The Verification-based Analysis of Reliable Multicast Protocol

NASA Technical Reports Server (NTRS)

Wu, Yunqing

1996-01-01

Reliable Multicast Protocol (RMP) is a communication protocol that provides an atomic, totally ordered, reliable multicast service on top of unreliable IP Multicasting. In this paper, we develop formal models for R.W using existing automatic verification systems, and perform verification-based analysis on the formal RMP specifications. We also use the formal models of RW specifications to generate a test suite for conformance testing of the RMP implementation. Throughout the process of RMP development, we follow an iterative, interactive approach that emphasizes concurrent and parallel progress between the implementation and verification processes. Through this approach, we incorporate formal techniques into our development process, promote a common understanding for the protocol, increase the reliability of our software, and maintain high fidelity between the specifications of RMP and its implementation.

Thirteen years and counting: Outcomes of a concurrent ASN/BSN enrollment program.

PubMed

Heglund, Stephen; Simmons, Jessica; Wink, Diane; D'Meza Leuner, Jean

In their 2011 report, The Future of Nursing, the Institute of Medicine called for 80% of the nursing workforce to be comprised of baccalaureate prepared Registered Nurses by the year 2020. One suggested approach to achieve this goal is the creation of programs that allow students to progress through associate and baccalaureate nursing preparation simultaneously. This paper describes the University of Central Florida's 13-year experience after implementing a Concurrent Enrollment Program. Development and structure of the program, advisement and curriculum details, facilitators and barriers are described. Data on National Council Licensure Examination for Registered Nurses pass rates, completion rates, comparison with traditional RN-BSN students, and progression to graduate school are also included. The Concurrent Program model described here between a specific university and state college partners, demonstrated positive outcomes that support achievement of the Institute of Medicine's goals. Copyright © 2017 Elsevier Inc. All rights reserved.

High-dose versus standard-dose radiotherapy with concurrent chemotherapy in stages II-III esophageal cancer.

PubMed

Suh, Yang-Gun; Lee, Ik Jae; Koom, Wong Sub; Cha, Jihye; Lee, Jong Young; Kim, Soo Kon; Lee, Chang Geol

2014-06-01

In this study, we investigated the effects of radiotherapy ≥60 Gy in the setting of concurrent chemo-radiotherapy for treating patients with Stages II-III esophageal cancer. A total of 126 patients treated with 5-fluorouracilbased concurrent chemo-radiotherapy between January 1998 and February 2008 were retrospectively reviewed. Among these patients, 49 received a total radiation dose of <60 Gy (standard-dose group), while 77 received a total radiation dose of ≥60 Gy (high-dose group). The median doses in the standard- and high-dose groups were 54 Gy (range, 45-59.4 Gy) and 63 Gy (range, 60-81 Gy), respectively. The high-dose group showed significantly improved locoregional control (2-year locoregional control rate, 69 versus 32%, P < 0.01) and progression-free survival (2-year progression-free survival, 47 versus 20%, P = 0.01) than the standard-dose group. Median overall survival in the high- and the standard-dose groups was 28 and 18 months, respectively (P = 0.26). In multivariate analysis, 60 Gy or higher radiotherapy was a significant prognostic factor for improved locoregional control, progression-free survival and overall survival. No significant differences were found in frequencies of late radiation pneumonitis, post-treatment esophageal stricture or treatment-related mortality between the two groups. High-dose radiotherapy of 60 Gy or higher with concurrent chemotherapy improved locoregional control and progression-free survival without a significant increase of in treatment-related toxicity in patients with Stages II-III esophageal cancer. Our study could provide the basis for future randomized clinical trials. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Towards PCC for Concurrent and Distributed Systems (Work in Progress)

NASA Technical Reports Server (NTRS)

Henriksen, Anders S.; Filinski, Andrzej

2009-01-01

We outline some conceptual challenges in extending the PCC paradigm to a concurrent and distributed setting, and sketch a generalized notion of module correctness based on viewing communication contracts as economic games. The model supports compositional reasoning about modular systems and is meant to apply not only to certification of executable code, but also of organizational workflows.

Concurrent Chemoradiotherapy with Temozolomide Followed by Adjuvant Temozolomide for Newly Diagnosed Glioblastoma Patients: A Retrospective Multicenter Observation Study in Korea.

PubMed

Kim, Byung Sup; Seol, Ho Jun; Nam, Do-Hyun; Park, Chul-Kee; Kim, Il Han; Kim, Tae Min; Kim, Jeong Hoon; Cho, Young Hyun; Yoon, Sang Min; Chang, Jong Hee; Kang, Seok-Gu; Kim, Eui Hyun; Suh, Chang-Ok; Jung, Tae-Young; Lee, Kyung-Hwa; Kim, Chae-Yong; Kim, In Ah; Hong, Chang-Ki; Yoo, Heon; Kim, Jin Hee; Kang, Shin-Hyuk; Kang, Min Kyu; Kim, Eun-Young; Kim, Sun-Hwan; Chung, Dong-Sup; Hwang, Sun-Chul; Song, Joon-Ho; Cho, Sung Jin; Lee, Sun-Il; Lee, Youn-Soo; Ahn, Kook-Jin; Kim, Se Hoon; Lim, Do Hun; Gwak, Ho-Shin; Lee, Se-Hoon; Hong, Yong-Kil

2017-01-01

The purpose of this study was to investigate the feasibility and survival benefits of combined treatment with radiotherapy and adjuvant temozolomide (TMZ) in a Korean sample. A total of 750 Korean patients with histologically confirmed glioblastoma multiforme, who received concurrent chemoradiotherapy with TMZ (CCRT) and adjuvant TMZ from January 2006 until June 2011, were analyzed retrospectively. After the first operation, a gross total resection (GTR), subtotal resection (STR), partial resection (PR), biopsy alone were achieved in 388 (51.7%), 159 (21.2%), 96 (12.8%), and 107 (14.3%) patients, respectively. The methylation status of O 6 -methylguanine-DNA methyltransferase (MGMT) was reviewed retrospectively in 217 patients. The median follow-up period was 16.3 months and the median overall survival (OS) was 17.5 months. The actuarial survival rates at the 1-, 3-, and 5-year OS were 72.1%, 21.0%, and 9.0%, respectively. The median progression-free survival (PFS) was 10.1 months, and the actuarial PFS at 1-, 3-, and 5-year PFS were 42.2%, 13.0%, and 7.8%, respectively. The patients who received GTR showed a significantly longer OS and PFS than those who received STR, PR, or biopsy alone, regardless of the methylation status of the MGMT promoter. Patients with a methylated MGMT promoter also showed a significantly longer OS and PFS than those with an unmethylated MGMT promoter. Patients who received more than six cycles of adjuvant TMZ had a longer OS and PFS than those who received six or fewer cycles. Hematologic toxicity of grade 3 or 4 was observed in 8.4% of patients during the CCRT period and in 10.2% during the adjuvant TMZ period. Patients treated with CCRT followed by adjuvant TMZ had more favorable survival rates and tolerable toxicity than those who did not undergo this treatment.

Reciprocal Activating Crosstalk between c-Met and Caveolin 1 Promotes Invasive Phenotype in Hepatocellular Carcinoma

PubMed Central

Korhan, Peyda; Erdal, Esra; Kandemiş, Emine; Çokaklı, Murat; Nart, Deniz; Yılmaz, Funda; Can, Alp; Atabey, Neşe

2014-01-01

c-Met, the receptor for Hepatocyte Growth Factor (HGF), overexpressed and deregulated in Hepatocellular Carcinoma (HCC). Caveolin 1 (CAV1), a plasma membrane protein that modulates signal transduction molecules, is also overexpressed in HCC. The aim of this study was to investigate biological and clinical significance of co-expression and activation of c-Met and CAV1 in HCC. We showed that c-Met and CAV1 were co-localized in HCC cells and HGF treatment increased this association. HGF-triggered c-Met activation caused a concurrent rise in both phosphorylation and expression of CAV1. Ectopic expression of CAV1 accelerated c-Met signaling, resulted in enhanced migration, invasion, and branching-morphogenesis. Silencing of CAV1 downregulated c-Met signaling, and decreased migratory/invasive capability of cells and attenuated branching morphogenesis. In addition, activation and co-localization of c-Met and CAV1 were elevated during hepatocarcinogenesis. In conclusion reciprocal activating crosstalk between c-Met and CAV1 promoted oncogenic signaling of c-Met contributed to the initiation and progression of HCC. PMID:25148256

Reciprocal activating crosstalk between c-Met and caveolin 1 promotes invasive phenotype in hepatocellular carcinoma.

PubMed

Korhan, Peyda; Erdal, Esra; Kandemiş, Emine; Cokaklı, Murat; Nart, Deniz; Yılmaz, Funda; Can, Alp; Atabey, Neşe

2014-01-01

c-Met, the receptor for Hepatocyte Growth Factor (HGF), overexpressed and deregulated in Hepatocellular Carcinoma (HCC). Caveolin 1 (CAV1), a plasma membrane protein that modulates signal transduction molecules, is also overexpressed in HCC. The aim of this study was to investigate biological and clinical significance of co-expression and activation of c-Met and CAV1 in HCC. We showed that c-Met and CAV1 were co-localized in HCC cells and HGF treatment increased this association. HGF-triggered c-Met activation caused a concurrent rise in both phosphorylation and expression of CAV1. Ectopic expression of CAV1 accelerated c-Met signaling, resulted in enhanced migration, invasion, and branching-morphogenesis. Silencing of CAV1 downregulated c-Met signaling, and decreased migratory/invasive capability of cells and attenuated branching morphogenesis. In addition, activation and co-localization of c-Met and CAV1 were elevated during hepatocarcinogenesis. In conclusion reciprocal activating crosstalk between c-Met and CAV1 promoted oncogenic signaling of c-Met contributed to the initiation and progression of HCC.

A Concurrent Mixed Methods Approach to Examining the Quantitative and Qualitative Meaningfulness of Absolute Magnitude Estimation Scales in Survey Research

ERIC Educational Resources Information Center

Koskey, Kristin L. K.; Stewart, Victoria C.

2014-01-01

This small "n" observational study used a concurrent mixed methods approach to address a void in the literature with regard to the qualitative meaningfulness of the data yielded by absolute magnitude estimation scaling (MES) used to rate subjective stimuli. We investigated whether respondents' scales progressed from less to more and…

Concurrent Validity and Sensitivity to Change of Direct Behavior Rating Single-Item Scales (DBR-SIS) within an Elementary Sample

ERIC Educational Resources Information Center

Smith, Rhonda L.; Eklund, Katie; Kilgus, Stephen P.

2018-01-01

The purpose of this study was to evaluate the concurrent validity, sensitivity to change, and teacher acceptability of Direct Behavior Rating single-item scales (DBR-SIS), a brief progress monitoring measure designed to assess student behavioral change in response to intervention. Twenty-four elementary teacher-student dyads implemented a daily…

Functioning and disability in adults with myotonic dystrophy type 1.

PubMed

Kierkegaard, Marie; Harms-Ringdahl, Karin; Holmqvist, Lotta Widén; Tollbäck, Anna

2011-01-01

 To provide a comprehensive description of functioning and disability with regard to stages of disease progression in adults with myotonic dystrophy type 1 (DM1). Further to explore associations of measures of manual dexterity and of walking capacity with measures of activities of daily living (ADL) and participation in social and lifestyle activities. Seventy persons with DM1 underwent examinations, tests and answered questionnaires. Stages of disease progression were based on the muscular impairment rating scale.  Overweight, cardiac dysfunctions, respiratory restrictions, fatigue and/or low physical activity levels were found in approximately 40% of those with DM1. Over 75% had muscle impairments, and activity limitations in manual dexterity and walking. Dependence in personal and instrumental ADL was found in 16% and 39%, respectively, and participation restrictions in social and lifestyle activities in 52%. The presence of concurrent body-function impairments, activity limitations and participation restrictions was high. Significant differences were found in muscle impairment, manual dexterity, mobility, ADL and social and lifestyle activities with regard to disease progression. Cut-off values in measures of manual dexterity and walking capacity associated to functioning are proposed.  This information can be used for developing clinical practise and for health promotion for persons with DM1.

Radiation therapy in the management of head-and-neck cancer of unknown primary origin: how does the addition of concurrent chemotherapy affect the therapeutic ratio?

PubMed

Chen, Allen M; Farwell, D Gregory; Lau, Derick H; Li, Bao-Qing; Luu, Quang; Donald, Paul J

2011-10-01

To determine how the addition of cisplatin-based concurrent chemotherapy to radiation therapy influences outcomes among a cohort of patients treated for head-and-neck cancer of unknown primary origin. The medical records of 60 consecutive patients treated by radiation therapy for squamous cell carcinoma of the head and neck presenting as cervical lymph node metastasis of occult primary origin were reviewed. Thirty-two patients (53%) were treated by concurrent chemoradiation, and 28 patients (47%) were treated by radiation therapy alone. Forty-five patients (75%) received radiation therapy after surgical resection, and 15 patients (25%) received primary radiation therapy. Thirty-five patients (58%) were treated by intensity-modulated radiotherapy. The 2-year estimates of overall survival, local-regional control, and progression-free survival were 89%, 89%, and 79%, respectively, among patients treated by chemoradiation, compared to 90%, 92%, and 83%, respectively, among patients treated by radiation therapy alone (p > 0.05, for all). Exploratory analysis failed to identify any subset of patients who benefited from the addition of concurrent chemotherapy to radiation therapy. The use of concurrent chemotherapy was associated with a significantly increased incidence of Grade 3+ acute and late toxicity (p < 0.001, for both). Concurrent chemoradiation is associated with significant toxicity without a clear advantage to overall survival, local-regional control, and progression-free survival in the treatment of head-and-neck cancer of unknown primary origin. Although selection bias cannot be ignored, prospective data are needed to further address this question. Copyright © 2011 Elsevier Inc. All rights reserved.

Obesity-Induced Diabetes and Lower Urinary Tract Fibrosis Promote Urinary Voiding Dysfunction in a Mouse Model

PubMed Central

Gharaee-Kermani, Mehrnaz; Rodriguez-Nieves, Jose A.; Mehra, Rohit; Vezina, Chad A.; Sarma, Aruna V.; Macoska, Jill A.

2017-01-01

BACKGROUND Progressive aging- and inflammation-associated fibrosis effectively remodels the extracellular matrix (ECM) to increase prostate tissue stiffness and reduce urethral flexibility, resulting in urinary flow obstruction and lower urinary tract symptoms (LUTS). In the current study, we sought to test whether senescence-accelerated mouse prone (SAMP)6 mice, which were reported to develop prostatic fibrosis, would also develop LUTS, and whether these symptoms would be exacerbated by diet-induced obesity and concurrent Type 2 Diabetes Mellitus (T2DM). METHODS To accomplish this, SAMP6 and AKR/J background strain mice were fed regular mouse chow, low fat diet chow, or high fat diet chow for 8 months, then subjected to glucose tolerance tests, assessed for plasma insulin levels, evaluated for urinary voiding function, and assessed for lower urinary tract fibrosis. RESULTS The results of these studies show that SAMP6 mice and AKR/J background strain mice develop diet-induced obesity and T2DM concurrent with urinary voiding dysfunction. Moreover, urinary voiding dysfunction was more severe in SAMP6 than AKR/J mice and was associated with pronounced prostatic and urethral tissue fibrosis. CONCLUSIONS Taken together, these studies suggest that obesity, T2DM, lower urinary tract fibrosis, and urinary voiding dysfunction are inextricably and biologically linked. Prostate. PMID:23532836

The specification-based validation of reliable multicast protocol: Problem Report. M.S. Thesis

NASA Technical Reports Server (NTRS)

Wu, Yunqing

1995-01-01

Reliable Multicast Protocol (RMP) is a communication protocol that provides an atomic, totally ordered, reliable multicast service on top of unreliable IP multicasting. In this report, we develop formal models for RMP using existing automated verification systems, and perform validation on the formal RMP specifications. The validation analysis help identifies some minor specification and design problems. We also use the formal models of RMP to generate a test suite for conformance testing of the implementation. Throughout the process of RMP development, we follow an iterative, interactive approach that emphasizes concurrent and parallel progress of implementation and verification processes. Through this approach, we incorporate formal techniques into our development process, promote a common understanding for the protocol, increase the reliability of our software, and maintain high fidelity between the specifications of RMP and its implementation.

Using a Self-Control Training Procedure To Increase Appropriate Behavior.

ERIC Educational Resources Information Center

Dixon, Mark R.; Hayes, Linda J.; Binder, Lisa M.; Manthey, Sharon; Sigman, Connie; Zdanowski, Darlene M.

1998-01-01

A study evaluated teaching a technique for self-control to three adults with developmental disabilities. Concurrent fixed-duration/progressive-duration reinforcement schedules were introduced in which both smaller and larger reinforcers were available immediately. When progressively increasing delays were introduced for the larger reinforcer,…

Concurrent apatinib and local radiation therapy for advanced gastric cancer

PubMed Central

Zhang, Ming; Deng, Weiye; Cao, Xiaoci; Shi, Xiaoming; Zhao, Huanfen; Duan, Zheping; Lv, Bonan; Liu, Bin

2017-01-01

Abstract Rationale: Apatinib is a novel anti-angiogenic agent targeting vascular endothelial growth factor receptor-2, which is effective in patients with chemotherapy-refractory gastric cancer. There are no reports of concurrent apatinib with local radiation therapy in elderly patients with advanced gastric cancer. Patient concerns and Diagnoses: we present the first published report of a 70-year-old male patient with advanced gastric cancer who received concurrent apatinib and local radiation therapy after failure of oxaliplatin and S-1 chemotherapy. Interventions and Outcomes: The patient received concurrent apatinib and local radiation therapy and was followed up 7 months after therapy without disease progress, 14 months later indicated extensive metastasis and this patient died of pulmonary infection. Lessons: Elderly patients with advanced gastric cancer may benefit from concurrent apatinib with local radiation therapy when chemotherapy is not tolerated or successful. Further studies are needed to investigate the clinical outcomes and toxicities associated with concurrent apatinib and radiation therapy in gastric cancer. PMID:28248891

Concurrent apatinib and local radiation therapy for advanced gastric cancer: A case report and review of the literature.

PubMed

Zhang, Ming; Deng, Weiye; Cao, Xiaoci; Shi, Xiaoming; Zhao, Huanfen; Duan, Zheping; Lv, Bonan; Liu, Bin

2017-03-01

Apatinib is a novel anti-angiogenic agent targeting vascular endothelial growth factor receptor-2, which is effective in patients with chemotherapy-refractory gastric cancer. There are no reports of concurrent apatinib with local radiation therapy in elderly patients with advanced gastric cancer. PATIENT CONCERNS AND DIAGNOSES:: we present the first published report of a 70-year-old male patient with advanced gastric cancer who received concurrent apatinib and local radiation therapy after failure of oxaliplatin and S-1 chemotherapy. The patient received concurrent apatinib and local radiation therapy and was followed up 7 months after therapy without disease progress, 14 months later indicated extensive metastasis and this patient died of pulmonary infection. Elderly patients with advanced gastric cancer may benefit from concurrent apatinib with local radiation therapy when chemotherapy is not tolerated or successful. Further studies are needed to investigate the clinical outcomes and toxicities associated with concurrent apatinib and radiation therapy in gastric cancer.

Reducing Concurrent Sexual Partnerships Among Blacks in the Rural Southeastern United States: Development of Narrative Messages for a Radio Campaign.

PubMed

Cates, Joan R; Francis, Diane B; Ramirez, Catalina; Brown, Jane D; Schoenbach, Victor J; Fortune, Thierry; Powell Hammond, Wizdom; Adimora, Adaora A

2015-01-01

In the United States, heterosexual transmission of HIV infection is dramatically higher among Blacks than among Whites. Overlapping (concurrent) sexual partnerships promote HIV transmission. The authors describe their process for developing a radio campaign (Escape the Web) to raise awareness among 18-34-year-old Black adults of the effect of concurrency on HIV transmission in the rural South. Radio is a powerful channel for the delivery of narrative-style health messages. Through six focus groups (n = 51) and 42 intercept interviews, the authors explored attitudes toward concurrency and solicited feedback on sample messages. Men were advised to (a) end concurrent partnerships and not to begin new ones; (b) use condoms consistently with all partners; and (c) tell others about the risks of concurrency and benefits of ending concurrent partnerships. The narrative portrayed risky behaviors that trigger initiation of casual partnerships. Women were advised to (a) end partnerships in which they are not their partner's only partner; (b) use condoms consistently with all partners; and (c) tell others about the risks of concurrency and benefits of ending concurrent partnerships. Messages for all advised better modeling for children.

Reducing Concurrent Sexual Partnerships Among Blacks in the Rural Southeastern United States: Development of Narrative Messages for a Radio Campaign

PubMed Central

CATES, JOAN R.; FRANCIS, DIANE B.; RAMIREZ, CATALINA; BROWN, JANE D.; SCHOENBACH, VICTOR J.; FORTUNE, THIERRY; HAMMOND, WIZDOM POWELL; ADIMORA, ADAORA A.

2015-01-01

In the United States, heterosexual transmission of HIV infection is dramatically higher among Blacks than among Whites. Overlapping (concurrent) sexual partnerships promote HIV transmission. The authors describe their process for developing a radio campaign (Escape the Web) to raise awareness among 18–34-year-old Black adults of the effect of concurrency on HIV transmission in the rural South. Radio is a powerful channel for the delivery of narrative-style health messages. Through six focus groups (n = 51) and 42 intercept interviews, the authors explored attitudes toward concurrency and solicited feedback on sample messages. Men were advised to (a) end concurrent partnerships and not to begin new ones; (b) use condoms consistently with all partners; and (c) tell others about the risks of concurrency and benefits of ending concurrent partnerships. The narrative portrayed risky behaviors that trigger initiation of casual partnerships. Women were advised to (a) end partnerships in which they are not their partner’s only partner; (b) use condoms consistently with all partners; and (c) tell others about the risks of concurrency and benefits of ending concurrent partnerships. Messages for all advised better modeling for children. PMID:26134387

Concurrent progressive ratio schedules: Effects of reinforcer probability on breakpoint and response allocation.

PubMed

Jarmolowicz, David P; Sofis, Michael J; Darden, Alexandria C

2016-07-01

Although progressive ratio (PR) schedules have been used to explore effects of a range of reinforcer parameters (e.g., magnitude, delay), effects of reinforcer probability remain underexplored. The present project used independently progressing concurrent PR PR schedules to examine effects of reinforcer probability on PR breakpoint (highest completed ratio prior to a session terminating 300s pause) and response allocation. The probability of reinforcement on one lever remained at 100% across all conditions while the probability of reinforcement on the other lever was systematically manipulated (i.e., 100%, 50%, 25%, 12.5%, and a replication of 25%). Breakpoints systematically decreased with decreasing reinforcer probabilities while breakpoints on the control lever remained unchanged. Patterns of switching between the two levers were well described by a choice-by-choice unit price model that accounted for the hyperbolic discounting of the value of probabilistic reinforcers. Copyright © 2016 Elsevier B.V. All rights reserved.

Assessing Self-Control Training in Children with Attention Deficit Hyperactivity Disorder

ERIC Educational Resources Information Center

Bloh, Christopher

2009-01-01

This study examined the use of a progressive delay procedure with and without a concurrent activity to teach self-control to children with attention deficit hyperactivity disorder. Three participants were initially required to wait progressively longer periods of time for access to preferred edible reinforcers. After demonstrating this…

A Concurrent Mixed Method Study of Preservice Teachers' Attitudes toward the Inclusion of Students with Autism in General Education Classrooms

ERIC Educational Resources Information Center

Cordoves, Jose L.

2013-01-01

Research indicates that many general education teachers have negative attitudes about the inclusion of students with disabilities. Ways to promote positive attitudes in preservice teachers are needed, particularly in Puerto Rico, where the autism identification rate is the highest in the world. The purposes of this concurrent mixed method study…

Radiation Therapy in the Management of Head-and-Neck Cancer of Unknown Primary Origin: How Does the Addition of Concurrent Chemotherapy Affect the Therapeutic Ratio?

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

Chen, Allen M., E-mail: allen.chen@ucdmc.ucdavis.edu; Farwell, D. Gregory; Lau, Derick H.

2011-10-01

Purpose: To determine how the addition of cisplatin-based concurrent chemotherapy to radiation therapy influences outcomes among a cohort of patients treated for head-and-neck cancer of unknown primary origin. Methods and Materials: The medical records of 60 consecutive patients treated by radiation therapy for squamous cell carcinoma of the head and neck presenting as cervical lymph node metastasis of occult primary origin were reviewed. Thirty-two patients (53%) were treated by concurrent chemoradiation, and 28 patients (47%) were treated by radiation therapy alone. Forty-five patients (75%) received radiation therapy after surgical resection, and 15 patients (25%) received primary radiation therapy. Thirty-five patientsmore » (58%) were treated by intensity-modulated radiotherapy. Results: The 2-year estimates of overall survival, local-regional control, and progression-free survival were 89%, 89%, and 79%, respectively, among patients treated by chemoradiation, compared to 90%, 92%, and 83%, respectively, among patients treated by radiation therapy alone (p > 0.05, for all). Exploratory analysis failed to identify any subset of patients who benefited from the addition of concurrent chemotherapy to radiation therapy. The use of concurrent chemotherapy was associated with a significantly increased incidence of Grade 3+ acute and late toxicity (p < 0.001, for both). Conclusions: Concurrent chemoradiation is associated with significant toxicity without a clear advantage to overall survival, local-regional control, and progression-free survival in the treatment of head-and-neck cancer of unknown primary origin. Although selection bias cannot be ignored, prospective data are needed to further address this question.« less

Is the progression free survival advantage of concurrent gemcitabine plus cisplatin and radiation followed by adjuvant gemcitabine and cisplatin in patients with advanced cervical cancer worth the additional cost? A cost-effectiveness analysis.

PubMed

Smith, B; Cohn, D E; Clements, A; Tierney, B J; Straughn, J M

2013-09-01

The objective of this study is to determine whether concurrent and adjuvant chemoradiation with gemcitabine/cisplatin is cost-effective in patients with stage IIB to IVA cervical cancer. A cost-effectiveness model compared two arms of the trial performed by Duenas-Gonzalez et al. [1]: concurrent and adjuvant chemoradiation with gemcitabine/cisplatin (RT/GC+GC) versus concurrent radiation with cisplatin (RT/C). Major adverse events (AEs) and progression free survival (PFS) rates of each arm were incorporated in the model. AEs were defined as any hospitalization including grade 4 anemia, grade 4 neutropenia, and death. Medicare data and literature review were used to estimate costs. Incremental cost-effectiveness ratios (ICERs) per progression-free life-year saved (PF-LYS) were calculated. Sensitivity analyses were performed for pertinent uncertainties. For 10,000 women with locally advanced cervical cancer, the cost of therapy and AEs was $173.9 million (M) for RT/C versus $259.8M for RT/GC+GC. There were 879 additional 3-year progression-free survivors in the RT/GC+GC arm. The ICER for RT/GC+GC was $97,799 per PF-LYS. When the rate of hospitalization was equalized to 4.3%, the ICER for RT/GC+GC exceeded $80,000. The resultant ICER when increasing PFS in the RT/GC+GC arm by 5% was $62,605 per PF-LYS. When the cost of chemotherapy was decreased by 50%, the ICER was below $50,000 at $41,774 per PF-LYS. Radiation and gemcitabine/cisplatin for patients with stage IIB to IVA cervical cancer are not cost-effective. The increased financial burden of radiation with gemcitabine/cisplatin and associated toxicities appears to outweigh the benefit of increased 3-year PFS and is primarily dependent on chemotherapy drug costs. Copyright © 2013 Elsevier Inc. All rights reserved.

Requiem for a Data Base System.

DTIC Science & Technology

1979-01-18

were defined -- - 2) the final syntax and semantics of QUEL were defined 3) protection was figured out 14) EQUEL was designed 5) concurrency control and...features which were not thought about in the initial design (such as concurrency control and recovery) and began worrying about distributed data...made in progress rather than on eventual corrections. Some attention is also given to the role of structured design in a data base system implementation

Generation of Marker-free Transgenic Plants Concurrently Resistant to a DNA Geminivirus and a RNA Tospovirus

PubMed Central

Yang, Ching-Fu; Chen, Kuan-Chun; Cheng, Ying-Hui; Raja, Joseph A. J.; Huang, Ya-Ling; Chien, Wan-Chu; Yeh, Shyi-Dong

2014-01-01

Global threats of ssDNA geminivirus and ss(-)RNA tospovirus on crops necessitate the development of transgenic resistance. Here, we constructed a two-T DNA vector carrying a hairpin of the intergenic region (IGR) of Ageratum yellow vein virus (AYVV), residing in an intron inserted in an untranslatable nucleocapsid protein (NP) fragment of Melon yellow spot virus (MYSV). Transgenic tobacco lines highly resistant to AYVV and MYSV were generated. Accumulation of 24-nt siRNA, higher methylation levels on the IGR promoters of the transgene, and suppression of IGR promoter activity of invading AYVV indicate that AYVV resistance is mediated by transcriptional gene silencing. Lack of NP transcript and accumulation of corresponding siRNAs indicate that MYSV resistance is mediated through post-transcriptional gene silencing. Marker-free progenies with concurrent resistance to both AYVV and MYSV, stably inherited as dominant nuclear traits, were obtained. Hence, we provide a novel way for concurrent control of noxious DNA and RNA viruses with less biosafety concerns. PMID:25030413

Three gene expression vector sets for concurrently expressing multiple genes in Saccharomyces cerevisiae.

PubMed

Ishii, Jun; Kondo, Takashi; Makino, Harumi; Ogura, Akira; Matsuda, Fumio; Kondo, Akihiko

2014-05-01

Yeast has the potential to be used in bulk-scale fermentative production of fuels and chemicals due to its tolerance for low pH and robustness for autolysis. However, expression of multiple external genes in one host yeast strain is considerably labor-intensive due to the lack of polycistronic transcription. To promote the metabolic engineering of yeast, we generated systematic and convenient genetic engineering tools to express multiple genes in Saccharomyces cerevisiae. We constructed a series of multi-copy and integration vector sets for concurrently expressing two or three genes in S. cerevisiae by embedding three classical promoters. The comparative expression capabilities of the constructed vectors were monitored with green fluorescent protein, and the concurrent expression of genes was monitored with three different fluorescent proteins. Our multiple gene expression tool will be helpful to the advanced construction of genetically engineered yeast strains in a variety of research fields other than metabolic engineering. © 2014 Federation of European Microbiological Societies. Published by John Wiley & Sons Ltd. All rights reserved.

Paradox in Progressive Educational Reform: The South and the Education of Blacks in the Depression Years

ERIC Educational Resources Information Center

Goodenow, Ronald K.

1978-01-01

Progressive educational reform in the South during the Great Depression is examined. Ways in which educational change seemingly functioned to serve modernization while concurrently maintaining racist patterns are illustrated. It is suggested that fundamental change in the conditions of oppression may not be possible without addressing the…

Internet-based group contingency management to promote abstinence from cigarette smoking: A feasibility study

PubMed Central

Meredith, Steven E.; Grabinski, Michael J.; Dallery, Jesse

2011-01-01

Background In contingency management (CM) interventions, monetary consequences are contingent on evidence of drug abstinence. Typically, these consequences are contingent on individual performance. Consequences contingent on group performance may promote social support (e.g., praise). Methods Thus, to combine social support with the monetary incentives of CM, we integrated independent and interdependent group contingencies of reinforcement into an Internet-based intervention to promote smoking abstinence. Breath carbon monoxide (CO) measures were compared between treatment conditions and a baseline control condition. Thirteen participants were divided into 5 groups or “teams” (n = 2–3 per team). Each participant submitted video recordings of CO measurement twice daily via the Internet. Teammates could monitor each other’s progress and communicate with one another through an online peer support forum. During a 4-day tapering condition, vouchers exchangeable for goods were contingent on gradual reductions in breath CO. During a 10-day abstinence induction condition, vouchers were contingent on abstinence (CO ≤4 ppm). In both treatment conditions, concurrent independent and interdependent group contingencies were arranged (i.e., a mixed contingency arrangement). Results Less than 1% of CO samples submitted during baseline were ≤4 ppm, compared to 57% submitted during abstinence induction. Sixty-five percent of participants’ comments on the online peer support forum were rated as positive by independent observers. Participants rated the intervention favorably on a treatment acceptability questionnaire. Conclusion The results suggest that the intervention is feasible and acceptable for promoting abstinence from cigarette smoking. PMID:21414733

Preliminary Results of Whole Brain Radiotherapy With Concurrent Trastuzumab for Treatment of Brain Metastases in Breast Cancer Patients

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

Chargari, Cyrus; Idrissi, Hind Riahi; Pierga, Jean-Yves

2011-11-01

Purpose: To assess the use of trastuzumab concurrently with whole brain radiotherapy (WBRT) for patients with brain metastases from human epidermal growth factor receptor-2-positive breast cancer. Methods and Materials: Between April 2001 and April 2007, 31 patients with brain metastases from human epidermal growth factor receptor-2-positive breast cancer were referred for WBRT with concurrent trastuzumab. At brain progression, the median age was 55 years (range, 38-73), and all patients had a performance status of 0-2. The patients received trastuzumab 2 mg/kg weekly (n = 17) or 6 mg/kg repeated every 21 days (n = 14). In 26 patients, concurrent WBRTmore » delivered 30 Gy in 10 daily fractions. In 6 patients, other fractionations were chosen because of either poor performance status or patient convenience. Results: After WBRT, radiologic responses were observed in 23 patients (74.2%), including 6 (19.4%) with a complete radiologic response and 17 (54.8%) with a partial radiologic response. Clinical responses were observed in 27 patients (87.1%). The median survival time from the start of WBRT was 18 months (range, 2-65). The median interval to brain progression was 10.5 months (range, 2-27). No Grade 2 or greater acute toxicity was observed. Conclusion: The low toxicity of trastuzumab concurrently with WBRT should probably not justify delays. Although promising, these preliminary data warrant additional validation of trastuzumab as a potential radiosensitizer for WBRT in brain metastases from breast cancer in the setting of a clinical trial.« less

Progression of abnormal MIB-1 staining patterns of reserve cells in cervical smears from women ultimately developing high grade squamous intraepithelial lesions.

PubMed

Siemens, Frederike C; van Haaften, Carolien; Kuijpers, Johan C; Helmerhorst, Theo J M; Boon, Mathilde E

2006-01-01

To assess, in a longitudinal study in women diagnosed with high grade squamous epithelial lesion (HSIL), the progression over time of proliferative activity in reserve cells using population screening cervical cytology specimens. Twenty consecutive, unselected patients with HSIL lesions were part of the national cervical screening program. From the archives, for each patient, the last prior normal population screening smear was included in the study. Concurrent sets of cervical smears from 80 age-matched women without pathology formed the controls. The original slides were stained using MIB-1 monoclonal antibody. The fraction of MIB-1-positive reserve cells was assessed using systematic random sampling and running progressive means assessment to ensure a sufficient sample size. The proliferation fraction in reserve cells of HSIL patients was significantly raised (mean, 65.0%; range, 53.5-94.1%; p < 0.01) as compared with that in concurrent controls (mean, 12.8%; range, 1.9-45.4%). Prior smears from HSIL patients, although without morphologic abnormalities, had abnormally high proliferation fractions (mean, 59.1%; range, 1.0-94.7%), significantly raised over those from concurrent controls (mean, 9.4%; range In population-based cervical smear screening, HSIL patients already have abnormally raised proliferation fractions of reserve cells, even without morphologic changes in squamous cells, 1-5 (mean, 3.6) years prior to diagnosis.

Cell Division Synchronization

DTIC Science & Technology

The report summarizes the progress in the design and construction of automatic equipment for synchronizing cell division in culture by periodic...Concurrent experiments in hypothermic synchronization of algal cell division are reported.

Association of perceived partner non-monogamy with prevalent and incident sexual concurrency

PubMed Central

Sanchez, Diana M; Schoenbach, Victor J; Harvey, S Marie; Warren, Jocelyn T; Adimora, Adaora A; Poole, Charles; Leone, Peter A; Agnew, Christopher R

2016-01-01

Objectives Concurrency is suggested as an important factor in sexually transmitted infection transmission and acquisition, though little is known regarding factors that may predict concurrency initiation. We examined the association between perception of a partner’s non-monogamy (PPNM) and simultaneous or subsequent concurrency among at-risk heterosexual young adults in the Los Angeles area. Methods We used Poisson regression models to estimate the relationship between PPNM and incident concurrency among 536 participants participating in a cohort study, interviewed at 4-month periods during 1 year. Concurrency was defined as an overlap in reported sexual partnership dates; PPNM was defined as believing a partner was also having sex with someone else. Results Participants (51% female; 30% non-Hispanic white, 28% non-Hispanic black, 27% Hispanic/Latino) had a mean age of 23 years and lifetime median of nine sex partners. At each interview (baseline, 4-month, 8-month and 12-month), 4-month concurrency prevalence was, respectively, 38.8%, 27.4%, 23.1% and 24.5%. Four-month concurrency incidence at 4, 8 and 12 months was 8.5%, 10.6% and 17.8%, respectively. Participants with recent PPNM were more likely to initiate concurrency (crude 4-month RR=4.6; 95% CI 3.0, 7.0; adjusted 4-month RR=4.0, 95% CI 2.6 to 6.1). Conclusions Recent PPNM was associated with incident concurrency. Among young adults, onset of concurrency may be stimulated, relatively quickly, by the PPNM. Programmes which promote relationship communication skills and explicit monogamy expectations may help reduce concurrency. PMID:26574570

How Formal Dynamic Verification Tools Facilitate Novel Concurrency Visualizations

NASA Astrophysics Data System (ADS)

Aananthakrishnan, Sriram; Delisi, Michael; Vakkalanka, Sarvani; Vo, Anh; Gopalakrishnan, Ganesh; Kirby, Robert M.; Thakur, Rajeev

With the exploding scale of concurrency, presenting valuable pieces of information collected by formal verification tools intuitively and graphically can greatly enhance concurrent system debugging. Traditional MPI program debuggers present trace views of MPI program executions. Such views are redundant, often containing equivalent traces that permute independent MPI calls. In our ISP formal dynamic verifier for MPI programs, we present a collection of alternate views made possible by the use of formal dynamic verification. Some of ISP’s views help pinpoint errors, some facilitate discerning errors by eliminating redundancy, while others help understand the program better by displaying concurrent even orderings that must be respected by all MPI implementations, in the form of completes-before graphs. In this paper, we describe ISP’s graphical user interface (GUI) capabilities in all these areas which are currently supported by a portable Java based GUI, a Microsoft Visual Studio GUI, and an Eclipse based GUI whose development is in progress.

EXPERIMENTAL ANALYSIS OF THE CONTROL OF SPEECH PRODUCTION AND PERCEPTION. PROGRESS REPORT NO. I, FEBRUARY 1--SEPTEMBER 1, 1961.

ERIC Educational Resources Information Center

LANE, HARLAN; AND OTHERS

THIS DOCUMENT IS THE FIRST IN A SERIES REPORTING ON PROGRESS OF AN EXPERIMENTAL RESEARCH PROGRAM IN SPEECH CONTROL. THE TOPICS DISCUSSED ARE--(1) THE DISCONTINUITY OF AUDITORY DISCRIMINATION LEARNING IN HUMAN ADULTS, (2) DISCRIMINATIVE CONTROL OF CONCURRENT RESPONSES--THE RELATIONS AMONG RESPONSE FREQUENCY, LATENCY, AND TOPOGRAPHY IN AUDITORY…

Association of perceived partner non-monogamy with prevalent and incident sexual concurrency.

PubMed

Sanchez, Diana M; Schoenbach, Victor J; Harvey, S Marie; Warren, Jocelyn T; Adimora, Adaora A; Poole, Charles; Leone, Peter A; Agnew, Christopher R

2016-06-01

Concurrency is suggested as an important factor in sexually transmitted infection transmission and acquisition, though little is known regarding factors that may predict concurrency initiation. We examined the association between perception of a partner's non-monogamy (PPNM) and simultaneous or subsequent concurrency among at-risk heterosexual young adults in the Los Angeles area. We used Poisson regression models to estimate the relationship between PPNM and incident concurrency among 536 participants participating in a cohort study, interviewed at 4-month periods during 1 year. Concurrency was defined as an overlap in reported sexual partnership dates; PPNM was defined as believing a partner was also having sex with someone else. Participants (51% female; 30% non-Hispanic white, 28% non-Hispanic black, 27% Hispanic/Latino) had a mean age of 23 years and lifetime median of nine sex partners. At each interview (baseline, 4-month, 8-month and 12-month), 4-month concurrency prevalence was, respectively, 38.8%, 27.4%, 23.1% and 24.5%. Four-month concurrency incidence at 4, 8 and 12 months was 8.5%, 10.6% and 17.8%, respectively. Participants with recent PPNM were more likely to initiate concurrency (crude 4-month RR=4.6; 95% CI 3.0, 7.0; adjusted 4-month RR=4.0, 95% CI 2.6 to 6.1). Recent PPNM was associated with incident concurrency. Among young adults, onset of concurrency may be stimulated, relatively quickly, by the PPNM. Programmes which promote relationship communication skills and explicit monogamy expectations may help reduce concurrency. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Prognostic implication of simultaneous anemia and lymphopenia during concurrent chemoradiotherapy in cervical squamous cell carcinoma.

PubMed

Cho, Oyeon; Chun, Mison; Oh, Young-Taek; Noh, O Kyu; Chang, Suk-Joon; Ryu, Hee-Sug; Lee, Eun Ju

2017-10-01

Radioresistance often leads to poor survival in concurrent chemoradiotherapy-treated cervical squamous cell carcinoma, and reliable biomarkers can improve prognosis. We compared the prognostic potential of hemoglobin, absolute neutrophil count, and absolute lymphocyte count with that of squamous cell carcinoma antigen in concurrent chemoradiotherapy-treated squamous cell carcinoma. We analyzed 152 patients with concurrent chemoradiotherapy and high-dose-rate intracavitary brachytherapy-treated cervical squamous cell carcinoma. Hemoglobin, absolute neutrophil count, absolute lymphocyte count, and squamous cell carcinoma antigen were quantitated and correlated with survival, using Cox regression, receiver operating characteristic curve analysis, and Kaplan-Meier plots. Both hemoglobin and absolute lymphocyte count in the second week of concurrent chemoradiotherapy (Hb2 and ALC2) and squamous cell carcinoma antigen in the third week of concurrent chemoradiotherapy (mid-squamous cell carcinoma antigen) correlated significantly with disease-specific survival and progression-free survival. The ratio of high-dose-rate intracavitary brachytherapy dose to total dose (high-dose-rate intracavitary brachytherapy ratio) correlated significantly with progression-free survival. Patients with both low Hb2 (≤11 g/dL) and ALC2 (≤639 cells/µL) showed a lower 5-year disease-specific survival rate than those with high Hb2 and/or ALC2, regardless of mid-squamous cell carcinoma antigen (mid-squamous cell carcinoma antigen: ≤4.7 ng/mL; 5-year disease-specific survival rate: 85.5% vs 94.6%, p = 0.0096, and mid-squamous cell carcinoma antigen: >4.7 ng/mL; 5-year disease-specific survival rate: 43.8% vs 66.7%, p = 0.192). When both Hb2 and ALC2 were low, the low high-dose-rate intracavitary brachytherapy ratio (≤0.43) subgroup displayed significantly lower 5-year disease-specific survival rate compared to the subgroup high high-dose-rate intracavitary brachytherapy ratio (>0.43) (62.5% vs 88.2%, p = 0.0067). Patients with both anemia and lymphopenia during concurrent chemoradiotherapy showed poor survival, independent of mid-squamous cell carcinoma antigen, and escalating high-dose-rate intracavitary brachytherapy ratio might improve survival.

Concurrent Androgen Deprivation Therapy During Salvage Prostate Radiotherapy Improves Treatment Outcomes in High-Risk Patients

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

Soto, Daniel E., E-mail: dsoto2@partners.org; Passarelli, Michael N.; Daignault, Stephanie

2012-03-01

Purpose: To determine whether concurrent androgen deprivation therapy (ADT) during salvage radiotherapy (RT) improves prostate cancer treatment outcomes. Methods and Materials: A total of 630 postprostatectomy patients were retrospectively identified who were treated with three-dimensional conformal RT. Of these, 441 were found to be treated for salvage indications. Biochemical failure was defined as prostate-specific antigen (PSA) of 0.2 ng/mL or greater above nadir with another PSA increase or the initiation of salvage ADT. Progression-free survival (PFS) was defined as the absence of biochemical failure, continued PSA rise despite salvage therapy, initiation of systemic therapy, clinical progression, or distant failure. Multivariate-adjustedmore » Cox proportional hazards modeling was performed to determine which factors predict PFS. Results: Low-, intermediate-, and high-risk patients made up 10%, 24%, and 66% of patients, respectively. The mean RT dose was 68 Gy. Twenty-four percent of patients received concurrent ADT (cADT). Regional pelvic nodes were treated in 16% of patients. With a median follow-up of 3 years, the 3-year PFS was 4.0 years for cADT vs. 3.4 years for cADT patients (p = 0.22). Multivariate analysis showed that concurrent ADT (p = 0.05), Gleason score (p < 0.001), and pre-RT PSA (p = 0.03) were independent predictors of PFS. When patients were stratified by risk group, the benefits of cADT (hazard ratio, 0.65; p = 0.046) were significant only for high-risk patients. Conclusions: This retrospective study showed a PFS benefit of concurrent ADT during salvage prostate RT. This benefit was observed only in high-risk patients.« less

Patterns of Failure After Concurrent Bevacizumab and Hypofractionated Stereotactic Radiation Therapy for Recurrent High-Grade Glioma

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

Shapiro, Lauren Q.; Beal, Kathryn, E-mail: bealk@mskcc.org; Goenka, Anuj

2013-03-01

Purpose: Concurrent bevacizumab with hypofractionated stereotactic radiation therapy (HSRT) is safe and effective for the treatment of recurrent high-grade gliomas (HGG). The objective of this study was to characterize the patterns of failure after this treatment regimen. Methods and Materials: Twenty-four patients with recurrent enhancing HGG were previously treated on an institutional review board-approved protocol of concurrent bevacizumab and reirradiation. Patients received 30 Gy in 5 fractions to the recurrent tumor with HSRT. Brain magnetic resonance imaging (MRI) was performed every 2 cycles, and bevacizumab was continued until clinical or radiographic tumor progression according to the criteria of Macdonald etmore » al. MRI at the time of progression was fused to the HSRT treatment plan, and the location of recurrence was classified on the basis of volume within the 95% isodose line. Outcomes based on patient characteristics, tumor grade, recurrence pattern, and best response to treatment were analyzed by the Kaplan-Meier method. Results: Twenty-two patients experienced either clinical or radiographic progression. Recurrent tumor was enhancing in 15 (71.4%) and nonenhancing in 6 (28.6%) patients. Eleven patients (52.4%) had recurrence within the radiation field, 5 patients (23.8%) had marginal recurrence, and 5 patients had recurrence outside the radiation field. Pattern of enhancement and location of failure did not correlate with overall survival or progression-free survival. Radiographic response was the only variable to significantly correlate with progression-free survival. Conclusions: Despite the promising initial response seen with the addition of HSRT to bevacizumab as salvage treatment for recurrent HGG, approximately half of patients ultimately still experience failure within the radiation field. The rate of local failure with the addition of HSRT seems to be lower than that seen with bevacizumab alone in the salvage setting. Our data underscore the radioresistance of HGG and the need for better salvage treatments.« less

Prognostic Significance of Carbohydrate Antigen 19-9 in Unresectable Locally Advanced Pancreatic Cancer Treated With Dose-Escalated Intensity Modulated Radiation Therapy and Concurrent Full-Dose Gemcitabine: Analysis of a Prospective Phase 1/2 Dose Escalation Study

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

Vainshtein, Jeffrey M., E-mail: jvainsh@med.umich.edu; Schipper, Matthew; Zalupski, Mark M.

2013-05-01

Purpose: Although established in the postresection setting, the prognostic value of carbohydrate antigen 19-9 (CA19-9) in unresectable locally advanced pancreatic cancer (LAPC) is less clear. We examined the prognostic utility of CA19-9 in patients with unresectable LAPC treated on a prospective trial of intensity modulated radiation therapy (IMRT) dose escalation with concurrent gemcitabine. Methods and Materials: Forty-six patients with unresectable LAPC were treated at the University of Michigan on a phase 1/2 trial of IMRT dose escalation with concurrent gemcitabine. CA19-9 was obtained at baseline and during routine follow-up. Cox models were used to assess the effect of baseline factorsmore » on freedom from local progression (FFLP), distant progression (FFDP), progression-free survival (PFS), and overall survival (OS). Stepwise forward regression was used to build multivariate predictive models for each endpoint. Results: Thirty-eight patients were eligible for the present analysis. On univariate analysis, baseline CA19-9 and age predicted OS, CA19-9 at baseline and 3 months predicted PFS, gross tumor volume (GTV) and black race predicted FFLP, and CA19-9 at 3 months predicted FFDP. On stepwise multivariate regression modeling, baseline CA19-9, age, and female sex predicted OS; baseline CA19-9 and female sex predicted both PFS and FFDP; and GTV predicted FFLP. Patients with baseline CA19-9 ≤90 U/mL had improved OS (median 23.0 vs 11.1 months, HR 2.88, P<.01) and PFS (14.4 vs 7.0 months, HR 3.61, P=.001). CA19-9 progression over 90 U/mL was prognostic for both OS (HR 3.65, P=.001) and PFS (HR 3.04, P=.001), and it was a stronger predictor of death than either local progression (HR 1.46, P=.42) or distant progression (HR 3.31, P=.004). Conclusions: In patients with unresectable LAPC undergoing definitive chemoradiation therapy, baseline CA19-9 was independently prognostic even after established prognostic factors were controlled for, whereas CA19-9 progression strongly predicted disease progression and death. Future trials should stratify by baseline CA19-9 and incorporate CA19-9 progression as a criterion for progressive disease.« less

Whatever happened to "What might have been"? Regrets, happiness, and maturity.

PubMed

King, Laura A; Hicks, Joshua A

2007-10-01

Although lost opportunities and mistaken expectations are unpleasant to think and talk about, these experiences may have a role to play in personality development. Drawing on research using narratives of lost possible selves, the authors review the relations of regrettable experiences to 2 important and independent aspects of maturity, happiness and complexity. Thinking about a lost possible self is related to concurrent regrets, distress, and lowered well-being; however, elaborating on a lost possible self is related, concurrently, to complexity and predicts complexity, prospectively, over time. In this article, the authors describe the role that regrettable experiences have in promoting both happiness and complexity. Finally, expanding on previous work, the authors examine potential affordances of happy maturity and suggest psychological capacities that may promote happy maturity. Copyright 2007 APA, all rights reserved.

