (using our established system) and p16 immunohistochemistry, all surgically resected cases (149) were reviewed. Anaplasia was defined as any ×40 field with ≥ 3 tumor nuclei with diameters ≥ 5 lymphocyte nuclei (~25 μm), and multinucleation was defined as any ×40 field with ≥ 3 tumor cells with multiple nuclei. p16 was positive in 128 cases (85.9%), 64 cases (43.0%) showed anaplasia, and 71 (47.7%) showed multinucleation. Anaplasia and multinucleation were highly related (P < 0.001), and both also correlated with histologic type (P < 0.001 and P = 0.01, respectively), p16 status (P = 0.09 and 0.03, respectively), and partially with nodal extracapsular extension. There was no correlation with any of the other variables. In univariate analysis, cases showing anaplasia or multinucleation had worse overall, disease-specific, and disease-free survival (P < 0.006 for all). Higher T-stage, keratinizing histologic type, extracapsular extension, and smoking also all correlated with worse survival. In multivariate analysis, anaplasia and multinucleation both predicted worse disease-specific survival (hazard ratio 9.9, P = 0.04; and hazard ratio 11.9, P = 0.02, respectively) independent of the other variables. In summary, among surgically resectable oropharyngeal SCC (including among just the p16-positive cohort), tumor cell anaplasia and multinucleation independently correlated with disease recurrence and poorer survival. PMID:22743286

MR imaging of silicone breast implants: evaluation of prospective and retrospective interpretations and interobserver agreement.

PubMed

Quinn, S F; Neubauer, N M; Sheley, R C; Demlow, T A; Szumowski, J

1996-01-01

MR imaging was used to evaluate the integrity of silicone breast implants in 54 women with 108 implants. MR images were interpreted by relatively inexperienced readers who tried to reproduce the experiences reported in the literature. The study examines the interobserver agreement using different diagnostic signs and the influence of experience on interpretation errors. Prospective and retrospective interpretations were compared with surgical findings at the time of explanation. Diagnostic indicators, including the linguine sign, the inverted tear drop sign, the C sign, water droplets mixed with silicone, and extracapsular globules of silicone, were evaluated for diagnostic efficacy and interobserver agreement. The prospective sensitivity and specificity were 87% and 78%, respectively. With the retrospective interpretations, the sensitivity and specificity increased to 93% and 92%, respectively. Most of the prospective false-positive interpretations were due to misinterpreting radial folds as signs of implant rupture. Six implants interpreted retrospectively as false positives had gross amounts of silicone around the implants at surgery but there were no obvious rents in the implant shells. There was fair to excellent interobserver agreement with the individual diagnostic signs except for extracapsular globules of silicone. All of the signs had specificities of greater than 90%. The sensitivities of the individual signs were less than the overall retrospective sensitivity. With experience, the sensitivity improved from 87% to 93% and the specificity improved from 78% to 92%. This study helps substantiate the use of diagnostic signs used by other authors to detect silicone loss from breast implants by MR imaging; however, questions remain as to the clinical role of MR imaging in evaluating implants for silicone loss.

Factors influencing the indication for tonsillectomy: a historical overview and current concepts.

PubMed

Hultcrantz, Elisabeth; Ericsson, Elisabeth

2013-01-01

Tonsil surgery has been performed for more than 3,000 years. During the 19th century when anesthesia became available, techniques were refined and the number of procedures performed increased. Repeated throat infections often causing big tonsils was the reason why parents asked for the procedure. During the preantibiotic era, scarlet fever was feared since potential heart or kidney complications were life-threatening. The technique used before 1900 was tonsillotomy since neither a fingernail, snare nor the later 'guillotine' were used extracapsularly. Bleeding was small and the surgery ambulatory. Extracapsular tonsillectomy developed around the turn of the 20th century with the purpose of avoiding remnants - the 'focal infection theory' was prevailing. The whole tonsil was now extirpated with good visibility of the tonsillar area in a deeply anesthetized patient. During the first half of the 20th century, the two methods competed, but by 1950, total tonsillectomy had become the only 'correct' tonsil surgery. The indication was still recurrent infections. The risk for serious bleeding increased; therefore large clinics arose where patients remained for at least a week after tonsillectomy. When oral penicillin for children became available during the 1960s, the threat of throat infection decreased and the number of tonsillectomies declined. The awareness of obstructive problems in children rose at the same time when obstructive sleep apnea syndrome became a disease for adults (1970s). Tonsillotomy was revived during the 1990s and is today used increasingly in many countries. The indication is mainly obstructive sleep apnea syndromeor sleep-disordered breathing, especially in small children. Total tonsillectomy is still preferred for recurrent infections, which include periodic fever/adenitis/pharyngitis/aphthous ulcer syndrome and recurrent peritonsillitis. Copyright © 2013 S. Karger AG, Basel.

A survey of perceived training differences between ophthalmology residents in Hong Kong and China.

PubMed

Young, Alvin L; Jhanji, Vishal; Liang, Yuanbo; Congdon, Nathan; Chow, Simon; Wang, Fenghua; Zhang, Xiujuan; Man, Xiaofei; Yang, Mingming; Lin, Zhong; Yuen, Hunter G L; Lam, Dennis S C

2015-09-28

To study the differences in ophthalmology resident training between China and the Hong Kong Special Administrative Region (HKSAR). Training programs were selected from among the largest and best-known teaching hospitals. Ophthalmology residents were sent an anonymous 48-item questionnaire by mail. Work satisfaction, time allocation between training activities and volume of surgery performed were determined. 50/75 residents (66.7 %) from China and 20/26 (76.9 %) from HKSAR completed the survey. Age (28.9 ± 2.5 vs. 30.2 ± 2.9 years, p = 0.15) and number of years in training (3.4 ± 1.6 vs. 2.8 ± 1.5, p = 0.19) were comparable between groups. The number of cataract procedures performed by HKSAR trainees (extra-capsular, median 80.0, quartile range: 30.0, 100.0; phacoemulsification, median: 20.0, quartile range: 0.0, 100.0) exceeded that for Chinese residents (extra-capsular: median = 0, p < 0.0001; phacoemulsification: median = 0, p < 0.0001). Chinese trainees spent more time completing medical charts (>50 % of time on charts: 62.5 % versus 5.3 %, p < 0.0001) and received less supervision (≥90 % of training supervised: 4.4 % versus 65 %, p < 0.0001). Chinese residents were more likely to feel underpaid (96.0 % vs. 31.6 %, p < 0.0001) and hoped their children would not practice medicine (69.4 % vs. 5.0 %, p = 0.0001) compared HKSAR residents. In this study, ophthalmology residents in China report strikingly less surgical experience and supervision, and lower satisfaction than HKSAR residents. The HKSAR model of hands-on resident training might be useful in improving the low cataract surgical rate in China.

The epidemiology and functional outcomes of operative fixation of extracapsular proximal femoral fractures (AO 31-A) in young adults.

PubMed

Ramoutar, D N; Kodumuri, P; Rodrigues, J N; Olewicz, S; Moran, C G; Ollivere, B J; Forward, D P

2017-02-01

Proximal femoral fractures in adults under 50 years are not as common as in the elderly, but may have just as significant an impact. There is little in the literature describing the functional outcomes of fixation in this age group. Our aim was to assess the clinical and functional outcomes of operative management of extracapsular proximal femoral fractures (AO 31-A) in the young adult (<50 years). Consecutive skeletally mature patients <50 years undergoing operative fixation of these fractures were obtained from a prospective database over a 12-year period. Complications and mortality data were obtained from this database and case note review. Outcome scores were obtained via postal questionnaires. Eighty-eight patients were included in the study of which 74 (84%) had fixation with the dynamic hip screw. The mean age was 39 years (range 17-50) with a male preponderance (73.8%). Mean hospital stay was 14 days (range 2-94). Seventeen (19.3%) patients had died at a mean of 40 months from their operation date. The 1-year mortality was 4.5%. There were five complications (5.7%). SF-36 and EuroQol 5D scores showed that 5-10% had severe problems with a 20% decrease in quality of life compared to population norms. The biggest differences were in the physical function modalities. One-third had fair to poor hip function as assessed by the Oxford Hip Score. Though these injuries are relatively rare in this age group, they do have significant mortality and functional impairment reflecting a higher energy of injury rather than the frailty seen in the elderly.

Comparison of the Walz Nomogram and Presence of Secondary Circulating Prostate Cells for Predicting Early Biochemical Failure after Radical Prostatectomy for Prostate Cancer in Chilean Men.

PubMed

Murray, Nigel P; Reyes, Eduardo; Orellana, Nelson; Fuentealba, Cynthia; Jacob, Omar

2015-01-01

To determine the utility of secondary circulating prostate cells for predicting early biochemical failure after radical prostatectomy for prostate cancer and compare the results with the Walz nomagram. A single centre, prospective study of men with prostate cancer treated with radical prostatectomy between 2004 and 2014 was conducted, with registration of clinical-pathological details, total serum PSA pre-surgery, Gleason score, extracapsular extension, positive surgical margins, infiltration of lymph nodes, seminal vesicles and pathological stage. Secondary circulating prostate cells were obtained using differential gel centrifugation and assessed using standard immunocytochemistry with anti-PSA. Biochemical failure was defined as a PSA >0.2ng/ml, predictive values werecalculated using the Walz nomagram and CPC detection. A total of 326 men participated, with a median follow up of 5 years; 64 had biochemical failure within two years. Extracapsular extension, positive surgical margins, pathological stage, Gleason score ≥ 8, infiltration of seminal vesicles and lymph nodes were all associated with higher risk of biochemical failure. The discriminative value for the nomogram and circulating prostate cells was high (AUC >0.80), predictive values were higher for circulating prostate cell detection, with a negative predictive value of 99%, sensitivity of 96% and specificity of 75%. The nomagram had good predictive power to identify men with a high risk of biochemical failure within two years. The presence of circulating prostate cells had the same predictive power, with a higher sensitivity and negative predictive value. The presence of secondary circulating prostate cells identifies a group of men with a high risk of early biochemical failure. Those negative for secondary CPCs have a very low risk of early biochemical failure.

Surgical treatment of scapulohumeral subluxation in an alpaca (Vicugna pacos) using osteotomy of the acromion, open reduction and extracapsular tension sutures.

PubMed

Kofler, J; Eberspächer, E; Fischl, K; Vidoni, B

2016-05-01

A 3.3-year-old male alpaca, weighing 60 kg was referred for investigation of a severe left forelimb lameness of 4 weeks duration. A scapulohumeral subluxation had been diagnosed radiographically by the referring veterinarian. Based on clinical, ultrasonographic and radiographic findings the diagnosis of cranio-lateral subluxation of the left humeral head was confirmed. In addition, a full thickness lesion (approximately 1×1 cm) of the articular cartilage on the caudomedial aspect of the humeral head was diagnosed by arthroscopy. Treatment included open reduction with internal fixation. Severe muscle contraction and local tissue fibrosis around the scapulohumeral joint (SHJ) required osteotomy of the acromion 3 cm proximal to the distal acromial edge, to allow adequate access. Internal stabilisation was achieved by placing tension band sutures between one cortical screw in the scapular neck and two cortical screws, with washers, craniolaterally on the greater tubercle of the humerus. Post-surgery, a carpal flexion sling was applied with the carpus maintained in 70° flexion for 4 weeks to avoid postoperative weight-bearing. An exercise programme was started 8 days after surgery and continued for 12 weeks. The alpaca had an uneventful postsurgical recovery and showed no lameness after 8 weeks. The long-term outcome was excellent; 21 months after surgery the alpaca was sound and the range of movement of the left SHJ was equal to the right SHJ. Even in this chronic case of subluxation of the SHJ of 4 weeks duration, surgical treatment using osteotomy of the acromion, open reduction and internal fixation with extracapsular scapulohumeral tension sutures resulted in an excellent long-term outcome in this alpaca, despite the presence of a cartilage lesion.

Can computerized tomography accurately stage childhood renal tumors?

PubMed

Abdelhalim, Ahmed; Helmy, Tamer E; Harraz, Ahmed M; Abou-El-Ghar, Mohamed E; Dawaba, Mohamed E; Hafez, Ashraf T

2014-07-01

Staging of childhood renal tumors is crucial for treatment planning and outcome prediction. We sought to identify whether computerized tomography could accurately predict the local stage of childhood renal tumors. We retrospectively reviewed our database for patients diagnosed with childhood renal tumors and treated surgically between 1990 and 2013. Inability to retrieve preoperative computerized tomography, intraoperative tumor spillage and nonWilms childhood renal tumors were exclusion criteria. Local computerized tomography stage was assigned by a single experienced pediatric radiologist blinded to the pathological stage, using a consensus similar to the Children's Oncology Group Wilms tumor staging system. Tumors were stratified into up-front surgery and preoperative chemotherapy groups. The radiological stage of each tumor was compared to the pathological stage. A total of 189 tumors in 179 patients met inclusion criteria. Computerized tomography staging matched pathological staging in 68% of up-front surgery (70 of 103), 31.8% of pre-chemotherapy (21 of 66) and 48.8% of post-chemotherapy scans (42 of 86). Computerized tomography over staged 21.4%, 65.2% and 46.5% of tumors in the up-front surgery, pre-chemotherapy and post-chemotherapy scans, respectively, and under staged 10.7%, 3% and 4.7%. Computerized tomography staging was more accurate in tumors managed by up-front surgery (p <0.001) and those without extracapsular extension (p <0.001). The validity of computerized tomography staging of childhood renal tumors remains doubtful. This staging is more accurate for tumors treated with up-front surgery and those without extracapsular extension. Preoperative computerized tomography can help to exclude capsular breach. Treatment strategy should be based on surgical and pathological staging to avoid the hazards of inaccurate staging. Copyright © 2014 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

Recruitment for health disparities preventive intervention trials: the early childhood caries collaborating centers.

PubMed

Tiwari, Tamanna; Casciello, Alana; Gansky, Stuart A; Henshaw, Michelle; Ramos-Gomez, Francisco; Rasmussen, Margaret; Garcia, Raul I; Albino, Judith; Batliner, Terrence S

2014-08-07

Four trials of interventions designed to prevent early childhood caries are using community-engagement strategies to improve recruitment of low-income, racial/ethnic minority participants. The trials are being implemented by 3 centers funded by the National Institute of Dental and Craniofacial Research and known as the Early Childhood Caries Collaborating Centers (EC4): the Center for Native Oral Health Research at the University of Colorado, the Center to Address Disparities in Children's Oral Health at the University of California San Francisco, and the Center for Research to Evaluate and Eliminate Dental Disparities at Boston University. The community contexts for the EC4 trials include urban public housing developments, Hispanic communities near the US-Mexican border, and rural American Indian reservations. These communities have a high prevalence of early childhood caries, suggesting the need for effective, culturally acceptable interventions. Each center's intervention(s) used community-based participatory research approaches, identified community partners, engaged the community through various means, and developed communication strategies to enhance recruitment. All 3 centers have completed recruitment. Each center implemented several new strategies and approaches to enhance recruitment efforts, such as introducing new communication techniques, using media such as radio and newspapers to spread awareness about the studies, and hosting community gatherings. Using multiple strategies that build trust in the community, are sensitive to cultural norms, and are adaptable to the community environment can enhance recruitment in underserved communities.

Ethical bodies: are they possible under democratic systems? The Turkish example.

PubMed

Arda, Berna

2009-09-01

In this article, the relationship between ethics bodies and democratic concepts will be introduced. One should bear in mind that the relationship between the flourishing of ethics committees (EC) and democracy is by no means undirectional. The line of causation can easily be reversed as a higher level of democracy is likely to lead to a spurt in such committees at different levels of society. It is not a coincidence that they appear in larger numbers in relatively more open and democratic societies. In this sense, their sheer existence might be taken as a sign of a higher level of awareness for openness and democracy. EC seems to have some functions theoretically: To contribute to the eradication of corruption in society; To increase the accountability of different sections of the population; To play an important part in increasing the awareness about the rights and duties; To contribute to the spread of self-disciplining behavior in society; One final point to be emphasized is that for ethical committees to fulfill the above functions they should have a clear set of guidelines, powers to enforce them and effective deterrents to prevent wayward behavior. The principal question of how it does works in Turkey--a country located at the junction of Europe and Asia--ought to be perceived from the point of view of a medical ethicist from a developing country.

Leachate pollution management to overcome global climate change impact in Piyungan Landfill, Indonesia

NASA Astrophysics Data System (ADS)

Harjito; Suntoro; Gunawan, T.; Maskuri, M.

2018-03-01

Environmental problems associated with the landfill system are generated by domestic waste landfills, especially those with open dumping systems. In these systems, waste degrades and produces some gases, namely methane gas (CH4) and carbon dioxide (CO2), which can cause global climate change. This research aimed at identifying the areas that experience groundwater pollution and the spread pattern of leachate movement to the vicinity as well as to develop a leachate management model. The Electricity Resistivity Tomography (ERT) survey is deployed to assess the distribution of electrical resistivity in the polluted areas. In this study, the groundwater contamination is at a very low in the aquifer zone, i.e., 3-9 Ωm. It is caused by the downward migration of leachate to water table that raises the ion concentration of groundwater. These ions will increase the electrical conductivity (EC), i.e., up to 1,284 μmhos/cm, and decrease the electrical resistivity. The leachate spreads westward and northward at a depth of 6-17 m (aquifer) with a thickness of pollution between 4 and11 m.The recommended landfill management model involves the installation of rainwater drainage, use of cover and baseliner made of waterproof materials, and massive waste treatment.

An intelligent and secure system for predicting and preventing Zika virus outbreak using Fog computing

NASA Astrophysics Data System (ADS)

Sareen, Sanjay; Gupta, Sunil Kumar; Sood, Sandeep K.

2017-10-01

Zika virus is a mosquito-borne disease that spreads very quickly in different parts of the world. In this article, we proposed a system to prevent and control the spread of Zika virus disease using integration of Fog computing, cloud computing, mobile phones and the Internet of things (IoT)-based sensor devices. Fog computing is used as an intermediary layer between the cloud and end users to reduce the latency time and extra communication cost that is usually found high in cloud-based systems. A fuzzy k-nearest neighbour is used to diagnose the possibly infected users, and Google map web service is used to provide the geographic positioning system (GPS)-based risk assessment to prevent the outbreak. It is used to represent each Zika virus (ZikaV)-infected user, mosquito-dense sites and breeding sites on the Google map that help the government healthcare authorities to control such risk-prone areas effectively and efficiently. The proposed system is deployed on Amazon EC2 cloud to evaluate its performance and accuracy using data set for 2 million users. Our system provides high accuracy of 94.5% for initial diagnosis of different users according to their symptoms and appropriate GPS-based risk assessment.

Electrochemical disinfection of toilet wastewater using wastewater electrolysis cell.

PubMed

Huang, Xiao; Qu, Yan; Cid, Clément A; Finke, Cody; Hoffmann, Michael R; Lim, Keahying; Jiang, Sunny C

2016-04-01

The paucity of proper sanitation facilities has contributed to the spread of waterborne diseases in many developing countries. The primary goal of this study was to demonstrate the feasibility of using a wastewater electrolysis cell (WEC) for toilet wastewater disinfection. The treated wastewater was designed to reuse for toilet flushing and agricultural irrigation. Laboratory-scale electrochemical (EC) disinfection experiments were performed to investigate the disinfection efficiency of the WEC with four seeded microorganisms (Escherichia coli, Enterococcus, recombinant adenovirus serotype 5, and bacteriophage MS2). In addition, the formation of organic disinfection byproducts (DBPs) trihalomethanes (THMs) and haloacetic acids (HAA5) at the end of the EC treatment was also investigated. The results showed that at an applied cell voltage of +4 V, the WEC achieved 5-log10 reductions of all four seeded microorganisms in real toilet wastewater within 60 min. In contrast, chemical chlorination (CC) disinfection using hypochlorite [NaClO] was only effective for the inactivation of bacteria. Due to the rapid formation of chloramines, less than 0.5-log10 reduction of MS2 was observed in toilet wastewater even at the highest [NaClO] dosage (36 mg/L, as Cl2) over a 1 h reaction. Experiments using laboratory model waters showed that free reactive chlorine generated in situ during EC disinfection process was the main disinfectant responsible for the inactivation of microorganisms. However, the production of hydroxyl radicals [OH], and other reactive oxygen species by the active bismuth-doped TiO2 anode were negligible under the same electrolytic conditions. The formation of THMs and HAA5 were found to increase with higher applied cell voltage. Based on the energy consumption estimates, the WEC system can be operated using solar energy stored in a DC battery as the sole power source. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

The Serum Resistome of a Globally Disseminated Multidrug Resistant Uropathogenic Escherichia coli Clone

PubMed Central

Phan, Minh-Duy; Peters, Kate M.; Sarkar, Sohinee; Lukowski, Samuel W.; Allsopp, Luke P.; Moriel, Danilo Gomes; Achard, Maud E. S.; Totsika, Makrina; Marshall, Vikki M.; Upton, Mathew; Beatson, Scott A.; Schembri, Mark A.

2013-01-01

Escherichia coli ST131 is a globally disseminated, multidrug resistant clone responsible for a high proportion of urinary tract and bloodstream infections. The rapid emergence and successful spread of E. coli ST131 is strongly associated with antibiotic resistance; however, this phenotype alone is unlikely to explain its dominance amongst multidrug resistant uropathogens circulating worldwide in hospitals and the community. Thus, a greater understanding of the molecular mechanisms that underpin the fitness of E. coli ST131 is required. In this study, we employed hyper-saturated transposon mutagenesis in combination with multiplexed transposon directed insertion-site sequencing to define the essential genes required for in vitro growth and the serum resistome (i.e. genes required for resistance to human serum) of E. coli EC958, a representative of the predominant E. coli ST131 clonal lineage. We identified 315 essential genes in E. coli EC958, 231 (73%) of which were also essential in E. coli K-12. The serum resistome comprised 56 genes, the majority of which encode membrane proteins or factors involved in lipopolysaccharide (LPS) biosynthesis. Targeted mutagenesis confirmed a role in serum resistance for 46 (82%) of these genes. The murein lipoprotein Lpp, along with two lipid A-core biosynthesis enzymes WaaP and WaaG, were most strongly associated with serum resistance. While LPS was the main resistance mechanism defined for E. coli EC958 in serum, the enterobacterial common antigen and colanic acid also impacted on this phenotype. Our analysis also identified a novel function for two genes, hyxA and hyxR, as minor regulators of O-antigen chain length. This study offers novel insight into the genetic make-up of E. coli ST131, and provides a framework for future research on E. coli and other Gram-negative pathogens to define their essential gene repertoire and to dissect the molecular mechanisms that enable them to survive in the bloodstream and cause disease. PMID:24098145

The serum resistome of a globally disseminated multidrug resistant uropathogenic Escherichia coli clone.

PubMed

Phan, Minh-Duy; Peters, Kate M; Sarkar, Sohinee; Lukowski, Samuel W; Allsopp, Luke P; Gomes Moriel, Danilo; Achard, Maud E S; Totsika, Makrina; Marshall, Vikki M; Upton, Mathew; Beatson, Scott A; Schembri, Mark A

2013-01-01

Escherichia coli ST131 is a globally disseminated, multidrug resistant clone responsible for a high proportion of urinary tract and bloodstream infections. The rapid emergence and successful spread of E. coli ST131 is strongly associated with antibiotic resistance; however, this phenotype alone is unlikely to explain its dominance amongst multidrug resistant uropathogens circulating worldwide in hospitals and the community. Thus, a greater understanding of the molecular mechanisms that underpin the fitness of E. coli ST131 is required. In this study, we employed hyper-saturated transposon mutagenesis in combination with multiplexed transposon directed insertion-site sequencing to define the essential genes required for in vitro growth and the serum resistome (i.e. genes required for resistance to human serum) of E. coli EC958, a representative of the predominant E. coli ST131 clonal lineage. We identified 315 essential genes in E. coli EC958, 231 (73%) of which were also essential in E. coli K-12. The serum resistome comprised 56 genes, the majority of which encode membrane proteins or factors involved in lipopolysaccharide (LPS) biosynthesis. Targeted mutagenesis confirmed a role in serum resistance for 46 (82%) of these genes. The murein lipoprotein Lpp, along with two lipid A-core biosynthesis enzymes WaaP and WaaG, were most strongly associated with serum resistance. While LPS was the main resistance mechanism defined for E. coli EC958 in serum, the enterobacterial common antigen and colanic acid also impacted on this phenotype. Our analysis also identified a novel function for two genes, hyxA and hyxR, as minor regulators of O-antigen chain length. This study offers novel insight into the genetic make-up of E. coli ST131, and provides a framework for future research on E. coli and other Gram-negative pathogens to define their essential gene repertoire and to dissect the molecular mechanisms that enable them to survive in the bloodstream and cause disease.

Electrochemical disinfection of toilet wastewater using wastewater electrolysis cell

PubMed Central

Huang, Xiao; Qu, Yan; Cid, Clément A.; Finke, Cody; Hoffmann, Michael R.; Lim, Keahying; Jiang, Sunny C.

2016-01-01

The paucity of proper sanitation facilities has contributed to the spread of waterborne diseases in many developing countries. The primary goal of this study was to demonstrate the feasibility of using a wastewater electrolysis cell (WEC) for toilet wastewater disinfection. The treated wastewater was designed to reuse for toilet flushing and agricultural irrigation. Laboratory-scale electrochemical (EC) disinfection experiments were performed to investigate the disinfection efficiency of the WEC with four seeded microorganisms (Escherichia coli, Enterococcus, recombinant adenovirus serotype 5, and bacteriophage MS2). In addition, the formation of organic disinfection byproducts (DBPs) trihalomethanes (THMs) and haloacetic acids (HAA5) at the end of the EC treatment was also investigated. The results showed that at an applied cell voltage of +4 V, the WEC achieved 5-log10 reductions of all four seeded microorganisms in real toilet wastewater within 60 min. In contrast, chemical chlorination (CC) disinfection using hypochlorite [NaClO] was only effective for the inactivation of bacteria. Due to the rapid formation of chloramines, less than 0.5-log10 reduction of MS2 was observed in toilet wastewater even at the highest [NaClO] dosage (36 mg/L, as Cl2) over a 1 h reaction. Experiments using laboratory model waters showed that free reactive chlorine generated in situ during EC disinfection process was the main disinfectant responsible for the inactivation of microorganisms. However, the production of hydroxyl radicals [•OH], and other reactive oxygen species by the active bismuth-doped TiO2 anode were negligible under the same electrolytic conditions. The formation of THMs and HAA5 were found to increase with higher applied cell voltage. Based on the energy consumption estimates, the WEC system can be operated using solar energy stored in a DC battery as the sole power source. PMID:26854604

Characteristics and sources of the fine carbonaceous aerosols in Haikou, China

NASA Astrophysics Data System (ADS)

Liu, Baoshuang; Zhang, Jiaying; Wang, Lu; Liang, Danni; Cheng, Yuan; Wu, Jianhui; Bi, Xiaohui; Feng, Yinchang; Zhang, Yufen; Yang, Haihang

2018-01-01

Ambient PM2.5 samples were collected from January to September 2015 in Haikou. The carbonaceous fractions included OC, EC, OC1, OC2, OC3, OC4, EC1, EC2, EC3, Char-EC (EC1 minus POC) and Soot-EC (EC2 plus EC3) were analysed in this study. The results indicate that the mean concentrations of OC and EC are 5.6 and 2.5 μg/m3 during the sampling period, respectively; and the concentrations of most of carbonaceous fractions are the highest in winter and the lowest in spring. The seasonal variations of Soot-EC and Char-EC concentrations show distinct differences. The concentrations of Char-EC are higher in winter and lower in spring; while those of Soot-EC are lower in winter and higher in summer. Compared to Char-EC, the concentrations of Soot-EC show smaller seasonal-variation in Haikou. The Char-EC has the higher correlations with OC and EC (r = 0.91 and 0.95, P < 0.01), while the correlation between the Soot-EC and either OC or EC is absent (r = 0.15 and 0.11, P > 0.05). The average ratios of Char-EC/Soot-EC are in the order of winter (15.9) > autumn (4.9) > summer (4.0) > spring (3.6), with an average value of 7.1. According to error estimation (EE) diagnostics analysis, four factors are revealed in Positive Matrix Factorization (PMF) analysis during each season. The combined gasoline/diesel vehicle exhaust, coal combustion, biomass burning and specific diesel vehicle exhaust are identified as the major sources of carbonaceous aerosols, and their contributions during the whole year are up to 29.3%, 27.4%, 17.9% and 15.9%, respectively. The transport trajectories of the air masses illustrate distinct differences during different seasons, and the transport trajectories are mainly derived from the mainland China (i.e. Jiangxi, Fujian and Guangdong provinces) in winter, likely caused by higher contribution of coal combustion.

Measuring eating competence: psychometric properties and validity of the ecSatter Inventory.

PubMed

Lohse, Barbara; Satter, Ellyn; Horacek, Tanya; Gebreselassie, Tesfayi; Oakland, Mary Jane

2007-01-01

Assess validity of the ecSatter Inventory (ecSI) to measure eating competence (EC). Concurrent administration of ecSI with validated measures of eating behaviors using on-line and paper-pencil formats. The on-line survey was completed by 370 participants; 462 completed the paper version. Participants included 863 adults with 832 usable surveys from respondents (mean age 36.2 +/- 13.4 years) without eating disorders, mostly female, white, educated, overweight, physically active, and food secure. Of those indicating intent to complete the on-line survey, 80.3% did so; 54% of mailed surveys were returned. Eating and food behaviors compared among EC tertiles and between dichotomous EC categories; internal consistency of ecSI. Analysis of variance, independent t tests, chi-square, factor analysis, logistic regression. Significance level was P < .05. Mean ecSI score was 31.1 +/- 7.5. ecSI included 4 subscales with internal reliability and content validity. Construct validity was supported by specific behavioral profiles for ecSI tertiles and ecSI dichotomized categories. Persons unsatisfied with weight were 54% less likely to be EC; unit increase in the food like index was associated with nearly 3 times greater likelihood of being EC. The ecSatter Inventory is a valid measure of EC and can be used for descriptive and outcome measurements.

Attenuation of Hind-Limb Ischemia in Mice with Endothelial-Like Cells Derived from Different Sources of Human Stem Cells

PubMed Central

Chan, Yau-Chi; Ng, Joyce H. L.; Au, Ka-Wing; Wong, Lai-Yung; Siu, Chung-Wah; Tse, Hung-Fat

2013-01-01

Functional endothelial-like cells (EC) have been successfully derived from different cell sources and potentially used for treatment of cardiovascular diseases; however, their relative therapeutic efficacy remains unclear. We differentiated functional EC from human bone marrow mononuclear cells (BM-EC), human embryonic stem cells (hESC-EC) and human induced pluripotent stem cells (hiPSC-EC), and compared their in-vitro tube formation, migration and cytokine expression profiles, and in-vivo capacity to attenuate hind-limb ischemia in mice. Successful differentiation of BM-EC was only achieved in 1/6 patient with severe coronary artery disease. Nevertheless, BM-EC, hESC-EC and hiPSC-EC exhibited typical cobblestone morphology, had the ability of uptaking DiI-labeled acetylated low-density-lipoprotein, and binding of Ulex europaeus lectin. In-vitro functional assay demonstrated that hiPSC-EC and hESC-EC had similar capacity for tube formation and migration as human umbilical cord endothelial cells (HUVEC) and BM-EC (P>0.05). While increased expression of major angiogenic factors including epidermal growth factor, hepatocyte growth factor, vascular endothelial growth factor, placental growth factor and stromal derived factor-1 were observed in all EC cultures during hypoxia compared with normoxia (P<0.05), the magnitudes of cytokine up-regulation upon hypoxic were more dramatic in hiPSC-EC and hESC-EC (P<0.05). Compared with medium, transplanting BM-EC (n = 6), HUVEC (n = 6), hESC-EC (n = 8) or hiPSC-EC (n = 8) significantly attenuated severe hind-limb ischemia in mice via enhancement of neovascularization. In conclusion, functional EC can be generated from hECS and hiPSC with similar therapeutic efficacy for attenuation of severe hind-limb ischemia. Differentiation of functional BM-EC was more difficult to achieve in patients with cardiovascular diseases, and hESC-EC or iPSC-EC are readily available as “off-the-shelf” format for the treatment of tissue ischemia. PMID:23472116

Molecular Signatures of Tissue-Specific Microvascular Endothelial Cell Heterogeneity in Organ Maintenance and Regeneration

PubMed Central

Nolan, Daniel J.; Ginsberg, Michael; Israely, Edo; Palikuqi, Brisa; Poulos, Michael G.; James, Daylon; Ding, Bi-Sen; Schachterle, William; Liu, Ying; Rosenwaks, Zev; Butler, Jason M.; Xiang, Jenny; Rafii, Arash; Shido, Koji; Rabbany, Sina Y.; Elemento, Olivier; Rafii, Shahin

2013-01-01

SUMMARY Microvascular endothelial cells (ECs) within different tissues are endowed with distinct but as yet unrecognized structural, phenotypic, and functional attributes. We devised EC purification, cultivation, profiling, and transplantation models that establish tissue-specific molecular libraries of ECs devoid of lymphatic ECs or parenchymal cells. These libraries identify attributes that confer ECs with their organotypic features. We show that clusters of transcription factors, angiocrine growth factors, adhesion molecules, and chemokines are expressed in unique combinations by ECs of each organ. Furthermore, ECs respond distinctly in tissue regeneration models, hepatectomy, and myeloablation. To test the data set, we developed a transplantation model that employs generic ECs differentiated from embryonic stem cells. Transplanted generic ECs engraft into regenerating tissues and acquire features of organotypic ECs. Collectively, we demonstrate the utility of informational databases of ECs toward uncovering the extravascular and intrinsic signals that define EC heterogeneity. These factors could be exploited therapeutically to engineer tissue-specific ECs for regeneration. PMID:23871589

Reactions of singly-reduced ethylene carbonate in lithium battery electrolytes: a molecular dynamics simulation study using the ReaxFF.

PubMed

Bedrov, Dmitry; Smith, Grant D; van Duin, Adri C T

2012-03-22

We have conducted quantum chemistry calculations and gas- and solution-phase reactive molecular dynamics simulation studies of reactions involving the ethylene carbonate (EC) radical anion EC(-) using the reactive force field ReaxFF. Our studies reveal that the substantial barrier for transition from the closed (cyclic) form, denoted c-EC(-), of the radical anion to the linear (open) form, denoted o-EC(-), results in a relatively long lifetime of the c-EC(-) allowing this compound to react with other singly reduced alkyl carbonates. Using ReaxFF, we systematically investigate the fate of both c-EC(-) and o-EC(-) in the gas phase and EC solution. In the gas phase and EC solutions with a relatively low concentration of Li(+)/x-EC(-) (where x = o or c), radical termination reactions between radical pairs to form either dilithium butylene dicarbonate (CH(2)CH(2)OCO(2)Li)(2) (by reacting two Li(+)/o-EC(-)) or ester-carbonate compound (by reacting Li(+)/o-EC(-) with Li(+)/c-EC(-)) are observed. At higher concentrations of Li(+)/x-EC(-) in solution, we observe the formation of diradicals which subsequently lead to formation of longer alkyl carbonates oligomers through reaction with other radicals or, in some cases, formation of (CH(2)OCO(2)Li)(2) through elimination of C(2)H(4). We conclude that the local ionic concentration is important in determining the fate of x-EC(-) and that the reaction of c-EC(-) with o-EC(-) may compete with the formation of various alkyl carbonates from o-EC(-)/o-EC(-) reactions. © 2012 American Chemical Society

In vitro analysis of human periodontal microvascular endothelial cells.

PubMed

Tsubokawa, Mizuki; Sato, Soh

2014-08-01

Endothelial cells (ECs) participate in key aspects of vascular biology, such as maintenance of capillary permeability, initiation of coagulation, and regulation of inflammation. According to previous reports, ECs have revealed highly specific characteristics depending on the organs and tissues. However, some reports have described the characteristics of the capillaries formed by human periodontal ECs. Therefore, the aim of the present study is to examine the functional characteristics of the periodontal microvascular ECs in vitro. Human periodontal ligament-endothelial cells (HPDL-ECs) and human gingiva-endothelial cells (HG-ECs) were isolated by immunoprecipitation with magnetic beads conjugated to a monoclonal anti-CD31 antibody. The isolated HPDL-ECs and HG-ECs were characterized to definitively demonstrate that these cell cultures represented pure ECs. Human umbilical-vein ECs and human dermal microvascular ECs were used for comparison. These cells were compared according to the proliferation potential, the formation of capillary-like tubes, the transendothelial electric resistance (TEER), and the expression of tight junction proteins. HPDL-ECs and HG-ECs with characteristic cobblestone monolayer morphology were obtained, as determined by light microscopy at confluence. Furthermore, the HPDL-ECs and HG-ECs expressed the EC markers platelet endothelial cell adhesion molecule-1 (also known as CD31), von Willebrand factor, and Ulex europaeus agglutinin 1, and the cells stained strongly positive for CD31 and CD309. In addition, the HPDL-ECs and HG-ECs were observed to form capillary-like tubes, and they demonstrated uptake of acetylated low-density lipoprotein. Functional analyses of the HPDL-ECs and HG-ECs showed that, compared to the control cells, tube formation persisted for only a brief period of time, and TEER was substantially reduced at confluence. Furthermore, the cells exhibited delocalization of zonula occludens-1 and occludin at cell-cell contact sites. The present results provide new evidence that HPDL-ECs and HG-ECs have characteristics of fenestrated capillaries. Therefore, capillaries in human periodontal tissues have functional characteristics of fenestrated capillaries, which might be related to the onset and the progression of systemic diseases and inflammation.

Activin receptor-like kinase 5 inhibition reverses impairment of endothelial cell viability by endogenous islet mesenchymal stromal cells.

PubMed

Clarkin, Claire E; King, Aileen J; Dhadda, Paramjeet; Chagastelles, Pedro; Nardi, Nance; Wheeler-Jones, Caroline P; Jones, Peter M

2013-03-01

Following islet transplantation, islet graft revascularization is compromised due to loss of endothelial cells (ECs) during islet culture. TGF-β signaling pathways are essential for vascular homeostasis but their importance for islet EC function is unclear. We have identified a population of multipotent mesenchymal stromal cells (MSCs) within islets and investigated how modulation of TGF-β signaling by these cells influences islet EC viability. Cultured islets exhibited reduced expression of EC markers (VEGFR2, VE-cadherin and CD31), which was associated with diminished but sustained expression of endoglin a marker of both ECs and MSCs. Double fluorescent labeling of islets in situ with the EC marker CD31 disclosed a population of CD31-negative cells which were positive for endoglin. In vitro coculture of microvascular ECs with endoglin-positive, CD31-negative islet MSCs reduced VEGFR2 protein expression, disrupted EC angiogenic behavior, and increased EC detachment. Medium conditioned by islet MSCs significantly decreased EC viability and increased EC caspase 3/7 activity. EC:MSC cocultures showed enhanced Smad2 phosphorylation consistent with altered ALK5 signaling. Pharmacological inhibition of ALK5 activity with SB431542 (SB) improved EC survival upon contact with MSCs, and SB-treated cultured islets retained EC marker expression and sensitivity to exogenous VEGF164 . Thus, endoglin-expressing islet MSCs influence EC ALK5 signaling in vitro, which decreases EC viability, and changes in ALK5 activity in whole cultured islets contribute to islet EC loss. Modifying TGF-β signaling may enable maintenance of islet ECs during islet isolation and thus improve islet graft revascularization post-transplantation. Copyright © 2013 AlphaMed Press.

Performance evaluation of multi-material electronic cleansing for ultra-low-dose dual-energy CT colonography

NASA Astrophysics Data System (ADS)

Tachibana, Rie; Kohlhase, Naja; Näppi, Janne J.; Hironaka, Toru; Ota, Junko; Ishida, Takayuki; Regge, Daniele; Yoshida, Hiroyuki

2016-03-01

Accurate electronic cleansing (EC) for CT colonography (CTC) enables the visualization of the entire colonic surface without residual materials. In this study, we evaluated the accuracy of a novel multi-material electronic cleansing (MUMA-EC) scheme for non-cathartic ultra-low-dose dual-energy CTC (DE-CTC). The MUMA-EC performs a wateriodine material decomposition of the DE-CTC images and calculates virtual monochromatic images at multiple energies, after which a random forest classifier is used to label the images into the regions of lumen air, soft tissue, fecal tagging, and two types of partial-volume boundaries based on image-based features. After the labeling, materials other than soft tissue are subtracted from the CTC images. For pilot evaluation, 384 volumes of interest (VOIs), which represented sources of subtraction artifacts observed in current EC schemes, were sampled from 32 ultra-low-dose DE-CTC scans. The voxels in the VOIs were labeled manually to serve as a reference standard. The metric for EC accuracy was the mean overlap ratio between the labels of the reference standard and the labels generated by the MUMA-EC, a dualenergy EC (DE-EC), and a single-energy EC (SE-EC) scheme. Statistically significant differences were observed between the performance of the MUMA/DE-EC and the SE-EC methods (p<0.001). Visual assessment confirmed that the MUMA-EC generated less subtraction artifacts than did DE-EC and SE-EC. Our MUMA-EC scheme yielded superior performance over conventional SE-EC scheme in identifying and minimizing subtraction artifacts on noncathartic ultra-low-dose DE-CTC images.

Provision of emergency contraception at student health centers in California community colleges.

PubMed

Trieu, Sang Leng; Shenoy, Divya P; Bratton, Sally; Marshak, Helen Hopp

2011-01-01

Approximately half of all pregnancies in the United States are unintended, with the highest rates reported among college-age women. The availability of emergency contraception (EC) pills can be an important component of efforts to reduce unintended pregnancy. Student health centers at community colleges can uniquely support student retention and academic achievement among college students by making EC available to reduce the rate of unintended pregnancy and prevent college drop-out. This article highlights findings from an assessment of EC provision in student health centers within the California community college system (n = 73). A web-based survey was used to explore the provision of EC, challenges and barriers of EC administration, promotion of EC availability, and attitudes toward EC. Descriptive statistics conducted revealed that more than 6 out of 10 (62%) student health centers provided EC, 77% of which dispense EC on site during clinic visits. The most common EC promotion methods were providing brochures at the health center (80%) and through information provided at family planning or primary care visits (73%). Challenges to EC administration included a perceived lack of awareness of EC among students (71%), followed by the notion that some students may overutilize EC (40%). Attitudes toward EC provision were more favorable among health center staff whose campuses offered EC than those who did not (p < .05). This article provides recommendations for community college health centers to improve access and delivery of EC by addressing issues such as cost and offering more novel EC promotion methods. Copyright © 2011 Jacobs Institute of Women's Health. Published by Elsevier Inc. All rights reserved.

Do e-cigarettes have the potential to compete with conventional cigarettes?: a survey of conventional cigarette smokers' experiences with e-cigarettes.

PubMed

Kralikova, Eva; Novak, Jan; West, Oliver; Kmetova, Alexandra; Hajek, Peter

2013-11-01

Electronic cigarettes (ECs) are becoming increasingly popular globally. If they were to replace conventional cigarettes, it could have a substantial impact on public health. To evaluate EC's potential for competing with conventional cigarettes as a consumer product, we report the first data, to our knowledge, on the proportion of smokers who try ECs and become regular users. A total of 2,012 people seen smoking or buying cigarettes in the Czech Republic were approached to answer questions about smoking, with no mention made of ECs to avoid the common bias in surveys of EC users. During the interview, the volunteers' experience with ECs was then discussed. A total of 1,738 smokers (86%) participated. One-half reported trying ECs at least once. Among those who tried ECs, 18.3% (95% CI, 0.15.7%-20.9%) reported using them regularly, and 14% (95% CI, 11.6%-16.2%) used them daily. On average, regular users used ECs daily for 7.1 months. The most common reason for using ECs was to reduce consumption of conventional cigarettes; 60% of regular EC users reported that ECs helped them to achieve this. Being older and having a more favorable initial experience with ECs explained 19% of the variance in progressing to regular EC use. Almost one-fifth of smokers who try ECs once go on to become regular users. ECs may develop into a genuine competitor to conventional cigarettes. Government agencies preparing to regulate ECs need to ensure that such moves do not create a market monopoly for conventional cigarettes.

Cardiac Endothelial Cell Transcriptome.

PubMed

Lother, Achim; Bergemann, Stella; Deng, Lisa; Moser, Martin; Bode, Christoph; Hein, Lutz

2018-03-01

Endothelial cells (ECs) are a highly specialized cell type with marked diversity between different organs or vascular beds. Cardiac ECs are an important player in cardiac physiology and pathophysiology but are not sufficiently characterized yet. Thus, the aim of the present study was to analyze the cardiac EC transcriptome. We applied fluorescence-assisted cell sorting to isolate pure ECs from adult mouse hearts. RNAseq revealed 1288 genes predominantly expressed in cardiac ECs versus heart tissue including several transcription factors. We found an overrepresentation of corresponding transcription factor binding motifs within the promotor region of EC-enriched genes, suggesting that they control the EC transcriptome. Cardiac ECs exhibit a distinct gene expression profile when compared with renal, cerebral, or pulmonary ECs. For example, we found the Meox2 / Tcf15, Fabp4 , and Cd36 signaling cascade higher expressed in cardiac ECs which is a key regulator of fatty acid uptake and involved in the development of atherosclerosis. The results from this study provide a comprehensive resource of gene expression and transcriptional control in cardiac ECs. The cardiac EC transcriptome exhibits distinct differences in gene expression compared with other cardiac cell types and ECs from other organs. We identified new candidate genes that have not been investigated in ECs yet as promising targets for future evaluation. © 2018 American Heart Association, Inc.

Polyethylene Glycol Camouflaged Earthworm Hemoglobin.

PubMed

Jani, Vivek P; Jelvani, Alborz; Moges, Selamawit; Nacharaju, Parimala; Roche, Camille; Dantsker, David; Palmer, Andre; Friedman, Joel M; Cabrales, Pedro

2017-01-01

Nearly 21 million components of blood and whole blood and transfused annually in the United States, while on average only 13.6 million units of blood are donated. As the demand for Red Blood Cells (RBCs) continues to increase due to the aging population, this deficit will be more significant. Despite decades of research to develop hemoglobin (Hb) based oxygen (O2) carriers (HBOCs) as RBC substitutes, there are no products approved for clinical use. Lumbricus terrestris erythrocruorin (LtEc) is the large acellular O2 carrying protein complex found in the earthworm Lumbricus terrestris. LtEc is an extremely stable protein complex, resistant to autoxidation, and capable of transporting O2 to tissue when transfused into mammals. These characteristics render LtEc a promising candidate for the development of the next generation HBOCs. LtEc has a short half-life in circulation, limiting its application as a bridge over days, until blood became available. Conjugation with polyethylene glycol (PEG-LtEc) can extend LtEc circulation time. This study explores PEG-LtEc pharmacokinetics and pharmacodynamics. To study PEG-LtEc pharmacokinetics, hamsters instrumented with the dorsal window chamber were subjected to a 40% exchange transfusion with 10 g/dL PEG-LtEc or LtEc and followed for 48 hours. To study the vascular response of PEG-LtEc, hamsters instrumented with the dorsal window chamber received multiple infusions of 10 g/dL PEG-LtEc or LtEc solution to increase plasma LtEc concentration to 0.5, then 1.0, and 1.5 g/dL, while monitoring the animals' systemic and microcirculatory parameters. Results confirm that PEGylation of LtEc increases its circulation time, extending the half-life to 70 hours, 4 times longer than that of unPEGylated LtEc. However, PEGylation increased the rate of LtEc oxidation in vivo. Vascular analysis verified that PEG-LtEc showed the absence of microvascular vasoconstriction or systemic hypertension. The molecular size of PEG-LtEc did not change the colloid osmotic pressure or blood volume expansion capacity compared to LtEc, due to LtEc's already large molecular size. Taken together, these results further encourage the development of PEG-LtEc as an O2 carrying therapeutic.

Retrieval of atmospheric elemental carbon records using lake sediments: Implications in radiative forcing

NASA Astrophysics Data System (ADS)

Ahmed, Tanveer

Elemental or black carbon (EC or BC) aerosols produced during incomplete combustion strongly absorb solar radiation and contribute to global warming, and cause cardiopulmonary disease. Long-term atmospheric EC measurements, [EC]atm, are needed to validate global climate models to estimate the impact of EC on earth's temperature. Such data is sparse. In this work, a new technique was developed to retrieve the historical record of [EC]atm in the Northeastern US for the past two centuries. Measurements of [EC]atm were made in the monthly composites of daily filters collected over ˜30 yr at Whiteface Mountain (WFM), NY using the thermal optical method. Bottom sediment cores were collected from four lakes near WFM. They were sliced in horizontal sections, freeze dried, and their ages determined 210Pb dating technique. EC in sediments was chemically separated and its concentration determined using the same thermal-optical method. It was shown that [EC]sed = K [EC]atm where K is constant (m3/g). Measurements of [EC]atm and [EC]sed for the ˜1978 to 2005 period was used to determine the value for K. The value of K and [EC]sed for periods before 1978 were used to determine [EC]atm for the past ˜100 yrs. [EC]atm in the preindustrial period in US, ˜1850, varied between 38 and 73 ng/m3, with a mean value of 56 +/- 14 ng/m3. [EC]atm was found to increase sharply with rapid industrialization and reached its maximum value of 751 +/- 265 ng/m3 during 1920s, which was a factor of ˜12 higher compared to the mean preindustrial level. The [EC]atm declined gradually until ˜1980 and then decreased sharply. Directly measured values of [EC]atm are only ˜25% higher compared to the mean preindustrial level. Model US EC emissions estimates of Novakov et al. (2003), based on energy consumptions, reproduce our [EC]sed trends quite well for the ˜1900 to 1930 period. Subsequently, the model EC values drop-off more rapidly than our [EC]atm. To extend the technique where long tern [EC]atm are not available, a new generalized mathematical model expression to determine K was developed. The value of K calculated using the model agreed within +/-30% with the measurements.

An evolving new paradigm: endothelial cells – conditional innate immune cells

PubMed Central

2013-01-01

Endothelial cells (ECs) are a heterogeneous population that fulfills many physiological processes. ECs also actively participate in both innate and adaptive immune responses. ECs are one of the first cell types to detect foreign pathogens and endogenous metabolite-related danger signals in the bloodstream, in which ECs function as danger signal sensors. Treatment with lipopolysaccharide activates ECs, causing the production of pro-inflammatory cytokines and chemokines, which amplify the immune response by recruiting immune cells. Thus, ECs function as immune/inflammation effectors and immune cell mobilizers. ECs also induce cytokine production by immune cells, in which ECs function as immune regulators either by activating or suppressing immune cell function. In addition, under certain conditions, ECs can serve as antigen presenting cells (antigen presenters) by expressing both MHC I and II molecules and presenting endothelial antigens to T cells. These facts along with the new concept of endothelial plasticity suggest that ECs are dynamic cells that respond to extracellular environmental changes and play a meaningful role in immune system function. Based on these novel EC functions, we propose a new paradigm that ECs are conditional innate immune cells. This paradigm provides a novel insight into the functions of ECs in inflammatory/immune pathologies. PMID:23965413

An evolving new paradigm: endothelial cells--conditional innate immune cells.

PubMed

Mai, Jietang; Virtue, Anthony; Shen, Jerry; Wang, Hong; Yang, Xiao-Feng

2013-08-22

Endothelial cells (ECs) are a heterogeneous population that fulfills many physiological processes. ECs also actively participate in both innate and adaptive immune responses. ECs are one of the first cell types to detect foreign pathogens and endogenous metabolite-related danger signals in the bloodstream, in which ECs function as danger signal sensors. Treatment with lipopolysaccharide activates ECs, causing the production of pro-inflammatory cytokines and chemokines, which amplify the immune response by recruiting immune cells. Thus, ECs function as immune/inflammation effectors and immune cell mobilizers. ECs also induce cytokine production by immune cells, in which ECs function as immune regulators either by activating or suppressing immune cell function. In addition, under certain conditions, ECs can serve as antigen presenting cells (antigen presenters) by expressing both MHC I and II molecules and presenting endothelial antigens to T cells. These facts along with the new concept of endothelial plasticity suggest that ECs are dynamic cells that respond to extracellular environmental changes and play a meaningful role in immune system function. Based on these novel EC functions, we propose a new paradigm that ECs are conditional innate immune cells. This paradigm provides a novel insight into the functions of ECs in inflammatory/immune pathologies.

Assesing the effect of an olive mill wastewater evaporation pond in Sousse, Tunisia

NASA Astrophysics Data System (ADS)

S'habou, Rakia; Zairi, Moncef; Kallel, Amjed; Aydi, Abdelwaheb; Ben Dhia, Hamed

2009-08-01

Olive oil is a typical and valuable agro-industrial product in Mediterranean countries. In Tunisia, olive mill wastewaters (OMW) reach an amount of about 1,000,000 t year-1 and constitute a serious organic pollution risk because of the high chemical oxygen demand values and the presence of phytotoxic and antibacterial polyphenols. OMW have been generally stored in pond sites to be eliminated by natural evaporation or valorised by spreading on cultivated soils or by composting. Many researches on the interactions of OMW with soils at laboratory scale (columns) have been reported, but less attention have been paid to the effect of OMW on soils at field scale. The aim of this work is to investigate an area used for >15 years as an uncontrolled OMW pond site. The transformations of soil properties and groundwater occurring during OMW storage were characterised by the pH, phenolic contents, electrical conductivity (EC), moisture content and organic contents. The soil samples were taken from two borings and compared to those of a control one located near the pond site. Groundwater samples were taken on the accessible and nearest water wells to the evaporation ponds. The permeable silty and sandy layers in the site support the infiltration of OMW near the evaporation ponds. This infiltration has reached a depth of 6 m at a distance of almost 50 m laterally. The results show that the OMW infiltration in the subsoil has affected the pH, EC, organic content, phenolic compounds and the moisture.

Prospective case-control study of efficacy of bilateral selective neck dissection in primary surgical treatment of supraglottic laryngeal cancers with clinically negative cervical findings (N0).

PubMed

Djordjevic, V; Bukurov, B; Arsovic, N; Dimitrijevic, M; Jesic, S; Nesic, V; Petrovic, Z

2016-12-01

To evaluate the efficacy of bilateral selective neck dissection of levels II-IV in elective and therapeutic management of the neck as a part of primary surgical treatment of patients with supraglottic laryngeal cancer and clinically negative cervical findings (N0). Institutional, observational, case-control study with historic control of patients who underwent primary supraglottic tumour surgery, and a prospective cohort of patient, who underwent, besides the operation of primary tumour, bilateral selective neck dissection (level II-IV). University, tertiary level hospital, national referral centre. The study included 193 patients with supraglottic cancer and without palpable or ultrasound positive cervical findings who were surgically treated from 1988 to 2005. Besides the operation of primary tumour, all patients in the study group underwent bilateral selective neck dissection (level II-IV). Patients in the control group (N = 51) underwent primary tumour operation only and were followed up regularly. In cases with postoperative regional recurrences, the radical neck dissection was performed. All patients with histopathological confirmation of occult metastases were administered radiotherapy treatment (60 Gy) in the postoperative period. Five-year overall survival rate. Occult cervical metastases were found in 18% of patients. They were present in level II in 77.5%, in level III in 20% of cases and in one patient in level IV (2.5%); the extracapsular spread was observed in 20% of cases. Postoperative regional metastases were found in 4.15% of cases in the study group, and in 11.8% in the control group, which proved to be significantly higher. The five-year overall survival rate showed no significant difference between the study group and the control group. The incidence of postoperative regional recurrences could be reduced by performing bilateral selective neck dissection simultaneously with primary tumour operation, but with no influence on the survival rate. © 2015 John Wiley & Sons Ltd.

Roles of endothelial A-type lamins in migration of T cells on and under endothelial layers

NASA Astrophysics Data System (ADS)

Song, Kwang Hoon; Lee, Jaehyun; Park, Hyoungjun; Kim, Hye Mi; Park, Jeehun; Kwon, Keon Woo; Doh, Junsang

2016-03-01

Stiff nuclei in cell-dense microenvironments may serve as distinct biomechanical cues for cell migration, but such a possibility has not been tested experimentally. As a first step addressing this question, we altered nuclear stiffness of endothelial cells (ECs) by reducing the expression of A-type lamins using siRNA, and investigated the migration of T cells on and under EC layers. While most T cells crawling on control EC layers avoided crossing over EC nuclei, a significantly higher fraction of T cells on EC layers with reduced expression of A-type lamins crossed over EC nuclei. This result suggests that stiff EC nuclei underlying T cells may serve as “duro-repulsive” cues to direct T cell migration toward less stiff EC cytoplasm. During subendothelial migration under EC layers with reduced expression of A-type lamins, T cells made prolonged contact and substantially deformed EC nuclei, resulting in reduced speed and directional persistence. This result suggests that EC nuclear stiffness promotes fast and directionally persistent subendothelial migration of T cells by allowing minimum interaction between T cells and EC nuclei.

SERENITY Aware Development of Security and Dependability Solutions

NASA Astrophysics Data System (ADS)

Serrano, Daniel; Maña, Antonio; Llarena, Rafael; Crespo, Beatriz Gallego-Nicasio; Li, Keqin

This chapter presents an infrastructure supporting the implementation of Executable Components (ECs). ECs represent S&D solutions at the implementation level, that is, by means of pieces of executable code. ECs are instantiated by the Serenity runtime Framework (SRF) as a result of requests coming from applications. The development of ECs requires programmers having specific technical knowledge about SERENITY, since they need to implement certain interfaces of the ECs according to SERENITY standards. Every EC has to implement, the interface between the SRF and the EC itself, and the interface that the EC offers to applications.

Amelioration of cadmium- and mercury-induced liver and kidney damage in rats by genetically engineered probiotic Escherichia coli Nissle 1917 producing pyrroloquinoline quinone with oral supplementation of citric acid.

PubMed

Raghuvanshi, Ruma; Chaudhari, Archana; Kumar, G Naresh

2016-01-01

Antioxidants, chelating agents, and probiotics are used to manage the toxic effects of cadmium (Cd) and mercury (Hg). The aim of this study was to investigate the combined effects of antioxidants, chelating agents, and probiotics against heavy metal toxicity. Genetically modified probiotic Escherichia coli Nissle 1917 (EcN-20) producing a potent water soluble antioxidant pyrroloquinoline quinone (PQQ) was supplemented with oral citric acid and compared with another genetically modified probiotic EcN-21 producing PQQ and citric acid against oxidative stress induced by Cd and Hg. Rats were independently given 100 ppm Cd and 80 ppm Hg in drinking water for 4 wk. EcN-20 was found to be more effective than EcN-2 (EcN strain with genomic integration of vgb and gfp genes) with orally given PQQ against oxidative stress induced by Cd and Hg. EcN-20 supplemented with oral citric acid was more effective against Cd and Hg toxicity compared with EcN-2+citric acid (oral), EcN-2+PQQ (oral), EcN-2+PQQ (oral)+citric acid (oral), EcN-20, and EcN-21. However, protection shown by EcN-21 was similar to EcN-20. The combination therapy involving probiotic EcN-20 producing PQQ with citric acid given orally was found to be a moderately effective strategy against toxicity induced by Cd and Hg, whereas the protective effect of EcN-21 was the same as EcN-20. Copyright © 2016 Elsevier Inc. All rights reserved.

Day/night difference in extradural cortical stimulation for motor relearning in a subacute stroke rat model.

PubMed

Kim, Joo Yeon; Sun, Woong; Park, Eunhee; Lee, Jiyeong; Kim, Hyun; Shin, Yong-Il; Kim, Yun-Hee; Chang, Won Hyuk

2016-02-24

The aim of this study was to assess the proper timing of extradural cortical stimulation (ECS) on the motor relearning in a rat model of subacute photothrombotic stroke. Photothrombotic infarction was induced on the dominant sensorimotor cortex in male Sprague-Dawley rats after training in a single-pellet reaching task (SPRT). Rats were randomly divided into three groups after stroke: ECS during the inactive period (Day-ECS group), ECS during the active period (Night-ECS group) and no ECS (Non-stimulated group). Six sham-operated rats were assigned to the control group. The Day- and Night-ECS group received continuous ECS for 12 hours during the day or night for 2 weeks from day 4 after the stroke. Behavioral assessment with SPRT was performed daily. SPRT showed a significantly faster and greater improvement in the Day and Night-ECS groups than in the Non-stimulated group. In the Day- and Night-ECS groups, the success rate of SPRT differed significantly from Non-stimulated group on day 11 and day 8, respectively. In addition, the Night-ECS group showed a significantly higher SPRT success rate than the Day-ECS group from days 10 to 13. ECS during the active period might be more effective for motor relearning in the subacute stroke rat model.

Evaluating the role of phase I expansion cohorts in oncologic drug development.

PubMed

Norris, Robin E; Behtaj, Mohadese; Fu, Pingfu; Dowlati, Afshin

2017-02-01

Importance Use of expansion cohorts (EC) in phase I trials is increasing. However, the utility of phase I EC in aiding drug development is unclear. We sought to determine factors associated with the inclusion of EC in phase I studies and the impact of EC on subsequent clinical development. Methods We performed a systematic review of all phase I trials published in the Journal of Clinical Oncology between June 2004 and May 2014. Presence of an EC, number of participants, funding source, class of agent, tumor type, and maximum tolerated dose (MTD)/recommended phase 2 dose (RP2D) were identified. Subsequent conduct of phase II studies and FDA approval of the study agent was also assessed. Results We identified 252 phase I studies. An EC was included in 105 studies. Average accrual on EC studies was 47 compared to 31 in studies without EC (p < 0.0001). There was no impact of time on the inclusion of EC. Only 4 % of phase I studies with an EC provided sample size justification. Source of funding had the only significant association with inclusion of EC. Addition of a phase I EC did not impact the phase I MTD/RP2D, subsequent phase II trial, or FDA approval. Conclusion The importance of including an EC in phase I trials is subject to ongoing debate. Our results demonstrated little benefit to including EC in phase I studies. These findings support that innovative design strategies are needed to optimize the utility of EC in phase I studies.

78 FR 56597 - Airworthiness Directives; Eurocopter Deutschland GmbH Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2013-09-13

... Airworthiness Directives; Eurocopter Deutschland GmbH Helicopters AGENCY: Federal Aviation Administration (FAA... Deutschland GmbH (ECD) Model EC135P1, EC135P2, EC135P2+, EC135T1, EC135T2, and EC135T2+ helicopters with... directive (AD): 2013-18-05 Eurocopter Deutschland GmbH: Amendment 39-17578; Docket No. FAA-2013-0398...

78 FR 26715 - Airworthiness Directives; Eurocopter Deutschland GmbH Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2013-05-08

... Deutschland GmbH Helicopters AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed... GmbH (ECD) Model EC135P1, EC135P2, EC135P2+, EC135T1, EC135T2, and EC135T2+ helicopters with certain... airworthiness directive (AD): Eurocopter Deutschland GmbH: Docket No. FAA-2013-0398; Directorate Identifier 2011...