Preexisting MEK1 Exon 3 Mutations in V600E/KBRAF Melanomas Do Not Confer Resistance to BRAF Inhibitors

PubMed Central

Shi, Hubing; Moriceau, Gatien; Kong, Xiangju; Koya, Richard C.; Nazarian, Ramin; Pupo, Gulietta M.; Bacchiocchi, Antonella; Dahlman, Kimberly B.; Chmielowski, Bartosz; Sosman, Jeffrey A.; Halaban, Ruth; Kefford, Richard F.; Long, Georgina V.; Ribas, Antoni; Lo, Roger S.

2012-01-01

BRAF inhibitors (BRAFi) induce antitumor responses in nearly 60% of patients with advanced V600E/KBRAF melanomas. Somatic activating MEK1 mutations are thought to be rare in melanomas, but their potential concurrence with V600E/KBRAF may be selected for by BRAFi. We sequenced MEK1/2 exon 3 in melanomas at baseline and upon disease progression. Of 31 baseline V600E/KBRAF melanomas, 5 (16%) carried concurrent somatic BRAF/MEK1 activating mutations. Three of 5 patients with BRAF/MEK1 double-mutant baseline melanomas showed objective tumor responses, consistent with the overall 60% frequency. No MEK1 mutation was found in disease progression melanomas, except when it was already identified at baseline. MEK1-mutant expression in V600E/KBRAF melanoma cell lines resulted in no significant alterations in p-ERK1/2 levels or growth-inhibitory sensitivities to BRAFi, MEK1/2 inhibitor (MEKi), or their combination. Thus, activating MEK1 exon 3 mutations identified herein and concurrent with V600E/KBRAF do not cause BRAFi resistance in melanoma. SIGNIFICANCE As BRAF inhibitors gain widespread use for treatment of advanced melanoma, bio-markers for drug sensitivity or resistance are urgently needed. We identify here concurrent activating mutations in BRAF and MEK1 in melanomas and show that the presence of a downstream mutation in MEK1 does not necessarily make BRAF–mutant melanomas resistant to BRAF inhibitors. PMID:22588879

A Novel, Non-Apoptotic Role for Scythe/BAT3: A Functional Switch between the Pro- and Anti-Proliferative Roles of p21 during the Cell Cycle

PubMed Central

Yong, Sheila T.; Wang, Xiao-Fan

2012-01-01

Background Scythe/BAT3 is a member of the BAG protein family whose role in apoptosis has been extensively studied. However, since the developmental defects observed in Bat3-null mouse embryos cannot be explained solely by defects in apoptosis, we investigated whether BAT3 is also involved in cell-cycle progression. Methods/Principal Findings Using a stable-inducible Bat3-knockdown cellular system, we demonstrated that reduced BAT3 protein level causes a delay in both G1/S transition and G2/M progression. Concurrent with these changes in cell-cycle progression, we observed a reduction in the turnover and phosphorylation of the CDK inhibitor p21, which is best known as an inhibitor of DNA replication; however, phosphorylated p21 has also been shown to promote G2/M progression. Our findings indicate that in Bat3-knockdown cells, p21 continues to be synthesized during cell-cycle phases that do not normally require p21, resulting in p21 protein accumulation and a subsequent delay in cell-cycle progression. Finally, we showed that BAT3 co-localizes with p21 during the cell cycle and is required for the translocation of p21 from the cytoplasm to the nucleus during the G1/S transition and G2/M progression. Conclusion: Our study reveals a novel, non-apoptotic role for BAT3 in cell-cycle regulation. By maintaining a low p21 protein level during the G1/S transition, BAT3 counteracts the inhibitory effect of p21 on DNA replication and thus enables the cells to progress from G1 to S phase. Conversely, during G2/M progression, BAT3 facilitates p21 phosphorylation by cyclin A/Cdk2, an event required for G2/M progression. BAT3 modulates these pro- and anti-proliferative roles of p21 at least in part by regulating cyclin A abundance, as well as p21 translocation between the cytoplasm and the nucleus to ensure that it functions in the appropriate intracellular compartment during each phase of the cell cycle. PMID:22761665

Continued EGFR-TKI with concurrent radiotherapy to improve time to progression (TTP) in patients with locally progressive non-small cell lung cancer (NSCLC) after front-line EGFR-TKI treatment.

PubMed

Wang, Y; Li, Y; Xia, L; Niu, K; Chen, X; Lu, D; Kong, R; Chen, Z; Sun, J

2018-03-01

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is the optimal treatment for EGFR-mutant advanced non-small cell lung cancer (NSCLC). However, most patients developed systemic or local progression due to acquired EGFR-TKI resistance. This retrospective study aimed to evaluate the feasibility of continued EGFR-TKI with concurrent radiotherapy (CTCRT) in patients with local progression after front-line EGFR-TKI treatment. Advanced NSCLC patients with active EGFR mutation who received EGFR-TKI were treated with CTCRT after local progression. Medical data were analyzed for time to progression (TTP), progression-free survival (PFS), tumor response rate, overall survival (OS) and adverse events. A total of 50 irradiated lesions from 44 patients were included. Median TTP and PFS of measurable lesions (n = 31) were both significantly prolonged after local radiotherapy (TTP1 + TTP2 vs. TTP1: 21.7 vs. 16.0 months, P = 0.010; PFS1 + PFS2 vs. PFS1: 21.3 vs. 16.0 months, P = 0.027). For all lesions (n = 50), objective response rate (ORR) and local tumor control rate (LCR) were 54.0 and 84.0%, respectively. Median OS was 26.6 months. There were no serious adverse events before or after radiotherapy. The treatment modality of CTCRT is considerable and effective for EGFR-mutant NSCLC patients even with local failure from front-line EGFR-TKI treatment.

Erythrocyte membrane-encapsulated celecoxib improves the cognitive decline of Alzheimer's disease by concurrently inducing neurogenesis and reducing apoptosis in APP/PS1 transgenic mice.

PubMed

Guo, Jing-Wen; Guan, Pei-Pei; Ding, Wei-Yan; Wang, Si-Ling; Huang, Xue-Shi; Wang, Zhan-You; Wang, Pu

2017-11-01

Alzheimer's disease (AD) is characterized by the loss of neurogenesis and excessive induction of apoptosis. The induction of neurogenesis and inhibition of apoptosis may be a promising therapeutic approach to combating the disease. Celecoxib (CB), a cyclooxygenase-2 specific inhibitor, could offer neuroprotection. Specifically, the CB-encapsulated erythrocyte membranes (CB-RBCMs) sustained the release of CB over a period of 72 h in vitro and exhibited high brain biodistribution efficiency following intranasal administration, which resulted in the clearance of aggregated β-amyloid proteins (Aβ) in neurons. The high accumulation of the CB-RBCMs in neurons resulted in a decrease in the neurotoxicity of CB and an increase in the migratory activity of neurons, and alleviated cognitive decline in APP/PS1 transgenic (Tg) mice. Indeed, COX-2 metabolic products including prostaglandin E2 (PGE 2 ) and PGD 2 , PGE 2 induced neurogenesis by enhancing the expression of SOD2 and 14-3-3ζ, and PGD 2 stimulated apoptosis by increasing the expression of BIK and decreasing the expression of ARRB1. To this end, the CB-RBCMs achieved better effects on concurrently increasing neurogenesis and decreasing apoptosis than the phospholipid membrane-encapsulated CB liposomes (CB-PSPD-LPs), which are critical for the development and progression of AD. Therefore, CB-RBCMs provide a rational design to treat AD by promoting the self-repairing capacity of the brain. Copyright © 2017 Elsevier Ltd. All rights reserved.

Inflammation-induced reversible switch of the neuron-specific enolase promoter from Purkinje neurons to Bergmann glia.

PubMed

Sawada, Yusuke; Konno, Ayumu; Nagaoka, Jun; Hirai, Hirokazu

2016-06-13

Neuron-specific enolase (NSE) is a glycolytic isoenzyme found in mature neurons and cells of neuronal origin. Injecting adeno-associated virus serotype 9 (AAV9) vectors carrying the NSE promoter into the cerebellar cortex is likely to cause the specific transduction of neuronal cells, such as Purkinje cells (PCs) and interneurons, but not Bergmann glia (BG). However, we found BG-predominant transduction without PC transduction along a traumatic needle tract for viral injection. The enhancement of neuroinflammation by the co-application of lipopolysaccharide (LPS) with AAV9 significantly expanded the BG-predominant area concurrently with the potentiated microglial activation. The BG-predominant transduction was gradually replaced by the PC-predominant transduction as the neuroinflammation dissipated. Experiments using glioma cell cultures revealed significant activation of the NSE promoter due to glucose deprivation, suggesting that intracellularly stored glycogen is metabolized through the glycolytic pathway for energy. Activation of the glycolytic enzyme promoter in BG concurrently with inactivation in PC may have pathophysiological significance for the production of lactate in activated BG and the utilization of lactate, which is provided by the BG-PC lactate shuttle, as a primary energy resource in injured PCs.

Subregional laminar cartilage MR spin-spin relaxation times (T2) in osteoarthritic knees with and without medial femorotibial cartilage loss - data from the Osteoarthritis Initiative (OAI).

PubMed

Wirth, W; Maschek, S; Beringer, P; Eckstein, F

2017-08-01

To explore whether subregional laminar femorotibial cartilage spin-spin relaxation time (T2) is associated with subsequent radiographic progression and cartilage loss and/or whether one-year change in subregional laminar femorotibial cartilage T2 is associated with concurrent progression in knees with established radiographic OA (ROA). In this case-control study, Osteoarthritis Initiative (OAI) knees with medial femorotibial progression were selected based on one-year loss in both quantitative cartilage thickness Magnetic resonance imaging (MRI) and radiographic joint space width (JSW). Non-progressor knees were matched by sex, Body mass index (BMI), baseline Kellgren-Lawrence-grade (2/3), and pain. Baseline and one-year follow-up superficial and deep cartilage T2 was analyzed in 16 femorotibial subregions using multi-echo spin-echo MRI. 37 knees showed medial femorotibial progression whereas 37 matched controls had no medial or lateral compartment progression. No statistically significant baseline differences between progressor and non-progressor knees in medial femorotibial cartilage T2 were observed in the superficial (48.9 ± 3.0 ms; 95% CI: [47.9, 49.9] vs 47.8 ± 3.6 ms; 95% CI: [46.6, 49.0], P = 0.07) or deep cartilage layer (40.8 ± 3.6 ms; 95% CI: [39.5, 42.0] vs 40.1 ± 4.7 ms; 95% CI: [38.5, 41.6], P = 0.29). Concurrent T2 change was more pronounced in the deep than the superficial cartilage layer. In the medial femorotibial compartment (MFTC), longitudinal change was greater in the deep layer of progressor than non-progressor knees (1.8 ± 4.5 ms; 95% CI: [0.3, 3.3] vs -0.2 ± 1.9 ms; 95% CI: [-0.8, 0.5], P = 0.02), whereas no difference was observed in the superficial layer. Medial compartment cartilage T2 did not appear to be a strong prognostic factor for subsequent structural progression in the same compartment of knees with established ROA, when appropriately controlling for covariates. Yet, deep layer T2 change in the medial compartment occurred concurrent with medial femorotibial progression. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

Drug-resistant herpes simplex virus in HIV infected patients.

PubMed

Lolis, Margarita S; González, Lenis; Cohen, Philip J; Schwartz, Robert A

2008-01-01

Herpes simplex virus type 2 (HSV2) infection is a major source of morbidity in human immunodeficiency virus (HIV)-infected patients, since reactivations - whether symptomatic or asymptomatic - are associated with increased HIV viral load and viral shedding. Acyclovir, valacyclovir and famcyclovir are indicated for the treatment of HSV2 in HIV patients. This class of drugs has been shown to enhance survival in HIV-infected individuals. However, with the emergence of drug-resistant strains of HSV2, the rates of resistance among HIV patients are almost ten-fold those in immunocompetent individuals, comparing 0.6% to 6%. These HSV2 infections tend to be more severe and to recur. More ominously, disease progression of HIV is promoted by concurrent infection with HSV2. Intravenous foscarnet and cidofovir may be used for acyclovir-resistant HSV; however, resistance to these drugs has been documented. Newer therapies such as the toll-like receptor agonist imiquimod and immunomodulating dipeptides offer promise for the treatment of HSV2 in HIV-infected individuals.

Quality of life with cediranib in relapsed ovarian cancer: The ICON6 phase 3 randomized clinical trial.

PubMed

Stark, Dan P; Cook, Adrian; Brown, Julia M; Brundage, Michael D; Embleton, Andrew C; Kaplan, Richard S; Raja, Fharat A; Swart, Ann Marie W; Velikova, Galina; Qian, Wendi; Ledermann, Jonathan A

2017-07-15

The ICON6 trial showed that cediranib, an oral inhibitor of vascular endothelial growth factor receptors 1, 2, and 3, improved clinical outcomes for patients with platinum-sensitive relapsed ovarian cancer when it was used with chemotherapy and was continued as maintenance therapy. This study describes health-related quality of life (QOL) during the first year of treatment. Four hundred fifty-six women were randomly allocated to receive standard chemotherapy only, chemotherapy with concurrent cediranib, or chemotherapy with cediranib administered concurrently and continued as maintenance. Patients completed QOL questionnaires until disease progression every 3 weeks during chemotherapy and then every 6 weeks to 1 year. Patients alive with disease progression completed a QOL form 1 year after randomization. The primary QOL endpoint was the global score from the Quality of Life Questionnaire Core 30 (of the European Organization for Research and Treatment of Cancer) at 1 year, with the standard chemotherapy group compared with the concurrent-maintenance cediranib group. The rate of questionnaire compliance was 90% at the baseline and 76% at 1 year and was similar across the 3 groups. The mean global QOL score at 1 year was 62.6 points for the standard chemotherapy group and 68.7 points for the concurrent-maintenance group (+4.5; 95% confidence interval, -2.0 to 11.0; P = .18). Sensitivity analyses suggested that this finding was robust to the effect of missing data, and the improvement became statistically significant after adjustments for self-reported diarrhea. The 6th study by the International Collaboration in Ovarian Neoplasm (ICON6) showed a significant improvement in progression-free survival with cediranib as concurrent and maintenance therapy. No QOL detriment with cediranib was found 1 year after treatment was commenced. The maintenance of QOL along with prolonged cancer control suggests that cediranib has a valuable role in the treatment of relapsed ovarian cancer. Cancer 2017;123:2752-61. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society.

Concurrent versus sequential sorafenib therapy in combination with radiation for hepatocellular carcinoma.

PubMed

Wild, Aaron T; Gandhi, Nishant; Chettiar, Sivarajan T; Aziz, Khaled; Gajula, Rajendra P; Williams, Russell D; Kumar, Rachit; Taparra, Kekoa; Zeng, Jing; Cades, Jessica A; Velarde, Esteban; Menon, Siddharth; Geschwind, Jean F; Cosgrove, David; Pawlik, Timothy M; Maitra, Anirban; Wong, John; Hales, Russell K; Torbenson, Michael S; Herman, Joseph M; Tran, Phuoc T

2013-01-01

Sorafenib (SOR) is the only systemic agent known to improve survival for hepatocellular carcinoma (HCC). However, SOR prolongs survival by less than 3 months and does not alter symptomatic progression. To improve outcomes, several phase I-II trials are currently examining SOR with radiation (RT) for HCC utilizing heterogeneous concurrent and sequential treatment regimens. Our study provides preclinical data characterizing the effects of concurrent versus sequential RT-SOR on HCC cells both in vitro and in vivo. Concurrent and sequential RT-SOR regimens were tested for efficacy among 4 HCC cell lines in vitro by assessment of clonogenic survival, apoptosis, cell cycle distribution, and γ-H2AX foci formation. Results were confirmed in vivo by evaluating tumor growth delay and performing immunofluorescence staining in a hind-flank xenograft model. In vitro, concurrent RT-SOR produced radioprotection in 3 of 4 cell lines, whereas sequential RT-SOR produced decreased colony formation among all 4. Sequential RT-SOR increased apoptosis compared to RT alone, while concurrent RT-SOR did not. Sorafenib induced reassortment into less radiosensitive phases of the cell cycle through G1-S delay and cell cycle slowing. More double-strand breaks (DSBs) persisted 24 h post-irradiation for RT alone versus concurrent RT-SOR. In vivo, sequential RT-SOR produced the greatest tumor growth delay, while concurrent RT-SOR was similar to RT alone. More persistent DSBs were observed in xenografts treated with sequential RT-SOR or RT alone versus concurrent RT-SOR. Sequential RT-SOR additionally produced a greater reduction in xenograft tumor vascularity and mitotic index than either concurrent RT-SOR or RT alone. In conclusion, sequential RT-SOR demonstrates greater efficacy against HCC than concurrent RT-SOR both in vitro and in vivo. These results may have implications for clinical decision-making and prospective trial design.

Concurrent versus Sequential Sorafenib Therapy in Combination with Radiation for Hepatocellular Carcinoma

PubMed Central

Chettiar, Sivarajan T.; Aziz, Khaled; Gajula, Rajendra P.; Williams, Russell D.; Kumar, Rachit; Taparra, Kekoa; Zeng, Jing; Cades, Jessica A.; Velarde, Esteban; Menon, Siddharth; Geschwind, Jean F.; Cosgrove, David; Pawlik, Timothy M.; Maitra, Anirban; Wong, John; Hales, Russell K.; Torbenson, Michael S.; Herman, Joseph M.; Tran, Phuoc T.

2013-01-01

Sorafenib (SOR) is the only systemic agent known to improve survival for hepatocellular carcinoma (HCC). However, SOR prolongs survival by less than 3 months and does not alter symptomatic progression. To improve outcomes, several phase I-II trials are currently examining SOR with radiation (RT) for HCC utilizing heterogeneous concurrent and sequential treatment regimens. Our study provides preclinical data characterizing the effects of concurrent versus sequential RT-SOR on HCC cells both in vitro and in vivo. Concurrent and sequential RT-SOR regimens were tested for efficacy among 4 HCC cell lines in vitro by assessment of clonogenic survival, apoptosis, cell cycle distribution, and γ-H2AX foci formation. Results were confirmed in vivo by evaluating tumor growth delay and performing immunofluorescence staining in a hind-flank xenograft model. In vitro, concurrent RT-SOR produced radioprotection in 3 of 4 cell lines, whereas sequential RT-SOR produced decreased colony formation among all 4. Sequential RT-SOR increased apoptosis compared to RT alone, while concurrent RT-SOR did not. Sorafenib induced reassortment into less radiosensitive phases of the cell cycle through G1-S delay and cell cycle slowing. More double-strand breaks (DSBs) persisted 24 h post-irradiation for RT alone versus concurrent RT-SOR. In vivo, sequential RT-SOR produced the greatest tumor growth delay, while concurrent RT-SOR was similar to RT alone. More persistent DSBs were observed in xenografts treated with sequential RT-SOR or RT alone versus concurrent RT-SOR. Sequential RT-SOR additionally produced a greater reduction in xenograft tumor vascularity and mitotic index than either concurrent RT-SOR or RT alone. In conclusion, sequential RT-SOR demonstrates greater efficacy against HCC than concurrent RT-SOR both in vitro and in vivo. These results may have implications for clinical decision-making and prospective trial design. PMID:23762417

Validating Neuro-QoL short forms and targeted scales with people who have multiple sclerosis.

PubMed

Miller, Deborah M; Bethoux, Francois; Victorson, David; Nowinski, Cindy J; Buono, Sarah; Lai, Jin-Shei; Wortman, Katy; Burns, James L; Moy, Claudia; Cella, David

2016-05-01

Multiple sclerosis (MS) is a chronic, progressive, and disabling disease of the central nervous system with dramatic variations in the combination and severity of symptoms it can produce. The lack of reliable disease-specific health-related quality of life (HRQL) measures for use in clinical trials prompted the development of the Neurology Quality of Life (Neuro-QOL) instrument, which includes 13 scales that assess physical, emotional, cognitive, and social domains, for use in a variety of neurological illnesses. The objective of this research paper is to conduct an initial assessment of the reliability and validation of the Neuro-QOL short forms (SFs) in MS. We assessed reliability, concurrent validity, known groups validity, and responsiveness between cross-sectional and longitudinal data in 161 recruited MS patients. Internal consistency was high for all measures (α = 0.81-0.95) and ICCs were within the acceptable range (0.76-0.91); concurrent and known groups validity were highest with the Global HRQL question. Longitudinal assessment was limited by the lack of disease progression in the group. The Neuro-QOL SFs demonstrate good internal consistency, test-re-test reliability, and concurrent and known groups validity in this MS population, supporting the validity of Neuro-QOL in adults with MS. © The Author(s), 2015.

Monitoring Progress in Vocal Development in Young Cochlear Implant Recipients: Relationships between Speech Samples and Scores from the Conditioned Assessment of Speech Production (CASP)

PubMed Central

Ertmer, David J.; Jung, Jongmin

2012-01-01

Background Evidence of auditory-guided speech development can be heard as the prelinguistic vocalizations of young cochlear implant recipients become increasingly complex, phonetically diverse, and speech-like. In research settings, these changes are most often documented by collecting and analyzing speech samples. Sampling, however, may be too time-consuming and impractical for widespread use in clinical settings. The Conditioned Assessment of Speech Production (CASP; Ertmer & Stoel-Gammon, 2008) is an easily administered and time-efficient alternative to speech sample analysis. The current investigation examined the concurrent validity of the CASP and data obtained from speech samples recorded at the same intervals. Methods Nineteen deaf children who received CIs before their third birthdays participated in the study. Speech samples and CASP scores were gathered at 6, 12, 18, and 24 months post-activation. Correlation analyses were conducted to assess the concurrent validity of CASP scores and data from samples. Results CASP scores showed strong concurrent validity with scores from speech samples gathered across all recording sessions (6 – 24 months). Conclusions The CASP was found to be a valid, reliable, and time-efficient tool for assessing progress in vocal development during young CI recipient’s first 2 years of device experience. PMID:22628109

Systematic review of the concurrent and predictive validity of MRI biomarkers in OA

PubMed Central

Hunter, D.J.; Zhang, W.; Conaghan, Philip G.; Hirko, K.; Menashe, L.; Li, L.; Reichmann, W.M.; Losina, E.

2012-01-01

SUMMARY Objective To summarize literature on the concurrent and predictive validity of MRI-based measures of osteoarthritis (OA) structural change. Methods An online literature search was conducted of the OVID, EMBASE, CINAHL, PsychInfo and Cochrane databases of articles published up to the time of the search, April 2009. 1338 abstracts obtained with this search were preliminarily screened for relevance by two reviewers. Of these, 243 were selected for data extraction for this analysis on validity as well as separate reviews on discriminate validity and diagnostic performance. Of these 142 manuscripts included data pertinent to concurrent validity and 61 manuscripts for the predictive validity review. For this analysis we extracted data on criterion (concurrent and predictive) validity from both longitudinal and cross-sectional studies for all synovial joint tissues as it relates to MRI measurement in OA. Results Concurrent validity of MRI in OA has been examined compared to symptoms, radiography, histology/pathology, arthroscopy, CT, and alignment. The relation of bone marrow lesions, synovitis and effusion to pain was moderate to strong. There was a weak or no relation of cartilage morphology or meniscal tears to pain. The relation of cartilage morphology to radiographic OA and radiographic joint space was inconsistent. There was a higher frequency of meniscal tears, synovitis and other features in persons with radiographic OA. The relation of cartilage to other constructs including histology and arthroscopy was stronger. Predictive validity of MRI in OA has been examined for ability to predict total knee replacement (TKR), change in symptoms, radiographic progression as well as MRI progression. Quantitative cartilage volume change and presence of cartilage defects or bone marrow lesions are potential predictors of TKR. Conclusion MRI has inherent strengths and unique advantages in its ability to visualize multiple individual tissue pathologies relating to pain and also predict clinical outcome. The complex disease of OA which involves an array of tissue abnormalities is best imaged using this imaging tool. PMID:21396463

Concurrent Chemotherapy and Intensity-Modulated Radiotherapy for Locoregionally Advanced Laryngeal and Hypopharyngeal Cancers

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

Lee, Nancy Y.; O'Meara, William; Chan, Kelvin

2007-10-01

Purpose: To perform a retrospective review of laryngeal/hypopharyngeal carcinomas treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT). Methods and Materials: Between January 2002 and June 2005, 20 laryngeal and 11 hypopharyngeal carcinoma patients underwent IMRT with concurrent platinum-based chemotherapy; most patients had Stage IV disease. The prescription of the planning target volume for gross, high-risk, and low-risk subclinical disease was 70, 59.4, and 54 Gy, respectively. Acute/late toxicities were retrospectively scored using the Common Toxicity Criteria scale. The 2-year local progression-free, regional progression-free, laryngectomy-free, distant metastasis-free, and overall survival rates were calculated using the Kaplan-Meier method. Results: The median follow-upmore » of the living patients was 26 months (range, 17-58 months). The 2-year local progression-free, regional progression-free, laryngectomy-free, distant metastasis-free, and overall survival rate was 86%, 94%, 89%, 92%, and 63%, respectively. Grade 2 mucositis or higher occurred in 48% of patients, and all experienced Grade 2 or higher pharyngitis during treatment. Xerostomia continued to decrease over time from the end of RT, with none complaining of Grade 2 toxicity at this analysis. The 2-year post-treatment percutaneous endoscopic gastrostomy-dependency rate for those with hypopharyngeal and laryngeal tumors was 31% and 15%, respectively. The most severe late complications were laryngeal necrosis, necrotizing fascitis, and a carotid rupture resulting in death 3 weeks after salvage laryngectomy. Conclusion: These preliminary results have shown that IMRT achieved encouraging locoregional control of locoregionally advanced laryngeal and hypopharyngeal carcinomas. Xerostomia improved over time. Pharyngoesophageal stricture with percutaneous endoscopic gastrostomy dependency remains a problem, particularly for patients with hypopharyngeal carcinoma and, to a lesser extent, those with laryngeal cancer. Strategies using IMRT to limit the dose delivered to the esophagus/inferior constrictor musculature without compromising target coverage might be useful to further minimize this late complication.« less

Concurrent chemotherapy and pelvic radiation therapy compared with pelvic radiation therapy alone as adjuvant therapy after radical surgery in high-risk early-stage cancer of the cervix.

PubMed

Peters, W A; Liu, P Y; Barrett, R J; Stock, R J; Monk, B J; Berek, J S; Souhami, L; Grigsby, P; Gordon, W; Alberts, D S

2000-04-01

To determine whether the addition of cisplatin-based chemotherapy (CT) to pelvic radiation therapy (RT) will improve the survival of early-stage, high-risk patients with cervical carcinoma. Patients with clinical stage IA(2), IB, and IIA carcinoma of the cervix, initially treated with radical hysterectomy and pelvic lymphadenectomy, and who had positive pelvic lymph nodes and/or positive margins and/or microscopic involvement of the parametrium were eligible for this study. Patients were randomized to receive RT or RT + CT. Patients in each group received 49.3 GY RT in 29 fractions to a standard pelvic field. Chemotherapy consisted of bolus cisplatin 70 mg/m(2) and a 96-hour infusion of fluorouracil 1,000 mg/m(2)/d every 3 weeks for four cycles, with the first and second cycles given concurrent to RT. Between 1991 and 1996, 268 patients were entered onto the study. Two hundred forty-three patients were assessable (127 RT + CT patients and 116 RT patients). Progression-free and overall survival are significantly improved in the patients receiving CT. The hazard ratios for progression-free survival and overall survival in the RT only arm versus the RT + CT arm are 2.01 (P =.003) and 1.96 (P =. 007), respectively. The projected progression-free survivals at 4 years is 63% with RT and 80% with RT + CT. The projected overall survival rate at 4 years is 71% with RT and 81% with RT + CT. Grades 3 and 4 hematologic and gastrointestinal toxicity were more frequent in the RT + CT group. The addition of concurrent cisplatin-based CT to RT significantly improves progression-free and overall survival for high-risk, early-stage patients who undergo radical hysterectomy and pelvic lymphadenectomy for carcinoma of the cervix.

EAT-UP™ Family-Centered Feeding Intervention to Promote Food Acceptance and Decrease Challenging Behaviors: A Single-Case Experimental Design Replicated across Three Families of Children with Autism Spectrum Disorder

ERIC Educational Resources Information Center

Cosbey, Joanna; Muldoon, Deirdre

2017-01-01

This study evaluated the effectiveness of a family-centered feeding intervention, Easing Anxiety Together with Understanding and Perseverance (EAT-UP™), for promoting food acceptance of children with autism spectrum disorder at home. A concurrent multiple-baseline design was used with systematic replication across three families. Baseline was…

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

Jalali, Rakesh, E-mail: rjalali@tmc.gov.i; Raut, Nirmal; Arora, Brijesh

Purpose: To present outcome data in a prospective study of radiotherapy (RT) with concurrent and adjuvant temozolomide (TMZ) in children with diffuse intrinsic pontine gliomas (DIPGs). Methods and Materials: Pediatric patients with newly diagnosed DIPGs were prospectively treated with focal RT to a dose of 54 Gy in 30 fractions along with concurrent daily TMZ (75 mg/m{sup 2}, Days 1-42). Four weeks after completing the initial RT-TMZ schedule, adjuvant TMZ (200 mg/m{sup 2}, Days 1-5) was given every 28 days to a maximum of 12 cycles. Response was evaluated clinically and radiologically with magnetic resonance imaging and positron emission tomographymore » scans. Results: Between March 2005 and November 2006, 20 children (mean age, 8.3 years) were accrued. Eighteen patients have died from disease progression, one patient is alive with progressive disease, and one patient is alive with stable disease. Median overall survival and progression-free survival were 9.15 months and 6.9 months, respectively. Grade III/IV toxicity during the concurrent RT-TMZ phase included thrombocytopenia in 3 patients, leucopenia in 2, and vomiting in 7. Transient Grade II skin toxicity developed in the irradiated fields in 18 patients. During the adjuvant TMZ phase, Grade III/IV leucopenia developed in 2 patients and Grade IV thrombocytopenia in 1 patient. Patients with magnetic resonance imaging diagnosis of a high-grade tumor had worse survival than those with a low-grade tumor (p = 0.001). Patients with neurologic improvement after RT-TMZ had significantly better survival than those who did not (p = 0.048). Conclusions: TMZ with RT has not yielded any improvement in the outcome of DIPG compared with RT alone. Further clinical trials should explore novel treatment modalities.« less

Prospective Study of Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Concurrent With Individualized Radiotherapy for Patients With Locally Advanced or Metastatic Non-Small-Cell Lung Cancer

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

Wang Jing; Xia Tingyi, E-mail: xiatingyi1959@21cn.com; Wang Yingjie

Purpose: To establish the safety profile and efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) concurrent with individualized radiotherapy (RT) in patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC). Patients and Methods: Between June 2007 and January 2010, 26 patients with Stage III/IV NSCLC were enrolled in this prospective study. These patients were treated with EGFR-TKIs (gefitinib 250 mg or erlotinib 150 mg, oral daily) concurrent with individualized RT with curative intent. The thoracic RT plans were individually designed on the basis of tumor size and normal tissue volume constraints. All patients were assessed for toxicity,more » and 25 patients were available for efficacy. The primary endpoints were acute toxicity, overall survival, and median survival time. The secondary endpoints included local control rate, time to tumor progression, and progression-free survival (PFS). Results: Median gross tumor volume, mean lung dose, and lung V20 were 56 cm{sup 3}, 8.6 Gy, and 14%, respectively. Median thoracic radiation dose was 70 Gy at a margin of gross tumor volume (range, 42-82 Gy), and median biological equivalent dose was 105 Gy (range, 60-119 Gy). Acute skin, hematologic, esophageal, and pulmonary toxicities were acceptable and manageable. Severe adverse events included neutropenia (Grade 4, 4%) and thrombocytopenia (Grade 4, 8%), esophagitis (Grade 3, 4%), and pneumonitis (Grade 3, 4%). With a median follow-up of 10.2 months, a local control rate of 96% was achieved for thoracic tumor. Median time to progression, median PFS, and median survival time were 6.3, 10.2, and 21.8 months, respectively. The 1- and 2-year PFS rates were both 42%, and 1-, 2-, and 3-year overall survival rates were 57%, 45%, and 30%, respectively. Conclusion: Concurrent EGFR-TKIs with individualized RT shows a favorable safety profile and promising outcome, therefore serving as a therapeutic option for patients with locally advanced or metastatic NSCLC.« less

Hydroxylamine addition impact to Nitrosomonas europaea activity in the presence of monochloramine

EPA Science Inventory

In drinking water, monochloramine may promote ammonia–oxidizing bacteria (AOB) growth because of concurrent ammonia presence. AOB use (i) ammonia monooxygenase for biological ammonia oxidation to hydroxylamine and (ii) hydroxylamine oxidoreductase for hydroxylamine oxidation to ...

A phase II study of nab-paclitaxel plus carboplatin in combination with thoracic radiation in patients with locally advanced non–small-cell lung cancer

PubMed Central

Hasegawa, Takaaki; Futamura, Yohei; Horiba, Akane; Yoshida, Tsutomu; Suzuki, Toshitaka; Kato, Tatsuo; Kaito, Daizo; Ohno, Yasuhi; Iida, Takayoshi; Hayashi, Shinya; Sawa, Toshiyuki

2016-01-01

We investigated the efficacy and safety of albumin-bound paclitaxel (nab-PTX) and carboplatin (CBDCA) with concurrent radiotherapy for unresectable locally advanced non–small-cell lung cancer (NSCLC). Patients with Stage III NSCLC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. Concurrent chemoradiotherapy consisted of weekly administration of nab-PTX (40 mg/m2) plus CBDCA (area under the plasma concentration time curve (AUC) 2) and thoracic radiotherapy (60 Gy/30 fractions) for a total of 6 weeks. After concurrent chemoradiotherapy, patients received an additional two cycles of consolidation phase chemotherapy that consisted of 4-week cycles of nab-PTX (100 mg/m2 on Days 1, 8 and 15)/CBDCA (AUC 5 mg/ml/min on Day 1). Response was evaluated in accordance with the Response Evaluation Criteria in Solid Tumors. Progression-free survival and overall survival were estimated using the Kaplan–Meier method. Toxicity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events. A total of 10 patients were enrolled in this trial between September 2013 and January 2014 from three institutes. The overall response rate was 40.0% and the median progression-free survival was 6.7 months. Treatment-related death occurred in two patients. Grade 2 or worse severe radiation pneumonitis was observed in all three patients that had the volume of lung receiving at least 20 Gy (V20) >30%. The results of this study indicate that no further investigation is warranted into nab-PTX and CBDCA with concurrent thoracic radiation for Stage III NSCLC with V20 > 30% due to severe toxicity. PMID:26442970

Evolution of microstructure and elastic wave velocities in dehydrated gypsum samples

NASA Astrophysics Data System (ADS)

Milsch, Harald; Priegnitz, Mike

2012-12-01

We report on changes in P and S-wave velocities and rock microstructure induced by devolatilization reactions using gypsum as a reference analog material. Cylindrical samples of natural alabaster were dehydrated in air, at ambient pressure, and temperatures between 378 and 423 K. Dehydration did not proceed homogeneously but via a reaction front moving sample inwards separating an outer highly porous rim from the remaining gypsum which, above approximately 393 (±5) K, concurrently decomposed into hemihydrate. Overall porosity was observed to continuously increase with reaction progress from approximately 2% for fully hydrated samples to 30% for completely dehydrated ones. Concurrently, P and S-wave velocities linearly decreased with porosity from 5.2 and 2.7 km/s to 1.0 and 0.7 km/s, respectively. It is concluded that a linearized empirical Raymer-type model extended by a critical porosity term and based on the respective time dependent mineral and pore volumes reasonably replicates the P and S-wave data in relation to reaction progress and porosity.

Methylation of HOXA9 and ISL1 Predicts Patient Outcome in High-Grade Non-Invasive Bladder Cancer

PubMed Central

Kitchen, Mark O.; Bryan, Richard T.; Haworth, Kim E.; Emes, Richard D.; Luscombe, Christopher; Gommersall, Lyndon; Cheng, K. K.; Zeegers, Maurice P.; James, Nicholas D.; Devall, Adam J.; Fryer, Anthony A.; Farrell, William E.

2015-01-01

Introduction Inappropriate DNA methylation is frequently associated with human tumour development, and in specific cases, is associated with clinical outcomes. Previous reports of DNA methylation in low/intermediate grade non-muscle invasive bladder cancer (NMIBC) have suggested that specific patterns of DNA methylation may have a role as diagnostic or prognostic biomarkers. In view of the aggressive and clinically unpredictable nature of high-grade (HG) NMIBC, and the current shortage of the preferred treatment option (Bacillus:Calmette-Guerin), novel methylation analyses may similarly reveal biomarkers of disease outcome that could risk-stratify patients and guide clinical management at initial diagnosis. Methods Promoter-associated CpG island methylation was determined in primary tumour tissue of 36 initial presentation high-grade NMIBCs, 12 low/intermediate-grade NMIBCs and 3 normal bladder controls. The genes HOXA9, ISL1, NKX6-2, SPAG6, ZIC1 and ZNF154 were selected for investigation on the basis of previous reports and/or prognostic utility in low/intermediate-grade NMIBC. Methylation was determined by Pyrosequencing of sodium-bisulphite converted DNA, and then correlated with gene expression using RT-qPCR. Methylation was additionally correlated with tumour behaviour, including tumour recurrence and progression to muscle invasive bladder cancer or metastases. Results The ISL1 genes’ promoter-associated island was more frequently methylated in recurrent and progressive high-grade tumours than their non-recurrent counterparts (60.0% vs. 18.2%, p = 0.008). ISL1 and HOXA9 showed significantly higher mean methylation in recurrent and progressive tumours compared to non-recurrent tumours (43.3% vs. 20.9%, p = 0.016 and 34.5% vs 17.6%, p = 0.017, respectively). Concurrent ISL1/HOXA9 methylation in HG-NMIBC reliably predicted tumour recurrence and progression within one year (Positive Predictive Value 91.7%), and was associated with disease-specific mortality (DSM). Conclusions In this study we report methylation differences and similarities between clinical sub-types of high-grade NMIBC. We report the potential ability of methylation biomarkers, at initial diagnosis, to predict tumour recurrence and progression within one year of diagnosis. We found that specific biomarkers reliably predict disease outcome and therefore may help guide patient treatment despite the unpredictable clinical course and heterogeneity of high-grade NMIBC. Further investigation is required, including validation in a larger patient cohort, to confirm the clinical utility of methylation biomarkers in high-grade NMIBC. PMID:26332997

18F-fluorodeoxyglucose imaging of primary malignant pericardial mesothelioma with concurrent pericardial and pleural effusions and bone metastasis: A case report.

PubMed

Li, Xiaohui; Lu, Rugang; Zhao, Youcai; Wang, Feng; Shao, Guoqiang

2018-06-01

Primary malignant pericardial mesothelioma (PMPM) is an aggressive tumor that originates from the mesothelial cells of the pericardium. PMPM with extensive atrial infiltration and bone metastasis is extremely rare. The diagnosis and staging of PMPM based on anatomical imaging may be difficult when concurrent pericardial and pleural effusions are present. A 28-year-old man presented with progressive chest pain. Concurrent pericardial and pleural effusions were identified on computed tomography. On echocardiography, mild thickening and adhesions of the pericardium with the right ventricle and atrium were observed. 18 F-fluorodeoxyglucose (FDG) metabolism imaging revealed increased accumulation in the pericardium and adjacent right atrium. Ring-shaped radioactivity aggregation and bone destruction in the sacrum were demonstrated on 18 F-FDG and 99m Tc-methyl diphosphonate imaging. The diagnosis of PMPM was subsequently confirmed by pathology. The patient survived for >1.5 years with comprehensive treatment.

Prognostic value of resident clinical performance ratings.

PubMed

Williams, Reed G; Dunnington, Gary L

2004-10-01

This study investigated the concurrent and predictive validity of end-of-rotation (EOR) clinical performance ratings. Surgeon EOR ratings of residents were collected and compared with end-of-year (EOY) progress decisions and to EOR and EOY confidential judgments of resident ability to provide patient care without direct supervision. Eighty percent to 85% of EOR ratings were Excellent or Very Good. Five percent or fewer were Fair or Poor. Almost all residents receiving Excellent or Very Good EOR ratings also received positive EOR judgments about ability to provide patient care without direct supervision. Residents rated Fair or Poor received negative EOR judgments about ability to provide patient care without direct supervision. As the cumulative percent of Good, Fair, and Poor EOR ratings increased, the number of residents promoted without stipulations at the end of the year decreased and the percentage of faculty members who judged the residents capable of providing effective patient care without direct supervision at the end of the year declined. All residents receiving 40% or more EOR ratings below Very Good had stipulations associated with their promotion. Despite use of descriptive anchors on the scale, clinical performance ratings have no direct meaning. Their meaning needs to be established in the same manner as is done in setting normal values for diagnostic tests, ie, by establishing the relationship between EOR ratings and practice outcomes.

Nomograms Predicting Progression-Free Survival, Overall Survival, and Pelvic Recurrence in Locally Advanced Cervical Cancer Developed From an Analysis of Identifiable Prognostic Factors in Patients From NRG Oncology/Gynecologic Oncology Group Randomized Trials of Chemoradiotherapy

PubMed Central

Rose, Peter G.; Java, James; Whitney, Charles W.; Stehman, Frederick B.; Lanciano, Rachelle; Thomas, Gillian M.; DiSilvestro, Paul A.

2015-01-01

Purpose To evaluate the prognostic factors in locally advanced cervical cancer limited to the pelvis and develop nomograms for 2-year progression-free survival (PFS), 5-year overall survival (OS), and pelvic recurrence. Patients and Methods We retrospectively reviewed 2,042 patients with locally advanced cervical carcinoma enrolled onto Gynecologic Oncology Group clinical trials of concurrent cisplatin-based chemotherapy and radiotherapy. Nomograms for 2-year PFS, five-year OS, and pelvic recurrence were created as visualizations of Cox proportional hazards regression models. The models were validated by bootstrap-corrected, relatively unbiased estimates of discrimination and calibration. Results Multivariable analysis identified prognostic factors including histology, race/ethnicity, performance status, tumor size, International Federation of Gynecology and Obstetrics stage, tumor grade, pelvic node status, and treatment with concurrent cisplatin-based chemotherapy. PFS, OS, and pelvic recurrence nomograms had bootstrap-corrected concordance indices of 0.62, 0.64, and 0.73, respectively, and were well calibrated. Conclusion Prognostic factors were used to develop nomograms for 2-year PFS, 5-year OS, and pelvic recurrence for locally advanced cervical cancer clinically limited to the pelvis treated with concurrent cisplatin-based chemotherapy and radiotherapy. These nomograms can be used to better estimate individual and collective outcomes. PMID:25732170

77 FR 59014 - Sunshine Act Meeting; Notice

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-25

... the meetings of the Institutional Advancement Committee and the Audit Committee, which will run... Eastern Daylight Time. ** The meeting of the Institutional Advancement Committee will run concurrently.... Institutional Advancement Committee** 5. Audit Committee Monday, October 1, 2012 1. Promotion & Provision for...

Metabolic disorders causing childhood ataxia.

PubMed

Parker, Colette C; Evans, Owen B

2003-09-01

Ataxia is a common neurologic finding in many disease processes of the nervous system, and has classically been associated with numerous metabolic disorders. An error of metabolism should be considered when the ataxia is either intermittent or progressive. Acute exacerbation or worsening after high protein ingestion, concurrent febrile illness, or other physical stress is also suggestive. A positive family history can be an important diagnostic clue. Progressive molecular and biochemical techniques are revolutionizing this area of medicine, and there has been rapid advancement in understanding of the disease processes.

Biology Division progress report, October 1, 1983-September 30, 1984

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

Griesmer, R.A.

1985-01-01

The report provides summaries of the aims, scope and progress from October 1983 through September 1984. Major interest was focused on the health effects of neutron- and heavy-ion radiations on animals with particular attention to the carcinogenic responses to low dose levels and to the RBE of various forms of radiation. Among chemical agents, activities concentrated on evaluating and understanding the toxicological interations when mammals are exposed to complex mixtures, either concurrently or successively. Separate abstracts have been prepared for individual sections. (ACR)

An Ugi Reaction Incorporating a Redox-Neutral Amine C-H Functionalization Step.

PubMed

Zhu, Zhengbo; Seidel, Daniel

2016-02-19

Pyrrolidine and 1,2,3,4-tetrahydroisoquinoline (THIQ) undergo redox-neutral α-amidation with concurrent N-alkylation upon reaction with aromatic aldehydes and isocyanides. Reactions are promoted by acetic acid and represent a new variant of the Ugi reaction.

Assessing physiotherapists' communication skills for promoting patient autonomy for self-management: reliability and validity of the communication evaluation in rehabilitation tool.

PubMed

Murray, Aileen; Hall, Amanda; Williams, Geoffrey C; McDonough, Suzanne M; Ntoumanis, Nikos; Taylor, Ian; Jackson, Ben; Copsey, Bethan; Hurley, Deirdre A; Matthews, James

2018-02-27

To assess the inter-rater reliability and concurrent validity of the Communication Evaluation in Rehabilitation Tool, which aims to externally assess physiotherapists competency in using Self-Determination Theory-based communication strategies in practice. Audio recordings of initial consultations between 24 physiotherapists and 24 patients with chronic low back pain in four hospitals in Ireland were obtained as part of a larger randomised controlled trial. Three raters, all of whom had Ph.Ds in psychology and expertise in motivation and physical activity, independently listened to the 24 audio recordings and completed the 18-item Communication Evaluation in Rehabilitation Tool. Inter-rater reliability between all three raters was assessed using intraclass correlation coefficients. Concurrent validity was assessed using Pearson's r correlations with a reference standard, the Health Care Climate Questionnaire. The total score for the Communication Evaluation in Rehabilitation Tool is an average of all 18 items. Total scores demonstrated good inter-rater reliability (Intraclass Correlation Coefficient (ICC) = 0.8) and concurrent validity with the Health Care Climate Questionnaire total score (range: r = 0.7-0.88). Item-level scores of the Communication Evaluation in Rehabilitation Tool identified five items that need improvement. Results provide preliminary evidence to support future use and testing of the Communication Evaluation in Rehabilitation Tool. Implications for Rehabilitation Promoting patient autonomy is a learned skill and while interventions exist to train clinicians in these skills there are no tools to assess how well clinicians use these skills when interacting with a patient. The lack of robust assessment has severe implications regarding both the fidelity of clinician training packages and resulting outcomes for promoting patient autonomy. This study has developed a novel measurement tool Communication Evaluation in Rehabilitation Tool and a comprehensive user manual to assess how well health care providers use autonomy-supportive communication strategies in real world-clinical settings. This tool has demonstrated good inter-rater reliability and concurrent validity in its initial testing phase. The Communication Evaluation in Rehabilitation Tool can be used in future studies to assess autonomy-supportive communication and undergo further measurement property testing as per our recommendations.

Asian Versus Non-Asian Outcomes in Nasopharyngeal Carcinoma: A North American Population-based Analysis.

PubMed

Hamilton, Sarah N; Ho, Cheryl; Laskin, Janessa; Zhai, Yongliang; Mak, Paul; Wu, Jonn

2016-12-01

The effect of ethnicity on nasopharyngeal cancer (NPC) outcomes is unclear. This retrospective analysis examines survival and the impact of concurrent chemoradiation (chemoRT) among Asian and non-Asian patients. Subjects included 380 consecutive patients with NPC treated at a Canadian institution from 2000 to 2009. Five-year Kaplan-Meier progression-free survival (PFS), disease-specific survival (DSS), and overall survival (OS) were compared between Asian (n=279) and non-Asian (n=101) subjects. Multivariable analysis was performed using Cox regression modeling. Two-variable interaction terms with concurrent chemoRT were used to examine whether concurrent chemoRT conferred different effects among subgroups. Asian subjects presented with earlier stage (P=0.005), were younger, had better performance status, and were less likely smokers (all P<0.001). Survival among Asian versus non-Asian subjects with stage I/II NPC were: PFS 68% versus 59% (P=0.04), DSS 87% versus 77% (P=0.08), and OS 84% versus 74% (P=0.003). Corresponding rates with stage III/IVA/IVB disease were PFS 49% versus 42% (P=0.12), DSS 72% versus 46% (P=0.001), and OS 70% versus 44% (P<0.001). On multivariable analysis, Asian ethnicity, age below 65 years, ECOG performance status 0-1, early stage, staging MRI use, and concurrent chemoRT were associated with improved DSS and OS (P<0.05). On testing interactions with concurrent chemoRT, Asian versus non-Asian ethnicity was significant (hazard ratio 3.9), suggesting that concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects. In this population-based study, Asian ethnicity was associated with improved DSS and OS. Concurrent chemoRT conferred more benefit among non-Asian compared with Asian subjects.

Resveratrol and pterostilbene as a microRNA-mediated chemopreventive and therapeutic strategy in prostate cancer

USDA-ARS?s Scientific Manuscript database

Growing evidence indicates deregulation of the epigenetic machinery comprising the microRNA (miRNA) network as a critical factor in the progression of various diseases including cancer. Concurrently, dietary phytochemicals are being intensively studied for their miRNA-mediated health beneficial prop...

Comparing two methods to promote generalization of receptive identification in children with autism spectrum disorders.

PubMed

Dufour, Marie-Michèle; Lanovaz, Marc J

2017-11-01

The purpose of our study was to compare the effects of serial and concurrent training on the generalization of receptive identification in children with autism spectrum disorders (ASD). We taught one to three pairs of stimulus sets to nine children with ASD between the ages of three and six. One stimulus set within each pair was taught using concurrent training and the other using serial training. We alternated the training sessions within a multielement design and staggered the introduction of subsequent pairs for each participant as in a multiple baseline design. Overall, six participants generalized at least one stimulus set more rapidly with concurrent training whereas two participants showed generalization more rapidly with serial training. Our results differ from other comparison studies on the topic and indicate that practitioners should consider assessing the effects of both procedures prior to teaching receptive identification to children with ASD.

Phase II study of imatinib mesylate plus hydroxyurea in adults with recurrent glioblastoma multiforme.

PubMed

Reardon, David A; Egorin, Merrill J; Quinn, Jennifer A; Rich, Jeremy N; Rich, Jeremy N; Gururangan, Sridharan; Gururangan, Idharan; Vredenburgh, James J; Desjardins, Annick; Sathornsumetee, Sith; Provenzale, James M; Herndon, James E; Dowell, Jeannette M; Badruddoja, Michael A; McLendon, Roger E; Lagattuta, Theodore F; Kicielinski, Kimberly P; Dresemann, Gregor; Sampson, John H; Friedman, Allan H; Salvado, August J; Friedman, Henry S

2005-12-20

We performed a phase II study to evaluate the combination of imatinib mesylate, an adenosine triphosphate mimetic, tyrosine kinase inhibitor, plus hydroxyurea, a ribonucleotide reductase inhibitor, in patients with recurrent glioblastoma multiforme (GBM). Patients with GBM at any recurrence received imatinib mesylate plus hydroxyurea (500 mg twice a day) orally on a continuous, daily schedule. The imatinib mesylate dose was 500 mg twice a day for patients on enzyme-inducing antiepileptic drugs (EIAEDs) and 400 mg once a day for those not on EIAEDs. Assessments were performed every 28 days. The primary end point was 6-month progression-free survival (PFS). Thirty-three patients enrolled with progressive disease after prior radiotherapy and at least temozolomide-based chemotherapy. With a median follow-up of 58 weeks, 27% of patients were progression-free at 6 months, and the median PFS was 14.4 weeks. Three patients (9%) achieved radiographic response, and 14 (42%) achieved stable disease. Cox regression analysis identified concurrent EIAED use and no more than one prior progression as independent positive prognostic factors of PFS. The most common toxicities included grade 3 neutropenia (16%), thrombocytopenia (6%), and edema (6%). There were no grade 4 or 5 events. Concurrent EIAED use lowered imatinib mesylate exposure. Imatinib mesylate clearance was decreased at day 28 compared with day 1 in all patients, suggesting an effect of hydroxyurea. Imatinib mesylate plus hydroxyurea is well tolerated and associated with durable antitumor activity in some patients with recurrent GBM.

Progress Evaluation for the Restaurant Industry Assessed by a Voluntary Marketing-Mix and Choice-Architecture Framework That Offers Strategies to Nudge American Customers toward Healthy Food Environments, 2006-2017.

PubMed

Kraak, Vivica; Englund, Tessa; Misyak, Sarah; Serrano, Elena

2017-07-12

Consumption of restaurant food and beverage products high in fat, sugar and sodium contribute to obesity and non-communicable diseases. We evaluated restaurant-sector progress to promote healthy food environments for Americans. We conducted a desk review of seven electronic databases (January 2006-January 2017) to examine restaurant strategies used to promote healthful options in the United States (U.S.). Evidence selection ( n = 84) was guided by the LEAD principles (i.e., locate, evaluate, and assemble evidence to inform decisions) and verified by data and investigator triangulation. A marketing-mix and choice-architecture framework was used to examine eight voluntary strategies (i.e., place, profile, portion, pricing, promotion, healthy default picks, priming or prompting and proximity) to evaluate progress (i.e., no, limited, some or extensive) toward 12 performance metrics based on available published evidence. The U.S. restaurant sector has made limited progress to use pricing, profile (reformulation), healthy default picks (choices), promotion (responsible marketing) and priming and prompting (information and labeling); and some progress to reduce portions. No evidence was available to assess progress for place (ambience) and proximity (positioning) to promote healthy choices during the 10-year review period. Chain and non-chain restaurants can apply comprehensive marketing-mix and nudge strategies to promote healthy food environments for customers.

Progress Evaluation for the Restaurant Industry Assessed by a Voluntary Marketing-Mix and Choice-Architecture Framework That Offers Strategies to Nudge American Customers toward Healthy Food Environments, 2006–2017

PubMed Central

Misyak, Sarah; Serrano, Elena

2017-01-01

Consumption of restaurant food and beverage products high in fat, sugar and sodium contribute to obesity and non-communicable diseases. We evaluated restaurant-sector progress to promote healthy food environments for Americans. We conducted a desk review of seven electronic databases (January 2006–January 2017) to examine restaurant strategies used to promote healthful options in the United States (U.S.). Evidence selection (n = 84) was guided by the LEAD principles (i.e., locate, evaluate, and assemble evidence to inform decisions) and verified by data and investigator triangulation. A marketing-mix and choice-architecture framework was used to examine eight voluntary strategies (i.e., place, profile, portion, pricing, promotion, healthy default picks, priming or prompting and proximity) to evaluate progress (i.e., no, limited, some or extensive) toward 12 performance metrics based on available published evidence. The U.S. restaurant sector has made limited progress to use pricing, profile (reformulation), healthy default picks (choices), promotion (responsible marketing) and priming and prompting (information and labeling); and some progress to reduce portions. No evidence was available to assess progress for place (ambience) and proximity (positioning) to promote healthy choices during the 10-year review period. Chain and non-chain restaurants can apply comprehensive marketing-mix and nudge strategies to promote healthy food environments for customers. PMID:28704965

Does monitoring goal progress promote goal attainment? A meta-analysis of the experimental evidence.

PubMed

Harkin, Benjamin; Webb, Thomas L; Chang, Betty P I; Prestwich, Andrew; Conner, Mark; Kellar, Ian; Benn, Yael; Sheeran, Paschal

2016-02-01

Control theory and other frameworks for understanding self-regulation suggest that monitoring goal progress is a crucial process that intervenes between setting and attaining a goal, and helps to ensure that goals are translated into action. However, the impact of progress monitoring interventions on rates of behavioral performance and goal attainment has yet to be quantified. A systematic literature search identified 138 studies (N = 19,951) that randomly allocated participants to an intervention designed to promote monitoring of goal progress versus a control condition. All studies reported the effects of the treatment on (a) the frequency of progress monitoring and (b) subsequent goal attainment. A random effects model revealed that, on average, interventions were successful at increasing the frequency of monitoring goal progress (d+ = 1.98, 95% CI [1.71, 2.24]) and promoted goal attainment (d+ = 0.40, 95% CI [0.32, 0.48]). Furthermore, changes in the frequency of progress monitoring mediated the effect of the interventions on goal attainment. Moderation tests revealed that progress monitoring had larger effects on goal attainment when the outcomes were reported or made public, and when the information was physically recorded. Taken together, the findings suggest that monitoring goal progress is an effective self-regulation strategy, and that interventions that increase the frequency of progress monitoring are likely to promote behavior change. (c) 2016 APA, all rights reserved).

Beta-adrenergic signaling promotes tumor angiogenesis and prostate cancer progression through HDAC2-mediated suppression of thrombospondin-1.

PubMed

Hulsurkar, M; Li, Z; Zhang, Y; Li, X; Zheng, D; Li, W

2017-03-01

Chronic behavioral stress and beta-adrenergic signaling have been shown to promote cancer progression, whose underlying mechanisms are largely unclear, especially the involvement of epigenetic regulation. Histone deacetylase-2 (HDAC2), an epigenetic regulator, is critical for stress-induced cardiac hypertrophy. It is unknown whether it is necessary for beta-adrenergic signaling-promoted cancer progression. Using xenograft models, we showed that chronic behavioral stress and beta-adrenergic signaling promote angiogenesis and prostate cancer progression. HDAC2 was induced by beta-adrenergic signaling in vitro and in mouse xenografts. We next uncovered that HDAC2 is a direct target of cAMP response element-binding protein (CREB) that is activated by beta-adrenergic signaling. Notably, HDAC2 is necessary for beta-adrenergic signaling to induce angiogenesis. We further demonstrated that, upon CREB activation, HDAC2 represses thrombospondin-1 (TSP1), a potent angiogenesis inhibitor, through epigenetic regulation. Together, these data establish a novel pathway that HDAC2 and TSP1 act downstream of CREB activation in beta-adrenergic signaling to promote cancer progression.

Sex ratio, poverty, and concurrent partnerships among men and women in the United States: a multilevel analysis.

PubMed

Adimora, Adaora A; Schoenbach, Victor J; Taylor, Eboni M; Khan, Maria R; Schwartz, Robert J; Miller, William C

2013-11-01

Social and economic contextual factors may promote concurrent sexual partnerships, which can accelerate population HIV transmission and are more common among African Americans than U.S. Whites. We investigated the relationship between contextual factors and concurrency. We analyzed past 12-month concurrency prevalence in the 2002 National Survey of Family Growth and its contextual database in relation to county sex ratio (among respondent's racial and ethnic group), percentage in poverty (among respondent's racial and ethnic group), and violent crime rate. Analyses examined counties with balanced (0.95-1.05 males/female) or low (<0.9) sex ratios. Concurrency prevalence was greater (odds ratio [OR]; 95% confidence interval [CI]) in counties with low sex ratios (OR, 1.67; 95% CI, 1.17-2.39), more poverty (OR, 1.18; 95% CI, 0.98-1.42 per 10 percentage-point increase), and higher crime rates (OR, 1.04; 95% CI, 1.00-1.09 per 1000 population/year). Notably, 99.5% of Whites and 93.7% of Hispanics, but only 7.85% of Blacks, lived in balanced sex ratio counties; about 5% of Whites, half of Hispanics, and three-fourths of Blacks resided in counties with >20% same-race poverty. The dramatic Black-White differences in contextual factors in the United States and their association with sexual concurrency could contribute to the nation's profound racial disparities in HIV infection. Copyright © 2013 Elsevier Inc. All rights reserved.

Formation and implications of alpha-synuclein radical in Maneb- and paraquat-induced models of Parkinson’s disease

PubMed Central

Kumar, Ashutosh; Leinisch, Fabian; Kadiiska, Maria B.; Corbett, Jean; Mason, Ronald P.

2015-01-01

Parkinson’s disease (PD) is a debilitating, progressive, neurodegenerative disorder characterized by progressive loss of dopaminergic neurons and motor deficits. Alpha-synuclein-containing aggregates represent a feature of a variety of neurodegenerative disorders, including PD; however, the mechanism that initiates and promotes intraneuronal alpha-synuclein aggregation remains unknown. We hypothesized protein radical formation as an initiating mechanism for alpha-synuclein aggregation. Therefore, we used the highly sensitive immuno-spin trapping technique to investigate protein radical formation as a possible mechanism of alpha-synuclein aggregation as well as to investigate the source of protein radical formation in the midbrains of Maneb and paraquat coexposed mice. Coexposure to Maneb and paraquat for 6 weeks resulted in active microgliosis, NADPH oxidase activation, and inducible nitric oxide synthase (iNOS) induction, which culminated in protein radical formation in the midbrains of mice. Results obtained with immuno-spin trapping and immunoprecipitation experiments confirmed formation of alpha-synuclein radicals in dopaminergic neurons of exposed mice. Free radical formation requires NADPH oxidase and iNOS, as indicated by decreased protein radical formation in knockout mice (P47phox−/− and iNOS−/−) and in mice treated with inhibitors such as FeTPPS (a peroxynitrite decomposition catalyst), 1400W (an iNOS inhibitor), or apocynin (a NADPH oxidase inhibitor). Concurrence of protein radical formation with dopaminergic neuronal death indicated a link between protein radicals and disease progression. Taken together, these results show for the first time the formation and detection of the alpha-synuclein radical and suggest that NADPH oxidase and iNOS play roles in peroxynitrite-mediated protein radical formation and subsequent neuronal death in the midbrains of Maneb and paraquat coexposed mice. PMID:25952542

Tumor-derived CXCL8 signaling augments stroma-derived CCL2-promoted proliferation and CXCL12-mediated invasion of PTEN-deficient prostate cancer cells

PubMed Central

Maxwell, Pamela J.; Neisen, Jessica; Messenger, Johanna; Waugh, David J.J.

2014-01-01

Impaired PTEN function is a genetic hallmark of aggressive prostate cancers (CaP) and is associated with increased CXCL8 expression and signaling. The current aim was to further characterize biological responses and mechanisms underpinning CXCL8-promoted progression of PTEN-depleted prostate cancer, focusing on characterizing the potential interplay between CXCL8 and other disease-promoting chemokines resident within the prostate tumor microenvironment. Autocrine CXCL8-stimulation (i) increased expression of CXCR1 and CXCR2 in PTEN-deficient CaP cells suggesting a self-potentiating signaling axis and (ii) induced expression of CXCR4 and CCR2 in PTEN-wild-type and PTEN-depleted CaP cells. In contrast, paracrine CXCL8 signaling induced expression and secretion of the chemokines CCL2 and CXCL12 from prostate stromal WPMY-1 fibroblasts and monocytic macrophage-like THP-1 cells. In vitro studies demonstrated functional co-operation of tumor-derived CXCL8 with stromal-derived chemokines. CXCL12-induced migration of PC3 cells and CCL2-induced proliferation of prostate cancer cells were dependent upon intrinsic CXCL8 signaling within the prostate cancer cells. For example, in co-culture experiments, CXCL12/CXCR4 signaling but not CCL2/CCR2 signaling supported fibroblast-mediated migration of PC3 cells while CXCL12/CXCR4 and CCL2/CCR2 signaling underpinned monocyte-enhanced migration of PC3 cells. Combined inhibition of both CXCL8 and CXCL12 signaling was more effective in inhibiting fibroblast-promoted cell motility while repression of CXCL8 attenuated CCL2-promoted proliferation of prostate cancer cells. We conclude that tumor-derived CXCL8 signaling from PTEN-deficient tumor cells increases the sensitivity and responsiveness of CaP cells to stromal chemokines by concurrently upregulating receptor expression in cancer cells and inducing stromal chemokine synthesis. Combined chemokine targeting may be required to inhibit their multi-faceted actions in promoting the invasion and proliferation of aggressive CaP. PMID:24970800

The role biomedical science laboratories can play in improving science knowledge and promoting first-year nursing academic success

NASA Astrophysics Data System (ADS)

Arneson, Pam

The Role Biomedical Science Laboratories Can Play In Improving Science Knowledge and Promoting First-Year Nursing Academic Success The need for additional nursing and health care professionals is expected to increase dramatically over the next 20 years. With this in mind, students must have strong biomedical science knowledge to be competent in their field. Some studies have shown that participation in bioscience laboratories can enhance science knowledge. If this is true, an analysis of the role bioscience labs have in first-year nursing academic success is apposite. In response, this study sought to determine whether concurrent enrollment in anatomy and microbiology lecture and lab courses improved final lecture course grades. The investigation was expanded to include a comparison of first-year nursing GPA and prerequisite bioscience concurrent lecture/lab enrollment. Additionally, research has indicated that learning is affected by student perception of the course, instructor, content, and environment. To gain an insight regarding students' perspectives of laboratory courses, almost 100 students completed a 20-statement perception survey to understand how lab participation affects learning. Data analyses involved comparing anatomy and microbiology final lecture course grades between students who concurrently enrolled in the lecture and lab courses and students who completed the lecture course alone. Independent t test analyses revealed that there was no significant difference between the groups for anatomy, t(285) = .11, p = .912, but for microbiology, the lab course provided a significant educational benefit, t(256) = 4.47, p = .000. However, when concurrent prerequisite bioscience lecture/lab enrollment was compared to non-concurrent enrollment for first-year nursing GPA using independent t test analyses, no significant difference was found for South Dakota State University, t(37) = -1.57, p = .125, or for the University of South Dakota, t(38) = -0.46, p = .651. Student perception survey examination included computation of means and standard deviations for statements related to the educational importance of lab courses, the value of lab experimentation, and the usefulness of concurrent lecture/lab enrollment. Independent t test analyses sought to determine differences within the courses of anatomy lab and microbiology lab as well as differences between the instructors involved. Results suggested that student perceptions may be dependent on the course, the instructor, and possibly the content.

Progression of external and internal carotid artery stenosis is associated with a higher risk of ischemic neurologic events in patients with asymptomatic carotid artery stenosis.

PubMed

Masoomi, Reza; Shah, Zubair; Dawn, Buddhadeb; Vamanan, Karthik; Nanjundappa, Aravinda; Gupta, Kamal

2017-10-01

A small percentage of patients with asymptomatic carotid artery stenosis (ACAS) who are on optimal medical management do go on to develop ischemic stroke or transient ischemic attacks (IS/TIA). Several diagnostic tools have been studied to identify those patients who are at increased risk. However, most of these diagnostic tools are not available for routine clinical use or are resource intensive. We performed a retrospective study to assess the incremental value of external carotid artery stenosis progression (ECASP) along with internal carotid artery stenosis progression (ICASP) in predicting risk of ipsilateral IS/TIA in a cohort of patients with ACAS. We conducted a retrospective analysis of patients with ACAS who had at least two serial duplex ultrasounds (DUS) at our center. A total of 356 patients (712 carotid arteries) were included in the study (mean age 74.7±9 years, 49.2% male) with a mean follow-up of 60.7±32.7 months. In univariate analysis, concurrent progression of ICA and ECA stenosis on the same side arteries was associated with a very significant increased risk of ipsilateral IS/TIA (14.7% vs 4.6%, p<0.001). Also, multivariable regression analysis showed that concurrent ECA/ICA progression was an independent predictor of IS/TIA (OR=3.6, 95% CI 1.64-7.8; p=0.001). ECASP along with ICASP is significantly associated with increased risk of ipsilateral IS/TIA and provides incremental risk stratification over that provided by ICASP alone. The ECA is routinely evaluated in clinical practice, and it could serve as an additional marker for identifying higher risk patients with ACAS.

Epidemiological and morphological studies of double-chambered right ventricle in dogs.

PubMed

Fukushima, Ryuji; Tanaka, Ryou; Suzuki, Shuji; Hamabe, Rina; Machida, Noboru; Nakao, Shu; Saida, Yuto; Takashima, Kazuaki; Matsumoto, Hirotaka; Koyama, Hidekazu; Hirose, Hisashi; Yamane, Yoshihisa

2011-10-01

The double-chambered right ventricle (DCRV) is a rare congenital cardiac disease in dogs, and its detailed epidemiological and morphological features are not clearly understood. By investigating the profile, clinical signs, and characteristics of examination findings of eleven dogs with DCRV by means of a retrospective study, we attempted to clarify the epidemiology and morphology of the condition. The study group consisted of nine males and two females. Breeds included Pug (n=3), Miniature Dachshund (n=1), French Bull-dog (n=1), Shiba (n=1), and Retrievers (n=5). The attachment site of the anomalous muscular bundle was continuous with the cardiac apex in nine dogs, and it was attached to the right ventricle free wall in the other two dogs. In dogs with DCRV, at least one of the following conditions was present concurrently: congenital or acquired tricuspid valve regurgitation (TR), ventricular septal defect, and atrial septal defect. Also, the pressure difference between the two chambers increased over time, and progressive right-sided heart failure was observed. In summary, DCRV occurs in small breeds of dog as well as in large breeds of dog and it may be more prevalent in males. The existence of two types of DCRV in dogs was established. Dog with DCRVs will have a high incidence of concurrent cardiac abnormalities. Concurrent TR may be either congenital or acquired. DCRV is a congenital disorder, but the clinical condition progresses as the dog develops.

Diabetic Ketoacidosis with Concurrent Pancreatitis, Pancreatic β Islet Cell Tumor, and Adrenal Disease in an Obese Ferret (Mustela putorius furo)

PubMed Central

Phair, Kristen A; Carpenter, James W; Schermerhorn, Thomas; Ganta, Chanran K; DeBey, Brad M

2011-01-01

A 5.5-y-old spayed female ferret (Mustela putorius furo) with a history of adrenal disease, respiratory disease, and chronic obesity was evaluated for progressive lethargy and ataxia, diminished appetite, and possible polyuria and polydipsia. Physical examination revealed obesity, lethargy, tachypnea, dyspnea, a pendulous abdomen, significant weakness and ataxia of the hindlimbs, prolonged skin tenting, and mild tail-tip alopecia. Clinicopathologic analysis revealed severe hyperglycemia, azotemia, an increased anion gap, glucosuria, ketonuria, proteinuria, and hematuria. Abdominal ultrasonography showed hyperechoic hepatomegaly, bilateral adrenomegaly, splenic nodules, mild peritoneal effusion, and thickened and mildly hypoechoic limbs of the pancreas with surrounding hyperechoic mesentery. Fine-needle aspirates of the liver were highly suggestive of hepatic lipidosis. In light of a diagnosis of concurrent diabetic ketoacidosis and pancreatitis, the ferret was treated with fluid therapy, regular and long-acting insulin administration, and pain medication. However, electrolyte derangements, metabolic acidosis, dyspnea, and the clinical appearance of the ferret progressively worsened despite treatment, and euthanasia was elected. Necropsy revealed severe hepatic lipidosis, severe suppurative pancreatitis and vacuolar degeneration of pancreatic islet cells, a pancreatic β islet cell tumor, bilateral adrenal cortical adenomas, and myocardial fibrosis. To our knowledge, this case represents the first report of concurrent diabetes mellitus, pancreatitis, pancreatic β islet cell tumor (insulinoma), and adrenal disease in a domestic ferret. The simultaneous existence of 3 endocrine diseases, pancreatitis, and their associated complications is a unique and clinically challenging situation. PMID:21838985

Concurrent tamoxifen-related Müllerian adenofibromas in uterus and ovary.

PubMed

Shi, Haiyan; Chen, Xiaoduan; Lv, Bingjian; Zhang, Xiaofei

2015-01-01

Tamoxifen is a widely used in anti-oestrogen treatment of breast cancer. Previous reports showed that tamoxifen is associated with proliferative endometrial lesions. We herein reported an unusual case of concurrent hyperplastic lesions in the uterine cavity and right ovary in a 45-year-old woman with tamoxifen therapy. Regular vaginal ultrasonography showed the progressive endometrial thickening and right ovary enlargement during the period of drug use. Both lesions in the uterine cavity and right ovary showed characteristics resembling that of Müllerian adenofibroma. There were also foci of endometriosis in her bilateral ovarian surfaces. We suggest that women taking tamoxifen with a known history of endometriosis should be followed with transvaginal ultrasonography periodically.

The motor and cognitive features of Parkinson's disease in patients with concurrent Gaucher disease over 2 years: a case series.

PubMed

Collins, Lucy M; Williams-Gray, Caroline H; Morris, Elizabeth; Deegan, Patrick; Cox, Timothy M; Barker, Roger A

2018-05-29

We report the cognitive features and progression of Parkinson's disease (PD) in five patients with concurrent Gaucher disease. The patients presented at an earlier age than patients with sporadic PD, as previously noted by others; but in contrast to many previous reports, our patients followed a variable clinical course. While two patients developed early cognitive deficits and dementia, three others remained cognitively intact over the follow-up period. Thus, in this small case series, PD in the context of GD more closely resembles idiopathic PD in terms of its clinical heterogeneity in contrast to PD associated with GBA heterozygote mutations.

Involved-Field Radiotherapy versus Elective Nodal Irradiation in Combination with Concurrent Chemotherapy for Locally Advanced Non-Small Cell Lung Cancer: A Prospective Randomized Study

PubMed Central

Chen, Ming; Bao, Yong; Ma, Hong-Lian; Wang, Jin; Wang, Yan; Peng, Fang; Zhou, Qi-Chao; Xie, Cong-Hua

2013-01-01

This prospective randomized study is to evaluate the locoregional failure and its impact on survival by comparing involved field radiotherapy (IFRT) with elective nodal irradiation (ENI) in combination with concurrent chemotherapy for locally advanced non-small cell lung cancer. It appears that higher dose could be delivered in IFRT arm than that in ENI arm, and IFRT did not increase the risk of initially uninvolved or isolated nodal failures. Both a tendency of improved locoregional progression-free survival and a significant increased overall survival rate are in favor of IFRT arm in this study. PMID:23762840

"Boomerang Neuropathology" of Late-Onset Alzheimer's Disease is Shrouded in Harmful "BDDS": Breathing, Diet, Drinking, and Sleep During Aging.

PubMed

Daulatzai, Mak Adam

2015-07-01

Brain damage begins years before substantial neurodegeneration and Alzheimer's dementia. Crucial fundamental activities of life are breathing, eating, drinking, and sleeping. When these pivotal functions are maligned over a prolonged period, they impart escalating dyshomeostasis. The latter may lead to disastrous consequences including cognitive dysfunction and Alzheimer's disease (AD). The current theme here is that multiple pathophysiological derangements are promoted over a prolonged period by the very fundamental activities of life-when "rendered unhealthy." They may converge on several regulating/modulating factors (e.g., mitochondrial energy production, oxidative stress, innate immunity, and vascular function) and promote insidious neuropathology that culminates in cognitive decline in the aged. This is of course associated with the accumulation of amyloid beta and phosphorylated tau in the brain. Epidemiological, biomarker, and neuroimaging studies have provided significant copious evidence on the presence of indolent prodromal AD neuropathology many years prior to symptomatic onset. Progressive oxidative damage to specific gene promoters may result in gene silencing. A mechanistic link may possibly exist between epigenomic state, DNA damage, and chronically unhealthy/dysfunctional body systems. This paper, therefore, addresses and delineates the deleterious pathophysiological impact triggered by dysfunctional breathing, harmful diet, excess of alcohol consumption, and sleep deprivation; indeed, their impact may alter epigenetic state. It is mandatory, therefore, to abrogate cognitive decline and attenuate AD pathology through adoption of a healthy lifestyle, in conjunction with combination therapy with known moderators of cognitive decline. This strategy may thwart multiple concurrent and synergistic pathologies, including epigenetic dysfunction. A multi-factorial therapeutic intervention is required to overcome wide ranging neuropathology and multi-faceted disease process. Such an approach may attenuate neuropathology and ameliorate memory dysfunction.

The wound healing, chronic fibrosis, and cancer progression triad

PubMed Central

Rybinski, Brad; Franco-Barraza, Janusz

2014-01-01

For decades tumors have been recognized as “wounds that do not heal.” Besides the commonalities that tumors and wounded tissues share, the process of wound healing also portrays similar characteristics with chronic fibrosis. In this review, we suggest a tight interrelationship, which is governed as a concurrence of cellular and microenvironmental reactivity among wound healing, chronic fibrosis, and cancer development/progression (i.e., the WHFC triad). It is clear that the same cell types, as well as soluble and matrix elements that drive wound healing (including regeneration) via distinct signaling pathways, also fuel chronic fibrosis and tumor progression. Hence, here we review the relationship between fibrosis and cancer through the lens of wound healing. PMID:24520152

PROGRESSIVE MUSCULAR DYSTROPHY—A Preliminary Report on Treatment with Amino Acids, Folic Acid and Vitamins

PubMed Central

Van Meter, J. Ray

1953-01-01

Ten patients with progressive muscular dystrophy were given daily oral doses of amino acids, folic acid and selected vitamins. At the time of this report they had been treated by this means for periods varying from two months to one year. Only one had other therapy concurrently. Definite and progressive improvement, objective and subjective, occurred in all cases. Among objective changes noted—not all of them in all cases—were return of strength, increase in size and tonus of atrophic muscles, restoration of normal respiratory action and relief of depression. Patients reported a sense of well-being, increase in strength and a feeling of bodily warmth. PMID:13094541

Concurrent activation of β2-adrenergic receptor and blockage of GPR55 disrupts pro-oncogenic signaling in glioma cells.

PubMed

Wnorowski, Artur; Such, Justyna; Paul, Rajib K; Wersto, Robert P; Indig, Fred E; Jozwiak, Krzysztof; Bernier, Michel; Wainer, Irving W

2017-08-01

Activation of β 2 -adrenergic receptor (β 2 AR) and deorphanized GPR55 has been shown to modulate cancer growth in diverse tumor types in vitro and in xenograft models in vivo. (R,R')-4'-methoxy-1-naphthylfenoterol [(R,R')-MNF] is a bivalent compound that agonizes β 2 AR but inhibits GPR55-mediated pro-oncogenic responses. Here, we investigated the molecular mechanisms underlying the anti-tumorigenic effects of concurrent β 2 AR activation and GPR55 blockade in C6 glioma cells using (R,R')-MNF as a marker ligand. Our data show that (R,R')-MNF elicited G1-phase cell cycle arrest and apoptosis, reduced serum-inducible cell motility, promoted the phosphorylation of PKA target proteins, and inhibited constitutive activation of ERK and AKT in the low nanomolar range, whereas high nanomolar levels of (R,R')-MNF were required to block GPR55-mediated cell motility. siRNA knockdown and pharmacological inhibition of β 2 AR activity were accompanied by significant upregulation of AKT and ERK phosphorylation, and selective alteration in (R,R')-MNF responsiveness. The effects of agonist stimulation of GPR55 on various readouts, including cell motility assays, were suppressed by (R,R')-MNF. Lastly, a significant increase in phosphorylation-mediated inactivation of β-catenin occurred with (R,R')-MNF, and we provided new evidence of (R,R')-MNF-mediated inhibition of oncogenic β-catenin signaling in a C6 xenograft tumor model. Thus, simultaneous activation of β 2 AR and blockade of GPR55 may represent a novel therapeutic approach to combat the progression of glioblastoma cancer. Published by Elsevier Inc.

Breast-feeding duration for the prevention of excess body weight of mother-child pairs concurrently: a 2-year cohort study.

PubMed

Mastroeni, Marco Fabio; Mastroeni, Silmara Salete de Barros Silva; Czarnobay, Sandra Ana; Ekwaru, John Paul; Loehr, Sarah A; Veugelers, Paul J

2017-10-01

To examine the association between breast-feeding duration and the risk of excess body weight (children >85th percentile, mothers BMI≥25·0 kg/m2) concurrently in mother-child pairs two years after delivery. Prospective cohort study in Joinville, Brazil. Multivariable logistic regression was used to examine the independent relationship between breast-feeding duration and risk of excess body weight. Brazilian public maternity hospital. Three hundred and five mother-child pairs. At 2-year follow-up, 23·6 % of mother-child pairs had excess body weight. Children breast-fed for <2 months were more likely to have excess body weight than children breast-fed for ≥6 months (OR=2·4; 95 % CI 1·1, 5·1). Breast-feeding for <2 months was also associated with a greater likelihood of maternal excess body weight compared with those who breast-fed for ≥6 months (OR=2·9; 95 % CI 1·1, 8·1). There was a progressive increase in the likelihood of mother-child pairs having excess body weight as breast-feeding duration decreased. In addition to breast-feeding duration, other independent determinants of excess body weight were pre-pregnancy weight, gestational weight gain and number of pregnancies in mothers, and birth weight in children. Breast-feeding for a longer duration has a parallel protective effect on the risk of excess body weight in mother-child pairs two years after birth. Since members of the same family could be influenced by the same risk factors, continued promotion and support of breast-feeding may help to attenuate the rising prevalence of overweight in mother-child pairs.

Indirect Effects of Cognitive Self-Regulation on the Relation between Emotion Knowledge and Emotionality

ERIC Educational Resources Information Center

Ferrier, David E.; Karalus, Samantha P.; Denham, Susanne A.; Bassett, Hideko H.

2018-01-01

Between three and five years of age, both emotional competence (EC) and cognitive self-regulation (CSR) have been documented as undergoing remarkable growth and as being strong predictors of concurrent and future positive outcomes. EC encompasses three interrelated and progressively developing skills: emotion knowledge, emotion regulation, and…

Utah System of Higher Education 2015-16 Annual Report

ERIC Educational Resources Information Center

Utah System of Higher Education, 2016

2016-01-01

This annual report describes Utah System of Higher Education's progress in the 2015-2016 academic year in the following areas: (1) Strategic plan; (2) Enrollment and completion; (3) Paying for college; (4) Funding higher education; (5) College preparation; (6) Concurrent enrollment and math; (7) Outreach and access; and (8) Industry and the…

The Effects of Alzheimer's Disease on Close Relationships between Patients and Caregivers.

ERIC Educational Resources Information Center

Blieszner, Rosemary; Shifflett, Peggy A.

1990-01-01

Interviewed 11 caregivers for early-stage Alzheimer's patients to investigate changes in relationships concurrently with onset and progress of disease. Over 18 months, intimacy declined in both spouse and parent-child relationships. Caregivers were saddened at loss of reciprocal aspects of relationship and had difficulty coping with uncertain…

Tracking in 4 dimensions

DOE PAGES

Cartiglia, N.; Arcidiacono, R.; Baldassarri, B.; ...

2016-06-03

In this contribution we will review the progresses toward the construction of a tracking system able to measure the passage of charged particles with a combined precision of ~10 ps and ~10 μm, either using a single type of sensor, able to concurrently measure position and time, or a combination of position and time sensors.

Developing Information Fluency in Introductory Biology Students in the Context of an Investigative Laboratory

ERIC Educational Resources Information Center

Lindquester, Gary J.; Burks, Romi L.; Jaslow, Carolyn R.

2005-01-01

Students of biology must learn the scientific method for generating information in the field. Concurrently, they should learn how information is reported and accessed. We developed a progressive set of exercises for the undergraduate introductory biology laboratory that combine these objectives. Pre- and postassessments of approximately 100…

Intersensory Redundancy Enhances Memory in Bobwhite Quail Embryos

ERIC Educational Resources Information Center

Lickliter, Robert; Bahrick, Lorraine E.; Honeycutt, Hunter

2004-01-01

Information presented concurrently and redundantly to 2 or more senses (intersensory redundancy) has been shown to recruit attention and promote perceptual learning of amodal stimulus properties in animal embryos and human infants. This study examined whether the facilitative effect of intersensory redundancy also extends to the domain of memory.…

A Multicenter Phase II Trial of S-1 With Concurrent Radiation Therapy for Locally Advanced Pancreatic Cancer

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

Ikeda, Masafumi, E-mail: masikeda@east.ncc.go.jp; Ioka, Tatsuya; Ito, Yoshinori

2013-01-01

Purpose: The aim of this trial was to evaluate the efficacy and toxicity of S-1 and concurrent radiation therapy for locally advanced pancreatic cancer (PC). Methods and Materials: Locally advanced PC patients with histologically or cytologically confirmed adenocarcinoma or adenosquamous carcinoma, who had no previous therapy were enrolled. Radiation therapy was delivered through 3 or more fields at a total dose of 50.4 Gy in 28 fractions over 5.5 weeks. S-1 was administered orally at a dose of 80 mg/m{sup 2} twice daily on the day of irradiation during radiation therapy. After a 2- to 8-week break, patients received amore » maintenance dose of S-1 (80 mg/m{sup 2}/day for 28 consecutive days, followed by a 14-day rest period) was then administered until the appearance of disease progression or unacceptable toxicity. The primary efficacy endpoint was survival, and the secondary efficacy endpoints were progression-free survival, response rate, and serum carbohydrate antigen 19-9 (CA19-9) response; the safety endpoint was toxicity. Results: Of the 60 evaluable patients, 16 patients achieved a partial response (27%; 95% confidence interval [CI], 16%-40%). The median progression-free survival period, overall survival period, and 1-year survival rate of the evaluable patients were 9.7 months (95% CI, 6.9-11.6 months), 16.2 months (95% CI, 13.5-21.3 months), and 72% (95%CI, 59%-82%), respectively. Of the 42 patients with a pretreatment serum CA19-9 level of {>=}100 U/ml, 34 (81%) patients showed a decrease of greater than 50%. Leukopenia (6 patients, 10%) and anorexia (4 patients, 7%) were the major grade 3-4 toxicities with chemoradiation therapy. Conclusions: The effect of S-1 with concurrent radiation therapy in patients with locally advanced PC was found to be very favorable, with only mild toxicity.« less

Impact of weight change during the course of concurrent chemoradiation therapy on outcomes in stage IIIB non-small cell lung cancer patients: retrospective analysis of 425 patients.

PubMed

Topkan, Erkan; Parlak, Cem; Selek, Ugur

2013-11-15

We retrospectively investigated the impact of weight change (WC) during concurrent chemoradiation therapy (C-CRT) on clinical outcomes of stage 3B non-small cell lung cancer (NSCLC) patients. A total of 425 patients treated with C-CRT were included. All patients received 60 to 66 Gy of thoracic radiation therapy concurrently with 1 to 3 cycles of platinum-based chemotherapy. Pre- and posttreatment weight measurements on first and last days of C-CRT were used for WC. Patients were divided into 2 groups: group 1=weight loss (WL); group 2=weight preservation/gain (WP) for comparative analyses. Following C-CRT, 252 patients (59.3%) experienced WL, while 89 patients (20.9%) and 84 patients (19.8%) showed WP or WG. At median 24.2 months of follow-up, 142 patients (33.4%) were alive (84 WP [48.6%] and 58 WL [23.0%]), and 58 (13.6%) of them were free of disease progression (41 [23.7%] for WP and 17 [6.7%] for WL). Median overall survival (OS), locoregional progression-free survival (LRPFS), progression-free survival (PFS), and distant metastases-free survival (DMFS) for the entire population were 22.8, 14.4, 10.6, and 11.7 months, respectively. Intergroup comparisons between WP and WL cohorts revealed significantly superior OS, LRPFS, PFS, and DMFS in WP patients (P<.05 for each). On multivariate analyses, only WL and advanced T stage were associated with poor prognosis (P<.05). Present results in 425 stage 3B NSCLC patients demonstrated that WL during C-CRT is strongly associated with inferior survival outcomes compared to WP. This emerging finding might be useful by forming an encouraging basis for future investigations in facilitating a way to improve the outcomes of these patients experiencing WL during C-CRT. Copyright © 2013 Elsevier Inc. All rights reserved.

{sup 18}F-Fluorodeoxyglucose/Positron Emission Tomography Predicts Patterns of Failure After Definitive Chemoradiation Therapy for Locally Advanced Non-Small Cell Lung Cancer

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

Ohri, Nitin, E-mail: ohri.nitin@gmail.com; Bodner, William R.; Halmos, Balazs

Background: We previously reported that pretreatment positron emission tomography (PET) identifies lesions at high risk for progression after concurrent chemoradiation therapy (CRT) for locally advanced non-small cell lung cancer (NSCLC). Here we validate those findings and generate tumor control probability (TCP) models. Methods: We identified patients treated with definitive, concurrent CRT for locally advanced NSCLC who underwent staging {sup 18}F-fluorodeoxyglucose/PET/computed tomography. Visible hypermetabolic lesions (primary tumors and lymph nodes) were delineated on each patient's pretreatment PET scan. Posttreatment imaging was reviewed to identify locations of disease progression. Competing risks analyses were performed to examine metabolic tumor volume (MTV) and radiation therapymore » dose as predictors of local disease progression. TCP modeling was performed to describe the likelihood of local disease control as a function of lesion size. Results: Eighty-nine patients with 259 hypermetabolic lesions (83 primary tumors and 176 regional lymph nodes) met the inclusion criteria. Twenty-eight patients were included in our previous report, and the remaining 61 constituted our validation cohort. The median follow-up time was 22.7 months for living patients. In 20 patients, the first site of progression was a primary tumor or lymph node treated with radiation therapy. The median time to progression for those patients was 11.5 months. Data from our validation cohort confirmed that lesion MTV predicts local progression, with a 30-month cumulative incidence rate of 23% for lesions above 25 cc compared with 4% for lesions below 25 cc (P=.008). We found no evidence that radiation therapy dose was associated with local progression risk. TCP modeling yielded predicted 30-month local control rates of 98% for a 1-cc lesion, 94% for a 10-cc lesion, and 74% for a 50-cc lesion. Conclusion: Pretreatment FDG-PET identifies lesions at risk for progression after CRT for locally advanced NSCLC. Strategies to improve local control should be tested on high-risk lesions, and treatment deintensification for low-risk lesions should be explored.« less

Adventures in hepatocarcinogenesis.

PubMed

Pitot, Henry C

2007-01-01

Neoplasia is a heritably altered, relatively autonomous growth of tissue. Hepatocarcinogenesis, the pathogenesis of neoplasia in liver, as modeled in the rat exhibits three distinct, quantifiable stages: initiation, promotion, and progression. Simple mutations and/or epigenetic alterations may result in the irreversible stage of initiation. The stage of promotion results from selective enhancement of cell replication and selective inhibition of cellular apoptosis of initiated cells dependent on the genetic and/or epigenetic alterations of the latter. The irreversible stage of progression results from initial karyotypic alterations that evolve into greater degrees of genomic instability. The initial genomic alteration in the transition from promotion to progression may involve primarily epigenetic mechanisms driven by epigenetic and genetic alterations fixed during the stage of promotion.

Partially methylated alleles, microdeletion, and tissue mosaicism in a fragile X male with tremor and ataxia at 30 years of age: A case report.

PubMed

Hwang, Yun Tae; Aliaga, Solange Mabel; Arpone, Marta; Francis, David; Li, Xin; Chong, Belinda; Slater, Howard Robert; Rogers, Carolyn; Bretherton, Lesley; Hunter, Matthew; Heard, Robert; Godler, David Eugeny

2016-12-01

CGG repeat expansion >200 within FMR1, termed full mutation (FM), has been associated with promoter methylation, consequent silencing of gene expression and fragile X syndrome (FXS)-a common cause of intellectual disability and co-morbid autism. Unmethylated premutation (55-199 repeats) and FM alleles have been associated with fragile X related tremor/ataxia syndrome (FXTAS), a late onset neurodegenerative disorder. Here we present a 33-year-old male with FXS, with white matter changes and progressive deterioration in gait with cerebellar signs consistent with probable FXTAS; there was no evidence of any other cerebellar pathology. We show that he has tissue mosaicism in blood, saliva, and buccal samples for the size and methylation of his expanded alleles and a de novo, unmethylated microdeletion. This microdeletion involves a ∼80 bp sequence in the FMR1 promoter as well as complete loss of the CGG repeat in a proportion of cells. Despite FMR1 mRNA levels in blood within the normal range, the methylation and CGG sizing results are consistent with the diagnosis of concurrent FXS and probable FXTAS. The demonstrated presence of unmethylated FM alleles would explain the manifestation of milder than expected cognitive and behavioral impairments and early onset of cerebellar ataxia. Our case suggests that individuals with FXS, who manifest symptoms of FXTAS, may benefit from more detailed laboratory testing. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Sleep, health behaviors, and behavioral interventions: Reducing the risk of cardiovascular disease in adults

PubMed Central

Kaar, Jill L; Luberto, Christina M; Campbell, Kirsti A; Huffman, Jeff C

2017-01-01

Numerous health behaviors, including physical activity, diet, smoking, and sleep, play a major role in preventing the development and progression of cardiovascular disease (CVD). Among these behaviors, sleep may play a pivotal role, yet it has been studied somewhat less than other behaviors and there have been few well-designed sleep intervention studies targeting CVD. Furthermore, despite the fact that these behaviors are often interrelated, interventions tend to focus on changing one health behavior rather than concurrently intervening on multiple behaviors. Psychological constructs from depression to positive affect may also have a major effect on these health behaviors and ultimately on CVD. In this review, we summarize the existing literature on the impact of sleep and other cardiac health behaviors on CVD onset and prognosis. We also describe interventions that may promote these behaviors, from established interventions such as motivational interviewing and cognitive behavioral therapy, to more novel approaches focused on mindfulness and other positive psychological constructs. Finally, we outline population-health-level care management approaches for patients with psychiatric conditions (e.g., depression) that may impact cardiac health, and discuss their potential utility in improving mental health, promoting health behaviors, and reducing CVD-related risk. Much work is still needed to better understand how sleep and other health behaviors may uniquely contribute to CVD risk, and additional high-quality studies of interventions designed to modify cardiac health behaviors are required to improve cardiovascular health in individuals and the population at large. PMID:28603586

A phase II study of nab-paclitaxel plus carboplatin in combination with thoracic radiation in patients with locally advanced non-small-cell lung cancer.

PubMed

Hasegawa, Takaaki; Futamura, Yohei; Horiba, Akane; Yoshida, Tsutomu; Suzuki, Toshitaka; Kato, Tatsuo; Kaito, Daizo; Ohno, Yasuhi; Iida, Takayoshi; Hayashi, Shinya; Sawa, Toshiyuki

2016-01-01

We investigated the efficacy and safety of albumin-bound paclitaxel (nab-PTX) and carboplatin (CBDCA) with concurrent radiotherapy for unresectable locally advanced non-small-cell lung cancer (NSCLC). Patients with Stage III NSCLC and an Eastern Cooperative Oncology Group performance status of 0 or 1 were eligible. Concurrent chemoradiotherapy consisted of weekly administration of nab-PTX (40 mg/m(2)) plus CBDCA (area under the plasma concentration time curve (AUC) 2) and thoracic radiotherapy (60 Gy/30 fractions) for a total of 6 weeks. After concurrent chemoradiotherapy, patients received an additional two cycles of consolidation phase chemotherapy that consisted of 4-week cycles of nab-PTX (100 mg/m(2) on Days 1, 8 and 15)/CBDCA (AUC 5 mg/ml/min on Day 1). Response was evaluated in accordance with the Response Evaluation Criteria in Solid Tumors. Progression-free survival and overall survival were estimated using the Kaplan-Meier method. Toxicity was graded using the National Cancer Institute Common Terminology Criteria for Adverse Events. A total of 10 patients were enrolled in this trial between September 2013 and January 2014 from three institutes. The overall response rate was 40.0% and the median progression-free survival was 6.7 months. Treatment-related death occurred in two patients. Grade 2 or worse severe radiation pneumonitis was observed in all three patients that had the volume of lung receiving at least 20 Gy (V20) >30%. The results of this study indicate that no further investigation is warranted into nab-PTX and CBDCA with concurrent thoracic radiation for Stage III NSCLC with V20 > 30% due to severe toxicity. © The Author 2015. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Hallucinations and sleep disorders in PD

PubMed Central

Goetz, Christopher G.; Ouyang, Bichun; Negron, Alice; Stebbins, Glenn T.

2010-01-01

Objective: To assess prospectively progression and relationship of hallucinations and sleep disorders over a 10-year longitudinal study of patients with Parkinson disease (PD). Methods: Eighty-nine patients with PD were recruited to fill cells of normal sleep without hallucinations (n = 20), sleep fragmentation only (n = 20), vivid dreams/nightmares (n = 20), hallucinations with insight (n = 20), and hallucinations without insight (n = 9). At baseline, 0.5, 1.5, 4, 6, and 10 years, sleep disorders and hallucinations were assessed by standardized scales with the longitudinal data analyzed by generalized estimating equations with assumptions of linearity in time. Results: At 10 years, we could account for all subjects (27 interviewed, 61 deceased, and 1 too ill for interview). Hallucination prevalence and severity increased over time (p < 0.0001, p = 0.0001). Acting out dreams also increased over time (p = 0.001). In contrast, presence of vivid dreams/nightmares or sleep fragmentation did not increase over time. For all visits, the prevalence of sleep fragmentation did not differ between subjects with vs without hallucinations (odds ratio [OR] = 1.50, p = 0.09). However, severe sleep fragmentation was associated with concurrent hallucinations (OR 2.01, p = 0.006). The presence of hallucinations was also highly associated with concurrent vivid dreams/nightmares (OR = 2.60, p < 0.0001) and with concurrent acting out dreams (OR = 2.38, p = 0.0004). Among the baseline nonhallucinators, no sleep abnormalities at study entry predicted future development of hallucinations. Conclusions: Hallucinations and sleep abnormalities follow very different patterns of progression in PD over 10 years. Whereas patients with hallucinations often have concurrent sleep aberrations, no sleep problem is predictive of future hallucinations. GLOSSARY CI = confidence interval; GEE = generalized estimating equation; MMSE = Mini-Mental State Examination; OR = odds ratio; PD = Parkinson disease; PSQI = Pittsburgh Sleep Quality Index; UPDRS = Unified Parkinson's Disease Rating Scale; UPDRSm = motor section of the Unified Parkinson's Disease Rating Scale. PMID:20962287

Concurrent nuclear ERG and MYC protein overexpression defines a subset of locally advanced prostate cancer: Potential opportunities for synergistic targeted therapeutics.

PubMed

Udager, Aaron M; DeMarzo, Angelo M; Shi, Yang; Hicks, Jessica L; Cao, Xuhong; Siddiqui, Javed; Jiang, Hui; Chinnaiyan, Arul M; Mehra, Rohit

2016-06-01

Recurrent ERG gene fusions, the most common genetic alterations in prostate cancer, drive overexpression of the nuclear transcription factor ERG, and are early clonal events in prostate cancer progression. The nuclear transcription factor MYC is also frequently overexpressed in prostate cancer and may play a role in tumor initiation and/or progression. The relationship between nuclear ERG and MYC protein overexpression in prostate cancer, as well as the clinicopathologic characteristics and prognosis of ERG-positive/MYC high tumors, is not well understood. Immunohistochemistry (IHC) for ERG and MYC was performed on formalin-fixed, paraffin-embedded tissue from prostate cancer tissue microarrays (TMAs), and nuclear staining was scored semi-quantitatively (IHC product score range = 0-300). Correlation between nuclear ERG and MYC protein expression and association with clinicopathologic parameters and biochemical recurrence after radical prostatectomy was assessed. 29.1% of all tumor nodules showed concurrent nuclear ERG and MYC protein overexpression (i.e., ERG-positive/MYC high), including 35.0% of secondary nodules. Overall, there was weak positive correlation between ERG and MYC expression across all tumor nodules (rpb  = 0.149, P = 0.045), although this correlation was strongest in secondary nodules (rpb  = 0.520, P = 0.019). In radical prostatectomy specimens, ERG-positive/MYC high tumors were positively associated with the presence of extraprostatic extension (EPE), relative to all other ERG/MYC expression subgroups, however, there was no significant association between concurrent nuclear ERG and MYC protein overexpression and time to biochemical recurrence. Concurrent nuclear ERG and MYC protein overexpression is common in prostate cancer and defines a subset of locally advanced tumors. Recent data indicates that BET bromodomain proteins regulate ERG gene fusion and MYC gene expression in prostate cancer, suggesting possible synergistic targeted therapeutics in ERG-positive/MYC high tumors. Prostate 76:845-853, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Factors associated with kyphosis progression in older women: 15 years' experience in the study of osteoporotic fractures.

PubMed

Kado, Deborah M; Huang, Mei-Hua; Karlamangla, Arun S; Cawthon, Peggy; Katzman, Wendy; Hillier, Teresa A; Ensrud, Kristine; Cummings, Steven R

2013-01-01

Age-related hyperkyphosis is thought to be a result of underlying vertebral fractures, but studies suggest that among the most hyperkyphotic women, only one in three have underlying radiographic vertebral fractures. Although commonly observed, there is no widely accepted definition of hyperkyphosis in older persons, and other than vertebral fracture, no major causes have been identified. To identify important correlates of kyphosis and risk factors for its progression over time, we conducted a 15-year retrospective cohort study of 1196 women, aged 65 years and older at baseline (1986 to 1988), from four communities across the United States: Baltimore County, MD; Minneapolis, MN; Portland, OR; and the Monongahela Valley, PA. Cobb angle kyphosis was measured from radiographs obtained at baseline and an average of 3.7 and 15 years later. Repeated measures, mixed effects analyses were performed. At baseline, the mean kyphosis angle was 44.7 degrees (SE = 0.4, SD = 11.9) and significant correlates included a family history of hyperkyphosis, prevalent vertebral fracture, low bone mineral density, greater body weight, degenerative disc disease, and smoking. Over an average of 15 years, the mean increase in kyphosis was 7.1 degrees (SE = 0.25). Independent determinants of greater kyphosis progression were prevalent and incident vertebral fractures, low bone mineral density and concurrent bone density loss, low body weight, and concurrent weight loss. Thus, age-related kyphosis progression may be best prevented by slowing bone density loss and avoiding weight loss. Copyright © 2013 American Society for Bone and Mineral Research.