Stabilization of Wind Energy Conversion System with Hydrogen Generator by Using EDLC Energy Storage System

NASA Astrophysics Data System (ADS)

Shishido, Seiji; Takahashi, Rion; Murata, Toshiaki; Tamura, Junji; Sugimasa, Masatoshi; Komura, Akiyoshi; Futami, Motoo; Ichinose, Masaya; Ide, Kazumasa

The spread of wind power generation is progressed hugely in recent years from a viewpoint of environmental problems including global warming. Though wind power is considered as a very prospective energy source, wind power fluctuation due to the random fluctuation of wind speed has still created some problems. Therefore, research has been performed how to smooth the wind power fluctuation. This paper proposes Energy Capacitor System (ECS) for the smoothing of wind power which consists of Electric Double-Layer Capacitor (EDLC) and power electronics devices and works as an electric power storage system. Moreover, hydrogen has received much attention in recent years from a viewpoint of exhaustion problem of fossil fuel. Therefore it is also proposed that a hydrogen generator is installed at the wind farm to generate hydrogen. In this paper, the effectiveness of the proposed system is verified by the simulation analyses using PSCAD/EMTDC.

Solvation-controlled lithium-ion complexes in a nonflammable solvent containing ethylene carbonate: structural and electrochemical aspects.

PubMed

Sogawa, Michiru; Kawanoue, Hikaru; Todorov, Yanko Marinov; Hirayama, Daisuke; Mimura, Hideyuki; Yoshimoto, Nobuko; Morita, Masayuki; Fujii, Kenta

2018-02-28

The structural and electrochemical properties of lithium-ion solvation complexes in a nonflammable organic solvent, tris(2,2,2-trifluoroethyl)phosphate (TFEP) containing ethylene carbonate (EC), were investigated using vibrational spectroscopic and electrochemical measurements. Based on quantitative Raman and infrared (IR) spectral analysis of the Li bis(trifluoromethanesulfonyl)amide (TFSA) salt in TFEP + EC electrolytes, we successfully evaluated the individual solvation numbers of EC (n EC ), TFEP (n TFEP ), and TFSA - (n TFSA ) in the first solvation sphere of the Li-ion. We found that the n EC value linearly increased with increasing EC mole fraction (x EC ), whereas the n TFEP and n TFSA values gradually decreased with increasing n EC . The ionic conductivity and viscosity (Walden plots) indicated that mainly Li + TFSA - ion pairs formed in neat TFEP (x EC = 0). This ion pair gradually dissociated into positively charged Li-ion complexes as x EC increased, which was consistent with the Raman/IR spectroscopy results. The redox reaction corresponding to an insertion/desertion of Li-ion into/from the graphite electrode occurred in the LiTFSA/TFEP + EC system at x EC ≥ 0.25. The same was not observed in the lower x EC cases. We discussed the relation between Li-ion solvation and electrode reaction behaviors at the molecular level and proposed that n EC plays a crucial role in the electrode reaction, particularly in terms of solid electrolyte interphase formation on the graphite electrode.

42 CFR 488.115 - Care guidelines.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 42 Public Health 5 2010-10-01 2010-10-01 false Care guidelines. 488.115 Section 488.115 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED... § 488.115 Care guidelines. EC01JA91.110 EC01JA91.111 EC01JA91.112 EC01JA91.113 EC01JA91.114 EC01JA91.115...

Stable estimate of primary OC/EC ratios in the EC tracer method

NASA Astrophysics Data System (ADS)

Chu, Shao-Hang

In fine particulate matter studies, the primary OC/EC ratio plays an important role in estimating the secondary organic aerosol contribution to PM2.5 concentrations using the EC tracer method. In this study, numerical experiments are carried out to test and compare various statistical techniques in the estimation of primary OC/EC ratios. The influence of random measurement errors in both primary OC and EC measurements on the estimation of the expected primary OC/EC ratios is examined. It is found that random measurement errors in EC generally create an underestimation of the slope and an overestimation of the intercept of the ordinary least-squares regression line. The Deming regression analysis performs much better than the ordinary regression, but it tends to overcorrect the problem by slightly overestimating the slope and underestimating the intercept. Averaging the ratios directly is usually undesirable because the average is strongly influenced by unrealistically high values of OC/EC ratios resulting from random measurement errors at low EC concentrations. The errors generally result in a skewed distribution of the OC/EC ratios even if the parent distributions of OC and EC are close to normal. When measured OC contains a significant amount of non-combustion OC Deming regression is a much better tool and should be used to estimate both the primary OC/EC ratio and the non-combustion OC. However, if the non-combustion OC is negligibly small the best and most robust estimator of the OC/EC ratio turns out to be the simple ratio of the OC and EC averages. It not only reduces random errors by averaging individual variables separately but also acts as a weighted average of ratios to minimize the influence of unrealistically high OC/EC ratios created by measurement errors at low EC concentrations. The median of OC/EC ratios ranks a close second, and the geometric mean of ratios ranks third. This is because their estimations are insensitive to questionable extreme values. A real world example is given using the ambient data collected from an Atlanta STN site during the winter of 2001-2002.

Procedure for the Isolation of Endothelial Cells from Human Cerebral Arteriovenous Malformation (cAVM) Tissues.

PubMed

Hao, Qiang; Chen, Xiao-Lin; Ma, Li; Wang, Tong-Tong; Hu, Yue; Zhao, Yuan-Li

2018-01-01

In this study, we successfully established a stable method for the isolation of endothelial cells (ECs) from human cerebral arteriovenous malformation (cAVM) tissues. Despite human cAVM tissues having a minor population of ECs, they play an important role in the manifestation and development of cAVM as well as in hemorrhagic stroke and thrombogenesis. To characterize and understand the biology of ECs in human cAVM (cAVM-ECs), methods for the isolation and purification of these cells are necessary. We have developed this method to reliably obtain pure populations of ECs from cAVMs. To obtain pure cell populations, cAVM tissues were mechanically and enzymatically digested and the resulting single cAVM-ECs suspensions were then labeled with antibodies of specific cell antigens and selected by flow cytometry. Purified ECs were detected using specific makers of ECs by immunostaining and used to study different cellular mechanisms. Compared to the different methods of isolating ECs from tissues, we could isolate ECs from cAVMs confidently, and the numbers of cAVM-ECs harvested were almost similar to the amounts present in vessel components. In addition to optimizing the protocol for isolation of ECs from human cAVM tissues, the protocol could also be applied to isolate ECs from other human neurovascular-diseased tissues. Depending on the tissues, the whole procedure could be completed in about 20 days.

Multilocus enzyme electrophoresis on agarose gel as an aid to the identification of entomopathogenic Bacillus sphaericus strains.

PubMed

Zahner, V; Rabinovitch, L; Cavados, C F; Momen, H

1994-04-01

Sixty strains of Bacillus sphaericus, including 31 insect pathogens were studied by multilocus enzyme electrophoresis and were classified into 44 zymovars (electrophoretic types). Among the entomopathogenic strains, 11 belong to the same zymovar (Z59) indicating a widespread frequent genotype. Bands of enzyme activity were not detected among the strains for the loci GPI (E.C.5.3.1.9), G6P (E.C.1.1.1.49), 6PG (E.C.1.1.1.44) and ME (E.C.1.1.1.40). The enzymatic loci NP (E.C.2.4.2.1) and ACON (E.C.4.2.1.3) were monomorphic while the other enzymes, MDH (E.C.1.1.1.37), LeDH (E.C.1.4.1.9), ADH (E.C.1.4.1.1), EST (E.C.3.1.1.1), PEP-2 (E.C.3.4.11.1), PEP-3 (E.C.3.4.11) and PEP-D (E.C. 3.4.13.9) were polymorphic. The genetic variation in the non-insect pathogenic group seemed to be greater than in the entomopathogenic group. This latter group appears to be distinct from other strains of these species. All insect pathogens were recovered in the same phenetic cluster and a diagnostic allele is reported for the identification of entomopathogenic strains.

Effects of cellular origin on differentiation of human induced pluripotent stem cell–derived endothelial cells

PubMed Central

Zhao, Ming-Tao; Jahanbani, Fereshteh; Lee, Won Hee; Snyder, Michael P.

2016-01-01

Human induced pluripotent stem cells (iPSCs) can be derived from various types of somatic cells by transient overexpression of 4 Yamanaka factors (OCT4, SOX2, C-MYC, and KLF4). Patient-specific iPSC derivatives (e.g., neuronal, cardiac, hepatic, muscular, and endothelial cells [ECs]) hold great promise in drug discovery and regenerative medicine. In this study, we aimed to evaluate whether the cellular origin can affect the differentiation, in vivo behavior, and single-cell gene expression signatures of human iPSC–derived ECs. We derived human iPSCs from 3 types of somatic cells of the same individuals: fibroblasts (FB-iPSCs), ECs (EC-iPSCs), and cardiac progenitor cells (CPC-iPSCs). We then differentiated them into ECs by sequential administration of Activin, BMP4, bFGF, and VEGF. EC-iPSCs at early passage (10 < P < 20) showed higher EC differentiation propensity and gene expression of EC-specific markers (PECAM1 and NOS3) than FB-iPSCs and CPC-iPSCs. In vivo transplanted EC-iPSC–ECs were recovered with a higher percentage of CD31+ population and expressed higher EC-specific gene expression markers (PECAM1, KDR, and ICAM) as revealed by microfluidic single-cell quantitative PCR (qPCR). In vitro EC-iPSC–ECs maintained a higher CD31+ population than FB-iPSC–ECs and CPC-iPSC–ECs with long-term culturing and passaging. These results indicate that cellular origin may influence lineage differentiation propensity of human iPSCs; hence, the somatic memory carried by early passage iPSCs should be carefully considered before clinical translation. PMID:27398408

The politics of place: presidential voting patterns and Providers' prescription of emergency contraception.

PubMed

Cleland, Kelly; Wagner, Brandon; Batur, Pelin; McNamara, Megan; Wu, Justine; Rothberg, Michael B

2018-05-17

The most effective forms of emergency contraception (EC) require a prescription or a medical procedure; therefore, provider willingness to offer EC remains critical to patient access. This study seeks to assess whether political alignment of a provider's county is associated with provider attitudes and behaviors regarding EC. We analyzed survey data collected from 1313 healthcare providers from February 2013 to April 2014 at 14 academic medical centers in the United States. Using logistic regression, we estimated associations between the county political alignment of a provider's practice and his or her EC-related beliefs and practices: 1) if the provider is aware of the most effective EC methods; 2) if knowing that a hypothetical EC method prevented implantation would make a provider less likely to prescribe that method because of personal ethical or religious reasons; and 3) if the provider prescribes any form of EC in his or her practice. In multivariate models, a one percentage-point increase in county Republican vote share was associated with a 2.9% decrease in the odds of a provider prescribing EC, after accounting for provider knowledge and attitudes about EC. EC provides a critical last chance to prevent pregnancy after unprotected sex, yet women living in Republican-leaning counties may face difficulty obtaining EC from healthcare providers. Programs seeking to improve access to EC should focus on areas likely to have fewer providers willing to prescribe EC, which may be those that are more Republican-leaning. The most effective forms of emergency contraception (EC) require a prescription or a medical procedure; therefore, provider willingness to offer EC remains critical to patient access. Women living in Republican-leaning counties may face difficulty obtaining emergency contraception from healthcare providers. Copyright © 2018. Published by Elsevier Inc.

Emerging effortful control in toddlerhood: the role of infant orienting/regulation, maternal effortful control, and maternal time spent in caregiving activities.

PubMed

Bridgett, David J; Gartstein, Maria A; Putnam, Samuel P; Lance, Kate Oddi; Iddins, Erin; Waits, Robin; Vanvleet, Jessica; Lee, Lindsay

2011-02-01

Latent growth modeling (LGM) was used to examine the contribution of changes in infant orienting/regulation (O/R) to the emergence of toddler effortful control (EC), the contributions of maternal EC to the development of infant O/R and the emergence of toddler EC, the influence of maternal time spent in caregiving activities on toddler EC and the slope of infant O/R, and the contribution of maternal EC to subsequent maternal time spent in caregiving activities. Mothers from 158 families completed a self-report measure of EC when their infants were 4 months of age, a measure of infant O/R when their infants were 4, 6, 8, 10, and 12 months of age, and a measure of toddler EC when their children reached 18 months of age. Information concerning maternal time spent in various interactive caregiving activities was collected when infants were 6 months old. Results indicated higher maternal EC predicted interindividual differences in the intercept (i.e., higher intercepts), but not slope, of infant O/R and that higher maternal EC, higher infant O/R intercept, and higher infant O/R slope contributed to higher toddler EC. Furthermore, higher maternal EC predicted greater maternal time spent in interactive caregiving activities with their infants and greater maternal time in interactive caregiving with infants also contributed to higher toddler EC after controlling for maternal EC. These findings contribute to the understanding of the influence of maternal EC, directly and through caregiving, on toddler EC. Additional implications as they are related to early developing regulatory aspects of temperament are discussed. Copyright © 2010 Elsevier Inc. All rights reserved.

Nitroprusside and ECS-induced retrograde amnesia.

PubMed

Sudha, S; Andrade, C; Anand, A; Guido, S; Venkataraman, B V

2001-03-01

Previous research found that the administration of verapamil and felodipine immediately before electroconvulsive shocks (ECS) attenuated ECS-induced retrograde amnesia. This study examined whether sodium nitroprusside, an antihypertensive drug that does not affect calcium channels, has a similar action. Adult male Sprague-Dawley rats received nitroprusside (0.5 mg/kg ip) or saline 3 minutes before each of three once-daily true or sham ECS. Retention of pre-ECS learning was studied 1 day after ECS using a passive avoidance task. Nitroprusside was associated with increased seizure duration in ECS-treated rats, and with enhanced recall in both true and sham ECS groups. The latter finding suggests that nitroprusside nonspecifically improves cognitive functions, and does not support the hypothesis that ECS-induced cognitive impairment is a result of blood-brain barrier breach. Nitric oxide mechanisms may underlie the benefits purveyed by nitroprusside.

Pre-electroconvulsive shock administration of calcium channel blockers reduces retrograde amnesia induced by ECS.

PubMed

Sushma, M; Sudha, S; Guido, S

2004-11-01

Effect of pre-electroconvulsive shock (ECS) administration of calcium channel blockers (CCBs) like verapamil, diltiazem, nifedipine, nimodipine, flunarizine and cinnarizine on retrograde amnesia induced by ECS was examined using passive avoidance paradigm in rats. The groups (Gr 1-7) of adult, male Wistar rats received true ECS with CCBs (5mg/kg; i.p) or vehicle (10 ml/kg; ip) and other groups (Gr 8-14) received sham ECS with CCBs (5mg/kg; i.p) or vehicle (10 ml/kg; i.p). The anti-amnestic activity of CCBs were evaluated using the passive avoidance paradigm in rats. Results showed that, the baseline latencies for all the groups did not differ significantly. Rats receiving true ECS produced significantly lower latencies. There was increase in the post ECS step through latencies of the rats administered CCBs before ECS. Therefore, pre-ECS administration of calcium channel blockers might reduce retrograde amnesia produced by ECS without altering seizure duration.

Improving adolescent knowledge of emergency contraception: challenges and solutions

PubMed Central

Seetharaman, Sujatha; Yen, Sophia; Ammerman, Seth D

2016-01-01

Globally, unintended adolescent pregnancies pose a significant burden. One of the most important tools that can help prevent unintended pregnancy is the timely use of emergency contraception (EC), which in turn will decrease the need for abortions and complications related to adolescent pregnancies. Indications for the use of EC include unprotected sexual intercourse, contraceptive failure, or sexual assault. Use of EC is recommended within 120 hours, though is most effective if used as soon as possible after unprotected sex. To use EC, adolescents need to be equipped with knowledge about the various EC methods, and how and where EC can be accessed. Great variability in the knowledge and use of EC around the world exists, which is a major barrier to its use. The aims of this paper were to 1) provide a brief overview of EC, 2) discuss key social determinants affecting knowledge and use of EC, and 3) explore best practices for overcoming the barriers of lack of knowledge, use, and access of EC. PMID:29386948

Laminar activity in the hippocampus and entorhinal cortex related to novelty and episodic encoding

PubMed Central

Maass, Anne; Schütze, Hartmut; Speck, Oliver; Yonelinas, Andrew; Tempelmann, Claus; Heinze, Hans-Jochen; Berron, David; Cardenas-Blanco, Arturo; Brodersen, Kay H.; Enno Stephan, Klaas; Düzel, Emrah

2014-01-01

The ability to form long-term memories for novel events depends on information processing within the hippocampus (HC) and entorhinal cortex (EC). The HC–EC circuitry shows a quantitative segregation of anatomical directionality into different neuronal layers. Whereas superficial EC layers mainly project to dentate gyrus (DG), CA3 and apical CA1 layers, HC output is primarily sent from pyramidal CA1 layers and subiculum to deep EC layers. Here we utilize this directionality information by measuring encoding activity within HC/EC subregions with 7 T high resolution functional magnetic resonance imaging (fMRI). Multivariate Bayes decoding within HC/EC subregions shows that processing of novel information most strongly engages the input structures (superficial EC and DG/CA2–3), whereas subsequent memory is more dependent on activation of output regions (deep EC and pyramidal CA1). This suggests that while novelty processing is strongly related to HC–EC input pathways, the memory fate of a novel stimulus depends more on HC–EC output. PMID:25424131

Endothelial cells (ECs) for vascular tissue engineering: venous ECs are less thrombogenic than arterial ECs.

PubMed

Geenen, I L A; Molin, D G M; van den Akker, N M S; Jeukens, F; Spronk, H M; Schurink, G W H; Post, M J

2015-05-01

Primary endothelial cells (ECs) are the preferred cellular source for luminal seeding of tissue-engineered (TE) vascular grafts. Research into the potential of ECs for vascular TE has focused particularly on venous rather than arterial ECs. In this study we evaluated the functional characteristics of arterial and venous ECs, relevant for vascular TE. Porcine ECs were isolated from femoral artery (PFAECs) and vein (PFVECs). The proliferation rate was comparable for both EC sources, whereas migration, determined through a wound-healing assay, was less profound for PFVECs. EC adhesion was lower for PFVECs on collagen I, measured after 10 min of arterial shear stress. Gene expression was analysed by qRT-PCR for ECs cultured under static conditions and after exposure to arterial shear stress and revealed differences in gene expression, with lower expression of EphrinB2 and VCAM-1 and higher levels of vWF and COUP-TFII in PFVECs than in PFAECs. PFVECs exhibited diminished platelet adhesion under flow and cell-based thrombin generation was delayed for PFVECs, indicating diminished tissue factor (TF) activity. After stimulation, prostacyclin secretion, but not nitric oxide (NO), was lower in PFVECs. Our data support the use of venous ECs for TE because of their beneficial antithrombogenic profile. Copyright © 2012 John Wiley & Sons, Ltd.

Development and internal validation of a side-specific, multiparametric magnetic resonance imaging-based nomogram for the prediction of extracapsular extension of prostate cancer.

PubMed

Martini, Alberto; Gupta, Akriti; Lewis, Sara C; Cumarasamy, Shivaram; Haines, Kenneth G; Briganti, Alberto; Montorsi, Francesco; Tewari, Ashutosh K

2018-04-19

To develop a nomogram for predicting side-specific extracapsular extension (ECE) for planning nerve-sparing radical prostatectomy. We retrospectively analysed data from 561 patients who underwent robot-assisted radical prostatectomy between February 2014 and October 2015. To develop a side-specific predictive model, we considered the prostatic lobes separately. Four variables were included: prostate-specific antigen; highest ipsilateral biopsy Gleason grade; highest ipsilateral percentage core involvement; and ECE on multiparametric magnetic resonance imaging (mpMRI). A multivariable logistic regression analysis was fitted to predict side-specific ECE. A nomogram was built based on the coefficients of the logit function. Internal validation was performed using 'leave-one-out' cross-validation. Calibration was graphically investigated. The decision curve analysis was used to evaluate the net clinical benefit. The study population consisted of 829 side-specific cases, after excluding negative biopsy observations (n = 293). ECE was reported on mpMRI and final pathology in 115 (14%) and 142 (17.1%) cases, respectively. Among these, mpMRI was able to predict ECE correctly in 57 (40.1%) cases. All variables in the model except highest percentage core involvement were predictors of ECE (all P ≤ 0.006). All variables were considered for inclusion in the nomogram. After internal validation, the area under the curve was 82.11%. The model demonstrated excellent calibration and improved clinical risk prediction, especially when compared with relying on mpMRI prediction of ECE alone. When retrospectively applying the nomogram-derived probability, using a 20% threshold for performing nerve-sparing, nine out of 14 positive surgical margins (PSMs) at the site of ECE resulted above the threshold. We developed an easy-to-use model for the prediction of side-specific ECE, and hope it serves as a tool for planning nerve-sparing radical prostatectomy and in the reduction of PSM in future series. © 2018 The Authors BJU International © 2018 BJU International Published by John Wiley & Sons Ltd.

[Oncological results of active surveillance in prostate cancer: A retrospective multicentric cohort].

PubMed

Mortier, P; Bastide, C; Lechevallier, E; Walz, J; Fournier, R; Savoie, P-H; Ben Othman, K; Giorgi, R; André, M; Giusiano, S; Rossi, D

2017-01-01

To report oncological outcomes of patients with prostate cancer undergoing active surveillance according to SURACAP criteria. This multicentric study included patients who were initially treated with active surveillance for localized prostate cancer according to the SURACAP criteria. The duration of active surveillance as well as the causes of discontinuing the protocol and the definitive pathological results of patients who further underwent radical prostatectomy were retrospectively evaluated. The predictors of discontinuing active surveillance were assessed using a univariable Cox Model. In addition, the predictive value of initial MRI was assessed for patients who performed such imagery. Between 2007 and 2013, 80 patients were included, with a median age of 64 years [47-74]. Median follow-up was 52.9 months [24-108]. At 5 years follow-up, 43.4% patients were still under surveillance. Among patients that underwent surgery, 17.8% had an extra-capsular extension. The risk of discontinuing was not significantly greater for patients with tumor size of 2 or 3mm versus 1mm (HR=0.9 [0.46-1.75], P=0.763), 2 positives cores versus 1 (HR=0.98 [0.48-2.02], P=0.967), T2a vs. T1c stage (HR=2.18 [0.77-6.18], P=0.133), increased PSA level (HR=1 [0.96-1.15], P=0.975) or the patient's age (HR=1 [0.93-1.16], P=0.966). Among the 50 patients who performed initial MRI, the results of such imagery was not significantly associated to the risk of discontinuing active surveillance MRI (HR=1.49 [0.63-3.52], P=0.36). Although this study reveals a high rate of release from active surveillance at 5 years, the rate of extra-capsular tumors reported in the group of patients that underwent surgery is among the lowest in literature. 4. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Extracapsular cataract extraction training: junior ophthalmology residents' self-reported satisfaction level with their proficiency and initial learning barrier.

PubMed

Ting, Daniel Shu Wei; Tan, Sarah; Lee, Shu Yen; Rosman, Mohamad; Aw, Ai Tee; Yeo, Ian Yew San

2015-07-01

To investigate residents' self-reported satisfaction level with their proficiency in extracapsular cataract extraction (ECCE) surgery and the initial barriers to learning the procedure. This is a single-centre prospective descriptive case series involving eight first-year ophthalmology residents in Singapore National Eye Center. We recorded the demographics, frequency of review by the residents of their own surgical videos and their satisfaction level with their proficiency at each of the ECCE steps using a 5-point Likert scale. All ECCE surgical videos between October 2013 and May 2014 were collected and analysed for the overall time taken for the surgery and the time taken to perform the individual steps of the procedure. The mean age of the residents was 27.6 ± 1.5 years and 62.5% (5/8) were women. More than half (62.5%, 5/8) reviewed their own surgical videos while 37.5% (3/8) discussed the surgical videos with their peers or supervisors. Of the ECCE steps, the residents were most dissatisfied with their proficiency in performing irrigation and aspiration (87.5%, 7/8), followed by suturing (62.5%, 5/8), intraocular lens insertion (62.5%, 5/8) and tin can capsulotomy (62.5%, 5/8). The average time taken for each ECCE case was 55.0 ± 12.2 min and, of all the steps, most time was spent on suturing (20.5 ± 6.8 min), followed by irrigation and aspiration (5.5 ± 3.6 min) and tin can capsulotomy (3.3 ± 1.8 min). The first-year ophthalmology residents were most dissatisfied with their proficiency in irrigation/aspiration, suturing and tin can capsulotomy. More training needs to be directed to these areas during teaching sessions in the operating room, wet laboratory or cataract simulation training sessions. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Analysis of 30 breast implant rupture cases.

PubMed

Tark, Kwan Chul; Jeong, Hii Sun; Roh, Tae Suk; Choi, Jong Woo

2005-01-01

Breast implants used for augmentation mammoplasty or breast reconstruction could rupture from various causes such as trauma or spontaneous failure. The objectives of this study were to investigate the relationships between the causes of implant rupture and the degree of capsular contracture, and then to evaluate the relative efficacies of specific signs on magnetic resonance imaging (MRI) known to be beneficial for diagnosing the rupture. A retrospective review identified patients with prosthetic implant rupture or impending rupture treated by the senior author. The 30 cases of implant rupture available for review were classified into two groups: intracapsular and extracapsular ruptures. The 30 cases of breast implant ruptures were analyzed with respect to the clinical symptoms and signs, the causes of rupture, the degree of capsular contracture, and therapeutic plans. Among the 30 cases, 14 patients who had undergone MRI during the diagnostic period were analyzed with respect to the relationships between MRI readings and operative findings. Spontaneous rupture of membranes was most common (80%), followed by failure because of trauma (7%) and valve or implant base (4%). The symptoms during implant rupture were contour deformity, palpated mass-like lesions, pain, and focal inflammation. According to the analysis of specific MRI signs, the sensitivity and specificity of the linguine sign were 87% and 100%, respectively, for intracapsular rupture. For extracapsular rupture, the sensitivity and specificity of the linguine sign were, respectively, 67% and 75%. The sensitivity and specificity of the rat-tail sign and tear drop sign were 14% and 50%, respectively. Breast implant rupture was correlated with the degree of capsular contracture in our study. Among the various specific MRI signs used in diagnosing the rupture, the linguine sign was reliable and had a high sensitivity and specificity, especially in cases of intracapsular rupture. On the other hand, the rat-tail and tear drop signs were nonspecific signs for diagnosing the rupture of breast implant.

Once-Daily Radiation Therapy for Inflammatory Breast Cancer

DOE Office of Scientific and Technical Information (OSTI.GOV)

Brown, Lindsay; Harmsen, William; Blanchard, Miran

2014-08-01

Purpose: Inflammatory breast cancer (IBC) is a rare and aggressive breast cancer variant treated with multimodality therapy. A variety of approaches intended to escalate the intensity and efficacy of radiation therapy have been reported, including twice-daily radiation therapy, dose escalation, and aggressive use of bolus. Herein, we examine our outcomes for patients treated with once-daily radiation therapy with aggressive bolus utilization, focusing on treatment technique. Methods and Materials: A retrospective review of patients with nonmetastatic IBC treated from January 1, 2000, through December 31, 2010, was performed. Locoregional control (LRC), disease-free survival (DFS), overall survival (OS) and predictors thereof weremore » assessed. Results: Fifty-two women with IBC were identified, 49 (94%) of whom were treated with neoadjuvant chemotherapy. All underwent mastectomy followed by adjuvant radiation therapy. Radiation was delivered in once-daily fractions of 1.8 to 2.25 Gy (median, 2 Gy). Patients were typically treated with daily 1-cm bolus throughout treatment, and 33 (63%) received a subsequent boost to the mastectomy scar. Five-year Kaplan Meier survival estimates for LRC, DFS, and OS were 81%, 56%, and 64%, respectively. Locoregional recurrence was associated with poorer OS (P<.001; hazard ratio [HR], 4.1). Extracapsular extension was associated with worse LRC (P=.02), DFS (P=.007), and OS (P=.002). Age greater than 50 years was associated with better DFS (P=.03). Pathologic complete response was associated with a trend toward improved LRC (P=.06). Conclusions: Once-daily radiation therapy with aggressive use of bolus for IBC results in outcomes consistent with previous reports using various intensified radiation therapy regimens. LRC remains a challenge despite modern systemic therapy. Extracapsular extension, age ≤50 years, and lack of complete response to chemotherapy appear to be associated with worse outcomes. Novel strategies are needed in IBC, particularly among these subsets of patients.« less

Accuracy of Computed Tomography for Predicting Pathologic Nodal Extracapsular Extension in Patients With Head-and-Neck Cancer Undergoing Initial Surgical Resection

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prabhu, Roshan S., E-mail: roshansprabhu@gmail.com; Winship Cancer Institute, Emory University, Atlanta, Georgia; Magliocca, Kelly R.

2014-01-01

Purpose: Nodal extracapsular extension (ECE) in patients with head-and-neck cancer increases the loco-regional failure risk and is an indication for adjuvant chemoradiation therapy (CRT). To reduce the risk of requiring trimodality therapy, patients with head-and-neck cancer who are surgical candidates are often treated with definitive CRT when preoperative computed tomographic imaging suggests radiographic ECE. The purpose of this study was to assess the accuracy of preoperative CT imaging for predicting pathologic nodal ECE (pECE). Methods and Materials: The study population consisted of 432 consecutive patients with oral cavity or locally advanced/nonfunctional laryngeal cancer who underwent preoperative CT imaging before initialmore » surgical resection and neck dissection. Specimens with pECE had the extent of ECE graded on a scale from 1 to 4. Results: Radiographic ECE was documented in 46 patients (10.6%), and pECE was observed in 87 (20.1%). Sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 43.7%, 97.7%, 82.6%, and 87.3%, respectively. The sensitivity of radiographic ECE increased from 18.8% for grade 1 to 2 ECE, to 52.9% for grade 3, and 72.2% for grade 4. Radiographic ECE criteria of adjacent structure invasion was a better predictor than irregular borders/fat stranding for pECE. Conclusions: Radiographic ECE has poor sensitivity, but excellent specificity for pECE in patients who undergo initial surgical resection. PPV and NPV are reasonable for clinical decision making. The performance of preoperative CT imaging increased as pECE grade increased. Patients with resectable head-and-neck cancer with radiographic ECE based on adjacent structure invasion are at high risk for high-grade pECE requiring adjuvant CRT when treated with initial surgery; definitive CRT as an alternative should be considered where appropriate.« less

Improving consent in patients undergoing surgery for fractured neck of femur.

PubMed

Thiruchandran, Gajendiran; McKean, Andrew R; Rudran, Branavan; Imam, Mohamed A; Yeong, Keefai; Hassan, Abdel

2018-05-02

Background Neck of femur fractures and their subsequent operative fixation are associated with high rates of perioperative morbidity and mortality. Consenting in this setting is suboptimal with the Montgomery court ruling changing the perspective of consent. This quality improvement project assessed the adequacy of consenting against British Orthopaedic Association-endorsed guidance and implemented a series of changes to improve the documentation of risks associated with surgery for fractured neck of femur. Methods Seventy consecutive patients who underwent any operative fixation of a neck of femur fracture were included over a 6-month period at a single centre. Patients unable to consent or without electronic notes were excluded. Consent forms were analysed and the documented potential risks or complications associated with surgery were compared to British Orthopaedic Association-endorsed guidance. A series of changes (using the plan, do study, act (PDSA) approach) was implemented to improve the adequacy of consent. Results Documentation of four out of 12 potential risks or complications was recorded in <50% of cases for patients with intracapsular fractures (n=35), and documentation of seven out of 12 potential risks or complications was recorded in <50% of cases for patients with extracapsular fractures (n=35). Re-audit following raising awareness and attaching consent guidance showed 100% documentation of potential risks or complications in patients with intracapsular and extracapsular fractures (n=70). A neck of femur fracture-specific consent form has been implemented which will hopefully lead to sustained improvement. Conclusions Consenting patients with fractured neck of femur for surgery in the authors' unit was suboptimal when compared to British Orthopaedic Association-endorsed consent guidance. This project has shown that ensuring such guidance is readily available has improved the adequacy of consent. The authors hope that introduction of a neck of femur fracture-specific consent form within their unit will lead to sustained adequate documentation of risks associated with surgery.

In vitro characteristics of endothelial cells prepared from human cerebral arteriovenous malformation lesions using a novel method.

PubMed

Hao, Q; Chen, X L; Ma, L; Ye, X; Wang, H; Wang, T T; Hu, Y; Zhao, Y L

2018-03-01

The cerebral arteriovenous malformation (cAVM) is a usual and continually unaware reason of heamorrhage and seizure. It contains of feeder arteries, drain veins and abnormal vessel nets. However, pathologic mechanisms of the development of cAVM are unknown. The purpose of this study was to explore a novel protocol to isolate, culture and passage endothelial cells (ECs) from human cAVM lesions. We developed a protocol for isolating and growing ECs from eight patients with cAVM. The tissues were microsurgically removed from cAVM lesion and were digested by 0.25% Trypsin-EDTA, and cultured in ECM medium. ECs were selected by FACS and confirmed their EC origin by immunocytochemistry of the basic expression patterns of CD31 and CD34. LDL-uptake and capillary tube formation were used to determine their functional features. The isolated cAVM-ECs exhibited contact inhibition of growth and appearance of rounded cobblestone. cAVM-ECs were CD31- and CD34-positive. In functional assays, cAVM-ECs were able to uptake LDL and form capillary tubes. cAVM-ECs from younger patients proliferated faster than that from elders, and cAVM-ECs were less stable than normal artery ECs. In addition, cAVM-ECs appeared to more easily transform into mesenchymal cells than normal artery ECs. Using the protocol, isolated cAVM-ECs are stably established, and retain their endothelial phenotypes. These cAVM-ECs may provide a biological tool to examine molecular phenotypes and mechanisms responsible for human cAVM. Copyright © 2017 Elsevier Inc. All rights reserved.

Correlation of hepatic fractional extracellular space using gadolinium enhanced MRI with liver stiffness using magnetic resonance elastography.

PubMed

Wells, Michael L; Moynagh, Michael R; Carter, Rickey E; Childs, Robert A; Leitch, Cameron E; Fletcher, Joel G; Yeh, Benjamin M; Venkatesh, Sudhakar K

2017-01-01

To compare MR hepatic fractional extracellular space (fECS) to liver stiffness (LS) with magnetic resonance elastography (MRE) for evaluation of liver fibrosis. 71 consecutive patients with suspected chronic liver disease underwent standard liver MRI with MR elastography and additional delayed Gd-DTPA-enhanced sequences at 5 and 10 min in order to calculate hepatic fECS (%) and LS (kilopascals, kPa). Two radiologists blinded to clinical history examined MR images and calculated fECS and LS in identical locations for every patient. Interobserver agreement was calculated using the intraclass correlation coefficient. Pearson's correlation was calculated for LS and fECS measures, as was the area under the receiver operatic curve (AUROC), sensitivity and specificity of fECS to predict liver stiffness ≥2.93 and ≥5 kPa. The sensitivity of fECS for detecting fibrosis was separately analyzed in the subgroup of patients without anatomic findings of cirrhosis. Substantial to excellent interobserver agreement for both LS and fECS measurements was seen with intraclass correlation of 0.88 (95% CI 0.81-0.92) for LS, 0.77 (95% CI 0.66-0.85) for fECS 5 and 0.76 (95% CI 0.64-0.84) for fECS 10 . A significant correlation was found between MRE and fECS 5 (r = 0.47, p < 0.0001) and fECS 10 (r = 0.44, p < 0.0001). The performance of fECS improved for detection of advanced fibrosis (≥5 kPa) with AUROC, sensitivity and specificity of 0.72, 38%, and 94% for fECS 5 and 0.72, 67%, and 66% for fECS 10 . fECS correlates modestly with MRE-determined LS. fECS at MRI is a simple calculation to perform and may represent a practical way to suggest the presence of fibrosis during routine liver evaluation.

SIRT1 Overexpression Maintains Cell Phenotype and Function of Endothelial Cells Derived from Induced Pluripotent Stem Cells.

PubMed

Jiang, Bin; Jen, Michele; Perrin, Louisiane; Wertheim, Jason A; Ameer, Guillermo A

2015-12-01

Endothelial cells (ECs) that are differentiated from induced pluripotent stem cells (iPSCs) can be used in establishing disease models for personalized drug discovery or developing patient-specific vascularized tissues or organoids. However, a number of technical challenges are often associated with iPSC-ECs in culture, including instability of the endothelial phenotype and limited cell proliferative capacity over time. Early senescence is believed to be the primary mechanism underlying these limitations. Sirtuin1 (SIRT1) is an NAD(+)-dependent deacetylase involved in the regulation of cell senescence, redox state, and inflammatory status. We hypothesize that overexpression of the SIRT1 gene in iPSC-ECs will maintain EC phenotype, function, and proliferative capacity by overcoming early cell senescence. SIRT1 gene was packaged into a lentiviral vector (LV-SIRT1) and transduced into iPSC-ECs at passage 4. Beginning with passage 5, iPSC-ECs exhibited a fibroblast-like morphology, whereas iPSC-ECs overexpressing SIRT1 maintained EC cobblestone morphology. SIRT1 overexpressing iPSC-ECs also exhibited a higher percentage of canonical markers of endothelia (LV-SIRT1 61.8% CD31(+) vs. LV-empty 31.7% CD31(+), P < 0.001; LV-SIRT1 46.3% CD144(+) vs. LV-empty 20.5% CD144(+), P < 0.02), with a higher nitric oxide synthesis, lower β-galactosidase production indicating decreased senescence (3.4% for LV-SIRT1 vs. 38.6% for LV-empty, P < 0.001), enhanced angiogenesis, increased deacetylation activity, and higher proliferation rate. SIRT1 overexpressing iPSC-ECs continued to proliferate through passage 9 with high purity of EC-like characteristics, while iPSC-ECs without SIRT1 overexpression became senescent after passage 5. Taken together, SIRT1 overexpression in iPSC-ECs maintains EC phenotype, improves EC function, and extends cell lifespan, overcoming critical hurdles associated with the use of iPSC-ECs in translational research.

Developmental regulation of ecdysone receptor (EcR) and EcR-controlled gene expression during pharate-adult development of honeybees (Apis mellifera)

PubMed Central

Mello, Tathyana R. P.; Aleixo, Aline C.; Pinheiro, Daniel G.; Nunes, Francis M. F.; Bitondi, Márcia M. G.; Hartfelder, Klaus; Barchuk, Angel R.; Simões, Zilá L. P.

2014-01-01

Major developmental transitions in multicellular organisms are driven by steroid hormones. In insects, these, together with juvenile hormone (JH), control development, metamorphosis, reproduction and aging, and are also suggested to play an important role in caste differentiation of social insects. Here, we aimed to determine how EcR transcription and ecdysteroid titers are related during honeybee postembryonic development and what may actually be the role of EcR in caste development of this social insect. In addition, we expected that knocking-down EcR gene expression would give us information on the participation of the respective protein in regulating downstream targets of EcR. We found that in Apis mellifera females, EcR-A is the predominantly expressed variant in postembryonic development, while EcR-B transcript levels are higher in embryos, indicating an early developmental switch in EcR function. During larval and pupal stages, EcR-B expression levels are very low, while EcR-A transcripts are more variable and abundant in workers compared to queens. Strikingly, these transcript levels are opposite to the ecdysteroid titer profile. 20-hydroxyecdysone (20E) application experiments revealed that low 20E levels induce EcR expression during development, whereas high ecdysteroid titers seem to be repressive. By means of RNAi-mediated knockdown (KD) of both EcR transcript variants we detected the differential expression of 234 poly-A+ transcripts encoding genes such as CYPs, MRJPs and certain hormone response genes (Kr-h1 and ftz-f1). EcR-KD also promoted the differential expression of 70 miRNAs, including highly conserved ones (e.g., miR-133 and miR-375), as well honeybee-specific ones (e.g., miR-3745 and miR-3761). Our results put in evidence a broad spectrum of EcR-controlled gene expression during postembryonic development of honeybees, revealing new facets of EcR biology in this social insect. PMID:25566327

Actively Transmitting New DCPs - Hydrometeorological Automated Data System

Science.gov Websites

CT ASPETUCK RIVER NEAR ASPETUCK, C 411343 -0731926 SIGNAL ENG. HG VB 2013085 USGS01 DE2234D6 010000 CT BYRAM RIVER AT PEMBERWICK 410137 -0733940 SIGNAL ENG. HG PC VB 2013085 USGS01 17955470 010000 CT CT-CL 223 411832 -0723255 UNKNOWN HG WV WV VB HG WV WV HG EC EC EC EC EC EC 2016154 USGS01 DD3C65BA

Sound pressure distribution within natural and artificial human ear canals: forward stimulation.

PubMed

Ravicz, Michael E; Tao Cheng, Jeffrey; Rosowski, John J

2014-12-01

This work is part of a study of the interaction of sound pressure in the ear canal (EC) with tympanic membrane (TM) surface displacement. Sound pressures were measured with 0.5-2 mm spacing at three locations within the shortened natural EC or an artificial EC in human temporal bones: near the TM surface, within the tympanic ring plane, and in a plane transverse to the long axis of the EC. Sound pressure was also measured at 2-mm intervals along the long EC axis. The sound field is described well by the size and direction of planar sound pressure gradients, the location and orientation of standing-wave nodal lines, and the location of longitudinal standing waves along the EC axis. Standing-wave nodal lines perpendicular to the long EC axis are present on the TM surface >11-16 kHz in the natural or artificial EC. The range of sound pressures was larger in the tympanic ring plane than at the TM surface or in the transverse EC plane. Longitudinal standing-wave patterns were stretched. The tympanic-ring sound field is a useful approximation of the TM sound field, and the artificial EC approximates the natural EC.

Testing the relationships between energy consumption, CO2 emissions, and economic growth in 24 African countries: a panel ARDL approach.

PubMed

Asongu, Simplice; El Montasser, Ghassen; Toumi, Hassen

2016-04-01

This study complements existing literature by examining the nexus between energy consumption (EC), CO2 emissions (CE), and economic growth (GDP; gross domestic product) in 24 African countries using a panel autoregressive distributed lag (ARDL) approach. The following findings are established. First, there is a long-run relationship between EC, CE, and GDP. Second, a long-term effect from CE to GDP and EC is apparent, with reciprocal paths. Third, the error correction mechanisms are consistently stable. However, in cases of disequilibrium, only EC can be significantly adjusted to its long-run relationship. Fourth, there is a long-run causality running from GDP and CE to EC. Fifth, we find causality running from either CE or both CE and EC to GDP, and inverse causal paths are observable. Causality from EC to GDP is not strong, which supports the conservative hypothesis. Sixth, the causal direction from EC to GDP remains unobservable in the short term. By contrast, the opposite path is observable. There are also no short-run causalities from GDP, or EC, or EC, and GDP to EC. Policy implications are discussed.

Visual gene-network analysis reveals the cancer gene co-expression in human endometrial cancer

PubMed Central

2014-01-01

Background Endometrial cancers (ECs) are the most common form of gynecologic malignancy. Recent studies have reported that ECs reveal distinct markers for molecular pathogenesis, which in turn is linked to the various histological types of ECs. To understand further the molecular events contributing to ECs and endometrial tumorigenesis in general, a more precise identification of cancer-associated molecules and signaling networks would be useful for the detection and monitoring of malignancy, improving clinical cancer therapy, and personalization of treatments. Results ECs-specific gene co-expression networks were constructed by differential expression analysis and weighted gene co-expression network analysis (WGCNA). Important pathways and putative cancer hub genes contribution to tumorigenesis of ECs were identified. An elastic-net regularized classification model was built using the cancer hub gene signatures to predict the phenotypic characteristics of ECs. The 19 cancer hub gene signatures had high predictive power to distinguish among three key principal features of ECs: grade, type, and stage. Intriguingly, these hub gene networks seem to contribute to ECs progression and malignancy via cell-cycle regulation, antigen processing and the citric acid (TCA) cycle. Conclusions The results of this study provide a powerful biomarker discovery platform to better understand the progression of ECs and to uncover potential therapeutic targets in the treatment of ECs. This information might lead to improved monitoring of ECs and resulting improvement of treatment of ECs, the 4th most common of cancer in women. PMID:24758163

Formulation and Evaluation of Morin-Loaded Solid Lipid Nanoparticles.

PubMed

Ikeuchi-Takahashi, Yuri; Ishihara, Chizuko; Onishi, Hiraku

2016-09-01

In this study, solid lipid nanoparticle (SLN) suspensions were prepared using a base of hard fat with or without ethylcellulose (EC) and polyvinyl alcohols (PVA) and polysorbate (Tween) 60 surfactants. Commercially available PVAs vary in their degree of saponification and polymerization, and the appropriate PVAs to form SLNs from hard fat with or without EC were investigated. A relatively low-saponification-degree PVA was required to reproducibly form SLN suspensions without EC and relatively high-saponification-degree PVAs were suitable for SLNs with EC. The release of morin from SLNs with EC was more sustained than that from SLNs without EC. The maximum plasma concentration (Cmax) of SLNs with and without EC were almost the same, and both were higher than that of a morin suspension. The area under the curve for 0 to 360 min (AUC0-360) of SLNs with EC was increased compared with those of a morin suspension and SLNs without EC. The median diameter of SLNs with EC and a very low-saponification-degree PVA was decreased compared to other formulation, and morin release was more sustained for this formulation. SLNs with EC and a very low-saponification-degree PVA showed higher Cmax and AUC0-360 than SLNs with EC lacking a very low-saponification-degree PVA. The optimized SLNs with EC and a very low-saponification-degree PVA improved bioavailability via increased accessibility to the enterocyte surface by decreased particle size and increased permeation of SLN encapsulated morin through the intestinal membrane by sustained release properties.

A comparison of the pro-angiogenic potential of human induced pluripotent stem cell derived endothelial cells and induced endothelial cells in a murine model of peripheral arterial disease.

PubMed

Clayton, Zoe E; Yuen, Gloria S C; Sadeghipour, Sara; Hywood, Jack D; Wong, Jack W T; Huang, Ngan F; Ng, Martin K C; Cooke, John P; Patel, Sanjay

2017-05-01

Endothelial cells derived from human induced pluripotent stem cells (iPSC-ECs) promote angiogenesis, and more recently induced endothelial cells (iECs) have been generated via fibroblast trans-differentiation. These cell types have potential as treatments for peripheral arterial disease (PAD). However, it is unknown whether different reprogramming methods produce cells that are equivalent in terms of their pro-angiogenic capabilities. We aimed to directly compare iPSC-ECs and iECs in an animal model of PAD, in order to identify which cell type, if any, displays superior therapeutic potential. IPSC-ECs and iECs were generated from human fibroblasts, and transduced with a reporter construct encoding GFP and firefly luciferase for bioluminescence imaging (BLI). Endothelial phenotype was confirmed using in vitro assays. NOD-SCID mice underwent hindlimb ischaemia surgery and received an intramuscular injection of either 1×10 6 iPSC-ECs, 1×10 6 iECs or control vehicle only. Perfusion recovery was measured by laser Doppler. Hindlimb muscle samples were taken for histological analyses. Perfusion recovery was enhanced in iPSC-EC treated mice on day 14 (Control vs. iPSC-EC; 0.35±0.04 vs. 0.54±0.08, p<0.05) and in iEC treated mice on days 7 (Control vs. iEC; 0.23±0.02 vs. 0.44±0.06, p<0.05), 10 (0.31±0.04 vs. 0.64±0.07, p<0.001) and 14 (0.35±0.04 vs. 0.68±0.07, p<0.001) post-treatment. IEC-treated mice also had greater capillary density in the ischaemic gastrocnemius muscle (Control vs. iEC; 125±10 vs. 179±11 capillaries/image; p<0.05). BLI detected iPSC-EC and iEC presence in vivo for two weeks post-treatment. IPSC-ECs and iECs exhibit similar, but not identical, endothelial functionality and both cell types enhance perfusion recovery after hindlimb ischaemia. Copyright © 2017 Elsevier B.V. All rights reserved.

Assessing the quality of the ecological component of English Environmental Statements.

PubMed

Drayson, Katherine; Wood, Graham; Thompson, Stewart

2015-09-01

Environmental Impact Assessment (EIA) is a key tool to help ensure sustainable built development in more than 200 countries worldwide. Ecology is frequently a component of EIA and early reviews of Ecological Impact Assessment (EcIA) chapters identified scope for improvement at almost every stage of the EcIA process, regardless of country. However, there have been no reviews of UK EcIA chapters since 2000, despite important changes in biodiversity and planning legislation, policy and guidance. In addition, no UK EcIA chapter reviews have attempted to assign a grade or score to EcIA chapters (as has been done for reviews of US, Finnish and Indian EcIA chapters). Furthermore, no EcIA chapter reviews have attempted to use a scoring system to identify which variables determine EcIA chapter information content, beyond straightforward comparisons of EcIA chapters before and after the introduction of guidelines. A variant of the Biodiversity Assessment Index (BAI) was used to assign scores between zero and one to EcIA chapters based on a series of 47 questions drawn from EU legislation and professional guidance. 112 EcIA chapters for proposed developments that were subsequently granted planning permission in England were assessed. The mean BAI score was less than 0.5, indicating the presence of considerable information gaps in the majority of EcIA chapters. Of 13 predictor variables identified as having the potential to affect EcIA chapter quality, 10 were identified as significantly related to the BAI scores. A backward stepwise Generalized Linear Model identified the use of professional guidance, the ecological consultancy type and the length of the EcIA chapter as having the greatest combined explanatory power. As a result, several recommendations are made to help improve future EcIA chapter content, including formal EcIA chapter review, publicising the professional guidance to consultants, the provision of training and the introduction of an accreditation scheme for consultants involved in EcIA This approach could be replicated in other countries that conduct EIA. Context-dependent EcIA chapter review criteria (as in this paper) would help to identify targeted recommendations for improvement. Alternatively, a global set of review criteria could highlight areas of best practice that could then be exported to other countries. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

Grouper (Epinephelus coioides) IL-34/MCSF2 and MCSFR1/MCSFR2 were involved in mononuclear phagocytes activation against Cryptocaryon irritans infection.

PubMed

Mo, Ze-Quan; Li, Yan-Wei; Zhou, Ling; Li, An-Xing; Luo, Xiao-Chun; Dan, Xue-Ming

2015-03-01

MCSF and its well-known receptor MCSFR had been well studied in humans, regulating the differentiation, proliferation, and survival of the mononuclear phagocyte system. IL-34, which is an alternative ligand of MCSF receptor, was recently identified as a novel cytokine and functionally overlaps with MCSF. However, the functional study of these receptors and their ligands in fish are largely unknown. In the present study, the cDNA of two potential grouper MCSFR ligands have been cloned, EcIL-34 (657 bp) and EcMCSF2 (804 bp), as well as an additional copy of grouper MCSFR, EcMCSFR2 (3141 bp). Sequence analysis showed that these three molecules had higher identities with other fish counterparts compared to mammals and their conserved structures and important functional residues were also analyzed. Tissue distribution analysis showed that EcIL-34 is dominant in brain, gill and spleen compared to EcMCSF2, which is dominant in head kidney, trunk kidney, skin, heart and muscle. EcMCSFR1 was dominant in the most tissues except head kidney and liver compared to EcMCSFR2. The different tissue distribution patterns of these two grouper MCSF receptors and their two ligands indicate the different mononuclear phagocyte differentiation and activation modes in different tissues. In Cryptocaryon irritans infected grouper, EcIL-34 and EcMCSFR2 were the most strongly up-regulated ligand and receptor in the infected sites, gill and skin. Their up-regulation confirmed the proliferation and activation of phagocytes in C. irritans infected sites, which would improve the antigen presentation and elicit the host local specific immune response. In C. irritans infected grouper head kidney, both ligands EcIL-34 and EcMCSF2 (especially EcMCSF2) were up-regulated, but both receptors EcMCSFR1 and EcMCSFR2 were down-regulated, which indicated that the phagocytes differentiation and proliferation may have occurred in this hemopoietic organ, and after that they migrated to the infected cites. The down-regulation of EcIL-34 and EcMCSF2 and no significant change of EcMCSFR1 and EcMCSFR2 in most time point of grouper spleen showed it was less involved in phagocytes response to C. irritans infection. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neutrophil Activation of Endothelial Cell-Expressed TRPM2 Mediates Transendothelial Neutrophil Migration and Vascular Injury.

PubMed

Mittal, Manish; Nepal, Saroj; Tsukasaki, Yoshikazu; Hecquet, Claudie M; Soni, Dheeraj; Rehman, Jalees; Tiruppathi, Chinnaswamy; Malik, Asrar B

2017-10-13

TRPM2 (transient receptor potential melastatin-2) expressed in endothelial cells (ECs) is a cation channel mediating Ca 2+ entry in response to intracellular generation of adenosine diphosphoribose-the TRPM2 ligand. Because polymorphonuclear neutrophils (PMN) interaction with ECs generates reactive oxygen species, we addressed the possible role of TRPM2 expressed in ECs in the mechanism of transendothelial migration of PMNs. We observed defective PMN transmigration in response to lipopolysaccharide challenge in adult mice in which the EC expressed TRPM2 is conditionally deleted ( Trpm2 iΔEC ). PMN interaction with ECs induced the entry of Ca 2+ in ECs via the EC-expressed TRPM2. Prevention of generation of adenosine diphosphoribose in ECs significantly reduced Ca 2+ entry in response to PMN activation of TRPM2 in ECs. PMNs isolated from gp91phox -/- mice significantly reduced Ca 2+ entry in ECs via TRPM2 as compared with wild-type PMNs and failed to induce PMN transmigration. Overexpression of the adenosine diphosphoribose insensitive TRPM2 mutant channel (C1008→A) in ECs suppressed the Ca 2+ entry response. Further, the forced expression of TRPM2 mutant channel (C1008→A) or silencing of poly ADP-ribose polymerase in ECs of mice prevented PMN transmigration. Thus, endotoxin-induced transmigration of PMNs was secondary to TRPM2-activated Ca 2+ signaling and VE-cadherin phosphorylation resulting in the disassembly of adherens junctions and opening of the paracellular pathways. These results suggest blocking TRPM2 activation in ECs is a potentially important means of therapeutically modifying PMN-mediated vascular inflammation. © 2017 American Heart Association, Inc.

Differential plastic changes in synthesis and binding in the mouse somatostatin system after electroconvulsive stimulation.

PubMed

Olesen, Mikkel Vestergaard; Gøtzsche, Casper René; Christiansen, Søren Hofman; Woldbye, David Paul Drucker

2018-03-21

Electroconvulsive therapy (ECT) is regularly used to treat patients with severe major depression, but the mechanisms underlying the beneficial effects remain uncertain. Electroconvulsive stimulation (ECS) regulates diverse neurotransmitter systems and induces anticonvulsant effects, properties implicated in mediating therapeutic effects of ECT. Somatostatin (SST) is a candidate for mediating these effects because it is upregulated by ECS and exerts seizure-suppressant effects. However, little is known about how ECS might affect the SST receptor system. The present study examined effects of single and repeated ECS on the synthesis of SST receptors (SSTR1-4) and SST, and SST receptor binding ([125I]LTT-SST28) in mouse hippocampal regions and piriform/parietal cortices. A complex pattern of plastic changes was observed. In the dentate gyrus, SST and SSTR1 expression and the number of hilar SST immunoreactive cells were significantly increased at 1 week after repeated ECS while SSTR2 expression was downregulated by single ECS, and SSTR3 mRNA and SST binding were elevated 24 h after repeated ECS. In hippocampal CA1 and parietal/piriform cortices, we found elevated SST mRNA levels 1 week after repeated ECS and elevated SST binding after single ECS and 24 h after repeated ECS. In hippocampal CA3, repeated ECS increased SST expression 1 week after and SST binding 24 h after. In the parietal cortex, SSTR2 mRNA expression was downregulated after single ECS while SSTR4 mRNA expression was upregulated 24 h after repeated ECS. Considering the known anticonvulsant effects of SST, it is likely that these ECS-induced neuroplastic changes in the SST system could participate in modulating neuronal excitability and potentially contribute to therapeutic effects of ECT.

Intercomparison of thermal-optical method with different temperature protocols: Implications from source samples and solvent extraction

NASA Astrophysics Data System (ADS)

Cheng, Yuan; Duan, Feng-kui; He, Ke-bin; Du, Zhen-yu; Zheng, Mei; Ma, Yong-liang

2012-12-01

Three temperature protocols with different peak inert mode temperature (Tpeak-inert) were compared based on source and ambient samples (both untreated and extracted using a mixture of hexane, methylene chloride, and acetone) collected in Beijing, China. The ratio of EC580 (elemental carbon measured by the protocol with a Tpeak-inert of 580 °C; similar hereinafter) to EC850 could be as high as 4.8 for biomass smoke samples whereas the ratio was about 1.0 for diesel and gasoline exhaust samples. The EC580 to EC850 ratio averaged 1.95 ± 0.89 and 1.13 ± 0.20 for the untreated and extracted ambient samples, whereas the EC580 to EC650 ratio of ambient samples was 1.22 ± 0.10 and 1.20 ± 0.12 before and after extraction. It was suggested that there are two competing mechanisms for the effects of Tpeak-inert on the EC results such that when Tpeak-inert is increased, one mechanism tends to decrease EC by increasing the amount of charring whereas the other tends to increase EC through promoting more charring to evolve before native EC. Results from this study showed that EC does not always decrease when increasing the peak inert mode temperature. Moreover, reducing the charring amount could improve the protocols agreement on EC measurements, whereas temperature protocol would not influence the EC results if no charring is formed. This study also demonstrated the benefits of allowing for the OC and EC split occurring in the inert mode when a high Tpeak-inert is used (e.g., 850 °C).

Knowledge, attitudes and prescribing pattern of emergency contraceptives by health care workers in Kampala, Uganda.

PubMed

Byamugisha, Josaphat K; Mirembe, Florence M; Faxelid, Elisabeth; Gemzell-Danielsson, Kristina

2007-01-01

Health care workers (HCWs) play an important role in making emergency contraceptives (ECs) available to clients. They can influence accessibility positively through counselling, prescribing or advocating the use of ECs. However, in some settings, HCWs have been blamed for unfavourable attitudes and lack of accurate information. Objective. To assess the knowledge, attitudes and prescribing pattern of EC by HCWs in Kampala district, Uganda. The total number of health units at different levels of health care delivery in Kampala (894) was obtained. Probability proportional to size (PPS) technique of sampling was applied. Some 247 HCWs completed a self-administered questionnaire on their knowledge about EC, including methods, mechanism of action, prescription of EC, sources of information, attitudes towards EC, and if and how it should be made available. Of the HCWs, 80% had knowledge of ECs. However, 1 in every 4 was not sure about the time limit within which EC is effective. A total of 50% of the participants had obtained information from a physician (26.4%) or from a training school (24%). The Yuzpe regimen was the most commonly mentioned and prescribed method of EC. The HCWs attitudes to EC were generally positive, and it was suggested that the community should be informed and sensitised about EC. There was a significant difference between having had a family planning educational update or not in the last year and knowledge of EC (p=0.005). Most HCWs were aware of EC, but some lacked important knowledge on its use or available methods. HCWs should have regular (annual) in-service training in reproductive health issues, such as counselling on EC. This will enable them to keep up to date with the current evidence-based recommendations in the field of contraceptive technology.

Family history of cancer predicts endometrial cancer risk independently of Lynch Syndrome: Implications for genetic counselling.

PubMed

Johnatty, Sharon E; Tan, Yen Y; Buchanan, Daniel D; Bowman, Michael; Walters, Rhiannon J; Obermair, Andreas; Quinn, Michael A; Blomfield, Penelope B; Brand, Alison; Leung, Yee; Oehler, Martin K; Kirk, Judy A; O'Mara, Tracy A; Webb, Penelope M; Spurdle, Amanda B

2017-11-01

To determine endometrial cancer (EC) risk according to family cancer history, including assessment by degree of relatedness, type of and age at cancer diagnosis of relatives. Self-reported family cancer history was available for 1353 EC patients and 628 controls. Logistic regression was used to quantify the association between EC and cancer diagnosis in ≥1 first or second degree relative, and to assess whether level of risk differed by degree of relationship and/or relative's age at diagnosis. Risk was also evaluated for family history of up to three cancers from known familial syndromes (Lynch, Cowden, hereditary breast and ovarian cancer) overall, by histological subtype and, for a subset of 678 patients, by EC tumor mismatch repair (MMR) gene expression. Report of EC in ≥1 first- or second-degree relative was associated with significantly increased risk of EC (P=3.8×10 -7 ), independent of lifestyle risk factors. There was a trend in increasing EC risk with closer relatedness and younger age at EC diagnosis in relatives (P Trend =4.43×10 -6 ), and with increasing numbers of Lynch cancers in relatives (P Trend ≤0.0001). EC risk associated with family history did not differ by proband tumor MMR status, or histological subtype. Reported EC in first- or second-degree relatives remained associated with EC risk after conservative correction for potential misreported family history (OR 2.0; 95% CI, 1.24-3.37, P=0.004). The strongest predictor of EC risk was closer relatedness and younger EC diagnosis age in ≥1 relative. Associations remained significant irrespective of proband MMR status, and after excluding MMR pathogenic variant carriers, indicating that Lynch syndrome genes do not fully explain familial EC risk. Copyright © 2017 Elsevier Inc. All rights reserved.

Altered lung biology of healthy never smokers following acute inhalation of E-cigarettes.

PubMed

Staudt, Michelle R; Salit, Jacqueline; Kaner, Robert J; Hollmann, Charleen; Crystal, Ronald G

2018-05-14

Little is known about health risks associated with electronic cigarette (EC) use although EC are rising in popularity and have been advocated as a means to quit smoking cigarettes. Ten never-smokers, without exposure history to tobacco products or EC, were assessed at baseline with questionnaire, chest X-ray, lung function, plasma levels of endothelial microparticles (EMP), and bronchoscopy to obtain small airway epithelium (SAE) and alveolar macrophages (AM). One week later, subjects inhaled 10 puffs of "Blu" brand EC, waited 30 min, then another 10 puff; n = 7 were randomized to EC with nicotine and n = 3 to EC without nicotine to assess biological responses in healthy, naive individuals. Two hr. post-EC exposure, subjects were again assessed as at baseline. No significant changes in clinical parameters were observed. Biological changes were observed compared to baseline, including altered transcriptomes of SAE and AM for all subjects and elevated plasma EMP levels following inhalation of EC with nicotine. This study provides in vivo human data demonstrating that acute inhalation of EC aerosols dysregulates normal human lung homeostasis in a limited cohort of healthy naïve individuals. These observations have implications to new EC users, nonsmokers exposed to secondhand EC aerosols and cigarette smokers using EC to quit smoking. ClinicalTrials.gov NCT01776398 (registered 10/12/12), NCT02188511 (registered 7/2/14).

Measuring Eating Competence: Psychometric Properties and Validity of the ecSatter Inventory

ERIC Educational Resources Information Center

Lohse, Barbara; Satter, Ellyn; Horacek, Tanya; Gebreselassie, Tesfayi; Oakland, Mary Jane

2007-01-01

Objective: Assess validity of the ecSatter Inventory (ecSI) to measure eating competence (EC). Design: Concurrent administration of ecSI with validated measures of eating behaviors using on-line and paper-pencil formats. Setting: The on-line survey was completed by 370 participants; 462 completed the paper version. Participants: Participants…

Knowledge and Usage of Emergency Contraceptives Among University Students in Ghana.

PubMed

Darteh, Eugene Kofuor Maafo; Doku, David Teye

2016-02-01

Contraceptive use is an important strategy for the prevention of unwanted pregnancy and avoidance of induced abortion. Of all the contraception methods, emergency contraceptive (EC) offers the last chance to achieve this. However, few studies have documented the use of EC among young people in Ghana. This study explored knowledge and usage of EC as well as the factors associated with it among University of Cape Coast students. Data were obtained on the knowledge and usage of ECs among University of Cape Coast students in 2013. Logistic regression analysis was used to investigate the association between students' socio-demographic characteristics and EC knowledge and use. More male students (72%) than females (59%) were sexually active. Fifty-seven percent of the respondents had ever heard of EC and 36% had ever used EC. Although males were more likely to be sexually active, females were more likely to have knowledge of EC use compared to males. The study underscores the need to increase awareness regarding EC among University students in order to offer them the opportunity that EC provides if other forms of contraceptives are missed.