Factors Associated With Kyphosis Progression in Older Women: 15 years experience in the Study of Osteoporotic Fractures

PubMed Central

Kado, DM; Huang, MH; Karlamangla, AS; Cawthon, P; Katzman, W; Hillier, TA; Ensrud, K; Cummings, SR

2012-01-01

Age-related hyperkyphosis is thought to be a result of underlying vertebral fractures, but studies suggest that among the most hyperkyphotic women, only one in three have underlying radiographic vertebral fractures. Although commonly observed, there is no widely accepted definition of hyperkyphosis in older persons, and other than vertebral fracture, no major causes have been identified. To identify important correlates of kyphosis and risk factors for its progression over time, we conducted a 15 year retrospective cohort study of 1,196 women, aged 65 years and older at baseline (1986–88), from four communities across the United States: Baltimore County, MD; Minneapolis, MN, Portland, Oregon, and the Monongahela Valley, PA. Cobb angle kyphosis was measured from radiographs obtained at baseline and an average of 3.7 and 15 years later. Repeated measures, mixed effects analyses were performed. At baseline, the mean kyphosis angle was 44.7 degrees (standard error 0.4, standard deviation 11.9) and significant correlates included a family history of hyperkyphosis, prevalent vertebral fracture, low bone mineral density, greater body weight, degenerative disc disease, and smoking. Over an average of 15 years, the mean increase in kyphosis was 7.1 degrees (standard error 0.25). Independent determinants of greater kyphosis progression were prevalent and incident vertebral fractures, low bone mineral density and concurrent bone density loss, low body weight, and concurrent weight loss. Thus, age-related kyphosis progression may be best prevented by slowing bone density loss and avoiding weight loss. PMID:22865329

TLR5 signaling, commensal microbiota and systemic tumor promoting inflammation: the three parcae of malignant progression.

PubMed

Rutkowski, Melanie R; Conejo-Garcia, Jose R

2015-08-01

We have reported that TLR5-mediated recognition of commensal microbiota modulates systemic tumor-promoting inflammation and malignant progression of tumors at distal locations. Approximately 7-10% of the general population harbors a deleterious single nucleotide polymorphism in TLR5, implicating a novel role for genetic variation during the initiation and progression of cancer.

Folic Acid Supplementation Promotes Mammary Tumor Progression in a Rat Model

PubMed Central

Deghan Manshadi, Shaidah; Ishiguro, Lisa; Sohn, Kyoung-Jin; Medline, Alan; Renlund, Richard; Croxford, Ruth; Kim, Young-In

2014-01-01

Folic acid supplementation may prevent the development of cancer in normal tissues but may promote the progression of established (pre)neoplastic lesions. However, whether or not folic acid supplementation can promote the progression of established (pre)neoplastic mammary lesions is unknown. This is a critically important issue because breast cancer patients and survivors in North America are likely exposed to high levels of folic acid owing to folic acid fortification and widespread supplemental use after cancer diagnosis. We investigated whether folic acid supplementation can promote the progression of established mammary tumors. Female Sprague-Dawley rats were placed on a control diet and mammary tumors were initiated with 7,12-dimethylbenza[a]anthracene at puberty. When the sentinel tumor reached a predefined size, rats were randomized to receive a diet containing the control, 2.5x, 4x, or 5x supplemental levels of folic acid for up to 12 weeks. The sentinel mammary tumor growth was monitored weekly. At necropsy, the sentinel and all other mammary tumors were analyzed histologically. The effect of folic acid supplementation on the expression of proteins involved in proliferation, apoptosis, and mammary tumorigenesis was determined in representative sentinel adenocarcinomas. Although no clear dose-response relationship was observed, folic acid supplementation significantly promoted the progression of the sentinel mammary tumors and was associated with significantly higher sentinel mammary tumor weight and volume compared with the control diet. Furthermore, folic acid supplementation was associated with significantly higher weight and volume of all mammary tumors. The most significant and consistent mammary tumor-promoting effect was observed with the 2.5x supplemental level of folic acid. Folic acid supplementation was also associated with an increased expression of BAX, PARP, and HER2. Our data suggest that folic acid supplementation may promote the progression of established mammary tumors. The potential tumor-promoting effect of folic acid supplementation in breast cancer patients and survivors needs further clarification. PMID:24465421

Concurrency of Guillain-Barre syndrome and acute transverse myelitis: a case report and review of literature.

PubMed

Tolunay, Orkun; Çelik, Tamer; Çelik, Ümit; Kömür, Mustafa; Tanyeli, Zeynep; Sönmezler, Abdurrahman

2016-11-01

Guillain-Barré syndrome and acute transverse myelitis manifest as demyelinating diseases of the peripheral and central nervous system. Concurrency of these two disorders is rarely documented in literature. A 4-year-old girl presenting with cough, fever, and an impaired walking ability was admitted to hospital. She had no previous complaints in her medical history. A physical examination revealed lack of muscle strength of the lower extremities and deep tendon reflexes. MRI could not be carried out due to technical problems; therefore, both Guillain-Barré syndrome and acute transverse myelitis were considered for the diagnosis. Intravenous immunoglobulin treatment was started as first line therapy. Because this treatment did not relieve the patient's symptoms, spinal MRI was carried out on the fourth day of admission and demyelinating areas were identified. Based on the new findings, the patient was diagnosed with acute transverse myelitis, and high dose intravenous methylprednisolone therapy was started. Electromyography findings were consistent with acute polyneuropathy affecting both motor and sensory fibers. Therefore, the patient was diagnosed with concurrency of Guillain-Barré syndrome and acute transverse myelitis. Interestingly, while concurrency of these 2 disorders is rare, this association has been demonstrated in various recent publications. Progress in diagnostic tests (magnetic resonance imaging and electrophysiological examination studies) has enabled clinicians to establish the right diagnosis. The possibility of concurrent Guillain-Barré syndrome and acute transverse myelitis should be considered if recovery takes longer than anticipated.

Increasing Social Behaviors in Young Children with Social-Communication Delays in a Group Arrangement in Preschool

ERIC Educational Resources Information Center

Lane, Justin D.; Gast, David L.; Ledford, Jennifer R.; Shepley, Collin

2017-01-01

Young children with disabilities are less likely to display age-appropriate social behaviors than same-age peers with typical social development, especially children who display social-communication delays. In this study, two concurrently operating single case designs were used to evaluate the use of progressive time delay (PTD) to teach children…

Beyond Screening and Progress Monitoring: An Examination of the Reliability and Concurrent Validity of Maze Comprehension Assessments for Fourth-Grade Students

ERIC Educational Resources Information Center

Brasher, Casey F.

2017-01-01

Reading comprehension assessments often lack instructional utility because they do not accurately pinpoint why a student has difficulty. The varying formats, directions, and response requirements of comprehension assessments lead to differential measurement of underlying skills and contribute to noted amounts of unshared variance among tests. Maze…

Progress and Backlash in the Wake of "Obergefell": Reaching Conservative Southern Teachers through the Power of Literature

ERIC Educational Resources Information Center

Beck, Scott A.; Walker-DeVose, Dina; Agnich, Laura E.; Town, Caren; Smith, Trina

2017-01-01

This paper uses a mixed narrative and quantitative analysis to examine how a graduate class of predominantly politically and religiously conservative (self-identified), elementary teachers in the South made discursive sense of gender and sexually diverse (GSD) young adult and children's literature in the context of concurrent, relevant national…

Improvements in Intracorporeal Lithotripters for Percutaneous Nephrolithotomy

NASA Astrophysics Data System (ADS)

Kuo, Ramsay L.

2007-04-01

Percutaneous nephrolithotomy (PNL) is an effective minimally invasive surgical approach for the treatment of large renal stone burden. Intracorporeal lithotripters (ICL) are utilized during PNL to fragment calculi, with some devices capable of concurrently removing fragments as well. Much progress has been made in the design of ICL devices, resulting in potentially more efficient treatment of nephrolithiasis.

Illness in the Family: Old Myths and New Truths! Unit for Child Studies. Selected Papers Number 19.

ERIC Educational Resources Information Center

Perkins, Richard; Oldenburg, Brian

A multifactorial model of phases in the development and progress of physical illness is described, and the model's utility is illustrated. The model consists of antecedent and concurrent conditions and consequences related to physical, psychological, and social factors and their interaction. The application of the model is illustrated by a…

Ultrasonic histogram assessment of early response to concurrent chemo-radiotherapy in patients with locally advanced cervical cancer: a feasibility study.

PubMed

Xu, Yan; Ru, Tong; Zhu, Lijing; Liu, Baorui; Wang, Huanhuan; Zhu, Li; He, Jian; Liu, Song; Zhou, Zhengyang; Yang, Xiaofeng

To monitor early response for locally advanced cervical cancers undergoing concurrent chemo-radiotherapy (CCRT) by ultrasonic histogram. B-mode ultrasound examinations were performed at 4 time points in thirty-four patients during CCRT. Six ultrasonic histogram parameters were used to assess the echogenicity, homogeneity and heterogeneity of tumors. I peak increased rapidly since the first week after therapy initiation, whereas W low , W high and A high changed significantly at the second week. The average ultrasonic histogram progressively moved toward the right and converted into more symmetrical shape. Ultrasonic histogram could be served as a potential marker to monitor early response during CCRT. Copyright © 2018 Elsevier Inc. All rights reserved.

Cooperating knowledge-based systems

NASA Technical Reports Server (NTRS)

Feigenbaum, Edward A.; Buchanan, Bruce G.

1988-01-01

This final report covers work performed under Contract NCC2-220 between NASA Ames Research Center and the Knowledge Systems Laboratory, Stanford University. The period of research was from March 1, 1987 to February 29, 1988. Topics covered were as follows: (1) concurrent architectures for knowledge-based systems; (2) methods for the solution of geometric constraint satisfaction problems, and (3) reasoning under uncertainty. The research in concurrent architectures was co-funded by DARPA, as part of that agency's Strategic Computing Program. The research has been in progress since 1985, under DARPA and NASA sponsorship. The research in geometric constraint satisfaction has been done in the context of a particular application, that of determining the 3-D structure of complex protein molecules, using the constraints inferred from NMR measurements.

Three-dimensional conformal radiotherapy with concurrent chemotherapy for postoperative recurrence of esophageal squamous cell carcinoma: clinical efficacy and failure pattern

PubMed Central

2013-01-01

Background To assess the therapeutic outcome and failure pattern of three-dimensional conformal radiotherapy (3D-CRT)-based concurrent chemoradiotherapy (CCRT) for recurrence of esophageal squamous cell carcinoma (SCC) after radical surgery. Methods Treatment outcome and failure pattern were retrospectively evaluated in 83 patients with localized cervical and thoracic recurrences after radical surgery for thoracic esophageal SCC. All patients were treated with 3DCRT-based CCRT (median radiation dose 60 Gy), in which 39 received concurrent cisplatin plus 5-fluorouracil (PF), and 44 received concurrent docetaxel plus cisplatin (TP). Treatment response was evaluated at 1–3 months after CCRT. Results With a median follow-up of 34 months (range, 2–116 months), the 3-year overall survival (OS) of all the patients was 51.8% and the median OS time was 43.0 months. The overall tumor response rate was 75.9% (63/83), with a complete remission (CR) rate of 44.6% (37/83). In univariate analysis, tumor response after CCRT (p = 0.000), recurrence site (p = 0.028) and concurrent chemotherapy (p = 0.090) showed a trend favoring better OS. Multivariate analysis revealed that tumor response after CCRT (p = 0.000) and concurrent chemotherapy (p = 0.010) were independent predictors of OS. Forty-seven patients had progressive diseases after CCRT, 27 had local failure (27/47, 57.4%), 18 had distant metastasis (18/47, 38.3%) and 2 had both local and distant failures (2/47, 4.3%). Conclusions 3DCRT-based CCRT is effective in postoperatively recurrent esophageal SCC. Patients that obtained complete remission after CCRT appeared to achieve long-term OS and might benefit from concurrent TP regimen. Local and distant failures remained high and prospective studies are needed to validate these factors. PMID:24139225

Three-dimensional conformal radiotherapy with concurrent chemotherapy for postoperative recurrence of esophageal squamous cell carcinoma: clinical efficacy and failure pattern.

PubMed

Bao, Yong; Liu, ShiLiang; Zhou, QiChao; Cai, PeiQiang; Anfossi, Simone; Li, QiaoQiao; Hu, YongHong; Liu, MengZhong; Fu, JianHua; Rong, TieHua; Li, Qun; Liu, Hui

2013-10-18

To assess the therapeutic outcome and failure pattern of three-dimensional conformal radiotherapy (3D-CRT)-based concurrent chemoradiotherapy (CCRT) for recurrence of esophageal squamous cell carcinoma (SCC) after radical surgery. Treatment outcome and failure pattern were retrospectively evaluated in 83 patients with localized cervical and thoracic recurrences after radical surgery for thoracic esophageal SCC. All patients were treated with 3DCRT-based CCRT (median radiation dose 60 Gy), in which 39 received concurrent cisplatin plus 5-fluorouracil (PF), and 44 received concurrent docetaxel plus cisplatin (TP). Treatment response was evaluated at 1-3 months after CCRT. With a median follow-up of 34 months (range, 2-116 months), the 3-year overall survival (OS) of all the patients was 51.8% and the median OS time was 43.0 months. The overall tumor response rate was 75.9% (63/83), with a complete remission (CR) rate of 44.6% (37/83). In univariate analysis, tumor response after CCRT (p = 0.000), recurrence site (p = 0.028) and concurrent chemotherapy (p = 0.090) showed a trend favoring better OS. Multivariate analysis revealed that tumor response after CCRT (p = 0.000) and concurrent chemotherapy (p = 0.010) were independent predictors of OS. Forty-seven patients had progressive diseases after CCRT, 27 had local failure (27/47, 57.4%), 18 had distant metastasis (18/47, 38.3%) and 2 had both local and distant failures (2/47, 4.3%). 3DCRT-based CCRT is effective in postoperatively recurrent esophageal SCC. Patients that obtained complete remission after CCRT appeared to achieve long-term OS and might benefit from concurrent TP regimen. Local and distant failures remained high and prospective studies are needed to validate these factors.

Concurrent Psychosocial Predictors of Sun Safety among Middle School Youth

ERIC Educational Resources Information Center

Andreeva, Valentina A.; Reynolds, Kim D.; Buller, David B.; Chou, Chih-Ping; Yaroch, Amy L.

2008-01-01

Background: Sun-induced skin damage, which increases skin cancer risk, is initiated in early life and promoted through later sun exposure patterns. If sun safety determinants are well understood and addressed during the school years, skin cancer incidence might be reduced. This study tested psychosocial influences on youth's sun safety and…

Deciphering the physics and chemistry of perovskites with transmission electron microscopy.

PubMed

Polking, Mark J

2016-03-28

Perovskite oxides exhibit rich structural complexity and a broad range of functional properties, including ferroelectricity, ferromagnetism, and superconductivity. The development of aberration correction for the transmission electron microscope and concurrent progress in electron spectroscopy, electron holography, and other techniques has fueled rapid progress in the understanding of the physics and chemistry of these materials. New techniques based on the transmission electron microscope are first surveyed, and the applications of these techniques for the study of the structure, chemistry, electrostatics, and dynamics of perovskite oxides are then explored in detail, with a particular focus on ferroelectric materials.

Genetic alterations in the phosphatidylinositol-3 kinase/Akt pathway in thyroid cancer.

PubMed

Xing, Mingzhao

2010-07-01

Aberrant activation of the phosphatidylinositol-3 kinase (PI3K)/Akt pathway plays a fundamental role in thyroid tumorigenesis, particularly in follicular thyroid cancer (FTC) and aggressive thyroid cancer, such as anaplastic thyroid cancer (ATC). As the drivers of this process, many genetic alterations activating the PI3K/Akt pathway have been identified in thyroid cancer in recent years. This review summarizes the current knowledge on major genetic alterations in the PI3K/Akt pathway. These include PIK3CA mutations and genomic amplification/copy gain, Ras mutations, PTEN mutations, RET/PTC and PPARgamma/Pax8 rearrangements, as well as amplification/copy gain of PIK3CB, PDK1, Akt, and various receptor tyrosine kinase genes. Most of these genetic alterations are particularly common in FTC and many of them are even more common in ATC; they are generally less common in papillary thyroid cancer (PTC), in which the MAP kinase (MAPK) pathway activated by the BRAF mutation instead plays a major role. Methylation and, thus, epigenetic silencing of PTEN, a major negative regulator of the PI3K/Akt pathway, occurs in close association with activating genetic alterations of the PI3K/Akt pathway, constituting a unique self-enhancement mechanism for this pathway. Many of these genetic alterations are mutually exclusive in differentiated thyroid tumors, but with increasing concurrence from benign tumors to FTC to ATC. RET/PTC, Ras, and receptor tyrosine kinase could dually activate the PI3K/Akt and MAPK pathways. Most cases of ATC harbor genetic alterations in these genes or other genetic combinations that can activate both pathways. It is proposed that genetic alterations in the PI3K/Akt pathway promote thyroid cell transformation to FTC and that genetic alterations in the MAPK pathway promote cell transformation to PTC; accumulation of multiple genetic alterations that can activate both pathways promotes thyroid cancer aggressiveness and progression to ATC. Genetic alterations are common in the PI3K/Akt pathway in thyroid cancer and play a fundamental role in the tumorigenesis and progression of this cancer. This provides a strong basis for the emerging development of novel genetic-based diagnostic, prognostic, and therapeutic strategies for thyroid cancer.

Pooled Analysis of Individual Patient Data on Concurrent Chemoradiotherapy for Stage III Non-Small-Cell Lung Cancer in Elderly Patients Compared With Younger Patients Who Participated in US National Cancer Institute Cooperative Group Studies.

PubMed

Stinchcombe, Thomas E; Zhang, Ying; Vokes, Everett E; Schiller, Joan H; Bradley, Jeffrey D; Kelly, Karen; Curran, Walter J; Schild, Steven E; Movsas, Benjamin; Clamon, Gerald; Govindan, Ramaswamy; Blumenschein, George R; Socinski, Mark A; Ready, Neal E; Akerley, Wallace L; Cohen, Harvey J; Pang, Herbert H; Wang, Xiaofei

2017-09-01

Purpose Concurrent chemoradiotherapy is standard treatment for patients with stage III non-small-cell lung cancer. Elderly patients may experience increased rates of adverse events (AEs) or less benefit from concurrent chemoradiotherapy. Patients and Methods Individual patient data were collected from 16 phase II or III trials conducted by US National Cancer Institute-supported cooperative groups of concurrent chemoradiotherapy alone or with consolidation or induction chemotherapy for stage III non-small-cell lung cancer from 1990 to 2012. Overall survival (OS), progression-free survival, and AEs were compared between patients age ≥ 70 (elderly) and those younger than 70 years (younger). Unadjusted and adjusted hazard ratios (HRs) for survival time and CIs were estimated by single-predictor and multivariable frailty Cox models. Unadjusted and adjusted odds ratio (ORs) for AEs and CIs were obtained from single-predictor and multivariable generalized linear mixed-effect models. Results A total of 2,768 patients were classified as younger and 832 as elderly. In unadjusted and multivariable models, elderly patients had worse OS (HR, 1.20; 95% CI, 1.09 to 1.31 and HR, 1.17; 95% CI, 1.07 to 1.29, respectively). In unadjusted and multivariable models, elderly and younger patients had similar progression-free survival (HR, 1.01; 95% CI, 0.93 to 1.10 and HR, 1.00; 95% CI, 0.91 to 1.09, respectively). Elderly patients had a higher rate of grade ≥ 3 AEs in unadjusted and multivariable models (OR, 1.35; 95% CI, 1.07 to 1.70 and OR, 1.38; 95% CI, 1.10 to 1.74, respectively). Grade 5 AEs were significantly higher in elderly compared with younger patients (9% v 4%; P < .01). Fewer elderly compared with younger patients completed treatment (47% v 57%; P < .01), and more discontinued treatment because of AEs (20% v 13%; P < .01), died during treatment (7.8% v 2.9%; P < .01), and refused further treatment (5.8% v 3.9%; P = .02). Conclusion Elderly patients in concurrent chemoradiotherapy trials experienced worse OS, more toxicity, and had a higher rate of death during treatment than younger patients.

Internal consistency, concurrent validity, and discriminant validity of a measure of public support for policies for active living in transportation (PAL-T) in a population-based sample of adults.

PubMed

Fuller, Daniel; Gauvin, Lise; Fournier, Michel; Kestens, Yan; Daniel, Mark; Morency, Patrick; Drouin, Louis

2012-04-01

Active living is a broad conceptualization of physical activity that incorporates domains of exercise; recreational, household, and occupational activities; and active transportation. Policy makers develop and implement a variety of transportation policies that can influence choices about how to travel from one location to another. In making such decisions, policy makers act in part in response to public opinion or support for proposed policies. Measures of the public's support for policies aimed at promoting active transportation can inform researchers and policy makers. This study examined the internal consistency, and concurrent and discriminant validity of a newly developed measure of the public's support for policies for active living in transportation (PAL-T). A series of 17 items representing potential policies for promoting active transportation was generated. Two samples of participants (n = 2,001 and n = 2,502) from Montreal, Canada, were recruited via random digit dialling. Analyses were conducted on the combined data set (n = 4,503). Participants were aged 18 through 94 years (58% female). The concurrent and discriminant validity of the PAL-T was assessed by examining relationships with physical activity and smoking. To explore the usability of the PAL-T, predicted scale scores were compared to the summed values of responses. Results showed that the internal consistency of the PAL-T was 0.70. Multilevel regression demonstrated no relationship between the PAL-T and smoking status (p > 0.05) but significant relationships with utilitarian walking (p < 0.05) and cycling (p < 0.01) for at least 30 minutes on 5 days/week. The PAL-T has acceptable internal consistency and good concurrent and discriminant validity. Measuring public opinion can inform policy makers and support advocacy efforts aimed at making built environments more suitable for active transportation while allowing researchers to examine the antecedents and consequences of public support for policies.

Social networks and concurrent sexual relationships--a qualitative study among men in an urban South African community.

PubMed

Ragnarsson, Anders; Townsend, Loraine; Thorson, Anna; Chopra, Mickey; Ekstrom, Anna Mia

2009-10-01

The aim was to explore and describe characteristics of males' social and sexual networks in a South African peri-urban community. Twenty in-depth interviews were conducted with men participating in a larger quantitative study where the median age of the men was 28.7 years and almost 56% had some high-school education, 17.2% were unemployed and 94.7% were not married. A Thematic Question Guide with open-ended questions was used for the interviews. A thematic content analysis was conducted to explore the characteristics and dynamics of social and sexual relationships among these men. A high number of temporary and stable concurrent female sexual partners, geographic mobility and high levels of unprotected sex were common. Increased status as a man and lack of trust in women's fidelity were given as important reasons for concurrent female sexual relationships. Strong social networks within male core groups provided economic and social support for the pursuit and maintenance of this behaviour. Concurrent sexual relationships in combination with high viral loads among newly infected individuals unaware of their HIV status create an extremely high-risk environment for the spread of HIV in this population. Interventions targeting men at high risk of HIV need to challenge current societal norms of masculinity to help promote individual sexual risk reduction strategies. Such strategies should go beyond increasing condom use, to include a reduction in the number of concurrent sexual partners.

The developmental switch in GABA polarity is delayed in fragile X mice.

PubMed

He, Qionger; Nomura, Toshihiro; Xu, Jian; Contractor, Anis

2014-01-08

Delays in synaptic and neuronal development in the cortex are key hallmarks of fragile X syndrome, a prevalent neurodevelopmental disorder that causes intellectual disability and sensory deficits and is the most common known cause of autism. Previous studies have demonstrated that the normal progression of plasticity and synaptic refinement during the critical period is altered in the cortex of fragile X mice. Although the disruptions in excitatory synapses are well documented in fragile X, there is less known about inhibitory neurotransmission during the critical period. GABAergic transmission plays a crucial trophic role in cortical development through its early depolarizing action. At the end of cortical critical period, response properties of GABA transform into their mature hyperpolarizing type due to developmental changes in intracellular chloride homeostasis. We found that the timing of the switch from depolarizing to hyperpolarizing GABA is delayed in the cortex of fragile X mice and there is a concurrent alteration in the expression of the neuronal chloride cotransporter NKCC1 that promotes the accumulation of intracellular chloride. Disruption of the trophic effects of GABA during cortical development could contribute to the altered trajectory of synaptic maturation in fragile X syndrome.

The Role of Hypoxia in the Tumor Microenvironment: Implications for Ovarian Cancer Therapy

DTIC Science & Technology

2017-07-01

microenvironmental factor promoting metastatic progression. A critical step in metastatic tumor progression is the ability of tumor cells to evade immune attack...Tumor cells utilize a complex set of mechanisms that prevent the immune system from mounting effective anti-tumor responses. Moreover, the hypoxic...promote the immunosuppressive phenotypes of both tumor cells as well as infiltrating immune cells . However, the mechanisms by which hypoxia promotes

Developing a "toolkit" to measure implementation of concurrent palliative care in rural community cancer centers.

PubMed

Zubkoff, Lisa; Dionne-Odom, J Nicholas; Pisu, Maria; Babu, Dilip; Akyar, Imatullah; Smith, Tasha; Mancarella, Gisella A; Gansauer, Lucy; Sullivan, Margaret Murray; Swetz, Keith M; Azuero, Andres; Bakitas, Marie A

2018-02-01

Despite national guidelines recommending early concurrent palliative care for individuals newly diagnosed with metastatic cancer, few community cancer centers, especially those in underserved rural areas do so. We are implementing an early concurrent palliative care model, ENABLE (Educate, Nurture, Advise, Before Life Ends) in four, rural-serving community cancer centers. Our objective was to develop a "toolkit" to assist community cancer centers that wish to integrate early palliative care for patients with newly diagnosed advanced cancer and their family caregivers. Guided by the RE-AIM (Reach, Effectiveness-Adoption, Implementation, Maintenance) framework, we undertook an instrument-development process based on the literature, expert and site stakeholder review and feedback, and pilot testing during site visits. We developed four instruments to measure ENABLE implementation: (1) the ENABLE RE-AIM Self-Assessment Tool to assess reach, adoption, implementation, and maintenance; (2) the ENABLE General Organizational Index to assess institutional implementation; (3) an Implementation Costs Tool; and (4) an Oncology Clinicians' Perceptions of Early Concurrent Oncology Palliative Care survey. We developed four measures to determine early palliative care implementation. These measures have been pilot-tested, and will be integrated into a comprehensive "toolkit" to assist community cancer centers to measure implementation outcomes. We describe the lessons learned and recommend strategies for promoting long-term program sustainability.

Effect of concurrent training on risk factors and hepatic steatosis in obese adolescents

PubMed Central

Antunes, Barbara de Moura M.; Monteiro, Paula Alves; Silveira, Loreana Sanches; Cayres, Suziane Ungari; da Silva, Camila Buonani; F., Ismael Forte

2013-01-01

OBJECTIVE To analyze the effects of a 20-week concurrent training on the variables of body composition, lipid profile, and fatty liver diagnosis in obese adolescents. METHODS An open clinical trial was carried out with 34 obese adolescents aged between 12 and 15 years. Total body fat, trunk fat mass, total cholesterol and its fractions (HDL, LDL and VLDL), and triglycerides were analyzed; an upper abdominal ultrasound was performed in order to diagnose fatty liver. The participants underwent concurrent training (association of weight training with aerobic training) three times per week, lasting one hour for 20 weeks. Statistical analysis included paired Studentâ€(tm)s t-test and frequency analysis in order to verify the relative and absolute reductions of fatty liver diagnosis, being significant p<0.05. RESULTS The studied adolescents showed statistically significant improvement in body composition, with a decrease of total body fat percentage, total fat mass, trunk fat, and an a increase in the lean body mass. They also presented reduced size of liver lobes, decrease in total cholesterol and in LDL-cholesterol, with a lower prevalence of fatty liver. CONCLUSIONS The concurrent training was effective for promoting significant improvements in body fat composition and lipid profile variables, besides reducing fatty liver prevalence rate. PMID:24142321

Responding to the Psychological Needs of OEF-OIF Military: A Commentary on Progress in Treatment Development

ERIC Educational Resources Information Center

Keane, Terence M.

2011-01-01

America's involvement in the wars in Afghanistan and Iraq (i.e., OEF-OIF) is entering its 9th year with casualties exceeding 5,000 American deaths and many times that number with serious physical injuries. Epidemiological surveys and mental health screening concurrent with service and at the point of discharge provide us with important information…

From Desktop to Teraflop: Exploiting the U.S. Lead in High Performance Computing. NSF Blue Ribbon Panel on High Performance Computing.

ERIC Educational Resources Information Center

National Science Foundation, Washington, DC.

This report addresses an opportunity to accelerate progress in virtually every branch of science and engineering concurrently, while also boosting the American economy as business firms also learn to exploit these new capabilities. The successful rapid advancement in both science and technology creates its own challenges, four of which are…

MIT Laboratory for Computer Science Progress Report 27

DTIC Science & Technology

1990-06-01

because of the natural, yet unexploited, concurrence that characterizes contemporary and prospective applications from business to sensory computing...432. 14 Advanced Network Architecture Academic Staff D. Clark, Group Leader D. Tennenhouse J. Saltzer Research Staff J. Davin K. Sollins Graduate...Murray Hill, NJ, July 1989. 23 24 Clinical Decision Making Academic Staff R. Patil P. Szolovits, Group Leader G. Rennels Collaborating Investigators M

Concurrent and Longitudinal Predictors of Reading for Deaf and Hearing Children in Primary School

ERIC Educational Resources Information Center

Harris, Margaret; Terlektsi, Emmanouela; Kyle, Fiona Elizabeth

2017-01-01

Forty-one children with severe-profound prelingual hearing loss were assessed on single word reading, reading comprehension, English vocabulary, phonological awareness and speechreading at three time points, 1 year apart (T1-T3). Their progress was compared with that of a group of hearing children of similar nonverbal IQ, initially reading at the…

Preference for Progressive Delays and Concurrent Physical Therapy Exercise in an Adult with Acquired Brain Injury

ERIC Educational Resources Information Center

Dixon, Mark R.; Falcomata, Terry S.

2004-01-01

The purpose of this study was to increase self-control and engagement in a physical therapy task (head holding) for a man with acquired traumatic brain injury. Once impulsivity was observed (i.e., repeated impulsive choices), an experimental condition was introduced that consisted of choices between a small immediate reinforcer, a large…

Adaptation and psychometric assessment of the Hebrew version of the Recovery Promoting Relationships Scale (RPRS).

PubMed

Moran, Galia S; Zisman-Ilani, Yaara; Garber-Epstein, Paula; Roe, David

2014-03-01

Recovery is supported by relationships that are characterized by human centeredness, empowerment and a hopeful approach. The Recovery Promoting Relationships Scale (RPRS; Russinova, Rogers, & Ellison, 2006) assesses consumer-provider relationships from the consumer perspective. Here we present the adaptation and psychometric assessment of a Hebrew version of the RPRS. The RPRS was translated to Hebrew (RPRS-Heb) using multiple strategies to assure conceptual soundness. Then 216 mental health consumers were administered the RPRS-Heb as part of a larger project initiative implementing illness management and recovery intervention (IMR) in community settings. Psychometric testing included assessment of the factor structure, reliability, and validity using the Hope Scale, the Working Alliance Inventory, and the Recovery Assessment Scale. The RPRS-Heb factor structure replicated the two factor structures found in the original scale with minor exceptions. Reliability estimates were good: Cronbach's alpha for the total scale was 0.94. An estimate of 0.93 for the Recovery-Promoting Strategies factor, and 0.86 for the Core Relationship. Concurrent validity was confirmed using the Working Alliance Scale (rp = .51, p < .001) and the Hope Scale (rp = .43, p < .001). Criterion validity was examined using the Recovery Assessment Scale (rp = .355, p < .05). The study yielded a 23-item RPRS-Heb version with a psychometrically sound factor structure, satisfactory reliability, and concurrent validity tested against the Hope, Alliance, and Recovery Assessment scales. Outcomes are discussed in the context of the original scale properties and a similar Dutch initiative. The RPRS-Heb can serve as a valuable tool for studying recovery promoting relationships with Hebrew speaking population.

Early disease progression in patients with localized natural killer/T-cell lymphoma treated with concurrent chemoradiotherapy.

PubMed

Yamaguchi, Motoko; Suzuki, Ritsuro; Kim, Seok Jin; Ko, Young Hyeh; Oguchi, Masahiko; Asano, Naoko; Miyazaki, Kana; Terui, Yasuhiko; Kubota, Nobuko; Maeda, Takeshi; Kobayashi, Yukio; Amaki, Jun; Soejima, Toshinori; Saito, Bungo; Shimoda, Emiko; Fukuhara, Noriko; Tsukamoto, Norifumi; Shimada, Kazuyuki; Choi, Ilseung; Utsumi, Takahiko; Ejima, Yasuo; Kim, Won Seog; Katayama, Naoyuki

2018-03-30

Prognosis of patients with localized nasal extranodal natural killer/T-cell lymphoma, nasal type (ENKL) has been improved by non-anthracycline-containing treatments such as concurrent chemoradiotherapy (CCRT). However, some patients experience early disease progression. To clarify the clinical features and outcomes of these patients, data from 165 patients with localized nasal ENKL who were diagnosed between 2000 and 2013 at 31 institutes in Japan and who received radiotherapy with dexamethasone, etoposide, ifosfamide, and carboplatin (RT-DeVIC) were retrospectively analyzed. Progression of disease within 2 years after diagnosis (POD24) was used as the definition of early progression. An independent dataset of 60 patients with localized nasal ENKL who received CCRT at Samsung Medical Center was used in the validation analysis. POD24 was documented in 23% of patients who received RT-DeVIC and in 25% of patients in the validation cohort. Overall survival (OS) from risk-defining events of the POD24 group was inferior to that of the reference group in both cohorts (P < .00001). In the RT-DeVIC cohort, pretreatment elevated levels of serum soluble interleukin-2 receptor (sIL-2R), lactate dehydrogenase, C-reactive protein, and detectable Epstein-Barr virus DNA in peripheral blood were associated with POD24. In the validation cohort, no pretreatment clinical factor associated with POD24 was identified. Our study indicates that POD24 is a strong indicator of survival in localized ENKL, despite the different CCRT regimens adopted. In the treatment of localized nasal ENKL, POD24 is useful for identifying patients who have unmet medical needs. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

THE 6-MINUTE WALK TEST AND OTHER CLINICAL ENDPOINTS IN DUCHENNE MUSCULAR DYSTROPHY: RELIABILITY, CONCURRENT VALIDITY, AND MINIMAL CLINICALLY IMPORTANT DIFFERENCES FROM A MULTICENTER STUDY

PubMed Central

McDonald, Craig M; Henricson, Erik K; Abresch, R Ted; Florence, Julaine; Eagle, Michelle; Gappmaier, Eduard; Glanzman, Allan M; Spiegel, Robert; Barth, Jay; Elfring, Gary; Reha, Allen; Peltz, Stuart W

2013-01-01

Introduction: An international clinical trial enrolled 174 ambulatory males ≥5 years old with nonsense mutation Duchenne muscular dystrophy (nmDMD). Pretreatment data provide insight into reliability, concurrent validity, and minimal clinically important differences (MCIDs) of the 6-minute walk test (6MWT) and other endpoints. Methods: Screening and baseline evaluations included the 6-minute walk distance (6MWD), timed function tests (TFTs), quantitative strength by myometry, the PedsQL, heart rate–determined energy expenditure index, and other exploratory endpoints. Results: The 6MWT proved feasible and reliable in a multicenter context. Concurrent validity with other endpoints was excellent. The MCID for 6MWD was 28.5 and 31.7 meters based on 2 statistical distribution methods. Conclusions: The ratio of MCID to baseline mean is lower for 6MWD than for other endpoints. The 6MWD is an optimal primary endpoint for Duchenne muscular dystrophy (DMD) clinical trials that are focused therapeutically on preservation of ambulation and slowing of disease progression. Muscle Nerve 48: 357–368, 2013 PMID:23674289

Management of Locally Advanced Cancer Cervix an Indian Perspective.

PubMed

Singh, J K; Chauhan, Richa

2015-01-01

Cervical cancer has a major impact on the lives of Indian women with an estimated 122, 844 new cases of cervical cancer in the year 2012. About 80% of these cases present in a locally advanced stage leading to high morbidity and mortality. Because of lack of public awareness and infrastructure for screening and early detection in developing countries, this late presentation is likely to continue in the coming years. Radiation therapy has been the treatment of choice for patients with locally advanced cancer cervix. Many clinical trials and meta-analyses have shown a significant improvement in overall and progression-free survival with decreased local and distant recurrences with the use of concurrent chemotherapy with radiation. Most of these trials have been done in women from developed countries where the patient and disease profile are entirely different from ours. Recently, few trials from India have also shown promising results in locally advanced cancer cervix with concurrent chemoradiotherapy but toxicities remain a major concern. Further exploration is required for the use of concurrent chemo radiation prior to incorporating it into routine clinical practice.

Hypofractionated Palliative Radiotherapy with Concurrent Radiosensitizing Chemotherapy for Advanced Head and Neck Cancer Using the "QUAD-SHOT Regimen".

PubMed

Gamez, Mauricio E; Agarwal, Manuj; Hu, Kenneth S; Lukens, John N; Harrison, Louis B

2017-02-01

To analyze the outcomes using the hypofractionated palliative radiotherapy regimen "QUAD-Shot" with concurrent radiosensitizing chemotherapy for advanced head and neck cancer. We analyzed twenty-one patients with newly-diagnosed or recurrent head and neck cancer treated with palliative hypofractionated concurrent chemoradiation using the QUAD-Shot regimen. All patients received at least one cycle of RT, with sixteen patients (76%) completing all three cycles. 85.7 % of patients had objective response to therapy with five patients (23.8%) demonstrating complete response (CR) and thirteen patients (61.9%) demonstrating partial response (PR). Palliation of symptoms was achieved in all (100%) of the sixteen patients that completed the three cycles. Median overall survival and median progression-free survival were 7 and 4 months, respectively. QUAD-Shot palliative radiation therapy coupled with radiosensitizing chemotherapy is efficacious and well-tolerated in patients with newly-diagnosed or recurrent head and neck cancer not amenable to curative therapy. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Treatment of progressive multiple sclerosis: what works, what does not, and what is needed.

PubMed

Feinstein, Anthony; Freeman, Jenny; Lo, Albert C

2015-02-01

Disease-modifying drugs have mostly failed as treatments for progressive multiple sclerosis. Management of the disease therefore solely aims to minimise symptoms and, if possible, improve function. The degree to which this approach is based on empirical data derived from studies of progressive disease or whether treatment decisions are based on what is known about relapsing-remitting disease remains unclear. Symptoms rated as important by patients with multiple sclerosis include balance and mobility impairments, weakness, reduced cardiovascular fitness, ataxia, fatigue, bladder dysfunction, spasticity, pain, cognitive deficits, depression, and pseudobulbar affect; a comprehensive literature search shows a notable paucity of studies devoted solely to these symptoms in progressive multiple sclerosis, which translates to few proven therapeutic options in the clinic. A new strategy that can be used in future rehabilitation trials is therefore needed, with the adoption of approaches that look beyond single interventions to concurrent, potentially synergistic, treatments that maximise what remains of neural plasticity in patients with progressive multiple sclerosis. Copyright © 2015 Elsevier Ltd. All rights reserved.

Setting Adolescents up for Success: Promoting a Policy to Delay High School Start Times

ERIC Educational Resources Information Center

Barnes, Margaux; Davis, Krista; Mancini, Mackenzie; Ruffin, Jasmine; Simpson, Tina; Casazza, Krista

2016-01-01

Background: A unique biological shift in sleep cycles occurs during adolescence causing later sleep and wake times. This shift is not matched by a concurrent modification in school start times, resulting in sleep curtailment for a large majority of adolescents. Chronic inadequate sleep is associated with poor academic performance including…

Offering an Anatomy and Physiology Course through a High School-University Partnership: The Minnesota Model

ERIC Educational Resources Information Center

Jensen, Murray; Mattheis, Allison; Loyle, Anne

2013-01-01

This article describes a one-semester anatomy and physiology course that is currently offered through the concurrent enrollment program at the University of Minnesota. The article explains how high school teachers are prepared to teach the course and describes efforts to promote program quality, student inquiry, and experiential learning.…

β-Cell Hyperplasia Induced by Hepatic Insulin Resistance

PubMed Central

Escribano, Oscar; Guillén, Carlos; Nevado, Carmen; Gómez-Hernández, Almudena; Kahn, C. Ronald; Benito, Manuel

2009-01-01

OBJECTIVE Type 2 diabetes results from a combination of insulin resistance and impaired insulin secretion. To directly address the effects of hepatic insulin resistance in adult animals, we developed an inducible liver-specific insulin receptor knockout mouse (iLIRKO). RESEARCH DESIGN AND METHODS Using this approach, we were able to induce variable insulin receptor (IR) deficiency in a tissue-specific manner (liver mosaicism). RESULTS iLIRKO mice presented progressive hepatic and extrahepatic insulin resistance without liver dysfunction. Initially, iLIRKO mice displayed hyperinsulinemia and increased β-cell mass, the extent of which was proportional to the deletion of hepatic IR. Our studies of iLIRKO suggest a cause-and-effect relationship between progressive insulin resistance and the fold increase of plasma insulin levels and β-cell mass. Ultimately, the β-cells failed to secrete sufficient insulin, leading to uncontrolled diabetes. We observed that hepatic IGF-1 expression was enhanced in iLIRKO mice, resulting in an increase of circulating IGF-1. Concurrently, the IR-A isoform was upregulated in hyperplastic β-cells of iLIRKO mice and IGF-1–induced proliferation was higher than in the controls. In mouse β-cell lines, IR-A, but not IR-B, conferred a proliferative capacity in response to insulin or IGF-1, providing a potential explanation for the β-cell hyperplasia induced by liver insulin resistance in iLIRKO mice. CONCLUSIONS Our studies of iLIRKO mice suggest a liver-pancreas endocrine axis in which IGF-1 functions as a liver-derived growth factor to promote compensatory pancreatic islet hyperplasia through IR-A. PMID:19136656

On the genesis of unilateral micrographia of the progressive type.

PubMed

Barbarulo, Anna Maria; Grossi, Dario; Merola, Stefania; Conson, Massimiliano; Trojano, Luigi

2007-04-09

We report a patient who, following a focal ischemic lesion of the left basal ganglia, developed right hand micrographia characterised by progressive reduction of letter size during writing (progressive micrographia). The patient did not show relevant cognitive impairments, but achieved pathological scores in tests for verbal fluency, and cognitive flexibility and monitoring. A systematic investigation of the writing performances demonstrated that micrographia showed a clear length effect in whatever writing style or task, while it was not observed in drawing, or in left hand writing to a comparable extent. Right hand progressive micrographia was not affected by a concurrent motor and cognitive load; instead, switching between two kinds of allographic responses and presenting one letter at a time in copying tasks reduced severity of micrographia significantly. These findings support the view that progressive micrographia in our patient could be ascribed to a defect in regulating the motor output on the basis of self-generated strategies. This conclusion would be consistent with neuroimaging evidence about the role of the basal ganglia in the control of motor sequencing, and could suggest that progressive micrographia might be associated with specific executive defects.

Procarbazine and CCNU Chemotherapy for Recurrent Glioblastoma with MGMT Promoter Methylation.

PubMed

Kim, Se-Hyuk; Yoo, Heon; Chang, Jong Hee; Kim, Chae-Yong; Chung, Dong Sup; Kim, Se Hoon; Park, Sung-Hae; Lee, Youn Soo; Yang, Seung Ho

2018-06-11

While procarbazine, CCNU (lomustine), and vincristine (PCV) has been an alternative chemotherapy option for malignant gliomas, it is worth investigating whether the combination of only procarbazine and CCNU is comparable because vincristine adds toxicity with uncertain benefit. The purpose of this study was to evaluate the feasibility of procarbazine and CCNU chemotherapy for recurrent glioblastoma multiforme (GBM) with O 6 -methylguanine-DNA-methyltransferase (MGMT) promoter methylation. Eight patients with recurrent GBM following concurrent chemoradiotherapy and temozolomide (TMZ) adjuvant therapy were enrolled in this trial; they received no other chemotherapeutic agents or target therapy. They received CCNU (75 mg/m 2 ) on day 1 and procarbazine (60 mg/m 2 ) through days 11 and 24 every 4 weeks. The median cycle of CCNU and procarbazine was 3.5 (range: 2-6). One patient achieved stable disease. The median progression-free survival (PFS) with procarbazine and CCNU chemotherapy was eight weeks (range: 5-73), and the PFS rates were 25% and 12.5% at 16 and 30 weeks, respectively. The median overall survival (OS) from the initial diagnosis to death was 40 months, and the median OS from the administration of procarbazine and CCNU chemotherapy to death was 9.7 months (95% confidence interval: 6.7-12.7). Serious adverse events were found at six visits, and two cases were considered to be grade 3 toxicities. The efficacy of procarbazine and CCNU chemotherapy is not satisfactory. This study suggests the need to develop other treatment strategies for recurrent and TMZ-refractory GBM. Trial registry at ClinicalTrials.gov, NCT017337346.

Embryonic Stem Cell-Derived Exosomes Promote Endogenous Repair Mechanisms and Enhance Cardiac Function Following Myocardial Infarction

PubMed Central

Khan, Mohsin; Nickoloff, Emily; Abramova, Tatiana; Johnson, Jennifer; Verma, Suresh Kumar; Krishnamurthy, Prasanna; Mackie, Alexander Roy; Vaughan, Erin; Garikipati, Venkata Naga Srikanth; Benedict, Cynthia; Ramirez, Veronica; Lambers, Erin; Ito, Aiko; Gao, Erhe; Misener, Sol; Luongo, Timothy; Elrod, John; Qin, Gangjian; Houser, Steven R; Koch, Walter J; Kishore, Raj

2015-01-01

Rationale Embryonic stem cells (ESCs) hold great promise for cardiac regeneration but are susceptible to various concerns. Recently, salutary effects of stem cells have been connected to exosome secretion. ESCs have the ability to produce exosomes however their effect in the context of the heart is unknown. Objective Determine the effect of ESC-derived exosome for the repair of ischemic myocardium and whether c-kit+ CPCs function can be enhanced with ESC exosomes Methods and Results This study demonstrates that mouse ESC derived exosomes (mES Ex) possess ability to augment function in infarcted hearts. mES Ex enhanced neovascularization, cardiomyocyte survival and reduced fibrosis post infarction consistent with resurgence of cardiac proliferative response. Importantly, mES Ex augmented cardiac progenitor cell (CPC) survival, proliferation and cardiac commitment concurrent with increased c-kit+ CPCs in vivo 8 weeks after in vivo transfer along with formation of bonafide new cardiomyocytes in the ischemic heart. miRNA array revealed significant enrichment of miR290–295 cluster and particularly miR-294 in ESC exosomes. The underlying basis for the beneficial effect of mES Ex was tied to delivery of ESC specific miR-294 to CPCs promoting increased survival, cell cycle progression and proliferation. Conclusions mES Ex provide a novel cell free system that utilizes the immense regenerative power of ES cells while avoiding the risks associated with direct ES or ES derived cell transplantation and risk of teratomas. ESC exosomes possess cardiac regeneration ability and modulate both cardiomyocyte and CPC based repair programs in the heart. PMID:25904597

Tumor-derived inducible heat-shock protein 70 (HSP70) is an essential component of anti-tumor immunity.

PubMed

Dodd, K; Nance, S; Quezada, M; Janke, L; Morrison, J B; Williams, R T; Beere, H M

2015-03-05

The anti-apoptotic function and tumor-associated expression of heat-shock protein 70 (HSP70) is consistent with HSP70 functioning as a survival factor to promote tumorigenesis. However, its immunomodulatory activities to induce anti-tumor immunity predict the suppression of tumor growth. Using the Hsp70.1/3(-/-)(Hsp70(-/-)) mouse model, we observed that tumor-derived HSP70 was neither required for cellular transformation nor for in vivo tumor growth. Hsp70(-/-) murine embryonic fibroblasts (MEFs) were transformed by E1A/Ras and generated tumors in immunodeficient hosts as efficiently as wild-type (WT) transformants. Comparison of Bcr-Abl-mediated transformation of WT and Hsp70(-/-) bone marrow and progression of B-cell leukemogenesis in vivo revealed no differences in disease onset or survival rates, and Eμ-Myc-driven lymphoma in Hsp70(-/-) mice was phenotypically indistinguishable from that in WT Eμ-Myc mice. However, Hsp70(-/-) E1A/Ras MEFs generated significantly larger tumors than their WT counterparts in C57BL/6 J immune-competent hosts. Concurrent with this was a reduction in intra-tumoral infiltration of innate and adaptive immune cells, including macrophages and CD8(+) T cells. Evaluation of several potential mechanisms revealed an HSP70-chemokine-like activity to promote cellular migration. These observations support a role for tumor-derived HSP70 in facilitating anti-tumor immunity to limit tumor growth and highlight the potential consequences of anti-HSP70 therapy as an efficacious anti-cancer strategy.

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

Hoppe, Bradford S., E-mail: bhoppe@floridaproton.org; Henderson, Randal; Pham, Dat

Purpose: Proton therapy has been shown to reduce radiation dose to organs at risk (OAR) and could be used to safely escalate the radiation dose. We analyzed outcomes in a group of phase 2 study patients treated with dose-escalated proton therapy with concurrent chemotherapy for stage 3 non-small cell lung cancer (NSCLC). Methods and Materials: From 2009 through 2013, LU02, a phase 2 trial of proton therapy delivering 74 to 80 Gy at 2 Gy/fraction with concurrent chemotherapy for stage 3 NSCLC, was opened to accrual at our institution. Due to slow accrual and competing trials, the study was closed after justmore » 14 patients (stage IIIA, 9 patients; stage IIIB, 5 patients) were accrued over 4 years. During that same time period, 55 additional stage III patients were treated with high-dose proton therapy, including 7 in multi-institutional proton clinical trials, 4 not enrolled due to physician preference, and 44 who were ineligible based on strict entry criteria. An unknown number of patients were ineligible for enrollment due to insurance coverage issues and thus were treated with photon radiation. Median follow-up of surviving patients was 52 months. Results: Two-year overall survival and progression-free survival rates were 57% and 25%, respectively. Median lengths of overall survival and progression-free survival were 33 months and 14 months, respectively. There were no acute grade 3 toxicities related to proton therapy. Late grade 3 gastrointestinal toxicity and pulmonary toxicity each occurred in 1 patient. Conclusions: Dose-escalated proton therapy with concurrent chemotherapy was well tolerated with encouraging results among a small cohort of patients. Unfortunately, single-institution proton studies may be difficult to accrue and consideration for pragmatic and/or multicenter trial design should be considered when developing future proton clinical trials.« less

Treatment of isolated mediastinal and hilar recurrence of lung cancer with bronchoscopic endobronchial ultrasound guided intratumoral injection of chemotherapy with cisplatin.

PubMed

Mehta, Hiren J; Begnaud, Abbie; Penley, Andrea M; Wynne, John; Malhotra, Paras; Fernandez-Bussy, Sebastian; Cope, Jessica M; Shuster, Jonathan J; Jantz, Michael A

2015-12-01

A common pattern of recurrence in lung cancer after receiving full dose external beam radiation therapy (EBRT) to targeted sites is isolated mediastinal and hilar recurrence (IMHR). Treatment options for these patients are limited to palliative radiation, chemotherapy, and/or best supportive care. We describe our experience with treating IMHR with bronchoscopic endobronchial ultrasound (EBUS) guided intratumoral injection of cisplatin (ITC). Patients treated between Jan 2009-September 2014 with ITC for IMHR were included. Patient demographics, tumor histology, size, concurrent therapy, location, number of sites treated, treatment sessions, and encounters were abstracted. Responses were analyzed on follow-up scans 8-12 weeks after the last treatment session using RECIST 1.1 criteria. Locoregional recurrence, progression-free survival (PFS), and overall survival were measured. 50 sites were treated in 36 patients (19 males, 17 females) with mean age 61.9±8.5 years. Eight sites treated on subsequent encounters were excluded and one patient had an unevaluable response, leaving 35 patients and 41 sites for final analysis. 24/35 (69%) had complete or partial response (responders), whereas 11/35 (31%) had stable or progressive disease (non-responders). There were no significant differences in response based on histology, size, and concurrent therapy. Median survival for the group was 8 months (95% CI of 6-11 mo). Responders had significantly higher survival and PFS than non-responders. Two patients treated with concurrent EBRT, developed broncho-mediastinal fistula. EBUS guided intratumoral cisplatin for IMHR appears to be safe and effective, and may represent a new treatment paradigm for this patient population. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Prospective Pilot Study of Consolidation Chemotherapy With Docetaxel and Cisplatin After Concurrent Chemoradiotherapy for Advanced Head and Neck Cancer

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

Lee, Kyun Chan; Lee, Seok Ho; Lee, Yuna

Purpose: With the improvement concurrent chemoradiotherapy (CCRT) in the management of patients with locoregionally advanced head and neck squamous cell carcinoma (HNSCC), distant failures have become a more relevant problem in terms of survival. The primary objective of this Phase II study is to assess the feasibility of docetaxel and cisplatin consolidation after primary CCRT for patients with HNSCC. Methods and Materials: Patients with locoregionally advanced HNSCC received chemotherapy with three cycles of cisplatin, 100 mg/m{sup 2}, on Days 1, 22, and 43. Concurrent radiotherapy to the primary tumor and neck was given in a daily dose of 2 Gymore » to a total dose of 70-70.2 Gy over 7 weeks. After completion of CCRT, patients without evidence of disease progression received an additional four cycles of consolidation chemotherapy with docetaxel, 75 mg/m{sup 2}, and cisplatin, 75 mg/m{sup 2}, every 3 weeks. Results: Of 33 patients, 27 (81%) completed CCRT. After CCRT, three complete and 19 partial responses were recorded, giving an overall response rate of 67%. Of 19 patients who went to the consolidation phase, only 4 (21%) received all four cycles of docetaxel and cisplatin. Causes of failure of consolidation chemotherapy were toxicity in 11 patients, including three treatment-related deaths, and progression in 4 patients. Three patients died of sepsis during the consolidation phase. Median survival was 11 months for all patients and 8 months for those treated with consolidation chemotherapy. Conclusion: The poor compliance and high incidence of severe toxicities prompted no further evaluation of this consolidation chemotherapy after CCRT.« less

Phase II Study of Oral S-1 and Concurrent Radiotherapy in Patients With Unresectable Locally Advanced Pancreatic Cancer

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

Sudo, Kentaro, E-mail: kentarosudo9@yahoo.co.j; Yamaguchi, Taketo; Ishihara, Takeshi

2011-05-01

Purpose: S-1 is an oral fluoropyrimidine derivative that has demonstrated favorable antitumor activity in patients with metastatic pancreatic cancer. The aim of this study was to evaluate safety and efficacy of S-1 and concurrent radiotherapy in patients with unresectable locally advanced pancreatic cancer. Methods and Materials: Patients with histopathologically proven, unresectable, locally advanced pancreatic cancer were eligible. Radiotherapy was delivered in 1.8 Gy daily fractions to a total dose of 50.4 Gy over 5.5 weeks. S-1 was administered orally twice a day at a dose of 80 mg/m{sup 2}/day from day 1 to 14 and 22 to 35. Two weeksmore » after the completion of chemoradiotherapy, maintenance chemotherapy with S-1 was administered for 28 days every 6 weeks until progression. Results: Thirty-four patients were enrolled in this study. The most common Grade 3 toxicities during chemoradiotherapy were anorexia (24%) and nausea (12%). The overall response rate was 41% (95% confidence interval, 25%-58%) and overall disease control rate (partial response plus stable disease) was 97%. More than 50% decrease in serum CA 19-9 was seen in 27 of 29 evaluable patients (93%). The median progression-free survival was 8.7 months. The median overall survival and 1-year survival rate were 16.8 months and 70.6%, respectively. Conclusions: Oral S-1 and concurrent radiotherapy exerted a promising antitumor activity with acceptable toxicity in patients with locally advanced pancreatic cancer. This combination therapy seems to be an attractive alternative to conventional chemoradiotherapy using 5-fluorouracil infusion.« less

Unified Behavior Framework for Reactive Robot Control in Real-Time Systems

DTIC Science & Technology

2007-03-01

maintain coherent operation in concurrent programs by employing standard communication and synchronization patterns. Some typical ones are: semaphores ...through the semaphore . Signals, whether persistent or transient, are used to communicate between threads as a means of synchronizing their progress...tasks to be decomposed into collections of low-level primitive behaviors, Figure 2.b. This approach takes on the self- contradictory term, reactive

A phase 1 trial of ABT-510 concurrent with standard chemoradiation for patients with newly diagnosed glioblastoma.

PubMed

Nabors, Louis B; Fiveash, John B; Markert, James M; Kekan, Manasi S; Gillespie, George Y; Huang, Zhi; Johnson, Martin J; Meleth, Sreelatha; Kuo, Huichien; Gladson, Candece L; Fathallah-Shaykh, Hassan M

2010-03-01

To determine the maximum tolerated dose of ABT-510, a thrombospondin-1 mimetic drug with antiangiogenic properties, when used concurrently with temozolomide and radiotherapy in patients with newly diagnosed glioblastoma. Phase 1 dose-escalation clinical trial. Comprehensive Cancer Center, University of Alabama at Birmingham. Patients A total of 23 patients with newly diagnosed, histologically verified glioblastoma enrolled between April 2005 and January 2007. Four cohorts of 3 patients each received subcutaneous ABT-510 injection at doses of 20, 50, 100, or 200 mg/d. The maximum cohort was expanded to 14 patients to obtain additional safety and gene expression data. The treatment plan included 10 weeks of induction phase (temozolomide and radiotherapy with ABT-510 for 6 weeks plus ABT-510 monotherapy for 4 weeks) followed by a maintenance phase of ABT-510 and monthly temozolomide. Patients were monitored with brain magnetic resonance imaging and laboratory testing for dose-limiting toxicities, defined as grades 3 or 4 nonhematological toxicities and grade 4 hematological toxicities. Therapy was discontinued if 14 maintenance cycles were completed, disease progression occurred, or if the patient requested withdrawal. Disease progression, survival statistics, and gene expression arrays were analyzed. There were no grade 3 or 4 dose-limiting toxicity events that appeared related to ABT-510 for the dose range of 20 to 200 mg/d. A maximum tolerated dose was not defined. Most adverse events were mild, and injection-site reactions. The median time to tumor progression was 45.9 weeks, and the median overall survival time was 64.4 weeks. Gene expression analysis using TaqMan low-density arrays identified angiogenic genes that were differentially expressed in the brains of controls compared with patients with newly diagnosed glioblastoma, and identified FGF-1 and TIE-1 as being downregulated in patients who had better clinical outcomes. ABT-510, at subcutaneous doses up to 200 mg/d, is tolerated well with concurrent temozolomide and radiotherapy in patients with newly diagnosed glioblastoma, and low-density arrays provide a useful method of exploring gene expression profiles.

Concurrent and aerobic exercise training promote similar benefits in body composition and metabolic profiles in obese adolescents.

PubMed

Monteiro, Paula Alves; Chen, Kong Y; Lira, Fabio Santos; Saraiva, Bruna Thamyres Cicotti; Antunes, Barbara Moura Mello; Campos, Eduardo Zapaterra; Freitas, Ismael Forte

2015-11-26

The prevalence of obesity in pediatric population is increasing at an accelerated rate in many countries, and has become a major public health concern. Physical activity, particularly exercise training, remains to be a cornerstone of pediatric obesity interventions. The purpose of our current randomized intervention trial was to compare the effects of two types of training matched for training volume, aerobic and concurrent, on body composition and metabolic profile in obese adolescents. Thus the aim of the study was compare the effects of two types of training matched for training volume, aerobic and concurrent, on body composition and metabolic profile in obese adolescents. 32 obese adolescents participated in two randomized training groups, concurrent or aerobic, for 20 weeks (50 mins x 3 per week, supervised), and were compared to a 16-subject control group. We measured the percentage body fat (%BF, primary outcome), fat-free mass, percentage of android fat by dual energy x-ray absorptiometry, and others metabolic profiles at baseline and after interventions, and compared them between groups using the Intent-to-treat design. In 20 weeks, both exercise training groups significantly reduced %BF by 2.9-3.6% as compare to no change in the control group (p = 0.042). There were also positive changes in lipid levels in exercise groups. No noticeable changes were found between aerobic and concurrent training groups. The benefits of exercise in reducing body fat and metabolic risk profiles can be achieved by performing either type of training in obese adolescents. RBR-4HN597.

Serial monogamy and biologic concurrency: measurement of the gaps between sexual partners to inform targeted strategies.

PubMed

Mercer, Catherine H; Aicken, Catherine R H; Tanton, Clare; Estcourt, Claudia S; Brook, M Gary; Keane, Frances; Cassell, Jackie A

2013-07-15

Having multiple sexual partners concurrently increases the risk of transmission of a sexually transmitted infection. Even if partnerships do not overlap, transmission potential exists when the gap between partnerships is shorter than the remaining infectious period. In the present article, we quantify the gap between partners to assess transmission potential using data collected by a cross-sectional survey of 2,203 genitourinary medicine clinic patients in England in 2009. Questionnaires asked about patients' 3 most recent partnerships. Gaps were calculated as time (days) between the last sexual encounter with a former partner and the first sexual encounter with the next partner. Among 1,875 patients who reported 1 or more partners in the previous 3 months, 47.6% of men and 27.7% of women reported 2 or more partners. Forty-two percent of the gaps were negative (i.e., partnerships that were concurrent); the median gaps were -7 and -17 days for men and women, respectively (i.e., overlaps were 7 and 17 days for men and women, respectively). Although half of the gaps were positive (serially monogamous partnerships), many were of short duration; the median gaps were 14 and 24 days for men and women, respectively. In over half of the gaps, condoms were used inconsistently with one or both partners, and in one-quarter, condoms were never used with either partner. There is thus a high potential for sexually transmitted infections, as even if partnerships are not behaviorally concurrent, they may be biologically concurrent. These data have important implications for designing and targeting effective health promotion messages.

Model-Based Systems Engineering in Concurrent Engineering Centers

NASA Technical Reports Server (NTRS)

Iwata, Curtis; Infeld, Samantha; Bracken, Jennifer Medlin; McGuire; McQuirk, Christina; Kisdi, Aron; Murphy, Jonathan; Cole, Bjorn; Zarifian, Pezhman

2015-01-01

Concurrent Engineering Centers (CECs) are specialized facilities with a goal of generating and maturing engineering designs by enabling rapid design iterations. This is accomplished by co-locating a team of experts (either physically or virtually) in a room with a focused design goal and a limited timeline of a week or less. The systems engineer uses a model of the system to capture the relevant interfaces and manage the overall architecture. A single model that integrates other design information and modeling allows the entire team to visualize the concurrent activity and identify conflicts more efficiently, potentially resulting in a systems model that will continue to be used throughout the project lifecycle. Performing systems engineering using such a system model is the definition of model-based systems engineering (MBSE); therefore, CECs evolving their approach to incorporate advances in MBSE are more successful in reducing time and cost needed to meet study goals. This paper surveys space mission CECs that are in the middle of this evolution, and the authors share their experiences in order to promote discussion within the community.

Model-Based Systems Engineering in Concurrent Engineering Centers

NASA Technical Reports Server (NTRS)

Iwata, Curtis; Infeld, Samatha; Bracken, Jennifer Medlin; McGuire, Melissa; McQuirk, Christina; Kisdi, Aron; Murphy, Jonathan; Cole, Bjorn; Zarifian, Pezhman

2015-01-01

Concurrent Engineering Centers (CECs) are specialized facilities with a goal of generating and maturing engineering designs by enabling rapid design iterations. This is accomplished by co-locating a team of experts (either physically or virtually) in a room with a narrow design goal and a limited timeline of a week or less. The systems engineer uses a model of the system to capture the relevant interfaces and manage the overall architecture. A single model that integrates other design information and modeling allows the entire team to visualize the concurrent activity and identify conflicts more efficiently, potentially resulting in a systems model that will continue to be used throughout the project lifecycle. Performing systems engineering using such a system model is the definition of model-based systems engineering (MBSE); therefore, CECs evolving their approach to incorporate advances in MBSE are more successful in reducing time and cost needed to meet study goals. This paper surveys space mission CECs that are in the middle of this evolution, and the authors share their experiences in order to promote discussion within the community.

Brief report: Assessing dispositional optimism in adolescence--factor structure and concurrent validity of the Life Orientation Test--Revised.

PubMed

Monzani, Dario; Steca, Patrizia; Greco, Andrea

2014-02-01

Dispositional optimism is an individual difference promoting psychosocial adjustment and well-being during adolescence. Dispositional optimism was originally defined as a one-dimensional construct; however, empirical evidence suggests two correlated factors in the Life Orientation Test - Revised (LOT-R). The main aim of the study was to evaluate the dimensionality of the LOT-R. This study is the first attempt to identify the best factor structure, comparing congeneric, two correlated-factor, and two orthogonal-factor models in a sample of adolescents. Concurrent validity was also assessed. The results demonstrated the superior fit of the two orthogonal-factor model thus reconciling the one-dimensional definition of dispositional optimism with the bi-dimensionality of the LOT-R. Moreover, the results of correlational analyses proved the concurrent validity of this self-report measure: optimism is moderately related to indices of psychosocial adjustment and well-being. Thus, the LOT-R is a useful, valid, and reliable self-report measure to properly assess optimism in adolescence. Copyright © 2013 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.

Communication modality sampling for a toddler with Angelman syndrome.

PubMed

Hyppa Martin, Jolene; Reichle, Joe; Dimian, Adele; Chen, Mo

2013-10-01

Vocal, gestural, and graphic communication modes were implemented concurrently with a toddler with Angelman syndrome to identify the most efficiently learned communication mode to emphasize in an initial augmentative communication system. Symbols representing preferred objects were introduced in vocal, gestural, and graphic communication modes using an alternating treatment single-subject experimental design. Conventionally accepted prompting strategies were used to teach symbols in each communication mode. Because the learner did not vocally imitate, vocal mode intervention focused on increasing vocal frequency as an initial step. When graphic and gestural mode performances were compared, the learner most accurately produced requests in graphic mode (percentage of nonoverlapping data = 96). Given the lack of success in prompting vocal productions, a comparison between vocal and the other two communication modes was not made. A growing body of evidence suggests that concurrent modality sampling is a promising low-inference, data-driven procedure that can be used to inform selection of a communication mode(s) for initial emphasis with young children. Concurrent modality sampling can guide clinical decisions regarding the allocation of treatment resources to promote success in building an initial communicative repertoire.

[Initial outcome of induction chemotherapy with weekly paclitaxel followed by three-dimensional conformal radiotherapy and concurrent weekly paclitaxel for stage III non-small cell lung cancer].

PubMed

Wang, Wei-Hua; Bao, Yong; Chen, Ming; Zhang, Li; Li, Kai-Xin; Xu, Guang-Chuan; Deng, Xiao-Wu; Lu, Tai-Xiang; Cui, Nian-Ji

2006-10-01

The efficacy of radiotherapy alone on locally advanced non-small cell lung cancer (NSCLC) is poor. Although the combined modality of chemoradiotherapy and dose-escalation of radiotherapy have been the main trends, the optimal modality still remains unknown. This study was to evaluate the toxicity and efficacy of induction chemotherapy (ICT) followed by three-dimensional conformal radiotherapy (3D CRT) and concurrent weekly paclitaxel on unresectable NSCLC. Stage III NSCLC patients with favorable conditions were treated with 2 to 4 cycles of carboplatin (AUC=5-6, d1) combined with paclitaxel (175 mg/m(2), d1), then followed by weekly paclitaxel (40 mg/m(2)) and concurrent 3D CRT within 3-4 weeks. The prescription dose was given as high as possible under the condition that V20 < or =31% and spinal cord dose < or =50 Gy. Thirty-one patients were enrolled. ICT was well tolerated. During the concurrent chemoradiotherapy, the treatment of 3 patients was ended ahead of the schedule because of severe pulmonary and heart toxicities; the treatment of 2 patients was delayed for 7 and 12 days because of fatigue. Myelosuppression was mild (16/31): all were grade 1-2 except 1 was grade 3. Lymphocytopenia was more obvious (29/31, grade 3 in 21). Three patients developed grade 3 radiation-induced esophagitis, and 2 developed grade 3-4 radiation-induced pneumonitis. Two developed grade 3 esophageal stricture. No grade 3-4 pulmonary fibrosis was observed. The overall response rate was 74.1%. The 1-, 2-, 3-year overall survival rates were 74.2%, 41.9%, and 34.6%, respectively, with the median survival time of 18.5 months. The 1-, 2-, 3-year local progression-freely survival rates were 64.5%, 32.3%, and 20.5%, respectively, with the median local progression-freely survival time of 14.3 months. The program of ICT followed by weekly paclitaxel and 3D CRT is accomplished in most of the favorable stage III NSCLC patients. The toxicity is tolerable, and the response rate is inspiriting.

Arterial hypertension and skin allergy are risk factors for progression from dengue to dengue hemorrhagic fever: a case control study.

PubMed

Teixeira, Maria Glória; Paixão, Enny S; Costa, Maria da Conceição N; Cunha, Rivaldo V; Pamplona, Luciano; Dias, Juarez P; Figueiredo, Camila A; Figueiredo, Maria Aparecida A; Blanton, Ronald; Morato, Vanessa; Barreto, Maurício L; Rodrigues, Laura C

2015-05-01

Currently, knowledge does not allow early prediction of which cases of dengue fever (DF) will progress to dengue hemorrhagic fever (DHF), to allow early intervention to prevent progression or to limit severity. The objective of this study is to investigate the hypothesis that some specific comorbidities increase the likelihood of a DF case progressing to DHF. A concurrent case-control study, conducted during dengue epidemics, from 2009 to 2012. Cases were patients with dengue fever that progressed to DHF, and controls were patients of dengue fever who did not progress to DHF. Logistic regression was used to estimate the association between DHF and comorbidities. There were 490 cases of DHF and 1,316 controls. Among adults, progression to DHF was associated with self-reported hypertension (OR = 1.6; 95% CI 1.1-2.1) and skin allergy (OR = 1.8; 95% CI 1.1-3.2) with DHF after adjusting for ethnicity and socio-economic variables. There was no statistically significant association between any chronic disease and progression to DHF in those younger than 15 years. Physicians attending patients with dengue fever should keep those with hypertension or skin allergies in health units to monitor progression for early intervention. This would reduce mortality by dengue.

SOX5 predicts poor prognosis in lung adenocarcinoma and promotes tumor metastasis through epithelial-mesenchymal transition

PubMed Central

Chen, Xin; Fu, Yufei; Xu, Hongfei; Teng, Peng; Xie, Qiong; Zhang, Yiran; Yan, Caochong; Xu, Yiqiao; Li, Chunqi; Zhou, Jianying; Ni, Yiming; Li, Weidong

2018-01-01

Lung cancer is the leading cause of cancer-related death worldwide. Epithelial-mesenchymal transition (EMT) promotes lung cancer progression and metastasis, especially in lung adenocarcinoma. Sex determining region Y-box protein 5 (SOX5) is known to stimulate the progression of various cancers. Here, we used immunohistochemical analysis to reveal that SOX5 levels were increased in 90 lung adenocarcinoma patients. The high SOX5 expression in lung adenocarcinoma and non-tumor counterparts correlated with the patients’ poor prognosis. Inhibiting SOX5 expression attenuated metastasis and progression in lung cancer cells, while over-expressing SOX5 accelerated lung adenocarcinoma progression and metastasis via EMT. An in vivo zebrafish xenograft cancer model also showed SOX5 knockdown was followed by reduced lung cancer cell proliferation and metastasis. Our results indicate SOX5 promotes lung adenocarcinoma tumorigenicity and can be a novel diagnosis and prognosis marker of the disease. PMID:29541384

The Perception of Concurrent Sound Objects in Harmonic Complexes Impairs Gap Detection

ERIC Educational Resources Information Center

Leung, Ada W. S.; Jolicoeur, Pierre; Vachon, Francois; Alain, Claude

2011-01-01

Since the introduction of the concept of auditory scene analysis, there has been a paucity of work focusing on the theoretical explanation of how attention is allocated within a complex auditory scene. Here we examined signal detection in situations that promote either the fusion of tonal elements into a single sound object or the segregation of a…

The Development and Implementation of a Peer-Led Intervention to Prevent Smoking among Secondary School Students Using Their Established Social Networks

ERIC Educational Resources Information Center

Audrey, Suzanne; Cordall, Kathleen; Moore, Laurence; Cohen, David; Campbell, Rona

2004-01-01

Objective: To design, implement and evaluate a peer-led intervention to reduce smoking amongst secondary school students. Design: A health promotion intervention combining peer education with diffusion of innovation theory, to be rigorously evaluated by means of a cluster randomised controlled trial with concurrent process and economic…

Cognitive tasks promote automatization of postural control in young and older adults.

PubMed

Potvin-Desrochers, Alexandra; Richer, Natalie; Lajoie, Yves

2017-09-01

Researchers looking at the effects of performing a concurrent cognitive task on postural control in young and older adults using traditional center-of-pressure measures and complexity measures found discordant results. Results of experiments showing improvements of stability have suggested the use of strategies such as automatization of postural control or stiffening strategy. This experiment aimed to confirm in healthy young and older adults that performing a cognitive task while standing leads to improvements that are due to automaticity of sway by using sample entropy. Twenty-one young adults and twenty-five older adults were asked to stand on a force platform while performing a cognitive task. There were four cognitive tasks: simple reaction time, go/no-go reaction time, equation and occurrence of a digit in a number sequence. Results demonstrated decreased sway area and variability as well as increased sample entropy for both groups when performing a cognitive task. Results suggest that performing a concurrent cognitive task promotes the adoption of an automatic postural control in young and older adults as evidenced by an increased postural stability and postural sway complexity. Copyright © 2017 Elsevier B.V. All rights reserved.

Protocol for the CONVERT trial-Concurrent ONce-daily VErsus twice-daily RadioTherapy: an international 2-arm randomised controlled trial of concurrent chemoradiotherapy comparing twice-daily and once-daily radiotherapy schedules in patients with limited stage small cell lung cancer (LS-SCLC) and good performance status.

PubMed

Faivre-Finn, Corinne; Falk, Sally; Ashcroft, Linda; Bewley, Michelle; Lorigan, Paul; Wilson, Elena; Groom, Nicki; Snee, Michael; Fournel, Pierre; Cardenal, Felipe; Bezjak, Andrea; Blackhall, Fiona

2016-01-20

Concurrent ONce-daily VErsus twice-daily RadioTherapy (CONVERT) is the only multicentre, international, randomised, phase III trial open in Europe and Canada looking at optimisation of chemoradiotherapy (RT) in limited stage small cell lung cancer (LS-SCLC). Following on from the Turrisi trial of once-daily versus twice-daily (BD) concurrent chemoradiotherapy, there is a real need for a new phase III trial using modern conformal RT techniques and investigating higher once-daily radiation dose. This trial has the potential to define a new standard chemo-RT regimen for patients with LS-SCLC and good performance status. 447 patients with histologically or cytologically proven diagnosis of SCLC were recruited from 74 centres in eight countries between 2008 and 2013. Patients were randomised to receive either concurrent twice-daily RT(45 Gy in 30 twice-daily fractions over 3 weeks) or concurrent once-daily RT(66 Gy in 33 once-daily fractions over 6.5 weeks) both starting on day 22 of cycle 1. Patients are followed up until death. The primary end point of the study is overall survival and secondary end points include local progression-free survival, metastasis-free survival, acute and late toxicity based on the Common Terminology Criteria for Adverse Events V.3.0, chemotherapy and RTdose intensity. The trial received ethical approval from NRES Committee North West-Greater Manchester Central (07/H1008/229). There is a trial steering committee, including independent members and an independent data monitoring committee. Results will be published in a peer-reviewed journal and presented at international conferences. ISRCTN91927162; Pre-results. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Stereotactic body radiation therapy with concurrent full-dose gemcitabine for locally advanced pancreatic cancer: a pilot trial demonstrating safety

PubMed Central

2013-01-01

Background Concurrent chemoradiation is a standard option for locally advanced pancreatic cancer (LAPC). Concurrent conventional radiation with full-dose gemcitabine has significant toxicity. Stereotactic body radiation therapy (SBRT) may provide the opportunity to administer radiation in a shorter time frame with similar efficacy and reduced toxicity. This Pilot study assessed the safety of concurrent full-dose gemcitabine with SBRT for LAPC. Methods Patients received gemcitabine, 1000 mg/m2 for 6 cycles. During week 4 of cycle 1, patients received SBRT (25 Gy delivered in five consecutive daily fractions of 5 Gy prescribed to the 75-83% isodose line). Acute and late toxicities were assessed using NIH CTCAE v3. Tumor response was assessed by RECIST. Patients underwent an esophagogastroduodenoscopy at baseline, 2, and 6 months to assess the duodenal mucosa. Quality of life (QoL) data was collected before and after treatment using the QLQ-C30 and QLQ-PAN26 questionnaires. Results Between September 2009 and February 2011, 11 patients enrolled with one withdrawal during radiation therapy. Patients had grade 1 to 2 gastrointestinal toxicity from the start of SBRT to 2 weeks after treatment. There were no grade 3 or greater radiation-related toxicities or delays for cycle 2 of gemcitabine. On endoscopy, there were no grade 2 or higher mucosal toxicities. Two patients had a partial response. The median progression free and overall survival were 6.8 and 12.2 months, respectively. Global QoL did not change between baseline and immediately after radiation treatment. Conclusions SBRT with concurrent full dose gemcitabine is safe when administered to patients with LAPC. There is no delay in administration of radiation or chemotherapy, and radiation is completed with minimal toxicity. PMID:23452509

Advantages of concurrent biochemotherapy modified by decrescendo interleukin-2, granulocyte colony-stimulating factor, and tamoxifen for patients with metastatic melanoma.

PubMed

O'Day, S J; Gammon, G; Boasberg, P D; Martin, M A; Kristedja, T S; Guo, M; Stern, S; Edwards, S; Fournier, P; Weisberg, M; Cannon, M; Fawzy, N W; Johnson, T D; Essner, R; Foshag, L J; Morton, D L

1999-09-01

Concurrent biochemotherapy results in high response rates but also significant toxicity in patients with metastatic melanoma. We attempted to improve its efficacy and decrease its toxicity by using decrescendo dosing of interleukin-2 (IL-2), posttreatment granulocyte colony-stimulating factor (G-CSF), and low-dose tamoxifen. Forty-five patients with poor prognosis metastatic melanoma were treated at a community hospital inpatient oncology unit affiliated with the John Wayne Cancer Institute (Santa Monica, CA) between July 1995 and September 1997. A 5-day modified concurrent biochemotherapy regimen of dacarbazine, vinblastine, cisplatin, decrescendo IL-2, interferon alfa-2b, and tamoxifen was repeated at 21-day intervals. G-CSF was administered beginning on day 6 for 7 to 10 days. The overall response rate was 57% (95% confidence interval, 42% to 72%), the complete response rate was 23%, and the partial response rate was 34%. Complete remissions were achieved in an additional 11% of patients by surgical resection of residual disease after biochemotherapy. The median time to progression was 6.3 months and the median duration of survival was 11.4 months. At a maximum follow-up of 36 months (range, 10 to 36 months), 32% of patients are alive and 14% remain free of disease. Decrescendo IL-2 dosing and administration of G-CSF seemed to reduce toxicity, length of hospital stay, and readmission rates. No patient required intensive care unit monitoring, and there were no treatment-related deaths. The data from this study indicate that the modified concurrent biochemotherapy regimen reduces the toxicity of concurrent biochemotherapy with no apparent decrease in response rate in patients with poor prognosis metastatic melanoma.

Perivalvular pannus and valve thrombosis: two concurrent mechanisms of mechanical valve prosthesis dysfunction.

PubMed

Arnáiz-García, María Elena; González-Santos, Jose María; Bueno-Codoñer, María E; López-Rodríguez, Javier; Dalmau-Sorlí, María José; Arévalo-Abascal, Adolfo; Arribas-Jiménez, Antonio; Diego-Nieto, Alejandro; Rodríguez-Collado, Javier; Rodríguez-López, Jose María

2015-02-01

A 78-year-old woman was admitted to our institution with progressive dyspnea. She had previously been diagnosed with rheumatic heart disease and had undergone cardiac surgery for mechanical mitral valve replacement ten years previously. Transesophageal echocardiography revealed blockage of the mechanical prosthesis and the patient was scheduled for surgery, in which a thrombus was removed from the left atrial appendage. A partial thrombosis of the mechanical prosthesis and circumferential pannus overgrowth were concomitantly detected. Prosthetic heart valve blockage is a rare but life-threatening complication, the main causes of which are thrombosis and pannus formation. The two conditions are different but both are usually misdiagnosed. Two concurrent mechanisms of prosthesis blockage were found in this patient. Copyright © 2014 Sociedade Portuguesa de Cardiologia. Published by Elsevier España. All rights reserved.

Low-dose hydralazine prevents fibrosis in a murine model of acute kidney injury-to-chronic kidney disease progression.

PubMed

Tampe, Björn; Steinle, Ulrike; Tampe, Désirée; Carstens, Julienne L; Korsten, Peter; Zeisberg, Elisabeth M; Müller, Gerhard A; Kalluri, Raghu; Zeisberg, Michael

2017-01-01

Acute kidney injury (AKI) and progressive chronic kidney disease (CKD) are intrinsically tied syndromes. In this regard, the acutely injured kidney often does not achieve its full regenerative capacity and AKI directly transitions into progressive CKD associated with tubulointerstitial fibrosis. Underlying mechanisms of such AKI-to-CKD progression are still incompletely understood and specific therapeutic interventions are still elusive. Because epigenetic modifications play a role in maintaining tissue fibrosis, we used a murine model of ischemia-reperfusion injury to determine whether aberrant promoter methylation of RASAL1 contributes causally to the switch between physiological regeneration and tubulointerstitial fibrogenesis, a hallmark of AKI-to-CKD progression. It is known that the antihypertensive drug hydralazine has demethylating activity, and that its optimum demethylating activity occurs at concentrations below blood pressure-lowering doses. Administration of low-dose hydralazine effectively induced expression of hydroxylase TET3, which catalyzed RASAL1 hydroxymethylation and subsequent RASAL1 promoter demethylation. Hydralazine-induced CpG promoter demethylation subsequently attenuated renal fibrosis and preserved excretory renal function independent of its blood pressure-lowering effects. In comparison, RASAL1 demethylation and inhibition of tubulointerstitial fibrosis was not detected upon administration of the angiotensin-converting enzyme inhibitor Ramipril in this model. Thus, RASAL1 promoter methylation and subsequent transcriptional RASAL1 suppression plays a causal role in AKI-to-CKD progression. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Designing a National Longitudinal Faculty Development Curriculum Focused on Educational Scholarship: Process, Outcomes, and Lessons Learned.

PubMed

Chandran, Latha; Gusic, Maryellen E; Lane, J Lindsey; Baldwin, Constance D

2017-01-01

Clinical educators at U.S. academic health centers are frequently disadvantaged in the academic promotion system, lacking needed faculty development, mentoring, and networking support. In 2006, we implemented the national Educational Scholars Program to offer faculty development in educational scholarship for early career educators in pediatrics. We aimed to provide them with skills, experience, and initial success in educational scholarship and dissemination. The 3-year curriculum is delivered in interactive sessions at the annual pediatric academic meetings and online intersession modules. Curriculum content progresses from educational scholarship and implementing scholarly projects to dissemination and professional networking. Intersession modules address project planning, building an educator portfolio, reviewing the literature, using technology, authorship, and peer review. Concurrently, all scholars must complete a mentored educational project and demonstrate national dissemination of a peer-reviewed product to obtain a Certificate of Excellence in Educational Scholarship. The setting of this study was a national, longitudinal, cohort-based faculty development program built within the Academic Pediatric Association, a 2,000-member professional organization. In 10 years, the Educational Scholars Program has enrolled 172 scholars in 8 cohorts; 94 have graduated so far. We describe how formative evaluation guided curriculum refinement and process improvement. Summative evaluations show that faculty and scholars were satisfied with the program. Participant outcomes from Cohort 1, assessed at Kirkpatrick's four levels of evaluation, demonstrate increases in scholarly productivity, leadership activities, and academic promotions. Curriculum building is a dynamic process of ongoing evaluation and modification. Our program benefited from designing an integrated and focused curriculum, developing educational principles to guide program improvements, creating curricular tools to help learners organize and document their efforts, supporting project-based learning with expert mentoring, and facilitating peer and faculty networking and collaboration. A national, longitudinal faculty development program can support growth in academic knowledge and skills, promote professional networking, and thereby enrich educators' career opportunities.

Neuroprotective potential of high-dose biotin.

PubMed

McCarty, Mark F; DiNicolantonio, James J

2017-11-01

A recent controlled trial has established that high-dose biotin supplementation - 100 mg, three times daily - has a stabilizing effect on progression of multiple sclerosis (MS). Although this effect has been attributed to an optimization of biotin's essential cofactor role in the brain, a case can be made that direct stimulation of soluble guanylate cyclase (sGC) by pharmacological concentrations of biotin plays a key role in this regard. The utility of high-dose biotin in MS might reflect an anti-inflammatory effect of cGMP on the cerebral microvasculature, as well on oligodendrocyte differentiation and on Schwann cell production of neurotrophic factors thought to have potential for managing MS. But biotin's ability to boost cGMP synthesis in the brain may have broader neuroprotective potential. In many types of neurons and neural cells, cGMP exerts neurotrophic-mimetic effects - entailing activation of the PI3K-Akt and Ras-ERK pathways - that promote neuron survival and plasticity. Hippocampal long term potentiation requires nitric oxide synthesis, which in turn promotes an activating phosphorylation of CREB via a pathway involving cGMP and protein kinase G (PKG). In Alzheimer's disease (AD), amyloid beta suppresses this mechanism by inhibiting sGC activity; agents which exert a countervailing effect by boosting cGMP levels tend to restore effective long-term potentiation in rodent models of AD. Moreover, NO/cGMP suppresses amyloid beta production within the brain by inhibiting expression of amyloid precursor protein and BACE1. In conjunction with cGMP's ability to oppose neuron apoptosis, these effects suggest that high-dose biotin might have potential for the prevention and management of AD. cGMP also promotes neurogenesis, and may lessen stroke risk by impeding atherogenesis and hypertrophic remodeling in the cerebral vasculature. The neuroprotective potential of high-dose biotin likely could be boosted by concurrent administration of brain-permeable phosphodiesterase-5 inhibitors. Copyright © 2017 Elsevier Ltd. All rights reserved.

Interplay between Notch1 and Notch3 promotes EMT and tumor initiation in squamous cell carcinoma.

PubMed

Natsuizaka, Mitsuteru; Whelan, Kelly A; Kagawa, Shingo; Tanaka, Koji; Giroux, Veronique; Chandramouleeswaran, Prasanna M; Long, Apple; Sahu, Varun; Darling, Douglas S; Que, Jianwen; Yang, Yizeng; Katz, Jonathan P; Wileyto, E Paul; Basu, Devraj; Kita, Yoshiaki; Natsugoe, Shoji; Naganuma, Seiji; Klein-Szanto, Andres J; Diehl, J Alan; Bass, Adam J; Wong, Kwok-Kin; Rustgi, Anil K; Nakagawa, Hiroshi

2017-11-24

Notch1 transactivates Notch3 to drive terminal differentiation in stratified squamous epithelia. Notch1 and other Notch receptor paralogs cooperate to act as a tumor suppressor in squamous cell carcinomas (SCCs). However, Notch1 can be stochastically activated to promote carcinogenesis in murine models of SCC. Activated form of Notch1 promotes xenograft tumor growth when expressed ectopically. Here, we demonstrate that Notch1 activation and epithelial-mesenchymal transition (EMT) are coupled to promote SCC tumor initiation in concert with transforming growth factor (TGF)-β present in the tumor microenvironment. We find that TGFβ activates the transcription factor ZEB1 to repress Notch3, thereby limiting terminal differentiation. Concurrently, TGFβ drives Notch1-mediated EMT to generate tumor initiating cells characterized by high CD44 expression. Moreover, Notch1 is activated in a small subset of SCC cells at the invasive tumor front and predicts for poor prognosis of esophageal SCC, shedding light upon the tumor promoting oncogenic aspect of Notch1 in SCC.

Metastatic squamous cell carcinoma thyroid from functionally cured cancer cervix

PubMed Central

Vamsy, Mohana; Dattatreya, Palanki Satya; Sarma, Lella Yugandhar; Dayal, Monal; Janardhan, Nandigam; Rao, Vatturi Venkata Satya Prabhakar

2013-01-01

The authors report a very unusual occurrence of a metastatic squamous carcinoma to thyroid gland from a treated squamous cell carcinoma cervix 12 years before with no recurrence at the primary site. The case also has an additional complexity of rapid progression of the metastatic thyroid carcinoma to wide spread dissemination to lungs and bones while on concurrent chemo radio therapy confirming the aggressiveness of the entity. PMID:24163519

Department of Clinical Investigation Annual Research Progress Report, Fiscal Year 1993. Volume 1

DTIC Science & Technology

1993-10-01

monocytes, total periphernuclear cells, and alveolar macrophages from four study groups : patients with concurrent Mycobacterium tuberculosis (MTBI and...research design, similar to the Solomon Four Group design will be utilized to determine if the educational intervention provided has an impact on nurses...members with approved protocols: 173 Number of approved protocols held by this group : 230 Drug evaluation/comparison studies : 94 (Does not include

Confirming, Validating, and Norming the Factor Structure of Systemic Therapy Inventory of Change Initial and Intersession.

PubMed

Pinsof, William M; Zinbarg, Richard E; Shimokawa, Kenichi; Latta, Tara A; Goldsmith, Jacob Z; Knobloch-Fedders, Lynne M; Chambers, Anthony L; Lebow, Jay L

2015-09-01

Progress or feedback research tracks and feeds back client progress data throughout the course of psychotherapy. In the effort to empirically ground psychotherapeutic practice, feedback research is both a complement and alternative to empirically supported manualized treatments. Evidence suggests that tracking and feeding back progress data with individual or nonsystemic feedback systems improves outcomes in individual and couple therapy. The research reported in this article pertains to the STIC(®) (Systemic Therapy Inventory of Change)-the first client-report feedback system designed to empirically assess and track change within client systems from multisystemic and multidimensional perspectives in individual, couple, and family therapy. Clients complete the STIC Initial before the first session and the shorter STIC Intersession before every subsequent session. This study tested and its results supported the hypothesized factor structure of the six scales that comprise both STIC forms in a clinical outpatient sample and in a normal, random representative sample of the U.S. This study also tested the STIC's concurrent validity and found that its 6 scales and 40 of its 41 subscales differentiated the clinical and normal samples. Lastly, the study derived clinical cut-offs for each scale and subscale to determine whether and how much a client's score falls in the normal or clinical range. Beyond supporting the factorial and concurrent validity of both STIC forms, this research supported the reliabilities of the six scales (Omegahierarchical ) as well as the reliabilities of most subscales (alpha and rate-rerate). This article delineates clinical implications and directions for future research. © 2015 Family Process Institute.

Concurrent validation of two key health literacy instruments in a South Eastern European population.

PubMed

Toçi, Ervin; Burazeri, Genc; Sørensen, Kristine; Kamberi, Haxhi; Brand, Helmut

2015-06-01

Public health practice has come to increasing recognition of health promotion and the central role of knowledge, attitude, beliefs and practices in achieving health promotion. Health literacy (HL) is an under-explored topic in South Eastern European countries. There are no HL reports from Albania to date. The aim of this study was to assess the concurrent validity of the European Health Literacy Survey Questionnaire (HLS-EU-Q) and the Test of Functional Health Literacy in Adults (TOFHLA) in a population-based sample of adults in Albania. A cross-sectional study was conducted in 2013 in Tirana, Albania, including 239 individuals aged ≥ 18 years (61% women; 87% response). A structured interviewer-administered questionnaire was applied twice (test and retest procedure after 2 weeks) including HLS-EU-Q and TOFHLA instruments. The internal consistency was high for both instruments (Cronbach's alpha for the test procedure was 0.92 for TOFHLA and 0.98 for HLS-EU-Q). Both tools exhibited a high stability over time (Spearman's rho: 0.88 for TOFHLA and 0.87 for HLS-EU). Mean values of both instruments were similar in men and women (mean score for TOFHLA: 76.0 vs. 76.5, P = 0.83; mean score for HLS-EU-Q: 32.2 vs. 32.6, P = 0.63). For both instruments, higher HL scores were significantly associated with younger age, higher educational and economic level and lower body mass index. Our study provides valuable novel evidence on concurrent validation of two major HL instruments in a South Eastern European population-based sample. Future studies should be conducted in order to confirm and expand our findings. © The Author 2014. Published by Oxford University Press on behalf of the European Public Health Association. All rights reserved.

Prevalence and mortality of cancer among HIV-infected inpatients in Beijing, China.

PubMed

Yang, Jun; Su, Shu; Zhao, Hongxin; Wang, Dennis; Wang, Jiali; Zhang, Fujie; Zhao, Yan

2016-02-16

Cancer is responsible for elevated HIV-related morbidity and mortality. Research on HIV-infected patients with concurrent cancer is rare in China. The purpose of our study was to investigate the prevalence and risk factors associated with cancer among HIV-infected inpatients in Beijing, and to investigate the mortality and risk factors among HIV-infected inpatients with cancer. Hospital records from a total of 1946 HIV-infected patients were collected from the Beijing Ditan Hospital. The data, from 2008 to 2013, were collected retrospectively. The cancer diagnoses included AIDS-defining cancers (ADC) and non-AIDS defining cancers (NADC). Logistic regression was used to identify risk factors predicting the concurrence of cancer with HIV. Mortality was examined using Kaplan-Meier estimates and Cox proportional hazards models. 7.7 % (149 cases) of all HIV-infected inpatients had concurrent cancer at their first hospital admission; of those, 33.6 % (50 cases) had ADCs, and 66.4 % (99 cases) had NADCs. The most prevalent NADCs were Hodgkin's lymphoma, gastrointestinal cancer, liver cancer, and lung cancer. Patients who did not accept antiretroviral therapy (ART) were more likely to suffer from cancer [AOR = 2.07 (1.42-3.01), p = 0.001]. Kaplan-Meier curves indicated that the survival probability of HIV-positive cancer patients was significantly lower than that of HIV-positive cancer-free patients (log-rank test, p < 0.001). For patients diagnosed with cancer, the mortality was also higher among those who did not receive ART [AHR = 2.19 (1.84-2.61), p < 0.001]. The prevalence of cancer concurrence among hospitalized HIV-infected patients was 7.7 %. Concurrent cancer also increased mortality among HIV-infected patients. ART was protective against concurrent cancer as well as mortality among HIV-infected cancer patients. These results highlight the importance of promoting cancer screening and early ART initiation among HIV-infected patients.

Bone marrow mesenchymal stem cells promote head and neck cancer progression through Periostin-mediated phosphoinositide 3-kinase/Akt/mammalian target of rapamycin.

PubMed

Liu, Chuanxia; Feng, Xiaoxia; Wang, Baixiang; Wang, Xinhua; Wang, Chaowei; Yu, Mengfei; Cao, Guifen; Wang, Huiming

2018-03-01

Bone marrow mesenchymal stem cells (BMMSC) have been shown to be recruited to the tumor microenvironment and exert a tumor-promoting effect in a variety of cancers. However, the molecular mechanisms related to the tumor-promoting effect of BMMSC on head and neck cancer (HNC) are not clear. In this study, we investigated Periostin (POSTN) and its roles in the tumor-promoting effect of BMMSC on HNC. In vitro analysis of HNC cells cultured in BMMSC-conditioned media (MSC-CM) showed that MSC-CM significantly promoted cancer progression by enhancing cell proliferation, migration, epithelial-mesenchymal transformation (EMT), and altering expression of cell cycle regulatory proteins and inhibition of apoptosis. Moreover, MSC-CM promoted the expression of POSTN and POSTN promoted HNC progression through the activation of the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling pathway. In a murine model of HNC, we found that BMMSC promoted tumor growth, invasion, metastasis and enhanced the expression of POSTN and EMT in tumor tissues. Clinical sample analysis further confirmed that the expression of POSTN and N-cadherin were correlated with pathological grade and lymph node metastasis of HNC. In conclusion, this study indicated that BMMSC promoted proliferation, invasion, survival, tumorigenicity and migration of head and neck cancer through POSTN-mediated PI3K/Akt/mTOR activation. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

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

Zhang, Ying-Jie, E-mail: qfyingjie@iphy.ac.cn; Institute of Physics, Chinese Academy of Sciences, Beijing, 100190; Han, Wei

In this paper, we propose a scheme to enhance trapping of entanglement of two qubits in the environment of a photonic band gap material. Our entanglement trapping promotion scheme makes use of combined weak measurements and quantum measurement reversals. The optimal promotion of entanglement trapping can be acquired with a reasonable finite success probability by adjusting measurement strengths. - Highlights: • Propose a scheme to enhance entanglement trapping in photonic band gap material. • Weak measurement and its reversal are performed locally on individual qubits. • Obtain an optimal condition for maximizing the concurrence of entanglement trapping. • Entanglement suddenmore » death can be prevented by weak measurement in photonic band gap.« less

Formal Analysis of the Remote Agent Before and After Flight

NASA Technical Reports Server (NTRS)

Havelund, Klaus; Lowry, Mike; Park, SeungJoon; Pecheur, Charles; Penix, John; Visser, Willem; White, Jon L.

2000-01-01

This paper describes two separate efforts that used the SPIN model checker to verify deep space autonomy flight software. The first effort occurred at the beginning of a spiral development process and found five concurrency errors early in the design cycle that the developers acknowledge would not have been found through testing. This effort required a substantial manual modeling effort involving both abstraction and translation from the prototype LISP code to the PROMELA language used by SPIN. This experience and others led to research to address the gap between formal method tools and the development cycle used by software developers. The Java PathFinder tool which directly translates from Java to PROMELA was developed as part of this research, as well as automatic abstraction tools. In 1999 the flight software flew on a space mission, and a deadlock occurred in a sibling subsystem to the one which was the focus of the first verification effort. A second quick-response "cleanroom" verification effort found the concurrency error in a short amount of time. The error was isomorphic to one of the concurrency errors found during the first verification effort. The paper demonstrates that formal methods tools can find concurrency errors that indeed lead to loss of spacecraft functions, even for the complex software required for autonomy. Second, it describes progress in automatic translation and abstraction that eventually will enable formal methods tools to be inserted directly into the aerospace software development cycle.

Gait profile score and movement analysis profile in patients with Parkinson's disease during concurrent cognitive load

PubMed Central

Speciali, Danielli S.; Oliveira, Elaine M.; Cardoso, Jefferson R.; Correa, João C. F.; Baker, Richard; Lucareli, Paulo R. G.

2014-01-01

Background: Gait disorders are common in individuals with Parkinson's Disease (PD) and the concurrent performance of motor and cognitive tasks can have marked effects on gait. The Gait Profile Score (GPS) and the Movement Analysis Profile (MAP) were developed in order to summarize the data of kinematics and facilitate understanding of the results of gait analysis. Objective: To investigate the effectiveness of the GPS and MAP in the quantification of changes in gait during a concurrent cognitive load while walking in adults with and without PD. Method: Fourteen patients with idiopathic PD and nine healthy subjects participated in the study. All subjects performed single and dual walking tasks. The GPS/MAP was computed from three-dimensional gait analysis data. Results: Differences were found between tasks for GPS (P<0.05) and Gait Variable Score (GVS) (pelvic rotation, knee flexion-extension and ankle dorsiflexion-plantarflexion) (P<0.05) in the PD group. An interaction between task and group was observed for GPS (P<0.01) for the right side (Cohen's ¯d=0.99), left side (Cohen's ¯d=0.91), and overall (Cohen's ¯d=0.88). No interaction was observed only for hip internal-external rotation and foot internal-external progression GVS variables in the PD group. Conclusions: The results showed gait impairment during the dual task and suggest that GPS/MAP may be used to evaluate the effects of concurrent cognitive load while walking in patients with PD. PMID:25054382

Cutaneous xanthomas with concurrent demodicosis and dermatophytosis in a cat.