Exploring emotional climate in preservice science teacher education

NASA Astrophysics Data System (ADS)

Bellocchi, Alberto; Ritchie, Stephen M.; Tobin, Kenneth; Sandhu, Maryam; Sandhu, Satwant

2013-09-01

Classroom emotional climates (ECs) are interrelated with students' engagement with university courses. Despite growing interest in emotions and EC research, little is known about the ways in which social interactions and different subject matter mediate ECs in preservice science teacher education classes. In this study we investigated the EC and associated classroom interactions in a preservice science teacher education class. We were interested in the ways in which salient classroom interactions were related to the EC during lessons centered on debates about science-based issues (e.g., nuclear energy alternatives). Participants used audience response technology to indicate their perceptions of the EC. Analysis of conversation for salient video clips and analysis of non-verbal conduct (acoustic parameters, body movements, and facial expressions) supplemented EC data. One key contribution that this study makes to preservice science teacher education is to identify the micro-processes of successful and unsuccessful class interactions that were associated with positive and neutral EC. The structure of these interactions can inform the practice of other science educators who wish to produce positive ECs in their classes. The study also extends and explicates the construct of intensity of EC.

EcR expression in the prothoracicotropic hormone-producing neurosecretory cells of the Bombyx mori brain.

PubMed

Hossain, Monwar; Shimizu, Sakiko; Fujiwara, Haruhiko; Sakurai, Sho; Iwami, Masafumi

2006-08-01

The steroid hormone 20-hydroxyecdysone (20E) initiates insect molting and metamorphosis through binding with a heterodimer of two nuclear receptors, the ecdysone receptor (EcR) and ultraspiracle (USP). Expression of the specific isoforms EcR-A and EcR-B1 governs steroid-induced responses in the developing cells of the silkworm Bombyx mori. Here, analysis of EcR-A and EcR-B1 expression during larval-pupal development showed that both genes were up-regulated by 20E in the B. mori brain. Whole-mount in situ hybridization and immunohistochemistry revealed that EcR-A and EcR-B1 mRNAs and proteins were exclusively located in two pairs of lateral neurosecretory cells in the larval brain known as the prothoracicotropic hormone (PTTH)- producing cells (PTPCs). In the pupal brain, EcR-A and EcR-B1 expression was detected in tritocerebral cells and optic lobe cells in addition to PTPCs. As PTTH controls ecdysone secretion by the prothoracic gland, these results indicate that 20E-responsive PTPCs are the master cells of insect metamorphosis.

Quantifying sources of elemental carbon over the Guanzhong Basin of China: A consistent network of measurements and WRF-Chem modeling.

PubMed

Li, Nan; He, Qingyang; Tie, Xuexi; Cao, Junji; Liu, Suixin; Wang, Qiyuan; Li, Guohui; Huang, Rujin; Zhang, Qiang

2016-07-01

We conducted a year-long WRF-Chem (Weather Research and Forecasting Chemical) model simulation of elemental carbon (EC) aerosol and compared the modeling results to the surface EC measurements in the Guanzhong (GZ) Basin of China. The main goals of this study were to quantify the individual contributions of different EC sources to EC pollution, and to find the major cause of the EC pollution in this region. The EC measurements were simultaneously conducted at 10 urban, rural, and background sites over the GZ Basin from May 2013 to April 2014, and provided a good base against which to evaluate model simulation. The model evaluation showed that the calculated annual mean EC concentration was 5.1 μgC m(-3), which was consistent with the observed value of 5.3 μgC m(-3). Moreover, the model result also reproduced the magnitude of measured EC in all seasons (regression slope = 0.98-1.03), as well as the spatial and temporal variations (r = 0.55-0.78). We conducted several sensitivity studies to quantify the individual contributions of EC sources to EC pollution. The sensitivity simulations showed that the local and outside sources contributed about 60% and 40% to the annual mean EC concentration, respectively, implying that local sources were the major EC pollution contributors in the GZ Basin. Among the local sources, residential sources contributed the most, followed by industry and transportation sources. A further analysis suggested that a 50% reduction of industry or transportation emissions only caused a 6% decrease in the annual mean EC concentration, while a 50% reduction of residential emissions reduced the winter surface EC concentration by up to 25%. In respect to the serious air pollution problems (including EC pollution) in the GZ Basin, our findings can provide an insightful view on local air pollution control strategies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Requirement of a Relatively High Threshold Level of Mg2+ for Cell Growth of a Rhizoplane Bacterium, Sphingomonas yanoikuyae EC-S001

PubMed Central

Hoo, Henny; Hashidoko, Yasuyuki; Islam, Md. Tofazzal; Tahara, Satoshi

2004-01-01

Mg2+ is one of the essential elements for bacterial cell growth. The presence of the magnesium cation (Mg2+) in various concentrations often affects cell growth restoration in plant-associating bacteria. This study attempted to determine whether Mg2+ levels in Sphingomonas yanoikuyae EC-S001 affected cell growth restoration in the host plant and what the threshold level is. S. yanoikuyae EC-S001, isolated from the rhizoplane of spinach seedlings grown from surface-sterilized seeds under aseptic conditions, displayed uniform dispersion and attachment throughout the rhizoplane and phylloplane of the host seedlings. S. yanoikuyae EC-S001 did not grow in potato-dextrose broth medium but grew well in an aqueous extract of spinach leaves. Chemical investigation of the growth factor in the spinach leaf extract led to identification of the active principle as the magnesium cation. A concentration of ca. 0.10 mM Mg2+ or more allowed S. yanoikuyae EC-S001 to grow in potato-dextrose broth medium. Some saprophytic and/or diazotrophic bacteria used in our experiment were found to have diverse threshold levels for their Mg2+ requirements. For example, Burkholderia cepacia EC-K014, originally isolated from the rhizoplane of a Melastoma sp., could grow even in Mg2+-free Hoagland's no. 2 medium with saccharose and glutamine (HSG medium) and requires a trace level of Mg2+ for its growth. In contrast, S. yanoikuyae EC-S001, together with Bacillus subtilis IFO12113, showed the most drastic restoring responses to subsequent addition of 0.98 mM Mg2+ to Mg2+-free HSG medium. Our studies concluded that Mg2+ is more than just the essential trace element needed for cell growth restoration in S. yanoikuyae EC-S001 and that certain nonculturable bacteria may require a higher concentration of Mg2+ or another specific essential element for their growth. PMID:15345402

Future of emergency contraception lies in pharmacists' hands.

PubMed

Monastersky, Nicole; Landau, Sharon Cohen

2006-01-01

To increase community pharmacists' awareness about issues related to the provision of emergency contraception (EC) to women by describing pharmacist outreach and training programs and discussing pharmacy access and stocking issues, California's EC Pharmacy Program, methods for raising pharmacists' awareness, and professional development opportunities. EC is both safe and effective in reducing the risk of unintended pregnancy after unprotected intercourse, yet awareness of and demand for the medication has not been high, and it often is not stocked in pharmacies. Various advocacy organizations have engaged in educating the public and physicians about EC, but relatively little attention and few resources have been targeted to ensure that the pharmacy community is aware of and educated about EC. Increased visibility and access to EC in the several states that allow pharmacists to provide EC directly to women have resulted from the active participation and leadership of pharmacists. In these states, women are showing interest in and receptivity to reproductive health services provided by pharmacists. In California, some 3000 pharmacists statewide have completed training, and in 2004 they provided EC directly to approximately 175,000 women. Pharmacists who provide EC overwhelmingly (91%) report that they do so because they see it as an important community service, and many (57%) recognize the opportunity for professional development. Pharmacists are uniquely positioned to improve access to EC, and leadership within the pharmacy community can facilitate efforts to improve access. Increased education and training of pharmacists about EC--such as continuing education programs available online at www.pharmacyaccess. learnsomething.com--are critical to ensure not only that EC is available in pharmacies but also that pharmacists are engaged in meeting the reproductive health needs of women. Increased access to EC can expand pharmacists' role in health care provision. State-specific information about EC pharmacy access initiatives is available on the Web at www.GO2EC.org.

Use of refractometry as a new management tool in AI boar centers for quality assurance of extender preparations.

PubMed

Schulze, M; Rüdiger, K; Jung, M; Grossfeld, R

2015-01-01

A study was performed to see if refractometry can be used as a new quality control tool for boar semen extenders. For this the refractive index and osmolality of BTS extender concentrations (EC) were recorded in 10%-steps from 50% to 150% and 200% of the correct amount. Twelve boar ejaculates were evaluated for semen quality. The refractive index for the correctly prepared extender was 4.6±0.0°Bx, corresponded to 316±16mOsmkg(-1), and correlated highly with osmolality (r=0.99; P<0.001). Total sperm motility with 100% EC differed significantly from ≤70% EC (P<0.001) and 200% EC (P<0.001) on day 1 (d1) and d4, respectively. The percentage of motile spermatozoa in a thermoresistance test on d2 showed a significant drop using ≤70% EC (P=0.047) and ≥140% EC (P=0.004). Secondary apical ridge defects were significantly higher using 50% EC (P<0.001) and ≥150% EC (P=0.032) compared to 100% EC, respectively. An increased number of coiled tails were observed using ≤60% EC (P<0.001). Percentages of spermatozoa with intact membranes on d2 resulted in a significant decrease using 50% EC (P<0.001) and ≥150% EC (P=0.005), respectively. The mean percentage of PI negative spermatozoa with active mitochondria on d2 showed a significant difference using ≤60% EC (P=0.016) and ≥140% EC (P<0.001) compared to 100% EC, respectively. Boar sperm quality is affected by inexact extender preparation. The refractive-index is an indicator of osmolality and may be used to verify semen extender preparation. The sensitivity is sufficient to detect deviations from correct extender preparation before negative effects on sperm quality occur. Copyright © 2014 Elsevier B.V. All rights reserved.

Endothelial cell metabolism: A novel player in atherosclerosis? Basic principles and therapeutic opportunities.

PubMed

Pircher, Andreas; Treps, Lucas; Bodrug, Natalia; Carmeliet, Peter

2016-10-01

Atherosclerosis is a leading cause of morbidity and mortality in Western society. Despite improved insight into disease pathogenesis and therapeutic options, additional treatment strategies are required. Emerging evidence highlights the relevance of endothelial cell (EC) metabolism for angiogenesis, and indicates that EC metabolism is perturbed when ECs become dysfunctional to promote atherogenesis. In this review, we overview the latest insights on EC metabolism and discuss current knowledge on how atherosclerosis deregulates EC metabolism, and how maladaptation of deregulated EC metabolism can contribute to atherosclerosis progression. We will also highlight possible therapeutic avenues, based on targeting EC metabolism. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Inactivation of the Ecs ABC transporter of Staphylococcus aureus attenuates virulence by altering composition and function of bacterial wall.

PubMed

Jonsson, Ing-Marie; Juuti, Jarmo T; François, Patrice; AlMajidi, Rana; Pietiäinen, Milla; Girard, Myriam; Lindholm, Catharina; Saller, Manfred J; Driessen, Arnold J M; Kuusela, Pentti; Bokarewa, Maria; Schrenzel, Jacques; Kontinen, Vesa P

2010-12-02

Ecs is an ATP-binding cassette (ABC) transporter present in aerobic and facultative anaerobic gram-positive Firmicutes. Inactivation of Bacillus subtilis Ecs causes pleiotropic changes in the bacterial phenotype including inhibition of intramembrane proteolysis. The molecule(s) transported by Ecs is (are) still unknown. In this study we mutated the ecsAB operon in two Staphylococcus aureus strains, Newman and LS-1. Phenotypic and functional characterization of these Ecs deficient mutants revealed a defect in growth, increased autolysis and lysostaphin sensitivity, altered composition of cell wall proteins including the precursor form of staphylokinase and an altered bacterial surface texture. DNA microarray analysis indicated that the Ecs deficiency changed expression of the virulence factor regulator protein Rot accompanied by differential expression of membrane transport proteins, particularly ABC transporters and phosphate-specific transport systems, protein A, adhesins and capsular polysaccharide biosynthesis proteins. Virulence of the ecs mutants was studied in a mouse model of hematogenous S. aureus infection. Mice inoculated with the ecs mutant strains developed markedly milder infections than those inoculated with the wild-type strains and had consequently lower mortality, less weight loss, milder arthritis and decreased persistence of staphylococci in the kidneys. The ecs mutants had higher susceptibility to ribosomal antibiotics and plant alkaloids chelerythrine and sanguinarine. Our results show that Ecs is essential for staphylococcal virulence and antimicrobial resistance probably since the transport function of Ecs is essential for the normal structure and function of the cell wall. Thus targeting Ecs may be a new approach in combating staphylococcal infection.

Development of a yeast heterologous expression cassette based on the promoter and terminator elements of the Eremothecium cymbalariae translational elongation factor 1α (EcTEF1) gene.

PubMed

Linder, Tomas

2018-04-01

A new expression cassette ( EC0 ) consisting of the fused 5' and 3' intergenic regions (IGRs) of the Eremothecium cymbalariae translational elongation factor 1α ( EcTEF1 ) gene was evaluated through expression of the bacterial hygromycin B phosphotransferase ( hph ) resistance gene in the common baker's yeast Saccharomyces cerevisiae . Progressively shorter versions of the hph -containing EC cassette ( hphEC1 though hphEC6 ) with trimmed 5' and 3' EcTEF1 IGRs were tested for their ability to confer resistance to hygromycin B in S. cerevisiae . Hygromycin B resistance was retained in all six generated hphEC variants up to a concentration of 400 mg/L. The hphEC6 cassette was the shortest cassette to be assayed in this study with 366 and 155 bp of the EcTEF1 5' and 3' IGRs, respectively. When tested for deletion of the S. cerevisiae proline oxidase gene PUT1 , the hphEC6 cassette was shown to successfully act as a selection marker on hygromycin B-containing medium. The hphEC6 cassette could be placed immediately adjacent to a kanMX4 G418 disulfate resistance marker without any discernable effect on the ability of the yeast to grow in the presence of both hygromycin B and G418 disulfate. Co-cultivation experiments under non-selective conditions demonstrated that a PUT1 deletion strain carrying the hphEC6 cassette displayed equivalent fitness to an otherwise isogenic PUT1 deletion strain carrying the kanMX4 cassette.

Analysis of the release process of phenylpropanolamine hydrochloride from ethylcellulose matrix granules.

PubMed

Fukui, Atsuko; Fujii, Ryuta; Yonezawa, Yorinobu; Sunada, Hisakazu

2002-11-01

The release properties of phenylpropanolamine hydrochloride (PPA) from ethylcellulose (EC, ethylcellulose 10 cps (EC#10) and/or 100 cps (EC#100)) matrix granules prepared by the extrusion granulation method were examined. The release process could be divided into two parts, and was well analyzed by applying square-root time law and cube root law equations, respectively. The validity of the treatments was confirmed by the fitness of the simulation curve with the measured curve. At the initial stage, PPA was released from the gel layer of swollen EC in the matrix granules. At the second stage, the drug existing below the gel layer dissolved, and was released through the gel layer. Also, the time and release ratio at the connection point of the simulation curves was examined to determine the validity of the analysis. Comparing the release properties of PPA from the two types of EC matrix granules, EC#100 showed more effective sustained release than EC#10. On the other hand, changes in the release property of the EC#10 matrix granule were relatively more clear than that of the EC#100 matrix granule. Thus, it was supposed that EC#10 is more available for controlled and sustained release formulations than EC#100.

Validation of a measure of the Satter eating competence model with low-income females

PubMed Central

2011-01-01

Background The purpose of this study was to evaluate the construct validity of a version of the ecSatter Inventory (ecSI), a measure of eating competence (EC), as adapted for use in a low-income (LI) population. Methods Females (n = 507), aged 18 to 45 years, living in households with a history of participating in the Supplemental Nutrition Assistance Program completed a web-based survey that included the ecSI for LI (ecSI/LI) and valid measures of cognitive and affective eating behavior, food preference and practice, and food preparation. Results Most correlations and differences between eating competent and non-eating competent categories and among EC tertiles were compatible with hypothesized relationships. ecSI/LI scores were positively related with self-reported physical activity, food acceptance, fruit and vegetable intake, and food planning/resource management. ecSI/LI scores were negatively associated with body mass index, dissatisfaction with body weight, tendency to overeat in response to external or emotional stimuli, and indices of psychosocial attributes related to disordered eating. Conclusions The ecSI/LI is a valid measure of EC for low-income females and provides a tool for researchers and educators to assess intervention outcomes and further explore the EC construct. PMID:21473765

Evaluative Conditioning: The “How” Question

PubMed Central

Jones, Christopher R.; Olson, Michael A.; Fazio, Russell H.

2011-01-01

Evaluative conditioning (EC) refers to attitude formation or change toward an object due to that object's mere co-occurrence with another valenced object or objects. This chapter focuses on the “how” question, that is, the question of what cognitive processes intervene between mere co-occurrence and attitude formation or change. Though EC has typically been thought of as occurring through a single, albeit contentious, mechanism, we begin by pointing out that both the heterogeneity of EC methodologies and the abundance of inconsistent results suggest that multiple processes with different characteristics can produce EC. We describe how the earliest posited process of EC, Pavlovian conditioning or signal learning, is a valid mechanism of EC that appears to have operated in some experiments but is unlikely to have operated in others and also cannot account for various EC findings. We describe other mechanisms of EC, when they can be expected to occur, and what characteristics they have. We particularly focus our attention on a process model of EC we have recently introduced, the implicit misattribution model. Finally, we describe the implications of a multi-process view of EC, which we argue can help resolve theoretical controversies and further the application of EC as a practical intervention for influencing attitudes in various domains. PMID:22241936

Sound pressure distribution within natural and artificial human ear canals: Forward stimulation

PubMed Central

Ravicz, Michael E.; Tao Cheng, Jeffrey; Rosowski, John J.

2014-01-01

This work is part of a study of the interaction of sound pressure in the ear canal (EC) with tympanic membrane (TM) surface displacement. Sound pressures were measured with 0.5–2 mm spacing at three locations within the shortened natural EC or an artificial EC in human temporal bones: near the TM surface, within the tympanic ring plane, and in a plane transverse to the long axis of the EC. Sound pressure was also measured at 2-mm intervals along the long EC axis. The sound field is described well by the size and direction of planar sound pressure gradients, the location and orientation of standing-wave nodal lines, and the location of longitudinal standing waves along the EC axis. Standing-wave nodal lines perpendicular to the long EC axis are present on the TM surface >11–16 kHz in the natural or artificial EC. The range of sound pressures was larger in the tympanic ring plane than at the TM surface or in the transverse EC plane. Longitudinal standing-wave patterns were stretched. The tympanic-ring sound field is a useful approximation of the TM sound field, and the artificial EC approximates the natural EC. PMID:25480061

Exploring Dimensionality of Effortful Control Using Hot and Cool Tasks in a Sample of Preschool Children

PubMed Central

Allan, Nicholas P.; Lonigan, Christopher J.

2015-01-01

Effortful control (EC) is an important developmental construct associated with academic performance, socioemotional growth, and psychopathology. EC, defined as the ability to inhibit or delay a prepotent response typically in favor of a subdominant response, undergoes rapid development during children’s preschool years. Research involving EC in preschool children can be aided by ensuring that the measured model of EC matches the latent structure of EC. Extant research indicates that EC may be multidimensional, consisting of hot (affectively salient) and cool (affectively neutral) dimensions. However, there are several untested assumptions regarding the defining features of hot EC. Confirmatory factor analysis was used in a sample of 281 preschool children (Mage = 55.92 - months, SD = 4.16; 46.6% male and 53.4% female) to compare a multidimensional model composed of hot and cool EC factors with a unidimensional model. Hot tasks were created by adding affective salience to cool tasks so that hot and cool tasks varied only by this aspect of the tasks. Tasks measuring EC were best described by a single factor and not distinct hot and cool factors, indicating that affective salience alone does not differentiate between hot and cool EC. EC shared gender-invariant associations with academic skills and externalizing behavior problems. PMID:24518050

Exploring dimensionality of effortful control using hot and cool tasks in a sample of preschool children.

PubMed

Allan, Nicholas P; Lonigan, Christopher J

2014-06-01

Effortful control (EC) is an important developmental construct associated with academic performance, socioemotional growth, and psychopathology. EC, defined as the ability to inhibit or delay a prepotent response typically in favor of a subdominant response, undergoes rapid development during children's preschool years. Research involving EC in preschool children can be aided by ensuring that the measured model of EC matches the latent structure of EC. Extant research indicates that EC may be multidimensional, consisting of hot (affectively salient) and cool (affectively neutral) dimensions. However, there are several untested assumptions regarding the defining features of hot EC. Confirmatory factor analysis was used in a sample of 281 preschool children (Mage=55.92months, SD=4.16; 46.6% male and 53.4% female) to compare a multidimensional model composed of hot and cool EC factors with a unidimensional model. Hot tasks were created by adding affective salience to cool tasks so that hot and cool tasks varied only by this aspect of the tasks. Tasks measuring EC were best described by a single factor and not distinct hot and cool factors, indicating that affective salience alone does not differentiate between hot and cool EC. EC shared gender-invariant associations with academic skills and externalizing behavior problems. Copyright © 2013 Elsevier Inc. All rights reserved.

Validation of a measure of the Satter eating competence model with low-income females.

PubMed

Krall, Jodi S; Lohse, Barbara

2011-04-07

The purpose of this study was to evaluate the construct validity of a version of the ecSatter Inventory (ecSI), a measure of eating competence (EC), as adapted for use in a low-income (LI) population. Females (n=507), aged 18 to 45 years, living in households with a history of participating in the Supplemental Nutrition Assistance Program completed a web-based survey that included the ecSI for LI (ecSI/LI) and valid measures of cognitive and affective eating behavior, food preference and practice, and food preparation. Most correlations and differences between eating competent and non-eating competent categories and among EC tertiles were compatible with hypothesized relationships. ecSI/LI scores were positively related with self-reported physical activity, food acceptance, fruit and vegetable intake, and food planning/resource management. ecSI/LI scores were negatively associated with body mass index, dissatisfaction with body weight, tendency to overeat in response to external or emotional stimuli, and indices of psychosocial attributes related to disordered eating. The ecSI/LI is a valid measure of EC for low-income females and provides a tool for researchers and educators to assess intervention outcomes and further explore the EC construct. © 2011 Krall and Lohse; licensee BioMed Central Ltd.

Survey of selected tick-borne diseases in dogs in Finland.

PubMed

Pérez Vera, Cristina; Kapiainen, Suvi; Junnikkala, Sami; Aaltonen, Kirsi; Spillmann, Thomas; Vapalahti, Olli

2014-06-23

Due to climate changes during the last decades, ticks have progressively spread into higher latitudes in northern Europe. Although some tick borne diseases are known to be endemic in Finland, to date there is limited information with regard to the prevalence of these infections in companion animals. We determined the antibody and DNA prevalence of the following organisms in randomly selected client-owned and clinically healthy hunting dogs living in Finland: Ehrlichia canis (Ec), Anaplasma phagocytophilum (Ap), Borrelia burgdorferi (Bb) and Bartonella. Anti-Ap, -Bb and -Ec antibodies were determined in 340 Finnish pet dogs and 50 healthy hunting dogs using the 4DX Snap®Test (IDEXX Laboratories). In addition, PCRs for the detection of Ap and Bartonella DNA were performed. Univariate and multivariate logistic regression analyses were used to identify risk factors associated with seropositivity to a vector borne agent. The overall seroprevalence was highest for Ap (5.3%), followed by Bb (2.9%), and Ec (0.3%). Seropositivities to Ap and Bb were significantly higher in the Åland Islands (p <0.001), with prevalence of Ap and Bb antibodies of 45 and 20%, respectively. In healthy hunting dogs, seropositivity rates of 4% (2/50) and 2% (1/50) were recorded for Ap and Bb, respectively. One client-owned dog and one hunting dog, both healthy, were infected with Ap as determined by PCR, while being seronegative. For Bartonella spp., none of the dogs tested was positive by PCR. This study represents the first data of seroprevalence to tick borne diseases in the Finnish dog population. Our results indicate that dogs in Finland are exposed to vector borne diseases, with Ap being the most seroprevalent of the diseases tested, followed by Bb. Almost 50% of dogs living in Åland Islands were Ap seropositive. This finding suggests the possibility of a high incidence of Ap infection in humans in this region. Knowing the distribution of seroprevalence in dogs may help predict the pattern of a tick borne disease and may aid in diagnostic and prevention efforts.

Explaining the Ba, Y, Sr, and Eu abundance scatter in metal-poor halo stars: constraints to the r-process

NASA Astrophysics Data System (ADS)

Cescutti, G.; Chiappini, C.

2014-05-01

Context. Thanks to the heroic observational campaigns carried out in recent years we now have large samples of metal-poor stars for which measurements of detailed abundances exist. In particular, large samples of stars with metallicities -5 < [Fe/H] <-1 and measured abundances of Sr, Ba, Y, and Eu are now available. These data hold important clues on the nature of the contribution of the first stellar generations to the enrichment of our Galaxy. Aims: We aim to explain the scatter in Sr, Ba, Y, and Eu abundance ratio diagrams unveiled by the metal-poor halo stars. Methods: We computed inhomogeneous chemical evolution models for the Galactic halo assuming different scenarios for the r-process site: the electron-capture (EC) supernovae and the magnetorotationally driven (MRD) supernovae scenarios. We also considered models with and without the contribution of fast-rotating massive stars (spinstars) to an early enrichment by the s-process. A detailed comparison with the now large sample of stars with measured abundances of Sr, Ba, Y, Eu, and Fe is provided (both in terms of scatter plots and number distributions for several abundance ratios). Results: The scatter observed in these abundance ratios of the very metal-poor stars (with [Fe/H] <-2.5) can be explained by combining the s-process production in spinstars, and the r-process contribution coming from massive stars. For the r-process we have developed models for both the EC and the MRD scenarios that match the observations. Conclusions: With the present observational and theoretical constraints we cannot distinguish between the EC and the MRD scenarios in the Galactic halo. Independently of the r-process scenarios adopted, the production of elements by an s-process in spinstars is needed to reproduce the spread in abundances of the light neutron capture elements (Sr and Y) over heavy neutron capture elements (Ba and Eu). We provide a way to test our suggestions by means of the distribution of the Ba isotopic ratios in a [Ba/Fe] or [Sr/Ba] vs. [Fe/H] diagram. Appendix A is available in electronic form at http://www.aanda.org

CpG Oligodeoxynucleotides Facilitate Delivery of Whole Inactivated H9N2 Influenza Virus via Transepithelial Dendrites of Dendritic Cells in Nasal Mucosa

PubMed Central

Qin, Tao; Yin, Yinyan; Yu, Qinghua; Huang, Lulu; Wang, Xiaoqing; Lin, Jian

2015-01-01

ABSTRACT The spread of the low-pathogenicity avian H9N2 influenza virus has seriously increased the risk of a new influenza pandemic. Although whole inactivated virus (WIV) vaccine via intranasal pathway is the effective method of blocking virus transmission, the mucosal barrier seems to be a major factor hampering its development. CpG oligodeoxynucleotides, a known adjuvant, can target downstream dendritic cells (DCs) and effectively enhance the mucosal and systemic immune responses. However, the ability of CpGs to assist H9N2 WIV in transepithelial transport remains unknown. Here, in vitro and in vivo, we showed that CpGs provided assistance for H9N2 WIV in recruiting DCs to the nasal epithelial cells (ECs) and forming transepithelial dendrites (TEDs) to capture luminal viruses. CD103+ DCs participated in this process. Chemokine CCL20 from nasal ECs played a key role in driving DC recruitment and TED formation. Virus-loaded DCs quickly migrated into the draining cervical lymph nodes (CLNs) for antigen presentation. In addition, the competence of CpGs was independent of direct epithelial transport via the transcellular or paracellular pathway. Taken together, our data demonstrated that CpGs enhanced the transport of H9N2 WIV via TEDs of nasal DCs, which might be a novel mechanism for optimal adaptive immune responses. IMPORTANCE This paper demonstrates by both an in vivo and an in vitro coculture model that CpG oligodeoxynucleotides, known as an adjuvant generally targeting downstream immune responses, also are crucial for the transport of H9N2 WIV across nasal epithelial cells (ECs) via the uptake of transepithelial dendrites (TEDs). Our results prove for the first time to our knowledge that the immune-potentiating mechanism of CpGs is based on strengthening the transepithelial uptake of H9N2 WIV in nasal mucosa. These findings provide a fresh perspective for further improvement of intranasal influenza vaccines, which are urgently needed in the face of the potential threat of H9N2 influenza. PMID:25810544

The intrauterine device as emergency contraception: how much do young women know?

PubMed

Goodman, Suzan R; El Ayadi, Alison M; Rocca, Corinne H; Kohn, Julia E; Benedict, Courtney E; Dieseldorff, Jessica R; Harper, Cynthia C

2018-04-18

Unprotected intercourse is common, especially among teens and young women. Access to intrauterine device (IUD) as emergency contraception (EC) can help interested patients more effectively prevent unintended pregnancy and can also offer ongoing contraception. This study evaluated young women's awareness of IUD as EC and interest in case of need. We conducted a secondary analysis of data from young women aged 18-25 years, not desiring pregnancy within 12 months, and receiving contraceptive counseling within a cluster-randomized trial in 40 US Planned Parenthood health centers in 2011-2013 (n=1500). Heath centers were randomized to receive enhanced training on contraceptive counseling and IUD placement, or to provide standard care. The intervention did not focus specifically on IUD as EC. We assessed awareness of IUD as EC, desire to learn more about EC and most trusted source of information of EC among women in both intervention and control groups completing baseline and 3- or 6-month follow-up questionnaires (n=1138). At follow-up, very few young women overall (7.5%) visiting health centers had heard of IUD as EC. However, if they needed EC, most (68%) reported that they would want to learn about IUDs in addition to EC pills, especially those who would be very unhappy to become pregnant (adjusted odds ratio [aOR], 1.3; 95% confidence interval, 1.0-1.6, p<.05). Most (91%) reported a doctor or nurse as their most trusted source of EC information, over Internet (6%) or friends (2%), highlighting providers' essential role. Most young women at risk of unintended pregnancy are not aware of IUD as EC and look to their providers for trusted information. Contraceptive education should explicitly address IUD as EC. Few young women know that the IUD can be used for EC or about its effectiveness. However, if they needed EC, most reported that they would want to learn about IUDs in addition to EC pills, especially those very unhappy to become pregnant. Contraceptive education should explicitly address IUD as EC. Copyright © 2018 Elsevier Inc. All rights reserved.

Epigenetic reprogramming governs EcSOD expression during human mammary epithelial cell differentiation, tumorigenesis and metastasis

PubMed Central

Teoh-Fitzgerald, ML; Fitzgerald, MP; Zhong, W; Askeland, RW; Domann, FE

2013-01-01

Expression of the antioxidant enzyme EcSOD in normal human mammary epithelial cells was not recognized until recently. Although expression of EcSOD was not detectable in non-malignant human mammary epithelial cells (HMEC) cultured in conventional two-dimensional (2D) culture conditions, EcSOD protein expression was observed in normal human breast tissues, suggesting that the 2D-cultured condition induces a repressive status of EcSOD gene expression in HMEC. With the use of laminin-enriched extracellular matrix (lrECM), we were able to detect expression of EcSOD when HMEC formed polarized acinar structures in a 3D-culture condition. Repression of the EcSOD-gene expression was again seen when the HMEC acini were sub-cultured as a monolayer, implying that lrECM-induced acinar morphogenesis is essential in EcSOD-gene activation. We have further shown the involvement of DNA methylation in regulating EcSOD expression in HMEC under these cell culture conditions. EcSOD mRNA expression was strongly induced in the 2D-cultured HMEC after treatment with a DNA methyltransferase inhibitor. In addition, epigenetic analyses showed a decrease in the degree of CpG methylation in the EcSOD promoter in the 3D versus 2D-cultured HMEC. More importantly, >80% of clinical mammary adenocarcinoma samples showed significantly decreased EcSOD mRNA and protein expression levels compared with normal mammary tissues and there is an inverse correlation between the expression levels of EcSOD and the clinical stages of breast cancer. Combined bisulfite restriction analysis analysis of some of the tumors also revealed an association of DNA methylation with the loss of EcSOD expression in vivo. Furthermore, overexpression of EcSOD inhibited breast cancer metastasis in both the experimental lung metastasis model and the syngeneic mouse model. This study suggests that epigenetic silencing of EcSOD may contribute to mammary tumorigenesis and that restoring the extracellular superoxide scavenging activity could be an effective strategy for breast cancer treatment. PMID:23318435

Predicting ambient aerosol thermal-optical reflectance measurements from infrared spectra: elemental carbon

NASA Astrophysics Data System (ADS)

Dillner, A. M.; Takahama, S.

2015-10-01

Elemental carbon (EC) is an important constituent of atmospheric particulate matter because it absorbs solar radiation influencing climate and visibility and it adversely affects human health. The EC measured by thermal methods such as thermal-optical reflectance (TOR) is operationally defined as the carbon that volatilizes from quartz filter samples at elevated temperatures in the presence of oxygen. Here, methods are presented to accurately predict TOR EC using Fourier transform infrared (FT-IR) absorbance spectra from atmospheric particulate matter collected on polytetrafluoroethylene (PTFE or Teflon) filters. This method is similar to the procedure developed for OC in prior work (Dillner and Takahama, 2015). Transmittance FT-IR analysis is rapid, inexpensive and nondestructive to the PTFE filter samples which are routinely collected for mass and elemental analysis in monitoring networks. FT-IR absorbance spectra are obtained from 794 filter samples from seven Interagency Monitoring of PROtected Visual Environment (IMPROVE) sites collected during 2011. Partial least squares regression is used to calibrate sample FT-IR absorbance spectra to collocated TOR EC measurements. The FT-IR spectra are divided into calibration and test sets. Two calibrations are developed: one developed from uniform distribution of samples across the EC mass range (Uniform EC) and one developed from a uniform distribution of Low EC mass samples (EC < 2.4 μg, Low Uniform EC). A hybrid approach which applies the Low EC calibration to Low EC samples and the Uniform EC calibration to all other samples is used to produce predictions for Low EC samples that have mean error on par with parallel TOR EC samples in the same mass range and an estimate of the minimum detection limit (MDL) that is on par with TOR EC MDL. For all samples, this hybrid approach leads to precise and accurate TOR EC predictions by FT-IR as indicated by high coefficient of determination (R2; 0.96), no bias (0.00 μg m-3, a concentration value based on the nominal IMPROVE sample volume of 32.8 m3), low error (0.03 μg m-3) and reasonable normalized error (21 %). These performance metrics can be achieved with various degrees of spectral pretreatment (e.g., including or excluding substrate contributions to the absorbances) and are comparable in precision and accuracy to collocated TOR measurements. Only the normalized error is higher for the FT-IR EC measurements than for collocated TOR. FT-IR spectra are also divided into calibration and test sets by the ratios OC/EC and ammonium/EC to determine the impact of OC and ammonium on EC prediction. We conclude that FT-IR analysis with partial least squares regression is a robust method for accurately predicting TOR EC in IMPROVE network samples, providing complementary information to TOR OC predictions (Dillner and Takahama, 2015) and the organic functional group composition and organic matter estimated previously from the same set of sample spectra (Ruthenburg et al., 2014).

Predicting ambient aerosol Thermal Optical Reflectance (TOR) measurements from infrared spectra: elemental carbon

NASA Astrophysics Data System (ADS)

Dillner, A. M.; Takahama, S.

2015-06-01

Elemental carbon (EC) is an important constituent of atmospheric particulate matter because it absorbs solar radiation influencing climate and visibility and it adversely affects human health. The EC measured by thermal methods such as Thermal-Optical Reflectance (TOR) is operationally defined as the carbon that volatilizes from quartz filter samples at elevated temperatures in the presence of oxygen. Here, methods are presented to accurately predict TOR EC using Fourier Transform Infrared (FT-IR) absorbance spectra from atmospheric particulate matter collected on polytetrafluoroethylene (PTFE or Teflon) filters. This method is similar to the procedure tested and developed for OC in prior work (Dillner and Takahama, 2015). Transmittance FT-IR analysis is rapid, inexpensive, and non-destructive to the PTFE filter samples which are routinely collected for mass and elemental analysis in monitoring networks. FT-IR absorbance spectra are obtained from 794 filter samples from seven Interagency Monitoring of PROtected Visual Environment (IMPROVE) sites collected during 2011. Partial least squares regression is used to calibrate sample FT-IR absorbance spectra to collocated TOR EC measurements. The FTIR spectra are divided into calibration and test sets. Two calibrations are developed, one which is developed from uniform distribution of samples across the EC mass range (Uniform EC) and one developed from a~uniform distribution of low EC mass samples (EC < 2.4 μg, Low Uniform EC). A hybrid approach which applies the low EC calibration to low EC samples and the Uniform EC calibration to all other samples is used to produces predictions for low EC samples that have mean error on par with parallel TOR EC samples in the same mass range and an estimate of the minimum detection limit (MDL) that is on par with TOR EC MDL. For all samples, this hybrid approach leads to precise and accurate TOR EC predictions by FT-IR as indicated by high coefficient of variation (R2; 0.96), no bias (0.00 μg m-3, concentration value based on the nominal IMPROVE sample volume of 32.8 m-3), low error (0.03 μg m-3) and reasonable normalized error (21 %). These performance metrics can be achieved with various degrees of spectral pretreatment (e.g., including or excluding substrate contributions to the absorbances) and are comparable in precision and accuracy to collocated TOR measurements. Only the normalized error is higher for the FT-IR EC measurements than for collocated TOR. FT-IR spectra are also divided into calibration and test sets by the ratios OC/EC and ammonium/EC to determine the impact of OC and ammonium on EC prediction. We conclude that FT-IR analysis with partial least squares regression is a robust method for accurately predicting TOR EC in IMPROVE network samples; providing complementary information to TOR OC predictions (Dillner and Takahama, 2015) and the organic functional group composition and organic matter (OM) estimated previously from the same set of sample spectra (Ruthenburg et al., 2014).

Vape and Aviate: Electronic-Cigarette Use and Misuse in Naval Aviation.

PubMed

Hall, Matthew T; Austin, Ryan P; Do, Tai A; McGlynn, Andrea

2018-03-01

Electronic cigarettes (EC) are an emerging form of nicotine replacement that has had a discernible increase in prevalence in the general population. Little is known regarding EC use among different military demographic groups or the extent of influence that social determinants of health may have on the behavior. The purpose of this study was to assess the prevalence and correlates of EC use in a select population of active duty U.S. Naval personnel. This study is unique in that it allows for EC behavior comparison between a traditionally healthy demographic (aviators, a subset of aircrew) and a representative general military population sample. Cross-sectional survey data were collected anonymously and analyzed in 2015-2016. Active duty Naval personnel (n = 977) were asked about ever trying ECs, frequency of use, and when was the last time an EC was used. Participants were assessed similarly regarding cigarette use. Descriptive and inferential statistics as well as multinomial logistic regression analyses were conducted using categorical and ordinal variables assigned to usage and demographic factors. This protocol was approved by the Institutional Review Board at Naval Hospital Portsmouth located in Portsmouth, Virginia. Within the study population, 31.4% have tried ECs, 9.3% were current users, and only 3.8% were dual (EC and cigarettes) users. EC use was significantly associated with paygrade (enlisted), primary job duty (non-aircrew), and education (less than a bachelor degree, p < 0.001, p < 0.01, and p < 0.001, respectively). ECs were used at some point as a smoking cessation tool for 43.6% of current EC users (p < 0.001), 21.6% of current smokers, and only 5.6% of former smokers. Continued EC use after ever trying ECs (30.0%) was only slightly more prevalent as continued cigarette use after ever trying cigarettes (27.3%). Smokers were nearly five times more likely to currently use ECs compared with non-smokers. Trying cigarettes was associated with nearly 12 times the risk for trying ECs compared with those who never tried cigarettes. No significant misuse of ECs was noted; however, several cases of drinking, tasting, and touching EC fluid were reported. This study is unique in that it examines the use of electronic cigarettes among selected healthy and baseline groups within the active duty U.S. Navy population. The current prevalence of EC use among active duty personnel is much higher than previously thought. Continued use of ECs after ever trying them appears to exceed that of cigarettes even among healthy populations such as aircrew. The findings of increased risk of EC use among those with lower income and less than a bachelor's degree suggest social determinants of health implications. This study sheds new light on EC use, characteristics of use, addiction implications, and highlights concerns for a growing health risk behavior.

Evaluative Conditioning: Recent Developments and Future Directions

ERIC Educational Resources Information Center

Gast, Anne; Gawronski, Bertram; De Houwer, Jan

2012-01-01

Evaluative conditioning (EC) is generally considered to be one of the routes via which likes and dislikes are acquired. We identify recent trends in EC research and speculate about the topics that will dominate future research on EC. Many of the recent developments in EC research were shaped by functional definitions of EC that refer only to…

[Acute traumatic and especially neglected traumatic hip dislocations are very rare in children].

PubMed

Fernandez, F F; Wirth, T; Eberhardt, O

2012-09-01

We report about the first hip arthroscopies of extracapsular neglected hip dislocations with concomitant injuries in two children (2 and 4 years old). The major problem of traumatic hip dislocation is avascular necrosis. Further problems are possible concomitant injuries. It is important not to cause further damage by therapeutic procedures. In a 4-year-old child the hip could be reduced under visualization and in a 2-year-old child with epiphyseal fracture the extent of the operation could be reduced. In both children large avulsion injuries of the ligamentum capitis femoris could be resected via hip arthroscopy. Hip arthroscopy can reduce surgical morbidity considerably and can possibly contribute to prevention of the feared avascular necrosis of the femoral head.

[Results after planned extracapsular cataract extraction with the Klöti stripper and implantation of UV light-absorbent Simcoe lenses with a 10-degree loop tilt].

PubMed

Gnad, H D; Skorpik, C; Paroussis, P

1985-08-09

Planned ECCE remains a valuable alternative to phacoemulsification due to its protection of the endothelial cells of the cornea. In contrast to the most commonly used infusion-aspiration systems, Kloeti's vitreous stripper provides, in addition, an excellent cutting mechanism enabling the removal of hard parts of the parenchyma or capsular remnants. The aspheric shaped UV light absorbing Simcoe lenses with a 10 grade loop angle used as lens replacement over the past 2 years in 300 cases did not cause any noteworthy complications. In 94% of cases a visual acuity of at least 0.5 was achieved; no case of cystoid macular edema has been observed so far.

[Laser magnetotherapy after cataract extraction with implantation of intraocular lens].

PubMed

Maksimov, V Iu; Zakharova, N V; Maksimova, I S; Golushkov, G A; Evseev, S Iu

2002-01-01

Effects of low-intensive laser and alternating magnetic field on the course of the postoperative period were studied in patients with exudative reaction after extracapsular cataract extraction with implantation of intraocular lens (IOL). The results are analyzed for 148 eyes with early exudative reaction after IOL implantation (136 patients aged 42-75 years). The patients were observed for up to 6 months. The treatment efficiency was evaluated by the clinical picture of inflammatory reaction, visual acuity, and results of biochemical analysis of the lacrimal fluid (the ratio of lipid peroxidation products to antioxidants in cell membrane). The course of the postoperative period was more benign and recovery sooner in patients of the main group in comparison with the control.

Biodegradation of Ethyl Carbamate and Urea with Lysinibacillus sphaericus MT33 in Chinese Liquor Fermentation.

PubMed

Cui, Kaixiang; Wu, Qun; Xu, Yan

2018-02-14

It is important to reduce the concentration of ethyl carbamate (EC) in fermented foods. However, controlling the formation of EC and its precursor urea is difficult in spontaneous food fermentation because urea is a natural product of nitrogen metabolism. Biodegradation is a better solution to reduce the concentration of EC. This study aimed to reduce the concentration of EC in Chinese liquor via an indigenous strain Lysinibacillus sphaericus MT33. This strain produced urethanase (940 U/L) and urease (1580 U/L) and degraded 76.52% of EC and 56.48% of urea. After inoculation in liquor fermentation, the maximal relative abundance of Lysinibacillus increased from 0.02% to 8.46%, the final EC and urea contents decreased by 41.77% and 28.15%. Moreover, the concentration of EC decreased by 63.32% in liquor. The negative correlation between abundance of Lysinibacillus and contents of EC and urea indicated the effect of L. sphaericus on EC and urea degradation.

Redox Regulation of Endothelial Cell Fate

PubMed Central

Song, Ping; Zou, Ming-Hui

2014-01-01

Endothelial cells (ECs) are present throughout blood vessels and have variable roles in both physiological and pathological settings. EC fate is altered and regulated by several key factors in physiological or pathological conditions. Reactive nitrogen species and reactive oxygen species derived from NAD(P)H oxidases, mitochondria, or nitric oxide-producing enzymes are not only cytotoxic but also compose a signaling network in the redox system. The formation, actions, key molecular interactions, and physiological and pathological relevance of redox signals in ECs remain unclear. We review the identities, sources, and biological actions of oxidants and reductants produced during EC function or dysfunction. Further, we discuss how ECs shape key redox sensors and examine the biological functions, transcriptional responses, and post-translational modifications evoked by the redox system in ECs. We summarize recent findings regarding the mechanisms by which redox signals regulate the fate of ECs and address the outcome of altered EC fate in health and disease. Future studies will examine if the redox biology of ECs can be targeted in pathophysiological conditions. PMID:24633153

Uncovering inherent cellular plasticity of multiciliated ependyma leading to ventricular wall transformation and hydrocephalus.

PubMed

Abdi, Khadar; Lai, Chun-Hsiang; Paez-Gonzalez, Patricia; Lay, Mark; Pyun, Joon; Kuo, Chay T

2018-04-25

Specialized, differentiated cells often perform unique tasks that require them to maintain a stable phenotype. Multiciliated ependymal cells (ECs) are unique glial cells lining the brain ventricles, important for cerebral spinal fluid circulation. While functional ECs are needed to prevent hydrocephalus, they have also been reported to generate new neurons: whether ECs represent a stable cellular population remains unclear. Via a chemical screen we found that mature ECs are inherently plastic, with their multiciliated state needing constant maintenance by the Foxj1 transcription factor, which paradoxically is rapidly turned over by the ubiquitin-proteasome system leading to cellular de-differentiation. Mechanistic analyses revealed a novel NF-κB-independent IKK2 activity stabilizing Foxj1 in mature ECs, and we found that known IKK2 inhibitors including viruses and growth factors robustly induced Foxj1 degradation, EC de-differentiation, and hydrocephalus. Although mature ECs upon de-differentiation can divide and regenerate multiciliated ECs, we did not detect evidence supporting EC's neurogenic potential.

Myeloid-Derived Suppressor Cells Are Involved in Lysosomal Acid Lipase Deficiency-Induced Endothelial Cell Dysfunctions

PubMed Central

Zhao, Ting; Ding, Xinchun; Du, Hong; Yan, Cong

2014-01-01

The underlying mechanisms that lysosomal acid lipase (LAL) deficiency causes infiltration of myeloid-derived suppressor cells (MDSCs) in multiple organs and subsequent inflammation remain incompletely understood. Endothelial cells (ECs), lining the inner layer of blood vessels, constitute barriers regulating leukocytes transmigration to the site of inflammation. Therefore, we hypothesized that ECs are dysfunctional in LAL-deficient (lal−/−) mice. We found that Ly6G+ cells transmigrated more efficiently across lal−/− ECs than wild-type (lal+/+) ECs, which was associated with increased level of platelet endothelial cell adhesion molecule-1 (PECAM-1) and monocyte chemoattractant protein-1 (MCP-1) in lal−/− ECs. In addition, lal−/−ECs showed enhanced migration and proliferation, decreased apoptosis, but impaired tube formation and angiogenesis. lal−/− ECs also suppressed T cell proliferation in vitro. Interestingly, lal−/− Ly6G+ cells promoted in vivo angiogenesis (including a tumor model), EC tube formation and proliferation. Finally, the mammalian target of rapamycin (mTOR) pathway was activated in lal−/− ECs, and inhibition of mTOR reversed EC dysfunctions, including decreasing Ly6G+ cell transmigration, delaying migration, and relieving suppression of T cell proliferation, which was mediated by decreasing production of reactive oxygen species (ROS). Our results indicate that LAL regulates EC functions through interaction with MDSCs and modulation of the mTOR pathway, which may provide a mechanistic basis for targeting MDSCs or mTOR to rejuvenate EC functions in LAL-deficiency related diseases. PMID:25000979

Extracellular Superoxide Dismutase Inhibits Innate Immune Responses and Clearance of an Intracellular Bacterial Infection

PubMed Central

Break, Timothy J.; Jun, Sujung; Indramohan, Mohanalaxmi; Carr, Karen D.; Sieve, Amy N.; Dory, Ladislav; Berg, Rance E.

2012-01-01

Reactive oxygen and nitrogen species (ROS/RNS) play important roles during immune responses to bacterial pathogens. Extracellular superoxide dismutase (ecSOD) regulates extracellular concentrations of ROS/RNS and contributes to tissue protection during inflammatory insults. The participation of ecSOD in immune responses seems therefore intuitive, yet is poorly understood. In the present study, we utilized mice with varying levels of ecSOD activity to investigate the involvement of this enzyme in immune responses against Listeria monocytogenes. Surprisingly, our data demonstrate that, despite enhanced neutrophil recruitment to the liver, ecSOD activity negatively impacted host survival and bacterial clearance. Increased ecSOD activity was accompanied by decreased co-localization of neutrophils with bacteria, as well as increased neutrophil apoptosis, which reduced overall and neutrophil-specific TNF-α production. Liver leukocytes from mice lacking ecSOD produced equivalent nitric oxide (NO·) when compared to mice expressing ecSOD. However, during infection, there were higher levels of peroxynitrite (NO3·−) in livers from mice lacking ecSOD compared to mice expressing ecSOD. Neutrophil depletion studies revealed that high levels of ecSOD activity resulted in neutrophils with limited protective capacity, whereas neutrophils from mice lacking ecSOD provided superior protection compared to neutrophils from wild-type mice. Taken together, our data demonstrate that ecSOD activity reduces innate immune responses during bacterial infection and provides a potential target for therapeutic intervention. PMID:22393157

BDNF restores the expression of Jun and Fos inducible transcription factors in the rat brain following repetitive electroconvulsive seizures.

PubMed

Hsieh, T F; Simler, S; Vergnes, M; Gass, P; Marescaux, C; Wiegand, S J; Zimmermann, M; Herdegen, T

1998-01-01

The expression of inducible transcription factors was studied following repetitive electroconvulsive seizures (ECS), c-Fos, c-Jun, JunB, and JunD immunoreactivities were investigated following a single (1 x ECS) or repetitive ECS evoked once per day for 4, 5, or 10 days (4 x ECS, 5 x ECS, or 10 x ECS). Animals were killed 3 or 12 h following the last ECS. Three hours after 1 x ECS, c-Fos was expressed throughout the cortex and hippocampus. After 5 x ECS and 10 x ECS, c-Fos was reexpressed in the CA4 area, but was completely absent in the other hippocampal areas and cortex. In these areas, c-Fos became only reinducible when the time lag between two ECS stimuli was 5 days. In contrast to c-Fos, intense JunB expression was inducible in the cortex and hippocampus, but not CA4 subfield, after 1 x ECS, 5 x ECS, and 10 x ECS. Repetitive ECS did not effect c-Jun and JunD expression. In a second model of systemic excitation of the brain, repetitive daily injection of kainic acid for 4 days completely failed to express c-Fos, c-Jun, and JunB after the last application whereas injection of kainic acid once per week did not alter the strong expressions compared to a single application of kainic acid. In order to study the maintenance of c-Fos expression during repetitive seizures, brain-derived neurotrophic factor (BDNF) was applied in parallel for 5 or 10 days via miniosmotic pumps and permanent cannula targeted at the hippocampus or the parietal cortex. Infusion of BDNF completely reinduced c-Fos expression during 5 x ECS or 10 x ECS in the cortex ipsilaterally to the cannula and, to a less extent, also increased the expression of c-Jun and JunB when compared to saline-treated controls. BDNF had no effect on the expression patterns in the hippocampus. ECS with or without BDNF infusion did not change the expression patterns of the constitutive transcription factors ATF-2, CREB, and SRF. These data demonstrate that various transcription factors substantially differ in their response to acute and chronic neural stimulation. Repetitive pathophysiological excitation decreases the transcriptional actions of neurons over days in the adult brain, and this decrement can be prevented by BDNF restoring the neuroplasticity at the level of gene transcription.

Electrical and Network Neuronal Properties Are Preferentially Disrupted in Dorsal, But Not Ventral, Medial Entorhinal Cortex in a Mouse Model of Tauopathy

PubMed Central

Booth, Clair A.; Ridler, Thomas; Murray, Tracey K.; Ward, Mark A.; de Groot, Emily; Goodfellow, Marc; Phillips, Keith G.; Randall, Andrew D.

2016-01-01

The entorhinal cortex (EC) is one of the first areas to be disrupted in neurodegenerative diseases such as Alzheimer's disease and frontotemporal dementia. The responsiveness of individual neurons to electrical and environmental stimuli varies along the dorsal–ventral axis of the medial EC (mEC) in a manner that suggests this topographical organization plays a key role in neural encoding of geometric space. We examined the cellular properties of layer II mEC stellate neurons (mEC-SCs) in rTg4510 mice, a rodent model of neurodegeneration. Dorsoventral gradients in certain intrinsic membrane properties, such as membrane capacitance and afterhyperpolarizations, were flattened in rTg4510 mEC-SCs, while other cellular gradients [e.g., input resistance (Ri), action potential properties] remained intact. Specifically, the intrinsic properties of rTg4510 mEC-SCs in dorsal aspects of the mEC were preferentially affected, such that action potential firing patterns in dorsal mEC-SCs were altered, while those in ventral mEC-SCs were unaffected. We also found that neuronal oscillations in the gamma frequency band (30–80 Hz) were preferentially disrupted in the dorsal mEC of rTg4510 slices, while those in ventral regions were comparatively preserved. These alterations corresponded to a flattened dorsoventral gradient in theta-gamma cross-frequency coupling of local field potentials recorded from the mEC of freely moving rTg4510 mice. These differences were not paralleled by changes to the dorsoventral gradient in parvalbumin staining or neurodegeneration. We propose that the selective disruption to dorsal mECs, and the resultant flattening of certain dorsoventral gradients, may contribute to disturbances in spatial information processing observed in this model of dementia. SIGNIFICANCE STATEMENT The medial entorhinal cortex (mEC) plays a key role in spatial memory and is one of the first areas to express the pathological features of dementia. Neurons of the mEC are anatomically arranged to express functional dorsoventral gradients in a variety of neuronal properties, including grid cell firing field spacing, which is thought to encode geometric scale. We have investigated the effects of tau pathology on functional dorsoventral gradients in the mEC. Using electrophysiological approaches, we have shown that, in a transgenic mouse model of dementia, the functional properties of the dorsal mEC are preferentially disrupted, resulting in a flattening of some dorsoventral gradients. Our data suggest that neural signals arising in the mEC will have a reduced spatial content in dementia. PMID:26758825

Evolution of the magnetized, neutrino-cooled accretion disk in the aftermath of a black hole-neutron star binary merger

NASA Astrophysics Data System (ADS)

Hossein Nouri, Fatemeh; Duez, Matthew D.; Foucart, Francois; Deaton, M. Brett; Haas, Roland; Haddadi, Milad; Kidder, Lawrence E.; Ott, Christian D.; Pfeiffer, Harald P.; Scheel, Mark A.; Szilagyi, Bela

2018-04-01

Black hole-torus systems from compact binary mergers are possible engines for gamma-ray bursts (GRBs). During the early evolution of the postmerger remnant, the state of the torus is determined by a combination of neutrino cooling and magnetically driven heating processes, so realistic models must include both effects. In this paper, we study the postmerger evolution of a magnetized black hole-neutron star binary system using the Spectral Einstein Code (SpEC) from an initial postmerger state provided by previous numerical relativity simulations. We use a finite-temperature nuclear equation of state and incorporate neutrino effects in a leakage approximation. To achieve the needed accuracy, we introduce improvements to SpEC's implementation of general-relativistic magnetohydrodynamics (MHD), including the use of cubed-sphere multipatch grids and an improved method for dealing with supersonic accretion flows where primitive variable recovery is difficult. We find that a seed magnetic field triggers a sustained source of heating, but its thermal effects are largely cancelled by the accretion and spreading of the torus from MHD-related angular momentum transport. The neutrino luminosity peaks at the start of the simulation, and then drops significantly over the first 20 ms but in roughly the same way for magnetized and nonmagnetized disks. The heating rate and disk's luminosity decrease much more slowly thereafter. These features of the evolution are insensitive to grid structure and resolution, formulation of the MHD equations, and seed field strength, although turbulent effects are not fully converged.

A Dense Poly(ethylene glycol) Coating Improves Penetration of Large Polymeric Nanoparticles within Brain Tissue

PubMed Central

Nance, Elizabeth A.; Woodworth, Graeme F.; Sailor, Kurt A.; Shih, Ting-Yu; Xu, Qingguo; Swaminathan, Ganesh; Xiang, Dennis; Eberhart, Charles; Hanes, Justin

2013-01-01

Prevailing opinion suggests that only substances up to 64 nm in diameter can move at appreciable rates through the brain extracellular space (ECS). This size range is large enough to allow diffusion of signaling molecules, nutrients, and metabolic waste products, but too small to allow efficient penetration of most particulate drug delivery systems and viruses carrying therapeutic genes, thereby limiting effectiveness of many potential therapies. We analyzed the movements of nanoparticles of various diameters and surface coatings within fresh human and rat brain tissue ex vivo and mouse brain in vivo. Nanoparticles as large as 114-nm in diameter diffused within the human and rat brain, but only if they were densely coated with poly(ethylene glycol) (PEG). Using these minimally adhesive PEG-coated particles, we estimated that human brain tissue ECS has some pores larger than 200 nm, and that more than one-quarter of all pores are ≥100 nm. These findings were confirmed in vivo in mice, where 40- and 100-nm, but not 200-nm, nanoparticles, spread rapidly within brain tissue, only if densely coated with PEG. Similar results were observed in rat brain tissue with paclitaxel-loaded biodegradable nanoparticles of similar size (85 nm) and surface properties. The ability to achieve brain penetration with larger nanoparticles is expected to allow more uniform, longer-lasting, and effective delivery of drugs within the brain, and may find use in the treatment of brain tumors, stroke, neuroinflammation, and other brain diseases where the blood-brain barrier is compromised or where local delivery strategies are feasible. PMID:22932224

PROBING ELECTRON-CAPTURE SUPERNOVAE: X-RAY BINARIES IN STARBURSTS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Linden, T.; Sepinsky, J. F.; Kalogera, V.

We develop population models of high-mass X-ray binaries (HMXBs) formed after bursts of star formation and we investigate the effect of electron-capture supernovae (ECS) of massive ONeMg white dwarfs and the hypothesis that ECS events are associated with typically low supernova kicks imparted to the nascent neutron stars. We identify an interesting ECS bump in the time evolution of HMXB numbers; this bump is caused by significantly increased production of wind-fed HMXBs 20-60 Myr post-starburst. The amplitude and age extent of the ECS bump depend on the strength of ECS kicks and the mass range of ECS progenitors. We alsomore » find that ECS-HMXBs form through a specific evolutionary channel that is expected to lead to binaries with Be donors in wide orbits. These characteristics, along with their sensitivity to ECS properties, provide us with an intriguing opportunity to probe ECS physics and progenitors through studies of starbursts of different ages. Specifically, the case of the Small Magellanic Cloud, with a significant observed population of Be-HMXBs and starburst activity 30-60 Myr ago, arises as a promising laboratory for understanding the role of ECS in neutron star formation.« less

Experiences of using an Environmental Control System (ECS) for persons with high cervical spinal cord injury: the interplay between hassle and engagement.

PubMed

Verdonck, Michèle; Steggles, Elizabeth; Nolan, Maeve; Chard, Gill

2014-01-01

Environmental Control Systems (ECS) have many benefits; however studies of personal experience of ECS use are scarce. This qualitative study explored the insiders' experience of using an ECS. An ECS starter-pack was compiled and trialled for an eight-week period with six persons with high spinal cord injuries (SCI) living in Ireland. Semi-structured interviews were subsequently completed with each person and analysed using Interpretative Phenomenological Analysis (IPA). Two major themes emerged: "Taking back a little of what has been lost", and "Getting used to ECS" which is the focus of the current paper. This theme captured a dynamic interplay between the experience of "hassle" and "engagement" for new users of ECS. "Hassle" resulted from technological frustrations and the challenge of breaking familiar habits, while "Engagement" resulted from feeling good, having fun and being surprised. The complex interweaving of hassle and engagement experienced by new ECS users reflects the clinical experience of rehabilitation providers. The importance of overcoming initial hassle needs to be understood by clinicians and users in order to maximise the potential benefit of ECS. Non-use must be considered one reasonable outcome if based on realistic ECS trials.

Nicotine, aerosol particles, carbonyls and volatile organic compounds in tobacco- and menthol-flavored e-cigarettes.

PubMed

Lee, Mi-Sun; LeBouf, Ryan F; Son, Youn-Suk; Koutrakis, Petros; Christiani, David C

2017-04-27

We aimed to assess the content of electronic cigarette (EC) emissions for five groups of potentially toxic compounds that are known to be present in tobacco smoke: nicotine, particles, carbonyls, volatile organic compounds (VOCs), and trace elements by flavor and puffing time. We used ECs containing a common nicotine strength (1.8%) and the most popular flavors, tobacco and menthol. An automatic multiple smoking machine was used to generate EC aerosols under controlled conditions. Using a dilution chamber, we targeted nicotine concentrations similar to that of exposure in a general indoor environment. The selected toxic compounds were extracted from EC aerosols into a solid or liquid phase and analyzed with chromatographic and spectroscopic methods. We found that EC aerosols contained toxic compounds including nicotine, fine and nanoparticles, carbonyls, and some toxic VOCs such as benzene and toluene. Higher mass and number concentrations of aerosol particles were generated from tobacco-flavored ECs than from menthol-flavored ECs. We found that diluted machine-generated EC aerosols contain some pollutants. These findings are limited by the small number of ECs tested and the conditions of testing. More comprehensive research on EC exposure extending to more brands and flavor compounds is warranted.

The ICAM-1 expression level determines the susceptibility of human endothelial cells to simulated microgravity.