PubMed

Vogelnest, L J

2001-07-01

Multiple cutaneous xanthomas, associated with fasting hyperlipidaemia, are described in a 9-month-old domestic long-haired cat. A severely pruritic, papular, and crusting dermatitis affecting the head and neck, initially diagnosed as lesions of the eosinophilic granuloma complex, progressively developed on the head and pinnae. Pruritus was controlled with administration of prednisolone and chlorambucil. Repeat histological examination confirmed the diagnosis of cutaneous xanthoma and concurrent mild demodicosis. Marked fasting hypercholesterolaemia, hypertriglyceridaemia and transient hyperglycaemia were subsequently confirmed. Treatment for hyperlipidaemia and xanthomas with a low-fat diet (Hill's Feline r/d) and the previously unreported treatment for feline demodicosis of daily oral milbemycin were commenced. Multiple pink, alopecic plaques and papules gradually regressed, however pruritus recurred if immunosuppressive treatment was reduced, and well-demarcated areas of alopecia developed on the head, limbs and trunk, despite negative skin scrapings for demodex mites. Fungal culture of hair samples yielded Microsporum canis. All cutaneous lesions resolved with the addition of griseofulvin to the treatment regimen. Concurrent corneal ulceration and keratoconjunctivitis sicca ultimately resolved with treatment, including topical cyclosporin. Diabetes mellitus developed 6 months after resolution of skin lesions. No cutaneous or ocular abnormalities were present 6 months later with continued low-fat diet and insulin administration, although transient recurrence of papules and pruritus occurred after inadvertent access to a fatty meal. An underlying primary hyperlipidaemia was suspected, causing pruritic xanthomas. This may represent the first report of concurrent cutaneous xanthomas, demodicosis and dermatophytosis in a cat.

Comprehensive analysis of MGMT promoter methylation: correlation with MGMT expression and clinical response in GBM.

PubMed

Shah, Nameeta; Lin, Biaoyang; Sibenaller, Zita; Ryken, Timothy; Lee, Hwahyung; Yoon, Jae-Geun; Rostad, Steven; Foltz, Greg

2011-01-07

O⁶-methylguanine DNA-methyltransferase (MGMT) promoter methylation has been identified as a potential prognostic marker for glioblastoma patients. The relationship between the exact site of promoter methylation and its effect on gene silencing, and the patient's subsequent response to therapy, is still being defined. The aim of this study was to comprehensively characterize cytosine-guanine (CpG) dinucleotide methylation across the entire MGMT promoter and to correlate individual CpG site methylation patterns to mRNA expression, protein expression, and progression-free survival. To best identify the specific MGMT promoter region most predictive of gene silencing and response to therapy, we determined the methylation status of all 97 CpG sites in the MGMT promoter in tumor samples from 70 GBM patients using quantitative bisulfite sequencing. We next identified the CpG site specific and regional methylation patterns most predictive of gene silencing and improved progression-free survival. Using this data, we propose a new classification scheme utilizing methylation data from across the entire promoter and show that an analysis based on this approach, which we call 3R classification, is predictive of progression-free survival (HR  = 5.23, 95% CI [2.089-13.097], p<0.0001). To adapt this approach to the clinical setting, we used a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) test based on the 3R classification and show that this test is both feasible in the clinical setting and predictive of progression free survival (HR  = 3.076, 95% CI [1.301-7.27], p = 0.007). We discuss the potential advantages of a test based on this promoter-wide analysis and compare it to the commonly used methylation-specific PCR test. Further prospective validation of these two methods in a large independent patient cohort will be needed to confirm the added value of promoter wide analysis of MGMT methylation in the clinical setting.

Comprehensive Analysis of MGMT Promoter Methylation: Correlation with MGMT Expression and Clinical Response in GBM

PubMed Central

Shah, Nameeta; Lin, Biaoyang; Sibenaller, Zita; Ryken, Timothy; Lee, Hwahyung; Yoon, Jae-Geun; Rostad, Steven; Foltz, Greg

2011-01-01

O6-methylguanine DNA-methyltransferase (MGMT) promoter methylation has been identified as a potential prognostic marker for glioblastoma patients. The relationship between the exact site of promoter methylation and its effect on gene silencing, and the patient's subsequent response to therapy, is still being defined. The aim of this study was to comprehensively characterize cytosine-guanine (CpG) dinucleotide methylation across the entire MGMT promoter and to correlate individual CpG site methylation patterns to mRNA expression, protein expression, and progression-free survival. To best identify the specific MGMT promoter region most predictive of gene silencing and response to therapy, we determined the methylation status of all 97 CpG sites in the MGMT promoter in tumor samples from 70 GBM patients using quantitative bisulfite sequencing. We next identified the CpG site specific and regional methylation patterns most predictive of gene silencing and improved progression-free survival. Using this data, we propose a new classification scheme utilizing methylation data from across the entire promoter and show that an analysis based on this approach, which we call 3R classification, is predictive of progression-free survival (HR  = 5.23, 95% CI [2.089–13.097], p<0.0001). To adapt this approach to the clinical setting, we used a methylation-specific multiplex ligation-dependent probe amplification (MS-MLPA) test based on the 3R classification and show that this test is both feasible in the clinical setting and predictive of progression free survival (HR  = 3.076, 95% CI [1.301–7.27], p = 0.007). We discuss the potential advantages of a test based on this promoter-wide analysis and compare it to the commonly used methylation-specific PCR test. Further prospective validation of these two methods in a large independent patient cohort will be needed to confirm the added value of promoter wide analysis of MGMT methylation in the clinical setting. PMID:21249131

Promoting the Social Inclusion and Academic Progress of Gypsy, Roma and Traveller Children: A Secondary School Case Study

ERIC Educational Resources Information Center

Gould, Siobhan

2017-01-01

The aim of this study was to identify support strategies used to promote "social inclusion" and "academic progress" of Key Stage 3 and 4 Gypsy, Roma and Traveller (GRT) pupils. The study used an interpretivist approach, incorporating an embedded single case study with several participant groups, namely GRT pupils, GRT parents,…

Inhibitor of DNA binding 1 regulates cell cycle progression of endothelial progenitor cells through induction of Wnt2 expression

PubMed Central

Xia, Xi; Yu, Yang; Zhang, Li; Ma, Yang; Wang, Hong

2016-01-01

Endothelial injury is a risk factor for atherosclerosis. Endothelial progenitor cell (EPC) proliferation contributes to vascular injury repair. Overexpression of inhibitor of DNA binding 1 (Id1) significantly promotes EPC proliferation; however, the underlying molecular mechanism remains to be fully elucidated. The present study investigated the role of Id1 in cell cycle regulation of EPCs, which is closely associated with proliferation. Overexpression of Id1 increased the proportion of EPCs in the S/G2M phase and significantly increased cyclin D1 expression levels, while knockdown of Id1 arrested the cell cycle progression of EPCs in the G1 phase and inhibited cyclin D1 expression levels. In addition, it was demonstrated that Id1 upregulated wingless-type mouse mammary tumor virus integration site family member 2 (Wnt2) expression levels and promoted β-catenin accumulation and nuclear translocation. Furthermore, Wnt2 knockdown counteracted the effects of Id1 on cell cycle progression of EPCs. In conclusion, the results of the present study indicate that Id1 promoted Wnt2 expression, which accelerated cell cycle progression from G1 to S phase. This suggests that Id1 may promote cell cycle progression of EPCs, and that Wnt2 may be important in Id1 regulation of the cell cycle of EPCs. PMID:27432753

Recent Updates on Treatment of Ocular Microbial Infections by Stem Cell Therapy: A Review.

PubMed

Teh, Seoh Wei; Mok, Pooi Ling; Abd Rashid, Munirah; Bastion, Mae-Lynn Catherine; Ibrahim, Normala; Higuchi, Akon; Murugan, Kadarkarai; Mariappan, Rajan; Subbiah, Suresh Kumar

2018-02-13

Ocular microbial infection has emerged as a major public health crisis during the past two decades. A variety of causative agents can cause ocular microbial infections; which are characterized by persistent and destructive inflammation of the ocular tissue; progressive visual disturbance; and may result in loss of visual function in patients if early and effective treatments are not received. The conventional therapeutic approaches to treat vision impairment and blindness resulting from microbial infections involve antimicrobial therapy to eliminate the offending pathogens or in severe cases; by surgical methods and retinal prosthesis replacing of the infected area. In cases where there is concurrent inflammation, once infection is controlled, anti-inflammatory agents are indicated to reduce ocular damage from inflammation which ensues. Despite advances in medical research; progress in the control of ocular microbial infections remains slow. The varying level of ocular tissue recovery in individuals and the incomplete visual functional restoration indicate the chief limitations of current strategies. The development of a more extensive therapy is needed to help in healing to regain vision in patients. Stem cells are multipotent stromal cells that can give rise to a vast variety of cell types following proper differentiation protocol. Stem cell therapy shows promise in reducing inflammation and repairing tissue damage on the eye caused by microbial infections by its ability to modulate immune response and promote tissue regeneration. This article reviews a selected list of common infectious agents affecting the eye; which include fungi; viruses; parasites and bacteria with the aim of discussing the current antimicrobial treatments and the associated therapeutic challenges. We also provide recent updates of the advances in stem cells studies on sepsis therapy as a suggestion of optimum treatment regime for ocular microbial infections.

(Z)-3,5,4'-Trimethoxystilbene Limits Hepatitis C and Cancer Pathophysiology by Blocking Microtubule Dynamics and Cell Cycle Progression

PubMed Central

Nguyen, Charles B.; Kotturi, Hari; Waris, Gulam; Mohammed, Altaf; Chandrakesan, Parthasarathy; May, Randal; Sureban, Sripathi; Weygant, Nathaniel; Qu, Dongfeng; Rao, Chinthalapally V.; Dhanasekaran, Danny N.; Bronze, Michael S.; Houchen, Courtney W.; Ali, Naushad

2016-01-01

Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related deaths worldwide. Chronic hepatitis C virus (HCV) infection causes induction of several tumor/cancer stem cell (CSC) markers and is known to be a major risk factor for development of HCC. Therefore, drugs that simultaneously target viral replication and CSC properties are needed for a risk-free treatment of advanced stage liver diseases including HCC. Here, we demonstrated that (Z)-3,5,4’-trimethoxystilbene (Z-TMS) exhibits potent anti-tumor and anti-HCV activities without exhibiting cytotoxicity to human hepatocytes in vitro or in mice livers. Diethylnitrosamine (DEN)/carbon tetrachloride (CCl4) extensively induced expression of DCLK1 (a CSC marker) in the livers of C57BL/6 mice following hepatic injury. Z-TMS exhibited hepatoprotective effects against DEN/CCl4-induced injury by reducing DCLK1 expression and improving histological outcomes. The drug caused bundling of DCLK1 with microtubules and blocked cell cycle progression at G2/M phase in hepatoma cells via downregulation of CDK1, induction of p21cip1/waf1 expression, and inhibition of Akt (Ser473) phosphorylation. Z-TMS also inhibited proliferation of erlotinib-resistant lung adenocarcinoma cells (H1975) bearing the T790M EGFR mutation most likely by promoting autophagy and nuclear fragmentation. In conclusion, Z-TMS appears to be a unique therapeutic agent targeting HCV and concurrently eliminating cells with neoplastic potential during chronic liver diseases including HCC. It may also be a valuable drug for targeting drug-resistant carcinomas and cancers of the lungs, pancreas, colon, and intestine in which DCLK1 is involved in tumorigenesis. PMID:27287718

Recent Updates on Treatment of Ocular Microbial Infections by Stem Cell Therapy: A Review

PubMed Central

Teh, Seoh Wei; Mok, Pooi Ling; Abd Rashid, Munirah; Bastion, Mae-Lynn Catherine; Ibrahim, Normala; Higuchi, Akon; Murugan, Kadarkarai; Mariappan, Rajan

2018-01-01

Ocular microbial infection has emerged as a major public health crisis during the past two decades. A variety of causative agents can cause ocular microbial infections; which are characterized by persistent and destructive inflammation of the ocular tissue; progressive visual disturbance; and may result in loss of visual function in patients if early and effective treatments are not received. The conventional therapeutic approaches to treat vision impairment and blindness resulting from microbial infections involve antimicrobial therapy to eliminate the offending pathogens or in severe cases; by surgical methods and retinal prosthesis replacing of the infected area. In cases where there is concurrent inflammation, once infection is controlled, anti-inflammatory agents are indicated to reduce ocular damage from inflammation which ensues. Despite advances in medical research; progress in the control of ocular microbial infections remains slow. The varying level of ocular tissue recovery in individuals and the incomplete visual functional restoration indicate the chief limitations of current strategies. The development of a more extensive therapy is needed to help in healing to regain vision in patients. Stem cells are multipotent stromal cells that can give rise to a vast variety of cell types following proper differentiation protocol. Stem cell therapy shows promise in reducing inflammation and repairing tissue damage on the eye caused by microbial infections by its ability to modulate immune response and promote tissue regeneration. This article reviews a selected list of common infectious agents affecting the eye; which include fungi; viruses; parasites and bacteria with the aim of discussing the current antimicrobial treatments and the associated therapeutic challenges. We also provide recent updates of the advances in stem cells studies on sepsis therapy as a suggestion of optimum treatment regime for ocular microbial infections. PMID:29438279

Industry progress to market a healthful diet to American children and adolescents.

PubMed

Kraak, Vivica I; Story, Mary; Wartella, Ellen A; Ginter, Jaya

2011-09-01

The IOM released an expert committee report in 2005 that assessed the nature, extent, and influence of food and beverage marketing practices on the diets and health of American children and adolescents. The report concluded that prevailing marketing practices did not support a healthful diet and offered recommendations for diverse stakeholders to promote a healthful diet. The investigators evaluated progress made by food, beverage, and restaurant companies; trade associations; entertainment companies; and the media to achieve the IOM report recommendations over 5 years. A literature review was conducted of electronic databases and relevant government, industry, and media websites between December 1, 2005, and January 31, 2011. Evidence selection was guided by the IOM LEAD principles (i.e., locate, evaluate, and assemble evidence to inform decisions) and five qualitative-research criteria, and it was validated by data and investigator triangulation. The investigators selected and categorized 117 data sources into two evidence tables used to evaluate industry progress (i.e., no, limited, moderate, and extensive). Food and beverage companies made moderate progress; however, limited progress was made by other industry subsectors. Industry stakeholders used integrated marketing communications (IMC) to promote primarily unhealthy products, which threaten children's and adolescents' health and miss opportunities to promote a healthy eating environment. Diverse industry stakeholders have several untapped opportunities to advance progress by promoting IMC to support a healthful diet; substantially strengthening self-regulatory programs; supporting truthful and non-misleading product labeling and health claims; engaging in partnerships; and funding independent evaluations of collective efforts. Copyright © 2011 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

IL-17B activated mesenchymal stem cells enhance proliferation and migration of gastric cancer cells.

PubMed

Bie, Qingli; Zhang, Bin; Sun, Caixia; Ji, Xiaoyun; Barnie, Prince Amoah; Qi, Chen; Peng, Jingjing; Zhang, Danyi; Zheng, Dong; Su, Zhaoliang; Wang, Shengjun; Xu, Huaxi

2017-03-21

Mesenchymal stem cells are important cells in tumor microenvironment. We have previously demonstrated that IL-17B/IL-17RB signal promoted progression of gastric cancer. In this study, we further explored the effect of IL-17B on mesenchymal stem cells in tumor microenvironment and its impact on the tumor progression. The results showed that IL-17B induced the expression of stemness-related genes Nanog, Sox2, and Oct4 in mesenchymal stem cells and enhanced its tumor-promoting effect. The supernatant from cultured mesenchymal stem cells after treating with exogenous rIL-17B promoted the proliferation and migration of MGC-803, therefor suggesting that rIL-17B might promote mesenchymal stem cells to produce soluble factors. In addition, rIL-17B also activated the NF-κΒ, STAT3, β-catenin pathway in mesenchymal stem cells. Our data revealed a new mechanism that IL-17B enhanced the progression of gastric cancer by activating mesenchymal stem cells.

Permeability of gypsum samples dehydrated in air

NASA Astrophysics Data System (ADS)

Milsch, Harald; Priegnitz, Mike; Blöcher, Guido

2011-09-01

We report on changes in rock permeability induced by devolatilization reactions using gypsum as a reference analog material. Cylindrical samples of natural alabaster were dehydrated in air (dry) for up to 800 h at ambient pressure and temperatures between 378 and 423 K. Subsequently, the reaction kinetics, so induced changes in porosity, and the concurrent evolution of sample permeability were constrained. Weighing the heated samples in predefined time intervals yielded the reaction progress where the stoichiometric mass balance indicated an ultimate and complete dehydration to anhydrite regardless of temperature. Porosity showed to continuously increase with reaction progress from approximately 2% to 30%, whilst the initial bulk volume remained unchanged. Within these limits permeability significantly increased with porosity by almost three orders of magnitude from approximately 7 × 10-19 m2 to 3 × 10-16 m2. We show that - when mechanical and hydraulic feedbacks can be excluded - permeability, reaction progress, and porosity are related unequivocally.

Department of Clinical Investigation, Madigan Army Medical Center, Tacoma, Washington. Annual Research Progress Report, Fiscal Year 1993

DTIC Science & Technology

1993-09-30

history of deep vein thrombosis, cerebral embolus, stroke , congestive heart failure, or ischemic heart disease will not be eligible. No concurrent...Jabbari B Seizures , and Parkinsonism. Neurology 43(4): 836-38, 1993. I Mullin JC Localizing Right Septal Accessory Pathways Using the Maximally Pre...Encephalomyopathy, Lactic Acidosis, Stroke -like I Chuang S, Merante F, Episodes (MELAS): Clinical, Radiological, Pathological, and Genetic Robinson BH

Rapidly progressive effusive constrictive pericarditis caused by methicillin sensitive Staphylococcus aureus (MSSA). samraakhtar@hotmail.com.

PubMed

Akhtar, Naveed; Khalid, Ayesha; Ahmed, Waqas; Rasheed, Khalid

2010-04-01

Effusive-constrictive pericarditis is a clinical syndrome characterized by concurrent pericardial effusion and pericardial constriction, where constrictive hemodynamics are persistent after effusion is drained. It may present at any point along the clinical course, from the occurrence of an effusion to the development of chronic pericardial constriction. We refer an unusual case of effusive constrictive pericarditis developing rapidly within days, following purulent pericarditis secondary to chest trauma.

Concurrent renal amyloidosis and thymoma resulting in a fatal ventricular thrombus in a dog

PubMed Central

Loewen, Jennifer M.; Cianciolo, Rachel E.; Zhang, Liwen; Yaeger, Michael; Ward, Jessica L.; Smith, Jodi D.

2018-01-01

Thymoma‐associated nephropathies have been reported in people but not in dogs. In this report, we describe a dog with thymoma and concurrent renal amyloidosis. A 7‐year‐old castrated male Weimaraner was presented for progressive anorexia, lethargy, and tachypnea. The dog was diagnosed with azotemia, marked proteinuria, and a thymoma that was surgically removed. Postoperatively, the dog developed a large left ventricular thrombus and was euthanized. Necropsy confirmed the presence of a left ventricular thrombus and histopathology revealed renal amyloidosis. We speculate that the renal amyloidosis occurred secondary to the thymoma, with amyloidosis in turn leading to nephrotic syndrome, hypercoagulability, and ventricular thrombosis. This case illustrates the potential for thymoma‐associated nephropathies to occur in dogs and that dogs suspected to have thymoma should have a urinalysis and urine protein creatinine ratio performed as part of the pre‐surgical database. PMID:29485186

The effect of attention loading on the inhibition of choice reaction time to visual motion by concurrent rotary motion

NASA Technical Reports Server (NTRS)

Looper, M.

1976-01-01

This study investigates the influence of attention loading on the established intersensory effects of passive bodily rotation on choice reaction time (RT) to visual motion. Subjects sat at the center of rotation in an enclosed rotating chamber and observed an oscilloscope on which were, in the center, a tracking display and, 10 deg left of center, a RT line. Three tracking tasks and a no-tracking control condition were presented to all subjects in combination with the RT task, which occurred with and without concurrent cab rotations. Choice RT to line motions was inhibited (probability less than .001) both when there was simultaneous vestibular stimulation and when there was a tracking task; response latencies lengthened progressively with increased similarity between the RT and tracking tasks. However, the attention conditions did not affect the intersensory effect; the significance of this for the nature of the sensory interaction is discussed.

Integration of CuAAC Polymerization and Controlled Radical Polymerization into Electron Transfer Mediated "Click-Radical" Concurrent Polymerization.

PubMed

Xue, Wentao; Wang, Jie; Wen, Ming; Chen, Gaojian; Zhang, Weidong

2017-03-01

The successful chain-growth copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) polymerization employing Cu(0)/pentamethyldiethylenetriamine (PMDETA) and alkyl halide as catalyst is first investigated by a combination of nuclear magnetic resonance, gel-permeation chromatography, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. In addition, the electron transfer mediated "click-radical" concurrent polymerization utilizing Cu(0)/PMDETA as catalyst is successfully employed to generate well-defined copolymers, where controlled CuAAC polymerization of clickable ester monomer is progressed in the main chain acting as the polymer backbone, the controlled radical polymerization (CRP) of acrylic monomer is carried out in the side chain. Furthermore, it is found that there is strong collaborative effect and compatibility between CRP and CuAAC polymerization to improve the controllability. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

125I Brachytherapy in Locally Advanced Nonsmall Cell Lung Cancer After Progression of Concurrent Radiochemotherapy

PubMed Central

Xiang, Zhanwang; Li, Guohong; Liu, Zhenyin; Huang, Jinhua; Zhong, Zhihui; Sun, Lin; Li, Chuanxing; Zhang, Funjun

2015-01-01

Abstract To investigate the safety and effectiveness of computed tomography (CT)-guided 125I seed implantation for locally advanced nonsmall cell lung cancer (NSCLC) after progression of concurrent radiochemotherapy (CCRT). We reviewed 78 locally advanced NSCLC patients who had each one cycle of first-line CCRT but had progressive disease identified from January 2006 to February 2015 at our institution. A total of 37 patients with 44 lesions received CT-guided percutaneous 125I seed implantation and second-line chemotherapy (group A), while 41 with 41 lesions received second-line chemotherapy (group B). Patients in group A and B received a total of 37 and 41 first cycle of CCRT treatment. The median follow-up was 19 (range 3–36) months. After the second treatment, the total response rate (RR) in tumor response accounted for 63.6% in group A, which was significantly higher than that of group B (41.5%) (P = 0.033). The median progression-free survival time (PFST) was 8.00 ± 1.09 months and 5.00 ± 0.64 months in groups A and B (P = 0.011). The 1-, 2-, and 3-year overall survival (OS) rates for group A were 56.8%, 16.2%, and 2.7%, respectively. For group B, OS rates were 36.6%, 9.8%, and 2.4%, respectively. The median OS time was 14.00 ± 1.82 months and 10.00 ± 1.37 months for groups A and B, respectively (P = 0.059). Similar toxicity reactions were found in both groups. Tumor-related clinical symptoms were significantly reduced and the patients’ quality of life was obviously improved. CT-guided 125I seed implantation proved to be potentially beneficial in treating localized advanced NSCLC; it achieved good local control rates and relieved clinical symptoms without increasing side effects. PMID:26656370

Extracellular guanosine and GTP promote expression of differentiation markers and induce S-phase cell-cycle arrest in human SH-SY5Y neuroblastoma cells.

PubMed

Guarnieri, S; Pilla, R; Morabito, C; Sacchetti, S; Mancinelli, R; Fanò, G; Mariggiò, M A

2009-04-01

SH-SY5Y neuroblastoma cells, a model for studying neuronal differentiation, are able to differentiate into either cholinergic or dopaminergic/adrenergic phenotypes depending on media conditions. Using this system, we asked whether guanosine (Guo) or guanosine-5'-triphosphate (GTP) are able to drive differentiation towards one particular phenotype. Differentiation was determined by evaluating the frequency of cells bearing neurites and assessing neurite length after exposure to different concentrations of Guo or GTP for different durations. After 6 days, 0.3 mM Guo or GTP induced a significant increase in the number of cells bearing neurites and increased neurite length. Western blot analyses confirmed that purines induced differentiation; cells exposed to purines showed increases in the levels of GAP43, MAP2, and tyrosine hydroxylase. Proliferation assays and cytofluorimetric analyses indicated a significant anti-proliferative effect of purines, and a concentration-dependent accumulation of cells in S-phase, starting after 24 h of purine exposure and extending for up to 6 days. A transcriptional profile analysis using gene arrays showed that an up-regulation of cyclin E2/cdk2 evident after 24 h was responsible for S-phase entry, and a concurrent down-regulation of cell-cycle progression-promoting cyclin B1/B2 prevented S-phase exit. In addition, patch-clamp recordings revealed that 0.3 mM Guo or GTP, after 6 day incubation, significantly decreased Na(+) currents. In conclusion, we showed Guo- and GTP-induced cell-cycle arrest in neuroblastoma cells and suggest that this makes these cells more responsive to differentiation processes that favor the dopaminergic/adrenergic phenotype.

In Vivo Selection of CD4+ T Cells Transduced with a Gamma-Retroviral Vector Expressing a Single-Chain Intrabody Targeting HIV-1 Tat

PubMed Central

Braun, Stephen E.; Taube, Ran; Zhu, Quan; Wong, Fay Eng; Murakami, Akikazu; Kamau, Erick; Dwyer, Markryan; Qiu, Gang; Daigle, Janet; Carville, Angela; Johnson, R. Paul

2012-01-01

Abstract We evaluated the potential of an anti–human immunodeficiency virus (HIV) Tat intrabody (intracellular antibody) to promote the survival of CD4+ cells after chimeric simian immunodeficiency virus (SIV)/HIV (SHIV) infection in rhesus macaques. Following optimization of stimulation and transduction conditions, purified CD4+ T cells were transduced with GaLV-pseudotyped retroviral vectors expressing either an anti-HIV-1 Tat or a control single-chain intrabody. Ex vivo intrabody-gene marking was highly efficient, averaging four copies per CD4+ cell. Upon reinfusion of engineered autologous CD4+ cells into two macaques, high levels of gene marking (peak of 0.6% and 6.8% of peripheral blood mononuclear cells (PBMCs) and 0.3% or 2.2% of the lymph node cells) were detected in vivo. One week post cell infusion, animals were challenged with SHIV 89.6p and the ability of the anti-HIV Tat intrabody to promote cell survival was evaluated. The frequency of genetically modified CD4+ T cells progressively decreased, concurrent with loss of CD4+ cells and elevated viral loads in both animals. However, CD4+ T cells expressing the therapeutic anti-Tat intrabody exhibited a relative survival advantage over an 8- and 21-week period compared with CD4+ cells expressing a control intrabody. In one animal, this survival benefit of anti-Tat transduced cells was associated with a reduction in viral load. Overall, these results indicate that a retrovirus-mediated anti-Tat intrabody provided significant levels of gene marking in PBMCs and peripheral tissues and increased relative survival of transduced cells in vivo. PMID:22734618

Health Informatics 3.0 and other increasingly dispersed technologies require even greater trust: promoting safe evidence-based health informatics. Contribution of the IMIA Working Group on Technology Assessment & Quality Development in Health Informatics.

PubMed

Rigby, M; Ammenwerth, E; Talmon, J; Nykänen, P; Brender, J; de Keizer, N

2011-01-01

Health informatics is generally less committed to a scientific evidence-based approach than any other area of health science, which is an unsound position. Introducing the new Web 3.0 paradigms into health IT applications can unleash a further great potential, able to integrate and distribute data from multiple sources. The counter side is that it makes the user and the patient evermore dependent on the 'black box' of the system, and the re-use of the data remote from the author and initial context. Thus anticipatory consideration of uses, and proactive analysis of evidence of effects, are imperative, as only when a clinical technology can be proven to be trustworthy and safe should it be implemented widely - as is the case with other health technologies. To argue for promoting evidence-based health informatics as systems become more powerful and pro-active yet more dispersed and remote; and evaluation as the means of generating the necessary scientific evidence base. To present ongoing IMIA and EFMI initiatives in this field. Critical overview of recent developments in health informatics evaluation, alongside the precedents of other health technologies, summarising current initiatives and the new challenges presented by Health Informatics 3.0. Web 3.0 should be taken as an opportunity to move health informatics from being largely unaccountable to one of being an ethical and responsible science-based domain. Recent and planned activities of the EFMI and IMIA working groups have significantly progressed key initiatives. Concurrent with the emergence of Web 3.0 as a means of new-generation diffuse health information systems comes an increasing need for an evidence-based culture in health informatics.

African N Assessment

NASA Astrophysics Data System (ADS)

Bekunda, M.; Galford, G. L.; Hickman, J. E.; Palm, C.

2011-12-01

Africa's smallholder agricultural systems face unique challenges in planning for reducing poverty, concurrent with adaptation and mitigation to climate change. At continental level, policy seeks to promote a uniquely African Green Revolution to increase crop yields and food production, and improve local livelihoods. However, the consequences on the environment and climate are not clear; these pro-economic development measures should be linked to climate change adaptation and mitigation measures, and research is required to help achieve these policy proposals by identifying options, and testing impacts. In particular, increased nitrogen (N) inputs are essential for increasing food production in Africa, but are accompanied by inevitable increases in losses to the environment. These losses appear to be low at input levels promoted in agricultural development programs, while the increased N inputs both increase current food production and appear to reduce the vulnerability of food production to changes in climate. We present field and remote sensing evidence from Malawi that subsidizing improved seed and fertilizers increases resilience to drought without adding excess N to the environment. In Kenya, field research identified thresholds in N2O losses, where emissions are very low at fertilization rates of less than 200 kg ha-1. Village-scale models have identified potential inefficiencies in the food production process where the largest losses of reactive N occur, and which could be targeted to reduce the amount of N released to the environment. We further review some on-going research activities and progress in Africa that compare different methods of managing resources that target resilience in food production and adaptation to climate change, using nutrient N as an indicator, while evaluating the effects of these resource management practices on ecosystems and the environment.

The shopping brain: math anxiety modulates brain responses to buying decisions.

PubMed

Jones, William J; Childers, Terry L; Jiang, Yang

2012-01-01

Metacognitive theories propose that consumers track fluency feelings when buying, which may have biological underpinnings. We explored this using event-related potential (ERP) measures as twenty high-math anxiety (High MA) and nineteen low-math anxiety (Low MA) consumers made buying decisions for promoted (e.g., 15% discount) and non-promoted products. When evaluating prices, ERP correlates of higher perceptual and conceptual fluency were associated with buys, however only for High MA females under no promotions. In contrast, High MA females and Low MA males demonstrated greater FN400 amplitude, associated with enhanced conceptual processing, to prices of buys relative to non-buys under promotions. Concurrent late positive component (LPC) differences under no promotions suggest discrepant retrieval processes during price evaluations between consumer groups. When making decisions to buy or not, larger (smaller) P3, sensitive to outcome responses in the brain, was associated with buying for High MA females (Low MA females) under promotions, an effect also present for males under no promotions. Thus, P3 indexed decisions to buy differently between anxiety groups, but only for promoted items among females and for no promotions among males. Our findings indicate that perceptual and conceptual processes interact with anxiety and gender to modulate brain responses during consumer choices. Copyright © 2011 Elsevier B.V. All rights reserved.

Concurrent exercise training: do opposites distract?

PubMed Central

Coffey, Vernon G.

2016-01-01

Abstract Specificity is a core principle of exercise training to promote the desired adaptations for maximising athletic performance. The principle of specificity of adaptation is underpinned by the volume, intensity, frequency and mode of contractile activity and is most evident when contrasting the divergent phenotypes that result after undertaking either prolonged endurance or resistance training. The molecular profiles that generate the adaptive response to different exercise modes have undergone intense scientific scrutiny. Given divergent exercise induces similar signalling and gene expression profiles in skeletal muscle of untrained or recreationally active individuals, what is currently unclear is how the specificity of the molecular response is modified by prior training history. The time course of adaptation and when ‘phenotype specificity’ occurs has important implications for exercise prescription. This context is essential when attempting to concomitantly develop resistance to fatigue (through endurance‐based exercise) and increased muscle mass (through resistance‐based exercise), typically termed ‘concurrent training’. Chronic training studies provide robust evidence that endurance exercise can attenuate muscle hypertrophy and strength but the mechanistic underpinning of this ‘interference’ effect with concurrent training is unknown. Moreover, despite the potential for several key regulators of muscle metabolism to explain an incompatibility in adaptation between endurance and resistance exercise, it now seems likely that multiple integrated, rather than isolated, effectors or processes generate the interference effect. Here we review studies of the molecular responses in skeletal muscle and evidence for the interference effect with concurrent training within the context of the specificity of training adaptation. PMID:27506998

Exogenous fatty acid binding protein 4 promotes human prostate cancer cell progression.

PubMed

Uehara, Hisanori; Takahashi, Tetsuyuki; Oha, Mina; Ogawa, Hirohisa; Izumi, Keisuke

2014-12-01

Epidemiologic studies have found that obesity is associated with malignant grade and mortality in prostate cancer. Several adipokines have been implicated as putative mediating factors between obesity and prostate cancer. Fatty acid binding protein 4 (FABP4), a member of the cytoplasmic fatty acid binding protein multigene family, was recently identified as a novel adipokine. Although FABP4 is released from adipocytes and mean circulating concentrations of FABP4 are linked with obesity, effects of exogenous FABP4 on prostate cancer progression are unclear. In this study, we examined the effects of exogenous FABP4 on human prostate cancer cell progression. FABP4 treatment promoted serum-induced prostate cancer cell invasion in vitro. Furthermore, oleic acid promoted prostate cancer cell invasion only if FABP4 was present in the medium. These promoting effects were reduced by FABP4 inhibitor, which inhibits FABP4 binding to fatty acids. Immunostaining for FABP4 showed that exogenous FABP4 was taken up into DU145 cells in three-dimensional culture. In mice, treatment with FABP4 inhibitor reduced the subcutaneous growth and lung metastasis of prostate cancer cells. Immunohistochemical analysis showed that the number of apoptotic cells, positive for cleaved caspase-3 and cleaved PARP, was increased in subcutaneous tumors of FABP4 inhibitor-treated mice, as compared with control mice. These results suggest that exogenous FABP4 might promote human prostate cancer cell progression by binding with fatty acids. Additionally, exogenous FABP4 activated the PI3K/Akt pathway, independently of binding to fatty acids. Thus, FABP4 might be a key molecule to understand the mechanisms underlying the obesity-prostate cancer progression link. © 2014 UICC.

Dual therapeutic functions of F-5 fragment in burn wounds: preventing wound progression and promoting wound healing in pigs.

PubMed

Bhatia, Ayesha; O'Brien, Kathryn; Chen, Mei; Wong, Alex; Garner, Warren; Woodley, David T; Li, Wei

2016-01-01

Burn injuries are a leading cause of morbidity including prolonged hospitalization, disfigurement, and disability. Currently there is no Food and Drug Administration-approved burn therapeutics. A clinical distinction of burn injuries from other acute wounds is the event of the so-called secondary burn wound progression within the first week of the injury, in which a burn expands horizontally and vertically from its initial boundary to a larger area. Therefore, an effective therapeutics for burns should show dual abilities to prevent the burn wound progression and thereafter promote burn wound healing. Herein we report that topically applied F-5 fragment of heat shock protein-90α is a dual functional agent to promote burn wound healing in pigs. First, F-5 prevents burn wound progression by protecting the surrounding cells from undergoing heat-induced caspase 3 activation and apoptosis with increased Akt activation. Accordingly, F-5-treated burn and excision wounds show a marked decline in inflammation. Thereafter, F-5 accelerates burn wound healing by stimulating the keratinocyte migration-led reepithelialization, leading to wound closure. This study addresses a topical agent that is capable of preventing burn wound progression and accelerating burn wound healing.

The Indian Elder, A Forgotten American. Final Report on the National Indian Conference on Aging (1st, Phoenix, Arizona, June 15-17, 1976) Including Supplemental Documentation.

ERIC Educational Resources Information Center

Lyon, Juana P., Comp.

A culmination of the efforts of many Indian and concerned non-Indian people, the conference, attended by almost 1,500 American Indians and Alaska Natives representing 171 tribes, aimed to promote effective and adequate services needed by the Indian elderly. Based on input from the Indian community and service providers, five concurrent workshops…

A patient self-assessment tool for cardiac rehabilitation.

PubMed

Phelan, C; Finnell, M D; Mottla, K A

1989-01-01

A patient self-assessment tool was designed, tested, and implemented to promote cardiac-specific data collection, based on Gordon's Functional Health Patterns, to maximize patient/family involvement in determining a plan of care, and to streamline primary nurses' documentation requirements. Retrospective and concurrent chart reviews provided data for quality assurance monitoring. The results of the monitoring demonstrated that the self-assessment tool markedly improved the patient-specific data base.

Comparison of the clinical efficacy between single-agent and dual-agent concurrent chemoradiotherapy in the treatment of unresectable esophageal squamous cell carcinoma: a multicenter retrospective analysis.

PubMed

Li, Jie; Gong, Youling; Diao, Peng; Huang, Qingmei; Wen, Yixue; Lin, Binwei; Cai, Hongwei; Tian, Honggang; He, Bing; Ji, Lanlan; Guo, Ping; Miao, Jidong; Du, Xiaobo

2018-01-22

Some Chinese patients with esophageal squamous cell carcinomaare often treated with single-agent concurrent chemoradiotherapy. However, no results have been reported from randomized controlled clinical trials comparing single-agent with double-agent concurrent chemoradiotherapy. It therefore remains unclear whether these regimens are equally clinically effective. In this study, we retrospectively analyzed and compared the therapeutic effects of single-agent and double-agent concurrent chemoradiotherapy in patients with unresectable esophageal squamous cell carcinoma. This study enrolled 168 patients who received definitive concurrent chemoradiotherapy for locally advanced unresectable esophageal squamous carcinoma at 10 hospitals between 2010 and 2015. We evaluated survival time and toxicity. The Kaplan-Meier method was used to estimate survival data. The log-rank test was used in univariate analysis A Cox proportional hazards regression model was used to conduct a multivariate analysis of the effects of prognostic factors on survival. In this study, 100 (59.5%) and 68 patients (40.5%) received single-agent and dual-agent combination chemoradiotherapy, respectively. The estimate 5-year progression-free survival (PFS) rate and overall survival (OS) rate of dual-agent therapy was higher than that of single-agent therapy (52.5% and 40.9%, 78.2% and 60.7%, respectively), but there were no significant differences (P = 0.367 and 0.161, respectively). Multivariate analysis showed that sex, age,and radiotherapy dose had no significant effects on OS or PFS. Only disease stage was associated with OS and PFS in the multivariable analysis (P = 0.006 and 0.003, respectively). In dual-agent group, the incidence of acute toxicity and the incidence of 3 and4 grade toxicity were higher than single-agent group. The 5-year PFS and OS rates of dual-agent therapy were higher than those of single-agent concurrent chemoradiotherapy for patients with unresectable esophageal squamous cell carcinoma; however, there were no significant differences in univariate analysis and multivariable analysis. Single-agent concurrent chemotherapy had less toxicity than a double-drug regimen. Therefore, we suggest that single therapis not inferior to dual therapy y. In the future, we aim to confirm our hypothesis through a prospective randomized study.

Schwann cells induce cancer cell dispersion and invasion

PubMed Central

Deborde, Sylvie; Lyubchik, Anna; Zhou, Yi; He, Shizhi; McNamara, William F.; Chernichenko, Natalya; Lee, Sei-Young; Barajas, Fernando; Chen, Chun-Hao; Bakst, Richard L.; Vakiani, Efsevia; He, Shuangba; Hall, Alan; Wong, Richard J.

2016-01-01

Nerves enable cancer progression, as cancers have been shown to extend along nerves through the process of perineural invasion, which carries a poor prognosis. Furthermore, the innervation of some cancers promotes growth and metastases. It remains unclear, however, how nerves mechanistically contribute to cancer progression. Here, we demonstrated that Schwann cells promote cancer invasion through direct cancer cell contact. Histological evaluation of murine and human cancer specimens with perineural invasion uncovered a subpopulation of Schwann cells that associates with cancer cells. Coculture of cancer cells with dorsal root ganglion extracts revealed that Schwann cells direct cancer cells to migrate toward nerves and promote invasion in a contact-dependent manner. Upon contact, Schwann cells induced the formation of cancer cell protrusions in their direction and intercalated between the cancer cells, leading to cancer cell dispersion. The formation of these processes was dependent on Schwann cell expression of neural cell adhesion molecule 1 (NCAM1) and ultimately promoted perineural invasion. Moreover, NCAM1-deficient mice showed decreased neural invasion and less paralysis. Such Schwann cell behavior reflects normal Schwann cell programs that are typically activated in nerve repair but are instead exploited by cancer cells to promote perineural invasion and cancer progression. PMID:26999607

White Adipose Tissue Cells Are Recruited by Experimental Tumors and Promote Cancer Progression in Mouse Models

PubMed Central

Zhang, Yan; Daquinag, Alexes; Traktuev, Dmitry O.; Amaya-Manzanares, Felipe; Simmons, Paul J.; March, Keith L.; Pasqualini, Renata; Arap, Wadih; Kolonin, Mikhail G.

2010-01-01

The connection between obesity and accelerated cancer progression has been established, but the mediating mechanisms are not well understood. We have shown that stromal cells from white adipose tissue (WAT) cooperate with the endothelium to promote blood vessel formation through the secretion of soluble trophic factors. Here, we hypothesize that WAT directly mediates cancer progression by serving as a source of cells that migrate to tumors and promote neovascularization. To test this hypothesis, we have evaluated the recruitment of WAT-derived cells by tumors and the effect of their engraftment on tumor growth by integrating a transgenic mouse strain engineered for expansion of traceable cells with established allograft and xenograft cancer models. Our studies show that entry of adipose stromal and endothelial cells into systemic circulation leads to their homing to and engraftment into tumor stroma and vasculature, respectively. We show that recruitment of adipose stromal cells by tumors is sufficient to promote tumor growth. Finally, we show that migration of stromal and vascular progenitor cells from WAT grafts to tumors is also associated with acceleration of cancer progression. These results provide a biological insight for the clinical association between obesity and cancer, thus outlining potential avenues for preventive and therapeutic strategies. PMID:19491274

CAPIRI-IMRT: a phase II study of concurrent capecitabine and irinotecan with intensity-modulated radiation therapy for the treatment of recurrent rectal cancer.

PubMed

Cai, Gang; Zhu, Ji; Palmer, Joshua D; Xu, Ye; Hu, Weigang; Gu, Weilie; Cai, Sanjun; Zhang, Zhen

2015-02-28

This study investigated the local effect and acute toxicity of irinotecan and capecitabine with concurrent intensity-modulated radiation therapy (IMRT) for the treatment of recurrent rectal cancer without prior pelvic irradiation. Seventy-one patients diagnosed with recurrent rectal cancer who did not previously receive pelvic irradiation were treated in our hospital from October 2009 to July 2012. Radiotherapy was delivered to the pelvis, and IMRT of 45 Gy (1.8 Gy per fraction), followed by a boost of 10 Gy to 16 Gy (2 Gy per fraction), was delivered to the recurrent sites. The concurrent chemotherapy regimen was 50 mg/m(2) irinotecan weekly and 625 mg/m(2) capecitabine twice daily (Mon-Fri). Radical surgery was recommended for medically fit patients without extra-pelvic metastases. The patients were followed up every 3 months. Tumor response was evaluated using CT/MRIs according to the RECIST criteria or postoperative pathological findings. NCI-CTC 3.0 was used to score the toxicities. Forty-eight patients (67.6%) had confirmed recurrent rectal cancer without extra pelvic metastases, and 23 patients (32.4%) had extra pelvic metastases. Fourteen patients (19.7%) underwent radical resections (R0) post-chemoradiation. A pathologic complete response was observed in 7 of 14 patients. A clinical complete response was observed in 4 patients (5.6%), and a partial response was observed in 22 patients (31.0%). Only 5 patients (7.0%) showed progressive disease during or shortly after treatment. Of 53 symptomatic patients, clinical complete and partial symptom relief with chemoradiation was achieved in 56.6% and 32.1% of patients, respectively. Only 2 patients (2.8%) experienced grade 4 leukopenia. The most common grade 3 toxicity was diarrhea (16 [22.5%] patients). The median follow-up was 31 months. The cumulative local progression-free survival rate was 74.2% and 33.9% at 1 and 3 years after chemoradiation, respectively. The cumulative total survival rate was 80.1% and 36.5% at 1 and 3 years after chemoradiation, respectively. This study revealed that concurrent irinotecan and capecitabine with IMRT significantly relieves local symptoms and exhibits promising efficacy with manageable toxicities in recurrent rectal cancer without prior pelvic irradiation. Improving the rate of R0 resections will be investigated in a future study.

Syn-Extensional Constrictional Folding of the Gwoira Rider Block, a Large Fault-Bounded Slice Atop the Mai'iu Low-Angle Normal Fault, Woodlark Rift.

NASA Astrophysics Data System (ADS)

Little, T. A.; Webber, S. M.; Norton, K. P.; Mizera, M.; Oesterle, J.; Ellis, S. M.

2016-12-01

The Mai'iu Fault is an active and corrugated low-angle normal fault (LANF) in Woodlark Rift, Eastern Papua New Guinea, which dips 21° NNE, accommodating rapid N-S extension. The Gwoira rider block is a large fault-bounded sedimentary slice comprising the Gwoira Conglomerate, located within a large synformal megamullion in the Mai'iu Fault surface. The Gwoira Conglomerate was originally deposited on the Mai'iu Fault hanging wall concurrent with extension, and has since been buried to a maximum depth of 1600-2100 m (evidenced by vitrinite reflectance data), back-tilted, and synformally folded. Both the Gwoira Conglomerate (former hanging wall) and mylonitic foliation (footwall) of the Mai'iu Fault have been shortened E-W, perpendicular to the extension direction. We show that E-W synformal folding of the Gwoira Conglomerate was concurrent with ongoing sedimentation and extension on the Mai'iu Fault. Structurally shallower Gwoira Conglomerate strata are folded less than deeper strata, indicating that folding was progressively accrued concurrent with N-S extension. We also show that abandonment of the inactive strand of the Mai'iu Fault in favor of the Gwoira Fault, which resulted in formation of the Gwoira rider block, occurred in response to progressive megamullion amplification and resultant misorientation of the inactive strand of the Mai'iu Fault. We attribute E-W folding to extension-perpendicular constriction. This is consistent with observations of outcrop-scale conjugate strike-slip faults that deform the footwall and hanging wall of the Mai'iu Fault, and accommodate E-W shortening. Constrictional folding remains active in the near-surface as evidenced by synformal tilting of inferred Late Quaternary fluvial terraces atop the Gwoira rider block. This sequence of progressive constrictional folding is dated using 26Al/10Be terrestrial cosmogenic nuclide burial dating of the Gwoira Conglomerate. Finally, because rider block formation records abandonment of the uppermost part of a LANF, Coulomb fault mechanical analysis (after Choi and Buck, 2012) can be applied to field observations to provide an upper limit on LANF frictional strength (µf). Modelling constrains the µf for the Mai'iu Fault to ≤0.25, which suggests that the Mai'iu Fault is frictionally very weak.

3-D DNA methylation phenotypes correlate with cytotoxicity levels in prostate and liver cancer cell models

PubMed Central

2013-01-01

Background The spatial organization of the genome is being evaluated as a novel indicator of toxicity in conjunction with drug-induced global DNA hypomethylation and concurrent chromatin reorganization. 3D quantitative DNA methylation imaging (3D-qDMI) was applied as a cell-by-cell high-throughput approach to investigate this matter by assessing genome topology through represented immunofluorescent nuclear distribution patterns of 5-methylcytosine (MeC) and global DNA (4,6-diamidino-2-phenylindole = DAPI) in labeled nuclei. Methods Differential progression of global DNA hypomethylation was studied by comparatively dosing zebularine (ZEB) and 5-azacytidine (AZA). Treated and untreated (control) human prostate and liver cancer cells were subjected to confocal scanning microscopy and dedicated 3D image analysis for the following features: differential nuclear MeC/DAPI load and codistribution patterns, cell similarity based on these patterns, and corresponding differences in the topology of low-intensity MeC (LIM) and low in intensity DAPI (LID) sites. Results Both agents generated a high fraction of similar MeC phenotypes across applied concentrations. ZEB exerted similar effects at 10–100-fold higher drug concentrations than its AZA analogue: concentration-dependent progression of global cytosine demethylation, validated by measuring differential MeC levels in repeat sequences using MethyLight, and the concurrent increase in nuclear LIM densities correlated with cellular growth reduction and cytotoxicity. Conclusions 3D-qDMI demonstrated the capability of quantitating dose-dependent drug-induced spatial progression of DNA demethylation in cell nuclei, independent from interphase cell-cycle stages and in conjunction with cytotoxicity. The results support the notion of DNA methylation topology being considered as a potential indicator of causal impacts on chromatin distribution with a conceivable application in epigenetic drug toxicology. PMID:23394161

A phase I study of gefitinib with concurrent dose-escalated weekly docetaxel and conformal three-dimensional thoracic radiation followed by consolidative docetaxel and maintenance gefitinib for patients with stage III non-small cell lung cancer.

PubMed

Center, Brian; Petty, William Jeffrey; Ayala, Diandra; Hinson, William H; Lovato, James; Capellari, James; Oaks, Timothy; Miller, Antonius A; Blackstock, Arthur William

2010-01-01

Concurrent radiation and chemotherapy is the standard of care for good performance status patients with stage III non-small cell lung cancer. Locoregional control remains a significant factor relating to poor outcome. Preclinical and early clinical data suggest that docetaxel and gefitinib have radiosensitizing activity. This study sought to define the maximum tolerated dose of weekly docetaxel that could be given with daily gefitinib and concurrent thoracic radiation therapy. Patients with histologically confirmed, inoperable stage III non-small cell lung cancer and good performance status (Eastern Cooperative Oncology Group 0-1) were eligible for this study. Patients received three-dimensional conformal thoracic radiation to a dose of 70 Gy concurrently with oral gefitinib at a dose of 250 mg daily and intravenous, weekly docetaxel at escalating doses from 15 to 30 mg/m2 in cohorts of patients. Patients were given a 2-week rest period after the concurrent therapy, during which they received only gefitinib. After the 2-week rest period, patients received consolidation chemotherapy with docetaxel 75 mg/m2 given every 21 days for two cycles. Maintenance gefitinib was continued until disease progression or study completion. Sixteen patients were enrolled on the study between December 2003 and April 2007 with the following characteristics: median age, 64 years (range 43-79 years); M/F: 9/7; and performance status 0/1, 1/15. Dose-limiting pulmonary toxicity and esophagitis were encountered at a weekly docetaxel dose of 25 mg/m2, resulting in a maximum tolerated dose of 20 mg/m2/wk. Overall, grade 3/4 hematologic toxicity was observed in 27% of patients. Grade 3/4 esophageal and pulmonary toxicities were reported in 27% and 20% of patients, respectively. The overall response rate was 46%, and the median survival for all patients was 21 months. Concurrent thoracic radiation with weekly docetaxel and daily gefitinib is feasible but results in moderate toxicity. For further studies, the recommended weekly docetaxel dose for this chemoradiation regimen is 20 mg/m2.

Influence of residual moisture and sealing atmosphere on viability of two freeze-dried viral vaccines.

PubMed

Precausta, P M; Simatos, D; Le Pemp, M; Devaux, B; Kato, F

1980-10-01

This study demonstrated the complexity of the factors leading to changes in the infectivity titers of freeze-dried canine distemper and poultry infectious bronchitis viral vaccines. The change in moisture content during the storage period was an additional parameter which may influence the infectivity titer. The results emphasized the difficulty of predetermining variations in infectivity titers from the initial residual moisture. The analysis of the variations in infectivity titers during the storage of two vaccines led to the formulation of a hypothesis of the presence of two components of different thermostability. Moreover, the temporary increase in the infectivity titer of infectious bronchitis vaccine stored progressively dissociating during storage concurrent with a progressive inactivation of infectious particles.

Reconsidering community-based health promotion: promise, performance, and potential.

PubMed

Merzel, Cheryl; D'Afflitti, Joanna

2003-04-01

Contemporary public health emphasizes a community-based approach to health promotion and disease prevention. The evidence from the past 20 years indicates, however, that many community-based programs have had only modest impact, with the notable exception of a number of HIV prevention programs. To better understand the reasons for these outcomes, we conducted a systematic literature review of 32 community-based prevention programs. Reasons for poor performance include methodological challenges to study design and evaluation, concurrent secular trends, smaller-than-expected effect sizes, limitations of the interventions, and limitations of theories used. The effectiveness of HIV programs appears to be related in part to extensive formative research and an emphasis on changing social norms.

Dihydroartemisinin inhibits indoxyl sulfate (IS)-promoted cell cycle progression in mesangial cells by targeting COX-2/mPGES-1/PGE2 cascade.

PubMed

Mungun, Harr-Keshauve; Li, Shuzhen; Zhang, Yue; Huang, Songming; Jia, Zhanjun; Ding, Guixia; Zhang, Aihua

2018-01-01

Dihydroartemisinin (DHA) is a semisynthetic derivative of artemisinin and has been used as an antimalarial drug. Recently, roles of artemisinin and its derivatives in treating diseases besides antimalarial effect were documented. Thus, this study was undertaken to investigate the role of DHA in indoxyl sulfate (IS)-promoted cell cycle progression in glomerular mesangial cells, as well as the potential mechanisms. Under the basal condition, DHA significantly retarded the cell cycle progression as shown by decreased cell percentage in S phase and increased cell percentage in G1/G0 phases in line with reduced cell cycle proteins cyclin A2 and cyclin D1. Interestingly, DHA also inactivated the COX-2/mPGES-1/PGE 2 cascade which has been shown to play a critical role in promoting the mesangial cell cycle progression by our previous studies. Next, we investigated the role of DHA in IS-triggered cell cycle progression in this mesangial cell line. As expected, DHA treatment significantly retarded IS-induced cell cycle progression and inhibited the activation of COX-2/mPGES-1/PGE 2 cascade induced by IS. In summary, these data indicated that DHA inhibited the cell cycle progression in glomerular mesangial cells under normal condition or IS challenge possibly through the inhibition of COX-2/mPGES-1/PGE 2 cascade, suggesting a potential of DHA in treating glomerular diseases with mesangial cell proliferation.

[Macular choroidal blood flow in concurrent age-related macular degeneration and primary open-angle glaucoma].

PubMed

Panova, I E; Ermak, E M; Shaimova, T A; Shaimova, V A

2016-01-01

Ocular circulation disorders are an important factor in the development of primary open-angle glaucoma (POAG) and age-related macular degeneration (AMD). To date, however, there have been no studies on choroidal blood flow peculiarities in case of concurrent AMD and POAG. to determine distinctive features of choroidal blood flow characteristic of concurrent AMD and POAG and to assess their role in disease pathogenesis. Macular choroidal blood flow, including blood supply, was assessed in 54 patients (102 eyes) by means of Doppler ultrasound. Three groups were formed: group 1 - 38 eyes with both AMD and POAG; group 2 - 41 eyes with AMD and no signs of optic nerve pathology; and group 3 - 23 eyes with POAG and no signs of AMD. Groups 1 and 2 were subdivided into two subgroups each: А - atrophic AMD and B - macular drusen. The mean patient age was 78.7±8.4 years. The following parameters of choroidal blood flow were of interest: peak systolic velocity (Vps), end diastolic velocity (Ved), time-averaged maximum velocity (Vtamax), and resistance index (RI). Groups 1, 3, and 2A had an evident choroidal hypoperfusion in the macular area (decreased Vtamax) with uncompensated perfusion deficit, despite autoregulation efforts (decreased Vps, Ved, decreased or normal RI). Group 2B demonstrated a significantly higher rate of choroidal hyperperfusion (increased Vps, Ved, Vtamax, and RI). Concurrent AMD and POAG are notable for choroidal hypoperfusion in the macular area that leads to inadequate trophism of the neurosensory retina and can aggravate the course of AMD contributing to progression of its atrophic form.

Challenges in the concurrent management of malaria and HIV in pregnancy in sub-Saharan Africa.

PubMed

Brentlinger, Paula E; Behrens, Christopher B; Micek, Mark A

2006-02-01

Approximately one million pregnancies are complicated by both malaria and HIV infection in sub-Saharan Africa annually. Both infections have been associated with maternal and infant morbidity and mortality. Intermittent preventive treatment, usually with sulfadoxine-pyrimethamine, has been shown to prevent pregnancy-related malaria and its complications. Several different regimens of antiretroviral therapy are now available to prevent mother-to-child transmission of HIV and/or progression of maternal HIV infection during pregnancy. However, no published studies have yet shown whether standard intermittent preventive treatment and antiretroviral regimens are medically and operationally compatible in pregnancy. We reviewed existing policies regarding prevention and treatment of HIV and malaria in pregnancy, as well as published literature on adverse effects of antiretrovirals and antimalarials commonly used in pregnancy in developing countries, and found that concurrent prescription of sulfadoxine-pyrimethamine, co-trimoxazole (trimethoprim-sulfamethoxazole), and antiretroviral agents including nevirapine and zidovudine per existing protocols for prevention of malaria and vertical HIV transmission may result in adverse drug interactions or overlapping, diagnostically challenging drug toxicities. Insecticide-treated bednets should be provided for HIV-infected pregnant women at risk for malaria. Sulfadoxine-pyrimethamine should be prescribed cautiously in women concurrently receiving daily nevirapine and/or zidovudine, and should be avoided in women on daily co-trimoxazole. Further research is urgently needed to define safe and effective protocols for concurrent management of HIV and malaria in pregnancy, and to define appropriate interventions for different populations subject to differing levels of malaria transmission and antimalarial drug resistance.

Clinical outcomes in extracranial tumor sites and unusual toxicities with concurrent whole brain radiation (WBRT) and Erlotinib treatment in patients with non-small cell lung cancer (NSCLC) with brain metastasis.

PubMed

Olmez, Inan; Donahue, Bernadine R; Butler, James S; Huang, Yiwu; Rubin, Philip; Xu, Yiqing

2010-11-01

Thirty percent of newly diagnosed NSCLC patients present with synchronous brain metastases, most of whom are treated with whole brain radiation. Systemic chemotherapy is usually avoided during WBRT due to concerns regarding toxicity. However, concurrent administration of targeted agents, such as Erlotinib, during WBRT may address systemic disease without causing toxicity. We report our institutional data on outcomes and toxicities with this treatment approach. Medical records of patients with newly diagnosed NSCLC and brain metastases receiving concurrent WBRT and Erlotinib treatment were reviewed. Radiographic response to therapy and toxicities were analyzed. Eight patients were identified and 7 were evaluable for response. All patients had intracranial disease control. In the extracranial sites, 3 (37.5%, intent-to-treat) showed partial response (PR), 2 (25%) had stable disease (SD), 1 (12.5%) had progression (PD) and 1 (12.5%) had new air space disease obscuring tumor response assessment. Among the three responders, two were female never smokers, while one was a female current smoker. Unanticipated grade 3 hepatotoxitity, hyponatremia, mental status changes, grade 3 and 4 thrombocytopenia, and grade 4 neutropenia with sepsis were observed. Three deaths occurred without clear signs of disease progression: one from neutropenic sepsis, one from wide spread air space disease, and one from neurologic deterioration. Our data demonstrates a high percentage of extracranial tumor response rates with first line Erlotinib in selected NSCLC patients. We observed unexpected serious complications and postulate possible mechanisms. We recommend caution to be exercised when considering Erlotinib treatment during WBRT, particularly in regard to drug-drug interactions and infection control. Data from prospective trials are needed to determine the benefits and toxicities of Erlotinib during WBRT. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Early tumor shrinkage served as a prognostic factor for patients with stage III non-small cell lung cancer treated with concurrent chemoradiotherapy.

PubMed

Wei, Min; Ye, Qingqing; Wang, Xuan; Wang, Men; Hu, Yan; Yang, Yonghua; Yang, Jiyuan; Cai, Jun

2018-05-01

Lung cancer is the most common cause of cancer death. About 80% of patients are diagnosed at stage III in the non-small cell lung cancer (NSCLC). It is extremely important to understand the progression of this disease which has low survival times despite the advancing treatment modalities. We aimed to investigate the relationship between early tumor shrinkage (ETS) after initial concurrent chemoradiotherapy (C-CRT) and survival outcome in patients with stage III (NSCLC). A retrospective review of 103 patients with stage III NSCLC who had received C-CRT from January 2006 to October 2011 was performed. Patients were treated with systemic chemotherapy regimen of Cisplatin/Vp-16 and concurrent thoracic radiotherapy at a median dose of 66 Gy (range 60-70 Gy). All patients received a computed tomography (CT) examination before treatment. Also subsequently, chest CT scans were performed with the same imaging parameters at approximately 5 weeks after the initiation of treatment. ETS is here stratified by a decrease in tumor size ≥30% and <30% in the longest dimension of the target lesion within 5 weeks. Of the 103 patients, 59 ones showed a 30% decrease in tumor size, and the rest displayed a decrease of <30%. ETS showed no significant correlation with age, T classification, N classification, histological classification, smoking status, G classification, EGFR status, or acute pulmonary toxicity. In the current retrospective clinical study, Kaplan-Meier curves showed that patients with ETS ≥ 30% had a better progression-free survival and overall survival. The univariate and multivariate Cox regression analyses indicated that ETS < 30% was associated with a significantly increased risk of cancer-related death (P < .05) in stage IIINSCLC. ETS may be served as a useful prognostic factor to predict the outcome of stage III NSCLC patients treated with CCRT.

IDEAL-CRT: A Phase 1/2 Trial of Isotoxic Dose-Escalated Radiation Therapy and Concurrent Chemotherapy in Patients With Stage II/III Non-Small Cell Lung Cancer

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

Landau, David B., E-mail: david.landau@kcl.ac.uk; Hughes, Laura; Baker, Angela

2016-08-01

Purpose: To report toxicity and early survival data for IDEAL-CRT, a trial of dose-escalated concurrent chemoradiotherapy (CRT) for non-small cell lung cancer. Patients and Methods: Patients received tumor doses of 63 to 73 Gy in 30 once-daily fractions over 6 weeks with 2 concurrent cycles of cisplatin and vinorelbine. They were assigned to 1 of 2 groups according to esophageal dose. In group 1, tumor doses were determined by an experimental constraint on maximum esophageal dose, which was escalated following a 6 + 6 design from 65 Gy through 68 Gy to 71 Gy, allowing an esophageal maximum tolerated dose to be determined from early and late toxicities. Tumormore » doses for group 2 patients were determined by other tissue constraints, often lung. Overall survival, progression-free survival, tumor response, and toxicity were evaluated for both groups combined. Results: Eight centers recruited 84 patients: 13, 12, and 10, respectively, in the 65-Gy, 68-Gy, and 71-Gy cohorts of group 1; and 49 in group 2. The mean prescribed tumor dose was 67.7 Gy. Five grade 3 esophagitis and 3 grade 3 pneumonitis events were observed across both groups. After 1 fatal esophageal perforation in the 71-Gy cohort, 68 Gy was declared the esophageal maximum tolerated dose. With a median follow-up of 35 months, median overall survival was 36.9 months, and overall survival and progression-free survival were 87.8% and 72.0%, respectively, at 1 year and 68.0% and 48.5% at 2 years. Conclusions: IDEAL-CRT achieved significant treatment intensification with acceptable toxicity and promising survival. The isotoxic design allowed the esophageal maximum tolerated dose to be identified from relatively few patients.« less

Whole-pelvis, 'mini-pelvis,' or prostate-only external beam radiotherapy after neoadjuvant and concurrent hormonal therapy in patients treated in Radiation Therapy Oncology Group 9413 trial

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

Roach, Mack; De Silvio, Michelle; Valicenti, Richard

2006-11-01

Purpose: Radiation Therapy Oncology Group (RTOG) 9413 trial demonstrated a better progression-free survival (PFS) with whole-pelvis (WP) radiotherapy (RT) compared with prostate-only (PO) RT. This secondary analysis was undertaken to determine whether 'mini-pelvis' (MP; defined as {>=}10 x 11 cm but <11 x 11 cm) RT resulted in progression-free survival (PFS) comparable to that of WP RT. To avoid a timing bias, this analysis was limited to patients receiving neoadjuvant and concurrent hormonal therapy (N and CHT) in Arms 1 and 2 of the study. Methods and Materials: Eligible patients had a risk of lymph node (LN) involvement >15%. Neoadjuvantmore » and concurrent hormonal therapy (N and CHT) was administered 2 months before and during RT for 4 months. From April 1, 1995, to June 1, 1999, a group of 325 patients were randomized to WP RT + N and CHT and another group of 324 patients were randomized to receive PO RT + N and CHT. Patients randomized to PO RT were dichotomized by median field size (10 x 11 cm), with the larger field considered an 'MP' field and the smaller a PO field. Results: The median PFS was 5.2, 3.7, and 2.9 years for WP, MP, and PO fields, respectively (p = 0.02). The 7-year PFS was 40%, 35%, and 27% for patients treated to WP, MP, and PO fields, respectively. There was no association between field size and late Grade 3+ genitourinary toxicity but late Grade 3+ gastrointestinal RT complications correlated with increasing field size. Conclusions: This subset analysis demonstrates that RT field size has a major impact on PFS, and the findings support comprehensive nodal treatment in patients with a risk of LN involvement of >15%.« less

Phase 2 Study of Accelerated Hypofractionated Thoracic Radiation Therapy and Concurrent Chemotherapy in Patients With Limited-Stage Small-Cell Lung Cancer

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

Xia, Bing; Department of Radiation Oncology, Hangzhou Cancer Hospital, Hangzhou; Hong, Ling-Zhi

Purpose: To prospectively investigate the efficacy and toxicity of accelerated hypofractionated thoracic radiation therapy (HypoTRT) combined with concurrent chemotherapy in the treatment of limited-stage small-cell lung cancer (LS-SCLC), with the hypothesis that both high radiation dose and short radiation time are important in this setting. Methods and Materials: Patients with previously untreated LS-SCLC, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function were eligible. HypoTRT of 55 Gy at 2.5 Gy per fraction over 30 days was given on the first day of the second or third cycle of chemotherapy. An etoposide/cisplatin regimen was given to 4 tomore » 6 cycles. Patients who had a good response to initial treatment were offered prophylactic cranial irradiation. The primary endpoint was the 2-year progression-free survival rate. Results: Fifty-nine patients were enrolled from July 2007 through February 2012 (median age, 58 years; 86% male). The 2-year progression-free survival rate was 49.0% (95% confidence interval [CI] 35.3%-62.7%). Median survival time was 28.5 months (95% CI 9.0-48.0 months); the 2-year overall survival rate was 58.2% (95% CI 44.5%-71.9%). The 2-year local control rate was 76.4% (95% CI 63.7%-89.1%). The severe hematologic toxicities (grade 3 or 4) were leukopenia (32%), neutropenia (25%), and thrombocytopenia (15%). Acute esophagitis and pneumonitis of grade ≥3 occurred in 25% and 10% of the patients, respectively. Thirty-eight patients (64%) received prophylactic cranial irradiation. Conclusion: Our study showed that HypoTRT of 55 Gy at 2.5 Gy per fraction daily concurrently with etoposide/cisplatin chemotherapy has favorable survival and acceptable toxicity. This radiation schedule deserves further investigation in LS-SCLC.« less

Paclitaxel poliglumex, temozolomide, and radiation for newly diagnosed high-grade glioma: a Brown University Oncology Group Study.

PubMed

Jeyapalan, Suriya; Boxerman, Jerrold; Donahue, John; Goldman, Marc; Kinsella, Timothy; Dipetrillo, Thomas; Evans, Devon; Elinzano, Heinrich; Constantinou, Maria; Stopa, Edward; Puthawala, Yakub; Cielo, Deus; Santaniello, Alyson; Oyelese, Adetokunbo; Mantripragada, Kalyan; Rosati, Kayla; Isdale, Debora; Safran, Howard

2014-10-01

Paclitaxel poliglumex (PPX), a drug conjugate that links paclitaxel to poly-L-glutamic acid, is a potent radiation sensitizer. Prior studies in esophageal cancer have demonstrated that PPX (50 mg/m/wk) can be administered with concurrent radiation with acceptable toxicity. The primary objective of this study was to determine the safety of the combination of PPX with temozolomide and concurrent radiation for high-grade gliomas. Eligible patients were required to have WHO grade 3 or 4 gliomas. Patients received weekly PPX (50 mg/m/wk) combined with standard daily temozolomide (75 mg/m) for 6 weeks with concomitant radiation (2.0 Gy, 5 d/wk for a total dose of 60 Gy). Twenty-five patients were enrolled, 17 with glioblastoma and 8 with grade 3 gliomas. Seven of 25 patients had grade 4 myelosuppression. Hematologic toxicity lasted up to 5 months suggesting a drug interaction between PPX and temozolomide. For patients with glioblastoma, the median progression-free survival was 11.5 months and the median overall survival was 18 months. PPX could not be safely combined with temozolomide due to grade 4 hematologic toxicity. However, the favorable progression-free and overall survival suggest that PPX may enhance radiation for glioblastoma. A randomized study of single agent PPX/radiation versus temozolomide/radiation for glioblastoma without MGMT methylation is underway.

Dissociation of sensitivities to tumor promotion and progression in outbred and inbred SENCAR mice.

PubMed

Gimenez-Conti, I B; Bianchi, A B; Fischer, S M; Reiners, J J; Conti, C J; Slaga, T J

1992-06-15

The sensitivity of outbred SENCAR mice and inbred SENCAR (SSIN) mice to multistage carcinogenesis was studied. Tumors were induced using either 7,12-dimethylbenz[a]anthracene or N-methyl-N'-nitro-N-nitrosoguanidine as initiators and 12-O-tetradecanoylphorbol-13-acetate or benzoyl peroxide as promoting agents. Although the number of papillomas per mouse was higher in SSIN than in outbred SENCAR mice, the number of carcinomas observed in the SSIN strain was significantly lower regardless of the initiator or promoter used. It was also observed that the expression of markers of premalignant progression (i.e., dysplasia, expression of keratin K13, and loss of keratin K1 expression) was markedly suppressed in SSIN papillomas. After 50 wk of promotion with 12-O-tetradecanoylphorbol-13-acetate, the pattern of expression of K13 and K1 in SSIN mice was comparable to the pattern observed in outbred SENCAR mice after 10 to 20 wk of promotion with 12-O-tetradecanoylphorbol-13-acetate. It was also observed that 67% of the tumors induced in SSIN mice by initiation with 7,12-dimethylbenz[a]anthracene exhibited a mutation in codon 61 of the Ha-ras-1 gene. This latter finding suggests that the differences observed in tumor progression between the inbred strain and the outbred stock are not related to a genetic alteration in the Ha-ras-1 gene but rather to an independent event that we have postulated to involve a putative suppressor gene. The data reported here suggest that the putative gene(s) that confers susceptibility to tumor promotion was segregated from the gene(s) involved in tumor progression during selection and inbreeding of the SENCAR mouse stock.

Design and Analysis Techniques for Concurrent Blackboard Systems. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Mcmanus, John William

1992-01-01

Blackboard systems are a natural progression of knowledge-based systems into a more powerful problem solving technique. They provide a way for several highly specialized knowledge sources to cooperate to solve large, complex problems. Blackboard systems incorporate the concepts developed by rule-based and expert systems programmers and include the ability to add conventionally coded knowledge sources. The small and specialized knowledge sources are easier to develop and test, and can be hosted on hardware specifically suited to the task that they are solving. The Formal Model for Blackboard Systems was developed to provide a consistent method for describing a blackboard system. A set of blackboard system design tools has been developed and validated for implementing systems that are expressed using the Formal Model. The tools are used to test and refine a proposed blackboard system design before the design is implemented. My research has shown that the level of independence and specialization of the knowledge sources directly affects the performance of blackboard systems. Using the design, simulation, and analysis tools, I developed a concurrent object-oriented blackboard system that is faster, more efficient, and more powerful than existing systems. The use of the design and analysis tools provided the highly specialized and independent knowledge sources required for my concurrent blackboard system to achieve its design goals.

Metformin association with lower prostate cancer recurrence in type 2 diabetes: a systematic review and meta-analysis.

PubMed

Hwang, In Cheol; Park, Sang Min; Shin, Doosup; Ahn, Hong Yup; Rieken, Malte; Shariat, Shahrokh F

2015-01-01

Accumulating evidence suggests that metformin possesses anticarcinogenic properties, and its use is associated with favorable outcomes in several cancers. However, it remains unclear whether metformin influences prognosis in prostate cancer (PCa) with concurrent type 2 diabetes (T2D). We searched PubMed, EMBASE, and the Cochrane Library from database inception to April 16, 2014 without language restrictions to identify studies investigating the effect of metformin treatment on outcomes of PCa with concurrent T2D. We conducted a meta-analysis to quantify the risk of recurrence, progression, cancer-specific mortality, and all-cause mortality. Summary relative risks (RRs) with corresponding 95% confidence intervals (CIs) were calculated. Publication bias was assessed by Begg's rank correlation test. A total of eight studies fulfilled the eligibility criteria. We found that diabetic PCa patients who did not use metformin were at increased risk of cancer recurrence (RR, 1.20; 95%CI, 1.00-1.44), compared with those who used metformin. A similar trend was observed for other outcomes, but their relationships did not reach statistical significance. Funnel plot asymmetry was not observed among studies reporting recurrence (p=0.086). Our results suggest that metformin may improve outcomes in PCa patients with concurrent T2D. Well-designed large studies and collaborative basic research are warranted.

Computational fluid dynamics tools can be used to predict the progression of coronary artery disease

NASA Astrophysics Data System (ADS)

Coşkun, A. Ümit; Chen, Caixia; Stone, Peter H.; Feldman, Charles L.

2006-03-01

Atherosclerosis is focal and individual plaques evolve in an independent manner. The endothelium regulates arterial behavior by responding to its local shear stress. In vitro studies indicate that low endothelial shear stress (ESS) upregulates the genetic and molecular responses leading to the initiation and progression of atherosclerosis and promotes inflammation and formation of other features characteristic of vulnerable plaque. Physiologic ESS is vasculoprotective and fosters quiescence of the endothelium and vascular wall. High ESS promotes platelet aggregation. ESS and vascular wall morphology along the course of human coronary arteries can now be characterized in vivo, and may predict the focal areas in which atherosclerosis progression occurs. Rapidly evolving methodologies are able to characterize the arterial wall and the local hemodynamic factors likely responsible for progression of coronary disease in man. These new diagnostic modalities allow for identification of plaque progression. Accurate identification of arterial segments at high-risk for progression may permit pre-emptive intervention strategies to avoid adverse coronary events.

Development, reliability, and validity of the My Child's Play (MCP) questionnaire.

PubMed

Schneider, Eleanor; Rosenblum, Sara

2014-01-01

This article describes the development, reliability, and validity of My Child's Play (MCP), a parent questionnaire designed to evaluate the play of children ages 3-9 yr. The first phase of the study determined the questionnaire's content and face validity. Subsequently, the internal reliability consistency and construct and concurrent validity were demonstrated using 334 completed questionnaires. The MCP showed good internal consistency (α = .86). The factor analysis revealed four distinct factors with acceptable levels of internal reliability (Cronbach's αs = .63-.81) and gender- and age-related differences in play characteristics; both findings attest to the tool's construct validity. Significant correlations (r = .33, p < .0001) with the Parent as a Teacher Inventory demonstrate the MCP's concurrent validity. The MCP demonstrated acceptable reliability and validity. It appears to be a promising standardized assessment tool for use in research and practice to promote understanding of a child's play. Copyright © 2014 by the American Occupational Therapy Association, Inc.

Risperidone induced angioedema with concurrent EPS symptoms: a case report and review of literature

PubMed Central

Samra, Gursharan Singh; Kant, Saumitra; Chow, Robert

2018-01-01

ABSTRACT Angioedema has recently been reported as a side effect associated with the antipsychotic risperidone. We report a case of dystonia with concurrent angioedema due to risperidone. A 40-year-old male with a history of schizophrenia was started on 3 mg of risperidone BID and developed perioral and periorbital edema along with increased muscle rigidity and hand tremor within 24 h of initial administration. His symptoms abated after cessation of risperidone and intravenous administration of corticosteroids and antihistamine. This case study adds to the current literature, which has already established angioedema as a dose-dependent side effect of risperidone. Moreover, this case study aims to increase awareness about the potential for the simultaneous occurrence of angioedema and extrapyramidal symptoms, and promotes vigilance among prescribers so that the life-threatening consequences of such effects can be avoided. PMID:29686794

Chemically assisted mechanical refrigeration process

DOEpatents

Vobach, Arnold R.

1987-01-01

There is provided a chemically assisted mechanical refrigeration process including the steps of: mechanically compressing a refrigerant stream which includes vaporized refrigerant; contacting the refrigerant with a solvent in a mixer (11) at a pressure sufficient to promote substantial dissolving of the refrigerant in the solvent in the mixer (11) to form a refrigerant-solvent solution while concurrently placing the solution in heat exchange relation with a working medium to transfer energy to the working medium, said refrigerant-solvent solution exhibiting a negative deviation from Raoult's Law; reducing the pressure over the refrigerant-solvent solution in an evaporator (10) to allow the refrigerant to vaporize and substantially separate from the solvent while concurrently placing the evolving refrigerant-solvent solution in heat exchange relation with a working medium to remove energy from the working medium to thereby form a refrigerant stream and a solvent stream; and passing the solvent and refrigerant stream from the evaporator.

Chemically assisted mechanical refrigeration process

DOEpatents

Vobach, Arnold R.

1987-01-01

There is provided a chemically assisted mechanical refrigeration process including the steps of: mechanically compressing a refrigerant stream which includes vaporized refrigerant; contacting the refrigerant with a solvent in a mixer (11) at a pressure sufficient to promote substantial dissolving of the refrigerant in the solvent in the mixer (11) to form a refrigerant-solvent solution while concurrently placing the solution in heat exchange relation with a working medium to transfer energy to the working medium, said refrigerant-solvent solution exhibiting a negative deviation from Raoult's Law; reducing the pressure over the refrigerant-solvent solution in an evaporator (10) to allow the refrigerant to vaporize and substantially separate from the solvent while concurrently placing he evolving refrigerant-solvent solution in heat exchange relation with a working medium to remove energy from the working medium to thereby form a refrigerant stream and a solvent stream; and passing the solvent and refrigerant stream from the evaporator.

Chemically assisted mechanical refrigeration process

DOEpatents

Vobach, A.R.

1987-06-23

There is provided a chemically assisted mechanical refrigeration process including the steps of: mechanically compressing a refrigerant stream which includes vaporized refrigerant; contacting the refrigerant with a solvent in a mixer at a pressure sufficient to promote substantial dissolving of the refrigerant in the solvent in the mixer to form a refrigerant-solvent solution while concurrently placing the solution in heat exchange relation with a working medium to transfer energy to the working medium, said refrigerant-solvent solution exhibiting a negative deviation from Raoult's Law; reducing the pressure over the refrigerant-solvent solution in an evaporator to allow the refrigerant to vaporize and substantially separate from the solvent while concurrently placing the evolving refrigerant-solvent solution in heat exchange relation with a working medium to remove energy from the working medium to thereby form a refrigerant stream and a solvent stream; and passing the solvent and refrigerant stream from the evaporator. 5 figs.

Chemically assisted mechanical refrigeration process

DOEpatents

Vobach, A.R.

1987-11-24

There is provided a chemically assisted mechanical refrigeration process including the steps of: mechanically compressing a refrigerant stream which includes vaporized refrigerant; contacting the refrigerant with a solvent in a mixer at a pressure sufficient to promote substantial dissolving of the refrigerant in the solvent in the mixer to form a refrigerant-solvent solution while concurrently placing the solution in heat exchange relation with a working medium to transfer energy to the working medium, said refrigerant-solvent solution exhibiting a negative deviation from Raoult's Law; reducing the pressure over the refrigerant-solvent solution in an evaporator to allow the refrigerant to vaporize and substantially separate from the solvent while concurrently placing the evolving refrigerant-solvent solution in heat exchange relation with a working medium to remove energy from the working medium to thereby form a refrigerant stream and a solvent stream; and passing the solvent and refrigerant stream from the evaporator. 5 figs.

Mitochondrial Redox Signaling and Tumor Progression.

PubMed

Chen, Yuxin; Zhang, Haiqing; Zhou, Huanjiao Jenny; Ji, Weidong; Min, Wang

2016-03-25

Cancer cell can reprogram their energy production by switching mitochondrial oxidative phosphorylation to glycolysis. However, mitochondria play multiple roles in cancer cells, including redox regulation, reactive oxygen species (ROS) generation, and apoptotic signaling. Moreover, these mitochondrial roles are integrated via multiple interconnected metabolic and redox sensitive pathways. Interestingly, mitochondrial redox proteins biphasically regulate tumor progression depending on cellular ROS levels. Low level of ROS functions as signaling messengers promoting cancer cell proliferation and cancer invasion. However, anti-cancer drug-initiated stress signaling could induce excessive ROS, which is detrimental to cancer cells. Mitochondrial redox proteins could scavenger basal ROS and function as "tumor suppressors" or prevent excessive ROS to act as "tumor promoter". Paradoxically, excessive ROS often also induce DNA mutations and/or promotes tumor metastasis at various stages of cancer progression. Targeting redox-sensitive pathways and transcriptional factors in the appropriate context offers great promise for cancer prevention and therapy. However, the therapeutics should be cancer-type and stage-dependent.

Cholesterol import and steroidogenesis are biosignatures for gastric cancer patient survival

PubMed Central

Chang, Wei-Chun; Huang, Shang-Fen; Lee, Yang-Ming; Lai, Hsueh-Chou; Cheng, Bi-Hua; Cheng, Wei-Chung; Ho, Jason Yen-Ping; Jeng, Long-Bin; Ma, Wen-Lung

2017-01-01

Androgens, estrogens, progesterone and related signals are reported to be involved in the pathology of gastric cancer. However, varied conclusions exist based on serum hormone levels, receptor expressions, and in vitro or in vivo studies. This report used a web-based gene survival analyzer to evaluate biochemical processes, including cholesterol importing via lipoprotein/receptors (L/R route), steroidogenic enzymes, and steroid receptors, in gastric cancer patients prognosis. The sex hormone receptors (androgen receptor, progesterone receptor, and estrogen receptor ESR1 or ESR2), L/R route (low/high-density lipoprotein receptors, LDLR/LRP6/SR-B1 and lipoprotein lipase, LPL) and steroidogenic enzymes (CYP11A1, HSD3B1, CYP17, HSD17B1, HSD3B1, CYP19A1 and SRD5A1) were associated with 5-year survival of gastric cancer patients. The AR, PR, ESR1 and ESR2 are progression promoters, as are the L/R route LDLR, LRP6, SR-B1 and LPL. It was found that CYP11A1, HSD3B1, CYP17, HSD17B1 and CYP19A1 promote progression, but dihydrotestosterone (DHT) converting enzyme SRD5A1 suppresses progression. Analyzing steroidogenic lipidome with a hazard ratio score algorithm found that CYP19A1 is the progression confounder in surgery, HER2 positive or negative patients. Finally, in the other patient cohort from TCGA, CYP19A1 was expressed higher in the tumor compared to that in normal counterparts, and also promoted progression. Lastly, exemestrane (type II aromatase inhibitor) dramatically suppress GCa cell growth in pharmacological tolerable doses in vitro. This work depicts a route-specific outside-in delivery of cholesterol to promote disease progression, implicating a host-to-tumor macroenvironmental regulation. The result indicating lipoprotein-mediated cholesterol entry and steroidogenesis are GCa progression biosignatures. And the exemestrane clinical trial in GCa patients of unmet medical needs is suggested. PMID:27893427

Cholesterol import and steroidogenesis are biosignatures for gastric cancer patient survival.

PubMed

Chang, Wei-Chun; Huang, Shang-Fen; Lee, Yang-Ming; Lai, Hsueh-Chou; Cheng, Bi-Hua; Cheng, Wei-Chung; Ho, Jason Yen-Ping; Jeng, Long-Bin; Ma, Wen-Lung

2017-01-03

Androgens, estrogens, progesterone and related signals are reported to be involved in the pathology of gastric cancer. However, varied conclusions exist based on serum hormone levels, receptor expressions, and in vitro or in vivo studies. This report used a web-based gene survival analyzer to evaluate biochemical processes, including cholesterol importing via lipoprotein/receptors (L/R route), steroidogenic enzymes, and steroid receptors, in gastric cancer patients prognosis. The sex hormone receptors (androgen receptor, progesterone receptor, and estrogen receptor ESR1 or ESR2), L/R route (low/high-density lipoprotein receptors, LDLR/LRP6/SR-B1 and lipoprotein lipase, LPL) and steroidogenic enzymes (CYP11A1, HSD3B1, CYP17, HSD17B1, HSD3B1, CYP19A1 and SRD5A1) were associated with 5-year survival of gastric cancer patients. The AR, PR, ESR1 and ESR2 are progression promoters, as are the L/R route LDLR, LRP6, SR-B1 and LPL. It was found that CYP11A1, HSD3B1, CYP17, HSD17B1 and CYP19A1 promote progression, but dihydrotestosterone (DHT) converting enzyme SRD5A1 suppresses progression. Analyzing steroidogenic lipidome with a hazard ratio score algorithm found that CYP19A1 is the progression confounder in surgery, HER2 positive or negative patients. Finally, in the other patient cohort from TCGA, CYP19A1 was expressed higher in the tumor compared to that in normal counterparts, and also promoted progression. Lastly, exemestrane (type II aromatase inhibitor) dramatically suppress GCa cell growth in pharmacological tolerable doses in vitro. This work depicts a route-specific outside-in delivery of cholesterol to promote disease progression, implicating a host-to-tumor macroenvironmental regulation. The result indicating lipoprotein-mediated cholesterol entry and steroidogenesis are GCa progression biosignatures. And the exemestrane clinical trial in GCa patients of unmet medical needs is suggested.

Community-based intervention packages facilitated by NGOs demonstrate plausible evidence for child mortality impact.

PubMed

Ricca, Jim; Kureshy, Nazo; LeBan, Karen; Prosnitz, Debra; Ryan, Leo

2014-03-01

Evidence exists that community-based intervention packages can have substantial child and newborn mortality impact, and may help more countries meet Millennium Development Goal 4 (MDG 4) targets. A non-governmental organization (NGO) project using such programming in Mozambique documented an annual decline in under-five mortality rate (U5MR) of 9.3% in a province in which Demographic and Health Survey (DHS) data showed a 4.2% U5MR decline during the same period. To test the generalizability of this finding, the same analysis was applied to a group of projects funded by the US Agency for International Development. Projects supported implementation of community-based intervention packages aimed at increasing use of health services while improving preventive and home-care practices for children under five. All projects collect baseline and endline population coverage data for key child health interventions. Twelve projects fitted the inclusion criteria. U5MR decline was estimated by modelling these coverage changes in the Lives Saved Tool (LiST) and comparing with concurrent measured DHS mortality data. Average coverage changes for all interventions exceeded average concurrent trends. When population coverage changes were modelled in LiST, they were estimated to give a child mortality improvement in the project area that exceeded concurrent secular trend in the subnational DHS region in 11 of 12 cases. The average improvement in modelled U5MR (5.8%) was more than twice the concurrent directly measured average decline (2.5%). NGO projects implementing community-based intervention packages appear to be effective in reducing child mortality in diverse settings. There is plausible evidence that they raised coverage for a variety of high-impact interventions and improved U5MR by more than twice the concurrent secular trend. All projects used community-based strategies that achieved frequent interpersonal contact for health behaviour change. Further study of the effectiveness and scalability of similar packages should be part of the effort to accelerate progress towards MDG 4.

Dual therapeutic functions of F-5 fragment in burn wounds: preventing wound progression and promoting wound healing in pigs

PubMed Central

Bhatia, Ayesha; O’Brien, Kathryn; Chen, Mei; Wong, Alex; Garner, Warren; Woodley, David T.; Li, Wei

2016-01-01

Burn injuries are a leading cause of morbidity including prolonged hospitalization, disfigurement, and disability. Currently there is no Food and Drug Administration-approved burn therapeutics. A clinical distinction of burn injuries from other acute wounds is the event of the so-called secondary burn wound progression within the first week of the injury, in which a burn expands horizontally and vertically from its initial boundary to a larger area. Therefore, an effective therapeutics for burns should show dual abilities to prevent the burn wound progression and thereafter promote burn wound healing. Herein we report that topically applied F-5 fragment of heat shock protein-90α is a dual functional agent to promote burn wound healing in pigs. First, F-5 prevents burn wound progression by protecting the surrounding cells from undergoing heat-induced caspase 3 activation and apoptosis with increased Akt activation. Accordingly, F-5–treated burn and excision wounds show a marked decline in inflammation. Thereafter, F-5 accelerates burn wound healing by stimulating the keratinocyte migration-led reepithelialization, leading to wound closure. This study addresses a topical agent that is capable of preventing burn wound progression and accelerating burn wound healing. PMID:27382602

Tumor-associated myeloid cells promote tumorigenesis of non-tumorigenic human and murine prostatic epithelial cell lines.

PubMed

Sass, Stephanie N; Ramsey, Kimberley D; Egan, Shawn M; Wang, Jianmin; Cortes Gomez, Eduardo; Gollnick, Sandra O

2018-06-01

The etiology of prostate cancer is poorly understood, but it is a multi-step process that has been linked to environmental factors that induce inflammation within the gland. Glands of prostate cancer patients frequently contain multiple zones of disease at various stages of progression. The factors that drive disease progression from an indolent benign stage to aggressive disease are not well-defined. Prostate inflammation and carcinoma are associated with high levels of myeloid cell infiltration; these cells are linked to disease progression in other cancers, but their role in prostate cancer is unclear. To determine whether myeloid cells contribute to prostate cancer progression, the ability of prostate tumor-associated CD11b + cells (TAMC) to drive prostate epithelial cell tumorigenesis was tested. Co-culture of CD11b + TAMC with non-tumorigenic genetically primed prostate epithelial cells resulted in stable transformation and induction of tumorigenesis. RNA sequencing identified the IL-1α pathway as a potential molecular mechanism responsible for tumor promotion by TAMC. Inhibition of IL-1α delayed growth of TAMC-induced tumors. Further analysis showed that IL-1α inhibition led to decreased angiogenesis within tumors, suggesting that IL-1α promotes prostate tumor progression, potentially through augmentation of angiogenesis.

Smooth moves: bar and nightclub tobacco promotions that target young adults.

PubMed

Sepe, Edward; Ling, Pamela M; Glantz, Stanton A

2002-03-01

This article describes the tobacco industry's use of bars and nightclubs to encourage smoking among young adults. Previously secret tobacco industry marketing documents were analyzed. Tobacco industry bar and nightclub promotions in the 1980s and 1990s included aggressive advertising, tobacco brand--sponsored activities, and distribution of samples. Financial incentives for club owners and staff were used to encourage smoking through peer influence. Increased use of these strategies occurred concurrently with an increase in smoking among persons aged 18 through 24 years. The tobacco industry's bar and nightclub promotions are not yet politically controversial and are not regulated by the 1998 Master Settlement Agreement between the industry and the states. Tobacco control advocates should include young adults in research and advocacy efforts and should design interventions to counter this industry strategy to solidify smoking patterns and recruit young adult smokers.

Smooth Moves: Bar and Nightclub Tobacco Promotions That Target Young Adults

PubMed Central

Sepe, Edward; Ling, Pamela M.; Glantz, Stanton A.

2002-01-01

Objectives. This article describes the tobacco industry's use of bars and nightclubs to encourage smoking among young adults. Methods. Previously secret tobacco industry marketing documents were analyzed. Results. Tobacco industry bar and nightclub promotions in the 1980s and 1990s included aggressive advertising, tobacco brand–sponsored activities, and distribution of samples. Financial incentives for club owners and staff were used to encourage smoking through peer influence. Increased use of these strategies occurred concurrently with an increase in smoking among persons aged 18 through 24 years. Conclusions. The tobacco industry's bar and nightclub promotions are not yet politically controversial and are not regulated by the 1998 Master Settlement Agreement between the industry and the states. Tobacco control advocates should include young adults in research and advocacy efforts and should design interventions to counter this industry strategy to solidify smoking patterns and recruit young adult smokers. PMID:11867322

Lgr4 promotes prostate tumorigenesis through the Jmjd2a/AR signaling pathway.

PubMed

Zhang, Jianwei; Li, Qi; Zhang, Shaojin; Xu, Quanquan; Wang, Tianen

2016-11-15

Lgr4 (leucine-rich repeat domain containing G protein-coupled receptor 4) is implicated in the transcriptional regulation of multiple histone demethylases in the progression of diverse cancers, but there are few reports concerning the molecular mechanism by which Lgr4 regulates histone demethylase activation in prostate cancer (PCa) progression. As Jmjd2a is a histone demethylase, in the current study, we investigated the relationship between interaction Lgr4 with Jmjd 2a and Jmjd2a/androgen receptor (AR) signaling pathway in PCa progression. Firstly, Lgr4 was overexpressed by transfecting pcDNA3.1(+)/Lgr4 plasmids into PCa (LNCaP and PC-3) cell lines. Next, we found that Lgr4 overexpression promoted Jmjd2a mRNA expression, reduced cell apoptosis and arrested cell cycle in the S phase, these effects were reversed by Jmjd2a silencing. Moreover, Lgr4 overexpression markedly elevated AR levels and its interaction with Jmjd2a, which was tested by co-immunoprecipitation and luciferase reporter assays. Furthermore, interaction AR with PSA promoter (containing an AR response element) was obviously improved by Lgr4 overexpression, and PSA silencing reduced Lgr4-induced cell apoptosis and cell cycle arrest in PCa cells. Taken together, Lgr4 may be a novel tumor marker providing new mechanistic insights into PCa progression. Lgr4 activates Jmjd2a/AR signaling pathway to promote interaction AR with PSA promoter, causing reduction of PCa apoptosis and cell cycle arrest. Copyright © 2016 Elsevier Inc. All rights reserved.

Pupil Progression Plan: Requirements and Procedures 1982-83.

ERIC Educational Resources Information Center

Duval County School Board, Jacksonville, FL.

The Pupil Progression Plan detailed in this document was developed in response to Florida's Educational Accountability Act, which requires each school district to establish a comprehensive program for pupil progression, and to fulfill the requirements of school board policy. The first section details general procedures for promotion, grades K-12.…

Potential Proinvasive or Metastatic Effects of Preclinical Antiangiogenic Therapy Are Prevented by Concurrent Chemotherapy.

PubMed

Paez-Ribes, Marta; Man, Shan; Xu, Ping; Kerbel, Robert S

2015-12-15

To resolve a controversy involving the therapeutic impact of antiangiogenic drugs and particularly antibodies targeting the VEGF pathway, namely, a body of preclinical mouse therapy studies showing such drugs can promote invasion and/or distant metastasis when used as monotherapies. In contrast, clinical studies have not shown such promalignancy effects. However, most such clinical studies have involved patients also treated with concurrent chemotherapy highlighting the possibility that chemotherapy may prevent any potential promalignancy effect caused by an antiangiogenic drug treatment. The impact of antiangiogenic therapy using DC101, an antibody targeting mouse VEGFR-2 with or without concurrent chemotherapy was assessed in multiple human breast cancer xenograft models, where impact on orthotopic primary tumors was evaluated. Metastasis was also assessed during adjuvant and neoadjuvant plus adjuvant therapy, after surgical resection of primary tumors, with the same combination therapies. Antiangiogenic therapy, while blunting tumor volume growth, was found to increase local invasion in multiple primary tumor models, including a patient-derived xenograft, but this effect was blocked by concurrent chemotherapy. Similarly, the combination of paclitaxel with DC101 caused a marked reduction of micro- or macrometastatic disease in contrast to DC101 monotherapy, which was associated with small increases in metastatic disease. Conventional wisdom is that targeted biologic antiangiogenic agents such as bevacizumab when used with chemotherapy increase the efficacy of the chemotherapy treatment. Our results suggest the reverse may be true as well-chemotherapy may improve the impact of antiangiogenic drug treatment and, as a result, overall efficacy. Clin Cancer Res; 21(24); 5488-98. ©2015 AACR. ©2015 American Association for Cancer Research.

Concurrent exercise training: do opposites distract?

PubMed

Coffey, Vernon G; Hawley, John A

2017-05-01

Specificity is a core principle of exercise training to promote the desired adaptations for maximising athletic performance. The principle of specificity of adaptation is underpinned by the volume, intensity, frequency and mode of contractile activity and is most evident when contrasting the divergent phenotypes that result after undertaking either prolonged endurance or resistance training. The molecular profiles that generate the adaptive response to different exercise modes have undergone intense scientific scrutiny. Given divergent exercise induces similar signalling and gene expression profiles in skeletal muscle of untrained or recreationally active individuals, what is currently unclear is how the specificity of the molecular response is modified by prior training history. The time course of adaptation and when 'phenotype specificity' occurs has important implications for exercise prescription. This context is essential when attempting to concomitantly develop resistance to fatigue (through endurance-based exercise) and increased muscle mass (through resistance-based exercise), typically termed 'concurrent training'. Chronic training studies provide robust evidence that endurance exercise can attenuate muscle hypertrophy and strength but the mechanistic underpinning of this 'interference' effect with concurrent training is unknown. Moreover, despite the potential for several key regulators of muscle metabolism to explain an incompatibility in adaptation between endurance and resistance exercise, it now seems likely that multiple integrated, rather than isolated, effectors or processes generate the interference effect. Here we review studies of the molecular responses in skeletal muscle and evidence for the interference effect with concurrent training within the context of the specificity of training adaptation. © 2016 The Authors. The Journal of Physiology © 2016 The Physiological Society.

Analysis of Factors Associated With Radiation-Induced Bronchiolitis Obliterans Organizing Pneumonia Syndrome After Breast-Conserving Therapy

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

Katayama, Norihisa; Sato, Shuhei; Katsui, Kuniaki

Purpose: To evaluate factors associated with radiation-induced bronchiolitis obliterans organizing pneumonia (BOOP) syndrome after breast-conserving therapy. Methods and Materials: A total of 702 women with breast cancer who received radiotherapy after breast-conserving surgery at seven institutions between July 1995 and December 2006 were analyzed. In all patients, the whole breast was irradiated with two tangential photon beams. The criteria used for the diagnosis of radiation-induced BOOP syndrome were as follows: (1) radiotherapy to the breast within 12 months, (2) general and/or respiratory symptoms lasting for {>=}2 weeks, (3) radiographs showing lung infiltration outside the radiation port, and (4) no evidencemore » of a specific cause. Results: Radiation-induced BOOP syndrome was seen in 16 patients (2.3%). Eleven patients (68.8%) were administered steroids. The duration of steroid administration ranged from 1 week to 3.7 years (median, 1.1 years). Multivariate analysis revealed that age ({>=}50 years; odds ratio [OR] 8.88; 95% confidence interval [CI] 1.16-67.76; p = 0.04) and concurrent endocrine therapy (OR 3.05; 95% CI 1.09-8.54; p = 0.03) were significantly associated with BOOP syndrome. Of the 161 patients whose age was {>=}50 years and who received concurrent endocrine therapy, 10 (6.2%) developed BOOP syndrome. Conclusions: Age ({>=}50 years) and concurrent endocrine therapy can promote the development of radiation-induced BOOP syndrome after breast-conserving therapy. Physicians should carefully follow patients who received breast-conserving therapy, especially those who are older than 50 years and received concurrent endocrine therapy during radiotherapy.« less

Effects of concurrent exposure to tributyltin and 1,1-dichloro-2,2 bis (p-chlorophenyl) ethylene (p,p'-DDE) on immature male Wistar rats.

PubMed

Makita, Yuji; Omura, Minoru; Tanaka, Akiyo; Kiyohara, Chikako

2005-12-01

Tributyltin and 1, 1-dichloro-2, 2 bis (p-chlorophenyl) ethylene (p,p'-DDE) have been ubiquitously distributed over the world. In Japan, p,p'-DDE and tributyltin are ingested through marine products, in which these substances are accumulated through bio-concentration and the food chain. However, the consequence of potential combined hazards of these substances remains unknown. Therefore, the effects of concurrent exposure to 125 ppm p,p'-DDE and 25 ppm tributyltin were investigated in immature male Wistar rats by oral administration during puberty. In this study, tributyltin promoted the growth of pubertal male rats, while p,p'-DDE itself did not affect the growth but inhibited the growth enhancement by tributyltin. Furthermore, tributyltin reduced thymus weight but p,p'-DDE also prevented this weight reduction. Neither development of male sexual accessory organs nor sexual maturation was affected even by concurrent exposure to p,p'-DDE and tributyltin. No significant changes of serum testosterone, luteinizing hormone, follicle-stimulating hormone concentrations, and epididymal sperm numbers were observed with the administration of p,p'-DDE and/or tributyltin. These results indicate that sexual maturation, male reproductive organ development and sperm production is scarcely affected in immature male Wistar rats even by concurrent exposure to p,p'-DDE and tributyltin at a daily dose of ca. 2 mg/kg tributyltin and 10 mg/kg p,p'-DDE. Moreover, the simultaneous administration of p,p'-DDE with tributyltin counterbalanced the effects that were attributed to tributyltin alone.

An Analysis of AH-1Z Helicopter Pilots and Qualifications: The Impact of Fleet Squadron Training Progression Timelines

DTIC Science & Technology

2018-03-01

remaining 3000- series time block. Although there are fewer flight hours when compared to AHC, the coordination with external agencies may increase the...training duration to complete FAC(A). Additionally, pilots may conduct 4000 to 6000 series events concurrently, thus expanding the training time . 4...A)I training. Because FAC(A)I is included in the 5000- series training block, the time period cannot be finitely determined. 8. FL and AMC are the

Stacking transgenes in forest trees.