PubMed

Buravkova, Ludmila B; Rudimov, Eugene G; Andreeva, Elena R; Grigoriev, Anatoly I

2018-03-01

Microgravity is a principal risk factor hampering human cardiovascular regulation during space flights. Endothelial dysfunction associated with the impaired integrity and uniformity of the monolayer represents a potential trigger for vascular damage. We characterized the expression profile of the multi-step cascade of adhesion molecules (ICAM-1, VCAM-1, E-selectin, VE-cadherin) in umbilical cord endothelial cells (ECs) after 24 h of exposure to simulated microgravity (SMG), pro-inflammatory cytokine TNF-α, and the combination of the two. Random Positioning Machine (RPM)-mediated SMG was used to mimic microgravity effects. SMG stimulated the expression of E-selectin, which is known to be involved in slowing leukocyte rolling. Primary ECs displayed heterogeneity with respect to the proportion of ICAM-1-positive cells. ECs were divided into two groups: pre-activated ECs displaying high proportion of ICAM-1 + -cells (ECs-1) (greater than 50%) and non-activated ECs with low proportion of ICAM-1 + -cells (ECs-2) (less than 25%). Only non-activated ECs-2 responded to SMG by elevating gene transcription and increasing ICAM-1 and VE-cadherin expression. This effect was enhanced after cumulative SMG-TNF-α exposure. ECs-1 displayed an unexpected decrease in number of E-selectin- and ICAM-1-positive ECs and pronounced up-regulation of VCAM1 upon activation of inflammation, which was partially abolished by SMG. Thus, non-activated ECs-2 are quite resistant to the impacts of microgravity and even exhibited an elevation of the VE-cadherin gene and protein expression, thus improving the integrity of the endothelial monolayer. Pre-activation of ECs with inflammatory stimuli may disturb the EC adhesion profile, attenuating its barrier function. These alterations may be among the mechanisms underlying cardiovascular dysregulation in real microgravity conditions. © 2017 Wiley Periodicals, Inc.

Emergency Contraception.

PubMed

Batur, Pelin; Kransdorf, Lisa N; Casey, Petra M

2016-06-01

Emergency contraception (EC) may help prevent pregnancy in various circumstances, such as contraceptive method failure, unprotected sexual intercourse, or sexual assault, yet it remains underused. There are 4 approved EC options in the United States. Although ulipristal acetate requires a provider's prescription, oral levonorgestrel (LNG) is available over the counter for women of all ages. The most effective method of EC is the copper intrauterine device, which can be left in place for up to 10 years for efficacious, cost-effective, hormone-free, and convenient long-term primary contraception. Ulipristal acetate tends to be more efficacious in pregnancy prevention than is LNG, especially when taken later than 72 hours postcoitus. The mechanism of action of oral EC is delay of ovulation, and current evidence reveals that it is ineffective postovulation. Women who weigh more than 75 kg or have a body mass index greater than 25 kg/m(2) may have a higher risk of unintended pregnancy when using oral LNG EC; therefore, ulipristal acetate or copper intrauterine devices are preferable in this setting. Providers are often unaware of the range of EC options or are unsure of how to counsel patients regarding the access and use of EC. This article critically reviews current EC literature, summarizes recommendations, and provides guidance for counseling women about EC. Useful tips for health care providers are provided, with a focus on special populations, including breast-feeding women and those transitioning to long-term contraception after EC use. When treating women of reproductive age, clinicians should be prepared to counsel them about EC options, provide EC appropriately, and, if needed, refer for EC in a timely manner. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Effects of nicotine-containing and "nicotine-free" e-cigarette refill liquids on intracranial self-stimulation in rats.

PubMed

Harris, Andrew C; Muelken, Peter; Smethells, John R; Yershova, Katrina; Stepanov, Irina; Olson, Thao Tran; Kellar, Kenneth J; LeSage, Mark G

2018-04-01

Animal models are needed to inform FDA regulation of electronic cigarettes (ECs) because they avoid limitations associated with human studies. We previously reported that an EC refill liquid produced less aversive/anhedonic effects at a high nicotine dose than nicotine alone as measured by elevations in intracranial self-stimulation (ICSS) thresholds, which may reflect the presence of behaviorally active non-nicotine constituents (e.g., propylene glycol) in the EC liquids. The primary objective of this study was to assess the generality of our prior ICSS findings to two additional EC liquids. We also compared effects of "nicotine-free" varieties of these EC liquids on ICSS, as well as binding affinity and/or functional activity of nicotine alone, nicotine-containing EC liquids, and "nicotine-free" EC liquids at nicotinic acetylcholine receptors (nAChRs). Nicotine alone and nicotine dose-equivalent concentrations of both nicotine-containing EC liquids produced similar lowering of ICSS thresholds at low to moderate nicotine doses, indicating similar reinforcement-enhancing effects. At high nicotine doses, nicotine alone elevated ICSS thresholds (a measure of anhedonia-like behavior) while the EC liquids did not. Nicotine-containing EC liquids did not differ from nicotine alone in terms of binding affinity or functional activity at nAChRs. "Nicotine-free" EC liquids did not affect ICSS, but bound with low affinity at some (e.g., α4ß2) nAChRs. These findings suggest that non-nicotine constituents in these EC liquids do not contribute to their reinforcement-enhancing effects. However, they may attenuate nicotine's acute aversive/anhedonic and/or toxic effects, which may moderate the abuse liability and/or toxicity of ECs. Copyright © 2018 Elsevier B.V. All rights reserved.

Direct comparison of oligochaete erythrocruorins as potential blood substitutes

PubMed Central

Zimmerman, Devon; DiIusto, Matthew; Dienes, Jack; Abdulmalik, Osheiza

2017-01-01

Abstract While many blood substitutes are based on mammalian hemoglobins (e.g., human hemoglobin, HbA), the naturally extracellular hemoglobins of invertebrates (a.k.a. erythrocruorins, Ecs) are intriguing alternative oxygen carriers. Specifically, the erythrocruorin of Lumbricus terrestris has been shown to effectively deliver oxygen in mice and rats without the negative side effects observed with HbA. In this study, the properties of six oligochaete Ecs (Lumbricus terrestris, Eisenia hortensis, Eisenia fetida, Eisenia veneta, Eudrilus eugeniae, and Amynthas gracilis) were compared in vitro to identify the most promising blood substitute candidate(s). Several metrics were used to compare the Ecs, including their oxidation rates, dissociation at physiological pH, thermal stability, and oxygen transport characteristics. Overall, the Ecs of Lumbricus terrestris (LtEc) and Eisenia fetida (EfEc) were identified as promising candidates, since they demonstrated high thermal and oligomeric stability, while also exhibiting relatively low oxidation rates. Interestingly, the O2 affinity of LtEc (P 50 = 26.25 mmHg at 37 °C) was also observed to be uniquely lower than EfEc and all of the other Ecs (P 50 = 9.29–13.62 mmHg). Subsequent alignment of the primary sequences of LtEc and EfEc revealed several significant amino acid substitutions within the D subunit interfaces that may be responsible for this significant change in O2 affinity. Nonetheless, these results show that LtEc and EfEc are promising potential blood substitutes that are resistant to oxidation and denaturation, but additional experiments will need to be conducted to determine their safety, efficacy, and the effects of their disparate oxygen affinities in vivo. PMID:29313031

Externalizing symptoms, effortful control, and intrusive parenting: A test of bidirectional longitudinal relations during early childhood.

PubMed

Eisenberg, Nancy; Taylor, Zoe E; Widaman, Keith F; Spinrad, Tracy L

2015-11-01

At approximately 30, 42, and 54 months of age (N = 231), the relations among children's externalizing symptoms, intrusive maternal parenting, and children's effortful control (EC) were examined. Both intrusive parenting and low EC have been related to psychopathology, but children's externalizing problems and low EC might affect the quality of parenting and one another. Mothers' intrusive behavior with their children was assessed with observations, children's EC was measured with mothers' and caregivers' reports, and children's externalizing symptoms were assessed with mothers', fathers', and caregivers' reports. In a structural equation panel model, bidirectional relations between intrusive parenting and EC were found: EC at 30 and 42 months predicted low levels of intrusive parenting a year later, controlling for prior levels of parenting and vice versa. Moreover, high levels of children's externalizing problems at both 30 and 42 months negatively predicted EC a year later, controlling for prior levels of EC. Although externalizing problems positively predicted high EC over time, this appeared to be a suppression effect because these variables had a strong negative pattern in the zero-order correlations. Moreover, when controlling for the stability of intrusive parenting, EC, and externalizing (all exhibited significant stability across time) and the aforementioned cross-lagged predictive paths, EC and externalizing problems were still negatively related within the 54-month assessment. The findings are consistent with the view that children's externalizing behavior undermines their EC and contributes to intrusive mothering and that relations between intrusive parenting and EC are bidirectional across time. Thus, interventions that focus on modifying children's externalizing problems (as well as the quality of parenting) might affect the quality of parenting they receive and, hence, subsequent problems with adjustment.

Cancer cells cause vascular endothelial cell (vEC) retraction via 12(S)HETE secretion; the possible role of cancer cell derived microparticle.

PubMed

Uchide, Keiji; Sakon, Masato; Ariyoshi, Hideo; Nakamori, Syouji; Tokunaga, Masaru; Monden, Morito

2007-02-01

Cancer cell mediated vascular endothelial cell (vEC) retraction plays a pivotal role in cancer metastasis. The aim of this study is to clarify the biochemical character of vEC retraction factor derived from human breast cancer cell line, MCF-7. In order to estimate vEC retracting activity, transwell chamber assay system was employed. We first tested the effects of trypsin digestion as well as lipid extraction of culture medium (CM). Trypsin digestion of CM resulted in approximately 40% loss of vEC retracting activity and lipid extraction of CM by Brigh and Dyer methods recovered approximately 60% of vEC retracting activity, suggesting that approximately 60% of vEC retracting activity in MCF-7 derived CM is due to lipid. Although Nordihydroguaiaretic acid (NDGA), the specific lipoxygenase inhibitor, suppressed vEC retracting activity in CM, Acetyl salicylic acid (ASA), a specific cyclooxygenase inhibitor, did not affect the activity, suggesting that lipid exerting vEC retracting activity in CM belongs to lipoxygenase mediated arachidonate metabolites. Thin layer chromatography clearly demonstrated that Rf value of lipid vEC retracting factor in CM is identical to 12HETE. Authentic 12(S)HETE, but not 12(R)HETE, showed vEC retracting activity. After the ultracentrifugation of CM, most lipid vEC retracting activity was recovered from the pellet fraction, and flow cytometric analysis using specific antibody against 12(S)HETE clearly showed the association of 12(S)HETE with small particle in CM. These findings suggested the principal involvement of 12(S)HETE in cancer cell derived microparticles in cancer cell mediated vEC retraction.

Time course of the dependence of associative memory retrieval on the entorhinal cortex.

PubMed

Chen, Xi; Liao, Zhengli; Wong, Yin Ting; Guo, Yiping; He, Jufang

2014-12-01

As the gateway between the hippocampal system and the neocortex, the entorhinal cortex (EC) is hypothesized to be the hub in which the transformation of recent memory to remote memory is processed. We explored the role of the EC on the retrieval of recent and remote associative fear memory. A within-subject approach was adopted to compare the freezing rates of rats in EC intact and EC inactivated conditions following trace fear conditioning. The EC was inactivated by infusing an AMPA antagonist. The fear conditioning used a combined visual and auditory conditioned stimulus with a foot shock. On week 1 following the conditioning, the rats in the EC intact condition exhibited a freezing rate of 92.4±9.5% in response to the light stimulus compared with a 6.3±7.9% freezing rate in the EC inactivated condition. The freezing rates were 87.0±17.8% and 4.7±6.5% on week 2 in the EC intact and inactivated conditions, respectively. These results indicate that the EC participates in the retrieval of associative memory. Extinction of the fear memory was observed in the EC intact condition, as the mean freezing rate decreased to 62.7±23.0% on week 4 and 41.2±26.4% on week 5. However, the freezing rate increased to 26.8±14.2% on week 4 and 22.3±14.4% on week 5 in the EC inactivated condition. The normalized dependence of fear memory retrieval on the EC was 93.2±8.3% on week 1, and significantly decreased on weeks 4 and 5. In summary, the retrieval of associative memory depends on the EC, but this dependence decreases over time. Copyright © 2014 Elsevier Inc. All rights reserved.

An evaluation of HIV elite controller definitions within a large seroconverter cohort collaboration.

PubMed

Olson, Ashley D; Meyer, Laurence; Prins, Maria; Thiebaut, Rodolphe; Gurdasani, Deepti; Guiguet, Marguerite; Chaix, Marie-Laure; Amornkul, Pauli; Babiker, Abdel; Sandhu, Manjinder S; Porter, Kholoud

2014-01-01

Understanding the mechanisms underlying viral control is highly relevant to vaccine studies and elite control (EC) of HIV infection. Although numerous definitions of EC exist, it is not clear which, if any, best identify this rare phenotype. We assessed a number of EC definitions used in the literature using CASCADE data of 25,692 HIV seroconverters. We estimated proportions maintaining EC of total ART-naïve follow-up time, and disease progression, comparing to non-EC. We also examined HIV-RNA and CD4 values and CD4 slope during EC and beyond (while ART naïve). Most definitions classify ∼ 1% as ECs with median HIV-RNA 43-903 copies/ml and median CD4>500 cells/mm(3). Beyond EC status, median HIV-RNA levels remained low, although often detectable, and CD4 values high but with strong evidence of decline for all definitions. Median % ART-naïve time as EC was ≥ 92% although overlap between definitions was low. EC definitions with consecutive HIV-RNA measurements <75 copies/ml with follow-up ≥ six months, or with 90% of measurements <400 copies/ml over ≥ 10 year follow-up preformed best overall. Individuals thus defined were less likely to progress to endpoint (hazard ratios ranged from 12.5-19.0 for non-ECs compared to ECs). ECs are rare, less likely to progress to clinical disease, but may eventually lose control. We suggest definitions requiring individuals to have consecutive undetectable HIV-RNA measurements for ≥ six months or otherwise with >90% of measurements <400 copies/ml over ≥ 10 years be used to define this phenotype.

Scleroderma dermal microvascular endothelial cells exhibit defective response to pro-angiogenic chemokines

PubMed Central

Rabquer, Bradley J.; Ohara, Ray A.; Stinson, William A.; Campbell, Phillip L.; Amin, M. Asif; Balogh, Beatrix; Zakhem, George; Renauer, Paul A.; Lozier, Ann; Arasu, Eshwar; Haines, G. Kenneth; Kahaleh, Bashar; Schiopu, Elena; Khanna, Dinesh; Koch, Alisa E.

2016-01-01

Objectives. Angiogenesis plays a critical role in SSc (scleroderma). The aim of this study was to examine the expression of growth-regulated protein-γ (Gro-γ/CXCL3), granulocyte chemotactic protein 2 (GCP-2/CXCL6) and their receptor CXCR2 in endothelial cells (ECs) isolated from SSc skin and determine whether these cells mount an angiogenic response towards pro-angiogenic chemokines. The downstream signalling pathways as well as the pro-angiogenic transcription factor inhibitor of DNA-binding protein 1 (Id-1) were also examined. Methods. Skin biopsies were obtained from patients with dcSSc. ECs were isolated via magnetic positive selection. Angiogenesis was measured by EC chemotaxis assay. Results. Gro-γ/CXCL3 and GCP-2/CXCL6 were minimally expressed in both skin types but elevated in SSc serum. Pro-angiogenic chemokine mRNA was greater in SSc ECs than in normal ECs. SSc ECs did not migrate to vascular endothelial growth factor (VEGF), Gro-γ/CXCL3, GCP-2/CXCL6 or CXCL16. The signalling pathways stimulated by these chemokines were also dysregulated. Id-1 mRNA in SSc ECs was lower compared with normal ECs, and overexpression of Id-1 in SSc ECs increased their ability to migrate towards VEGF and CXCL16. Conclusion. Our results show that SSc ECs are unable to respond to pro-angiogenic chemokines despite their increased expression in serum and ECs. This might be due to the differences in the signalling pathways activated by these chemokines in normal vs SSc ECs. In addition, the lower expression of Id-1 also decreases the angiogenic response. The inability of pro-angiogenic chemokines to promote EC migration provides an additional mechanism for the impaired angiogenesis that characterizes SSc. PMID:26705326

Esophageal cancer in Kenya

PubMed Central

Odera, Joab Otieno; Odera, Elizabeth; Githang’a, Jessie; Walong, Edwin Oloo; Li, Fang; Xiong, Zhaohui; Chen, Xiaoxin Luke

2017-01-01

Kenya belongs to a high incidence region known as Africa’s esophageal cancer (EC) corridor. It has one of the highest incidence rates of EC worldwide, but research on EC in Kenya has gone highly unnoticed. EC in Kenya is unique in its high percentage of young cases (< 30 years of age). In this review, we show the current status of EC in the country. We mainly focus on significant risk factors such as alcohol drinking, genetic factors, malnutrition and hot food/drink. Future directions in the study and prevention of EC in Kenya are also discussed. PMID:29082268

Heterotypic contact reveals a COX-2-mediated suppression of osteoblast differentiation by endothelial cells: A negative modulatory role for prostanoids in VEGF-mediated cell: cell communication?

DOE Office of Scientific and Technical Information (OSTI.GOV)

Clarkin, Claire E.; Garonna, Elena; Pitsillides, Andrew A.

In bone, angiogenesis must be initiated appropriately, but limited once remodelling or repair is complete. Our recent findings have supported a role for prostaglandins (PG), known modulators of osteoblast (OB) and endothelial cell (EC) behaviour, in facilitating VEGF-mediated paracrine communication from OBs to 'remotely located' ECs, but the mechanism(s) regulating OB:EC crosstalk when these cells are closely opposed are undefined. In this study we have examined: (i) the effects of exogenous PGE{sub 2} on VEGF-driven events in ECs, and (ii) the role of endogenous COX-2-derived prostanoids in mediating communication between intimately opposed OBs and ECs in direct contact. Exposure ofmore » ECs to PGE{sub 2} increased ERK1/2 phosphorylation, COX-2 induction, 6-keto-PGF{sub 1{alpha}} release and EC proliferation. In contrast, PGE{sub 2} attenuated VEGF{sub 165}-induced VEGFR2/Flk1 phosphorylation, ERK1/2 activation and proliferation of ECs, suggesting that exogenous PGE{sub 2} restricts the actions of VEGF. However, the COX-2-selective inhibitor, NS398, also attenuated VEGF-induced proliferation, implying a distinct role for endogenous COX-2 activity in regulating EC behaviour. To examine the effect of OB:EC proximity and the role of COX-2 products further, we used a confrontational co-culture model. These studies showed that COX-2 blockade with NS398 enhanced EC-dependent increases in OB differentiation, that this effect was reversed by exogenous PGH{sub 2} (immediate COX-2 product), and that exogenous VEGF did not influence EC-dependent OB differentiation under these conditions. Our findings indicate that locally produced prostanoids may serve distinct roles depending on OB:EC proximity and negatively modulate VEGF-mediated changes in EC behaviour when these cells are closely opposed to control angiogenesis during bone (re)modelling.« less

Ecstasy induces reactive oxygen species, kidney water absorption and rhabdomyolysis in normal rats. Effect of N-acetylcysteine and Allopurinol in oxidative stress and muscle fiber damage

PubMed Central

de Bragança, Ana C.; Moreau, Regina L. M.; de Brito, Thales; Shimizu, Maria H. M.; Canale, Daniele; de Jesus, Denise A.; Silva, Ana M. G.; Gois, Pedro H.; Seguro, Antonio C.

2017-01-01

Background Ecstasy (Ec) use produces hyperthermia, excessive sweating, intense thirst, an inappropriate antidiuretic hormone secretion (SIADH) and a multisystemic toxicity due to oxidative stress (OS). Intense thirst induces high intake of pure water, which associated with SIADH, usually develops into acute hyponatremia (Hn). As Hn is induced rapidly, experiments to check if Ec acted directly on the Inner Medullary Collecting Ducts (IMCD) of rats were conducted. Rhabdomyolysis and OS were also studied because Ec is known to induce Reactive Oxygen Species (ROS) and tissue damage. To decrease OS, the antioxidant inhibitors N-acetylcysteine (NAC) and Allopurinol (Allo) were used. Methods Rats were maintained on a lithium (Li) diet to block the Vasopressin action before Ec innoculation. AQP2 (Aquaporin 2), ENaC (Epitheliun Sodium Channel) and NKCC2 (Sodium, Potassium, 2 Chloride) expression were determined by Western Blot in isolated IMCDs. The TBARS (thiobarbituric acid reactive substances) and GSH (reduced form of Glutathione) were determined in the Ec group (6 rats injected with Ec-10mg/kg), in Ec+NAC groups (NAC 100mg/Kg/bw i.p.) and in Allo+Ec groups (Allo 50mg/Kg/i.p.). Results Enhanced AQP2 expression revealed that Ec increased water transporter expression, decreased by Li diet, but the expression of the tubular transporters did not change. The Ec, Ec+NAC and Allo+Ec results showed that Ec increased TBARS and decreased GSH, showing evidence of ROS occurrence, which was protected by NAC and Allo. Rhabdomyolysis was only protected by Allo. Conclusion Results showed that Ec induced an increase in AQP2 expression, evidencing another mechanism that might contribute to cause rapid hyponatremia. In addition, they showed that NAC and Allo protected against OS, but only Allo decreased rhabdomyolysis and hyperthermia. PMID:28678861

Developing eco-friendly biofungicide for the management of major seed borne diseases of rice and assessing their physical stability and storage life.

PubMed

Naveenkumar, Ramasamy; Muthukumar, Arjunan; Sangeetha, Ganesan; Mohanapriya, Ramanathan

2017-04-01

Three plant oils (Cymbopogon citratus, Cymbopogon martini, and Pelargonium graveolens) were developed as EC formulations and tested for their physical stabilities. EC formulations (10EC, 20EC and 30EC) of C. citratus, C. martini and P. graveolens had emulsion stability, spontaneity property, heat and cold stability. EC formulated plant oils were screened against the major seed borne fungi of rice such as Curvularia lunata, Fusarium moniliforme, Bipolaris oryzae, and Sarocladium oryzae. The level of inhibition varied among the concentrations of EC formulations. Among the three EC formulations, that of C. citratus oil 30EC recorded 100% inhibition on the mycelial growth of test pathogens. In the blotter paper method, rice seeds treated with a formulation of C. citratus oil 30EC controlled the infection of C. lunata, F. moniliforme, B. oryzae and S. oryzae in rice seed to the tune of 66.0%, 60.4%, 66.0% and 69.1%, respectively. Seed soaking with formulation of C. citratus oil 30EC showed the highest percentage of normal seedlings, the lowest number of abnormal seedling and fresh ungerminated seeds when tested with the roll-towel method. Seed soaking with 30EC formulation of C. citratus oil increased seed germination, shoot length, root length and vigour of rice seedlings when tested with the plastic tray method. Transmission of pathogens from seed to seedling was reduced significantly by the 30EC formulation of C. citratus oil when tested with the plastic pot method. The effect of the storage life of the 30EC formulation of C. citratus oil showed that it had retained their antifungal effect till the end of the incubation period (120 days), and is able to inhibit the mycelial growth of all test pathogens to the 100% level. Copyright © 2017 Académie des sciences. Published by Elsevier Masson SAS. All rights reserved.

Endothelial cells of extremely premature infants display impaired immune response after proinflammatory stimulation.

PubMed

Wisgrill, Lukas; Muck, Martina; Wessely, Isabelle; Berger, Angelika; Spittler, Andreas; Förster-Waldl, Elisabeth; Sadeghi, Kambis

2018-01-01

BackgroundEndothelial cells (ECs) exert immunological functions such as production of proinflammatory cytokines/chemokines as well as facilitation of extravasation of immune cells into infected tissue. Limited data are available on the functionality of ECs from extremely preterm neonates during infection. Accordingly, the aim of our study was to investigate the immune response of premature ECs after proinflammatory stimulation.MethodsCell adhesion receptors' expression and function, nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NFκB) signaling, and chemokine production were analyzed in umbilical cord ECs from extremely preterm and term neonates after proinflammatory stimulation.ResultsP-selectin and E-selectin surface expression as well as NFκB signaling were lower after lipopolysaccharide (LPS) stimulation in premature ECs. Preterm ECs exhibited lower, but significant, cell-adhesive functions after LPS stimulation compared with term ECs. CCL2/CXCL8 chemokine secretion was significantly upregulated after proinflammatory stimulation in both groups. CXCL10 production was significantly increased in term but not in preterm ECs upon stimulation with tumor necrosis factor compared with unstimulated ECs.ConclusionExtremely premature ECs showed partly reduced expression levels and function of cell adhesion molecules. Both NFκB signaling and chemokine/cytokine production were reduced in premature ECs. The diminished endothelial proinflammatory immune response might result in impaired infection control of preterm newborns rendering them prone to severe infection.

Development of an indirect ELISA for the determination of ethyl carbamate in Chinese rice wine.

PubMed

Luo, Lin; Lei, Hong-Tao; Yang, Jin-Yi; Liu, Gong-Liang; Sun, Yuan-Ming; Bai, Wei-Dong; Wang, Hong; Shen, Yu-Dong; Chen, Sui; Xu, Zhen-Lin

2017-01-15

The widespread occurrence of ethyl carbamate (EC, 89.09 Da), a group 2A carcinogen, in fermented foods and alcoholic beverages has raised worldwide public health concern. Immunoassay for EC is unavailable due to the simple and small structure of EC. In this work, an initial attempt to produce antibody specific for EC, by using 4-((ethoxycarbonyl)amino)butanoic acid as hapten, was made but failed. However, since EC can easily react with 9-xanthydrol to form xanthyl ethyl carbamate (XEC), two haptens based on XEC structure were designed and synthesized. Polyclonal antibody against XEC, instead of EC was obtained and then used to develop a competitive indirect ELISA for EC via a pre-analysis derivatization. After optimization, the ciELISA was applied in analyzing Chinese rice wine with detection limit of 166 μg/L, and negligible cross-reactivity with EC analogs. Recoveries of EC in fortified samples were from 84.4% to 100.9%, with coefficients of variation below 10%. Results for analysis of real samples by the ci-ELISA correlated well with that by reference method GC-MS, suggesting the good accuracy and reproducibility of the proposed method. This is the first report of an immunoassay capable of detecting EC, which is suitable for monitoring EC in a large amount of samples. Copyright © 2016 Elsevier B.V. All rights reserved.

High Time- and Size-Resolved Measurements of PM and Chemical Composition from Coal Combustion: Implications for the EC Formation Process.

PubMed

Han, Yong; Chen, Yingjun; Ahmad, Saud; Feng, Yanli; Zhang, Fan; Song, Wenhuai; Cao, Fang; Zhang, Yanlin; Yang, Xin; Li, Jun; Zhang, Gan

2018-06-05

Inefficient coal combustion is a significant source of elemental carbon (EC) air pollution in China, but there is a limited understanding of EC's formation processes. In this study, high time-resolved particle number size distributions (PNSDs) and size-resolved chemical compositions were obtained from the combustion of four bituminous coals burned in a quartz tube furnace at 500 and 800 °C. Based on the distinct characteristics of PNSD, the flaming stage was divided into the first-flaming stage (with a PNSD peak at 0.3-0.4 μm) and the second-flaming stage (with a PNSD peak at 0.1-0.15 μm). For the size-segregated EC and OC measurements, more soot-EC was observed in particles larger than 0.3 μm, whereas the smaller ones possessed more char-EC. The results indicated that gas-phase and direct-conversion EC generation mechanisms dominate different burning stages. The analysis of 16 parent PAHs showed more high-molecular-weight PAHs in the second-flaming stage particles, which supports the idea of different formation processes for char-EC and soot-EC. For all four coals, the PNSD and chemical compositions shared a similar trend, confirming that the different formation processes of EC in different flaming stages were common. This study provides novel information concerning EC formation.

Effect of stimulus intensity and number of treatments on ECS-related seizure duration and retrograde amnesia in rats.

PubMed

Andrade, Chittaranjan; Thyagarajan, S; Vinod, P S; Srikanth, S N; Rao, N S K; Chandra, J Suresh

2002-12-01

Animal models are frequently used to generate and test hypotheses about amnesia resulting from electroconvulsive therapy (ECT). Although many predictors of ECT-induced amnesia are known, their relative effects have been inadequately researched in the context of the animal models. We sought to determine the relative retrograde amnestic effects of electroconvulsive shock (ECS) stimulus intensity (dose) and number on strong memories in rats. We also sought to identify dose-dependent ceiling amnestic effects, if any. Adult rats (n = 144) were overtrained in a passive avoidance task using a step down apparatus. The rats were then randomized in a factorial design to receive one, two, or three once-daily bilateral ECS at 0-mC (sham ECS), 30-mC, 60-mC, 120-mC, or 180-mC doses. Recall of the pre-ECS training was assessed 1 day after the last ECS. Retrograde amnesia was observed only in rats that received 3 ECS; dose-dependent amnestic effects did not emerge. Higher stimulus intensity was associated with a small (13%) but significant increase in motor seizure duration, but only at the first ECS; stimulus intensity did not influence the attenuation of seizure duration across repeated occasions of ECS. With bilateral ECS, the number of ECSs administered is a more important variable than the ECS dose in weakening a strong, recently acquired, noxious memory; this finding may have important clinical implications. Higher stimulus intensity marginally increases motor seizure duration at the first ECS but does not influence the decrease in seizure duration across repeated ECSs.

Budget analysis of Escherichia coli at a southern Lake Michigan Beach

USGS Publications Warehouse

Thupaki, P.; Phanikumar, M.S.; Beletsky, D.; Schwab, D.J.; Nevers, M.B.; Whitman, R.L.

2010-01-01

Escherichia coli (EC) concentrations at two beaches impacted by river plume dynamics in southern Lake Michigan were analyzed using three-dimensional hydrodynamic and transport models. The relative importance of various physical and biological processes influencing the fate and transport of EC were examined via budget analysis and a first-order sensitivity analysis of model parameters. The along-shore advective fluxofEC(CFU/m2·s)was found to be higher compared to its crossshore counterpart; however, the sum of diffusive and advective components was of a comparable magnitude in both directions showing the importance of cross-shore exchange in EC transport. Examination of individual terms in the EC mass balance equation showed that vertical turbulent mixing in the water column dominated the overall EC transport for the summer conditions simulated. Dilution due to advection and diffusion accounted for a large portion of the total EC budget in the nearshore, and the net EC loss rate within the water column (CFU/m3·s) was an order of magnitude smaller compared to the horizontal and vertical transport rates. This result has important implications for modeling EC at recreational beaches; however, the assessment of the magnitude of EC loss rate is complicated due to the strong coupling between vertical exchange and depth-dependent EC loss processes such as sunlight inactivation and settling. Sensitivity analysis indicated that solar inactivation has the greatest impact on EC loss rates. Although these results are site-specific, they clearly bring out the relative importance of various processes involved.

Mechano-sensing and transduction by endothelial surface glycocalyx: composition, structure, and function

PubMed Central

Fu, Bingmei M.; Tarbell, John M.

2014-01-01

The endothelial cells (ECs) lining every blood vessel wall are constantly exposed to the mechanical forces generated by blood flow. The EC responses to these hemodynamic forces play a critical role in the homeostasis of the circulatory system. To ensure proper EC mechano-sensing and transduction, there are a variety of mechano-sensors and transducers that have been identified on the EC surface, intra- and trans-EC membrane and within the EC cytoskeleton. Among them, the most recent candidate is the endothelial surface glycocalyx (ESG), which is a matrix-like thin layer covering the luminal surface of the EC. It consists of various proteoglycans, glycosaminoglycans, and plasma proteins, and is close to other prominent EC mechano-sensors and transducers. The ESG thickness was found to be in the order of 0.1–1 μm by different visualization techniques and in different types of vessels. Detailed analysis on the electron microscopy (EM) images of the microvascular ESG revealed a quasi-periodic substructure with the ESG fiber diameter of 10–12 and 20 nm spacing between adjacent fibers. Atomic force microscopy and optical tweezers were applied to investigate the mechanical properties of the ESG on the cultured EC monolayers and in solutions. Enzymatic degradation of specific ESG glycosaminoglycan components was used to directly elucidate the role of the ESG in EC mechano-sensing and transduction by measuring the shear-induced productions of nitric oxide and prostacyclin, two characteristic responses of the ECs to the flow. The unique location, composition, and structure of the ESG determine its role in EC mechano-sensing and transduction. PMID:23401243

Study on chemotherapeutic sensitizing effect of nimotuzumab on different human esophageal squamous carcinoma cells.

PubMed

Yang, Xiaoyu; Ji, Yinghua; Kang, Xiaochun; Chen, Meiling; Kou, Weizheng; Jin, Cailing; Lu, Ping

2016-02-01

Esophageal cancer is one of the leading causes of mortality worldwide. Although, surgery, radio- and chemotherapy are used to treat the disease, the identification of new drugs is crucial to increase the curative effect. The aim of the present study was to examine the chemotherapeutic sensitizing effect of nimotuzumab (h-R3) and cisplatin cytotoxic drugs cisplatin (DDP) and 5-fluorouracil (5-FU) on esophageal carcinoma cells with two different epidermal growth factor receptor (EGFR) expressions. The expression of EGFR was detected in the human EC1 or EC9706 esophageal squamous cell carcinoma cell line using immunohistochemistry. The inhibitory effect of DDP and 5-FU alone or combined with h-R3 on EC1 or EC9706 cell proliferation was detected using an MTT assay. Flow cytometry and the TUNEL assay were used to determine the effect of single or combined drug treatment on cell apoptosis. The results showed that the expression of EGFR was low in EC1 cells but high in EC9706 cells. The inhibitory effect of the single use of h-R3 on EC1 or EC9706 cell proliferation was decreased. The inhibitory effect between single use of h-R3 alone and combined use of the chemotherapy drugs showed no statistically significant difference (P>0.05) on the EC1 cell growth rate, but showed a statistically significant difference (a=0.05) on EC9706 cell growth rate. The results detected by flow cytometry and TUNEL assay showed that the difference between single use of h-R3 alone and the control group was statistically significant with regard to the EC1 apoptosis rate effect (P<0.05), but not statistically significant for EC9706 (P>0.05). However, statistically significant differences were identified in the apoptotic rate of EC9706 cells between the h-R3 combined chemotherapy group and single chemotherapy group (P<0.05), but not on in the EC1 chemotherapy group (P>0.05). In conclusion, the sensitization effect of h-R3 on chemotherapy drugs is associated with the expression level of EGFR in EC1 or EC9706 cells. The cell killing effect of the combined use of h-R3 with DDP and 5-FU showed no obvious synergistic effect compared to the single-drug group, but only an additive effect.

High but not low ECS stimulus intensity augments apomorphine-stimulated dopamine postsynaptic receptor functioning in rats.

PubMed

Andrade, Chittaranjan; Srinivasamurthy, Gurunath M; Vishwasenani, A; Prakash, G Sai; Srihari, B S; Chandra, J Suresh

2002-06-01

Clinical research shows that the antidepressant and cognitive adverse effects of electroconvulsive therapy are both dependent on the administered electrical stimulus intensity (dose); however, dose-dependent neurotransmitter system changes in the brain, which might underlie the therapeutic or adverse effects, remain to be demonstrated. We used a behavioral model to examine dose-related effects of electroconvulsive shock (ECS) on dopamine postsynaptic receptor functioning in the rat brain. In a factorially designed study, rats (n = 100) were treated with five once-daily ECSs at three levels (sham ECS, 30 mC ECS, and 120 mC ECS), and with drug at two levels (saline, and 1 mg/kg s.c. apomorphine). Motility was assessed in the small open field. Apomorphine-elicited, dopamine postsynaptic receptor-mediated hypermotility was significantly increased by 120 mC ECS but not by 30 mC ECS. An additional but unrelated finding was that, while the ECS seizure duration expectedly decreased across time, no dose-dependent effects were observed. ECS-induced dopamine postsynaptic receptor up-regulation may depend on the intensity of the administered electrical stimulus.

Pregnant Women's Perspectives on Expanded Carrier Screening.

PubMed

Propst, Lauren; Connor, Gwendolyn; Hinton, Megan; Poorvu, Tabitha; Dungan, Jeffrey

2018-02-23

Expanded carrier screening (ECS) is a relatively new carrier screening option that assesses many conditions simultaneously, as opposed to traditional ethnicity-based carrier screening for a limited number of conditions. This study aimed to explore pregnant women's perspectives on ECS, including reasons for electing or declining and anxiety associated with this decision-making. A total of 80 pregnant women were surveyed from Northwestern Medicine's Clinical Genetics Division after presenting for aneuploidy screening. Of the 80 participants, 40 elected and 40 declined ECS. Trends regarding reasons for electing or declining ECS include ethnicity, desire for genetic risk information, lack of family history, perceived likelihood of being a carrier, and perceived impact on reproductive decisions. Individuals who declined ECS seemed to prefer ethnicity-based carrier screening and believed that ECS would increase their anxiety, whereas individuals who elected ECS seemed to prefer more screening and tended to believe that ECS would reduce their anxiety. These findings provide insight on decision-making with regard to ECS and can help guide interactions that genetic counselors and other healthcare providers have with patients, including assisting patients in the decision-making process.

Emergency contraception in Honduras: knowledge, attitudes, and practice among urban family planning clients.

PubMed

García, Sandra G; Lara, Diana; Landis, Sarah H; Yam, Eileen A; Pavón, Suyapa

2006-09-01

Emergency contraception (EC) has the potential to improve women's reproductive health significantly. In Honduras, where nearly one-fourth of pregnancies are unplanned, the need for EC is substantial. To increase awareness of this option, nongovernmental organizations launched countrywide EC outreach activities in 2001-03. We conducted pre- and postintervention cross-sectional surveys among a total of 2,693 family planning clinic clients to assess EC knowledge, attitudes, and practice at baseline and at two years postintroduction. EC awareness increased over time, but remained at just 20 percent at follow-up. Respondents generally demonstrated a positive attitude and low rates of concern about EC. Awareness of and willingness to use EC were strongly associated with age, educational status, and city of residence. Public-sector acceptance of the method is essential to increase awareness of and access to EC. This study is intended to fill an information gap regarding EC in Latin America and the Caribbean and to be useful in determining educational messages and target audiences for future awareness campaigns in Honduras.

Plasmodium falciparum Adhesion on Human Brain Microvascular Endothelial Cells Involves Transmigration-Like Cup Formation and Induces Opening of Intercellular Junctions

PubMed Central

Jambou, Ronan; Combes, Valery; Jambou, Marie-Jose; Weksler, Babeth B.; Couraud, Pierre-Olivier; Grau, Georges E.

2010-01-01

Cerebral malaria, a major cause of death during malaria infection, is characterised by the sequestration of infected red blood cells (IRBC) in brain microvessels. Most of the molecules implicated in the adhesion of IRBC on endothelial cells (EC) are already described; however, the structure of the IRBC/EC junction and the impact of this adhesion on the EC are poorly understood. We analysed this interaction using human brain microvascular EC monolayers co-cultured with IRBC. Our study demonstrates the transfer of material from the IRBC to the brain EC plasma membrane in a trogocytosis-like process, followed by a TNF-enhanced IRBC engulfing process. Upon IRBC/EC binding, parasite antigens are transferred to early endosomes in the EC, in a cytoskeleton-dependent process. This is associated with the opening of the intercellular junctions. The transfer of IRBC antigens can thus transform EC into a target for the immune response and contribute to the profound EC alterations, including peri-vascular oedema, associated with cerebral malaria. PMID:20686652

Early diagnostic potential of APC hypermethylation in esophageal cancer.

PubMed

Wang, Bujiang; Song, Haojun; Jiang, Haizhong; Fu, Yangbo; Ding, Xiaoyun; Zhou, Chongchang

2018-01-01

The hypermethylation of APC gene is observed in various cancers, including esophageal cancer (EC). However, the association between APC methylation and the initiation and progression of EC is poorly understood. The current study systematically reviewed studies on abnormal methylation of APC in EC and quantitatively synthesized 18 studies by meta-analysis involving 1008 ECs, 570 Barrett's esophagus (BE), and 782 controls. Our results showed higher methylation of APC in EC (OR = 23.33, P < 0.001) and BE (OR = 9.34, P < 0.001) than in normal controls. Whereas APC methylation in EC was similar to that in BE ( P = 0.052), it was not associated with tumor stage ( P = 0.204). Additionally, APC methylation was not significantly associated with overall survival (OS) and relapse-free survival (RFS) in patients with EC. The performance of APC methylation for the detection of EC and BE achieved areas under the receiver operating characteristic curves of 0.94 and 0.88, respectively. Our results imply that APC methylation detection is a potential diagnostic biomarker for EC and BE.

Adopted Individuals' Views on the Utility and Value of Expanded Carrier Screening.

PubMed

Spencer, Sara; Ewing, Sarah; Calcagno, Kathryn; O'Neill, Suzanne

2018-03-30

Adoptees may not have family medical history and ethnicity information. Carrier screening assesses reproductive risk. Expanded carrier screening (ECS) screens for many genetic conditions regardless of a patient's knowledge of family history and ethnicity. This study aimed to better understand the opinions and attitudes of adopted individuals on the use of ECS in determining a patient's reproductive genetic risks. Specifically, the study assessed how adopted individuals feel that results of ECS may be useful to them and whether adoptees feel that meeting with a genetics professional in the process of undergoing ECS would be useful. Adult adoptees (N = 124) were recruited online. Their opinions on ECS were explored. The majority reported they had never been offered carrier screening (92%). The majority of adoptees wanted ECS (76%). Neither the amount of contact with biological relatives nor having medical knowledge about biological relatives was significantly associated with adoptees' desire to pursue ECS. There was a significant positive correlation between adoptees of higher education levels and the amount they would pay for ECS (p = 0.004). The majority of participants (95%) indicated a genetics professional would be helpful when undergoing ECS. The findings suggest this population may want ECS and support from genetics healthcare professionals. Advocacy for genetic counseling and testing for adoptees appears justifiable.

A Contact-Based Method for Differentiation of Human Mesenchymal Stem Cells into an Endothelial Cell-Phenotype.

PubMed

Joddar, Binata; Kumar, Shweta Anil; Kumar, Alok

2018-06-01

Adult stem cells such as mesenchymal stem cells (MSC) are known to possess the ability to augment neovascularization processes and are thus widely popular as an autologous source of progenitor cells. However there is a huge gap in our current knowledge of mechanisms involved in differentiating MSC into endothelial cells (EC), essential for lining engineered blood vessels. To fill up this gap, we attempted to differentiate human MSC into EC, by culturing the former onto chemically fixed layers of EC or its ECM, respectively. We expected direct contact of MSC when cultured atop fixed EC or its ECM, would coax the former to differentiate into EC. Results showed that human MSC cultured atop chemically fixed EC or its ECM using EC-medium showed enhanced expression of CD31, a marker for EC, compared to other cases. Further in all human MSC cultured using EC-medium, typically characteristic cobble stone shaped morphologies were noted in comparison to cells cultured using MSC medium, implying that the differentiated cells were sensitive to soluble VEGF supplementation present in the EC-medium. Results will enhance and affect therapies utilizing autologous MSC as a cell source for generating vascular cells to be used in a variety of tissue engineering applications.

Prevalence and Risk Factors of Esophageal Candidiasis in Healthy Individuals: A Single Center Experience in Korea

PubMed Central

Choi, Jae Hyeuk; Lee, Chang Geun; Kang, Hyoun Woo; Lim, Chi Yeon; Choi, Jong-Sun

2013-01-01

Purpose Esophageal candidiasis (EC) is the most frequent opportunistic fungal infection in immunocompromised host. However, we have found EC in healthy individuals through esophagogastroduodenoscopy (EGD). The aim of this study was to determine the prevalence and risk factors for EC in healthy individuals. Materials and Methods We retrospectively reviewed the medical records of 281 patients who had been incidentally diagnosed with EC. We also conducted age and sex matched case control study to identify the risk factor for EC. Results The prevalence of EC was 0.32% (281/88125). The most common coexisting EGD finding was reflux esophagitis (49/281, 17.4%). An antifungal agent was prescribed in about half of EC, 139 cases (49.5%). Follow-up EGD was undertaken in 83 cases (29.5%) and 20 cases of candidiasis was persistently found. Case control study revealed EC were more often found in user of antibiotics (p=0.015), corticosteroids (p=0.002) and herb medication (p=0.006) as well as heavy drinking (p<0.001). Conclusion The prevalence of EC was 0.32% (281/88125) in Korea. Use of antibiotics, corticosteroids and herb as well as heavy drinking were significant risk factors for EC in healthy individuals. PMID:23225813

Origins of Effortful Control: Infant and Parent Contributions

PubMed Central

Gartstein, Maria A.; Bridgett, David J.; Young, Brandi N.; Panksepp, Jaak; Power, Thomas

2012-01-01

Effortful control (EC) refers to the ability to inhibit a dominant response to perform a subdominant one and has been shown as protective against a myriad of difficulties. Research examining precursors of EC has been limited to date, and in this study, infancy contributors to toddler EC were examined. Specifically, parent/family background variables (e.g., education, income), maternal temperament, perceived stress, and internalizing symptoms were addressed, along with infant temperament: positive affectivity/surgency (PAS), negative emotionality (NE), and regulatory capacity/orienting (RCO); and laboratory observation-based indicators of attention. Infant attention indexed by the latency to look away after initially orienting to the presented stimuli emerged as an important predictor of later EC, after accounting for other child and parent/family attributes, with shorter latencies predicting higher levels of EC. Mothers’ extraversion and parenting stress were the only parent/family attributes to significantly contribute to the prediction of toddler EC, with the former promoting and the latter undermining the development of EC. Infant temperament factors were also examined as a moderator of parent/family influences, with results indicating a significant interaction between mothers’ EC and infant RCO, so that children with greater RCO and mothers high in EC exhibited the highest EC scores in toddlerhood. PMID:26269695

Acceptability and use of emergency contraception among married women in Bangalore, India.

PubMed

Rocca, Corinne H; Shankar, Mridula; Sreevathsa, Anuradha; Krishnan, Suneeta

2013-04-01

To assess knowledge, acceptability, and use of emergency contraceptive pills (ECs) among lower-income married women in Bangalore, India. EC counseling and supplies were offered to 322 women aged 18-25 years participating in a longitudinal reproductive health study. Participants completed interviews at enrollment and were followed for 1 year. EC acceptability and use were assessed, and factors associated with use were identified. 206/320 (64.4%) participants did not desire pregnancy but only 46/321 (14.3%) used an intrauterine device or contraceptive pills. Only 25 (7.8%) had heard of ECs. Overall, 123 (38.2%) participants requested advance provisions of ECs after counseling. Over a year, 37/263 (14.1%) women used ECs, usually within 3 days of unprotected sex (33 [89.2%]), and 32 (86.5%) took both pills together or 1 day apart. Thirty-six (97.3%) felt glad and 31 (83.8%) were relieved after taking ECs. Twenty-five (67.6%) women who used ECs sought permission from their husbands. The only factor associated with EC use was couples' pregnancy intentions (odds ratio 4.71; 95% confidence interval, 1.43-15.58; P≤0.01). Indian women with access to ECs generally used them correctly and found them acceptable. Efforts to expand EC knowledge and access should be coupled with efforts to promote gender equality in the reproductive sphere. Copyright © 2012 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

Carbonaceous aerosols from prescribed burning of a boreal forest ecosystem. Revision

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mazurek, M.A.; Cofer, W.R. III; Levine, J.S.

1990-10-01

The identity and ambient mass concentrations of radiatively important carbonaceous aerosols were measured for a boreal forest prescribed burn conducted in northern Ontario, CAN in August 1989. Nonsize-segregated airborne particles were collected for smoldering-fire and full-fire conditions using a helicopter sampling platform. Total carbon (TC), organic carbon (OC) and elemental carbon (EC) were measured. Smoke plume mass concentrations of the OC and EC particles were greatest for full-fire conditions and had ranges of 1.560 to 2.160 mg/m{sup {minus}1} (OC) and 0.120 to 0.160 mg/m{sup {minus}3} (EC) with OC:EC ratios of 10 to 18, respectively. Smoldering fire conditions showed smoke plumemore » OC and EC levels of 0.570--1.030 mg/m{sup {minus}3} (OC) and 0.006--0.050 mg/m{sup {minus}3} (EC) and much higher ratios of OC:EC (21 to 95). These aerosol data indicate the formation of EC particles is greatest during full-fire combustion of boreal forest material relative to smoldering combustion. However, EC particles comprise a minor fraction of the particulate carbon smoke aerosols for both full-fire and smoldering conditions; the major component of carbonaceous smoke aerosols emitted during the prescribed burn is OC. Overall, the OC and EC in-plume smoke aerosol data show nonuniform production of these particles during various stages of the prescribed burn, and major differences in the type of carbonaceous aerosol that is generated (OC versus EC).« less

Carbonaceous aerosols from prescribed burning of a boreal forest ecosystem

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mazurek, M.A.; Cofer, W.R. III; Levine, J.S.

1990-10-01

The identity and ambient mass concentrations of radiatively important carbonaceous aerosols were measured for a boreal forest prescribed burn conducted in northern Ontario, CAN in August 1989. Nonsize-segregated airborne particles were collected for smoldering-fire and full-fire conditions using a helicopter sampling platform. Total carbon (TC), organic carbon (OC) and elemental carbon (EC) were measured. Smoke plume mass concentrations of the OC and EC particles were greatest for full-fire conditions and had ranges of 1.560 to 2.160 mg/m{sup {minus}1} (OC) and 0.120 to 0.160 mg/m{sup {minus}3} (EC) with OC:EC ratios of 10 to 18, respectively. Smoldering fire conditions showed smoke plumemore » OC and EC levels of 0.570--1.030 mg/m{sup {minus}3} (OC) and 0.006--0.050 mg/m{sup {minus}3} (EC) and much higher ratios of OC:EC (21 to 95). These aerosol data indicate the formation of EC particles is greatest during full-fire combustion of boreal forest material relative to smoldering combustion. However, EC particles comprise a minor fraction of the particulate carbon smoke aerosols for both full-fire and smoldering conditions; the major component of carbonaceous smoke aerosols emitted during the prescribed burn is OC. Overall, the OC and EC in-plume smoke aerosol data show nonuniform production of these particles during various stages of the prescribed burn, and major differences in the type of carbonaceous aerosol that is generated (OC versus EC).« less

Sorption of biodegradation end products of nonylphenol polyethoxylates onto activated sludge.

PubMed

Hung, Nguyen Viet; Tateda, Masafumi; Ike, Michihiko; Fujita, Masanori; Tsunoi, Shinji; Tanaka, Minoru

2004-01-01

Nonylphenol(NP), nonylphenoxy acetic acid (NP1EC), nonylphenol monoethoxy acetic acid (NP2EC), nonylphenol monoethoxylate (NP1EO) and nonylphenol diethoxylate (NP2EO) are biodegradation end products (BEPs) of nonionic surfactant nonylphenolpolyethoxylates (NPnEO). In this research, sorption of these compounds onto model activated sludge was characterized. Sorption equilibrium experiments showed that NP, NP1EO and NP2EO reached equilibrium in about 12 h, while equilibrium of NP1EC and NP2EC were reached earlier, in about 4 h. In sorption isotherm experiments, obtained equilibrium data at 28 degrees C fitted well to Freundlich sorption model for all investigated compounds. For NP1EC, in addition to Freundlich, equilibrium data also fitted well to Langmuir model. Linear sorption model was also tried, and equilibrium data of all NP, NP1EO, NP2EO and NP2EC except NP1EC fitted well to this model. Calculated Freundlich coefficient (K(F)) and linear sorption coefficient (K(D)) showed that sorption capacity of the investigated compounds were in order NP > NP2EO > NP1EO > NP1EC approximately NP2EC. For NP, NP1EO and NP2EO, high values of calculated K(F) and K(D) indicated an easy uptake of these compounds from aqueous phase onto activated sludge. Whereas, NP1EC and NP2EC with low values of K(F) and K(D) absorbed weakly to activated sludge and tended to preferably remain in aqueous phase.

The molecular basis of conformational instability of the ecdysone receptor DNA binding domain studied by in silico and in vitro experiments.

PubMed

Szamborska-Gbur, Agnieszka; Rymarczyk, Grzegorz; Orłowski, Marek; Kuzynowski, Tomasz; Jakób, Michał; Dziedzic-Letka, Agnieszka; Górecki, Andrzej; Dobryszycki, Piotr; Ożyhar, Andrzej

2014-01-01

The heterodimer of the ecdysone receptor (EcR) and ultraspiracle (Usp), members of the nuclear receptors superfamily, regulates gene expression associated with molting and metamorphosis in insects. The DNA binding domains (DBDs) of the Usp and EcR play an important role in their DNA-dependent heterodimerization. Analysis of the crystal structure of the UspDBD/EcRDBD heterocomplex from Drosophila melanogaster on the hsp27 gene response element, suggested an appreciable similarity between both DBDs. However, the chemical denaturation experiments showed a categorically lower stability for the EcRDBD in contrast to the UspDBD. The aim of our study was an elucidation of the molecular basis of this intriguing instability. Toward this end, we mapped the EcRDBD amino acid sequence positions which have an impact on the stability of the EcRDBD. The computational protein design and in vitro analyses of the EcRDBD mutants indicate that non-conserved residues within the α-helix 2, forming the EcRDBD hydrophobic core, represent a specific structural element that contributes to instability. In particular, the L58 appears to be a key residue which differentiates the hydrophobic cores of UspDBD and EcRDBD and is the main reason for the low stability of the EcRDBD. Our results might serve as a benchmark for further studies of the intricate nature of the EcR molecule.

A nationally representative study of emotional competence and health.

PubMed

Mikolajczak, Moïra; Avalosse, Hervé; Vancorenland, Sigrid; Verniest, Rebekka; Callens, Michael; van Broeck, Nady; Fantini-Hauwel, Carole; Mierop, Adrien

2015-10-01

Emotional competence (EC; also called "emotional intelligence"), which refers to individual differences in the identification, understanding, expression, regulation, and use of one's emotions and those of others, has been found to be an important predictor of individuals' adaptation to their environment. Higher EC is associated with greater happiness, better mental health, more satisfying social and marital relationships, and greater occupational success. Whereas a considerable amount of research has documented the significance of EC, 1 domain has been crucially under investigated: the relationship between EC and physical health. We examined the relationship between EC and objective health indicators in 2 studies (N1 = 1,310; N2 = 9,616) conducted in collaboration with the largest Mutual Benefit Society in Belgium. These studies allowed us (a) to compare the predictive power of EC with other well-known predictors of health such as age, sex, Body Mass Index, education level, health behaviors (diet, physical activity, smoking and drinking habits), positive and negative affect, and social support; (b) to clarify the relative weight of the various EC dimensions in predicting health; and (c) to determine to what extent EC moderates the effect of already known predictors on health. Results show that EC is a significant predictor of health that has incremental predictive power over and above other predictors. Findings also show that high EC significantly attenuates (and sometimes compensates for) the impact of other risk factors. Therefore, we argue that EC deserves greater interest and attention from health professionals and governments. (c) 2015 APA, all rights reserved).

[Investigation into the relationship between outpatient haemodialysis centres and referring hospitals in Spain].

PubMed

Arenas, M D; Bernat, A; Ramos, R; Berdud, I; Blanco, A

2009-01-01

To guarantee continuity and equity in the clinical assistance of patients on hemodialysis in extrahospitalary centers (EC) a close relationship and a good level of communication between them and their reference hospitals (RH) is essential. The aim of this study was to assess the present situation of this relationship in our country (Spain) so as to be able to detect improvement opportunities. Descriptive and transversal study using two self-report anonymous surveys: one for EC (81 questions) and one for RH (56 questions) sent by e-mail to all Spanish EC and RH registered in the Spanish Society of Nephrology. We received answers from 80 EC and 30 RH. 70% of the EC were managed by multinational companies; only 16 % EC were placed in a hospital. 64% of the EC need to employ non-nephrological medical staff. Nearly 40% of the EC nephrologists also go on duty at their RH. More than three quarters of the EC nephrologists are alone during their workday. Bidirectional telephone communication is very frequent between EC and RH. Around a third of the patients sent from RH to EC arrive without current viral serology and/or without a functioning vascular access. Most of the patients sent from EC to RH bring an up-to-date complete medical report. 41,3 % of the EC answered that they were usually consulted by their RH doctor colleagues about decisions to be taken regarding their patients. Routine blood and other medical protocol tests of CE are well defined in the formal agreement with their RH in 65 % of the cases, although they can be modified by the EC through consensus with the RH in more than 50 % of the cases. 60 % of the EC can directly consult other specialists in the RH but more than 50 % need to do so through the RH nephrologist. Parenteral medication used in the ECs is mostly supplied by their RH, but a third of ECs have some limitations with uncommon or not concert-specified parenteral drugs. RHs refer that most of the vascular accesses are done in the hospital, whereas ECs say that this is true only in half of the cases. More than a third of the fistulae of predialysis patients are done in the ECs as part of their collaboration with RHs. The majority of ECs can share the decision about patients' inclusion in renal transplant waiting list. In only a fifth of the cases is there a common database between CE and RH, and less than half share common protocols or objectives. 62,5% of CEs participate with RHs in clinical trials. More than half of the dialysis private companies provide continuous training and education to their ECs personnel, either directly through the company or facilitating assistance to courses or congresses. Some of the relationship aspects that appear to be clearly improvable are: CEs nephrologist solitude and their limited access to continuous training and education, an adequate referral of the patients from the RHs, CEs nephrologist's autonomy at making consultations to specialists or their limitations when asking for hospital medications. A closer relationship between CEs and RHs is of the utmost importance in guaranteeing continuity and equity in the clinical assistance of our hemodialysis patients. The creation of a debate forum would favour discussion and common resolution of such aspects.

[The impact of the EU Regulation 536/2014 on the tasks and functioning of ethics committees in Germany].

PubMed

Hasford, Joerg

2017-08-01

The EU Clinical Trial Regulation 536/2014 (CTR) and its implementation in Germany led to substantial changes of the established, well-accepted and effective system of reviewing clinical trial applications by ethics committees (ECs), which impair their independence. For the first time, the German federal legislator specified in detail the composition, functioning, tasks and responsibilities of ECs. ECs have to be registered with the federal drug authority BfArM and if an EC does not perform properly the registration can be withdrawn. In addition, the drug authorities may override the negative opinion expressed by an EC. The ECs will also lose their financial autonomy as the fees will be fixed by the federal government. The tasks and responsibilities of the ECs remain almost entirely unchanged, however. The ECs remain involved in the assessment of both parts of the application dossier. Part I is assessed together with the drug authorities, the drug authorities having the lead. The assessment of part II remains the sole responsibility of the EC. As the deadlines for the assessment became rather short, in particular for multinational trials, and the communication with the sponsor will be in writing only, the established procedures of ECs have to be modified. Up to now it was common to verbally discuss problematic issues with the sponsor. The CTR is focused on written communication with the sponsor via the EU portal. ECs, their office staff and chairpersons will need considerable professionalism and respective training. The future workflow requires substantial IT support. The ECs and the Association of Medical Ethics Committees in Germany will do their utmost to protect efficiently the research subjects and to promote Germany as a major destination for clinical research.

Access to Emergency Contraception in the Over-the-Counter Era

PubMed Central

Cleland, Kelly; Bass, Jamie; Doci, Florida; Foster, Angel M.

2016-01-01

Introduction After years of complex regulatory changes, levonorgestrel emergency contraception (LNG EC) is now approved for unrestricted sale in the US. Timely access to EC pills is critical because they are more likely to work the sooner they are taken. This study assesses whether LNG EC is sold in accordance with current Food and Drug Administration regulations. Methods We distributed an online questionnaire through an EC-focused listserv for reproductive health professionals, asking data collectors to visit local stores and document product names, price, over-the-counter (OTC) shelf availability, and misinformation about age restrictions. We used Chi-square analysis to assess bivariate associations and t-tests and Wilcoxon rank-sum tests to determine differences in means. Results We collected information about 220 stores. The majority (65%) stocked EC on OTC shelves, although only 22% of these displayed it without a locked security enclosure. Chain pharmacies were more likely to shelf-stock EC than independent pharmacies (77% vs 5%; p=0.000), but variation existed among stores within the same chain. Among stores that were asked, 40% incorrectly reported an age restriction for non-prescription purchase of LNG EC, while 95% correctly reported that men can buy LNG EC. The average price of branded and generic LNG EC was $49.64 and $40.05, respectively. Conclusion Changes in the regulatory status of LNG EC have resulted in widespread confusion about how EC can be sold, and its high price contributes to access barriers. Retailers should ensure that consumers can access LNG EC quickly and easily by stocking the product on OTC shelves and educating staff about current regulations. PMID:27682018

Relationships of eating competence, sleep behaviors and quality, and overweight status among college students.

PubMed

Quick, Virginia; Shoff, Suzanne; Lohse, Barbara; White, Adrienne; Horacek, Tanya; Greene, Geoffrey

2015-12-01

Little is known about the relationships between eating competence (intra-individual approach to eating and food-related attitudes and behaviors that entrain positive bio-psychosocial outcomes) and sleep behaviors and quality in college students, a high-risk group for poor eating habits, weight gain, and inadequate sleep. Thus, data from full-time college students (N=1035; 82% White; 61% female) aged 18-24 years from 5 U.S. universities were obtained from online questionnaires (eating competence (ecSI), Pittsburg Sleep Quality Index (PSQI), physical activity, demographics) and physical assessments (measured height, weight), to explore sleep behavior and quality between eating-competent (EC; ecSI score≥32) and non-EC groups (ecSI<32). Generalized linear models controlling for gender, body mass index, and physical activity were utilized. A higher proportion of those in the EC group reported adequate sleep quality (67% vs. 57% in non-EC, p=0.001), sleep duration of ≥7 h nightly (58% vs. 50% in non-EC, p=0.007), and infrequent daytime dysfunction (72% vs. 65% in non-EC, p=0.02). When ecSI scores were grouped as tertiles, those in the highest tertile reported a higher prevalence of no sleep disturbances (7% vs. 2% in the lowest ecSI tertile, p=0.006) and lower prevalence of sleep medication use (10% vs. 15% in the lowest ecSI tertile, p=0.04). Results suggest that competent eaters are more likely to have better overall sleep quality and fewer sleep-related issuescompared to less competent eaters. These findings may inform future longitudinal studies, and health promotion and weight management interventions for young adults. Copyright © 2015 Elsevier Ltd. All rights reserved.

Reducing The Cost of Transport and Increasing Walking Distance After Stroke: A Randomized Controlled Trial on Fast Locomotor Training Combined With Functional Electrical Stimulation

PubMed Central

Awad, Louis N.; Reisman, Darcy S.; Pohlig, Ryan T.; Binder-Macleod, Stuart A.

2015-01-01

Background Neurorehabilitation efforts have been limited in their ability to restore walking function after stroke. Recent work has demonstrated proof-of-concept for a Functional Electrical Stimulation (FES)-based combination therapy designed to improve poststroke walking by targeting deficits in paretic propulsion. Objectives To determine the effects on the energy cost of walking (EC) and long-distance walking ability of locomotor training that combines fast walking with FES to the paretic ankle musculature (FastFES). Methods Fifty participants >6 months poststroke were randomized to 12 weeks of gait training at self-selected speeds (SS), fast speeds (Fast), or FastFES. Participants’ 6-Minute Walk Test (6MWT) distance and EC at comfortable (EC-CWS) and fast (EC-Fast) walking speeds were measured pretraining, posttraining, and at a 3-month follow-up. A reduction in EC-CWS, independent of changes in speed, was the primary outcome. Also evaluated were group differences in the number of 6MWT responders and moderation by baseline speed. Results When compared with SS and Fast, FastFES produced larger reductions in EC (p’s ≤0.03). FastFES produced reductions of 24% and 19% in EC-CWS and EC-Fast (p’s <0.001), whereas neither Fast nor SS influenced EC. Between-group 6MWT differences were not observed; however, 73% of FastFES and 68% of Fast participants were responders, in contrast to 35% of SS participants. Conclusions Combining fast locomotor training with FES is an effective approach to reducing the high EC of persons poststroke. Surprisingly, differences in 6MWT gains were not observed between groups. Closer inspection of the 6MWT and EC relationship and elucidation of how reduced EC may influence walking-related disability is warranted. PMID:26621366

Electronic cigarette use behaviors and motivations among smokers and non-smokers.

PubMed

Sussan, Thomas E; Shahzad, Fatima G; Tabassum, Eefa; Cohen, Joanna E; Wise, Robert A; Blaha, Michael J; Holbrook, Janet T; Biswal, Shyam

2017-09-08

The use of electronic cigarettes (EC) has risen exponentially over the past decade, including among never smokers, and ECs are now the most popular tobacco product among teenagers in the US. While, EC manufacturers utilize numerous marketing strategies to target both smokers and non-smokers, it is unclear how perceptions and behaviors differ between these two groups. We conducted a survey of 320 adults either via online surveys or in Baltimore vape shops to determine demographics, behaviors, perceptions, and motivations underlying use of ECs. Our survey respondents were predominantly young, Caucasian males, 74% of whom identified themselves as former smokers, while 20% identified as current smokers and 6% were never smokers. Former smokers reported a longer history of EC use and higher nicotine concentrations than current smokers. For former and current smokers, the primary motivation for EC use was assistance to quit smoking, and nearly half indicated that they plan to reduce their nicotine concentration and eventually quit using ECs. Among former smokers, self-reports on use and measures of dependence were consistent with nicotine replacement as their primary motivation. The majority of former and current smokers also reported that their respiratory health had improved as a result of EC use, although this effect was stronger for former smokers. Never smokers reported less frequent EC use and dependence compared to former and current smokers. Their motivations for use were more commonly for enjoyment and popularity, and they displayed a reduced desire to eventually quit using ECs. These responses provide insight into the underlying thoughts and behaviors of smoking and non-smoking EC users and also suggest that never smoking EC users are an emerging demographic with different motivations and perceptions than those of current and former smokers.

Intraindividual Covariation Between E-Cigarette and Combustible Cigarette Use in Korean American Emerging Adults

PubMed Central

Huh, Jimi; Leventhal, Adam M.

2017-01-01

Critical gaps exist in understanding the patterns and correlates of dual use of electronic cigarettes (ECs) and combustible cigarettes (CCs), particularly in ethnic minority populations. In this study, we assessed CC and EC use in the naturalistic environment using ecological momentary assessment (EMA). We hypothesized that within-subject variation in EC use (yes/no each day) would be inversely associated with within-subject variation in number of CCs consumed and craving during that same day. We also examined gender and nicotine dependence as moderators of the EC-CC and EC-craving covariations. Korean American emerging adult (KAEA; 18–25 years old) smokers (N = 78) completed 7 days of EMA. Participants completed EMA surveys throughout the day, which assessed CC craving, and end-of-day surveys, which assessed EC use and the number of CCs smoked that day. Generalized linear mixed models were used to predict day-level EC use, with number of CCs smoked and craving during that same day, gender, and nicotine dependence as predictors (n = 501). We found that within-subject variation in CC use was not associated with same-day EC use; neither was within-subject variation in craving (ps > .27). Gender moderated the relationship between craving and EC use on a given day (p = .03); only for females, on the days with higher craving, the likelihood of their EC use that day was significantly heightened. This study does not suggest that EC use is linked with lower CC smoking quantity, at least at the day level and among KAEA smokers. CC craving may play a role in dual EC-CC use for KAEA female smokers. PMID:26618795

Intraindividual covariation between e-cigarette and combustible cigarette use in Korean American emerging adults.

PubMed

Huh, Jimi; Leventhal, Adam M

2016-03-01

Critical gaps exist in understanding the patterns and correlates of dual use of electronic cigarettes (ECs) and combustible cigarettes (CCs), particularly in ethnic minority populations. In this study, we assessed CC and EC use in the naturalistic environment using ecological momentary assessment (EMA). We hypothesized that within-subject variation in EC use (yes/no each day) would be inversely associated with within-subject variation in number of CCs consumed and craving during that same day. We also examined gender and nicotine dependence as moderators of the EC-CC and EC-craving covariations. Korean American emerging adult (KAEA; 18-25 years old) smokers (N = 78) completed 7 days of EMA. Participants completed EMA surveys throughout the day, which assessed CC craving, and end-of-day surveys, which assessed EC use and the number of CCs smoked that day. Generalized linear mixed models were used to predict day-level EC use, with number of CCs smoked and craving during that same day, gender, and nicotine dependence as predictors (n = 501). We found that within-subject variation in CC use was not associated with same-day EC use; neither was within-subject variation in craving (ps > .27). Gender moderated the relationship between craving and EC use on a given day (p = .03); only for females, on the days with higher craving, the likelihood of their EC use that day was significantly heightened. This study does not suggest that EC use is linked with lower CC smoking quantity, at least at the day level and among KAEA smokers. CC craving may play a role in dual EC-CC use for KAEA female smokers. (c) 2016 APA, all rights reserved).

Fine carbonaceous aerosol characteristics at a megacity during the Chinese Spring Festival as given by OC/EC online measurements

NASA Astrophysics Data System (ADS)

Liu, Baoshuang; Bi, Xiaohui; Feng, Yinchang; Dai, Qili; Xiao, Zhimei; Li, Liwei; Wu, Jianhui; Yuan, Jie; Zhang, YuFen

2016-11-01

The OC/EC online monitoring campaign was carried out in Tianjin of China from 8th February to 15th March 2015 during the Chinese Spring Festival period (CSFP). The concentrations of OC, EC, BC and other ambient pollutants (e.g. SO2, NO2 and PM2.5, etc.) in high time resolution were measured with related online-monitoring instruments. During the CSFP, according to the peaks of PM2.5 concentrations and number concentrations (NC) of aerosol particles with aerodynamic diameters between 0.3 and 2.5 μm, five pollution-events were generally identified and displayed. These pollution-events were closely associated with large-scale fireworks displaying, combustion activities such as heating for winter, and the stable meteorological conditions, etc. During the CSFP, EC and OC concentrations showed variations up to one order of magnitude. The uncertainty of instrument itself and the difference for measured methods, further caused the differences between thermal OC (measured OC by thermal method) and optical OC (measured OC by optical method) concentrations, as well as between thermal EC (measured EC by thermal method) and optical EC (measured EC by optical method) concentrations. The high-concentration carbonaceous aerosols could enlarge the uncertainty of measuring instrument, reducing the correlations between OC and EC, and enhance the differences among thermal EC, optical BC and optical EC. The OC/EC ratios and the percentages of SOC/OC would be declined, when the pollution-events formed during the CSFP. Due to the different sources for thermal POC and thermal SOC, the correlation of the two was relatively lower (R2 = 0.39). Thermal POC dominated over thermal OC during the CSFP.

Relationships of eating competence, sleep behaviors and quality, and overweight status among college students

PubMed Central

Quick, Virginia; Shoff, Suzanne; Lohse, Barbara; White, Adrienne; Horacek, Tanya; Greene, Geoffrey

2015-01-01

Little is known about the relationships between eating competence (intra-individual approach to eating and food-related attitudes and behaviors that entrains positive bio-psychosocial outcomes), and sleep behaviors and quality in college students, a high risk group for poor eating habits, weight gain and inadequate sleep. Thus, data from full-time college students (N=1035; 82% White; 61% female) aged 18-24 years from 5 U.S. universities were obtained from online questionnaires (eating competence (ecSI), Pittsburg Sleep Quality Index (PSQI), physical activity, demographics) and physical assessments (measured height, weight), to explore sleep behavior and quality between eating competent (EC; ecSI score ≥ 32) and non-EC groups (ecSI < 32). Generalized linear models controlling for gender, body mass index, and physical activity were utilized. A higher proportion of those in the EC group reported adequate sleep quality (67% vs. 57% in non-EC, p=0.001), sleep duration of ≥ 7 hours nightly (58% vs. 50% in non-EC, p=0.007), and infrequent daytime dysfunction (72% vs. 65% in non-EC, p=0.02). When ecSI scores were grouped as tertiles, those in the highest tertile reported a higher prevalence of no sleep disturbances (7% vs. 2% in the lowest ecSI tertile, p=0.006) and lower prevalence of sleep medication use (10% vs. 15% in the lowest ecSI tertile, p=0.04). Results suggest that competent eaters are more likely to have better overall sleep quality and fewer sleep-related issues, compared to less competent eaters. These findings may inform future longitudinal studies, and health promotion and weight management interventions for young adults. PMID:26164670

Radiocarbon Analysis to Calculate New End-Member Values for Biomass Burning Source Samples Specific to the Bay Area

NASA Astrophysics Data System (ADS)

Yoon, S.; Kirchstetter, T.; Fairley, D.; Sheesley, R. J.; Tang, X.

2017-12-01

Elemental carbon (EC), also known as black carbon or soot, is an important particulate air pollutant that contributes to climate forcing through absorption of solar radiation and to adverse human health impacts through inhalation. Both fossil fuel combustion and biomass burning, via residential firewood burning, agricultural burning, wild fires, and controlled burns, are significant sources of EC. Our ability to successfully control ambient EC concentrations requires understanding the contribution of these different emission sources. Radiocarbon (14C) analysis has been increasingly used as an apportionment tool to distinguish between EC from fossil fuel and biomass combustion sources. However, there are uncertainties associated with this method including: 1) uncertainty associated with the isolation of EC to be used for radiocarbon analysis (e.g., inclusion of organic carbon, blank contamination, recovery of EC, etc.) 2) uncertainty associated with the radiocarbon signature of the end member. The objective of this research project is to utilize laboratory experiments to evaluate some of these uncertainties, particularly for EC sources that significantly impact the San Francisco Bay Area. Source samples of EC only and a mix of EC and organic carbon (OC) were produced for this study to represent known emission sources and to approximate the mixing of EC and OC that would be present in the atmosphere. These samples include a combination of methane flame soot, various wood smoke samples (i.e. cedar, oak, sugar pine, pine at various ages, etc.), meat cooking, and smoldering cellulose smoke. EC fractions were isolated using a Sunset Laboratory's thermal optical transmittance carbon analyzer. For 14C analysis, samples were sent to Woods Hole Oceanographic Institution for isotope analysis using an accelerated mass spectrometry. End member values and uncertainties for the EC isolation utilizing this method will be reported.

Antiinflammatory Activity of a Novel Folic Acid Targeted Conjugate of the mTOR Inhibitor Everolimus

PubMed Central

Lu, Yingjuan; Parker, Nikki; Kleindl, Paul J; Cross, Vicky A; Wollak, Kristin; Westrick, Elaine; Stinnette, Torian W; Gehrke, Mark A; Wang, Kevin; Santhapuram, Hari Krishna R; You, Fei; Hahn, Spencer J; Vaughn, Jeremy F; Klein, Patrick J; Vlahov, Iontcho R; Low, Philip S; Leamon, Christopher P

2015-01-01

Folate receptor (FR)-β has been identified as a promising target for antimacrophage and antiinflammatory therapies. In the present study, we investigated EC0565, a folic acid–derivative of everolimus, as a FR-specific inhibitor of the mammalian target of rapamycin (mTOR). Because of its amphiphilic nature, EC0565 was first evaluated for water solubility, critical micelle formation, stability in culture and FR-binding specificity. Using FR-expressing macrophages, the effect of EC0565 on mTOR signaling and cellular proliferation was studied. The pharmacokinetics, metabolism and bioavailability of EC0565 were studied in normal rats. The in vivo activity of EC0565 was assessed in rats with adjuvant arthritis, a “macrophage-rich” model with close resemblance to rheumatoid arthritis. EC0565 forms micellar aggregates in physiological buffers and demonstrates good water solubility as well as strong multivalent FR-binding capacity. EC0565 inhibited mTOR signaling in rat macrophages at nanomolar concentrations and induced G0/G1 cell cycle arrest in serum-starved RAW264.7 cells. Subcutaneously administered EC0565 in rats displayed good bioavailability and a relatively long half-life (~12 h). When given at 250 nmol/kg, EC0565 selectively inhibited proliferating cell nuclear antigen expression in thioglycollate-stimulated rat peritoneal cells. With limited dosing regimens, the antiarthritic activity of EC0565 was found superior to that of etanercept, everolimus and a nontargeted everolimus analog. The in vivo activity of EC0565 was also comparable to that of a folate-targeted aminopterin. Folate-targeted mTOR inhibition may be an effective way of suppressing activated macrophages in sites of inflammation, especially in nutrient-deprived conditions, such as in the arthritic joints. Further investigation and improvement upon the physical and biochemical properties of EC0565 are warranted. PMID:26181632

Emergency Contraception in Mexico: Trends in Knowledge and Ever-Use 2006-2014.

PubMed

Han, Leo; Saavedra-Avendano, Biani; Lambert, William; Fu, Rongwei; Rodriguez, Maria I; Edelman, Alison; Darney, Blair

2017-11-01

Objectives A package of interventions to introduce emergency contraception (EC) to Mexico was implemented, resulting in the addition of EC to the national family planning guidelines in 2004. We describe EC knowledge and use among women in Mexico over time. Methods We used the 2006, 2009, and 2014 of waves of a nationally representative demographic survey (ENADID). We assessed EC knowledge and usage in women ages 15-29 who are not using permanent methods and tested whether EC knowledge and use is changing over time after controlling for socio-demographic characteristics using logistic regression. Results Our sample included n = 99,223 (population N = 40,234,355) women ages 15-29. Overall, knowledge of EC increased over time: 62% in 2006 to 79% in 2009 to 83% in 2014 (p < 0.001). Among young women who have used contraception (n = 42,883; N = 16,816,701), the proportion that reported EC use increased from 3 to 11% to 29% (p < 0.001). Compared to non-users, women who had ever used EC were more likely to be using no method of contraception (44 vs. 35%) or barrier method (22 vs. 17%). Demographic factors including lower wealth, lower education, indigenous status and rural living are significantly associated with less EC knowledge and use. Stratified multivariate analysis found that demographic disadvantages magnify lower EC use among rural residents compared to non-rural residents. Conclusions for Practice Knowledge and use of EC are growing rapidly in Mexico, but disparities persist in demographically disadvantaged women, particularly those living in rural areas. Women who use EC appear to be at higher risk of unintended pregnancy based on current contraceptive use.

Effect of Ionic Diffusion on Extracellular Potentials in Neural Tissue

PubMed Central

Halnes, Geir; Mäki-Marttunen, Tuomo; Keller, Daniel; Pettersen, Klas H.; Andreassen, Ole A.

2016-01-01

Recorded potentials in the extracellular space (ECS) of the brain is a standard measure of population activity in neural tissue. Computational models that simulate the relationship between the ECS potential and its underlying neurophysiological processes are commonly used in the interpretation of such measurements. Standard methods, such as volume-conductor theory and current-source density theory, assume that diffusion has a negligible effect on the ECS potential, at least in the range of frequencies picked up by most recording systems. This assumption remains to be verified. We here present a hybrid simulation framework that accounts for diffusive effects on the ECS potential. The framework uses (1) the NEURON simulator to compute the activity and ionic output currents from multicompartmental neuron models, and (2) the electrodiffusive Kirchhoff-Nernst-Planck framework to simulate the resulting dynamics of the potential and ion concentrations in the ECS, accounting for the effect of electrical migration as well as diffusion. Using this framework, we explore the effect that ECS diffusion has on the electrical potential surrounding a small population of 10 pyramidal neurons. The neural model was tuned so that simulations over ∼100 seconds of biological time led to shifts in ECS concentrations by a few millimolars, similar to what has been seen in experiments. By comparing simulations where ECS diffusion was absent with simulations where ECS diffusion was included, we made the following key findings: (i) ECS diffusion shifted the local potential by up to ∼0.2 mV. (ii) The power spectral density (PSD) of the diffusion-evoked potential shifts followed a 1/f2 power law. (iii) Diffusion effects dominated the PSD of the ECS potential for frequencies up to several hertz. In scenarios with large, but physiologically realistic ECS concentration gradients, diffusion was thus found to affect the ECS potential well within the frequency range picked up in experimental recordings. PMID:27820827

Induced Pluripotent Stem Cell‐Derived Endothelial Cells Overexpressing Interleukin‐8 Receptors A/B and/or C‐C Chemokine Receptors 2/5 Inhibit Vascular Injury Response

PubMed Central

Giordano, Samantha; Zhao, Xiangmin; Chen, Yiu‐Fai; Litovsky, Silvio H.; Hage, Fadi G.; Townes, Tim M.; Sun, Chiao‐Wang; Wu, Li‐Chen; Oparil, Suzanne

2017-01-01

Abstract Recruitment of neutrophils and monocytes/macrophages to the site of vascular injury is mediated by binding of chemoattractants to interleukin (IL) 8 receptors RA and RB (IL8RA/B) C‐C chemokine receptors (CCR) 2 and 5 expressed on neutrophil and monocyte/macrophage membranes. Endothelial cells (ECs) derived from rat‐induced pluripotent stem cells (RiPS) were transduced with adenovirus containing cDNA of IL8RA/B and/or CCR2/5. We hypothesized that RiPS‐ECs overexpressing IL8RA/B (RiPS‐IL8RA/B‐ECs), CCR2/5 (RiPS‐CCR2/5‐ECs), or both receptors (RiPS‐IL8RA/B+CCR2/5‐ECs) will inhibit inflammatory responses and neointima formation in balloon‐injured rat carotid artery. Twelve‐week‐old male Sprague‐Dawley rats underwent balloon injury of the right carotid artery and intravenous infusion of (a) saline vehicle, (b) control RiPS‐Null‐ECs (ECs transduced with empty virus), (c) RiPS‐IL8RA/B‐ECs, (d) RiPS‐CCR2/5‐ECs, or (e) RiPS‐IL8RA/B+CCR2/5‐ECs. Inflammatory mediator expression and leukocyte infiltration were measured in injured and uninjured arteries at 24 hours postinjury by enzyme‐linked immunosorbent assay (ELISA) and immunohistochemistry, respectively. Neointima formation was assessed at 14 days postinjury. RiPS‐ECs expressing the IL8RA/B or CCR2/5 homing device targeted the injured arteries and decreased injury‐induced inflammatory cytokine expression, neutrophil/macrophage infiltration, and neointima formation. Transfused RiPS‐ECs overexpressing IL8RA/B and/or CCR2/5 prevented inflammatory responses and neointima formation after vascular injury. Targeted delivery of iPS‐ECs with a homing device to inflammatory mediators in injured arteries provides a novel strategy for the treatment of cardiovascular diseases. Stem Cells Translational Medicine 2017;6:1168–1177 PMID:28233474

Molecular identification of venous progenitors in the dorsal aorta reveals an aortic origin for the cardinal vein in mammals

PubMed Central

Lindskog, Henrik; Kim, Yung Hae; Jelin, Eric B.; Kong, Yupeng; Guevara-Gallardo, Salvador; Kim, Tyson N.; Wang, Rong A.

2014-01-01

Coordinated arterial-venous differentiation is crucial for vascular development and function. The origin of the cardinal vein (CV) in mammals is unknown, while conflicting theories have been reported in chick and zebrafish. Here, we provide the first molecular characterization of endothelial cells (ECs) expressing venous molecular markers, or venous-fated ECs, within the emergent dorsal aorta (DA). These ECs, expressing the venous molecular markers Coup-TFII and EphB4, cohabited the early DA with ECs expressing the arterial molecular markers ephrin B2, Notch and connexin 40. These mixed ECs in the early DA expressed either the arterial or venous molecular marker, but rarely both. Subsequently, the DA exhibited uniform arterial markers. Real-time imaging of mouse embryos revealed EC movement from the DA to the CV during the stage when venous-fated ECs occupied the DA. We analyzed mutants for EphB4, which encodes a receptor tyrosine kinase for the ephrin B2 ligand, as we hypothesized that ephrin B2/EphB4 signaling may mediate the repulsion of venous-fated ECs from the DA to the CV. Using an EC quantification approach, we discovered that venous-fated ECs increased in the DA and decreased in the CV in the mutants, whereas the rest of the ECs in each vessel were unaffected. This result suggests that the venous-fated ECs were retained in the DA and missing in the CV in the EphB4 mutant, and thus that ephrin B2/EphB4 signaling normally functions to clear venous-fated ECs from the DA to the CV by cell repulsion. Therefore, our cellular and molecular evidence suggests that the DA harbors venous progenitors that move to participate in CV formation, and that ephrin B2/EphB4 signaling regulates this aortic contribution to the mammalian CV. PMID:24550118

Identification of the IGF-1 processing product human Ec/rodent Eb peptide in various tissues: Evidence for its differential regulation after exercise-induced muscle damage in humans.

PubMed

Vassilakos, George; Philippou, Anastassios; Koutsilieris, Michael

2017-02-01

Insulin-like growth factor-1 (IGF-1) is a pleiotropic factor expressed in various tissues and plays a critical role in skeletal muscle physiology. Alternative splicing of the IGF-1 gene gives rise to different precursor polypeptides (isoforms) which could undergo post-translational cleavage, generating the common mature IGF-1 peptide and different carboxyl terminal extension (E-) peptides, with the fate of the latter being, so far, unknown. The objective if this study was to identify the IGF-1Ec forms or processing product(s), other than mature IGF-1, generated in different human and rodent tissues and particularly in human skeletal muscle after exercise-induced damage. Protein lysates from a wide range of human and rodent tissues were immunoblotted with a rabbit anti-human Ec polyclonal antibody raised against the last 24 amino acids of the C-terminal of the Ec peptide. This antibody can recognize the Ec peptide, both as part of IGF-1Ec and alone, and also the corresponding rodent forms, due to the high homology that the human Ec shares with the rodent Eb. We were able to confirm, for the first time, that the human Ec peptide and its rodent homologous Eb peptide are produced simultaneously with their precursor protein (pro-IGF-1Ec/Eb) in vivo, in a wide range of tissues (e.g. muscle, liver, heart). Proprotein convertase furin digestion of human muscle and liver protein lysates confirmed that the higher molecular form, pro-IGF-1Ec, can be cleaved to produce the free Ec peptide. Furthermore, initial evidence is provided that Ec peptide is differentially regulated during the process of muscle regeneration after exercise-induced damage in humans. The findings of this study possibly imply that the post-translational modification of the IGF-1Ec pro-peptide may regulate the bioavailability and activity of the processing product(s). Copyright © 2016. Published by Elsevier Ltd.

Effect of Ionic Diffusion on Extracellular Potentials in Neural Tissue.

PubMed

Halnes, Geir; Mäki-Marttunen, Tuomo; Keller, Daniel; Pettersen, Klas H; Andreassen, Ole A; Einevoll, Gaute T

2016-11-01

Recorded potentials in the extracellular space (ECS) of the brain is a standard measure of population activity in neural tissue. Computational models that simulate the relationship between the ECS potential and its underlying neurophysiological processes are commonly used in the interpretation of such measurements. Standard methods, such as volume-conductor theory and current-source density theory, assume that diffusion has a negligible effect on the ECS potential, at least in the range of frequencies picked up by most recording systems. This assumption remains to be verified. We here present a hybrid simulation framework that accounts for diffusive effects on the ECS potential. The framework uses (1) the NEURON simulator to compute the activity and ionic output currents from multicompartmental neuron models, and (2) the electrodiffusive Kirchhoff-Nernst-Planck framework to simulate the resulting dynamics of the potential and ion concentrations in the ECS, accounting for the effect of electrical migration as well as diffusion. Using this framework, we explore the effect that ECS diffusion has on the electrical potential surrounding a small population of 10 pyramidal neurons. The neural model was tuned so that simulations over ∼100 seconds of biological time led to shifts in ECS concentrations by a few millimolars, similar to what has been seen in experiments. By comparing simulations where ECS diffusion was absent with simulations where ECS diffusion was included, we made the following key findings: (i) ECS diffusion shifted the local potential by up to ∼0.2 mV. (ii) The power spectral density (PSD) of the diffusion-evoked potential shifts followed a 1/f2 power law. (iii) Diffusion effects dominated the PSD of the ECS potential for frequencies up to several hertz. In scenarios with large, but physiologically realistic ECS concentration gradients, diffusion was thus found to affect the ECS potential well within the frequency range picked up in experimental recordings.

Survival of the probiotic Escherichia coli Nissle 1917 (EcN) in the gastrointestinal tract given in combination with oral mesalamine to healthy volunteers.

PubMed

Joeres-Nguyen-Xuan, Thai Hoa; Boehm, Stephan Karl; Joeres, Lars; Schulze, Juergen; Kruis, Wolfgang

2010-02-01

Mesalamine and the probiotic E. coli Nissle 1917 (EcN) are both effective agents for the treatment of ulcerative colitis. A combined therapy may have more than additive efficacy. However, mesalamine may have antimicrobial effects on EcN. In this prospective, randomized, double-blind, placebo-controlled study, 48 healthy volunteers took EcN in a run-in phase for 17 days (5-50 x 10(9) viable bacteria od). If stool samples became positive for EcN, volunteers received combination treatment with EcN plus either mesalamine (1500 mg twice a day) or placebo for 1 week. Fecal samples were further tested for EcN in 2- to 3-day intervals until a maximum of 48 weeks after treatment. Patient diaries, blood, and urine were checked to assess safety, compliance, and tolerance. During run-in, viable EcN were detected in 45 of the 48 volunteers (94%); 2 volunteers were positive before taking EcN. From days 1 to 7 of combination treatment (n = 40), the number of EcN-positive volunteers varied between 70% and 80% in the mesalamine group and between 85% and 95% in the placebo group. Differences between the groups were not significant (normal approximation: day 3, P > 0.15; day 5, P > 0.25; day 7, P > 0.076). At treatment discontinuation, 16 of 20 volunteers in the mesalamine group and 15 of 20 volunteers in the placebo group were EcN positive, whereas this figure dropped continuously up to week 12 after discontinuation (mesalamine, 7 of 20; placebo, 4 of 20). No differences between the groups were seen with regard to tolerance and safety. The combination of EcN and mesalamine has no significant effect on the survival of EcN in healthy volunteers.

Electronic cigarettes for smoking cessation and reduction.

PubMed

McRobbie, Hayden; Bullen, Chris; Hartmann-Boyce, Jamie; Hajek, Peter

2014-01-01

Electronic cigarettes (ECs) are electronic devices that heat a liquid - usually comprising propylene glycol and glycerol, with or without nicotine and flavours, stored in disposable or refillable cartridges or a reservoir - into an aerosol for inhalation. Since ECs appeared on the market in 2006 there has been a steady growth in sales. Smokers report using ECs to reduce risks of smoking, but some healthcare organisations have been reluctant to encourage smokers to switch to ECs, citing lack of evidence of efficacy and safety. Smokers, healthcare providers and regulators are interested to know if these devices can reduce the harms associated with smoking. In particular, healthcare providers have an urgent need to know what advice they should give to smokers enquiring about ECs. To examine the efficacy of ECs in helping people who smoke to achieve long-term abstinence; to examine the efficacy of ECs in helping people reduce cigarette consumption by at least 50% of baseline levels; and to assess the occurrence of adverse events associated with EC use. We searched the Cochrane Tobacco Addiction Groups Trials Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, and two other databases for relevant records from 2004 to July 2014, together with reference checking and contact with study authors. We included randomized controlled trials (RCTs) in which current smokers (motivated or unmotivated to quit) were randomized to EC or a control condition, and which measured abstinence rates or changes in cigarette consumption at six months or longer. As the field of EC research is new, we also included cohort follow-up studies with at least six months follow-up. We included randomized cross-over trials and cohort follow-up studies that included at least one week of EC use for assessment of adverse events. One review author extracted data from the included studies and another checked them. Our main outcome measure was abstinence from smoking after at least six months follow-up, and we used the most rigorous definition available (continuous, biochemically validated, longest follow-up). For reduction we used a dichotomous approach (no change/reduction < 50% versus reduction by 50% or more of baseline cigarette consumption). We used a fixed-effect Mantel-Haenszel model to calculate the risk ratio (RR) with a 95% confidence interval (CI) for each study, and where appropriate we pooled data from these studies in meta-analyses. Our search identified almost 600 records, from which we include 29 representing 13 completed studies (two RCTs, 11 cohort). We identified nine ongoing trials. Two RCTs compared EC with placebo (non-nicotine) EC, with a combined sample size of 662 participants. One trial included minimal telephone support and one recruited smokers not intending to quit, and both used early EC models with low nicotine content. We judged the RCTs to be at low risk of bias, but under the GRADE system the overall quality of the evidence for our outcomes was rated 'low' or 'very low' because of imprecision due to the small number of trials. A 'low' grade means that further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. A 'very low' grade means we are very uncertain about the estimate. Participants using an EC were more likely to have abstained from smoking for at least six months compared with participants using placebo EC (RR 2.29, 95% CI 1.05 to 4.96; placebo 4% versus EC 9%; 2 studies; GRADE: low). The one study that compared EC to nicotine patch found no significant difference in six-month abstinence rates, but the confidence intervals do not rule out a clinically important difference (RR 1.26, 95% CI: 0.68 to 2.34; GRADE: very low). A higher number of people were able to reduce cigarette consumption by at least half with ECs compared with placebo ECs (RR 1.31, 95% CI 1.02 to 1.68, 2 studies; placebo: 27% versus EC: 36%; GRADE: low) and compared with patch (RR 1.41, 95% CI 1.20 to 1.67, 1 study; patch: 44% versus EC: 61%; GRADE: very low). Unlike smoking cessation outcomes, reduction results were not biochemically verified.None of the RCTs or cohort studies reported any serious adverse events (SAEs) that were considered to be plausibly related to EC use. One RCT provided data on the proportion of participants experiencing any adverse events. Although the proportion of participants in the study arms experiencing adverse events was similar, the confidence intervals are wide (ECs vs placebo EC RR 0.97, 95% CI 0.71 to 1.34; ECs vs patch RR 0.99, 95% CI 0.81 to 1.22). The other RCT reported no statistically significant difference in the frequency of AEs at three- or 12-month follow-up between the EC and placebo EC groups, and showed that in all groups the frequency of AEs (with the exception of throat irritation) decreased significantly over time. There is evidence from two trials that ECs help smokers to stop smoking long-term compared with placebo ECs. However, the small number of trials, low event rates and wide confidence intervals around the estimates mean that our confidence in the result is rated 'low' by GRADE standards. The lack of difference between the effect of ECs compared with nicotine patches found in one trial is uncertain for similar reasons. ECs appear to help smokers unable to stop smoking altogether to reduce their cigarette consumption when compared with placebo ECs and nicotine patches, but the above limitations also affect certainty in this finding. In addition, lack of biochemical assessment of the actual reduction in smoke intake further limits this evidence. No evidence emerged that short-term EC use is associated with health risk.

Human iPSC-Derived Endothelial Cell Sprouting Assay in Synthetic Hydrogel Arrays

EPA Science Inventory

Activation of vascular endothelial cells (ECs) by growth factors initiates a cascade of events in vivo consisting of EC tip cell selection, sprout formation, EC stalk cell proliferation, and ultimately vascular stabilization by support cells. Although EC functional assays can rec...

Sunlight-charged electrochromic battery based on hybrid film of tungsten oxide and polyaniline

NASA Astrophysics Data System (ADS)

Chang, Xueting; Hu, Ruirui; Sun, Shibin; Liu, Jingrong; Lei, Yanhua; Liu, Tao; Dong, Lihua; Yin, Yansheng

2018-05-01

Electrochromic (EC) energy storage devices that could realize the multifunctional integration of energy storage and electrochromism have gained much recent attention. Herein, an EC battery based on the hybrid film of W18O49 and polyaniline (PANI) is developed and assembled, which integrates energy storage and EC functions in one device. The W18O49/PANI-EC battery delivers a discharging capacity of 52.96 mA h g-1, which is about two times higher than that of the W18O49-EC battery. Sunlight irradiation could greatly promote the oxidation reactions of both W18O49 and PANI during the charging process of the W18O49/PANI-EC battery, thus effectively accelerating the charging rate. This work provides a green, convenient, environmentally friendly, and cost-free charging strategy for the EC energy systems and could further advance the development of the multifunctional EC devices based on the organic/inorganic composites.

Functional subregions of the human entorhinal cortex

PubMed Central

Maass, Anne; Berron, David; Libby, Laura A; Ranganath, Charan; Düzel, Emrah

2015-01-01

The entorhinal cortex (EC) is the primary site of interactions between the neocortex and hippocampus. Studies in rodents and nonhuman primates suggest that EC can be divided into subregions that connect differentially with perirhinal cortex (PRC) vs parahippocampal cortex (PHC) and with hippocampal subfields along the proximo-distal axis. Here, we used high-resolution functional magnetic resonance imaging at 7 Tesla to identify functional subdivisions of the human EC. In two independent datasets, PRC showed preferential intrinsic functional connectivity with anterior-lateral EC and PHC with posterior-medial EC. These EC subregions, in turn, exhibited differential connectivity with proximal and distal subiculum. In contrast, connectivity of PRC and PHC with subiculum followed not only a proximal-distal but also an anterior-posterior gradient. Our data provide the first evidence that the human EC can be divided into functional subdivisions whose functional connectivity closely parallels the known anatomical connectivity patterns of the rodent and nonhuman primate EC. DOI: http://dx.doi.org/10.7554/eLife.06426.001 PMID:26052749

Thymic stromal lymphopoietin-induced HOTAIR activation promotes endothelial cell proliferation and migration in atherosclerosis

PubMed Central

Peng, Yudong; Meng, Kai; Jiang, Lili; Zhong, Yucheng; Yang, Yong; Lan, Yin

2017-01-01

Endothelial cells’ (EC) injury is a major step for the pathological progression of atherosclerosis. Recent study demonstrated that thymic stromal lymphopoietin (TSLP) exerts a protective role in atherosclerosis. However, the effect of TSLP and the exact molecular mechanism involved in EC remains unknown. In the present study, we found that long noncoding RNA (lncRNA) HOTAIR was much lower in EC from atherosclerotic plaque. Functional assays showed that HOTAIR facilitated cell proliferation and migration, and suppressed apoptosis in EC. Moreover, we demonstrated that TSLP functions upstream of HOTAIR. We found that serum level of TSLP was decreased in atherosclerosis patients and serum TSLP level positively correlated with HOTAIR expression in EC. Further investigation demonstrated that TSLP activated HOTAIR transcription through PI3K/AKT-IRF1 pathway and then regulates the EC proliferation and migration. TSLP-HOTAIR axis also plays a protective role in low-density lipoprotein (ox-LDL)-induced EC injury. Taken together, TSLP-HOTAIR may be a potential therapy for EC dysfunction in atherosclerosis. PMID:28615347

Rejection Sensitivity and Executive Control: Joint predictors of Borderline Personality features

PubMed Central

Ayduk, Özlem; Zayas, Vivian; Downey, Geraldine; Cole, Amy Blum; Shoda, Yuichi; Mischel, Walter

2008-01-01

Two studies tested the hypothesis that rejection sensitivity (RS) and executive control (EC) jointly predict borderline personality (BP) features. We expected high RS to be related to increased vulnerability for BP features specifically in people who also had difficulties in executive control (EC). Study 1 tested this hypothesis using a sample of college students (N = 379) whereas Study 2 (N = 104) was conducted using a community sample of adults. Both studies operationalized EC by a self-report measure. For a subsample in Study 2 (N = 80), ability to delay gratification at age 4 was also used as an early behavioral precursor of EC in adulthood. In both studies, high RS was associated with increased BP features among people low in self-reported EC. Among those high in self-reported EC, the relationship between RS and BP features was attenuated. Study 2 found parallel findings using preschool delay ability as a behavioral index of EC. These findings suggest that EC may protect high RS people against BP features. PMID:18496604

Lagrangian sampling for emerging contaminants through an urban stream corridor in Colorado

USGS Publications Warehouse

Brown, J.B.; Battaglin, W.A.; Zuellig, R.E.

2009-01-01

Recent national concerns regarding the environmental occurrence of emerging contaminants (ECs) have catalyzed a series of recent studies. Many ECs are released into the environment through discharges from wastewater treatment plants (WWTPs) and other sources. In 2005, the U.S. Geological Survey and the City of Longmont initiated an investigation of selected ECs in a 13.8-km reach of St. Vrain Creek, Colorado. Seven sites were sampled for ECs following a Lagrangian design; sites were located upstream, downstream, and in the outfall of the Longmont WWTP, and at the mouths of two tributaries, Left Hand Creek and Boulder Creek (which is influenced by multiple WWTP outfalls). Samples for 61 ECs in 16 chemical use categories were analyzed and 36 were detected in one or more samples. Of these, 16 have known or suspected endocrine-disrupting potential. At and downstream from the WWTP outfall, detergent metabolites, fire retardants, and steroids were detected at the highest concentrations, which commonly exceeded 1 ??g/l in 2005 and 2 ??g/l in 2006. Most individual ECs were measured at concentrations less than 2 ??g/l. The results indicate that outfalls from WWTPs are the largest but may not be the sole source of ECs in St. Vrain Creek. In 2005, high discharge was associated with fewer EC detections, lower total EC concentrations, and smaller EC loads in St. Vrain Creek and its tributaries as compared with 2006. EC behavior differed by individual compound, and some differences between sites could be attributed to analytical variability or to other factors such as physical or chemical characteristics or distance from contributing sources. Loads of some ECs, such as diethoxynonylphenol, accumulated or attenuated depending on location, discharge, and distance downstream from the WWTP, whereas others, such as bisphenol A, were largely conservative. The extent to which ECs in St. Vrain Creek affect native fish species and macroinvertebrate communities is unknown, but recent studies have shown that fish respond to very low concentrations of ECs, and further study on the fate and transport of these contaminants in the aquatic environment is warranted. ?? 2008 American Water Resources Association.

Intra-Urban Variability in Elemental Carbon Deposition to Tree Canopies

NASA Astrophysics Data System (ADS)

Barrett, T. E.; Ponette-González, A.; Rindy, J. E.; Sheesley, R. J.

2017-12-01

Urban areas cover <1% of the earth's land surface, yet they represent globally significant sources of atmospheric elemental carbon (EC). A product of incomplete fossil fuel, biofuel, and biomass combustion, EC is a powerful climate-forcing agent and a significant component of fine particulate matter in urban atmospheres. Thus, understanding the factors that govern EC removal in urban areas could help mitigate climate change, while improving air quality for urban residents. EC particles can be removed from the atmosphere in precipitation (wet and fog deposition) or they can settle directly onto receptor surfaces (dry deposition). Only limited measurements indicate that EC deposition is higher in urban than in rural and remote regions. However, EC deposition likely exhibits considerable intra-urban variability, with tree canopies serving as potentially important sinks for EC on the cityscape. The goal of this research is to quantify spatial variability in total (wet + dry) EC deposition to urban tree canopies in the Dallas-Fort Worth Metroplex. Using a stratified non-random sampling design, 41 oak trees (22 post oak (Quercus stellata) and 19 live oak (Quercus virginiana)) were selected near (<100 m) and far from roads (>100 m) for measurements of throughfall (water that falls from the canopy to the forest floor). Additionally, 16 bulk rainfall samplers were deployed in grassy areas with no canopy cover. Results from one rain event indicate a volume weighted mean concentration of 83 µg EC L-1 in post oak throughfall, 36 µg EC L-1 in live oak throughfall, and 4 µg EC L-1 in bulk rainfall. Total EC deposition to oak tree canopies was 2.0 ± 2.1 (SD) mg m-2 for post oak and 0.7 ± 0.3 mg m-2 for live oak. Bulk rainfall deposition was 0.08 ± 0.1 mg m-2. Our preliminary findings show that trees are effective urban air filters, removing 9-25 times more EC from the atmosphere than rainwater alone. Resolving surface controls on atmospheric EC removal is key to developing and assessing near-term climate and air quality mitigation strategies.

Community pharmacists providing emergency contraception give little advice about future contraceptive use: a mystery shopper study.

PubMed

Glasier, Anna; Manners, Rachel; Loudon, Joanna C; Muir, Aileen

2010-12-01

UK women increasingly prefer to attend a pharmacy for emergency contraception (EC) rather than a doctor. Most women who use EC do not conceive and remain at risk of pregnancy unless they start regular contraception. We undertook a study to evaluate the quality of service provision in community pharmacies in Lothian, Scotland, and to determine what advice is given about contraception after EC use. Mystery shopper study. EC was unobtainable from 5/40 pharmacies (12.5%), refused because of "contraindications" in 7 (17.5%) and offered in 28 (70%). Most pharmacists appeared nonjudgemental, over 75% asked appropriate questions about eligibility, and over 90% gave appropriate advice about use. EC was universally refused beyond 72 h after sex but universally provided when the date of the last menstrual period was uncertain. Ongoing contraception after EC use was discussed in only 32.5% of all pharmacies and only 43% of those issuing EC. The quality of consultations for EC in pharmacies is generally good but only a minority discuss ongoing contraception after EC use. The implications for contraceptive use and unintended pregnancy rates are worrying. Copyright © 2010 Elsevier Inc. All rights reserved.

Tobacco Marketing, E-cigarette Susceptibility, and Perceptions among Adults.

PubMed

Nicksic, Nicole E; Snell, L Morgan; Rudy, Alyssa K; Cobb, Caroline O; Barnes, Andrew J

2017-09-01

Understanding the impact of tobacco marketing on e-cigarette (EC) susceptibility and perceptions is essential to inform efforts to mitigate tobacco product burden on public health. Data were collected online in 2016 from 634 conventional cigarette (CC) smokers and 393 non-smokers using a convenience sample from Amazon Mechanical Turk. Logistic regression models, stratified by smoking status and adjusted for socio-demographics, examined the relationship among tobacco advertisements and coupons, EC and CC susceptibility, and EC perceptions. Among non-smokers, increased exposure to tobacco advertising and receiving tobacco coupons was significantly related to measures of EC and CC susceptibility (p < .05). Older, more educated non-smokers had decreased odds of EC susceptibility (p < .05). Additionally, increased exposure to tobacco advertising was significantly associated with the perceptions of EC not containing nicotine and being less addictive than CC among smokers (p < .05). Increased exposure to tobacco advertising outlets could influence future EC and CC use in non-smokers and perceptions in smokers, while receiving coupons could affect EC and CC susceptibility among non-smokers. Future research is needed to determine whether policies to minimize exposure to tobacco marketing reduce EC use by decreasing susceptibility.

Epithelial Membrane Protein-2 Expression is an Early Predictor of Endometrial Cancer Development

PubMed Central

Habeeb, Omar; Goodglick, Lee; Soslow, Robert A.; Rao, Rajiv; Gordon, Lynn K.; Schirripa, Osvaldo; Horvath, Steve; Braun, Jonathan; Seligson, David B.; Wadehra, Madhuri

2010-01-01

BACKGROUND Endometrial cancer (EC) is a common malignancy worldwide. It is often preceded by endometrial hyperplasia, whose management and risk of neoplastic progression vary. Previously, we have shown that the tetraspan protein Epithelial Membrane Protein-2 (EMP2) is a prognostic indicator for EC aggressiveness and survival. Here we validate the expression of EMP2 in EC, and further examine whether EMP2 expression within preneoplastic lesions is an early prognostic biomarker for EC development. METHODS A tissue microarray (TMA) was constructed with a wide representation of benign and malignant endometrial samples. The TMA contains a metachronous cohort of cases from individuals who either developed or did not develop EC. Intensity and frequency of EMP2 expression were assessed using immunohistochemistry. RESULTS There was a stepwise, statistically-significant increase in the average EMP2 expression from benign to hyperplasia to atypia to EC. Furthermore, detailed analysis of EMP2 expression in potentially premalignant cases demonstrated that EMP2 positivity was a strong predictor for EC development. CONCLUSION EMP2 is an early predictor of EC development in preneoplastic lesions. In addition, combined with our previous findings, these results validate that EMP2 as a novel biomarker for EC development. PMID:20578181

Cognitive testing with female nutrition and education assistance program participants informs validity of the Satter eating competence inventory.

PubMed

Krall, Jodi Stotts; Lohse, Barbara

2010-01-01

Examine the validity of a self-report measure of eating competence with low-income women. Twenty-five females (18-49 years old) recruited from low-income venues in Pennsylvania completed cognitive testing through an iterative interview process. Respondents' oral responses were compared to researchers' intended meaning of ecSatter Inventory (ecSI) items; responses were mapped to evaluate the similarity between respondents' internally generated answers and their ecSI choices for survey items; and scored responses were compared among participants. Interview findings provided a rationale for modifying the ecSI prior to use with low-income women. Four items were misinterpreted for various reasons, including problems with clarity and wording. The modified ecSI, termed the ecSatter Inventory for Low-Income (ecSI/LI), was comprehended as intended by researchers. Congruence of cognitive responses and ecS/LI scores further supported the instrument's validity. Cognitive testing resulted in the development of an instrument to measure eating competence in low-income adults. The ecSI/LI requires validation with a large, heterogeneous low-income sample. Copyright 2010 Society for Nutrition Education. Published by Elsevier Inc. All rights reserved.

Emerging contaminants in surface waters in China—a short review

NASA Astrophysics Data System (ADS)

Yang, Guang; Fan, Maohong; Zhang, Guangming

2014-07-01

Emerging contaminants (ECs) have drawn attention to many countries due to their persistent input and potential threat to human health and the environment. This article reviews the current contamination sources and their status for surface waters in China. The contamination levels of ECs in surface waters are in the range ng L-1 to μg L-1 in China, apparently about the same as the situation in other countries. ECs enter surface water via runoff, drainage, rainfall, and wastewater treatment effluent. The frequency of occurrence of ECs increased rapidly from 2006 to 2011; a significant reason is the production and consumption of pharmaceuticals and personal care products. As for the distribution of EC pollution in China, the frequency of occurrence of ECs in eastern regions is higher than in western regions. A majority of EC studies have focused on surface waters of the Haihe River and Pearl River watersheds due to their highly developed industries and intense human activity. Legislative and administrative regulation of ECs is lacking in China. To remove ECs, a number of technologies, such as absorption by activated carbon, membrane filtration technology, and advanced oxidation processes, have been researched.

Serotonin-producing enterochromaffin (EC) cells of gastrointestinal mucosa in dexamethasone-treated rats.

PubMed

Glisić, Radmila; Koko, Vesna; Todorović, Vera; Drndarević, Neda; Cvijić, Gordana

2006-09-11

The aim of our study was to investigate the morphological, immunohistochemical and ultrastructural changes of rat serotonin-producing enterochromaffin (EC) cells of gastrointestinal mucosa in dexamethasone-treated rats (D). After 12-daily intraperitoneal administration of 2 mg/kg dexamethasone, rats developed diabetes similar to human diabetes type 2. Stomach, small and large intestines were examined. Large serotonin positive EC cells appeared in the corpus mucosa epithelium of D group of rats, although these cells were not present in control (C) rats. Both volume fraction and the number of EC cells per mm(2) of mucosa were significantly increased only in the duodenum. However, the number of EC cells per circular sections of both antrum and small intestine was increased, but reduced both in the ascending and descending colon in D group. The dexamethasone treatment caused a strong reduction in number of granules in the antral EC cells, while it was gradually increased beginning from the jejunum to descending colon. The mean granular content was reduced in the antral EC cells but increased in the jejunal EC cells in D group. In conclusion, the present study showed that morphological changes in gut serotonin-producing EC cells occurred in diabetic rats.

Isolation and genome-wide expression and methylation characterization of CD31+ cells from normal and malignant human prostate tissue

PubMed Central

Luo, Wei; Hu, Qiang; Wang, Dan; Deeb, Kristin K.; Ma, Yingyu; Morrison, Carl D.; Liu, Song; Johnson, Candace S.; Trump, Donald L.

2013-01-01

Endothelial cells (ECs) are an important component involved in the angiogenesis. Little is known about the global gene expression and epigenetic regulation in tumor endothelial cells. The identification of gene expression and epigenetic difference between human prostate tumor-derived endothelial cells (TdECs) and those in normal tissues may uncover unique biological features of TdEC and facilitate the discovery of new anti-angiogenic targets. We established a method for isolation of CD31+ endothelial cells from malignant and normal prostate tissues obtained at prostatectomy. TdECs and normal-derived ECs (NdECs) showed >90% enrichment in primary culture and demonstrated microvascular endothelial cell characteristics such as cobblestone morphology in monolayer culture, diI-acetyl-LDL uptake and capillary-tube like formation in Matrigel®. In vitro primary cultures of ECs maintained expression of endothelial markers such as CD31, von Willebrand factor, intercellular adhesion molecule, vascular endothelial growth factor receptor 1, and vascular endothelial growth factor receptor 2. We then conducted a pilot study of transcriptome and methylome analysis of TdECs and matched NdECs from patients with prostate cancer. We observed a wide spectrum of differences in gene expression and methylation patterns in endothelial cells, between malignant and normal prostate tissues. Array-based expression and methylation data were validated by qRT-PCR and bisulfite DNA pyrosequencing. Further analysis of transcriptome and methylome data revealed a number of differentially expressed genes with loci whose methylation change is accompanied by an inverse change in gene expression. Our study demonstrates the feasibility of isolation of ECs from histologically normal prostate and prostate cancer via CD31+ selection. The data, although preliminary, indicates that there exist widespread differences in methylation and transcription between TdECs and NdECs. Interestingly, only a small proportion of perturbed genes were overlapped between American (AA) and Caucasian American (CA) patients with prostate cancer. Our study indicates that identifying gene expression and/or epigenetic differences between TdECs and NdECs may provide us with new anti-angiogenic targets. Future studies will be required to further characterize the isolated ECs and determine the biological features that can be exploited in the prognosis and therapy of prostate cancer. PMID:23978847

Rapamycin-treated human endothelial cells preferentially activate allogeneic regulatory T cells

PubMed Central

Wang, Chen; Yi, Tai; Qin, Lingfeng; Maldonado, Roberto A.; von Andrian, Ulrich H.; Kulkarni, Sanjay; Tellides, George; Pober, Jordan S.

2013-01-01

Human graft endothelial cells (ECs) can act as antigen-presenting cells to initiate allograft rejection by host memory T cells. Rapamycin, an mTOR inhibitor used clinically to suppress T cell responses, also acts on DCs, rendering them tolerogenic. Here, we report the effects of rapamycin on EC alloimmunogenicity. Compared with mock-treated cells, rapamycin-pretreated human ECs (rapa-ECs) stimulated less proliferation and cytokine secretion from allogeneic CD4+ memory cells, an effect mimicked by shRNA knockdown of mTOR or raptor in ECs. The effects of rapamycin persisted for several days and were linked to upregulation of the inhibitory molecules PD-L1 and PD-L2 on rapa-ECs. Additionally, rapa-ECs produced lower levels of the inflammatory cytokine IL-6. CD4+ memory cells activated by allogeneic rapa-ECs became hyporesponsive to restimulation in an alloantigen-specific manner and contained higher percentages of suppressive CD4+CD25hiCD127loFoxP3+ cells that did not produce effector cytokines. In a human-mouse chimeric model of allograft rejection, rapamycin pretreatment of human arterial allografts increased graft EC expression of PD-L1 and PD-L2 and reduced subsequent infiltration of allogeneic effector T cells into the artery intima and intimal expansion. Preoperative conditioning of allograft ECs with rapamycin could potentially reduce immune-mediated rejection. PMID:23478407

Degradation of pentachlorophenol by hydroxyl radicals and sulfate radicals using electrochemical activation of peroxomonosulfate, peroxodisulfate and hydrogen peroxide.

PubMed

Govindan, Kadarkarai; Raja, Mohan; Noel, Michael; James, E J

2014-05-15

The present study is to investigate the reactivity of free radicals (SO4(-) and HO) generated from common oxidants (peroxomonosulfate (PMS), peroxodisulfate (PDS) and hydrogen peroxide (HP)) activated by electrochemically generated Fe(2+)/Fe(3+) ions which furthermore are evaluated to destroy pentachlorophenol (PCP) in aqueous solution. The effect of solution pH and amount of oxidants (PMS, PDS and HP) in electrocoagulation (EC) on PCP degradation is analyzed in detail. The experimental results reveal that, optimum initial solution pH is 4.5 and PMS is more efficient oxidant addition in EC. 75% PCP degradation is achieved at 60min electrolysis time from PMS assisted EC. According to the first order rate constant, faster PCP degradation rate is obtained by PMS assisted EC. The PCP degradation rate by oxidant assisted EC is observed in the following order: EC/PMS>EC/PDS>EC/HP>EC. Further to identify the influences of experimental factors involved in PCP degradation by oxidant assisted EC, an experimental design based on an orthogonal array (OA) L9 (3(3)) is proposed using Taguchi method. The factors that most significantly affect the process robustness are identified as A (oxidant) and B (pH) which together account for nearly 86% of the variance. Copyright © 2014 Elsevier B.V. All rights reserved.

FEMALE MICE ARE RESISTANT TO Fabp1 GENE ABLATION-INDUCED ALTERATIONS IN BRAIN ENDOCANNABINOID LEVELS

PubMed Central

Martin, Gregory G.; Chung, Sarah; Landrock, Danilo; Landrock, Kerstin K.; Dangott, Lawrence J.; Peng, Xiaoxue; Kaczocha, Martin; Murphy, Eric J.; Kier, Ann B.; Schroeder, Friedhelm

2017-01-01

Although liver fatty acid binding protein (FABP1, L-FABP) is not detectable in brain, Fabp1 gene ablation (LKO) markedly increases endocannabinoids (EC) in brains of male mice. Since the brain EC system of females differs significantly from that of males, it was important to determine if LKO differently impacted the brain EC system. LKO did not alter brain levels of arachidonic acid (ARA)-containing ECs, i.e arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG), but decreased non-ARA-containing N-acylethanolamides (OEA, PEA) and 2-oleoylglycerol (2-OG) that potentiate the actions of AEA and 2-AG. These changes in brain potentiating EC levels were not associated with: i) a net decrease in levels of brain membrane proteins associated with fatty acid uptake and EC synthesis; ii) a net increase in brain protein levels of cytosolic EC chaperones and enzymes in EC degradation; or iii) increased brain protein levels of EC receptors (CB1, TRVP1). Instead, the reduced or opposite responsiveness of female brain EC levels to loss of FABP1 (LKO) correlated with intrinsically lower FABP1 level in livers of WT females than males. These data show that female mouse brain endocannabinoid levels were unchanged (AEA, 2-AG) or decreased (OEA, PEA, 2-OG) by complete loss of FABP1 (LKO). PMID:27450559

Female Mice are Resistant to Fabp1 Gene Ablation-Induced Alterations in Brain Endocannabinoid Levels.

PubMed

Martin, Gregory G; Chung, Sarah; Landrock, Danilo; Landrock, Kerstin K; Dangott, Lawrence J; Peng, Xiaoxue; Kaczocha, Martin; Murphy, Eric J; Kier, Ann B; Schroeder, Friedhelm

2016-09-01

Although liver fatty acid binding protein (FABP1, L-FABP) is not detectable in the brain, Fabp1 gene ablation (LKO) markedly increases endocannabinoids (EC) in brains of male mice. Since the brain EC system of females differs significantly from that of males, it was important to determine if LKO differently impacted the brain EC system. LKO did not alter brain levels of arachidonic acid (ARA)-containing EC, i.e. arachidonoylethanolamide (AEA) and 2-arachidonoylglycerol (2-AG), but decreased non-ARA-containing N-acylethanolamides (OEA, PEA) and 2-oleoylglycerol (2-OG) that potentiate the actions of AEA and 2-AG. These changes in brain potentiating EC levels were not associated with: (1) a net decrease in levels of brain membrane proteins associated with fatty acid uptake and EC synthesis; (2) a net increase in brain protein levels of cytosolic EC chaperones and enzymes in EC degradation; or (3) increased brain protein levels of EC receptors (CB1, TRVP1). Instead, the reduced or opposite responsiveness of female brain EC levels to loss of FABP1 (LKO) correlated with intrinsically lower FABP1 level in livers of WT females than males. These data show that female mouse brain endocannabinoid levels were unchanged (AEA, 2-AG) or decreased (OEA, PEA, 2-OG) by complete loss of FABP1 (LKO).

Histopathological features of endometrial carcinomas associated with POLE mutations: implications for decisions about adjuvant therapy.

PubMed

Bakhsh, Salwa; Kinloch, Mary; Hoang, Lien N; Soslow, Robert A; Köbel, Martin; Lee, Cheng-Han; McAlpine, Jessica N; McConechy, Melissa K; Gilks, C Blake

2016-05-01

To characterize the histomorphological features of endometrial carcinomas (ECs) harbouring polymerase ε (POLE) mutations. Forty-three ECs with POLE mutations were compared with a cohort of 202 ECs. Most POLE-mutated ECs were endometrioid [34/43 (79%)]; the remaining tumours were mixed [6/43 (14%)], serous [2/43 (5%)], and clear cell [1/43 (2%)]. The endometrioid carcinomas were predominantly International Federation of Gynecology and Obstetrics grade 3 (27/43, 63%). The histotype distribution did not differ from that of control ECs (P = 0.69), but the grade of the EC was higher (P < 0.0005). Both nuclear grade and mitotic index were significantly higher in POLE-mutated ECs than in the comparison cohort. POLE-mutated ECs were associated with peritumoral lymphocytes and numerous tumour-infiltrating lymphocytes. Lymphovascular invasion was present in 20 of 43 tumours. Adjuvant radiotherapy and adjuvant chemotherapy would be offered in up to 80% and 40% of patients, respectively, on the basis of stage, grade, lymphovascular invasion, and histotype. POLE-mutated ECs are typically of high grade, with prominent lymphocytic infiltration, but they are not sufficiently distinctive to allow accurate diagnosis based on routine haematoxylin and eosin staining. Even though POLE-mutated tumours are associated with an excellent prognosis, current guidelines for giving adjuvant treatment for EC result in most patients receiving adjuvant therapy. © 2015 John Wiley & Sons Ltd.

Testicular Sertoli cells influence the proliferation and immunogenicity of co-cultured endothelial cells

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fan, Ping, E-mail: fanpinggoodluck@163.com; He, Lan; Pu, Dan

Research highlights: {yields} The proliferation of dramatic increased by co-cultured with Sertoli cells. {yields} VEGF receptor-2 expression of ECs was up-regulated by co-cultured with Sertoli cells. {yields} The MHC expression of ECs induced by INF-{gamma} and IL-6, IL-8 and sICAM induced by TNF-{alpha} decreased respectively after co-cultured with Sertoli cells. {yields} ECs co-cultured with Sertoli cells also didn't increase the stimulation index of spleen lymphocytes. -- Abstract: The major problem of the application of endothelial cells (ECs) in transplantation is the lack of proliferation and their immunogenicity. In this study, we co-cultured ECs with Sertoli cells to monitor whether Sertolimore » cells can influence the proliferation and immunogenicity of co-cultured ECs. Sertoli cells were isolated from adult testicular tissue. ECs were divided into the control group and the experimental group, which included three sub-groups co-cultured with 1 x 10{sup 3}, 1 x 10{sup 4} or 1 x 10{sup 5} cell/ml of Sertoli cells. The growth and proliferation of ECs were observed microscopically, and the expression of vascular endothelial growth factor (VEGF) receptor-2 (KDR) was examined by Western blotting. In another experiment, ECs were divided into the control group, the single culture group and the co-culture group with the optimal concentration of Sertoli cells. After INF-{gamma} and TNF-{alpha} were added to the culture medium, MHC II antigen expression was detected by immunofluorescence staining and western blotting; interleukin (IL)-6, IL-8 and soluble intercellular adhesion molecule (sICAM) were measured in the culture medium by ELISA. We demonstrated that 1 x 10{sup 4} cell/ml Sertoli cells promoted the proliferation of co-cultured ECs more dramatically than that in other groups (P < 0.05). Western blotting showed that 1 x 10{sup 4} cell/ml of the Sertoli cells was most effective in the up-regulation of KDR expression in the co-cultured ECs (P < 0.05). Sertoli cells can effectively suppress INF-{gamma}-induced MHC II antigen expression in co-cultured ECs compared with single culture group (P < 0.05). TNF-{alpha} induced the expression of IL-6, IL-8 and sICAM in ECs. When co-cultured with Sertoli cells, their expressions were significantly lower than in the EC single culture group (P < 0.05). ECs co-cultured with Sertoli cells also did not significantly increase the stimulation index of spleen lymphocytes compared to the single culture group (P < 0.05). Our results suggested that co-culturing with Sertoli cells can significantly promote the proliferation of ECs, accelerate post-transplant angiogenesis, while reduce EC immunogenicity and stimulus to lymphocytes.« less

On the isolation of elemental carbon (EC) for micro-molar 14C accelerator mass spectrometry: development of a hybrid reference material for 14C-EC accuracy assurance, and a critical evaluation of the thermal optical kinetic (TOK) EC isolation procedure

NASA Astrophysics Data System (ADS)

Currie, L. A.; Kessler, J. D.

2005-10-01

The primary objective of the research reported here has been the development of a hybrid reference material (RM) to serve as a test of accuracy for elemental carbon (EC) isotopic (14C) speciation measurements. Such measurements are vital for the quantitative apportionment of fossil and biomass sources of "soot" (EC), the tracer of fire that has profound effects on health, atmospheric visibility, and climate. Previous studies of 14C-EC measurement quality, carried out with NIST SRM 1649a (Urban Dust), showed a range of results, but since the "truth" was not known for this natural matrix RM, one had to rely on isotopic-chemical consistency evidence (14C in PAH, EC) of measurement validity (Currie et al., 2002). Components of the new Hybrid RM (DiesApple), however, have known 14C and EC composition, and they are nearly orthogonal (isotopically and chemically). NIST SRM 2975 (Forklift Diesel Soot) has little or no 14C, and its major compositional component is EC; SRM 1515 (Apple Leaves) has the 14C content of biomass-C, and it has little or no EC. Thus, the Hybrid RM can serve as an absolute isotopic test for the absence of EC-mimicking pyrolysis-C (char) from SRM 1515 in the EC isolate of the Hybrid RM, as well as a test for conservation of its dominant soot fraction throughout the isolation procedure.

The secondary objective was to employ the Hybrid RM for the comparative evaluation of the thermal optical kinetic (TOK) and thermal optical transmission (TOT) methods for the isolation of EC for micro-molar carbon accelerator mass spectrometry (AMS). As part of this process, the relatively new TOK method was subjected to a critical evaluation and significant development. Key findings of our study are: (1) both methods exhibited biomass-C "leakage"; for TOT, the EC fraction isolated for AMS contained about 8% of the original biomass-C; for TOK, the refractory carbon (RC) isolated contained about 3% of the original biomass-C.; (2) the initial isothermal oxidation stage of the TOK method substantially reduced the transfer of artifact char to the RC fraction, improving isolation capabilities; (3) the Hybrid RM was not equal to the sum of its parts, with matrix interactions inducing premature loss of EC which, however, could be quantified and minimized; (4) the three-stage TOK method provided a superior capability for carbonate quantification at the sub-micromolar level, with "reagent-free" removal of carbonate-C from EC - essential for low-level EC-14C AMS.

Electron-Cloud Build-Up: Theory and Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Furman, M. A.

We present a broad-brush survey of the phenomenology, history and importance of the electron-cloud effect (ECE). We briefly discuss the simulation techniques used to quantify the electron-cloud (EC) dynamics. Finally, we present in more detail an effective theory to describe the EC density build-up in terms of a few effective parameters. For further details, the reader is encouraged to refer to the proceedings of many prior workshops, either dedicated to EC or with significant EC contents, including the entire 'ECLOUD' series. In addition, the proceedings of the various flavors of Particle Accelerator Conferences contain a large number of EC-related publications.more » The ICFA Beam Dynamics Newsletter series contains one dedicated issue, and several occasional articles, on EC. An extensive reference database is the LHC website on EC.« less

Adhesion Molecule Expression and Function of Primary Endothelial Cells in Benign and Malignant Tissues Correlates with Proliferation

PubMed Central

Sievert, Wolfgang; Tapio, Soile; Breuninger, Stephanie; Gaipl, Udo; Andratschke, Nicolaus; Trott, Klaus-Rüdiger; Multhoff, Gabriele

2014-01-01

Background Comparative analysis of the cellular biology of the microvasculature in different tissues requires the availability of viable primary endothelial cells (ECs). This study describes a novel method to isolate primary ECs from healthy organs, repair blastemas and tumors as examples of non-proliferating and proliferating benign and malignant tissues and their functional characterization. Methodology/Principal Findings Single cell suspensions from hearts, lungs, repair blastemas and tumors were incubated consecutively with an anti-CD31 antibody and magnetic micro-beads, coupled to a derivative of biotin and streptavidin, respectively. Following magnetic bead separation, CD31-positive ECs were released by biotin-streptavidin competition. In the absence of micro-beads, ECs became adherent to plastic surfaces. ECs from proliferating repair blastemas and tumors were larger and exhibited higher expression densities of CD31, CD105 and CD102 compared to those from non-proliferating normal tissues such as heart and lung. The expression density of CD34 was particularly high in tumor-derived ECs, and that of CD54 and CD144 in ECs of repair blastemas. Functionally, ECs of non-proliferating and proliferating tissues differed in their capacity to form tubes in matrigel and to align under flow conditions. Conclusions/Significance This method provides a powerful tool to generate high yields of viable, primary ECs of different origins. The results suggest that an altered expression of adhesion molecules on ECs in proliferating tissues contribute to loss of EC function that might cause a chaotic tumor vasculature. PMID:24632811

Vasohibin-1 is identified as a master-regulator of endothelial cell apoptosis using gene network analysis

PubMed Central

2013-01-01

Background Apoptosis is a critical process in endothelial cell (EC) biology and pathology, which has been extensively studied at protein level. Numerous gene expression studies of EC apoptosis have also been performed, however few attempts have been made to use gene expression data to identify the molecular relationships and master regulators that underlie EC apoptosis. Therefore, we sought to understand these relationships by generating a Bayesian gene regulatory network (GRN) model. Results ECs were induced to undergo apoptosis using serum withdrawal and followed over a time course in triplicate, using microarrays. When generating the GRN, this EC time course data was supplemented by a library of microarray data from EC treated with siRNAs targeting over 350 signalling molecules. The GRN model proposed Vasohibin-1 (VASH1) as one of the candidate master-regulators of EC apoptosis with numerous downstream mRNAs. To evaluate the role played by VASH1 in EC, we used siRNA to reduce the expression of VASH1. Of 10 mRNAs downstream of VASH1 in the GRN that were examined, 7 were significantly up- or down-regulated in the direction predicted by the GRN.Further supporting an important biological role of VASH1 in EC, targeted reduction of VASH1 mRNA abundance conferred resistance to serum withdrawal-induced EC death. Conclusion We have utilised Bayesian GRN modelling to identify a novel candidate master regulator of EC apoptosis. This study demonstrates how GRN technology can complement traditional methods to hypothesise the regulatory relationships that underlie important biological processes. PMID:23324451

Efficient generation of endothelial cells from human pluripotent stem cells and characterization of their functional properties.

PubMed

Song, Wei; Kaufman, Dan S; Shen, Wei

2016-03-01

Although endothelial cells (ECs) have been derived from human pluripotent stem cells (hPSCs), large-scale generation of hPSC-ECs remains challenging and their functions are not well characterized. Here we report a simple and efficient three-stage method that allows generation of approximately 98 and 9500 ECs on day 16 and day 34, respectively, from each human embryonic stem cell (hESC) input. The functional properties of hESC-ECs derived in the presence and absence of a TGFβ-inhibitory molecule SB431542 were characterized and compared with those of human umbilical vein endothelial cells (HUVECs). Confluent monolayers formed by SB431542 + hESC-ECs, SB431542 - hESC-ECs, and HUVECs showed similar permeability to 10,000 Da dextran, but these cells exhibited striking differences in forming tube-like structures in 3D fibrin gels. The SB431542 + hESC-ECs were most potent in forming tube-like structures regardless of whether VEGF and bFGF were present in the medium; less potent SB431542 - hESC-ECs and HUVECs responded differently to VEGF and bFGF, which significantly enhanced the ability of HUVECs to form tube-like structures but had little impact on SB431542 - hESC-ECs. This study offers an efficient approach to large-scale hPSC-EC production and suggests that the phenotypes and functions of hPSC-ECs derived under different conditions need to be thoroughly examined before their use in technology development. © 2015 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 678-687, 2016. © 2015 Wiley Periodicals, Inc.

Enzyme catalysis-electrophoresis titration for multiplex enzymatic assay via moving reaction boundary chip.

PubMed

Zhong, Ran; Xie, Haiyang; Kong, Fanzhi; Zhang, Qiang; Jahan, Sharmin; Xiao, Hua; Fan, Liuyin; Cao, Chengxi

2016-09-21

In this work, we developed the concept of enzyme catalysis-electrophoresis titration (EC-ET) under ideal conditions, the theory of EC-ET for multiplex enzymatic assay (MEA), and a related method based on a moving reaction boundary (MRB) chip with a collateral channel and cell phone imaging. As a proof of principle, the model enzymes horseradish peroxidase (HRP), laccase and myeloperoxidase (MPO) were chosen for the tests of the EC-ET model. The experiments revealed that the EC-ET model could be achieved via coupling EC with ET within a MRB chip; particularly the MEA analyses of catalysis rate, maximum rate, activity, Km and Kcat could be conducted via a single run of the EC-ET chip, systemically demonstrating the validity of the EC-ET theory. Moreover, the developed method had these merits: (i) two orders of magnitude higher sensitivity than a fluorescence microplate reader, (ii) simplicity and low cost, and (iii) fairly rapid (30 min incubation, 20 s imaging) analysis, fair stability (<5.0% RSD) and accuracy, thus validating the EC-ET method. Finally, the developed EC-ET method was used for the clinical assay of MPO activity in blood samples; the values of MPO activity detected via the EC-ET chip were in agreement with those obtained by a traditional fluorescence microplate reader, indicating the applicability of the EC-ET method. The work opens a window for the development of enzymatic research, enzyme assay, immunoassay, and point-of-care testing as well as titration, one of the oldest methods of analysis, based on a simple chip.

Antioxidant poly(lactic-co-glycolic) acid nanoparticles made with α-tocopherol-ascorbic acid surfactant.

PubMed

Astete, Carlos E; Dolliver, Debra; Whaley, Meocha; Khachatryan, Lavrent; Sabliov, Cristina M

2011-12-27

The goal of the study was to synthesize a surfactant made of α-tocopherol (vitamin E) and ascorbic acid (vitamin C) of antioxidant properties dubbed as EC, and to use this surfactant to make poly(lactic-co-glycolic) acid (PLGA) nanoparticles. Self-assembled EC nanostructures and PLGA-EC nanoparticles were made by nanoprecipitation, and their physical properties (size, size distribution, morphology) were studied at different salt concentrations, surfactant concentrations, and polymer/surfactant ratios. EC surfactant was shown to form self-assembled nanostructures in water with a size of 22 to 138 nm in the presence of sodium chloride, or 12 to 31 nm when synthesis was carried out in sodium bicarbonate. Polymeric PLGA-EC nanoparticles presented a size of 90 to 126 nm for 40% to 120% mass ratio PLGA to surfactant. For the same mass ratios, the PLGA-Span80 formed particles measured 155 to 216 nm. Span80 formed bilayers, whereas EC formed monolayers at the interfaces. PLGA-EC nanoparticles and EC showed antioxidant activity based on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging assay measurements using UV and EPR techniques, antioxidant activity which is not characteristic to commercially available Span80. The thiobarbituric acid reactive substances (TBARS) assay for lipid peroxidation showed that PLGA nanoparticles with EC performed better as antioxidants than the EC nanoassembly or the free vitamin C. Nanoparticles were readily internalized by HepG2 cells and were localized in the cytoplasm. The newly synthesized EC surfactant was therefore found successful in forming uniform, small size polymeric nanoparticles of intrinsic antioxidant properties.

Rapamycin inhibits the proliferation of endothelial cells in hemangioma by blocking the mTOR-FABP4 pathway.

PubMed

Wang, Ying; Chen, Jiarui; Tang, Weiqing; Zhang, Yanping; Li, Xiaoyan

2017-01-01

FABP4 is widely expressed in both normal and pathologic tissues. It promotes cell proliferation, survival and migration of endothelial cells, and therefore, angiogenesis. However, the role of FABP4 in hemangioma or hemangioma endothelial cells (HemECs) has not been explored. In this study, we investigated whether FABP4 directly regulates the proliferation of HemECs. The expression of cell cycle checkpoint genes was analyzed with the microarray data of human dermal microvascular endothelial cells (HDVECs) and infantile hemangioma endothelial cells. Real-time RT-PCR and western blotting were used to examine the expression of FABP4 in HemECs. Next, the FABP4 expression was inhibited in HemECs using siRNA or rapamycin and upregulated using retroviral transduction of HemECs to assess its influence on proliferation of HemECs. The microarray data showed that cell cycle checkpoint genes were upregulated in HemECs. Moreover, HemECs showed significantly higher proliferation rates than HDVECs. The expression of FABP4 and mTOR was increased in the HemECs. While FABP4 knockdown reduced the BrdU incorporation and cell number of HemECs as expected, cell proliferation was accelerated by FABP4 over-expression. Moreover, rapamycin (10nM) inhibited mTOR-FABP4 signaling and HemEC proliferation. Taken together, these results indicated that mTOR signaling pathway-activated FABP4 directly regulates the proliferation of endothelial cells in hemangioma. Rapamycin and inhibitors of FABP4 have therapeutic potential for treating infantile hemangiomas. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Do electronic cigarettes impart a lower potential disease burden than conventional tobacco cigarettes? Review on E-cigarette vapor versus tobacco smoke.

PubMed

Oh, Anne Y; Kacker, Ashutosh

2014-12-01

Development and utilization of electronic cigarettes (ECs) resulted from the search for healthier alternatives to conventional tobacco cigarettes (TCs) and the search for alternative methods for quitting TCs. This review compares the potential disease burden presented by TC smoke to that of EC vapor. Potential disease burden of EC vapor versus TC smoke was assessed by reviewing clinical studies that measured inhaled components. Chemicals and carcinogens produced by vapor versus smoke were compared. Studies show that EC vapors contain far less carcinogenic particles than TC smoke. Whereas ECs have the ability to reach peak serum cotinine/nicotine levels comparable to that of TCs, ECs do not cause an increase in total white blood cell count; thus, ECs have the potential to lower the risk of atherosclerosis and systemic inflammation. Use of ECs has been shown to improve indoor air quality in a home exposed to TC smoke. This reduces secondhand smoke exposure, thus having the potential to decrease respiratory illness/asthma, middle-ear disease, sudden infant death syndrome, and more. However, some studies claim that propylene glycol (PG) vapor can induce respiratory irritation and increase chances for asthma. To minimize risks, EC manufacturers are replacing PG with distilled water and glycerin for vapor production. Based on the comparison of the chemical analysis of EC and TC carcinogenic profiles and association with health-indicating parameters, ECs impart a lower potential disease burden than conventional TCs. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

An Educator's Perspective on Environmental Communications Today.

ERIC Educational Resources Information Center

Schoenfeld, Clay

Environmental communications (EC) display three aspects of import to journalism teachers and researchers: first, the EC research base is lean but growing; second, environmental communicators are widely dispersed among an EC ecosystem of varied components; and third, while the varied roots of EC precede the present decade by many years,…

Research on Intellectual Property Conflicts Identification in Knowledge Transferring among EC Enterprises

NASA Astrophysics Data System (ADS)

Su, Shibin

As the lacks of existing research about intellectual property conflicts management of EC enterprise, the paper analysis the intellectual property conflicts in knowledge transferring among EC enterprises by intellectual property types, then, the paper makes research on intellectual property conflicts identification in knowledge transferring among EC enterprises, and gives relative assumption, meanwhile, the paper makes quantities identification of intellectual property conflicts in knowledge transferring among EC enterprises by evidential theory, finally, the paper gives the further research orientations.

32 CFR Appendix C to Part 623 - Agreement for Loan of US Army Materiel (DA Form 4881-R)

Code of Federal Regulations, 2010 CFR

2010-07-01

... 32 National Defense 3 2010-07-01 2010-07-01 true Agreement for Loan of US Army Materiel (DA Form 4881-R) C Appendix C to Part 623 National Defense Department of Defense (Continued) DEPARTMENT OF THE... Loan of US Army Materiel (DA Form 4881-R) EC24OC91.013 EC24OC91.014 EC24OC91.015 EC24OC91.016 EC24OC91...

32 CFR Appendix C to Part 623 - Agreement for Loan of US Army Materiel (DA Form 4881-R)

Code of Federal Regulations, 2011 CFR

2011-07-01

... 32 National Defense 3 2011-07-01 2009-07-01 true Agreement for Loan of US Army Materiel (DA Form 4881-R) C Appendix C to Part 623 National Defense Department of Defense (Continued) DEPARTMENT OF THE... Loan of US Army Materiel (DA Form 4881-R) EC24OC91.013 EC24OC91.014 EC24OC91.015 EC24OC91.016 EC24OC91...

Effect of oxybuprocaine 0.4% in preventing surgically induced miosis.

PubMed Central

van Rij, G; Renardel de Lavalette, J G; Baarsma, G S; Jansen, J T

1984-01-01

In a group of 68 patients a double-blind study was performed to assess the effect of preoperative oxybuprocaine 0.4% (Dorsacaine, Novesin) eye drops in comparison with a placebo in preventing surgically induced miosis during extracapsular cataract extraction. One drop of oxybuprocaine 0.4% or placebo was instilled 10 and 5 minutes preoperatively. The pupil diameter was recorded at different stages of the operation. It was found that oxybuprocaine reduced the amount of pupil constriction during the operation significantly as compared with the placebo group, facilitating the removal of lens material and the implantation of an intraocular lens. The effect of oxybuprocaine is considered to be due to anaesthetic action on sensory nerves in the eye, which may inhibit the release of a miotic substance. PMID:6367812

Effect of oxybuprocaine 0.4% in preventing surgically induced miosis.

PubMed

van Rij, G; Renardel de Lavalette, J G; Baarsma, G S; Jansen, J T

1984-04-01

In a group of 68 patients a double-blind study was performed to assess the effect of preoperative oxybuprocaine 0.4% (Dorsacaine, Novesin) eye drops in comparison with a placebo in preventing surgically induced miosis during extracapsular cataract extraction. One drop of oxybuprocaine 0.4% or placebo was instilled 10 and 5 minutes preoperatively. The pupil diameter was recorded at different stages of the operation. It was found that oxybuprocaine reduced the amount of pupil constriction during the operation significantly as compared with the placebo group, facilitating the removal of lens material and the implantation of an intraocular lens. The effect of oxybuprocaine is considered to be due to anaesthetic action on sensory nerves in the eye, which may inhibit the release of a miotic substance.

Eye health care in the Czech Republic.

PubMed

Kocur, Ivo; Kuchynka, Pavel

2002-01-01

An analysis of eye health care in the Czech Republic as of 1998 was performed. A questionnaire was used to obtain information from all 59 in-patient eye departments. The number of ophthalmologists per 1 million inhabitants was 95. The number of cataract operations per 1 million inhabitants was 4,209: phaco-emulsification (36,926 surgeries, 85.2%), extracapsular extraction (6,094 surgeries, 14.1%) and intracapsular extraction (90 surgeries, 0.2%). Intra-ocular lenses were implanted in 99% of cases; 404 corneal transplantations and 1,220 operations for retinal detachment were performed. The number of pars plana vitrectomies for diabetic eye complications was 661. Selected regional clinical centres should be equipped and preferred by health insurance companies to provide comprehensive eye health care services and training. Copyright 2002 S. Karger AG, Basel

Anterior Cruciate Ligament Injury, Reconstruction, and the Optimization of Outcome

PubMed Central

Bliss, James Philip

2017-01-01

Anterior cruciate ligament reconstruction (ACLR) provides an established surgical intervention to control pathological tibiofemoral translational and rotational movement. ACLR is a safe and reproducible intervention, but there remains an underlying rate of failure to return to preinjury sporting activity levels. Postoperative pathological laxity and graft reinjury remain concerns. Previously, unrecognized meniscal lesions, disruption of the lateral capsule, and extracapsular structures offer potential avenues to treat and to therefore improve kinematic outcome and functional results, following reconstruction. Addressing laterally based injuries may also improve the durability of intraarticular ACLR. Improving the anterior cruciate ligament (ACL) graft replication of the normal ACL attachment points on the femur and the tibia, using either double bundle or anatomical single bundle techniques, improves kinematics, which may benefit outcome and functionality, following reconstruction. PMID:28966384

Male access to emergency contraception in pharmacies: a mystery shopper survey.

PubMed

Bell, David L; Camacho, Elvis J; Velasquez, Andrew B

2014-10-01

Pharmacy access to emergency contraception (EC) could involve men in pregnancy prevention. The objectives were to assess the availability and cost of EC. Male mystery shoppers visited 158 pharmacies in three neighborhoods in New York City. They asked for EC and its cost and noted weekend hours. Twenty-two (73.3%) of 30 pharmacies created barriers to get EC. The cost of EC was higher in the higher-socioeconomic status (SES) neighborhood (p<.001), and the higher-SES neighborhood pharmacies had a greater number of weekend hours (p<.001). Overall, males had a 20% probability of not being able to access EC. The national dialogue should include males. Copyright © 2014 Elsevier Inc. All rights reserved.

Aircraft Boundary-layer Measurements in the Gulf of Tehuantepec

NASA Astrophysics Data System (ADS)

Friehe, Carl; Melville, W. K.

2005-11-01

Airborne flux, meteorological, and wave measurements were made from the NSF/NCAR EC130Q aircraft in the Gulf of Tehuantepec under strong boundary-layer gap winds up to 25 m/sec at 33 m height. Statistics of flux estimates were obtained from multiple 33-m tracks flown under reasonably stationary and homogeneous conditions. Flux divergence was obtained from stack patterns flown at various distances from shore. Tracks flown at 33 m between the stacks provided the pressure gradient and advection terms in the momentum balance. Near shore, flux divergence was important and approximately balanced by the pressure gradient and advective terms; off-shore (400 km), divergence was small and again approximately in balance with the other two terms. Data from dropsondes and the Scanning Aerosol Backscatter LIDAR (SABL) revealed that the internal boundary layer initially thins off-shore as the gap wind field spreads horizontally, and then thickens due to turbulent mixing and possible hydraulic effects. Supported by NSF Division of Ocean Sciences.

Characteristics of size-segregated carbonaceous aerosols in the Beijing-Tianjin-Hebei region.

PubMed

Guo, Yuhong

2016-07-01

Mass concentrations of organic carbon (OC) and elemental carbon (EC) in size-resolved aerosols were investigated at four sites (three cities and one country) in the Beijing-Tianjin-Hebei region from September 2009 to August 2011. The size distributions of OC and EC presented large evolutions among rural and urban sites, and among four seasons, with highest peaks of OC and EC in fine mode in urban areas during winter. Geometric mean diameters (GMDs) of OC and EC in fine particles at urban sites during winter were lower than those at rural site mainly due to effects of fine particle coagulation and organic compound repartitioning. Fossil fuel emissions were a dominant source of OC and EC in urban areas, while biomass burning was a major source of OC and EC at rural site. Trajectory clustering and CWT analysis showed that regional transport was an important contributor to OC and EC in Beijing.

Characterization of ethyl cellulose polymer.

PubMed

Mahnaj, Tazin; Ahmed, Salah U; Plakogiannis, Fotios M

2013-01-01

Ethyl cellulose (EC) polymer was characterized for its property before considering the interactions with the plasicizer. Ethocel Std.10 FP Premium from Dow chemical company USA was tested for its solubility, morphology and thermal properties. Seven percentage of EC solution in ethanol was found to be the right viscosity used to prepare the film. The EC polymer and EC film without any plasticizers showed almost identical thermal behavior, but in X-ray diffraction showed different arrangements of crystallites and amorphous region. Dynamic mechanical analysis of film showed that without a plasticizer, EC film was not flexible and had very low elongation with high applied force. The aim of the work was to avoid using the commercially available EC dispersions Surelease® and Aquacoat®; both already have additives on it. Instead, Ethocel EC polymer (powder) was characterized in our laboratory in order to find out the properties of polymer before considering the interactions of the polymer with various plasticizers.

Opiate-like electroencephalographic and behavioral effects of electroconvulsive shock in rats.

PubMed

Tortella, F C; Cowan, A; Belenky, G L; Holaday, J W

1981-12-03

Rats were studied (a) after a single transauricular electroshock (acute ECS) and (b) following 10 consecutive once-daily shocks (chronic ECS). ECS produced a generalized convulsion marked by a polyspike EEG seizure. The seizure was followed by a period of postictal depression (PID) characterized by EEG high-voltage synchrony, EMG quietening, and an associated stuporous behavior in the rat. Acute ECS produced a maximal of 33 +/- 8 (S.E.) percent above control in the EEG voltage output during postictus, with the PID lasting 2680 +/- 658 sec. Chronic ECS resulted in a significant enhancement of these acute responses. Pretreating rats with naloxone (0.3-10 mg/kg s.c.) antagonized the postictal effects of acute ECS, but not of chronic ECS. These naloxone-sensitive postictal EEG and behavioral changes appear to reflect a release of endogenous opioid peptides during ictus, a finding consistent with the hypothesis that electroshock activates opioid systems.

Companies commit to emergency contraception -- have you?

PubMed

1999-12-01

Despite the efforts of the medical community, as well as promotional efforts by pharmaceutical companies, relatively few women in the US have heard of emergency contraceptives (ECs). Gynetics, marketer of Preven, plans to file a new drug application for a levonorgestrel EC by the end of 1999, with an anticipated approval in the second half of 2000. Women's Capital Corp., marketer of Plan B, is also aiming for a national commercial launch of its product. According to a recently published acceptability study, women will use ECs when they are made available. A survey among 235 women at 13 Kaiser Permanente medical offices in San Diego, California, regarding their experiences with ECs showed that 91% were satisfied with ECs, and 97% said they would use ECs for emergencies only--dispelling fears that women would forego use of ongoing contraception. About 70% of the women who participated in the study were using a contraceptive method when they requested ECs.

The Varied Circumstances Prompting Requests for Emergency Contraception at School-Based Clinics

ERIC Educational Resources Information Center

Sidebottom, Abbey; Harrison, Patricia A.; Amidon, Donna; Finnegan, Katie

2008-01-01

Background: Little is known about the circumstances that prompt teenagers to request emergency contraception (EC). This evaluation was designed to refine the EC clinical protocol and improve pregnancy prevention efforts in high school-based clinics by analyzing information on EC use and subsequent contraception use of EC patients. Methods: Sites…

76 FR 75772 - Airworthiness Directives; Eurocopter France Model EC 120B Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-05

... Airworthiness Directives; Eurocopter France Model EC 120B Helicopters AGENCY: Federal Aviation Administration... the Eurocopter France Model EC 120B helicopters. This AD requires modifying the pilot cyclic control... include an AD that would apply to Eurocopter France Model EC 120B helicopters. That NPRM was published in...

77 FR 69558 - Airworthiness Directives; Eurocopter Deutschland GmbH Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-20

... Airworthiness Directives; Eurocopter Deutschland GmbH Helicopters AGENCY: Federal Aviation Administration (FAA... airworthiness directive (AD) for Eurocopter Deutschland GmbH (ECD) Model EC135 P1, EC135 P2, EC135 P2+, EC135 T1... with this AD through an AMOC. (h) Additional Information (1) Eurocopter Emergency Alert Service...

Inflammatory Responses and Barrier Function of Endothelial Cells Derived from Human Induced Pluripotent Stem Cells.

PubMed

Halaidych, Oleh V; Freund, Christian; van den Hil, Francijna; Salvatori, Daniela C F; Riminucci, Mara; Mummery, Christine L; Orlova, Valeria V

2018-05-08

Several studies have reported endothelial cell (EC) derivation from human induced pluripotent stem cells (hiPSCs). However, few have explored their functional properties in depth with respect to line-to-line and batch-to-batch variability and how they relate to primary ECs. We therefore carried out accurate characterization of hiPSC-derived ECs (hiPSC-ECs) from multiple (non-integrating) hiPSC lines and compared them with primary ECs in various functional assays, which included barrier function using real-time impedance spectroscopy with an integrated assay of electric wound healing, endothelia-leukocyte interaction under physiological flow to mimic inflammation and angiogenic responses in in vitro and in vivo assays. Overall, we found many similarities but also some important differences between hiPSC-derived and primary ECs. Assessment of vasculogenic responses in vivo showed little difference between primary ECs and hiPSC-ECs with regard to functional blood vessel formation, which may be important in future regenerative medicine applications requiring vascularization. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

Single-trial evaluative conditioning can be moderated by instructed forgetting.

PubMed

Gast, Anne; Kattner, Florian

2016-09-01

Evaluative conditioning (EC) is a change in the valence of a conditioned stimulus (CS) due to previous pairing with an affective unconditioned stimulus (US). Several previous studies indicate that EC is related to memory of the CS-US pairs. Previous studies, however, typically cannot distinguish between the influence of CS-US knowledge during measurement and during encoding. In addition, by measuring rather than manipulating memory, they do not test the causal effect of memory on EC. The present study employed a "directed forgetting" procedure to the EC paradigm instructing participants to either forget or remember certain CS-US pairs. We found that EC effects after single learning trials were stronger for to-be-remembered than for to-be-forgotten pairs. Manipulation checks showed that the forgetting manipulation also successfully modulated memory for the target pairs and reduced both retroactive and proactive interference on memory for other pairs. Item-based analyses further demonstrated that the size of EC depended on CS-US memory. The results suggest that EC relies on available memory during measurement of the EC effect.

Relations among maternal socialization, effortful control, and maladjustment in early childhood.

PubMed

Eisenberg, Nancy; Spinrad, Tracy L; Eggum, Natalie M; Silva, Kassondra M; Reiser, Mark; Hofer, Claire; Smith, Cynthia L; Gaertner, Bridget M; Kupfer, Anne; Popp, Tierney; Michalik, Nicole

2010-08-01

In a sample of 18-, 30-, and 42-month-olds, the relations among parenting, effortful control (EC), and maladjustment were examined. Parenting was assessed with mothers' reports and observations; EC was measured with mothers' and caregivers' reports, as well as a behavioral task; and externalizing and internalizing symptoms were assessed with parents' and caregivers' reports. Although 18-month unsupportive (vs. supportive) parenting negatively predicted EC at 30 months, when the stability of these variables was taken into account, there was no evidence of additional potentially causal relations between these two constructs. Although EC was negatively related to both internalizing and externalizing problems within all three ages as well as across 1 year, EC did not predict maladjustment once the stability of the constructs and within time covariation between the constructs were taken into account. In addition, externalizing problems at 30 months negatively predicted EC at 42 months, and internalizing problems at 30 months positively predicted EC at 42 months, but only when the effects of externalizing on EC were controlled. The findings are discussed in terms of the reasons for the lack of causal relations over time.

ICECAP: an integrated, general-purpose, automation-assisted IC50/EC50 assay platform.

PubMed

Li, Ming; Chou, Judy; King, Kristopher W; Jing, Jing; Wei, Dong; Yang, Liyu

2015-02-01

IC50 and EC50 values are commonly used to evaluate drug potency. Mass spectrometry (MS)-centric bioanalytical and biomarker labs are now conducting IC50/EC50 assays, which, if done manually, are tedious and error-prone. Existing bioanalytical sample preparation automation systems cannot meet IC50/EC50 assay throughput demand. A general-purpose, automation-assisted IC50/EC50 assay platform was developed to automate the calculations of spiking solutions and the matrix solutions preparation scheme, the actual spiking and matrix solutions preparations, as well as the flexible sample extraction procedures after incubation. In addition, the platform also automates the data extraction, nonlinear regression curve fitting, computation of IC50/EC50 values, graphing, and reporting. The automation-assisted IC50/EC50 assay platform can process the whole class of assays of varying assay conditions. In each run, the system can handle up to 32 compounds and up to 10 concentration levels per compound, and it greatly improves IC50/EC50 assay experimental productivity and data processing efficiency. © 2014 Society for Laboratory Automation and Screening.

Oral administration of probiotic bacteria (E. coli Nissle, E. coli O83, Lactobacillus casei) influences the severity of dextran sodium sulfate-induced colitis in BALB/c mice.

PubMed

Kokesová, A; Frolová, L; Kverka, M; Sokol, D; Rossmann, P; Bártová, J; Tlaskalová-Hogenová, H

2006-01-01

Our study examined whether repeated preventive oral administration of live probiotic bacterial strains Escherichia coli O83:K24:H31 (Ec O83), Escherichia coli Nissle 1917 O6:K5:H1 (Ec Nis) and Lactobacillus casei DN 114001 (Lc) can protect mice against dextran sodium sulfate (DSS)-induced colitis. A significant decrease in average symptom score was observed in Ec O83-, Ec Nis- and Lc-pretreated group (p < 0.05). Significant differences in body mass loss between Lc pretreated mice with DSS-induced colitis were found when compared with nontreated mice (p < 0.05). PBS pretreated mice had a significantly shorter colon than Ec O83-, Ec Nis- and Lc-pretreated mice (p < 0.05). Administration of Lc significantly decreased the severity of DSS induced histological marks of inflammation (p < 0.05). A significant difference (p < 0.05) was also found in specific IgA level against given probiotic in enteral fluid between colitic mice and healthy mice pretreated with Ec 083 and Ec Nis.

Emergency Contraception in Emergency Departments in Oregon, 2003

PubMed Central

Rosenberg, Kenneth D.; DeMunter, Jodi K.; Liu, Jihong

2005-01-01

Objectives. We sought to learn about access to emergency contraception (EC) in Oregon emergency departments, both for women who are rape patients and for women who have had consensual unprotected sexual intercourse (“nonrape patients”). Methods. We interviewed emergency department staff in 54 of Oregon’s 57 licensed emergency departments in February–March 2003 (response rate = 94.7%). Results. Only 61.1% of Oregon emergency departments routinely offered EC to rape patients. Catholic hospitals were as likely as non-Catholic hospitals to routinely offer EC to rape patients. The hospitals most likely to routinely offer EC to rape patients had a written protocol for the care of rape patients that included offering EC (P = .02) and access to staff with specialized sexual assault training (P=.002). For nonrape patients, 46.3% of emergency departments discouraged the prescribing of EC. Catholic hospitals were significantly less likely than non-Catholic hospitals to provide access to EC for nonrape patients (P=.05). Conclusions. Oregon emergency departments do not routinely offer EC to women who have been raped or to women who have had consensual unprotected sexual intercourse. PMID:15985646

Endothelial permeability is controlled by spatially defined cytoskeletal mechanics: atomic force microscopy force mapping of pulmonary endothelial monolayer.

PubMed

Birukova, Anna A; Arce, Fernando T; Moldobaeva, Nurgul; Dudek, Steven M; Garcia, Joe G N; Lal, Ratnesh; Birukov, Konstantin G

2009-03-01

Actomyosin contraction directly regulates endothelial cell (EC) permeability, but intracellular redistribution of cytoskeletal tension associated with EC permeability is poorly understood. We used atomic force microscopy (AFM), EC permeability assays, and fluorescence microscopy to link barrier regulation, cell remodeling, and cytoskeletal mechanical properties in EC treated with barrier-protective as well as barrier-disruptive agonists. Thrombin, vascular endothelial growth factor, and hydrogen peroxide increased EC permeability, disrupted cell junctions, and induced stress fiber formation. Oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine, hepatocyte growth factor, and iloprost tightened EC barriers, enhanced peripheral actin cytoskeleton and adherens junctions, and abolished thrombin-induced permeability and EC remodeling. AFM force mapping and imaging showed differential distribution of cell stiffness: barrier-disruptive agonists increased stiffness in the central region, and barrier-protective agents decreased stiffness in the center and increased it at the periphery. Attenuation of thrombin-induced permeability correlates well with stiffness changes from the cell center to periphery. These results directly link for the first time the patterns of cell stiffness with specific EC permeability responses.

gp96 expression in neutrophils is critical for the onset of Escherichia coli K1 (RS218) meningitis.

PubMed

Mittal, Rahul; Prasadarao, Nemani V

2011-11-22

Despite the fundamental function of neutrophils (polymorphonuclear leukocytes (PMNs)) in innate immunity, their role in Escherichia coli K1 (EC-K1) -induced meningitis is unexplored. Here we show that PMN-depleted mice are resistant to EC-K1 (RS218) meningitis. EC-K1 survives and multiplies in PMNs for which outer membrane protein A (OmpA) expression is essential. EC-K1 infection of PMNs increases the cell surface expression of gp96, which acts as a receptor for bacterial entry. Suppression of gp96 expression in newborn mice prevents the onset of EC-K1 meningitis. Infection of PMNs with EC-K1 suppresses oxidative burst by downregulating rac1, rac2 and gp91(phox) transcription both in vitro and in vivo. The interaction of loop 2 of OmpA with gp96 is essential for EC-K1-mediated inhibition of oxidative burst. These results reveal that EC-K1 exploits surface-expressed gp96 in PMNs to prevent oxidative burst for the onset of neonatal meningitis.

gp96 expression in neutrophils is critical for the onset of Escherichia coli K1 (RS218) meningitis

PubMed Central

Mittal, Rahul; Prasadarao, Nemani V.

2012-01-01

Despite the fundamental function of neutrophils (PMNs) in innate immunity, their role in Escherichia coli K1 (EC-K1) induced meningitis is unexplored. Here we show that PMN-depleted mice are resistant to EC-K1 (RS218) meningitis. EC-K1 survives and multiplies in PMNs for which outer membrane protein A (OmpA) expression is essential. EC-K1infection of PMNs increases the cell surface expression of gp96, which acts as a receptor for bacterial entry. Suppression of gp96 expression in newborn mice prevents the onset of EC-K1 meningitis. Infection of PMNs with EC-K1 suppresses oxidative burst by down regulating rac1, rac2 and gp91phox transcription both in vitro and in vivo. The interaction of loop 2 of OmpA with gp96 is essential for EC-K1-mediated inhibition of oxidative burst. These results reveal that EC-K1 exploits surface expressed gp96 in PMNs to prevent oxidative burst for the onset of neonatal meningitis. PMID:22109526

Fatty acids rather than hormones restore in vitro angiogenesis in human male and female endothelial cells cultured in charcoal-stripped serum

PubMed Central

Vanetti, Claudia; Bifari, Francesco; Vicentini, Lucia M.

2017-01-01

Charcoal-stripped serum (CSS) is a well-accepted method to model effects of sex hormones in cell cultures. We have recently shown that human endothelial cells (ECs) fail to growth and to undergo in vitro angiogenesis when cultured in CSS. However, the mechanism(s) underlying the CSS-induced impairment of in vitro EC properties are still unknown. In addition, whether there is any sexual dimorphism in the CSS-induced EC phenotype remains to be determined. Here, by independently studying human male and female ECs, we found that CSS inhibited both male and female EC growth and in vitro angiogenesis, with a more pronounced effect on male EC sprouting. Reconstitution of CSS with 17-β estradiol, dihydrotestosterone, or the lipophilic thyroid hormone did not restore EC functions in both sexes. On the contrary, supplementation with palmitic acid or the acetyl-CoA precursor acetate significantly rescued the CSS-induced inhibition of growth and sprouting in both male and female ECs. We can conclude that the loss of metabolic precursors (e.g., fatty acids) rather than of hormones is involved in the impairment of in vitro proliferative and angiogenic properties of male and female ECs cultured with CSS. PMID:29232396

Akt Suppression of TGFβ Signaling Contributes to the Maintenance of Vascular Identity in Embryonic Stem Cell-Derived Endothelial Cells

PubMed Central

Israely, Edo; Ginsberg, Michael; Nolan, Daniel; Ding, Bi-Sen; James, Daylon; Elemento, Olivier; Rafii, Shahin; Rabbany, Sina Y

2016-01-01

The ability to generate and maintain stable in vitro cultures of mouse endothelial cells (EC) has great potential for genetic dissection of the numerous pathologies involving vascular dysfunction as well as therapeutic applications. However, previous efforts at achieving sustained cultures of primary stable murine vascular cells have fallen short, and the cellular requirements for EC maintenance in vitro remain undefined. In this study, we have generated vascular ECs from mouse embryonic stem (ES) cells, and show that active Akt is essential to their survival and propagation as homogeneous monolayers in vitro. These cells harbor the phenotypical, biochemical, and functional characteristics of ECs, and expand throughout long-term cultures, while maintaining their angiogenic capacity. Moreover, Akt-transduced embryonic ECs form functional perfused vessels in vivo that anastomose with host blood vessels. We provide evidence for a novel function of Akt in stabilizing EC identity, whereby the activated form of the protein protects mouse ES cell-derived ECs from TGFβ-mediated transdifferentiation by downregulating SMAD3. These findings identify a role for Akt in regulating the developmental potential of ES cell-derived ECs, and demonstrate that active Akt maintains endothelial identity in embryonic ECs by interfering with active TGFβ-mediated processes that would ordinarily usher these cells to alternate fates. PMID:23963623

The role of pharmacists and emergency contraception: Are pharmacists' perceptions of emergency contraception predictive of their dispensing practices?

PubMed

Richman, Alice R; Daley, Ellen M; Baldwin, Julie; Kromrey, Jeff; O'Rourke, Kathleen; Perrin, Kay

2012-10-01

Pharmacists can play a critical role in the access to emergency contraception (EC). We assessed if knowledge and attitudes were predictive of EC dispensing among a statewide sample of Florida pharmacists, who have legal authority to refuse to dispense medications. In 2008, surveys were mailed to a random sample of 1264 pharmacists registered with the Florida Board of Pharmacy. Data from 272 pharmacists (22% response rate) were analyzed using bivariate and multivariate logistic regression. Fifty-six percent of respondents incorrectly answered that EC causes birth defects, and 46% replied that it causes abortion. Only 22% said that EC can be purchased in advance of need. Many felt uncomfortable dispensing to adolescents (61%) and men (58%). Knowledge about EC was the most important predictor of dispensing [odds ratio (OR)=1.57, 95% confidence interval (CI) 1.22-2.03]. In particular, pharmacists who reported that EC does not act as an abortifacient were more likely to dispense it (OR=4.64, 95% CI 2.15-10.00). Correct information about EC was the most important predictor of pharmacists' dispensing EC. To expand availability of EC, pharmacists will have to become better informed. Copyright © 2012 Elsevier Inc. All rights reserved.

Emergency Childcare for Hospital Workers During Disasters.

PubMed

Charney, Rachel L; Rebmann, Terri; Flood, Robert G

2015-12-01

The objectives were to determine the impact of emergency childcare (EC) needs on health care workers' ability and likelihood to work during a pandemic versus an earthquake as well as to determine the anticipated need and expected use of an on-site, hospital-provided EC program. An online survey was distributed to all employees of an academic, urban pediatric hospital. Two disaster scenarios were presented (pandemic influenza and earthquake). Ability to work based on childcare needs, planned use of proposed hospital-provided EC, and demographics of children being brought in were obtained. A total of 685 employees participated (96.6% female, 79.6% white), with a 40% response rate. Those with children (n = 307) reported that childcare needs would affect their work decisions during a pandemic more than an earthquake (61.1% vs 56.0%; t = 3.7; P < 0.001). Only 28.0% (n = 80) of those who would need childcare (n = 257) report an EC plan. The scenario did not impact EC need or planned use; during scheduled versus unscheduled shifts, 40.7% versus 63.0% reported need for EC, and 50.8% versus 63.2% reported anticipated using EC. Hospital workers have a high anticipated use of hospital-provided EC. Provisions for EC should be an integral part of hospital disaster planning.

Ethyl carbamate induces cell death through its effects on multiple metabolic pathways.

PubMed

Liu, Huichang; Cui, Bo; Xu, Yi; Hu, Chaoyang; Liu, Ying; Qu, Guorun; Li, Dawei; Wu, Yongning; Zhang, Dabing; Quan, Sheng; Shi, Jianxin

2017-11-01

Ethyl carbamate (EC), a multisite carcinogenic chemical causing tumors in various animal species, is probably carcinogenic to humans. However, information about the possible carcinogenic and toxicological effects of EC in humans is quite limited. Because EC is found in many dietary foods (such as fermented foods) and tobacco and its products, and exposure of humans to EC often occurs inevitably, its toxicological effects in humans need to be studied. This study was conducted to understand the metabolomic and transcriptomic changes in human hepatocellular carcinoma cells (HepG2) exposed to 100 mM EC for short term (4 h) and long term (12 h) period, respectively. The results revealed multiple influences of EC on the metabolome and transcriptome of HepG2 cells, which was exposure time-dependent and well correlated with the kinetic changes of cell viability and mortality. EC treatment affected multiple metabolic pathways, inducing oxidative stress, reducing detoxification capacity, depleting energy, decreasing reducing power, disrupting membrane integrity, and damaging DNA and protein. These metabolomic and transcriptomic biomarkers of EC on human cell metabolism identified in this study would facilitate further studies on the risk assessment and the mitigation of dietary EC. Copyright © 2017 Elsevier B.V. All rights reserved.

Molecular mechanisms of euplotin C-induced apoptosis: involvement of mitochondrial dysfunction, oxidative stress and proteases.

PubMed

Cervia, Davide; Garcia-Gil, Mercedes; Simonetti, Elisa; Di Giuseppe, Graziano; Guella, Graziano; Bagnoli, Paola; Dini, Fernando

2007-08-01

The metabolite euplotin C (EC), isolated from the marine ciliate Euplotes crassus, is a powerful cytotoxic and pro-apoptotic agent in tumour cell lines. For instance, EC induces the rapid depletion of ryanodine Ca(2+) stores, the release of cytochrome c from the mitochondria, and the activation of caspase-3, leading to apoptosis. The purpose of this study was to gain further insight into the mechanisms of EC-induced apoptosis in rat pheochromocytoma PC12 cells. We found that EC increases Bax/Bcl-2 ratio and that Bax is responsible of the EC-induced dissipation of the mitochondrial membrane potential (Deltapsi(m)). In addition, EC induces the generation of reactive oxygene species (ROS) without involvement of p53. The inhibition of ROS generation prevents, at least in part, the pro-apoptotic effects of EC as well as the effects of EC on Bax, Deltapsi(m) and intracellular free Ca(2+), indicating a cross-talk between different pathways. However, definition of the effector cascade turns out to be more complex than expected and caspase-independent mechanisms, acting in parallel with caspases, should also be considered. Among them, EC increases the expression/activity of calpains downstream of ROS generation, although calpains seem to exert protective effects.

Electronic cigarettes: Review of use, content, safety, effects on smokers, and potential for harm and benefit

PubMed Central

Hajek, Peter; Etter, Jean-François; Benowitz, Neal; Eissenberg, Thomas; McRobbie, Hayden

2015-01-01

Aims We reviewed available research on the use, content and safety of electronic cigarettes (EC) and on their effects on users, to assess their potential for harm or benefit and to extract evidence that can guide future policy. Methods Studies were identified by systematic database searches and screening references to February 2014. Results EC aerosol can contain some of the toxicants present in tobacco smoke, but at levels which are much lower. Long-term health effects of EC use are unknown but compared with cigarettes, EC are likely to be much less, if at all, harmful to users or bystanders. EC are increasingly popular among smokers, but to date there is no evidence of regular use by never-smokers or by non-smoking children. EC enable some users to reduce or quit smoking. Conclusions Allowing EC to compete with cigarettes in the marketplace might decrease smoking-related morbidity and mortality. Regulating EC as strictly as cigarettes, or even more strictly as some regulators propose, is not warranted on current evidence. Health professionals may consider advising smokers unable or unwilling to quit through other routes to switch to EC as a safer alternative to smoking and a possible pathway to complete cessation of nicotine use. PMID:25078252

Akt suppression of TGFβ signaling contributes to the maintenance of vascular identity in embryonic stem cell-derived endothelial cells.

PubMed

Israely, Edo; Ginsberg, Michael; Nolan, Daniel; Ding, Bi-Sen; James, Daylon; Elemento, Olivier; Rafii, Shahin; Rabbany, Sina Y

2014-01-01

The ability to generate and maintain stable in vitro cultures of mouse endothelial cells (ECs) has great potential for genetic dissection of the numerous pathologies involving vascular dysfunction as well as therapeutic applications. However, previous efforts at achieving sustained cultures of primary stable murine vascular cells have fallen short, and the cellular requirements for EC maintenance in vitro remain undefined. In this study, we have generated vascular ECs from mouse embryonic stem (ES) cells and show that active Akt is essential to their survival and propagation as homogeneous monolayers in vitro. These cells harbor the phenotypical, biochemical, and functional characteristics of ECs and expand throughout long-term cultures, while maintaining their angiogenic capacity. Moreover, Akt-transduced embryonic ECs form functional perfused vessels in vivo that anastomose with host blood vessels. We provide evidence for a novel function of Akt in stabilizing EC identity, whereby the activated form of the protein protects mouse ES cell-derived ECs from TGFβ-mediated transdifferentiation by downregulating SMAD3. These findings identify a role for Akt in regulating the developmental potential of ES cell-derived ECs and demonstrate that active Akt maintains endothelial identity in embryonic ECs by interfering with active TGFβ-mediated processes that would ordinarily usher these cells to alternate fates. © AlphaMed Press.

Single-nanotube tracking reveals the nanoscale organization of the extracellular space in the live brain

NASA Astrophysics Data System (ADS)

Godin, Antoine G.; Varela, Juan A.; Gao, Zhenghong; Danné, Noémie; Dupuis, Julien P.; Lounis, Brahim; Groc, Laurent; Cognet, Laurent

2017-03-01

The brain is a dynamic structure with the extracellular space (ECS) taking up almost a quarter of its volume. Signalling molecules, neurotransmitters and nutrients transit via the ECS, which constitutes a key microenvironment for cellular communication and the clearance of toxic metabolites. The spatial organization of the ECS varies during sleep, development and aging and is probably altered in neuropsychiatric and degenerative diseases, as inferred from electron microscopy and macroscopic biophysical investigations. Here we show an approach to directly observe the local ECS structures and rheology in brain tissue using super-resolution imaging. We inject single-walled carbon nanotubes into rat cerebroventricles and follow the near-infrared emission of individual nanotubes as they diffuse inside the ECS for tens of minutes in acute slices. Because of the interplay between the nanotube geometry and the ECS local environment, we can extract information about the dimensions and local viscosity of the ECS. We find a striking diversity of ECS dimensions down to 40 nm, and as well as of local viscosity values. Moreover, by chemically altering the extracellular matrix of the brains of live animals before nanotube injection, we reveal that the rheological properties of the ECS are affected, but these alterations are local and inhomogeneous at the nanoscale.

A Parallel-Plate Flow Chamber for Mechanical Characterization of Endothelial Cells Exposed to Laminar Shear Stress

PubMed Central

Wong, Andrew K.; LLanos, Pierre; Boroda, Nickolas; Rosenberg, Seth R.; Rabbany, Sina Y.

2017-01-01

Shear stresses induced by laminar fluid flow are essential to properly recapitulate the physiological microenvironment experienced by endothelial cells (ECs). ECs respond to these stresses via mechanotransduction by modulating their phenotype and biomechanical characteristics, which can be characterized by Atomic Force Microscopy (AFM). Parallel Plate Flow Chambers (PPFCs) apply unidirectional laminar fluid flow to EC monolayers in vitro. Since ECs in sealed PPFCs are inaccessible to AFM probes, cone-and-plate viscometers (CPs) are commonly used to apply shear stress. This paper presents a comparison of the efficacies of both methods. Computational Fluid Dynamic simulation and validation testing using EC responses as a metric have indicated limitations in the use of CPs to apply laminar shear stress. Monolayers subjected to laminar fluid flow in a PPFC respond by increasing cortical stiffness, elongating, and aligning filamentous actin in the direction of fluid flow to a greater extent than CP devices. Limitations using CP devices to provide laminar flow across an EC monolayer suggest they are better suited when studying EC response for disturbed flow conditions. PPFC platforms allow for exposure of ECs to laminar fluid flow conditions, recapitulating cellular biomechanical behaviors, whereas CP platforms allow for mechanical characterization of ECs under secondary flow. PMID:28989541

Molecular basis for endothelial lumen formation and tubulogenesis during vasculogenesis and angiogenic sprouting

PubMed Central

Davis, George E.; Stratman, Amber N.; Sacharidou, Anastasia; Koh, Wonshill

2013-01-01

Many studies reveal a fundamental role for extracellular matrix-mediated signaling through integrins and Rho GTPases as well as matrix metalloproteinases (MMPs) in the molecular control of vascular tube morphogenesis in three-dimensional (3D) tissue environments. Recent work has defined an EC lumen signaling complex of proteins that controls these vascular morphogenic events. These findings reveal a signaling interdependence between Cdc42 and MT1-MMP to control the 3D matrix-specific process of EC tubulogenesis. The EC tube formation process results in the creation of a network of proteolytically-generated vascular guidance tunnels in 3D matrices that are utilized to remodel EC-lined tubes through EC motility and could facilitate processes such as flow-induced remodeling and arteriovenous EC sorting and differentiation. Within vascular guidance tunnels, key dynamic interactions occur between endothelial cells (ECs) and pericytes to affect vessel remodeling, diameter, and vascular basement membrane matrix assembly, a fundamental process necessary for endothelial tube maturation and stabilization. Thus, the EC lumen and tube formation mechanism coordinates the concomitant establishment of a network of vascular tubes within tunnel spaces to allow for flow responsiveness, EC-mural cell interactions, and vascular extracellular matrix assembly to control the development of the functional microcirculation. PMID:21482411

Molecular Analysis of Mixed Endometrioid and Serous Adenocarcinoma of the Endometrium

PubMed Central

Lawrenson, Kate; Pakzamir, Elham; Liu, Biao; Lee, Janet M.; Delgado, Melissa K.; Duncan, Kara; Gayther, Simon A.; Liu, Song; Roman, Lynda; Mhawech-Fauceglia, Paulette

2015-01-01

Background The molecular biology and cellular origins of mixed type endometrial carcinomas (MT-ECs) are poorly understood, and a Type II component of 10 percent or less may confer poorer prognoses. Methodology/Principal Findings We studied 10 cases of MT-EC (containing endometrioid and serous differentiation), 5 pure low-grade endometrioid adenocarcinoma (EAC) and 5 pure uterine serous carcinoma (USC). Endometrioid and serous components of the MT-ECs were macrodissected and the expression of 60 candidate genes compared between MT-EC, pure USC and pure EAC. We found that four genes were differentially expressed when MT-ECs were compared to pure low-grade EAC: CDKN2A (P = 0.006), H19 (P = 0.010), HOMER2 (P = 0.009) and TNNT1 (P = 0.006). Also while we found that even though MT-ECs closely resembled the molecular profiles of pure USCs, they also exhibit lower expression of PAX8 compared to all pure cases combined (P = 0.035). Conclusion Our data suggest that MT-EC exhibits the closest molecular and epidemiological similarities to pure USC and supports clinical observations that suggest patients with MT-EC should receive the same treatment as patients with pure serous carcinoma. Novel specific markers of MT-EC could be of diagnostic utility and could represent novel therapeutic targets in the future. PMID:26132201

Specific gene delivery to liver sinusoidal and artery endothelial cells.

PubMed

Abel, Tobias; El Filali, Ebtisam; Waern, Johan; Schneider, Irene C; Yuan, Qinggong; Münch, Robert C; Hick, Meike; Warnecke, Gregor; Madrahimov, Nodir; Kontermann, Roland E; Schüttrumpf, Jörg; Müller, Ulrike C; Seppen, Jurgen; Ott, Michael; Buchholz, Christian J

2013-09-19

Different types of endothelial cells (EC) fulfill distinct tasks depending on their microenvironment. ECs are therefore difficult to genetically manipulate ex vivo for functional studies or gene therapy. We assessed lentiviral vectors (LVs) targeted to the EC surface marker CD105 for in vivo gene delivery. The mouse CD105-specific vector, mCD105-LV, transduced only CD105-positive cells in primary liver cell cultures. Upon systemic injection, strong reporter gene expression was detected in liver where mCD105-LV specifically transduced liver sinusoidal ECs (LSECs) but not Kupffer cells, which were mainly transduced by nontargeted LVs. Tumor ECs were specifically targeted upon intratumoral vector injection. Delivery of the erythropoietin gene with mCD105-LV resulted in substantially increased erythropoietin and hematocrit levels. The human CD105-specific vector (huCD105-LV) transduced exclusively human LSECs in mice transplanted with human liver ECs. Interestingly, when applied at higher dose and in absence of target cells in the liver, huCD105-LV transduced ECs of a human artery transplanted into the descending mouse aorta. The data demonstrate for the first time targeted gene delivery to specialized ECs upon systemic vector administration. This strategy offers novel options to better understand the physiological functions of ECs and to treat genetic diseases such as those affecting blood factors.

Scheduling the Stork: Media Portrayals of Women's and Physicians' Reasons for Elective Cesarean Delivery.

PubMed

Campo-Engelstein, Lisa; Howland, Lauren E; Parker, Wendy M; Burcher, Paul

2015-06-01

Media interest in cesarean delivery has grown in recent years driven both by rising cesarean delivery rates and the decision by the American College of Obstetrics and Gynecology (ACOG) to permit elective cesarean (EC) delivery. A content analysis of United States newspaper and magazine articles from 2000 to 2013 (n = 131 articles) was completed to understand how the news media portrays ECs. The majority of articles (71.8%) emphasized reasons to support women having an EC, while 38.2 percent of the articles exhibited themes of physician support for ECs. Relatively few articles mentioned reasons against ECs either from the women's perspective (11.5%) or the practitioners' (3.8%). The most common themes given for women choosing ECs were convenience/scheduling (48.9%), avoidance of pain or fear of labor (29.8%), and physical harm to women from vaginal birth (17.6%). Doctors' perspectives were less prevalent in the media than women's perspectives, but when mentioned they were almost exclusively in support of ECs for reasons including avoiding malpractice (28.2%), avoiding physical harm to the woman or baby (16.8%), and timing/scheduling (14.5%). Media coverage suggests ECs are widely accepted by both women and doctors, with women choosing an EC mainly for convenience/scheduling and fear. However, 43 percent of doctors surveyed by ACOG said they were not willing to perform the procedure, and surveys report that mothers rarely request an EC. © 2015 Wiley Periodicals, Inc.

Dietary intake of acrylamide and endometrial cancer risk in the European Prospective Investigation into Cancer and Nutrition cohort

PubMed Central

Obón-Santacana, M; Kaaks, R; Slimani, N; Lujan-Barroso, L; Freisling, H; Ferrari, P; Dossus, L; Chabbert-Buffet, N; Baglietto, L; Fortner, R T; Boeing, H; Tjønneland, A; Olsen, A; Overvad, K; Menéndez, V; Molina-Montes, E; Larrañaga, N; Chirlaque, M-D; Ardanaz, E; Khaw, K-T; Wareham, N; Travis, R C; Lu, Y; Merritt, M A; Trichopoulou, A; Benetou, V; Trichopoulos, D; Saieva, C; Sieri, S; Tumino, R; Sacerdote, C; Galasso, R; Bueno-de-Mesquita, H B; Wirfält, E; Ericson, U; Idahl, A; Ohlson, N; Skeie, G; Gram, I T; Weiderpass, E; Onland-Moret, N C; Riboli, E; Duell, E J

2014-01-01

Background: Three prospective studies have evaluated the association between dietary acrylamide intake and endometrial cancer (EC) risk with inconsistent results. The objective of this study was to evaluate the association between acrylamide intake and EC risk: for overall EC, for type-I EC, and in never smokers and never users of oral contraceptives (OCs). Smoking is a source of acrylamide, and OC use is a protective factor for EC risk. Methods: Cox regression was used to estimate hazard ratios (HRs) for the association between acrylamide intake and EC risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. Acrylamide intake was estimated from the EU acrylamide monitoring database, which was matched with EPIC questionnaire-based food consumption data. Acrylamide intake was energy adjusted using the residual method. Results: No associations were observed between acrylamide intake and overall EC (n=1382) or type-I EC risk (n=627). We observed increasing relative risks for type-I EC with increasing acrylamide intake among women who both never smoked and were non-users of OCs (HRQ5vsQ1: 1.97, 95% CI: 1.08–3.62; likelihood ratio test (LRT) P-value: 0.01, n=203). Conclusions: Dietary intake of acrylamide was not associated with overall or type-I EC risk; however, positive associations with type I were observed in women who were both non-users of OCs and never smokers. PMID:24937665

Coculture with endothelial cells enhances osteogenic differentiation of periodontal ligament stem cells via cyclooxygenase-2/prostaglandin E2/vascular endothelial growth factor signaling under hypoxia.

PubMed

Zhao, Lixing; Wu, Yeke; Tan, Lijun; Xu, Zhenrui; Wang, Jun; Zhao, Zhihe; Li, Xiaoyu; Li, Yu; Yang, Pu; Tang, Tian

2013-12-01

During periodontitis and orthodontic tooth movement, periodontal vasculature is severely impaired, leading to a hypoxic microenvironment of periodontal cells. However, the impact of hypoxia on periodontal cells is poorly defined. The present study investigates responses of cocultured endothelial cells (ECs) and periodontal ligament stem cells (PDLSCs) to hypoxia. Osteogenic differentiation, molecular characterization, and various behaviors of PDLSCs and human umbilical venous ECs under hypoxia were assessed by quantitative real-time reverse-transcription polymerase chain reaction, Western blot, and enzyme-linked immunosorbent assay. Moreover, the effect of ECs on PDLSC osteogenic differentiation was tested using NS398 (cyclooxygenase 2 blocker), SU5416 (vascular endothelial growth factor [VEGF] receptor inhibitor), AH6809, L-798106, and L-161982 (EP1/2/3/4 antagonists). First, hypoxia promoted osteogenic differentiation in PDLSCs and enhanced EC migration, whereas PD98059 (extracellular signal-regulated protein kinase [ERK] inhibitor) blocked, and cocultured ECs further enhanced, hypoxia-induced osteogenic differentiation. Second, NS398 impaired EC migration and prostaglandin E2 (PGE2)/VEGF release, whereas cocultured PDLSCs and exogenous PGE2 partially reversed it. Third, NS398 (pretreated ECs) decreased PGE2/VEGF concentrations. NS398-treated ECs and AH6809/SU5416-treated PDLSCs impaired cocultured EC-induced enhancement of PDLSC osteogenic differentiation. Hypoxia enhances ERK-mediated osteogenic differentiation in PDLSCs. Coculture with EC further augments PDLSC osteogenic differentiation via cyclooxygenase-2/PGE2/VEGF signaling.

Hypomethylation associated enhanced transcription of trefoil factor-3 mediates tamoxifen-stimulated oncogenicity of ER+ endometrial carcinoma cells.

PubMed

Pandey, Vijay; Zhang, Min; Chong, Qing-Yun; You, Mingliang; Raquib, Ainiah Rushdiana; Pandey, Amit K; Liu, Dong-Xu; Liu, Liang; Ma, Lan; Jha, Sudhakar; Wu, Zheng-Sheng; Zhu, Tao; Lobie, Peter E

2017-09-29

Tamoxifen (TAM) is widely used as an adjuvant therapy for women with breast cancer (BC). However, TAM possesses partial oestrogenic activity in the uterus and its use has been associated with an increased incidence of endometrial carcinoma (EC). The molecular mechanism for these observations is not well understood. Herein, we demonstrated that forced expression of Trefoil factor 3 ( TFF3) , in oestrogen receptor-positive (ER+) EC cells significantly increased cell cycle progression, cell survival, anchorage-independent growth, invasiveness and tumour growth in xenograft models. Clinically, elevated TFF3 protein expression was observed in EC compared with normal endometrial tissue, and its increased expression in EC was significantly associated with myometrial invasion. TAM exposure increased expression of TFF3 in ER+ EC cells and its elevated expression resulted in increased oncogenicity and invasiveness. TAM-stimulated expression of TFF3 in EC cells was associated with hypomethylation of the TFF3 promoter sequence and c-JUN/SP1-dependent transcriptional activation. In addition, small interfering ( si) RNA -mediated depletion or polyclonal antibody inhibition of TFF3 significantly abrogated oncogenicity and invasiveness in EC cells consequent to TAM induction or forced expression of TFF3. Hence, TAM-stimulated upregulation of TFF3 in EC cells was critical in promoting EC progression associated with TAM treatment. Importantly, inhibition of TFF3 function might be an attractive molecular modality to abrogate the stimulatory effects of TAM on endometrial tissue and to limit the progression of EC.

Potential Metabolic Activation of a Representative C2-Alkylated Polycyclic Aromatic Hydrocarbon 6-Ethylchrysene Associated with the Deepwater Horizon Oil Spill in Human Hepatoma (HepG2) Cells

PubMed Central

2016-01-01

Exposure to polycyclic aromatic hydrocarbons (PAHs) is the major human health hazard associated with the Deepwater Horizon oil spill. C2-Chrysenes are representative PAHs present in crude oil and could contaminate the food chain. We describe the metabolism of a C2-chrysene regioisomer, 6-ethylchrysene (6-EC), in human HepG2 cells. The structures of the metabolites were identified by HPLC-UV-fluorescence detection and LC-MS/MS. 6-EC-tetraol isomers were identified as signature metabolites of the diol-epoxide pathway. O-Monomethyl-O-monosulfonated-6-EC-catechol, its monohydroxy products, and N-acetyl-l-cysteine(NAC)-6-EC-ortho-quinone were discovered as signature metabolites of the ortho-quinone pathway. Potential dual metabolic activation of 6-EC involving the formation of bis-electrophiles, i.e., a mono-diol-epoxide and a mono-ortho-quinone within the same structure, bis-diol-epoxides, and bis-ortho-quinones was observed as well. The identification of 6-EC-tetraol, O-monomethyl-O-monosulfonated-6-EC-catechol, its monohydroxy products, and NAC-6-EC-ortho-quinone supports potential metabolic activation of 6-EC by P450 and AKR enzymes followed by metabolic detoxification of the ortho-quinone through interception of its redox cycling capability by catechol-O-methyltransferase and sulfotransferase enzymes. The tetraols and catechol conjugates could be used as biomarkers of human exposure to 6-EC resulting from oil spills. PMID:27054409

Enhanced Skeletal Muscle Expression of EcSOD Mitigates Streptozotocin-Induced Diabetic Cardiomyopathy by Reducing Oxidative Stress and Aberrant Cell Signaling

PubMed Central

Call, Jarrod A.; Chain, Kristopher H.; Martin, Kyle S.; Lira, Vitor A.; Okutsu, Mitsuharu; Zhang, Mei; Yan, Zhen

2015-01-01

Background Exercise training enhances extracellular superoxide dismutase (EcSOD) expression in skeletal muscle and elicits positive health outcomes in individuals with diabetes. The goal of this study was to determine if enhanced skeletal muscle expression of EcSOD is sufficient to mitigate streptozotocin (STZ)-induced diabetic cardiomyopathy (DCM). Methods and Results Exercise training promotes EcSOD expression in skeletal muscle and provides protection against DCM; however, it is not known if enhanced EcSOD expression in skeletal muscle plays a functional role in this protection. Here, we show that skeletal muscle-specific EcSOD transgenic mice (TG) are protected from cardiac hypertrophy, fibrosis and dysfunction under the condition of type-1 diabetes induced by STZ injection. We also show that both exercise training and muscle-specific transgenic expression of EcSOD result in elevated EcSOD protein in the blood and heart without increased transcription in the heart, suggesting enhanced expression of EcSOD from skeletal muscle redistributes to the heart. Importantly, cardiac tissue in TG mice displayed significantly reduced oxidative stress, aberrant cell signaling and inflammatory cytokine expression compared with wild type mice under the same diabetic condition. Conclusions Enhanced expression of EcSOD in skeletal muscle is sufficient to mitigate STZ-induced DCM through attenuation of oxidative stress, aberrant cell signaling and inflammation, suggesting a cross-organ mechanism by which exercise training improves cardiac function in diabetes. PMID:25504759

Perfluoroalkyl-substituted ethylene carbonates: Novel electrolyte additives for high-voltage lithium-ion batteries

NASA Astrophysics Data System (ADS)

Zhu, Ye; Casselman, Matthew D.; Li, Yan; Wei, Alexander; Abraham, Daniel P.

2014-01-01

A new family of polyfluoroalkyl-substituted ethylene carbonates is synthesized and tested as additives in lithium-ion cells containing EC:EMC + LiPF6-based electrolyte. The influence of these compounds is investigated in Li1.2Ni0.15Mn0.55Co0.1O2//graphite cells via a combination of galvanostatic cycling and electrochemical impedance spectroscopy (EIS) tests. Among the four additives studied in this work (4-(trifluoromethyl)-1,3-dioxolan-2-one (TFM-EC), 4-(perfluorobutyl)-1,3-dioxolan-2-one (PFB-EC), 4-(perfluorohexyl)-1,3-dioxolan-2-one (PFH-EC), and 4-(perfluorooctyl)-1,3-dioxolan-2-one (PFO-EC)), small amounts (0.5 wt%) of PFO-EC is found to be most effective in lessening cell performance degradation during extended cycling. Linear sweep voltammetry (LSV), X-ray photoelectron spectroscopy (XPS) and Raman spectroscopy are used to further characterize the effects of PFO-EC on the positive and negative electrodes. LSV data from the electrolyte, and XPS analyses of electrodes harvested after cycling, suggest that PFO-EC is oxidized on the cathode forming surface films that slow electrode/cell impedance rise. Differential capacity (dQ/dV) plots from graphite//Li cells suggest that PFO-EC is involved in solid electrolyte interphase (SEI) formation. Raman data from anodes after cycling suggest that structural disordering of graphite is reduced by the addition of PFO-EC, which may explain the improved cell capacity retention.

Sample support and resistivity imaging interpretation

NASA Astrophysics Data System (ADS)

Bentley, L. R.; Gharibi, M.

2003-04-01

Three-D Electrical Resistivity Imaging (ERI) is a powerful technique that can be used to improve site characterization. In order to integrate ERI with other site characterization measurements such as soil and water chemistry, it is necessary to understand the sample support of various data. We have studied a decommissioned sour gas processing plant which has experienced releases of glycol and amine. Ammonium and acetic acid are degradation products that cause elevated electrical conductivity (EC) in groundwater and soils.The site is underlain by glacial till that is fractured and has thin sand lenses. 3-D ERI inversion results, direct push tool EC and core EC from the same location are well correlated. However, groundwater EC from piezometer installations are poorly correlated with ERI EC. We hypothesize that the ERI, direct push and core EC are mainly meausuring relatively immobile pore water EC in the fine grain matrix. Piezometer water is derived from mobile groundwater that travels in preferred flow paths such as fractures and higher permeability sand lenses. Due to dewatering and other remediation efforts, the mobile groundwater can have a different chemistry, concentration and EC than the immobile pore water. Consequently, the sample support is different for the groundwater samples and the difference explains the poor correlation between ERI EC and groundwater sample EC. In this particular case, we have the potential to monitor the chemical evolution of the source areas, but cannot use ERI to monitor the chemical evolution of mobile groundwater.

Enhancement of CCL15 expression and monocyte adhesion to endothelial cells (ECs) after hypoxia/reoxygenation and induction of ICAM-1 expression by CCL15 via the JAK2/STAT3 pathway in ECs.

PubMed

Park, Keun Hyung; Lee, Tae Hoon; Kim, Chan Woo; Kim, Jiyoung

2013-06-15

CCL15, a member of the CC chemokine family, is a potent chemoattractant for leukocytes and endothelial cells (ECs). Given that chemokines play key roles in vascular inflammation, we investigated the effects of hypoxia/reoxygenation (H/R) on expression of human CCL15 and a role of CCL15 in upregulating ICAM-1 in ECs. We found that exposure of ECs to H/R increased expression of CCL15 and ICAM-1, which resulted in an increase in monocyte adhesivity to the ECs. Further studies revealed that knockdown of CCL15 or CCR1 attenuated expression of ICAM-1 in ECs after H/R, suggesting that expression of ICAM-1 is upregulated by CCL15. Stimulation of ECs with CCL15 significantly increased expression of ICAM-1 predominantly via the CCR1 receptor. We observed that phosphorylation of JAK2 and STAT3 was stimulated by CCL15 treatment of ECs. Results from reporter and chromatin immunoprecipitation assays revealed that CCL15 activates transcription from the IFN-γ activation site promoter and stimulates binding of STAT3 to the ICAM-1 promoter. Our data also showed that CCL15 increased cell adhesion of human monocytes to ECs under static and shear-stress conditions. Pretreatment of these cells with inhibitors for JAK, PI3K, and AKT prevented the CCL15-induced expression of ICAM-1 and monocyte adhesion to ECs, suggesting the involvement of those signaling molecules in ICAM-1 gene activation by CCL15. The results suggest that CCR1 and its ligands may be a potential target for treating inflammatory diseases involving upregulation of cell adhesion molecules.

Laminar shear stress promotes mitochondrial homeostasis in endothelial cells.

PubMed

Wu, Li-Hong; Chang, Hao-Chun; Ting, Pei-Ching; Wang, Danny L

2018-06-01

Vascular endothelial cells (ECs) are constantly subjected to flow-induced shear stress that is crucial for endothelial functions. Laminar shear stress (LSS) exerts atheroprotection to ECs. Mitochondrial homeostasis is essential for cellular survival. However, the effects of LSS on mitochondrial homeostasis in ECs remain unclear. Mitochondrial homeostasis in ECs exposed to LSS was examined. Cultured human umbilical vein ECs were subjected to LSS (12 dynes/cm 2 ) generated by a parallel-plate flow chamber system. ECs subjected to LSS demonstrated an increment of mitochondria in tubular form coupled with the increase of fusion proteins (Mfn2, OPA1) and the decrease of fission protein (Fis1). An increase of both long- and short- OPA1 along with a higher protease YME1L level were observed. LSS triggered a rapid phosphorylation on S637 but a decrease on S616 of fission-controlled protein Drp1. Consistently, Drp1 translocation to mitochondria was decreased in sheared ECs, suggesting that LSS promotes mitochondrial fusion. Enhanced mitochondrial biogenesis in sheared ECs was shown by the increase of mitochondrial mass and its regulatory proeins (PGC1α, TFAM, Nrf1). LSS enhances the expression of mitochondrial antioxidant enzymes and improves mitochondrial functions indicated by the increase of mitochondrial membrane potential (ΔΨm) and ATP generation. TNFα treatment decreased mitochondrial tubular network and its functions in ECs. LSS mitigated TNFα-induced mitochondrial impairments in ECs. Our results clearly indicate that LSS promotes mitochondrial homeostasis and attenuates inflammation-induced mitochondrial impairments in ECs. Our results provide novel insights into the manner of mitochondrial dynamics and functions modulated by LSS that contribute to endothelial integrity. © 2017 Wiley Periodicals, Inc.

Unplanned pregnancy-risks and use of emergency contraception: a survey of two Nigerian Universities.

PubMed

Ajayi, Anthony Idowu; Nwokocha, Ezebunwa Ethelbert; Adeniyi, Oladele Vincent; Ter Goon, Daniel; Akpan, Wilson

2017-06-02

The vulnerabilities of young women of low socio-economic status and those with little or no formal education tend to dominate the discourse on unplanned pregnancy, unsafe abortion and emergency contraception (EC) in sub-Saharan Africa. This article draws on a survey conducted among female undergraduate students to shed light on sexual behaviour and the dynamics of emergency contraceptive use among this cohort. The survey involved 420 female undergraduate students drawn using a multistage sampling technique, while a self-administered questionnaire was used for data collection. Univariate and bivariate analyses were applied to examine the factors associated with the use of emergency contraception. Of the 176 female students who reported being sexually active in the year preceding the survey, only 38.6% reported the use of condom during the entire year. Of those who reported unplanned pregnancy anxiety n = 94, about 30.1% used EC, 20.4% used non-EC pills as EC, while others reported having used no EC. A few respondents (n = 3) had terminated a pregnancy under unsafe conditions. Awareness of EC (p < 0.001), knowledge of timing of EC (p = 0.001), perceived risk of unplanned pregnancy (p < 0.001), and level of study (p = 0.013), were significantly correlated with the use of EC. The study revealed that educated youths engaged in high-risk sexual activities and also, sought recourse to unproven and unsafe contraceptive methods. Poor knowledge of EC methods and timing of use, as well as wrong perception about EC side effects, are barriers to the utilisation of EC for the prevention of unplanned pregnancy among the study participants.

Environmental congruence and work-related stress in acute care hospital medical/surgical units: a descriptive, correlational study.

PubMed

Dendaas, Nancy

2011-01-01

To describe the degree to which Environmental Congruence (EC) is present in sampled units and considered important/desirable by staff RNs; staff RNs' reported level of work-related stress (WRS); the perceived contribution of the physical environment to WRS; and the relationship between existing levels of EC and WRS. Few studies have focused on how the physical environment might contribute to nurses' WRS and chronic nursing shortages. The construct of EC can be used, within a Person Environment (PE)-Fit framework, to assess the fit among nurses, nursing work, the physical work environment, and WRS. EC was measured using investigator-developed, literature/criterion-based survey instruments. Staff RNs reported WRS variables by using two single-item self-report measures. The final convenience sample consisted of 471 staff RNs from 39 medical/surgical units from 12 hospitals in the upper Midwest. Data were collected over a 7-month period. The mean level of existing EC in the sample was roughly 70% percent of highest capacity and that of important/desired EC in the sample was 93%. Staff RNs' mean level of WRS was 6.7; the mean contribution of the physical environment to WRS was 5.8. Moderate negative correlations were found between EC and WRS (r = -.41, p < .05), and between physical environment contribution to WRS and EC (r = -.55, p <.001). Staff RNs in the sampled units wanted a significantly higher level of EC. They rated their WRS moderately high and the contribution of the physical environment to it as moderate. A moderately negative relationship was found between EC and WRS. EC may be a useful construct in research that attempts to improve hospital nursing work environments.

Attenuation of tumor necrosis factor-induced endothelial cell cytotoxicity and neutrophil chemiluminescence

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zheng, H.; Crowley, J.J.; Chan, J.C.

Our laboratory has previously shown that the administration of tumor necrosis factor (TNF), a cytokine produced by activated mononuclear cells, to guinea pigs produces a syndrome similar to gram-negative sepsis or ARDS. Pentoxifylline (PTX), a methylxanthine, protects against TNF-induced and sepsis-induced acute lung injury in vivo. We now report on in vitro cellular studies of PMN-mediated cellular injury and its attenuation. We studied TNF-induced bovine pulmonary artery endothelial cell (EC) cytotoxicity both with and without PMN. A 51Cr release assay was used to measure EC damage. Further, we investigated PMN function in response to TNF by measuring chemiluminescence. Agents thatmore » attenuate EC damage and PMN activation were evaluated in the above assays. Results revealed that TNF causes EC injury (p less than 0.05) and PMN increase TNF-induced EC injury. Furthermore, PTX, aminophylline (AMPH), caffeine, and forskolin attenuate TNF-induced EC cytotoxicity only in the presence of PMN (p less than 0.05). Of interest, dibutyryl cAMP (DBcAMP) protects EC from TNF-induced injury both with and without PMN. Agents that may increase cAMP levels in PMN (PTX, DBcAMP, forskolin, isobutyl methylxanthine, and terbutaline) significantly attenuate TNF-induced PMN chemiluminescence (p less than 0.05). We conclude that TNF causes EC damage and PMN increase this damage. Furthermore, PTX, AMPH, caffeine, and forskolin can attenuate TNF-induced EC injury in the presence of PMN, whereas DBcAMP attenuates TNF-induced EC injury with and without PMN. In addition, agents that may increase intracellular cAMP levels in PMN can attenuate TNF-induced PMN chemiluminescence. Thus, these agents likely attenuate TNF-induced PMN-mediated EC injury through their inhibitory effects on PMN.« less

E-cigarettes and Urologic Health: A Collaborative Review of Toxicology, Epidemiology, and Potential Risks.

PubMed

Bourke, Liam; Bauld, Linda; Bullen, Christopher; Cumberbatch, Marcus; Giovannucci, Edward; Islami, Farhad; McRobbie, Hayden; Silverman, Debra T; Catto, James W F

2017-06-01

Use of electronic cigarettes (ECs) is on the rise in most high-income countries. Smoking conventional cigarettes is a known risk factor for urologic malignancy incidence, progression, and mortality, as well as for other urologic health indicators. The potential impact of EC use on urologic health is therefore of clinical interest to the urology community. To review the available data on current EC use, including potential benefits in urologic patients, potential issues linked to toxicology of EC constituents, and how this might translate into urologic health risks. A Medline search was carried out in August 2016 for studies reporting urologic health outcomes and EC use. Snowballing techniques were also used to identify relevant studies from recent systematic reviews. A narrative synthesis of data around EC health outcomes, toxicology, and potential use in smoking cessation and health policy was carried out. We found no studies to date that have been specifically designed to prospectively assess urologic health risks, even in an observational setting. Generating such data would be an important contribution to the debate on the role of ECs in public health and clinical practice. There is evidence from a recent Cochrane review of RCTs that ECs can support smoking cessation. There are emerging data indicating that potentially harmful components of ECs such as tobacco-specific nitrosamines, polyaromatic hydrocarbons, and heavy metals could be linked to possible urologic health risks. ECs might be a useful tool to encourage cessation of conventional cigarette smoking. However, data collection around the specific impact of ECs on urologic health is needed to clarify the possible patient benefits, outcomes, and adverse events. While electronic cigarettes might help some people to stop smoking, their overall impact on urologic health is not clear. Copyright © 2017 European Association of Urology. All rights reserved.

MiR-328 suppresses the survival of esophageal cancer cells by targeting PLCE1

DOE Office of Scientific and Technical Information (OSTI.GOV)

Han, Na; Zhao, Wenchao; Zhang, Zhongmian

2016-01-29

Esophageal cancer (EC) is the sixth leading cause of death worldwide. Recent studies have highlighted the vital role of microRNAs (miRNAs) in EC development and diagnosis. In our study, qPCR analysis showed that miRNA-328 was expressed at significantly low levels in EC109 and EC9706 cells. The results also showed that overexpression of miR-328 by lentivirus-mediated gene transfer markedly inhibited cell proliferation and invasion, and enhanced apoptosis; whereas, inhibition of miR-328 significantly promoted cell proliferation and invasion, and suppressed apoptosis in EC109 and EC9706 cells. Dual-luciferase reporter assay confirmed that miR-328 directly targeted phospholipase C epsilon 1 (PLCE1) by binding to target sequencesmore » in the 3′-UTR. qPCR and Western blot analysis showed that the PLCE1 was overexpressed in EC109 and EC9706 cells. Additionally, we found that miR-328 overexpression decreased PLCE1 mRNA and protein levels, while miR-328 inhibition enhanced the PLCE1 expression. Further analysis showed that PLCE1 overexpression rescued the inhibitory effect of miR-328 on cell proliferation and invasion, and repressed the promotive effect of miR-328 on cell apoptosis. In conclusion, our results suggest that miR-328 suppresses the survival of EC cells by regulating PLCE1 expression, which might be a potential therapeutic method for EC. - Highlights: • PLCE1 was a target gene of miR-328. • MiR-328 overexpression decreased PLCE1 expression. • PLCE1 overexpression rescued the inhibitory effect of miR-328 on the survival of EC cells.« less

Myocardial protective effect of extracellular superoxide dismutase gene modified bone marrow mesenchymal stromal cells on infarcted mice hearts.

PubMed

Pan, Qiao; Qin, Xing; Ma, Sai; Wang, Haichang; Cheng, Kang; Song, Xinxing; Gao, Haokao; Wang, Qiang; Tao, Rannie; Wang, Yabin; Li, Xiujuan; Xiong, Lize; Cao, Feng

2014-01-01

Extracellular superoxide dismutase (ecSOD) is a unique scavenger of superoxide anions and a promising target of gene therapy for ischemia/reperfusion injury (I/R). However, conventional gene therapies have limitation in effectiveness and efficiency. This study aimed to investigate the protective effects of ecSOD gene modified bone marrow mesenchymal stromal cells (BMSCs) on cardiac function improvement in mice infarcted heart. BMSCs were isolated from Fluc(+) transgenic mice (Tg FVB[Fluc(+)]) and transfected by adenovirus combined with human ecSOD gene. ELISA was performed to determine ecSOD protein level. Female syngeneic FVB mice were randomized into 5 groups: (1) Sham group (sham); (2) MI group (MI); (3) MI+BMSCs group (BMSC); (4) MI+BMSCs-vector group (BMSC-vector); (5) MI+ BMSCs-ecSOD group (BMSC-ecSOD). MI was accomplished by ligation of the left anterior descending artery. BMSCs (2 x 10(6)) were injected into the border zone of infarction. In vivo bioluminescence imaging (BLI) was performed to monitor transplanted BMSCs viability. Echocardiography and histological staining revealed that BMSCs-ecSOD significantly reduced myocardial infarction size and improved cardiac function. Lucigenin chemiluminescence, DHE and TUNEL staining demonstrated that BMSCs-ecSOD delivery reduced ROS level and cell apoptosis both in vivo and in vitro. Western blot assay revealed that ecSOD supplementation increased FoxO3a phosphorylation in cardiomyocytes. Moreover, quantitative real-time PCR showed that pro-apoptotic factors (bim and bax) were decreased while the anti-apoptotic factor mir-21 expression was increased after ecSOD intervention. Intra-myocardial transplantation of adenovirus-ecSOD transfected BMSCs could exert potential cardiac protection against MI, which may be partly through reduction of oxidative stress and improvement of BMSCs survival.

A composite model of the human postcapillary venule for investigation of microvascular leukocyte recruitment

PubMed Central

Lauridsen, Holly M.; Pober, Jordan S.; Gonzalez, Anjelica L.

2014-01-01

Neutrophil extravasation occurs across postcapillary venules, structures composed of endothelial cells (ECs), pericytes (PCs), and basement membrane (BM). We constructed composite models of the human postcapillary venule, combining ECs with PCs or PC-deposited BM, to better study this process. Quiescent and tumor necrosis factor α (TNF-α)-activated composites demonstrated in situ-like expression of cadherins, E-selectin, intercellular adhesion molecule 1 (ICAM-1), vascular cell adhesion molecule 1 (VCAM-1), platelet-endothelial cell adhesion molecule 1 (PECAM-1), CD99, and interleukin 8 (IL-8). After TNF-α activation, the ECs supported greater neutrophil adhesion (66.1 vs. 23.7% of input cells) and transmigration (35.1 vs. 7.20% of input cells) than did the PCs, but the composites behaved comparably (no significant difference) to ECs in both assays. TNF-α-activated EC-conditioned medium (CM) increased transmigration across the PCs, whereas TNF-α-activated PC-CM decreased transmigration across the ECs, and culturing on PC-derived BM decreased both adhesion to and transmigration across the ECs. Anti-very late antigen 4 (VLA-4; on neutrophils) inhibited adhesion to TNF-α-activated composites, but not to ECs alone. Anti-CD99 (expressed on all 3 cell types) inhibited transmigration across the composites (14.5% of control) more than across the ECs (39.0% of control), and venular shear stress reduced transmigration across the ECs (17.3% of static) more than across the composites (36.7% of static). These results provide proof of concept that our composite human EC/PC/BM venular construct can reveal new interactions in the inflammatory cascade.—Lauridsen, H. M., Pober, J. S., Gonzalez, A. L. A composite model of the human postcapillary venule for investigation of microvascular leukocyte recruitment. PMID:24297702

Response of transpiration to rain pulses for two tree species in a semiarid plantation.

PubMed

Chen, Lixin; Zhang, Zhiqiang; Zeppel, Melanie; Liu, Caifeng; Guo, Junting; Zhu, Jinzhao; Zhang, Xuepei; Zhang, Jianjun; Zha, Tonggang

2014-09-01

Responses of transpiration (Ec) to rain pulses are presented for two semiarid tree species in a stand of Pinus tabulaeformis and Robinia pseudoacacia. Our objectives are to investigate (1) the environmental control over the stand transpiration after rainfall by analyzing the effect of vapor pressure deficit (VPD), soil water condition, and rainfall on the post-rainfall Ec development and recovery rate, and (2) the species responses to rain pulses and implications on vegetation coverage under a changing rainfall regime. Results showed that the sensitivity of canopy conductance (Gc) to VPD varied under different incident radiation and soil water conditions, and the two species exhibited the same hydraulic control (-dG c/dlnVPD to Gcref ratio) over transpiration. Strengthened physiological control and low sapwood area of the stand contributed to low Ec. VPD after rainfall significantly influenced the magnitude and time series of post-rainfall stand Ec. The fluctuation of post-rainfall VPD in comparison with the pre-rainfall influenced the Ec recovery. Further, the stand Ec was significantly related to monthly rainfall, but the recovery was independent of the rainfall event size. Ec enhanced with cumulative soil moisture change (ΔVWC) within each dry-wet cycle, yet still was limited in large rainfall months. The two species had different response patterns of post-rainfall Ec recovery. Ec recovery of P. tabulaeformis was influenced by the pre- and post-rainfall VPD differences and the duration of rainless interval. R. pseudoacacia showed a larger immediate post-rainfall Ec increase than P. tabulaeformis did. We, therefore, concluded that concentrated rainfall events do not trigger significant increase of transpiration unless large events penetrate the deep soil and the species differences of Ec in response to pulses of rain may shape the composition of semiarid woodlands under future rainfall regimes.

Reprogramming of Adult Peripheral Blood Cells into Human Induced Pluripotent Stem Cells as a Safe and Accessible Source of Endothelial Cells.

PubMed

Simara, Pavel; Tesarova, Lenka; Rehakova, Daniela; Farkas, Simon; Salingova, Barbara; Kutalkova, Katerina; Vavreckova, Eva; Matula, Pavel; Matula, Petr; Veverkova, Lenka; Koutna, Irena

2018-01-01

New approaches in regenerative medicine and vasculogenesis have generated a demand for sufficient numbers of human endothelial cells (ECs). ECs and their progenitors reside on the interior surface of blood and lymphatic vessels or circulate in peripheral blood; however, their numbers are limited, and they are difficult to expand after isolation. Recent advances in human induced pluripotent stem cell (hiPSC) research have opened possible avenues to generate unlimited numbers of ECs from easily accessible cell sources, such as the peripheral blood. In this study, we reprogrammed peripheral blood mononuclear cells, human umbilical vein endothelial cells (HUVECs), and human saphenous vein endothelial cells (HSVECs) into hiPSCs and differentiated them into ECs. The phenotype profiles, functionality, and genome stability of all hiPSC-derived ECs were assessed and compared with HUVECs and HSVECs. hiPSC-derived ECs resembled their natural EC counterparts, as shown by the expression of the endothelial surface markers CD31 and CD144 and the results of the functional analysis. Higher expression of endothelial progenitor markers CD34 and kinase insert domain receptor (KDR) was measured in hiPSC-derived ECs. An analysis of phosphorylated histone H2AX (γH2AX) foci revealed that an increased number of DNA double-strand breaks upon reprogramming into pluripotent cells. However, differentiation into ECs restored a normal number of γH2AX foci. Our hiPSCs retained a normal karyotype, with the exception of the HSVEC-derived hiPSC line, which displayed mosaicism due to a gain of chromosome 1. Peripheral blood from adult donors is a suitable source for the unlimited production of patient-specific ECs through the hiPSC interstage. hiPSC-derived ECs are fully functional and comparable to natural ECs. The protocol is eligible for clinical applications in regenerative medicine, if the genomic stability of the pluripotent cell stage is closely monitored.

Follistatin-Like 3 Enhances the Function of Endothelial Cells Derived from Pluripotent Stem Cells by Facilitating β-Catenin Nuclear Translocation Through Inhibition of Glycogen Synthase Kinase-3β Activity.

PubMed

Kelaini, Sophia; Vilà-González, Marta; Caines, Rachel; Campbell, David; Eleftheriadou, Magdalini; Tsifaki, Marianna; Magee, Corey; Cochrane, Amy; O'neill, Karla; Yang, Chunbo; Stitt, Alan W; Zeng, Lingfang; Grieve, David J; Margariti, Andriana

2018-03-23

The fight against vascular disease requires functional endothelial cells (ECs) which could be provided by differentiation of induced Pluripotent Stem Cells (iPS Cells) in great numbers for use in the clinic. However, the great promise of the generated ECs (iPS-ECs) in therapy is often restricted due to the challenge in iPS-ECs preserving their phenotype and function. We identified that Follistatin-Like 3 (FSTL3) is highly expressed in iPS-ECs, and, as such, we sought to clarify its possible role in retaining and improving iPS-ECs function and phenotype, which are crucial in increasing the cells' potential as a therapeutic tool. We overexpressed FSTL3 in iPS-ECs and found that FSTL3 could induce and enhance endothelial features by facilitating β-catenin nuclear translocation through inhibition of glycogen synthase kinase-3β activity and induction of Endothelin-1. The angiogenic potential of FSTL3 was also confirmed both in vitro and in vivo. When iPS-ECs overexpressing FSTL3 were subcutaneously injected in in vivo angiogenic model or intramuscularly injected in a hind limb ischemia NOD.CB17-Prkdcscid/NcrCrl SCID mice model, FSTL3 significantly induced angiogenesis and blood flow recovery, respectively. This study, for the first time, demonstrates that FSTL3 can greatly enhance the function and maturity of iPS-ECs. It advances our understanding of iPS-ECs and identifies a novel pathway that can be applied in cell therapy. These findings could therefore help improve efficiency and generation of therapeutically relevant numbers of ECs for use in patient-specific cell-based therapies. In addition, it can be particularly useful toward the treatment of vascular diseases instigated by EC dysfunction. Stem Cells 2018. © 2018 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

Targeted delivery of human iPS-ECs overexpressing IL-8 receptors inhibits neointimal and inflammatory responses to vascular injury in the rat.

PubMed

Giordano, Samantha; Zhao, Xiangmin; Xing, Daisy; Hage, Fadi; Oparil, Suzanne; Cooke, John P; Lee, Jieun; Nakayama, Karina H; Huang, Ngan F; Chen, Yiu-Fai

2016-03-15

Interleukin-8 (IL8) is highly expressed by injured arteries in a variety of diseases and is a chemoattractant for neutrophils which express IL8 receptors IL8RA and RB (IL8RA/B) on their membranes. Neutrophils interact with the damaged endothelium and initiate an inflammatory cascade at the site of injury. We have generated a novel translational targeted cell therapy for acute vascular injury using adenoviral vectors to overexpress IL8RA/B and green fluorescent protein (GFP) on the surface of endothelial cells (ECs) derived from human induced pluripotent stem cells (HiPS-IL8RA/B-ECs). We hypothesize that HiPS-IL8RA/B-ECs transfused intravenously into rats with balloon injury of the carotid artery will target to the injured site and compete with neutrophils, thus inhibiting inflammation and neointima formation. Young adult male Sprague-Dawley rats underwent balloon injury of the right carotid artery and received intravenous transfusion of saline vehicle, 1.5 × 10(6) HiPS-ECs, 1.5 × 10(6) HiPS-Null-ECs, or 1.5 × 10(6) HiPS-IL8RA/B-ECs immediately after endoluminal injury. Tissue distribution of HiPS-IL8RA/B-ECs was analyzed by a novel GFP DNA qPCR method. Cytokine and chemokine expression and leukocyte infiltration were measured in injured and uninjured arteries at 24 h postinjury by ELISA and immunohistochemistry, respectively. Neointimal, medial areas, and reendothelialization were measured 14 days postinjury. HiPS-IL8RA/B-ECs homed to injured arteries, inhibited inflammatory mediator expression and inflammatory cell infiltration, accelerated reendothelialization, and attenuated neointima formation after endoluminal injury while control HiPS-ECs and HiPS-Null-ECs did not. HiPS-IL8RA/B-ECs transfused into rats with endoluminal carotid artery injury target to the injured artery and provide a novel strategy to treat vascular injury.

Targeted delivery of human iPS-ECs overexpressing IL-8 receptors inhibits neointimal and inflammatory responses to vascular injury in the rat

PubMed Central

Giordano, Samantha; Zhao, Xiangmin; Xing, Daisy; Hage, Fadi; Oparil, Suzanne; Cooke, John P.; Lee, Jieun; Nakayama, Karina H.; Huang, Ngan F.

2016-01-01

Interleukin-8 (IL8) is highly expressed by injured arteries in a variety of diseases and is a chemoattractant for neutrophils which express IL8 receptors IL8RA and RB (IL8RA/B) on their membranes. Neutrophils interact with the damaged endothelium and initiate an inflammatory cascade at the site of injury. We have generated a novel translational targeted cell therapy for acute vascular injury using adenoviral vectors to overexpress IL8RA/B and green fluorescent protein (GFP) on the surface of endothelial cells (ECs) derived from human induced pluripotent stem cells (HiPS-IL8RA/B-ECs). We hypothesize that HiPS-IL8RA/B-ECs transfused intravenously into rats with balloon injury of the carotid artery will target to the injured site and compete with neutrophils, thus inhibiting inflammation and neointima formation. Young adult male Sprague-Dawley rats underwent balloon injury of the right carotid artery and received intravenous transfusion of saline vehicle, 1.5 × 106 HiPS-ECs, 1.5 × 106 HiPS-Null-ECs, or 1.5 × 106 HiPS-IL8RA/B-ECs immediately after endoluminal injury. Tissue distribution of HiPS-IL8RA/B-ECs was analyzed by a novel GFP DNA qPCR method. Cytokine and chemokine expression and leukocyte infiltration were measured in injured and uninjured arteries at 24 h postinjury by ELISA and immunohistochemistry, respectively. Neointimal, medial areas, and reendothelialization were measured 14 days postinjury. HiPS-IL8RA/B-ECs homed to injured arteries, inhibited inflammatory mediator expression and inflammatory cell infiltration, accelerated reendothelialization, and attenuated neointima formation after endoluminal injury while control HiPS-ECs and HiPS-Null-ECs did not. HiPS-IL8RA/B-ECs transfused into rats with endoluminal carotid artery injury target to the injured artery and provide a novel strategy to treat vascular injury. PMID:26801304

Prognostic Significance of POLE Proofreading Mutations in Endometrial Cancer

PubMed Central

Church, David N.; Stelloo, Ellen; Nout, Remi A.; Valtcheva, Nadejda; Depreeuw, Jeroen; ter Haar, Natalja; Noske, Aurelia; Amant, Frederic; Wild, Peter J.; Lambrechts, Diether; Jürgenliemk-Schulz, Ina M.; Jobsen, Jan J.; Smit, Vincent T. H. B. M.; Creutzberg, Carien L.; Bosse, Tjalling

2015-01-01

Background: Current risk stratification in endometrial cancer (EC) results in frequent over- and underuse of adjuvant therapy, and may be improved by novel biomarkers. We examined whether POLE proofreading mutations, recently reported in about 7% of ECs, predict prognosis. Methods: We performed targeted POLE sequencing in ECs from the PORTEC-1 and -2 trials (n = 788), and analyzed clinical outcome according to POLE status. We combined these results with those from three additional series (n = 628) by meta-analysis to generate multivariable-adjusted, pooled hazard ratios (HRs) for recurrence-free survival (RFS) and cancer-specific survival (CSS) of POLE-mutant ECs. All statistical tests were two-sided. Results: POLE mutations were detected in 48 of 788 (6.1%) ECs from PORTEC-1 and-2 and were associated with high tumor grade (P < .001). Women with POLE-mutant ECs had fewer recurrences (6.2% vs 14.1%) and EC deaths (2.3% vs 9.7%), though, in the total PORTEC cohort, differences in RFS and CSS were not statistically significant (multivariable-adjusted HR = 0.43, 95% CI = 0.13 to 1.37, P = .15; HR = 0.19, 95% CI = 0.03 to 1.44, P = .11 respectively). However, of 109 grade 3 tumors, 0 of 15 POLE-mutant ECs recurred, compared with 29 of 94 (30.9%) POLE wild-type cancers; reflected in statistically significantly greater RFS (multivariable-adjusted HR = 0.11, 95% CI = 0.001 to 0.84, P = .03). In the additional series, there were no EC-related events in any of 33 POLE-mutant ECs, resulting in a multivariable-adjusted, pooled HR of 0.33 for RFS (95% CI = 0.12 to 0.91, P = .03) and 0.26 for CSS (95% CI = 0.06 to 1.08, P = .06). Conclusion: POLE proofreading mutations predict favorable EC prognosis, independently of other clinicopathological variables, with the greatest effect seen in high-grade tumors. This novel biomarker may help to reduce overtreatment in EC. PMID:25505230

Molecular cloning, characterization, and expression analysis of an ecdysone receptor homolog in Teleogryllus emma (Orthoptera: Gryllidae).

PubMed

He, Hui; Xi, Gengsi; Lu, Xiao

2015-01-01

Ecdysteroids are steroid hormones that play important roles in the regulation of Arthropoda animal growth development, larvae ecdysis, and reproduction. The effect of ecdysteroids is mediated by ecdysteroid receptor (EcR). The ecdysone receptor (EcR) belongs to the superfamily of nuclear receptors (NRs) that are ligand-dependent transcription factors. Ecdysone receptor is present only in invertebrates and plays a critical role in regulating the expression of a series of genes during development and reproduction. Here, we isolated and characterized cDNA of the cricket Teleopgryllus emma (Ohmachi & Matsuura) (Orthoptera: Gryllidae) and studied mRNA expression pattern using real time-polymerase chain reaction. The full-length cDNA of T. emma EcR, termed TeEcR, is 2,558 bp and contains a 5'-untranslated region of 555 bp and a 3'-untranslated region of 407 bp. The open reading frame of TeEcR encodes deduced 531-amino acid peptides with a predicted molecular mass of 60.7 kDa. The amino acid sequence of T. emma EcR was similar to that of known EcR especially in the ligand-binding domain of insect EcR. Real-time quantitative reverse transcription-polymerase chain reaction was performed to compare TeEcR mRNA expression level at the whole body and gonad during T. emma development. The data revealed that TeEcR mRNA is differentially expressed during T. emma development, with the highest expression level in late-instar larvae of the body and lowest in third instar. The levels of TeEcR transcripts also vary among gonads development, and levels in ovaries were higher than in testes at every developmental stage. These results suggest that TeEcR may have potential significance to regulate the morphological structure and gonad development of T. emma, due to its expression in different developmental periods. © The Author 2015. Published by Oxford University Press on behalf of the Entomological Society of America.

Molecular Cloning, Characterization, and Expression Analysis of an Ecdysone Receptor Homolog in Teleogryllus emma (Orthoptera: Gryllidae)

PubMed Central

He, Hui; Xi, Gengsi; Lu, Xiao

2015-01-01

Ecdysteroids are steroid hormones that play important roles in the regulation of Arthropoda animal growth development, larvae ecdysis, and reproduction. The effect of ecdysteroids is mediated by ecdysteroid receptor (EcR). The ecdysone receptor (EcR) belongs to the superfamily of nuclear receptors (NRs) that are ligand-dependent transcription factors. Ecdysone receptor is present only in invertebrates and plays a critical role in regulating the expression of a series of genes during development and reproduction. Here, we isolated and characterized cDNA of the cricket Teleopgryllus emma (Ohmachi & Matsuura) (Orthoptera: Gryllidae) and studied mRNA expression pattern using real time-polymerase chain reaction. The full-length cDNA of T. emma EcR, termed TeEcR, is 2,558 bp and contains a 5′-untranslated region of 555 bp and a 3′-untranslated region of 407 bp. The open reading frame of TeEcR encodes deduced 531-amino acid peptides with a predicted molecular mass of 60.7 kDa. The amino acid sequence of T. emma EcR was similar to that of known EcR especially in the ligand-binding domain of insect EcR. Real-time quantitative reverse transcription-polymerase chain reaction was performed to compare TeEcR mRNA expression level at the whole body and gonad during T. emma development. The data revealed that TeEcR mRNA is differentially expressed during T. emma development, with the highest expression level in late-instar larvae of the body and lowest in third instar. The levels of TeEcR transcripts also vary among gonads development, and levels in ovaries were higher than in testes at every developmental stage. These results suggest that TeEcR may have potential significance to regulate the morphological structure and gonad development of T. emma, due to its expression in different developmental periods. PMID:25797799

Histone Acetylation Regulates the Cell-Specific and Interferon-γ–Inducible Expression of Extracellular Superoxide Dismutase in Human Pulmonary Arteries

PubMed Central

Stepp, Marcus W.; Vorst, Alan L.; Folz, Rodney J.

2011-01-01

Extracellular superoxide dismutase (EC-SOD) is the major antioxidant enzyme present in the vascular wall, and is responsible for both the protection of vessels from oxidative stress and for the modulation of vascular tone. Concentrations of EC-SOD in human pulmonary arteries are very high relative to other tissues, and the expression of EC-SOD appears highly restricted to smooth muscle. The molecular basis for this smooth muscle–specific expression of EC-SOD is not known. Here we assessed the role of epigenetic factors in regulating the cell-specific and IFN-γ–inducible expression of EC-SOD in human pulmonary artery cells. The analysis of CpG site methylation within the promoter and coding regions of the EC-SOD gene demonstrated higher levels of DNA methylation within the distal promoter region in endothelial cells compared with smooth muscle cells. Exposure of both cell types to DNA demethylation agents reactivated the transcription of EC-SOD in endothelial cells alone. However, exposure to the histone deacetylase inhibitor trichostatin A (TSA) significantly induced EC-SOD gene expression in both endothelial cells and smooth muscle cells. Concentrations of EC-SOD mRNA were also induced up to 45-fold by IFN-γ in smooth muscle cells, but not in endothelial cells. The IFN-γ–dependent expression of EC-SOD was regulated by the Janus tyrosine kinase/signal transducers and activators of transcription proteins signaling pathway. Simultaneous exposure to TSA and IFN-γ produced a synergistic effect on the induction of EC-SOD gene expression, but only in endothelial cells. These findings provide strong evidence that EC-SOD cell-specific and IFN-γ–inducible expression in pulmonary artery cells is regulated, to a major degree, by epigenetic mechanisms that include histone acetylation and DNA methylation. PMID:21493784

Gaining control: changing relations between executive control and processing speed and their relevance for mathematics achievement over course of the preschool period

PubMed Central

Clark, Caron A. C.; Nelson, Jennifer Mize; Garza, John; Sheffield, Tiffany D.; Wiebe, Sandra A.; Espy, Kimberly Andrews

2014-01-01

Early executive control (EC) predicts a range of academic outcomes and shows particularly strong associations with children's mathematics achievement. Nonetheless, a major challenge for EC research lies in distinguishing EC from related cognitive constructs that also are linked to achievement outcomes. Developmental cascade models suggest that children's information processing speed is a driving mechanism in cognitive development that supports gains in working memory, inhibitory control and associated cognitive abilities. Accordingly, individual differences in early executive task performance and their relation to mathematics may reflect, at least in part, underlying variation in children's processing speed. The aims of this study were to: (1) examine the degree of overlap between EC and processing speed at different preschool age points; and (2) determine whether EC uniquely predicts children's mathematics achievement after accounting for individual differences in processing speed. As part of a longitudinal, cohort-sequential study, 388 children (50% boys; 44% from low income households) completed the same battery of EC tasks at ages 3, 3.75, 4.5, and 5.25 years. Several of the tasks incorporated baseline speeded naming conditions with minimal EC demands. Multidimensional latent models were used to isolate the variance in executive task performance that did not overlap with baseline processing speed, covarying for child language proficiency. Models for separate age points showed that, while EC did not form a coherent latent factor independent of processing speed at age 3 years, it did emerge as a distinct factor by age 5.25. Although EC at age 3 showed no distinct relation with mathematics achievement independent of processing speed, EC at ages 3.75, 4.5, and 5.25 showed independent, prospective links with mathematics achievement. Findings suggest that EC and processing speed are tightly intertwined in early childhood. As EC becomes progressively decoupled from processing speed with age, it begins to take on unique, discriminative importance for children's mathematics achievement. PMID:24596563

Incidence and outcomes of emergent cardiac surgery during transfemoral transcatheter aortic valve implantation (TAVI): insights from the European Registry on Emergent Cardiac Surgery during TAVI (EuRECS-TAVI).

PubMed

Eggebrecht, Holger; Vaquerizo, Beatriz; Moris, Cesar; Bossone, Eduardo; Lämmer, Johannes; Czerny, Martin; Zierer, Andreas; Schröfel, Holger; Kim, Won-Keun; Walther, Thomas; Scholtz, Smita; Rudolph, Tanja; Hengstenberg, Christian; Kempfert, Jörg; Spaziano, Marco; Lefevre, Thierry; Bleiziffer, Sabine; Schofer, Joachim; Mehilli, Julinda; Seiffert, Moritz; Naber, Christoph; Biancari, Fausto; Eckner, Dennis; Cornet, Charles; Lhermusier, Thibault; Philippart, Raphael; Siljander, Antti; Giuseppe Cerillo, Alfredo; Blackman, Daniel; Chieffo, Alaide; Kahlert, Philipp; Czerwinska-Jelonkiewicz, Katarzyna; Szymanski, Piotr; Landes, Uri; Kornowski, Ran; D'Onofrio, Augusto; Kaulfersch, Carl; Søndergaard, Lars; Mylotte, Darren; Mehta, Rajendra H; De Backer, Ole

2018-02-21

Life-threatening complications occur during transcatheter aortic valve implantation (TAVI) which can require emergent cardiac surgery (ECS). Risks and outcomes of patients needing ECS during or immediately after TAVI are still unclear. Incidence, risk factors, management, and outcomes of patients requiring ECS during transfemoral (TF)-TAVI were analysed from a contemporary real-world multicentre registry. Between 2013 and 2016, 27 760 patients underwent TF-TAVI in 79 centres. Of these, 212 (0.76%) patients required ECS (age 82.4 ± 6.3 years, 67.5% females, logistic EuroSCORE: 17.1%, STS-score 5.8%). The risk of ECS declined from 2013 (1.07%) to 2014 (0.70%) but remained stable since. Annual TF-TAVI numbers have more than doubled from 2013 to 2016. Leading causes for ECS were left ventricular perforation by the guidewire (28.3%) and annular rupture (21.2%). Immediate procedural mortality (<72 h) of TF-TAVI patients requiring ECS was 34.6%. Overall in-hospital mortality was 46.0%, and highest in case of annular rupture (62%). Independent predictors of in-hospital mortality following ECS were age > 85 years [odds ratio (OR) 1.87, 95% confidence interval (95% CI) (1.02-3.45), P = 0.044], annular rupture [OR 1.96, 95% CI (0.94-4.10), P = 0.060], and immediate ECS [OR 3.12, 95% CI (1.07-9.11), P = 0.037]. One year of survival of the 114 patients surviving the in-hospital period was only 40.4%. Between 2014 and 2016, the need for ECS remained stable around 0.7%. Left ventricular guidewire perforation and annular rupture were the most frequent causes, accounting for almost half of ECS cases. Half of the patients could be salvaged by ECS-nevertheless, 1 year of all-cause mortality was high even in those ECS patients surviving the in-hospital period. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

Determinants of the Spatial Distributions of Elemental Carbon and Particulate Matter in Eight Southern Californian Communities

PubMed Central

Urman, Robert; Gauderman, James; Fruin, Scott; Lurmann, Fred; Liu, Feifei; Hosseini, Reza; Franklin, Meredith; Avol, Edward; Penfold, Bryan; Gilliland, Frank; Brunekreef, Bert; McConnell, Rob

2014-01-01

Emerging evidence indicates that near-roadway pollution (NRP) in ambient air has adverse health effects. However, specific components of the NRP mixture responsible for these effects have not been established. A major limitation for health studies is the lack of exposure models that estimate NRP components observed in epidemiological studies over fine spatial scale of tens to hundreds of meters. In this study, exposure models were developed for fine-scale variation in biologically relevant elemental carbon (EC). Measurements of particulate matter (PM) and EC less than 2.5 μm in aerodynamic diameter (EC2.5) and of PM and EC of nanoscale size less than 0.2 μm were made at up to 29 locations in each of eight Southern California Children's Health Study communities. Regression-based prediction models were developed using a guided forward selection process to identify traffic variables and other pollutant sources, community physical characteristics and land use as predictors of PM and EC variation in each community. A combined eight-community model including only CALINE4 near-roadway dispersion-estimated vehicular emissions accounting for distance, distance-weighted traffic volume, and meteorology, explained 51% of the EC0.2 variability. Community-specific models identified additional predictors in some communities; however, in most communities the correlation between predicted concentrations from the eight-community model and observed concentrations stratified by community were similar to those for the community-specific models. EC2.5 could be predicted as well as EC0.2. EC2.5 estimated from CALINE4 and population density explained 53% of the within-community variation. Exposure prediction was further improved after accounting for between-community heterogeneity of CALINE4 effects associated with average distance to Pacific Ocean shoreline (to 61% for EC0.2) and for regional NOx pollution (to 57% for EC2.5). PM fine spatial scale variation was poorly predicted in both size fractions. In conclusion, models of exposure that include traffic measures such as CALINE4 can provide useful estimates for EC0.2 and EC2.5 on a spatial scale appropriate for health studies of NRP in selected Southern California communities. PMID:25313293

Ecdysone-dependent and ecdysone-independent programmed cell death in the developing optic lobe of Drosophila.

PubMed

Hara, Yusuke; Hirai, Keiichiro; Togane, Yu; Akagawa, Hiromi; Iwabuchi, Kikuo; Tsujimura, Hidenobu

2013-02-01

The adult optic lobe of Drosophila develops from the primordium during metamorphosis from mid-3rd larval stage to adult. Many cells die during development of the optic lobe with a peak of the number of dying cells at 24 h after puparium formation (h APF). Dying cells were observed in spatio-temporal specific clusters. Here, we analyzed the function of a component of the insect steroid hormone receptor, EcR, in this cell death. We examined expression patterns of two EcR isoforms, EcR-A and EcR-B1, in the optic lobe. Expression of each isoform altered during development in isoform-specific manner. EcR-B1 was not expressed in optic lobe neurons from 0 to 6h APF, but was expressed between 9 and 48 h APF and then disappeared by 60 h APF. In each cortex, its expression was stronger in older glia-ensheathed neurons than in younger ones. EcR-B1 was also expressed in some types of glia. EcR-A was expressed in optic lobe neurons and many types of glia from 0 to 60 h APF in a different pattern from EcR-B1. Then, we genetically analyzed EcR function in the optic lobe cell death. At 0 h APF, the optic lobe cell death was independent of any EcR isoforms. In contrast, EcR-B1 was required for most optic lobe cell death after 24 h APF. It was suggested that cell death cell-autonomously required EcR-B1 expressed after puparium formation. βFTZ-F1 was also involved in cell death in many dying-cell clusters, but not in some of them at 24 h APF. Altogether, the optic lobe cell death occurred in ecdysone-independent manner at prepupal stage and ecdysone-dependent manner after 24 h APF. The acquisition of ecdysone-dependence was not directly correlated with the initiation or increase of EcR-B1 expression. Copyright © 2012 Elsevier Inc. All rights reserved.

Characterization of pathogenic Enterococcus cecorum from different poultry groups: Broiler chickens, layers, turkeys, and waterfowl.

PubMed

Dolka, Beata; Chrobak-Chmiel, Dorota; Czopowicz, Michał; Szeleszczuk, Piotr

2017-01-01

Enterococcus cecorum (EC) is known as a commensal in the intestines of mammals and birds. However, it has been described as an emerging pathogen in poultry industry worldwide. The aim of this study was to analyze and compare EC isolated from clinical material collected from poultry groups with different production purposes. The genetic diversity among pathogenic EC in relation to each specific poultry type was examined. In total, 148 isolates from independent infection outbreaks (2011-2016) were used: 76 broiler chickens (CB), 37 broiler breeders (BB), 23 layers (CL), 7 waterfowl (W) and 5 turkey (T) flocks (1 isolate/1 flock). We provided age ranges at diagnosis of EC-infection for 5 poultry groups. Isolates obtained from CB were significantly more frequently retrieved from bone marrow, joints, spine, and contrary to BB, CL less frequently retrieved from respiratory system. The study showed differences between EC of various poultry types in relation to 10/32 (31.3%) biochemical parameters. EC isolates from CB were significantly more often positive for βGAL, βNAG, MLZ, and less often positive for PAL and βMAN than isolates from other poultry types. However, BB and W isolates showed higher ability to metabolise mannitol than CB, CL, and T. CB isolates showed lower ability to survive at 60°C. Only chicken EC-isolates harbored virulence genes: CB (8.1%) > BB (3.4%) > CL (2%). No specific pulsotype of EC was associated with a specific poultry. One or several various (up to 6) genetic types of EC may be involved in outbreaks in CB flocks within one year in one region. Outbreaks reported in following years in the same region were usually caused by a distinct set of EC-genetic types. PFGE results indicated at the genetic heterogeneity among pathogenic isolates involved in outbreaks in relation to each poultry type. To our best knowledge, this is the first study which provides a comparison between clinical EC from 5 poultry groups. The study provides a new insight into EC as pathogen of different bird species. The obtained data may be useful in further studies on EC-infections more focused on a specific type of poultry.

NP1EC Degradation Pathways Under Oxic and Microxic Conditions

DOE Office of Scientific and Technical Information (OSTI.GOV)

Montgomery-Brown, John; Li, Yongmei; Ding, Wang-Hsien

2008-03-22

The degradation pathway of nonylphenol ethoxyacetic acid (NP1EC) and the conditions favoring CAP1EC formation were studied in aerobic microcosms constructed with soil from the Mesa soil aquifer treatment (SAT) facility (Arizona, USA) and pristine sediments from Coyote Creek (California, USA). In the Mesa microcosms, para-NP1EC was transformed to para-NP, before being rapidly transformed to nonyl alcohols via ipso-hydroxylation. While the formation of NP from APEMs has been observed by several researchers under anaerobic conditions, this is the first time the transient formation of NP from APEMs has been observed under aerobic conditions. Unlike the Mesa microcosms, large quantities of CAP1ECsmore » were observed in the Coyote Creek microcosms. Initially, CA8P1ECs were the dominant metabolites, but as biodegradation continued, CA6P1ECs became the dominant metabolites. Compared to the CA8P1ECs, the number of CA6P1ECs peaks observed was small (<6) even though their concentrations were high. This suggests that several CA8P1ECs are degraded to only a few CA6P1EC isomers (i.e., the degradation pathway converges) or that some CA6P1EC metabolites are significantly more recalcitrant than others. The different biodegradation pathways observed in the Mesa and Coyote Creek microcosms result from the limited availability of dissolved oxygen in the Coyote Creek microcosms. In both sets of microcosms, the ortho isomers were transformed more slowly than the para isomers and in the Coyote Creek microcosms several ortho-CAP1ECs were observed. In addition, several unknown metabolites were observed in the Coyote Creek microcosms that were not seen in the abiotic or Mesa microcosms; these metabolites appear to be CAP1EC metabolites, have a -CH2-C6H4- fragment, and contain one carboxylic acid. Nitro-nonylphenol was observed in the Mesa microcosms, however, further experimentation illustrated that it was the product of an abiotic reaction between nitrite and nonylphenol under acidic conditions.« less

Nicotine delivery to users from cigarettes and from different types of e-cigarettes.

PubMed

Hajek, Peter; Przulj, Dunja; Phillips, Anna; Anderson, Rebecca; McRobbie, Hayden

2017-03-01

Delivering nicotine in the way smokers seek is likely to be the key factor in e-cigarette (EC) success in replacing cigarettes. We examined to what degree different types of EC mimic nicotine intake from cigarettes. Twelve participants ('dual users' of EC and cigarettes) used their own brand cigarette and nine different EC brands. Blood samples were taken at baseline and at 2-min intervals for 10 min and again at 30 min. Eleven smokers provided usable data. None of the EC matched cigarettes in nicotine delivery (C max  = 17.9 ng/ml, T max  = 4 min and AUC 0->30  = 315 ng/ml/min). The EC with 48 mg/ml nicotine generated the closest PK profile (C max  = 13.6 ng/ml, T max  = 4 min, AUC 0->30  = 245 ng/ml/min), followed by a third generation EC using 20 mg/ml nicotine (C max  = 11.9 ng/ml, T max  = 6 min, AUC 0->30  = 232 ng/ml/min), followed by the tank system using 20 mg/ml nicotine (C max  = 9.9 ng/ml, T max  = 6 min, AUC 0->30  = 201 ng/ml/min). Cig-a-like PK values were similar, ranging from C max 7.5 to 9.7 ng/ml, T max 4-6 min, and AUC 0->30 144 to 173 ng/ml/min. Moderate differences in e-liquid nicotine concentrations had little effect on nicotine delivery, e.g. the EC with 24 mg/ml cartridge had the same PK profile as ECs with 16 mg/ml cartridges. Using similar strength e-liquid, the tank EC provided significantly more nicotine than cig-a-like ECs. EC brands we tested do not deliver nicotine as efficiently as cigarettes, but newer EC products deliver nicotine more efficiently than cig-a-like brands. Moderate variations in nicotine content of e-liquid have little effect on nicotine delivery. Smokers who are finding cig-a-like EC unsatisfactory should be advised to try more advanced systems.

High-grade endometrial carcinoma: serous and grade 3 endometrioid carcinomas have different immunophenotypes and outcomes.

PubMed

Alkushi, Abdulmohsen; Köbel, Martin; Kalloger, Steve E; Gilks, C Blake

2010-07-01

High-grade endometrial carcinomas are a heterogeneous group of tumors and include grade 3 endometrioid (EC-3), serous (SC), and clear cell carcinomas (CCC). There are conflicting data about the prognosis of these subtypes of high-grade endometrial carcinoma; this may be a result of lack of reproducibility in classifying tumor cell type. The purpose of this study was to examine differences in immunophenotype and outcome in a series of high-grade endometrial carcinomas, focusing on the comparison of EC-3 versus SC. We selected 180 endometrial carcinomas of SC, EC, or CCC type. No mixed carcinomas were included in the study. We chose the following immunohistochemical markers, estrogen receptor (ER), insulin-like growth factor 2 mRNA-binding protein 3 (IMP3), p16, p53, progesterone receptor (PR), and phosphatase and tensin homolog (PTEN) as being significantly differentially expressed in endometrial carcinoma subtypes. The tumors were stratified into 4 groups on the basis of their cell type and grade: EC grade 1 or 2, EC-3, SC, and CCC. Univariate survival analysis revealed significant differences in outcome between the 4 groups (P<0.0001), with significantly longer disease-specific survival for grade 1 or 2 EC versus EC-3 (P=0.0001), and EC-3 versus SC (P=0.0003). p16, PTEN, and IMP3 expression was observed more frequently in SC compared with EC-3 (P<0.0001, P=0.021, and P=0.031, respectively). These 3 markers showed the highest sensitivity and specificity in distinguishing between EC-3 and SC, with receiver operating characteristics area under the curve of 0.85, 0.69, and 0.71, respectively. ER and p53 approached but did not reach significance for differential expression in EC-3 versus SC (P=0.055 and P=0.068, respectively). A combination of p16 and PTEN predicts EC-3 versus SC with a sensitivity of 90.0% and specificity of 96.8%. p16 and PTEN can aid in distinguishing between EC-3 and SC of the endometrium, and are superior to ER, PR, and p53 for this purpose. EC-3 carcinomas have a significantly better prognosis than SC carcinomas of the endometrium.

Enhanced Therapeutic and Long-Term Dynamic Vascularization Effects of Human Pluripotent Stem Cell-Derived Endothelial Cells Encapsulated in a Nanomatrix Gel.

PubMed

Lee, Shin-Jeong; Sohn, Young-Doug; Andukuri, Adinarayana; Kim, Sangsung; Byun, Jaemin; Han, Ji Woong; Park, In-Hyun; Jun, Ho-Wook; Yoon, Young-Sup

2017-11-14

Human pluripotent stem cell (hPSC)-derived endothelial cells (ECs) have limited clinical utility because of undefined components in the differentiation system and poor cell survival in vivo. Here, we aimed to develop a fully defined and clinically compatible system to differentiate hPSCs into ECs. Furthermore, we aimed to enhance cell survival, vessel formation, and therapeutic potential by encapsulating hPSC-ECs with a peptide amphiphile (PA) nanomatrix gel. We induced differentiation of hPSCs into the mesodermal lineage by culturing on collagen-coated plates with a glycogen synthase kinase 3β inhibitor. Next, vascular endothelial growth factor, endothelial growth factor, and basic fibroblast growth factor were added for endothelial lineage differentiation, followed by sorting for CDH5 (VE-cadherin). We constructed an extracellular matrix-mimicking PA nanomatrix gel (PA-RGDS) by incorporating the cell adhesive ligand Arg-Gly-Asp-Ser (RGDS) and a matrix metalloproteinase-2-degradable sequence. We then evaluated whether the encapsulation of hPSC-CDH5 + cells in PA-RGDS could enhance long-term cell survival and vascular regenerative effects in a hind-limb ischemia model with laser Doppler perfusion imaging, bioluminescence imaging, real-time reverse transcription-polymerase chain reaction, and histological analysis. The resultant hPSC-derived CDH5 + cells (hPSC-ECs) showed highly enriched and genuine EC characteristics and proangiogenic activities. When injected into ischemic hind limbs, hPSC-ECs showed better perfusion recovery and higher vessel-forming capacity compared with media-, PA-RGDS-, or human umbilical vein EC-injected groups. However, the group receiving the PA-RGDS-encapsulated hPSC-ECs showed better perfusion recovery, more robust and longer cell survival (> 10 months), and higher and prolonged angiogenic and vascular incorporation capabilities than the bare hPSC-EC-injected group. Surprisingly, the engrafted hPSC-ECs demonstrated previously unknown sustained and dynamic vessel-forming behavior: initial perivascular concentration, a guiding role for new vessel formation, and progressive incorporation into the vessels over 10 months. We generated highly enriched hPSC-ECs via a clinically compatible system. Furthermore, this study demonstrated that a biocompatible PA-RGDS nanomatrix gel substantially improved long-term survival of hPSC-ECs in an ischemic environment and improved neovascularization effects of hPSC-ECs via prolonged and unique angiogenic and vessel-forming properties. This PA-RGDS-mediated transplantation of hPSC-ECs can serve as a novel platform for cell-based therapy and investigation of long-term behavior of hPSC-ECs. © 2017 American Heart Association, Inc.

Does the Regulatory Environment for E-Cigarettes Influence the Effectiveness of E-Cigarettes for Smoking Cessation?: Longitudinal Findings From the ITC Four Country Survey.

PubMed

Yong, Hua-Hie; Hitchman, Sara C; Cummings, K Michael; Borland, Ron; Gravely, Shannon M L; McNeill, Ann; Fong, Geoffrey T

2017-11-01

To date, no studies have explored how different regulatory environments may influence the effectiveness of electronic cigarettes (ECs) as a smoking cessation aid. This study compares the real-world effectiveness of adult smokers using ECs for quitting compared with quitting unassisted or quitting with nicotine replacement therapy (NRT) and/or prescription medications in two countries with restrictive policies towards ECs (ie, Canada and Australia) versus two countries with less restrictive policies (ie, United States and United Kingdom). Data were drawn from the International Tobacco Control Four Country surveys, from the United States and Canada (2 waves, n = 318 and 380, respectively), the United Kingdom (3 waves, n = 439) and Australia (4 waves, n = 662), collected 2010-2014. Smokers at baseline wave who reported making a quit attempt at follow-up were included. The primary outcome was self-reported abstinence for at least 30 days regardless of smoking status at follow-up assessment. Data across waves were combined and analyzed using generalized estimating equations. Compared to unassisted quitting (ie, no medications or ECs), smokers who used ECs for quitting from countries with less restrictive EC policy environments were more likely (OR = 1.95, 95%CI = 1.19-3.20, p < .01), whereas smokers who used ECs for quitting from countries with more restrictive EC policies were less likely (OR = 0.36, 95%CI = 0.18-0.72, p < .01), to report sustained abstinence for at least 30 days. Use of ECs in the real world during a quit attempt appears only effective for sustaining smoking abstinence in a less restrictive EC environment suggesting that the benefits of ECs for smoking cessation are likely highly dependent on the regulatory environment. What this study adds: This is the first study to examine the impact of regulatory environment for ECs on their real-world effectiveness for smoking cessation. This study shows that in a less restrictive EC regulatory environment, use of ECs during a quit attempt facilitates, but in a more restrictive environment, it inhibits, short-term sustained abstinence. The findings underscore the need for careful consideration on how best to regulate this emerging product so that EC benefits for smoking cessation are maximized and its risks to public health are minimized. © The Author 2017. Published by Oxford University Press on behalf of the Society for Research on Nicotine and Tobacco.

Fluctuation of Dof1/Dof2 expression ratio under the influence of varying nitrogen and light conditions: involvement in differential regulation of nitrogen metabolism in two genotypes of finger millet (Eleusine coracana L.).

PubMed

Gupta, Supriya; Gupta, Sanjay Mohan; Gupta, Alok Kumar; Gaur, Vikram Singh; Kumar, Anil

2014-08-10

In order to gain insights into the mechanism of high nitrogen use efficiency (NUE) of finger millet (FM) the role of Dof2 transcription factor (TF), which is a repressor of genes involved in C/N metabolism was investigated. The partial cDNA fragment of EcDof2 (912-bp; GenBank acc. no. KF261117) was isolated and characterized from finger millet (FM) that showed 63% and 58% homology with Dof2 of Zea mays at nucleotide and protein level, respectively. Its expression studies were carried out along with the activator EcDof1 in two genotypes (GE3885, high protein genotype (HPG); GE1437, low protein genotype (LPG)) of FM differing in grain protein contents (13.8% and 6.2%) showed that EcDof2 is expressed in both shoot and root tissues with significantly (p≤0.05) higher expression in the roots. The diurnal expression of both EcDof1 and EcDof2 in shoots was differential having different time of peak expression indicating a differential response to diurnal condition. Under continuous dark conditions, expression of EcDof1 and EcDof2 oscillated in both the genotypes whereas on illumination, the fold expression of EcDof1 was higher as compared to EcDof2. Under increasing nitrate concentration, EcDof2 expression increases in roots and shoots of LPG while it remains unchanged in HPG. However, the EcDof1 expression was found to increase in both genotypes. Further, time kinetics studies under single nitrate concentration revealed that EcDof2 was repressed in the roots of both genotypes whereas EcDof1 oscillated with time. The EcDof1/EcDof2 ratio measured showed differential response under different light and nitrogen conditions. It was higher in the roots of HPG indicating higher activation of genes involved in N uptake and assimilation resulting in high grain protein accumulation. The results indicate that both light and nitrogen concentration influence Dof1 and Dof2 expression and suggests a complex pattern of regulation of genes influenced by these plant specific TFs. In nutshell, the Dof1/Dof2 ratio can serve as an index for measuring the N responsiveness and NUE of crops and can be further validated by Dof2 knock down approach. Copyright © 2014 Elsevier B.V. All rights reserved.

Sex Differences Influencing Micro- and Macrovascular Endothelial Phenotype In Vitro.

PubMed

Huxley, Virginia H; Kemp, Scott S; Schramm, Christine; Sieveking, Steve; Bingaman, Susan; Yu, Yang; Zaniletti, Isabella; Stockard, Kevin; Wang, Jianjie

2018-06-09

Endothelial dysfunction is an early hallmark of multiple disease states that also display sex differences with respect to age of onset, frequency, and severity. Results of in vivo studies of basal and stimulated microvascular barrier function revealed sex differences difficult to ascribe to specific cells or environmental factors. The present study evaluated endothelial cells (EC) isolated from macro- and/or microvessels of reproductively mature rats under the controlled conditions of low-passage culture to test the assumption that EC phenotype would be sex-independent. The primary finding was that EC, regardless of where they are derived, retain a sex-bias in low-passage culture, independent of varying levels of reproductive hormones. Implications of the work include the fallacy of expecting a universal set of mechanisms derived from study of EC from one sex and/or one vascular origin to apply uniformly to all EC under unstimulated conditions no less in the disease state. Vascular endothelial cells (EC) are heterogeneous with respect to phenotype reflecting at least organ of origin, location within the vascular network, and physical forces. Sex, as an independent influence on EC functions in health or etiology, susceptibility, and progression of dysfunction in numerous disease states, has been largely ignored. The current study focussed on EC isolated from aorta (macrovascular) and skeletal muscle vessels (microvascular) of age-matched male and female rats under identical conditions of short term (passage 4) culture. We tested the hypothesis that genomic sex would not influence endothelial growth, wound healing, morphology, lactate production, or messenger RNA and protein expression of key proteins (sex hormone receptors for androgen (AR) and oestrogen (ERα and ERβ); PECAM-1 and VE-CAD mediating barrier function; α v β 3 and N-Cadherin influencing matrix interactions; ICAM-1 and VCAM-1 mediating EC/white cell adhesion). The hypothesis was rejected as EC origin (macro- versus microvessel) and sex influenced multiple phenotypic characteristics. Statistical model analysis of EC growth demonstrated an hierarchy of variable importance, recapitulated for other phenotypic characteristics, wherein predictions assuming EC homogeneity < Sex < Vessel Origin < Sex and Vessel Origin. Further, patterns of EC mRNA expression by vessel origin and by sex did not predict protein expression. Overall the study demonstrated that accurate assessment of sex-linked EC dysfunction first requires understanding of EC function by position in the vascular tree and by sex. Results from a single EC tissue source/species/sex cannot provide universal insight into the mechanisms regulating in vivo endothelial function in health, no less disease. (250) This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Sources and mixing state of size-resolved elemental carbon particles in a European megacity: Paris

NASA Astrophysics Data System (ADS)

Healy, R. M.; Sciare, J.; Poulain, L.; Kamili, K.; Merkel, M.; Müller, T.; Wiedensohler, A.; Eckhardt, S.; Stohl, A.; Sarda-Estève, R.; McGillicuddy, E.; O'Connor, I. P.; Sodeau, J. R.; Wenger, J. C.

2012-02-01

An Aerosol Time-Of-Flight Mass Spectrometer (ATOFMS) was deployed to investigate the size-resolved chemical composition of single particles at an urban background site in Paris, France, as part of the MEGAPOLI winter campaign in January/February 2010. ATOFMS particle counts were scaled to match coincident Twin Differential Mobility Particle Sizer (TDMPS) data in order to generate hourly size-resolved mass concentrations for the single particle classes observed. The total scaled ATOFMS particle mass concentration in the size range 150-1067 nm was found to agree very well with the sum of concurrent High-Resolution Time-of-Flight Aerosol Mass Spectrometer (HR-ToF-AMS) and Multi-Angle Absorption Photometer (MAAP) mass concentration measurements of organic carbon (OC), inorganic ions and black carbon (BC) (R2 = 0.91). Clustering analysis of the ATOFMS single particle mass spectra allowed the separation of elemental carbon (EC) particles into four classes: (i) EC attributed to biomass burning (ECbiomass), (ii) EC attributed to traffic (ECtraffic), (iii) EC internally mixed with OC and ammonium sulfate (ECOCSOx), and (iv) EC internally mixed with OC and ammonium nitrate (ECOCNOx). Average hourly mass concentrations for EC-containing particles detected by the ATOFMS were found to agree reasonably well with semi-continuous quantitative thermal/optical EC and optical BC measurements (r2 = 0.61 and 0.65-0.68 respectively, n = 552). The EC particle mass assigned to fossil fuel and biomass burning sources also agreed reasonably well with BC mass fractions assigned to the same sources using seven-wavelength aethalometer data (r2 = 0.60 and 0.48, respectively, n = 568). Agreement between the ATOFMS and other instrumentation improved noticeably when a period influenced by significantly aged, internally mixed EC particles was removed from the intercomparison. 88% and 12% of EC particle mass was apportioned to fossil fuel and biomass burning respectively using the ATOFMS data compared with 85% and 15% respectively for BC estimated from the aethalometer model. On average, the mass size distribution for EC particles is bimodal; the smaller mode is attributed to locally emitted, mostly externally mixed EC particles, while the larger mode is dominated by aged, internally mixed ECOCNOx particles associated with continental transport events. Periods of continental influence were identified using the Lagrangian Particle Dispersion Model (LPDM) "FLEXPART". A consistent minimum between the two EC mass size modes was observed at approximately 400 nm for the measurement period. EC particles below this size are attributed to local emissions using chemical mixing state information and contribute 79% of the scaled ATOFMS EC particle mass, while particles above this size are attributed to continental transport events and contribute 21% of the EC particle mass. These results clearly demonstrate the potential benefit of monitoring size-resolved mass concentrations for the separation of local and continental EC emissions. Knowledge of the relative input of these emissions is essential for assessing the effectiveness of local abatement strategies.

OM/OC Ratio and Specific Attenuation Coefficient in Ambient Particulate Matter at a Rural Site in Southern Ontario: Implications for Aerosol Aging and Emission Sources

NASA Astrophysics Data System (ADS)

Chan, T. W.; Huang, L.; Leaitch, R.; Sharma, S.; Brook, J.; Slowik, J.; Abbatt, J.

2008-05-01

Carbonaceous species (organic carbon (OC) and elemental carbon (EC)) contribute a large portion of atmospheric fine particle mass and influence air quality, human health, and climate forcing. However, their emission sources and atmospheric aging processes are not well understood. The OM/OC ratio, defined as the organic mass per unit OC mass, is useful to understand the degree of oxidation of aerosol particles in atmospheric processes. We define the modified BC/EC (mod BC/EC) ratio as the ratio of the non-scattering corrected absorption coefficient per unit mass of EC. The mod BC/EC ratio has a similar meaning as the site specific attenuation coefficient, which is an important parameter used to convert light absorption measurements to black carbon mass. The mod BC/EC ratio can vary due to light scattering effect on absorption measurements, in which the oxygenated organics may play a role. The pyrolysis organic carbon (POC) is defined as the carbon mass fraction obtained at T= 870°C under a pure helium environment using the thermal separation method [Huang et al., 2006]. Since POC mass is generally proportional to the amount of oxygenated OC, studying the relationships among OC, EC, POC, as well as OM/OC and mod BC/EC ratios may help us understand the mechanisms of aerosol aging from different emission sources. Two 1-month field studies were conducted at a rural site in southern Ontario (NW of Toronto) during fall 2005 and spring 2007. Quartz filter samples were collected and analyzed for OC, POC, and EC concentrations using a thermal/optical method [Huang et al., 2006]. Together with the total organic matter measured by an Aerodyne Aerosol Mass Spectrometer (AMS) and the absorption coefficient obtained from a Particle Soot Absorption Photometer (PSAP), the OM/OC and mod BC/EC ratios for ambient aerosols were obtained. Our results show that when air mass was mainly from south, OC, POC, and EC were relatively high, with average ratios of OC/EC, OM/OC, and POC/EC as 1.94, 1.41, and 0.52, respectively; this indicates significant anthropogenic impacts and relatively large portion of oxygenated OC, which might be due to either primary emissions or photo-chemical reactions occurred in a short period of time. When air mass was mainly from north, OC, POC, and EC were much lower, with average ratios of OC/EC, OM/OC, and POC/EC as 3.10, 1.20, and 0.79, respectively; this suggests less influence from anthropogenic emissions and relatively aged air mass from biogenic-source dominated clean air. Using POC, we estimate the specific attenuation at the site to be 5.8 m2 g-1 independent of the air mass origin. The relationships among OM/OC, mod BC/EC, and POC will be further discussed. References: Huang, L., Brook, J.R., Zhang, W., Li, S.M., Graham, L., Ernst, D., Chivulescu, A., and Lu, G. (2006) Stable isotope measurements of carbon fractions (OC/EC) in airborne particulate: a new dimension for source characterization and apportionment, Atmospheric Environment, 40, 2690-2705.

Material System Engineering for Advanced Electrocaloric Cooling Technology

NASA Astrophysics Data System (ADS)

Qian, Xiaoshi

Electrocaloric effect refers to the entropy change and/or temperature change in dielectrics caused by the electric field induced polarization change. Recent discovery of giant ECE provides an opportunity to realize highly efficient cooling devices for a broad range of applications ranging from household appliances to industrial applications, from large-scale building thermal management to micro-scale cooling devices. The advances of electrocaloric (EC) based cooling device prototypes suggest that highly efficient cooling devices with compact size are achievable, which could lead to revolution in next generation refrigeration technology. This dissertation focuses on both EC based materials and cooling devices with their recent advances that address practical issues. Based on better understandings in designing an EC device, several EC material systems are studied and improved to promote the performances of EC based cooling devices. In principle, applying an electric field to a dielectric would cause change of dipolar ordering states and thus a change of dipolar entropy. Giant ECE observed in ferroelectrics near ferroelectric-paraelectric (FE-PE) transition temperature is owing to the large dipolar orientation change, between random-oriented dipolar states in paraelectric phase and spontaneous-ordered dipolar states in ferroelectric phases, which is induced by external electric fields. Besides pursuing large ECE, studies on EC cooling devices indicated that EC materials are required to possess wide operational temperature window, in which large ECE can be maintained for efficient operations. Although giant ECE was first predicted in ferroelectric polymers, where the large effect exhibits near FEPE phase transition, the narrow operation temperature window poses obstacles for these normal ferroelectrics to be conveniently perform in wide range of applications. In this dissertation, we demonstrated that the normal ferroelectric polymers can be converted to relaxor ferroelectric polymers which possess both giant ECE (27 Kelvin temperature drop) and much wider operating temperature window (over 50 kelvin covering RT) by proper defect modification which delicately tailors ferroelectrics in meso-, micro- and molecular scales. In addition, in order to be practical, EC device requires EC material can be driven at low electric fields upon achieve the large ECE. It is demonstrated in this dissertation that by facially modifying materials structure in meso-, micro- and molecular scale, lowfield ECE can be greatly improved. Large ECE, induced by low electric fields and existing in wide temperature window, is a major improvement in EC materials for practical applications. Besides EC polymers, this thesis also investigated EC ceramics. Due to several unique opportunities offered by the EC ceramics, Ba(ZrxTi 1-x)O3 (BZT), that is studied. (i) This class of EC ceramics offers a possibility to explore the invariant critical point (ICP), which maximizes the number of coexistent phase and provides a nearly vanishing energy barrier for switching among different phases. As demonstrated in this thesis, the BZT bulk ceramics at x˜ 0.2 exhibits a large adiabatic temperature drop DeltaTc=4.5 K, a large isothermal entropy change DeltaS = 8 Jkg-1K-1, a large EC coefficient (|DeltaT c/DeltaE| = 0.52x10-6 KmV-1 and DeltaS/DeltaE=0.93x10 -6 Jmkg-1K-1V-1) over a wide operating temperature range Tspan>30K. (ii) The thermal conductivity of EC ceramics is in general, much higher than that of EC polymers, and consequently they will allow EC cooling configurations which are not accessible by the EC polymers. Moreover, in the same device configuration, the high thermal conductivity of EC ceramics (kappa> 5 W/mK, compared with EC polymer, ˜ 0.25 W/mK) allows higher operation frequency and therefore a higher cooling power. (iii) Well-established fabrication processes of multilayer ceramic capacitor (MLCC) provide a foundation for the EC ceramic toward mass production. In this thesis, BZT thick film double layers have been fabricated and large ECE has been directly measured. EC induced temperature drop (DeltaT) around 6.3 °C and entropy change (DeltaS) of 11.0 Jkg-1K -1 are observed under an electric field of DeltaE=14.6 MV/m at 40 °C was observed in BZT thick film double layers. The result encourages further investigations on ECE in MLCC for practical applications. (Abstract shortened by ProQuest.).

CHARACTERIZATION OF PARTICULATE MATTER EMISSION FROM OPEN BURNING OF RICE STRAW

PubMed Central

Oanh, Nguyen Thi Kim; Bich, Thuy Ly; Tipayarom, Danutawat; Manadhar, Bhai R.; Prapat, Pongkiatkul; Simpson, Christopher D.; Liu, L-J Sally

2010-01-01

Emission from field burning of crop residue, a common practice in many parts of the world today, has potential effects on air quality, atmosphere and climate. This study provides a comprehensive size and compositional characterization of particulate matter (PM) emission from rice straw (RS) burning using both in situ experiments (11 spread field burning) and laboratory hood experiments (3 pile and 6 spread burning) that were conducted during 2003–2006 in Thailand. The carbon balance and emission ratio method was used to determine PM emission factors (EF) in the field experiments. The obtained EFs varied from field to hood experiments reflecting multiple factors affecting combustion and emission. In the hood experiments, EFs were found to be depending on the burning types (spread or pile), moisture content and the combustion efficiency. In addition, in the field experiments, burning rate and EF were also influenced by weather conditions, i.e. wind. Hood pile burning produced significantly higher EF (20±8 g kg−1 RS) than hood spread burning (4.7±2.2 g kg−1 RS). The majority of PM emitted from the field burning was PM2.5 with EF of 5.1±0.7 g m−2 or 8.3±2.7 g kg−1 RS burned. The coarse PM fraction (PM10-2.5) was mainly generated by fire attention activities and was relatively small, hence the resulting EF of PM10 (9.4±3.5 g kg−1 RS) was not significantly higher than PM2.5. PM size distribution was measured across 8 size ranges (from <0.4 μm to >9.0 μm). The largest fractions of PM, EC and OC were associated with PM1.1. The most significant components in PM2.5 and PM10 include OC, water soluble ions and levoglucosan. Relative abundance of some methoxyphenols (e.g., acetylsyringone), PAHs (e.g., fluoranthene and pyrene), organochlorine pesticides and PCBs may also serve as additional signatures for the PM emission. Presence of these toxic compounds in PM of burning smoke increases the potential toxic effects of the emission. For illustration, an estimation of the annual RS field burning in Thailand was made using the obtained in situ field burning EFs and preliminary burning activity data. PMID:21243095

(-) Epicatechin regulates blood lipids and attenuates hepatic steatosis in rats fed high fat diet

USDA-ARS?s Scientific Manuscript database

(-)-Epicatechin (EC) is a natural flavanol monomer found in cocoa, green tea and a variety of other plant foods. Recent studies have shown that EC and foods rich in EC exerted vascular protective effects. In this study, effects of EC on blood lipids and hepatic steatosis, and the underlying mechani...

77 FR 27661 - Airworthiness Directives; Eurocopter Deutschland GmbH Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2012-05-11

... Deutschland GmbH Helicopters AGENCY: Federal Aviation Administration (FAA), DOT. ACTION: Notice of proposed... Deutschland GmbH (ECD) model EC135 helicopters, except the EC 135 P2+ and T2+. This proposed AD was prompted...) Applicability This AD applies to all Eurocopter Deutschland GmbH (ECD) Model EC135 helicopters, except EC 135 P2...

77 FR 72913 - Airworthiness Directives; Eurocopter Deutschland GmbH Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2012-12-07

... Airworthiness Directives; Eurocopter Deutschland GmbH Helicopters AGENCY: Federal Aviation Administration (FAA... Eurocopter Deutschland GmbH (ECD) Model EC135 helicopters, except the EC 135 P2+ and T2+. This AD requires... apply to all Eurocopter Deutschland GmbH (ECD) model EC135 helicopters, except the EC 135 P2+ and T2...

Electron Cloud Effects in Accelerators

DOE Office of Scientific and Technical Information (OSTI.GOV)

Furman, M.A.

Abstract We present a brief summary of various aspects of the electron-cloud effect (ECE) in accelerators. For further details, the reader is encouraged to refer to the proceedings of many prior workshops, either dedicated to EC or with significant EC contents, including the entire ?ECLOUD? series [1?22]. In addition, the proceedings of the various flavors of Particle Accelerator Conferences [23] contain a large number of EC-related publications. The ICFA Beam Dynamics Newsletter series [24] contains one dedicated issue, and several occasional articles, on EC. An extensive reference database is the LHC website on EC [25].

Roadmap for the establishment of a European vaccine R&D infrastructure.

PubMed

Leroy, Odile; Geels, Mark; Korejwo, Joanna; Dodet, Betty; Imbault, Nathalie; Jungbluth, Stefan

2014-12-05

To consolidate the integration of the fragmented European vaccine development landscape, TRANSVAC - the European Network of Vaccine Research and Development, funded by the European Commission (EC) - has initiated the development of a roadmap through a process of stakeholder consultation. The outcome of this consultation highlighted the need for transnational cooperation and the opportunities that could be generated by such efforts. This cooperation can be achieved through the establishment of a European Vaccine Research and Development Infrastructure (EVRI). EVRI will support cooperation between existing vaccine Research and Development (R&D) organisations from the public and private sector and other networks throughout Europe. It will become sustainable over time by receiving support from multiple sources including the EC, European Union (EU) Member States, European vaccine companies, EVRI partner organisations, and by income generated. Different stakeholders have demonstrated support for the concept of a vaccine infrastructure and agree that such an infrastructure can function as leverage institution between public and private institutions thus making significant contributions to the vaccine field as a whole in its quest to develop vaccines. EVRI will be launched in three phases: preparatory (during which the legal and administrative framework will be defined and a business plan will be elaborated), implementation and operational. If sufficient political and financial commitment can be secured from relevant national and European entities as well as from the private sector and other stakeholders, it could enter into operational phase from 2017 onwards. In conclusion, EVRI can make vaccine R&D more efficient and help address European and global health challenges, help alleviate the burden and spread of infectious diseases, thus contributing to the sustainability of public healthcare systems. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Clinical Characteristics and Prognosis of Pulmonary Embolism Caused by Economy Class Syndrome.

PubMed

Abellás, María; Menéndez, Ana; Morillo, Raquel; Jara-Palomares, Luis; Barrios, Deisy; Nieto, Rosa; Barbero, Esther; Corres, Jesús; Ruiz-Artacho, Pedro; Jiménez, David

2017-09-01

Clinical presentation and short-term prognosis of patients with travel-associated acute pulmonary embolism (PE) (i.e., economy class syndrome [ECS]) is not well understood. In this retrospective cohort study of patients with acute PE identified from a single center registry, we assessed the clinical presentation and the association between ECS and the outcomes of all-cause mortality, PE-related mortality, nonfatal venous thromboembolism and nonfatal major bleeding rates through 30days after initiation of PE treatment. Of the 2,333 patients with acute symptomatic PE, 124 (5.3%; 95% confidence interval, 4.4-6.3%) had ECS. Patients with ECS were younger and had fewer comorbid diseases (recent bleeding, chronic obstructive pulmonary disease, congestive heart failure), but they presented with more signs of clinical severity (syncope [48% vs. 14%; P<.001], tachycardia [37% vs. 21%; P<.001], right ventricular dysfunction [31% vs. 19%; P<.01] and myocardial injury [57% vs. 28%; P<.001]) compared to those without ECS. Regression analyses showed a significantly lower risk of all-cause mortality for patients with ECS compared to patients without ECS (1.6% vs. 9.6%; P<.01). We did not detect a difference in PE-related mortality at 30days between those with and those without ECS (0.8% vs. 3.1%; P=.18). PE patients with ECS are younger and have fewer comorbid diseases compared to those without ECS. Though they present with more signs of clinical severity, their short-term prognosis is excellent. Copyright © 2017 SEPAR. Publicado por Elsevier España, S.L.U. All rights reserved.

High-temperature beverages and Foods and Esophageal Cancer Risk -- A Systematic Review

PubMed Central

Islami, Farhad; Boffetta, Paolo; Ren, JianSong; Pedoeim, Leah; Khatib, Dara; Kamangar, Farin

2009-01-01

Coffee, tea, and maté may cause esophageal cancer (EC) by causing thermal injury to the esophageal mucosa. If so, the risk of EC attributable to thermal injury could be large in populations in which these beverages are commonly consumed. In addition, these drinks may cause or prevent EC via their chemical constituents. Therefore, a large number of epidemiologic studies have investigated the association of an indicator of amount or temperature of use of these drinks or other hot foods and beverages with risk of EC. We conducted a systematic review of these studies, and report the results for amount and temperature of use separately. By searching PubMed and the ISI, we found 59 eligible studies. For coffee and tea, there was little evidence for an association between amount of use and EC risk; however, the majority of studies showed an increased risk of EC associated with higher drinking temperature which was statistically significant in most of them. For maté drinking, the number of studies was limited, but they consistently showed that EC risk increased with both amount consumed and temperature, and these two were independent risk factors. For other hot foods and drinks, over half of the studies showed statistically significant increased risks of EC associated with higher temperature of intake. Overall, the available results strongly suggest that high-temperature beverage drinking increases the risk of EC. Future studies will require standardized strategies that allow for combining data, and results should be reported by histological subtypes of EC. PMID:19415743

Relevance of estrogen-related receptor gene and ecdysone receptor gene in adult testis of the cricket Teleogryllus emma (Orthoptera: Gryllidae)

NASA Astrophysics Data System (ADS)

Jin, Wenjie; Jia, Yishu; Tan, E.; Xi, Gengsi

2017-12-01

Estrogen-related receptor gene ( ERR) and ecdysone receptor gene ( EcR) belong to the nuclear receptor gene superfamily, both of which are associated with the regulation of insect reproductive development. However, the relationship between ERR and EcR and whether ERR participates in the 20E signal pathway during male reproduction are unclear. In this paper, adult male crickets Teleogryllus emma Ohmschi & Matsumura were divided into the experimental group, negative group, and control group. Crickets of the experimental group were injected with TeERR or TeEcR-dsRNA, and those in the negative group received EGFP-dsRNA. The efficiency of TeERR and TeEcR-RNAi was detected in the experimental group. Furthermore, the transcription level, morphological characteristics as well as weight were analyzed in the TeERR or TeEcR knocked-down testis. Results showed that the expression level of TeERR or TeEcR was significantly down-regulated ( P < 0.05) when treated with 2000 ng TeERR or TeEcR-dsRNA for 48 h. The expression level of TeERR could be down-regulated ( P < 0.05) using TeEcR-RNAi and vice versa. TeERR and TeEcR-RNAi caused morphological changes in testes, but they had no obvious effect on weight ( P > 0.05). These results indicate that TeERR and TeEcR are intimately related to each other. In addition, TeERR may be involved in the 20E signal pathway and maintain the function of adult cricket testis.

Exemplary Care as a Mediator of the Effects of Caregiver Subjective Appraisal and Emotional Outcomes

PubMed Central

Harris, Grant M.; Durkin, Daniel W.; Allen, Rebecca S.; DeCoster, Jamie; Burgio, Louis D.

2011-01-01

Purpose: Exemplary care (EC) is a new construct encompassing care behaviors that warrants further study within stress process models of dementia caregiving. Previous research has examined EC within the context of cognitively intact older adult care recipients (CRs) and their caregivers (CGs). This study sought to expand our knowledge of quality of care by investigating EC within a diverse sample of dementia CGs. Design and Methods: We examined the relation between CG subjective appraisal (daily care bother, burden, and behavioral bother), EC, and CG emotional outcomes (depression and positive aspects of caregiving [PAC]). Specifically, EC was examined as a possible mediator of the effects of CG subjective appraisals on emotional outcomes. Using a bootstrapping method and an SPSS macro developed by Preacher and Hayes (2008 Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models), we tested the indirect effect of EC on the relation between CG subjective appraisals and CG emotional outcomes. Results: Overall, EC partially mediates the relation between the subjective appraisal variables (daily care bother, burden, and behavioral bother) and PAC. Results for depression were similar except that EC did not mediate the relation between burden and depression. This pattern of results varied by race/ethnicity. Implications: Overall, CGs’ perception of providing EC to individuals with dementia partially explains the relation between subjective appraisal and symptoms of depression and PAC. Results of this study suggest that interventions may benefit from training CGs to engage in EC to improve their emotional outcomes and quality of care. PMID:21350038

Clinical impact of endometrial cancer stratified by genetic mutational profiles, POLE mutation, and microsatellite instability.

PubMed

Haruma, Tomoko; Nagasaka, Takeshi; Nakamura, Keiichiro; Haraga, Junko; Nyuya, Akihiro; Nishida, Takeshi; Goel, Ajay; Masuyama, Hisashi; Hiramatsu, Yuji

2018-01-01

The molecular characterization of endometrial cancer (EC) can facilitate identification of various tumor subtypes. Although EC patients with POLE mutations reproducibly demonstrate better prognosis, the outcome of patients with microsatellite instability (MSI) remains controversial. This study attempted to interrogate whether genetic stratification of EC can identify distinct subsets with prognostic significance. A cohort of 138 EC patients who underwent surgical resection with curative intent was enrolled. Sanger sequencing was used to evaluate mutations in the POLE and KRAS genes. MSI analysis was performed using four mononucleotide repeat markers and methylation status of the MLH1 promoter was measured by a fluorescent bisulfite polymerase chain reaction (PCR). Protein expression for mismatch repair (MMR) proteins was evaluated by immunohistochemistry (IHC). Extensive hypermethylation of the MLH1 promoter was observed in 69.6% ECs with MLH1 deficiency and 3.5% with MMR proficiency, but in none of the ECs with loss of other MMR genes (P < .0001). MSI-positive and POLE mutations were found in 29.0% and 8.7% EC patients, respectively. Our MSI analysis showed a sensitivity of 92.7% for EC patients with MMR deficiency, and a specificity of 97.9% for EC patients with MMR proficiency. In univariate and multivariate analyses, POLE mutations and MSI status was significantly associated with progression-free survival (P = 0.0129 and 0.0064, respectively) but not with endometrial cancer-specific survival. This study provides significant evidence that analyses of proofreading POLE mutations and MSI status based on mononucleotide repeat markers are potentially useful biomarkers to identify EC patients with better prognosis.

Causes and treatment of mandibular and condylar fractures in children and adolescents: a review of 104 cases.

PubMed

Shi, Jun; Chen, Zhibiao; Xu, Bing

2014-03-01

There are no uniform treatments, standards, and specifications for conservative and surgical management of mandibular fractures in children and adolescents. To review the management of mandibular fractures in children and adolescents at our institution. The medical records of 104 children and adolescents (60 male and 44 female) treated for mandibular fractures from 2005 to 2012 at the Ninth People's Hospital, Shanghai, China, were retrospectively reviewed. The participants were classified as having deciduous dentition (age ≤6 years), mixed dentition (age >6 but <12 years), and permanent dentition (age ≥12 but ≤16 years). Conservative treatment and surgical management. Helkimo clinical dysfunction and anamnestic indices. Condylar process fractures accounted for 55.7% of the fractures (112 fractures of 201 total fracture sites), and symphysis fractures, parasymphysis fractures, fractures of the body, and fractures of the angle accounted for 20.9%, 11.9%, 7.0%, and 3.5% of the fractures, respectively. A total of 83 cases with 159 fracture sites with complete follow-up data were included in the treatment analysis. In these 83 patients, 77 fractures were dentigerous bone fractures, 46 were intracapsular fractures, and 36 were extracapsular fractures. Dentigerous bone fractures of the mandible were managed by closed or open reduction in children younger than 12 years and were managed more often by open reduction and fixation in those between ages 12 and 16 years. Closed treatment was performed for 22 condylar process fractures (28.6%), and open reduction was carried out for 55 condylar process fractures (71.4%). In patients with intracapsular fractures, there was no significant relationship between dentation age and treatment method (P = .06). Most patients with extracapsular fractures with permanent dentition underwent surgical fixation (73.3%), whereas most with deciduous dentition received conservative treatment (87.5%). In patients with condylar process fractures, there was no significant difference in Ai and Di based on treatment method (P = .49 and P = .76, respectively). The treatment of mandibular fractures in children and adolescents should be determined by clinical factors including age, location, and type of fracture.

Clinical comparison of a novel extracapsular stabilization procedure and tibial plateau leveling osteotomy for treatment of cranial cruciate ligament deficiency in dogs.

PubMed

Cook, James L; Luther, Jill K; Beetem, Jodi; Karnes, Josh; Cook, Cristi R

2010-04-01

To develop and test a novel extracapsular technique, TightRope CCL technique (TR), and compare its 6-month clinical outcomes to tibial plateau leveling osteotomy (TPLO) in dogs with cranial cruciate ligament (CCL) deficiency. Prospective clinical cohort study. Medium, large, and giant breed dogs (n=47) with CCL deficiency. Before clinical use, TR was evaluated by mechanical testing and the surgical technique was developed and evaluated in canine cadavers. For the clinical study, dogs were assigned to either TR (n=24) or TPLO (n=23) groups and the assigned technique performed after arthroscopic assessment and treatment of joint pathology. Postoperative management was standardized for both groups. Outcome measures were performed immediately postoperatively and up to 6 months after surgery and included complication types and rate, subjective measurement of cranial drawer and tibial thrust, subjective assessment of radiographic progression of osteoarthritis (OA), and function using a validated client questionnaire (6 months only). TR with a fiber tape suture had superior mechanical properties for creep, stiffness, yield load, and load at failure. Duration of anesthesia, total surgical time, and stabilization procedure (TR versus TPLO) were all significantly (P<.001) shorter for TR compared with TPLO. Complications requiring further treatment occurred in 12.5% of TR cases and 17.4% of TPLO cases. No significant differences were noted between groups for cranial tibial thrust, but cranial drawer was significantly (P<.05) lower in TR stifles at all postoperative time points. No significant differences were noted between groups for radiographic OA scores. No statistically or clinically significant differences were noted between TR and TPLO for scores for each of the client questionnaire categories. TR resulted in 6-month outcomes that were not different than TPLO in terms of radiographic progression of OA and client-evaluated level of function. TR was associated with shorter anesthesia and surgery times as well as a lower complication rate. The TR technique is safe and effective and can be considered an appropriate surgical option as part of the overall treatment plan for CCL deficiency in dogs.

Augmented reality fluoroscopy simulation of the guide-wire insertion in DHS surgery: A proof of concept study.

PubMed

van Duren, B H; Sugand, K; Wescott, R; Carrington, R; Hart, A

2018-05-01

Hip fractures contribute to a significant clinical burden globally with over 1.6 million cases per annum and up to 30% mortality rate within the first year. Insertion of a dynamic hip screw (DHS) is a frequently performed procedure to treat extracapsular neck of femur fractures. Poorly performed DHS fixation of extracapsular neck of femur fractures can result in poor mobilisation, chronic pain, and increased cut-out rate requiring revision surgery. A realistic, affordable, and portable fluoroscopic simulation system can improve performance metrics in trainees, including the tip-apex distance (the only clinically validated outcome), and improve outcomes. We developed a digital fluoroscopic imaging simulator using orthogonal cameras to track coloured markers attached to the guide-wire which created a virtual overlay on fluoroscopic images of the hip. To test the accuracy with which the augmented reality system could track a guide-wire, a standard workshop femur was used to calibrate the system with a positional marker fixed to indicate the apex; this allowed for comparison between guide-wire tip-apex distance (TAD) calculated by the system to be compared to that physically measured. Tests were undertaken to determine: (1) how well the apex could be targeted; (2) the accuracy of the calculated TAD. (3) The number of iterations through the algorithm giving the optimal accuracy-time relationship. The calculated TAD was found to have an average root mean square error of 4.2 mm. The accuracy of the algorithm was shown to increase with the number of iterations up to 20 beyond which the error asymptotically converged to an error of 2 mm. This work demonstrates a novel augmented reality simulation of guide-wire insertion in DHS surgery. To our knowledge this has not been previously achieved. In contrast to virtual reality, augmented reality is able to simulate fluoroscopy while allowing the trainee to interact with real instrumentation and performing the procedure on workshop bone models. Copyright © 2018 IPEM. Published by Elsevier Ltd. All rights reserved.

Prostate Postbrachytherapy Seed Distribution: Comparison of High-Resolution, Contrast-Enhanced, T1- and T2-Weighted Endorectal Magnetic Resonance Imaging Versus Computed Tomography: Initial Experience

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bloch, B. Nicolas; Department of Radiology, General Hospital Vienna, Medical University Vienna, Vienna; Lenkinski, Robert E.

2007-09-01

Purpose: To compare contrast-enhanced, T1-weighted, three-dimensional magnetic resonance imaging (CEMR) and T2-weighted magnetic resonance imaging (T2MR) with computed tomography (CT) for prostate brachytherapy seed location for dosimetric calculations. Methods and Materials: Postbrachytherapy prostate MRI was performed on a 1.5 Tesla unit with combined surface and endorectal coils in 13 patients. Both CEMR and T2MR used a section thickness of 3 mm. Spiral CT used a section thickness of 5 mm with a pitch factor of 1.5. All images were obtained in the transverse plane. Two readers using CT and MR imaging assessed brachytherapy seed distribution independently. The dependency of datamore » read by both readers for a specific subject was assessed with a linear mixed effects model. Results: The mean percentage ({+-} standard deviation) values of the readers for seed detection and location are presented. Of 1205 implanted seeds, CEMR, T2MR, and CT detected 91.5% {+-} 4.8%, 78.5% {+-} 8.5%, and 96.1% {+-} 2.3%, respectively, with 11.8% {+-} 4.5%, 8.5% {+-} 3.5%, 1.9% {+-} 1.0% extracapsular, respectively. Assignment to periprostatic structures was not possible with CT. Periprostatic seed assignments for CEMR and T2MR, respectively, were as follows: neurovascular bundle, 3.5% {+-} 1.6% and 2.1% {+-} 0.9%; seminal vesicles, 0.9% {+-} 1.8% and 0.3% {+-} 0.7%; periurethral, 7.1% {+-} 3.3% and 5.8% {+-} 2.9%; penile bulb, 0.6% {+-} 0.8% and 0.3% {+-} 0.6%; Denonvillier's Fascia/rectal wall, 0.5% {+-} 0.6% and 0%; and urinary bladder, 0.1% {+-} 0.3% and 0%. Data dependency analysis showed statistical significance for the type of imaging but not for reader identification. Conclusion: Both enumeration and localization of implanted seeds are readily accomplished with CEMR. Calculations with MRI dosimetry do not require CT data. Dose determinations to specific extracapsular sites can be obtained with MRI but not with CT.« less

A systematic analysis of online marketing materials used by providers of expanded carrier screening.

PubMed

Chokoshvili, Davit; Borry, Pascal; Vears, Danya F

2017-12-14

PurposeExpanded carrier screening (ECS) for a large number of recessive disorders is available to prospective parents through commercial providers. This study aimed to analyze the content of marketing materials on ECS providers' websites.MethodsTo identify providers of ECS tests, we undertook a comprehensive online search, reviewed recent academic literature on commercial carrier screening, and consulted with colleagues familiar with the current ECS landscape. The identified websites were archived in April 2017, and inductive content analysis was performed on website text, brochures and educational materials, and video transcripts.ResultsWe identified 18 ECS providers, including 16 commercial genetic testing companies. Providers typically described ECS as an important family planning tool. The content differed in both the tone used to promote ECS and the accuracy and completeness of the test information provided. We found that most providers offered complimentary genetic counseling to their consumers, although this was often optional, limited to the posttest context, and, in some cases, appeared to be available only to test-positive individuals.ConclusionThe quality of ECS providers' websites could be improved by offering more complete and accurate information about ECS and their tests. Providers should also ensure that all carrier couples receive posttest genetic counseling to inform their subsequent reproductive decision making.Genet Med advance online publication, 14 December 2017; doi:10.1038/gim.2017.222.

Probing the Interaction between Cyclic ADTC1 Ac-CADTPPVC-NH2) Peptide with EC1-EC2 domain of E-cadherin using Molecular Docking Approach

NASA Astrophysics Data System (ADS)

Siahaan, P.; Wuning, S.; Manna, A.; Prasasty, V. D.; Hudiyanti, D.

2018-04-01

Deeply understanding that intermolecular interaction between molecules on the paracellular pathway has given insight to its microscopic and macroscopic properties. In the paracellular pathway, synthetic cyclic ADTC1 (Ac-CADTPPVC-NH2) peptide has been studied to modulate EC1-EC2 domain, computationally using molecular docking method. The aim of this research is to probe the effect of amino acid alanine (A) of ADTC1 on its interaction properties. The study carried out in two steps: 1. the optimization using GROMACS v4.6.5 program and; 2. Determination of the interaction properties using AutoDock 4.2 program. The interaction was done for A-J box, and the best position of the binding site and binding energy on the OC and CC ADTC1 peptides against the EC1-EC2 domain of E-cadherin was selected. The result showed that the CC of the F box ADTC1 has the best interaction with binding energy of - 26.36 kJ/mol and its energy was lower than ADTC5 without alanine amino acid. ADTC1 interacted with EC1 of EC1-EC2 on Asp1, Trp2, Val3, Ile4, Ile24, Lys25, Ser26, Asn27, and Met92 residues.

Removal of metals in leachate from sewage sludge using electrochemical technology.

PubMed

Meunier, N; Drogui, P; Gourvenec, C; Mercier, G; Hausler, R; Blais, J F

2004-02-01

Heavy metals in acidic leachates from sewage sludge are usually removed by chemical precipitation, which often requires high concentration of chemicals and induces high metallic sludge production. Electrochemical technique has been explored as an alternative method in a laboratory pilot scale reactor for heavy metals (Cu and Zn) removal from sludge leachate. Three electrolytic cell arrangements using different electrodes materials were tested: mild steel or aluminium bipolar electrode (EC cell), Graphite/stainless steel monopolar electrodes (ER cell) and iron-monopolar electrodes (EC-ER cell). Results showed that the best performances of metal removal were obtained with EC and EC-ER cells using mild steel electrodes operated respectively at current intensities of 0.8 and 2.0 A through 30 and 60 min of treatment. The yields of Cu and Zn removal from leachate varied respectively from 92.4 to 98.9% and from 69.8 to 76.6%. The amounts of 55 and 44 kg tds(-1) of metallic sludge were respectively produced using EC and EC-ER cells. EC and EC-ER systems involved respectively a total cost of 21.2 and 13.1 CAN dollars per ton of dry sludge treated including only energy consumption and metallic sludge disposal. The treatment using EC-ER system was found to be effective and more economical than the traditional metal precipitation using either Ca(OH)2 and/or NaOH.

Probing the interaction between cHAVc3 peptide and the EC1 domain of E-cadherin using NMR and molecular dynamics simulations.

PubMed

Alaofi, Ahmed; Farokhi, Elinaz; Prasasty, Vivitri D; Anbanandam, Asokan; Kuczera, Krzysztof; Siahaan, Teruna J

2017-01-01

The goal of this work is to probe the interaction between cyclic cHAVc3 peptide and the EC1 domain of human E-cadherin protein. Cyclic cHAVc3 peptide (cyclo(1,6)Ac-CSHAVC-NH 2 ) binds to the EC1 domain as shown by chemical shift perturbations in the 2D 1 H,- 15 N-HSQC NMR spectrum. The molecular dynamics (MD) simulations of the EC1 domain showed folding of the C-terminal tail region into the main head region of the EC1 domain. For cHAVc3 peptide, replica exchange molecular dynamics (REMD) simulations generated five structural clusters of cHAVc3 peptide. Representative structures of cHAVc3 and the EC1 structure from MD simulations were used in molecular docking experiments with NMR constraints to determine the binding site of the peptide on EC1. The results suggest that cHAVc3 binds to EC1 around residues Y36, S37, I38, I53, F77, S78, H79, and I94. The dissociation constants (K d values) of cHAVc3 peptide to EC1 were estimated using the NMR chemical shifts data and the estimated K d s are in the range of .5 × 10 -5 -7.0 × 10 -5  M.

Structure-activity relationships of flavonoids as natural inhibitors against E. coli β-glucuronidase.

PubMed

Weng, Zi-Miao; Wang, Ping; Ge, Guang-Bo; Dai, Zi-Ru; Wu, Da-Chang; Zou, Li-Wei; Dou, Tong-Yi; Zhang, Tong-Yan; Yang, Ling; Hou, Jie

2017-11-01

Bacterial β-glucuronidases play key roles in the deconjugation of a variety of endogenous and drug glucuronides, thus have been recognized as important targets to modulate the enterohepatic circulation of various glucuronides. In this study, more than 30 natural flavonoids were collected and their inhibitory effects against E. coli β-glucuronidase (EcGUS) were assayed. The results demonstrated that some flavonoids including scutellarein, luteolin, baicalein, quercetin and scutellarin displayed strong to moderate inhibitory effects against EcGUS, with the IC 50 values ranging from 5.76 μM to 29.64 μM, while isoflavones and dihydroflavones displayed weak inhibitory effects against EcGUS. Further investigation on inhibition kinetics revealed that scutellarein and luteolin functioned as potent competitive inhibitors against EcGUS-mediated PNPG hydrolysis, with the K i values less than 3.0 μM. Molecular docking simulations demonstrated that scutellarein and luteolin could be well-docked into the catalytic site of EcGUS, while the binding areas of these two natural inhibitors on EcGUS were highly overlapped with that of PNPG on EcGUS. Additionally, the structure-inhibition relationships of natural flavonoids against EcGUS are also summarized, which will be very helpful for the medicinal chemists to design and develop more potent flavonoid-type inhibitors against EcGUS. Copyright © 2017 Elsevier Ltd. All rights reserved.

Status of Europe's contribution to the ITER EC system

NASA Astrophysics Data System (ADS)

Albajar, F.; Aiello, G.; Alberti, S.; Arnold, F.; Avramidis, K.; Bader, M.; Batista, R.; Bertizzolo, R.; Bonicelli, T.; Braunmueller, F.; Brescan, C.; Bruschi, A.; von Burg, B.; Camino, K.; Carannante, G.; Casarin, V.; Castillo, A.; Cauvard, F.; Cavalieri, C.; Cavinato, M.; Chavan, R.; Chelis, J.; Cismondi, F.; Combescure, D.; Darbos, C.; Farina, D.; Fasel, D.; Figini, L.; Gagliardi, M.; Gandini, F.; Gantenbein, G.; Gassmann, T.; Gessner, R.; Goodman, T. P.; Gracia, V.; Grossetti, G.; Heemskerk, C.; Henderson, M.; Hermann, V.; Hogge, J. P.; Illy, S.; Ioannidis, Z.; Jelonnek, J.; Jin, J.; Kasparek, W.; Koning, J.; Krause, A. S.; Landis, J. D.; Latsas, G.; Li, F.; Mazzocchi, F.; Meier, A.; Moro, A.; Nousiainen, R.; Purohit, D.; Nowak, S.; Omori, T.; van Oosterhout, J.; Pacheco, J.; Pagonakis, I.; Platania, P.; Poli, E.; Preis, A. K.; Ronden, D.; Rozier, Y.; Rzesnicki, T.; Saibene, G.; Sanchez, F.; Sartori, F.; Sauter, O.; Scherer, T.; Schlatter, C.; Schreck, S.; Serikov, A.; Siravo, U.; Sozzi, C.; Spaeh, P.; Spichiger, A.; Strauss, D.; Takahashi, K.; Thumm, M.; Tigelis, I.; Vaccaro, A.; Vomvoridis, J.; Tran, M. Q.; Weinhorst, B.

2015-03-01

The electron cyclotron (EC) system of ITER for the initial configuration is designed to provide 20MW of RF power into the plasma during 3600s and a duty cycle of up to 25% for heating and (co and counter) non-inductive current drive, also used to control the MHD plasma instabilities. The EC system is being procured by 5 domestic agencies plus the ITER Organization (IO). F4E has the largest fraction of the EC procurements, which includes 8 high voltage power supplies (HVPS), 6 gyrotrons, the ex-vessel waveguides (includes isolation valves and diamond windows) for all launchers, 4 upper launchers and the main control system. F4E is working with IO to improve the overall design of the EC system by integrating consolidated technological advances, simplifying the interfaces, and doing global engineering analysis and assessments of EC heating and current drive physics and technology capabilities. Examples are the optimization of the HVPS and gyrotron requirements and performance relative to power modulation for MHD control, common qualification programs for diamond window procurements, assessment of the EC grounding system, and the optimization of the launcher steering angles for improved EC access. Here we provide an update on the status of Europe's contribution to the ITER EC system, and a summary of the global activities underway by F4E in collaboration with IO for the optimization of the subsystems.

AKT inhibition mitigates GRP78 (glucose-regulated protein) expression and contribution to chemoresistance in endometrial cancers.

PubMed

Gray, Michael J; Mhawech-Fauceglia, Paulette; Yoo, Eunjeong; Yang, Wangrong; Wu, Eijean; Lee, Amy S; Lin, Yvonne G

2013-07-01

Overexpression of the unfolded protein response master regulator GRP78 is associated with poor prognosis and therapeutic resistance in numerous human cancers, yet its role in endometrial cancers (EC) is undefined. To better understand the contribution of GRP78 to EC, we examined its expression levels in EC patient samples and EC cell lines. We demonstrate that GRP78 overexpression occurs more frequently in EC tissues compared with that found in normal endometrium, and that GRP78 expression occurs in most EC cell lines examined. Functional analysis demonstrated that GRP78 is inducible by cisplatin in EC cells, and siRNA knockdown of GRP78 augments chemotherapy-mediated cell death. Examination of AKT and GRP78 expression demonstrated that inhibition of AKT activity by MK2206 blocks GRP78 expression in EC cells. SiRNA studies also revealed that knockdown of GRP78 reduces but does not abrogate AKT activity, demonstrating that GRP78 is required for optimal AKT activity. In the presence of MK2206, siRNA knockdown of GRP78 does not augment AKT mediated survival in response to cisplatin treatment, suggesting that GRP78's antiapoptosis functions are part of the AKT survival pathway. Targeted therapies that reduce GRP78 expression or activity in cancers may serve to increase the effectiveness of current therapies for EC patients. Copyright © 2012 UICC.

Associations between eating competence and cardiovascular disease biomarkers.

PubMed

Psota, Tricia L; Lohse, Barbara; West, Sheila G

2007-01-01

Explore the relationship between eating competence (EC) and biomarkers of risk for cardiovascular disease (CVD). Secondary analysis of data collected for a larger, 2-way crossover clinical trial. Outpatient clinical research center. Forty-eight hypercholesterolemic (LDL cholesterol > or = 110 mg/dL) men (n = 19) and women (n = 29) 21 to 70 years of age. Participant descriptives, cardiovascular disease biomarker levels, and eating competence (EC) determined by the ecSatter Inventory (ecSI). T tests for differences in eating competence between males and females, analysis of variance for differences in risk between those categorized as EC or not. Associations between EC and baseline biochemical measures, as well as participant characteristics and dietary intake, were assessed by Pearson correlation analyses. Logistic regression estimated relative risk of CVD risk factors from ecSI scores. Several significant associations were found between EC total and CVD risk factors. Eating competence was positively correlated with HDL-cholesterol, and inversely associated with systolic and diastolic blood pressure. High EC participants had significantly lower ratios of total cholesterol: HDL-cholesterol and triglycerides: HDL-cholesterol. Participants who were not eating competent were 5 times more likely to have LDL-cholesterol levels > or =130 mg/dL and 7 times more likely to have triglyceride levels > or =150 mg/dL. Eating competence appears to be a cognitive, affective construct with physiological manifestations, making nutrition education to increase eating competence a medical nutrition therapy.

Elevated carbon dioxide is predicted to promote coexistence among competing species in a trait-based model

DOE PAGES

Ali, Ashehad A.; Medlyn, Belinda E.; Aubier, Thomas G.; ...

2015-10-06

Differential species responses to atmospheric CO 2 concentration (C a) could lead to quantitative changes in competition among species and community composition, with flow-on effects for ecosystem function. However, there has been little theoretical analysis of how elevated C a (eC a) will affect plant competition, or how composition of plant communities might change. Such theoretical analysis is needed for developing testable hypotheses to frame experimental research. Here, we investigated theoretically how plant competition might change under eC a by implementing two alternative competition theories, resource use theory and resource capture theory, in a plant carbon and nitrogen cycling model.more » The model makes several novel predictions for the impact of eC a on plant community composition. Using resource use theory, the model predicts that eC a is unlikely to change species dominance in competition, but is likely to increase coexistence among species. Using resource capture theory, the model predicts that eC a may increase community evenness. Collectively, both theories suggest that eC a will favor coexistence and hence that species diversity should increase with eC a. Our theoretical analysis leads to a novel hypothesis for the impact of eC a on plant community composition. In this study, the hypothesis has potential to help guide the design and interpretation of eC a experiments.« less

Endothelial transplantation rejuvenates aged hematopoietic stem cell function

PubMed Central

Poulos, Michael G.; Gutkin, Michael C.; Llanos, Pierre; Gilleran, Katherine; Rabbany, Sina Y.; Butler, Jason M.

2017-01-01

Age-related changes in the hematopoietic compartment are primarily attributed to cell-intrinsic alterations in hematopoietic stem cells (HSCs); however, the contribution of the aged microenvironment has not been adequately evaluated. Understanding the role of the bone marrow (BM) microenvironment in supporting HSC function may prove to be beneficial in treating age-related functional hematopoietic decline. Here, we determined that aging of endothelial cells (ECs), a critical component of the BM microenvironment, was sufficient to drive hematopoietic aging phenotypes in young HSCs. We used an ex vivo hematopoietic stem and progenitor cell/EC (HSPC/EC) coculture system as well as in vivo EC infusions following myelosuppressive injury in mice to demonstrate that aged ECs impair the repopulating activity of young HSCs and impart a myeloid bias. Conversely, young ECs restored the repopulating capacity of aged HSCs but were unable to reverse the intrinsic myeloid bias. Infusion of young, HSC-supportive BM ECs enhanced hematopoietic recovery following myelosuppressive injury and restored endogenous HSC function in aged mice. Coinfusion of young ECs augmented aged HSC engraftment and enhanced overall survival in lethally irradiated mice by mitigating damage to the BM vascular microenvironment. These data lay the groundwork for the exploration of EC therapies that can serve as adjuvant modalities to enhance HSC engraftment and accelerate hematopoietic recovery in the elderly population following myelosuppressive regimens. PMID:29035282

Is evaluative conditioning really uncontrollable? A comparative test of three emotion-focused strategies to prevent the acquisition of conditioned preferences.

PubMed

Gawronski, Bertram; Mitchell, Derek G V; Balas, Robert

2015-10-01

Evaluative conditioning (EC) is defined as the change in the evaluation of a conditioned stimulus (CS) because of its pairing with a valenced unconditioned stimulus (US). Counter to views that EC is the product of automatic learning processes, recent research has revealed various characteristics of nonautomatic processing in EC. The current research investigated the controllability of EC by testing the effectiveness of 3 emotion-focused strategies in preventing the acquisition of conditioned preferences: (a) suppression of emotional reactions to the US, (b) reappraisal of the valence of the US, and (c) facial blocking of emotional responses. Although all 3 strategies reduced EC effects on self-reported evaluations by impairing recollective memory for CS-US pairings, they were ineffective in reducing EC effects on an evaluative priming measure. Regardless of the measure, effective control did not depend on the level of arousal elicited by the US. The results suggest that the 3 strategies can influence deliberate CS evaluations through memory-related processes, but they are ineffective in reducing EC effects on spontaneous evaluative responses. Implications for mental process theories of EC are discussed. (c) 2015 APA, all rights reserved).

Relations among maternal socialization, effortful control, and maladjustment in early childhood

PubMed Central

Eisenberg, Nancy; Spinrad, Tracy L.; Eggum, Natalie D.; Silva, Kassondra M.; Reiser, Mark; Hofer, Claire; Smith, Cynthia L.; Gaertner, Bridget M.; Kupfer, Anne; Popp, Tierney; Michalik, Nicole

2010-01-01

In a sample of 18-, 30-, and 42-month-olds, the relations among parenting, effortful control (EC), and maladjustment were examined. Parenting was assessed with mothers’ reports and observations; EC was measured with mothers’ and caregivers’ reports, as well as a behavioral task; and externalizing and internalizing symptoms were assessed with parents’ and caregivers’ reports. Although 18-month unsupportive (vs. supportive) parenting negatively predicted EC at 30 months, when the stability of these variables was taken into account, there was no evidence of additional potentially causal relations between these two constructs. Although EC was negatively related to both internalizing and externalizing problems within all three ages as well as across 1 year, EC did not predict maladjustment once the stability of the constructs and within time covariation between the constructs were taken into account. In addition, externalizing problems at 30 months negatively predicted EC at 42 months, and internalizing problems at 30 months positively predicted EC at 42 months, but only when the effects of externalizing on EC were controlled. The findings are discussed in terms of the reasons for the lack of causal relations over time. PMID:20576175

N-acyl homoserine lactone-degrading microbial enrichment cultures isolated from Penaeus vannamei shrimp gut and their probiotic properties in Brachionus plicatilis cultures.

PubMed

Tinh, Nguyen Thi Ngoc; Asanka Gunasekara, R A Y S; Boon, Nico; Dierckens, Kristof; Sorgeloos, Patrick; Bossier, Peter

2007-10-01

Three bacterial enrichment cultures (ECs) were isolated from the digestive tract of Pacific white shrimp Penaeus vannamei, by growing the shrimp microbial communities in a mixture of N-acyl homoserine lactone (AHL) molecules. The ECs, characterized by denaturing gradient gel electrophoresis analysis and subsequent rRNA sequencing, degraded AHL molecules in the degradation assays. Apparently, the resting cells of the ECs also degraded one of the three types of quorum-sensing signal molecules produced by Vibrio harveyi in vitro [i.e. harveyi autoinducer 1 (HAI-1)]. The most efficient AHL-degrading ECs, EC5, was tested in Brachionus experiments. EC5 degraded the V. harveyi HAI-1 autoinducer in vivo, neutralizing the negative effect of V. harveyi autoinducer 2 (AI-2) mutant, in which only the HAI-1- and CAI-1-mediated components of the quorum-sensing system are functional on the growth of Brachionus. This suggests that EC5 interferes with HAI-1-regulated metabolism in V. harveyi. These AHL-degrading ECs need to be tested in other aquatic systems for their probiotic properties, preferably in combination with specific AI-2-degrading bacteria.

[Diagnostic values of salivary versus and plasma microRNA-21 for early esophageal cancer].

PubMed

Ye, Minhua; Ye, Penghui; Zhang, Weizhu; Rao, Jiaqi; Xie, Zijun

2014-06-01

To evaluate the diagnostic value of salivary and plasma miR-21 in patients with esophageal cancer (EC). Total RNA was extracted from saliva and plasma samples from 50 stage I and 50 stage II patients with EC and 50 healthy controls for measurement of miR-21 levels using qPCR. The diagnostic values of salivary and plasma miR-21 levels were assessed for stage I, stage II, and stage I+II EC. Salivary and plasma miR-21 were significantly higher in the EC patients than in the control group. The diagnostic sensitivities of plasma miR-21 for stage I, stage II, and stage I+II EC were 96%, 64% and 97%, with specificities of 44%, 84%, and 56%, respectively; the sensitivities of salivary miR-21 were 90%, 88%, and 89%, respectively, with the same specificities of 64%. Regardless of EC staging, the expression of plasma miR-21 showed a significant positive correlation with that of salivary miR-21, and their diagnostic values were comparable. Both salivary and plasmatic miR-21 can be sensitive biomarkers for EC, and salivary miR-21 detection has the potential to replace plasma detection for EC diagnosis.

Direct measurement of electrocaloric effect in lead-free Ba(SnxTi1-x)O3 ceramics

NASA Astrophysics Data System (ADS)

Sanlialp, Mehmet; Luo, Zhengdong; Shvartsman, Vladimir V.; Wei, Xianzhu; Liu, Yang; Dkhil, Brahim; Lupascu, Doru C.

2017-10-01

In this study, we report on investigation of the electrocaloric (EC) effect in lead-free Ba(SnxTi1-x)O3 (BSnT) ceramics with compositions in the range of 0.08 ≤ x ≤ 0.15 by the direct measurement method using a differential scanning calorimeter. The maximum EC temperature change, ΔTEC-max = 0.63 K under an electric field of 2 kV/mm, was observed for the composition with x = 0.11 at ˜44 °C around the multiphase coexistence region. We observed that the EC effect also peaks at transitions between ferroelectric phases of different symmetries. Comparison with the results of indirect EC measurements from our previous work shows that the indirect approach provides reasonable estimations of the magnitude of the largest EC temperature changes and EC strength. However, it fails to describe correctly temperature dependences of the EC effect for the compositions showing relaxor-like behaviour (x = 0.14 and 0.15) because of their non-ergodic nature. Our study provides strong evidence supporting that looking for multiphase ferroelectric materials can be very useful to optimize EC performance.

Interactions of Human Endothelial and Multipotent Mesenchymal Stem Cells in Cocultures

PubMed Central

Ern, Christina; Krump-Konvalinkova, Vera; Docheva, Denitsa; Schindler, Stefanie; Rossmann, Oliver; Böcker, Wolfgang; Mutschler, Wolf; Schieker, Matthias

2010-01-01

Current strategies for tissue engineering of bone rely on the implantation of scaffolds, colonized with human mesenchymal stem cells (hMSC), into a recipient. A major limitation is the lack of blood vessels. One approach to enhance the scaffold vascularisation is to supply the scaffolds with endothelial cells (EC). The main goal of this study was to establish a coculture system of hMSC and EC for the purposes of bone tissue engineering. Therefore, the cell behaviour, proliferation and differentiation capacity in various cell culture media as well as cell interactions in the cocultures were evaluated. The differentiation capacity of hMSC along osteogenic, chondrogenic, and adipogenic lineage was impaired in EC medium while in a mixed EC and hMSC media, hMSC maintained osteogenic differentiation. In order to identify and trace EC in the cocultures, EC were transduced with eGFP. Using time-lapse imaging, we observed that hMSC and EC actively migrated towards cells of their own type and formed separate clusters in long term cocultures. The scarcity of hMSC and EC contacts in the cocultures suggest the influence of growth factor-mediated cell interactions and points to the necessity of further optimization of the coculture conditions. PMID:21625373

Application of the thiocarbohydrazide method for vicinal glycol group detection to the study of gastric mucosa endocrine cells.

PubMed

Lefranc, G; Chung, Y T; Barrière, P; Pradal, G

1980-01-01

The thiocarbohydrazide-silver proteinate (TCH SP) method was applied to the study of cat, rabbit and mouse gastric mucosa endocrine cells. After 24-h treatment with thiocarbohydrazide (TCH), glycogen was seen in the hyaloplasm of X, D, P, A and O cells but not in EC, EC-like or D1 cells. With flotation times as short as 30 to 40 min glycogen was readily detected in X cells. Secretory granules of EC cells were constantly stained, while those of D1 cells failed to react. In most experiments granules of X, A and O cells showed peripheral "staining", while in others staining of variable intensity affected the entire granular cross-section in X, D and P cells. With 72-h exposure to TCH, EC and EC-like cells showed particles resembling glycogen, even staining or only peripheral staining of certain EC cell granules. From the results of this and previous studies, EC cell staining is believed to be due wholly or partly, according to exposure times, to the action of silver proteinate, while that of certain non-EC cells is probably a specific indicator of complexed carbohydrates.

Lipid Droplet Biogenesis and Function in the Endothelium.

PubMed

Kuo, Andrew; Lee, Monica Y; Sessa, William C

2017-04-14

Fatty acids (FA) are transported across the capillary endothelium to parenchymal tissues. However, it is not known how endothelial cells (EC) from large vessels process a postprandial surge of FA. This study was designed to characterize lipid droplet (LD) formation in EC by manipulating pathways leading to the formation and degradation of LD. In addition, several functions of LD-derived FA were assessed. LD were present in EC lining the aorta after the peak in plasma triglycerides initiated by a gavage of olive oil in mice, in vivo. Similarly, in isolated aorta, oleic acid treatment generates LD in EC ex vivo. Cultured EC readily form LD largely via the enzyme DGAT (diacylglycerol O-acyltransferase 1) and degrade LD via ATGL (adipocyte triglyceride lipase) after FA loading. Functionally, LD-derived FA are dynamically regulated and function to protect EC from lipotoxic stress and provide FA for metabolic needs. Our results delineate endothelial LD dynamics for the first time in vivo and in vitro. Moreover, LD formation protects EC from lipotoxic stress, regulates EC glycolysis, and provides a source of FA for adjacent cells in the vessel wall or tissues. © 2017 American Heart Association, Inc.

Surfing on the morning after: analysis of an emergency contraception website.

PubMed

Gainer, Erin; Sollet, Christian; Ulmann, Marion; Lévy, Delphine; Ulmann, André

2003-03-01

The introduction of widespread nonprescription delivery of hormonal emergency contraception (EC) calls for development of innovative tools to provide information to and gather feedback from EC users. Individuals seeking confidential information on sexual health and contraception are increasingly turning to the Internet as the resource of choice. This study employed analytical software and manual content analysis to examine the use of a website dedicated to an EC product (www.norlevo.com) over the course of 2 years. Frequency of visits to and pageviews of the site increased consistently over the 2-year time period, and the bulk of the visitors to the site were EC users seeking responses to frequently asked questions. The most common concern raised by users was the occurrence of spotting and menstrual bleeding following EC use. This analysis reveals that within the context of nonprescription access to hormonal EC, a website can constitute a potent educational tool for health professionals and EC users and provide a valuable source of post-marketing feedback on product use.

Seasonal variations in elemental carbon aerosol, carbon monoxide and sulfur dioxide: Implications for sources

NASA Astrophysics Data System (ADS)

Antony Chen, L.-W.; Doddridge, Bruce G.; Dickerson, Russell R.; Chow, Judith C.; Mueller, Peter K.; Quinn, John; Butler, William A.

As part of Maryland Aerosol Research and CHaracterization (MARCH-Atlantic) study, measurements of 24-hr average elemental carbon (EC) aerosol concentration were made at Fort Meade, Maryland, USA, a suburban site within the Baltimore-Washington corridor during July 1999, October 1999, January 2000, April 2000 and July 2000. Carbon monoxide (CO) and sulfur dioxide (SO2) were also measured nearly continuously over the period. Tight correlation between EC and CO in every month suggests common or proximate sources, likely traffic emissions. The EC versus CO slope varies in different seasons and generally increases with ambient temperature. The temperature dependence of EC/CO ratios suggests that EC source strength peaks in summer. By using the well established emission inventory for CO, and EC/CO ratio found in this study, EC emission over North America is estimated at 0.31±0.12 Tg yr-1, on the low end but in reasonable agreement with prior inventories based on emission factors and fuel consumption.