PubMed

Halpin, Claire; Boerjan, Wout

2003-08-01

Huge potential exists for improving plant raw materials and foodstuffs via metabolic engineering. To date, progress has mostly been limited to modulating the expression of single genes of well-studied pathways, such as the lignin biosynthetic pathway, in model species. However, a recent report illustrates a new level of sophistication in metabolic engineering by overexpressing one lignin enzyme while simultaneously suppressing the expression of another lignin gene in a tree, aspen. This novel approach to multi-gene manipulation has succeeded in concurrently improving several wood-quality traits.

Compensatory balance reactions during forward and backward walking on a treadmill.

PubMed

Bolton, D A E; Misiaszek, J E

2012-04-01

Previous work suggests that balance perturbations to the body opposing the direction of progression during walking lead to larger amplitude corrective reactions than perturbations concurrent with walking direction. To test this hypothesis, subjects received forward and backward perturbations applied to the pelvis through a padded harness, while walking forwards or backwards on a treadmill. Contrary to our hypothesis, the greatest responses were associated with backward perturbations regardless of the direction of walking. Copyright © 2011 Elsevier B.V. All rights reserved.

Sensors 2000! Program: Advanced Biosensor and Measurement Systems Technologies for Spaceflight Research and Concurrent, Earth-Based Applications

NASA Technical Reports Server (NTRS)

Hines, J.

1999-01-01

Sensors 2000! (S2K!) is a specialized, integrated projects team organized to provide focused, directed, advanced biosensor and bioinstrumentation systems technology support to NASA's spaceflight and ground-based research and development programs. Specific technology thrusts include telemetry-based sensor systems, chemical/ biological sensors, medical and physiological sensors, miniaturized instrumentation architectures, and data and signal processing systems. A concurrent objective is to promote the mutual use, application, and transition of developed technology by collaborating in academic-commercial-govemment leveraging, joint research, technology utilization and commercialization, and strategic partnering alliances. Sensors 2000! is organized around three primary program elements: Technology and Product Development, Technology infusion and Applications, and Collaborative Activities. Technology and Product Development involves development and demonstration of biosensor and biotelemetry systems for application to NASA Space Life Sciences Programs; production of fully certified spaceflight hardware and payload elements; and sensor/measurement systems development for NASA research and development activities. Technology Infusion and Applications provides technology and program agent support to identify available and applicable technologies from multiple sources for insertion into NASA's strategic enterprises and initiatives. Collaborative Activities involve leveraging of NASA technologies with those of other government agencies, academia, and industry to concurrently provide technology solutions and products of mutual benefit to participating members.

Connected Health and Progress against Cancer

Cancer.gov

An NCI Cancer Currents blog post about a new report from President’s Cancer Panel outlining how connective technologies can promote cancer prevention, enhance patients’ treatment experience, and accelerate progress in cancer research.

[Emotional Intelligence Index: a tool for the routine assessment of mental health promotion programs in schools].

PubMed

Veltro, Franco; Ialenti, Valentina; Morales García, Manuel Alejandro; Gigantesco, Antonella

2016-01-01

After critical examination of several aspects relating to the evaluation of some dimensions of emotional intelligence through self-assessment tools, is described the procedure of construction and validation of an Index for its measurement, conceived only for the routine assessment of health promotion programs mental in schools that include among their objectives the improvement of emotional intelligence specifically "outcome-oriented". On the basis of the two most common international tools, are listed 27 items plus 6 of control, illustrated two Focus Group (FG) of students (face validity). The scale obtained by FG was administered to 300 students, and the results were submitted to factorial analysis (construct validity). It was also evaluated the internal consistency with Cronbach's Alpha and studied concurrent validity with the emotional quotient inventory, a scale of perceived self-efficacy and a stress test rating. From the analysis of FG all the original items were modified, deleted 4, and reduced the encoding system from 6 to 4 levels of Likert scale. Of the 23 items included in the analysis have emerged five factors (intra-psychic dimension, interpersonal, impulsivity, adaptive coping, sense of self-efficacy) for a total of 15 items. Very satisfactory were the results of the validation process of internal consistency (0.72) and the concurrent validity. The results are positive. It is obtained in fact the shortest routine assessment tool currently available in Italy which constitutes a real Index, for which compilation are required on average 3 minutes. Is emphasized the characteristic of an Index, and not of questionnaire or interview for clinical use, highlighting the only specific use for mental health promotion programs in schools.

The component leaching from decellularized pericardial bioscaffolds and its implication in the macrophage response.

PubMed

Mendoza-Novelo, Birzabith; Castellano, Laura E; Padilla-Miranda, Ruth G; Lona-Ramos, María C; Cuéllar-Mata, Patricia; Vega-González, Arturo; Murguía-Pérez, Mario; Mata-Mata, José L; Ávila, Eva E

2016-11-01

The extracellular matrix molecules remaining in bioscaffolds derived from decellularized xenogeneic tissues appear to be important for inducing cell functions conducting tissue regeneration. Here, we studied whether decellularization methods, that is, detergent Triton X-100 (TX) alone and TX combined with reversible alkaline swelling (STX), applied to bovine pericardial tissue, could affect the bioscaffold components. The in vitro macrophage response, subdermal biodegradation, and cell infiltration were also studied. The results indicate a lower leaching of fibronectin, but a higher leaching of laminin and sulfated glycosaminoglycans from tissues decellularized with STX and TX, respectively. The in vitro secretion of interleukin-6 and monocyte chemoattractant protein by RAW264.7 macrophages is promoted by decellularized bioscaffold leachates. A lower polymorphonuclear cell density is observed around decellularized bioscaffolds at 1-day implantation; concurrently showing a higher cell infiltration in STX- than in TX-implant. Cells infiltrated into TX-implant show a fibroblastic morphology at 7-day implantation, concurrently the capillary formation is observed at 14-day. Pericardial bioscaffolds suffer biodegradation more pronounced in STX- than in TX-implant. Both TX and STX decellularization methods favor a high leaching of basal lamina components, which presumably promotes a faster macrophage stimulation compared to nondecellularized tissue, and appear to be associated with an increased host cell infiltration in a rat subdermal implantation. Meanwhile, the connective tissue components leaching from TX decellularized bioscaffolds, unlike the STX ones, appear to be associated with an enhanced angiogenesis accompanied by an early-promoted fibroblastic cell transition. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2810-2822, 2016. © 2016 Wiley Periodicals, Inc.

Effects of protonation on the hydrolysis of triphosphate in vacuum and the implications for catalysis by nucleotide hydrolyzing enzymes.

PubMed

Kiani, Farooq Ahmad; Fischer, Stefan

2016-06-29

Nucleoside triphosphate (NTP) hydrolysis is a key reaction in biology. It involves breaking two very stable bonds (one P-O bond and one O-H bond of water), in either a concurrent or a sequential way. Here, we systematically examine how protonation of the triphosphate affects the mechanism of hydrolysis. The hydrolysis reaction of methyl triphosphate in vacuum is computed with protons in various numbers and position on the three phosphate groups. Protonation is seen to have a strong catalytic effect, with the reaction mechanism depending highly on the protonation pattern. This dependence is apparently complicated, but is shown to obey a well-defined set of rules: Protonation of the α- and β-phosphate groups favors a sequential hydrolysis mechanism, whereas γ-protonation favors a concurrent mechanism, the two effects competing with each other in cases of simultaneous protonation. The rate-limiting step is always the breakup of the water molecule while it attacks the γ-phosphorus, and its barrier is lowered by γ-protonation. This step has significantly lower barriers in the sequential reactions, because the dissociated γ-metaphosphate intermediate (P γ O 3 - ) is a much better target for water attack than the un-dissociated γ-phosphate (-P γ O 4 2- ). The simple chemical logic behind these rules helps to better understand the catalytic strategy used by NTPase enzymes, as illustrated here for the catalytic pocket of myosin. A set of rules was determined that describes how protonating the phosphate groups affects the hydrolysis mechanism of methyl triphosphate: Protonation of the α- and/or β- phosphate groups promotes a sequential mechanism in which P-O bond breaking precedes the breakup of the attacking water, whereas protonation of the γ-phosphate promotes a concurrent mechanism and lowers the rate-limiting barrier of water breakup. The role played by individual protein residues in the catalytic pocket of triphosphate hydrolysing enzymes can be assigned accordingly.

Adipose-derived mesenchymal stem cells promote cell proliferation and invasion of epithelial ovarian cancer

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

Chu, Yijing; Tang, Huijuan; Guo, Yan

Adipose-derived mesenchymal stem cell (ADSC) is an important component of tumor microenvironment. However, whether ADSCs have a hand in ovarian cancer progression remains unclear. In this study, we investigated the impact of human ADSCs derived from the omentum of normal donors on human epithelial ovarian cancer (EOC) cells in vitro and in vivo. Direct and indirect co-culture models including ADSCs and human EOC cell lines were established and the effects of ADSCs on EOC cell proliferation were evaluated by EdU incorporation and flow cytometry. Transwell migration assays and detection of MMPs were performed to assess the invasion activity of EOCmore » cells in vitro. Mouse models were established by intraperitoneal injection of EOC cells with or without concomitant ADSCs to investigate the role of ADSCs in tumor progression in vivo. We found that ADSCs significantly promoted proliferation and invasion of EOC cells in both direct and indirect co-culture assays. In addition, after co-culture with ADSCs, EOC cells secreted higher levels of matrix metalloproteinases (MMPs), and inhibition of MMP2 and MMP9 partially relieved the tumor-promoting effects of ADSCs in vitro. In mouse xenograft models, we confirmed that ADSCs promoted EOC growth and metastasis and elevated the expression of MMP2 and MMP9. Our findings indicate that omental ADSCs play a promotive role during ovarian cancer progression. - Highlights: • Omental adipose derived stem cells enhanced growth and invasion properties of ovarian cancer cells. • Adipose derived stem cells promoted the growth and metastasis of ovarian cancer in mice models. • Adipose derived stem cells promoted MMPs expression and secretion of ovarian cancer cells. • Elevated MMPs mediated the tumor promoting effects of ADSCs.« less

Late post-treatment radiographic changes 3 years following chemoradiation for glioma: the importance of histopathology.

PubMed

Galante, Joao R; Rodriguez, Fausto; Grossman, Stuart A; Strowd, Roy E

2017-07-18

Treatment-related changes can mimic brain tumor progression both clinically and radiographically. Distinguishing these two entities represents a major challenge in neuro-oncology. No single imaging modality is capable of reliably achieving such distinction. While histopathology remains the gold standard, definitive pathological criteria are also lacking which can further complicate such cases. We report a patient with high-grade glioma who, after initially presenting with histopathologically confirmed pseudoprogression 10 months following treatment, re-presented 3 years following concurrent chemoradiation with clinical and radiographic changes that were most consistent with progressive disease but for which histopathology revealed treatment effects without active glioma. This case highlights the potential late onset of treatment-related changes and underscores the importance of histopathologic assessment even years following initial therapy.

Successful Osimertinib Rechallenge with Steroid Therapy after Osimertinib-induced Interstitial Lung Disease.

PubMed

Kiriu, Tatsunori; Tamura, Daisuke; Tachihara, Motoko; Sekiya, Reina; Hazama, Daisuke; Katsurada, Masahiro; Nakata, Kyosuke; Nagano, Tatsuya; Yamamoto, Masatsugu; Kamiryo, Hiroshi; Kobayashi, Kazuyuki; Nishimura, Yoshihiro

2018-01-01

A 62-year-old male with lung adenocarcinoma harboring an exon 19 deletion in the Epidermal growth factor receptor (EGFR) was treated with EGFR-tyrosine kinase inhibitors (TKIs) and several cytotoxic agents. After administering a fifth-line chemotherapy regimen, a liver biopsy revealed a diagnosis of recurrence with a T790M mutation. After an 82-day course of osimertinib therapy, the patient developed osimertinib-induced interstitial lung disease (ILD). Osimertinib was discontinued, and oral prednisolone was started. The ILD quickly improved, but liver metastases progressed and osimertinib was restarted concurrently with prednisolone. The patient showed neither disease progression nor a recurrence of ILD at 5 months. In situations in which no alternative treatment is available, osimertinib rechallenge should thus be considered as an alternative treatment.

Successful Osimertinib Rechallenge with Steroid Therapy after Osimertinib-induced Interstitial Lung Disease

PubMed Central

Kiriu, Tatsunori; Tamura, Daisuke; Tachihara, Motoko; Sekiya, Reina; Hazama, Daisuke; Katsurada, Masahiro; Nakata, Kyosuke; Nagano, Tatsuya; Yamamoto, Masatsugu; Kamiryo, Hiroshi; Kobayashi, Kazuyuki; Nishimura, Yoshihiro

2017-01-01

A 62-year-old male with lung adenocarcinoma harboring an exon 19 deletion in the Epidermal growth factor receptor (EGFR) was treated with EGFR-tyrosine kinase inhibitors (TKIs) and several cytotoxic agents. After administering a fifth-line chemotherapy regimen, a liver biopsy revealed a diagnosis of recurrence with a T790M mutation. After an 82-day course of osimertinib therapy, the patient developed osimertinib-induced interstitial lung disease (ILD). Osimertinib was discontinued, and oral prednisolone was started. The ILD quickly improved, but liver metastases progressed and osimertinib was restarted concurrently with prednisolone. The patient showed neither disease progression nor a recurrence of ILD at 5 months. In situations in which no alternative treatment is available, osimertinib rechallenge should thus be considered as an alternative treatment. PMID:29033419

Evaluation of Absolute and Relative Reinforcer Value Using Progressive-Ratio Schedules

PubMed Central

Francisco, Monica T; Borrero, John C; Sy, Jolene R

2008-01-01

We evaluated behavior exhibited by individuals with developmental disabilities using progressive-ratio (PR) schedules. High- and low-preference stimuli were determined based on the results of a paired-stimulus preference assessment and were evaluated in subsequent reinforcer and PR assessments using concurrent and single schedules of presentation. In Experiment 1, results showed that for 2 of 3 participants, stimuli determined to be low-preference functioned as reinforcers when evaluated independent of high-preference stimuli. Further, the results from Experiment 2 showed that low-preference stimuli also functioned as reinforcers under gradually increasing PR requirements. Results suggest that for cases in which a high-preference stimulus is unavailable or impractical, the contingent delivery of relatively less preferred stimuli may maintain appropriate behavior, even as schedule requirements increase. PMID:18595283

Palliative Sedation and What Constitutes Active Dying: A Case of Severe Progressive Dystonia and Intractable Pain.

PubMed

Strand, Jacob J; Feely, Molly A; Kramer, Neha M; Moeschler, Susan M; Swetz, Keith M

2016-05-01

We present the case of a 34-year-old woman with Klippel-Feil syndrome who developed progressive generalized dystonia of unclear etiology, resulting in intractable pain despite aggressive medical and surgical interventions. Ultimately, palliative sedation was required to relieve suffering. Herein, we describe ethical considerations including defining sedation, determining prognosis in the setting of an undefined neurodegenerative condition, and use of treatments that concurrently might prolong or alter end-of-life trajectory. We highlight pertinent literature and how it may be applied in challenging and unique clinical situations. Finally, we discuss the need for expert multidisciplinary involvement when implementing palliative sedation and illustrate that procedures and rules need to be interpreted to deliver optimal patient-centered plan of care. © The Author(s) 2014.

Primary tonsillar mast cell tumour in a dog.

PubMed

Shekell, C C; Thomson, M J; Miller, R I; Mackie, J T

2018-05-01

A 6-year-old speyed female Bull Arab-cross dog was found to have a small tonsillar nodule. Histological examination revealed a well-differentiated mast cell tumour (MCT). At initial staging, no evidence of concurrent cutaneous or visceral MCTs was found on a complete blood count, a single lateral thoracic radiograph, abdominal ultrasound or cytology of the spleen and regional lymph nodes. A diagnosis of primary tonsillar MCT was made. At 40 months postoperatively, the dog is alive with no evidence of gross tumour progression, in contrast to some previous reports of rapid disease progression and metastasis in dogs with primary oral MCTs. To the authors' knowledge, no previous reports of a primary MCT of the tonsil in dogs exist in the veterinary literature. © 2018 Australian Veterinary Association.

Analyzing compound and project progress through multi-objective-based compound quality assessment.

PubMed

Nissink, J Willem M; Degorce, Sébastien

2013-05-01

Compound-quality scoring methods designed to evaluate multiple drug properties concurrently are useful to analyze and prioritize output from drug-design efforts. However, formalized multiparameter optimization approaches are not widely used in drug design. We rank molecules synthesized in drug-discovery projects using simple and aggregated desirability functions reflecting medicinal chemistry 'rules'. Our quality score deals transparently with missing data, a key requirement in drug-hunting projects where data availability is often limited. We further estimate confidence in the interpretation of such a compound-quality measure. Scores and associated confidences provide systematic insight in the quality of emerging chemical equity. Tracking quality of synthetic output over time yields valuable insight into the progress of drug-design teams, with potential applications in risk and resource management of a drug portfolio.

A correlational approach to predicting operator status

NASA Technical Reports Server (NTRS)

Shingledecker, Clark A.

1988-01-01

This paper discusses a research approach for identifying and validating candidate physiological and behavioral parameters which can be used to predict the performance capabilities of aircrew and other system operators. In this methodology, concurrent and advance correlations are computed between predictor values and criterion performance measures. Continuous performance and sleep loss are used as stressors to promote performance variation. Preliminary data are presented which suggest dependence of prediction capability on the resource allocation policy of the operator.

Caspase inhibitors promote vestibular hair cell survival and function after aminoglycoside treatment in vivo

NASA Technical Reports Server (NTRS)

Matsui, Jonathan I.; Haque, Asim; Huss, David; Messana, Elizabeth P.; Alosi, Julie A.; Roberson, David W.; Cotanche, Douglas A.; Dickman, J. David; Warchol, Mark E.

2003-01-01

The sensory hair cells of the inner ear undergo apoptosis after acoustic trauma or aminoglycoside antibiotic treatment, causing permanent auditory and vestibular deficits in humans. Previous studies have demonstrated a role for caspase activation in hair cell death and ototoxic injury that can be reduced by concurrent treatment with caspase inhibitors in vitro. In this study, we examined the protective effects of caspase inhibition on hair cell death in vivo after systemic injections of aminoglycosides. In one series of experiments, chickens were implanted with osmotic pumps that administrated the pan-caspase inhibitor z-Val-Ala-Asp(Ome)-fluoromethylketone (zVAD) into inner ear fluids. One day after the surgery, the animals received a 5 d course of treatment with streptomycin, a vestibulotoxic aminoglycoside. Direct infusion of zVAD into the vestibule significantly increased hair cell survival after streptomycin treatment. A second series of experiments determined whether rescued hair cells could function as sensory receptors. Animals treated with streptomycin displayed vestibular system impairment as measured by a greatly reduced vestibulo-ocular response (VOR). In contrast, animals that received concurrent systemic administration of zVAD with streptomycin had both significantly greater hair cell survival and significantly increased VOR responses, as compared with animals treated with streptomycin alone. These findings suggest that inhibiting the activation of caspases promotes the survival of hair cells and protects against vestibular function deficits after aminoglycoside treatment.

Mammalian O-Mannosylation Pathway: Glycan Structures, Enzymes, and Protein Substrates

PubMed Central

2015-01-01

The mammalian O-mannosylation pathway for protein post-translational modification is intricately involved in modulating cell–matrix interactions in the musculature and nervous system. Defects in enzymes of this biosynthetic pathway are causative for multiple forms of congenital muscular dystophy. The application of advanced genetic and biochemical technologies has resulted in remarkable progress in this field over the past few years, culminating with the publication of three landmark papers in 2013 alone. In this review, we will highlight recent progress focusing on the dramatic expansion of the set of genes known to be involved in O-mannosylation and disease processes, the concurrent acceleration of the rate of O-mannosylation pathway protein functional assignments, the tremendous increase in the number of proteins now known to be modified by O-mannosylation, and the recent progress in protein O-mannose glycan quantification and site assignment. Also, we attempt to highlight key outstanding questions raised by this abundance of new information. PMID:24786756

Acquired resistance and clonal evolution in melanoma during BRAF inhibitor therapy

PubMed Central

Kong, Xiangju; Hong, Aayoung; Koya, Richard C.; Moriceau, Gatien; Chodon, Thinle; Guo, Rongqing; Johnson, Douglas B.; Dahlman, Kimberly B.; Kelley, Mark C.; Kefford, Richard F.; Chmielowski, Bartosz; Glaspy, John A.; Sosman, Jeffrey A.; van Baren, Nicolas; Long, Georgina V.; Ribas, Antoni; Lo, Roger S.

2013-01-01

BRAF inhibitors elicit rapid anti-tumor responses in the majority of patients with V600BRAF mutant melanoma, but acquired drug resistance is almost universal. We sought to identify the core resistance pathways and the extent of tumor heterogeneity during disease progression. We show that MAPK reactivation mechanisms were detected among 70% of disease-progressive tissues, with RAS mutations, mutant BRAF amplification and alternative splicing being most common. We also detected PI3K-PTEN-AKT-upregulating genetic alterations among 22% of progressive melanomas. Distinct molecular lesions, in both core drug escape pathways, were commonly detected concurrently in the same tumor or among multiple tumors from the same patient. Beyond harboring extensively heterogeneous resistance mechanisms, melanoma re-growth emerging from BRAF inhibitor selection displayed branched evolution marked by altered mutational spectra/signatures and increased fitness. Thus, melanoma genomic heterogeneity contributes significantly to BRAF inhibitor treatment failure, implying upfront, co-targeting of two core pathways as an essential strategy for durable responses. PMID:24265155

Assessing progress during treatment for young children with autism receiving intensive behavioural interventions.

PubMed

Hayward, Diane; Eikeseth, Svein; Gale, Catherine; Morgan, Sally

2009-11-01

This study examined progress after 1 year of treatment for children with autism who received a mean of 36 hours per week one-to-one University of California at Los Angeles Applied Behavior Analysis (UCLA ABA) treatment. Two types of service provision were compared: an intensive clinic based treatment model with all treatment personnel (N = 23), and an intensive parent managed treatment model with intensive supervision only (N = 21). A non-concurrent multiple baseline design across participants (N = 13) examined whether progress was associated with ABA treatment or confounders. Between intake and follow-up, children in both groups improved significantly on IQ, visual-spatial IQ, language comprehension, expressive language, social skills, motor skills and adaptive behaviour. There were no significant differences between the two groups on any of the measures at follow-up. Mean IQ for participants in both groups increased by 16 points between intake and follow-up. These findings are consistent with previous studies demonstrating the benefits of ABA treatment.

Phase 2 study of high-dose proton therapy with concurrent chemotherapy for unresectable stage III nonsmall cell lung cancer.

PubMed

Chang, Joe Y; Komaki, Ritsuko; Lu, Charles; Wen, Hong Y; Allen, Pamela K; Tsao, Anne; Gillin, Michael; Mohan, Radhe; Cox, James D

2011-10-15

The authors sought to improve the toxicity of conventional concurrent chemoradiation therapy for stage III nonsmall cell lung cancer (NSCLC) by using proton-beam therapy to escalate the radiation dose to the tumor. They report early results of a phase 2 study of high-dose proton therapy and concurrent chemotherapy in terms of toxicity, failure patterns, and survival. Forty-four patients with stage III NSCLC were treated with 74 grays (radiobiologic equivalent) proton therapy with weekly carboplatin (area under the curve, 2 U) and paclitaxel (50 mg/m(2)). Disease was staged with positron emission tomography/computed tomography (CT), and treatments were simulated with 4-dimensional (4D) CT to account for tumor motion. Protons were delivered as passively scattered beams, and treatment simulation was repeated during the treatment process to determine the need for adaptive replanning. Median follow-up time was 19.7 months (range, 6.1-44.4 months), and median overall survival time was 29.4 months. No patient experienced grade 4 or 5 proton-related adverse events. The most common nonhematologic grade 3 toxicities were dermatitis (n = 5), esophagitis (n = 5), and pneumonitis (n = 1). Nine (20.5%) patients experienced local disease recurrence, but only 4 (9.1%) had isolated local failure. Four (9.1%) patients had regional lymph node recurrence, but only 1 (2.3%) had isolated regional recurrence. Nineteen (43.2%) patients developed distant metastasis. The overall survival and progression-free survival rates were 86% and 63% at 1 year. Concurrent high-dose proton therapy and chemotherapy are well tolerated, and the median survival time of 29.4 months is encouraging for unresectable stage III NSCLC. Copyright © 2011 American Cancer Society.

A Phase I Dose Escalation Study of Hypofractionated IMRT Field-in-Field Boost for Newly Diagnosed Glioblastoma Multiforme

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

Monjazeb, Arta M., E-mail: arta.monjazeb@ucdmc.ucdavis.edu; Ayala, Deandra; Jensen, Courtney

2012-02-01

Objectives: To describe the results of a Phase I dose escalation trial for newly diagnosed glioblastoma multiforme (GBM) using a hypofractionated concurrent intensity-modulated radiotherapy (IMRT) boost. Methods: Twenty-one patients were enrolled between April 1999 and August 2003. Radiotherapy consisted of daily fractions of 1.8 Gy with a concurrent boost of 0.7 Gy (total 2.5 Gy daily) to a total dose of 70, 75, or 80 Gy. Concurrent chemotherapy was not permitted. Seven patients were enrolled at each dose and dose limiting toxicities were defined as irreversible Grade 3 or any Grade 4-5 acute neurotoxicity attributable to radiotherapy. Results: All patientsmore » experienced Grade 1 or 2 acute toxicities. Acutely, 8 patients experienced Grade 3 and 1 patient experienced Grade 3 and 4 toxicities. Of these, only two reversible cases of otitis media were attributable to radiotherapy. No dose-limiting toxicities were encountered. Only 2 patients experienced Grade 3 delayed toxicity and there was no delayed Grade 4 toxicity. Eleven patients requiring repeat resection or biopsy were found to have viable tumor and radiation changes with no cases of radionecrosis alone. Median overall and progression-free survival for this cohort were 13.6 and 6.5 months, respectively. One- and 2-year survival rates were 57% and 19%. At recurrence, 15 patients received chemotherapy, 9 underwent resection, and 5 received radiotherapy. Conclusions: Using a hypofractionated concurrent IMRT boost, we were able to safely treat patients to 80 Gy without any dose-limiting toxicity. Given that local failure still remains the predominant pattern for GBM patients, a trial of dose escalation with IMRT and temozolomide is warranted.« less

Improved survival and complete response rates in patients with advanced melanoma treated with concurrent ipilimumab and radiotherapy versus ipilimumab alone.

PubMed

Koller, Kristian M; Mackley, Heath B; Liu, Jason; Wagner, Henry; Talamo, Giampaolo; Schell, Todd D; Pameijer, Colette; Neves, Rogerio I; Anderson, Bryan; Kokolus, Kathleen M; Mallon, Carol A; Drabick, Joseph J

2017-01-02

There is a growing body of evidence supporting the synergistic roles of radiotherapy and immunotherapy in the treatment of malignancy. Published case studies of the abscopal effect have been reported with the use of ipilimumab and radiotherapy in metastatic melanoma, but evidence supporting the routine use of this combination of therapy is limited. We conducted a retrospective analysis to evaluate patients treated with ipilimumab for advanced melanoma at a single institution from May 2011 to June 2015. Patients were grouped into those who had received concurrent radiotherapy while on ipilimumab (Ipi-RT), and those who did not. We then evaluated the treatment response following completion of ipilimumab. A total of 101 patients received ipilimumab in the prespecified time frame. 70 received Ipi-RT and 31 received ipilimumab without concurrent radiotherapy. Median overall survival (OS) was significantly increased in the concurrent Ipi-RT arm at 19 months vs. 10 months for ipilimumab alone (p = 0.01). Median progression free survival (PFS) was marginally increased in the Ipi-RT group compare with the ipilimumab alone group (5 months vs. 3 months, p = 0.20). Rates of complete response (CR) were significantly increased in the Ipi-RT group vs. ipilimumab alone (25.7% vs. 6.5%; p = 0.04), and rates of overall response (OR) in the groups were 37.1% vs. 19.4% (p = 0.11). No increase in toxicities was observed in the Ipi-RT group compare with ipilimumab alone. Prospective trials are needed to further clarify the role of radiotherapy with ipilimumab, but these encouraging preliminary observations suggest that this combination can induce more durable responses to immunotherapy.

Improved survival and complete response rates in patients with advanced melanoma treated with concurrent ipilimumab and radiotherapy versus ipilimumab alone

PubMed Central

Koller, Kristian M.; Mackley, Heath B.; Liu, Jason; Wagner, Henry; Talamo, Giampaolo; Schell, Todd D.; Pameijer, Colette; Neves, Rogerio I.; Anderson, Bryan; Kokolus, Kathleen M.; Mallon, Carol A.; Drabick, Joseph J.

2017-01-01

ABSTRACT There is a growing body of evidence supporting the synergistic roles of radiotherapy and immunotherapy in the treatment of malignancy. Published case studies of the abscopal effect have been reported with the use of ipilimumab and radiotherapy in metastatic melanoma, but evidence supporting the routine use of this combination of therapy is limited. We conducted a retrospective analysis to evaluate patients treated with ipilimumab for advanced melanoma at a single institution from May 2011 to June 2015. Patients were grouped into those who had received concurrent radiotherapy while on ipilimumab (Ipi-RT), and those who did not. We then evaluated the treatment response following completion of ipilimumab. A total of 101 patients received ipilimumab in the prespecified time frame. 70 received Ipi-RT and 31 received ipilimumab without concurrent radiotherapy. Median overall survival (OS) was significantly increased in the concurrent Ipi-RT arm at 19 months vs. 10 months for ipilimumab alone (p = 0.01). Median progression free survival (PFS) was marginally increased in the Ipi-RT group compare with the ipilimumab alone group (5 months vs. 3 months, p = 0.20). Rates of complete response (CR) were significantly increased in the Ipi-RT group vs. ipilimumab alone (25.7% vs. 6.5%; p = 0.04), and rates of overall response (OR) in the groups were 37.1% vs. 19.4% (p = 0.11). No increase in toxicities was observed in the Ipi-RT group compare with ipilimumab alone. Prospective trials are needed to further clarify the role of radiotherapy with ipilimumab, but these encouraging preliminary observations suggest that this combination can induce more durable responses to immunotherapy. PMID:27905824

Carbon Ion Radiation Therapy With Concurrent Gemcitabine for Patients With Locally Advanced Pancreatic Cancer

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

Shinoto, Makoto, E-mail: shinoto@saga-himat.jp; Ion Beam Therapy Center, SAGA HIMAT Foundation, Tosu; Department of Clinical Radiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka

Purpose: To determine, in the setting of locally advanced pancreatic cancer, the maximum tolerated dose of carbon ion radiation therapy (C-ion RT) and gemcitabine dose delivered concurrently and to estimate local effect and survival. Methods and Materials: Eligibility included pathologic confirmation of pancreatic invasive ductal carcinomas and radiographically unresectable disease without metastasis. Concurrent gemcitabine was administered on days 1, 8, and 15, and the dose levels were escalated from 400 to 1000 mg/m{sup 2} under the starting dose level (43.2 GyE) of C-ion RT. The dose levels of C-ion RT were escalated from 43.2 to 55.2 GyE at 12 fractions undermore » the fixed recommended gemcitabine dose determined. Results: Seventy-six patients were enrolled. Among the 72 treated patients, dose-limiting toxicity was observed in 3 patients: grade 3 infection in 1 patient and grade 4 neutropenia in 2 patients. Only 1 patient experienced a late grade 3 gastric ulcer and bleeding 10 months after C-ion RT. The recommended dose of gemcitabine with C-ion RT was found to be 1000 mg/m{sup 2}. The dose of C-ion RT with the full dose of gemcitabine (1000 mg/m{sup 2}) was safely increased to 55.2 GyE. The freedom from local progression rate was 83% at 2 years using the Response Evaluation Criteria in Solid Tumors. The 2-year overall survival rates in all patients and in the high-dose group with stage III (≥45.6 GyE) were 35% and 48%, respectively. Conclusions: Carbon ion RT with concurrent full-dose gemcitabine was well tolerated and effective in patients with unresectable locally advanced pancreatic cancer.« less

Concurrent, but not sequential, PD-1 blockade with a DNA vaccine elicits anti-tumor responses in patients with metastatic, castration-resistant prostate cancer.

PubMed

McNeel, Douglas G; Eickhoff, Jens C; Wargowski, Ellen; Zahm, Christopher; Staab, Mary Jane; Straus, Jane; Liu, Glenn

2018-05-22

T-cell checkpoint inhibitors have demonstrated dramatic clinical activity against multiple cancer types, however little activity in patients with prostate cancer. Conversely, an anti-tumor vaccine was approved for the treatment of prostate cancer, having demonstrated an improvement in overall survival, despite few objective disease responses. In murine studies, we found that PD-1 expression on CD8+ T cells increased following anti-tumor vaccination, and that PD-1/PD-L1 blockade at the time of immunization elicited greater anti-tumor responses. Based on these data we initiated a pilot trial evaluating the immunological and clinical efficacy of a DNA encoding prostatic acid phosphatase (PAP) when delivered in combination with pembrolizumab. 26 patients were treated for 12 weeks with vaccine and received pembrolizumab either during this time or during the subsequent 12 weeks. Adverse events included grade 2 and 3 fatigue, diarrhea, thyroid dysfunction, and hepatitis. Median time to radiographic progression was not different between study arms. 8/13 (62%) of patients treated concurrently, and 1/12 (8%, p=0.01) of patients treated sequentially, experienced PSA declines from baseline. Of these, two were over 50% and one was a complete PSA response. No confirmed CR or PR were observed, however 4/5 patients treated concurrently had measurable decreases in tumor volume at 12 weeks. PSA declines were associated with the development of PAP-specific Th1-biased T cell immunity and CD8+ T cell infiltration in metastatic tumor biopsy specimens. These data are the first report of a clinical trial demonstrating that the efficacy of an anti-tumor vaccine can be augmented by concurrent PD-1 blockade.

Developing strong concurrent multiphysics multiscale coupling to understand the impact of microstructural mechanisms on the structural scale

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

Foulk, James W.; Alleman, Coleman N.; Mota, Alejandro

The heterogeneity in mechanical fields introduced by microstructure plays a critical role in the localization of deformation. To resolve this incipient stage of failure, it is therefore necessary to incorporate microstructure with sufficient resolution. On the other hand, computational limitations make it infeasible to represent the microstructure in the entire domain at the component scale. In this study, the authors demonstrate the use of concurrent multi- scale modeling to incorporate explicit, finely resolved microstructure in a critical region while resolving the smoother mechanical fields outside this region with a coarser discretization to limit computational cost. The microstructural physics is modeledmore » with a high-fidelity model that incorporates anisotropic crystal elasticity and rate-dependent crystal plasticity to simulate the behavior of a stainless steel alloy. The component-scale material behavior is treated with a lower fidelity model incorporating isotropic linear elasticity and rate-independent J 2 plas- ticity. The microstructural and component scale subdomains are modeled concurrently, with coupling via the Schwarz alternating method, which solves boundary-value problems in each subdomain separately and transfers solution information between subdomains via Dirichlet boundary conditions. Beyond cases studies in concurrent multiscale, we explore progress in crystal plastic- ity through modular designs, solution methodologies, model verification, and extensions to Sierra/SM and manycore applications. Advances in conformal microstructures having both hexahedral and tetrahedral workflows in Sculpt and Cubit are highlighted. A structure-property case study in two-phase metallic composites applies the Materials Knowledge System to local metrics for void evolution. Discussion includes lessons learned, future work, and a summary of funded efforts and proposed work. Finally, an appendix illustrates the need for two-way coupling through a single degree of freedom.« less

Adult Human Nasal Mesenchymal-Like Stem Cells Restore Cochlear Spiral Ganglion Neurons After Experimental Lesion

PubMed Central

Bas, Esperanza; Van De Water, Thomas R.; Lumbreras, Vicente; Rajguru, Suhrud; Goss, Garrett; Hare, Joshua M.

2014-01-01

A loss of sensory hair cells or spiral ganglion neurons from the inner ear causes deafness, affecting millions of people. Currently, there is no effective therapy to repair the inner ear sensory structures in humans. Cochlear implantation can restore input, but only if auditory neurons remain intact. Efforts to develop stem cell-based treatments for deafness have demonstrated progress, most notably utilizing embryonic-derived cells. In an effort to bypass limitations of embryonic or induced pluripotent stem cells that may impede the translation to clinical applications, we sought to utilize an alternative cell source. Here, we show that adult human mesenchymal-like stem cells (MSCs) obtained from nasal tissue can repair spiral ganglion loss in experimentally lesioned cochlear cultures from neonatal rats. Stem cells engraft into gentamicin-lesioned organotypic cultures and orchestrate the restoration of the spiral ganglion neuronal population, involving both direct neuronal differentiation and secondary effects on endogenous cells. As a physiologic assay, nasal MSC-derived cells engrafted into lesioned spiral ganglia demonstrate responses to infrared laser stimulus that are consistent with those typical of excitable cells. The addition of a pharmacologic activator of the canonical Wnt/β-catenin pathway concurrent with stem cell treatment promoted robust neuronal differentiation. The availability of an effective adult autologous cell source for inner ear tissue repair should contribute to efforts to translate cell-based strategies to the clinic. PMID:24172073

PPARδ induces estrogen receptor-positive mammary neoplasia through an inflammatory and metabolic phenotype linked to mTOR activation.

PubMed

Yuan, Hongyan; Lu, Jin; Xiao, Junfeng; Upadhyay, Geeta; Umans, Rachel; Kallakury, Bhaskar; Yin, Yuhzi; Fant, Michael E; Kopelovich, Levy; Glazer, Robert I

2013-07-15

The peroxisome proliferator-activated receptor-δ (PPARδ) regulates a multitude of physiological processes associated with glucose and lipid metabolism, inflammation, and proliferation. One or more of these processes are potential risk factors for the ability of PPARδ agonists to promote tumorigenesis in the mammary gland. In this study, we describe a new transgenic mouse model in which activation of PPARδ in the mammary epithelium by endogenous or synthetic ligands resulted in progressive histopathologic changes that culminated in the appearance of estrogen receptor- and progesterone receptor-positive and ErbB2-negative infiltrating ductal carcinomas. Multiparous mice presented with mammary carcinomas after a latency of 12 months, and administration of the PPARδ ligand GW501516 reduced tumor latency to 5 months. Histopathologic changes occurred concurrently with an increase in an inflammatory, invasive, metabolic, and proliferative gene signature, including expression of the trophoblast gene, Plac1, beginning 1 week after GW501516 treatment, and remained elevated throughout tumorigenesis. The appearance of malignant changes correlated with a pronounced increase in phosphatidylcholine and lysophosphatidic acid metabolites, which coincided with activation of Akt and mTOR signaling that were attenuated by treatment with the mTOR inhibitor everolimus. Our findings are the first to show a direct role of PPARδ in the pathogenesis of mammary tumorigenesis, and suggest a rationale for therapeutic approaches to prevent and treat this disease. ©2013 AACR.

Comparing the effects of entertainment media and tobacco marketing on youth smoking.

PubMed

Sargent, J D; Gibson, J; Heatherton, T F

2009-02-01

To examine the concurrent effects of exposure to movie smoking and tobacco marketing receptivity on adolescent smoking onset and progression. Cross-sectional study of 4524 northern New England adolescents aged 10-14 in 1999 with longitudinal follow-up of 2603 baseline never-smokers. Cross-sectional outcomes included ever tried smoking and higher level of lifetime smoking among 784 experimenters. The longitudinal outcome was onset of smoking among baseline never-smokers two years later. Movie smoking exposure was modelled as four population quartiles, tobacco marketing receptivity included two levels-having a favourite tobacco advert and wanting/owning tobacco promotional items. All analyses controlled for sociodemographics, other social influences, personality characteristics of the adolescent and parenting style. In the full cross-sectional sample, 17.5% had tried smoking; both exposure to movie smoking and receptivity to tobacco marketing were associated with having tried smoking. Among experimental smokers, the majority (64%) were receptive to tobacco marketing, which had a multivariate association with higher level of lifetime smoking (movie smoking did not). In the longitudinal study 9.5% of baseline never-smokers tried smoking at follow-up. Fewer never-smokers (18.5%) were receptive to tobacco marketing. Movie smoking had a multivariate association with trying smoking (receptivity to tobacco marketing did not). The results suggest separate roles for entertainment media and tobacco marketing on adolescent smoking. Both exposures deserve equal emphasis from a policy standpoint.

Phloretin suppresses thrombin-mediated leukocyte-platelet-endothelial interactions.

PubMed

Kim, Min Soo; Park, Sin-Hye; Han, Seon-Young; Kim, Yun-Ho; Lee, Eun-Jung; Yoon Park, Jung Han; Kang, Young-Hee

2014-04-01

Thrombin playing a pivotal role in coagulation cascade may influence the onset and progression of atherosclerosis as a pro-inflammatory mediator. This study investigated whether phloretin found in apple tree leaves, severed a linkage between thrombosis and atherosclerosis by thrombin. Human endothelial cells were pre-treated with 1-20 μM phloretin and stimulated with 10 U/mL thrombin. Phloretin attenuated adhesion of THP-1 monocytes and platelets to thrombin-inflamed endothelial cells with concurrent inhibition of protease-activated receptor (PAR-1) induction. The thrombin induction of endothelial CD40, endothelial integrin β3 and P-selectin, and monocytic CD40L was dampened by phloretin. Additionally, phloretin inhibited monocyte secretion of MCP-1, IL-6 and IL-8 responsible for pro-inflammatory activity of thrombin inducing endothelial CD40. The monocyte COX-2 induction and PGE2 secretion due to thrombin were down-regulated by phloretin, deterring endothelial CD40 expression. Thrombin promoted production of PAI-1 and tissue factor in monocytes was attenuated by phloretin through blocking PAR-1 and CD40. Thrombin up-regulated the induction of endothelial connective tissue growth factor independent of PAR-1 activation, which was reversed by phloretin. Phloretin disturbed tethering and stable adhesion of monocytes and platelets onto endothelium during increased thrombosis by thrombin. Phloretin would be a potent agent preventing thrombosis and atherosclerosis. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Recapitulation of physiological spatiotemporal signals promotes in vitro formation of phenotypically stable human articular cartilage

PubMed Central

Wei, Yiyong; Zhou, Bin; Bernhard, Jonathan; Robinson, Samuel; Burapachaisri, Aonnicha; Guo, X. Edward

2017-01-01

Standard isotropic culture fails to recapitulate the spatiotemporal gradients present during native development. Cartilage grown from human mesenchymal stem cells (hMSCs) is poorly organized and unstable in vivo. We report that human cartilage with physiologic organization and in vivo stability can be grown in vitro from self-assembling hMSCs by implementing spatiotemporal regulation during induction. Self-assembling hMSCs formed cartilage discs in Transwell inserts following isotropic chondrogenic induction with transforming growth factor β to set up a dual-compartment culture. Following a switch in the basal compartment to a hypertrophic regimen with thyroxine, the cartilage discs underwent progressive deep-zone hypertrophy and mineralization. Concurrent chondrogenic induction in the apical compartment enabled the maintenance of functional and hyaline cartilage. Cartilage homeostasis, chondrocyte maturation, and terminal differentiation markers were all up-regulated versus isotropic control groups. We assessed the in vivo stability of the cartilage formed under different induction regimens. Cartilage formed under spatiotemporal regulation in vitro resisted endochondral ossification, retained the expression of cartilage markers, and remained organized following s.c. implantation in immunocompromised mice. In contrast, the isotropic control groups underwent endochondral ossification. Cartilage formed from hMSCs remained stable and organized in vivo. Spatiotemporal regulation during induction in vitro recapitulated some aspects of native cartilage development, and potentiated the maturation of self-assembling hMSCs into stable and organized cartilage resembling the native articular cartilage. PMID:28228529

Poetry as Progress: Balancing Standards-Based Reforms with Aesthetic Inquiry

ERIC Educational Resources Information Center

Liu, Laura B.

2011-01-01

The meaning of "progress" in U.S. educational institutions has undergone much debate (Tyack & Cuban, 1995). Standards-driven practices have often promoted a search for "right" answers in place of critical and diverse thinking. Globalization and its impacts compel us to continue revising and articulating the meaning of progress for 21st century…

Experiencing the Progress Report: An Analysis of Gender and Administration in Doctoral Candidature

ERIC Educational Resources Information Center

Mewburn, Inger; Cuthbert, Denise; Tokareva, Ekaterina

2014-01-01

Most universities around the world put in place administrative processes and systems to manage student progress. These processes usually involve filling out standardised forms and instruments: managerial tools intended to increase transparency, promote efficiency and ensure fairness by applying the same standards to all. The progress report is a…

Scientific progress without increasing verisimilitude: In response to Niiniluoto.

PubMed

Rowbottom, Darrell P

2015-06-01

First, I argue that scientific progress is possible in the absence of increasing verisimilitude in science's theories. Second, I argue that increasing theoretical verisimilitude is not the central, or primary, dimension of scientific progress. Third, I defend my previous argument that unjustified changes in scientific belief may be progressive. Fourth, I illustrate how false beliefs can promote scientific progress in ways that cannot be explicated by appeal to verisimilitude. Copyright © 2015 Elsevier Ltd. All rights reserved.

How does low-molecular-weight polystyrene dissolve: osmotic swelling vs. surface dissolution.

PubMed

Marcon, Valentina; van der Vegt, Nico F A

2014-12-07

By means of multiscale hierarchical modeling we study the real time evolution of low-molecular-weight polystyrene, below the glass transition temperature, in contact with its solvent, toluene. We observe two concurrent phenomena taking place: (1) the solvent diffuses into the polymer by a Case II mechanism, leading to osmotic driven swelling and progressive chain dilution (inside-out mechanism); (2) polymer chains are solvated, detach from the interface and move into the solvent before the film is completely swollen (outside-in mechanism). From our simulations we conclude that, below the entanglement length, a thin swollen layer, also observed in previous experiments, forms almost instantaneously, which allows for the outside-in mechanism to start a few tens of nanoseconds after the polymer-solvent initial contact. After this initial transient time the two mechanisms are concurrent. We furthermore observe that the presence of the solvent significantly enhances the mobility of the polymer chains of the surface layer, but only in the direction parallel to the interface.

Efficacy of vitrectomy and epiretinal membrane peeling in eyes with dry age-related macular degeneration.

PubMed

Mason, John O; Patel, Shyam A

2015-01-01

To study the efficacy of epiretinal membrane (ERM) peeling in eyes with dry age-related macular degeneration (AMD). We retrospectively analyzed patient charts on 17 eyes (16 patients) that underwent ERM peeling with a concurrent diagnosis of dry AMD. Eyes with concurrent dry AMD and with a good preoperative best-corrected visual acuity (BCVA) (better than or equal to 20/50) had a statistically significant mean BCVA improvement at 6 months after ERM peeling. There was a statistical increase in mean BCVA from 20/95 to 20/56 in dry AMD eyes, and no eyes showed worsening in BCVA at 6 months or at most recent follow-up. Five/seventeen (29.4%) eyes had cataract formation or progression. There were no other complications, reoperations, or reoccurrences. ERM peeling in eyes with dry AMD may show significant improvement, especially in eyes with good preoperative BCVA. The procedure is relatively safe with low complications and reoccurrences.

Passing waves from atomistic to continuum

NASA Astrophysics Data System (ADS)

Chen, Xiang; Diaz, Adrian; Xiong, Liming; McDowell, David L.; Chen, Youping

2018-02-01

Progress in the development of coupled atomistic-continuum methods for simulations of critical dynamic material behavior has been hampered by a spurious wave reflection problem at the atomistic-continuum interface. This problem is mainly caused by the difference in material descriptions between the atomistic and continuum models, which results in a mismatch in phonon dispersion relations. In this work, we introduce a new method based on atomistic dynamics of lattice coupled with a concurrent atomistic-continuum method to enable a full phonon representation in the continuum description. This permits the passage of short-wavelength, high-frequency phonon waves from the atomistic to continuum regions. The benchmark examples presented in this work demonstrate that the new scheme enables the passage of all allowable phonons through the atomistic-continuum interface; it also preserves the wave coherency and energy conservation after phonons transport across multiple atomistic-continuum interfaces. This work is the first step towards developing a concurrent atomistic-continuum simulation tool for non-equilibrium phonon-mediated thermal transport in materials with microstructural complexity.

A comparison of cognitive performance decreases during acute, progressive fatigue arising from different concurrent stressors.

PubMed

Fogt, Donovan L; Kalns, John E; Michael, Darren J

2010-12-01

Fatigue is known to impair cognitive performance, but it remains unclear whether concurrent common stressors affect cognitive performance similarly. We used the Stroop Color-Word Conflict Test to assess cognitive performance over 24 hours for four groups: control, sleep-deprived (SD), SD + energy deficit, and SD + energy deficit + fluid restricted. Fatigue levels were quantified using the Profile of Mood States (POMS) survey. Linear mixed-effects (LME) models allowed for testing of group-specific differences in cognitive performance while accounting for subject-level variation. Starting fatigue levels were similar among all groups, while 24-hour fatigue levels differed significantly. For each cognitive performance test, results were modeled separately. The simplest LME model contained a significant fixed-effects term for slope and intercept. Moreover, the simplest LME model used a single slope coefficient to fit data from all four groups, suggesting that loss in cognitive performance over a 24-hour duty cycle with respect to fatigue level is similar regardless of the cause.

Heparanase promotes myeloma progression by inducing mesenchymal features and motility of myeloma cells.

PubMed

Li, Juan; Pan, Qianying; Rowan, Patrick D; Trotter, Timothy N; Peker, Deniz; Regal, Kellie M; Javed, Amjad; Suva, Larry J; Yang, Yang

2016-03-08

Bone dissemination and bone disease occur in approximately 80% of patients with multiple myeloma (MM) and are a major cause of patient mortality. We previously demonstrated that MM cell-derived heparanase (HPSE) is a major driver of MM dissemination to and progression in new bone sites. However the mechanism(s) by which HPSE promotes MM progression remains unclear. In the present study, we investigated the involvement of mesenchymal features in HPSE-promoted MM progression in bone. Using a combination of molecular, biochemical, cellular, and in vivo approaches, we demonstrated that (1) HPSE enhanced the expression of mesenchymal markers in both MM and vascular endothelial cells; (2) HPSE expression in patient myeloma cells positively correlated with the expression of the mesenchymal markers vimentin and fibronectin. Additional mechanistic studies revealed that the enhanced mesenchymal-like phenotype induced by HPSE in MM cells is due, at least in part, to the stimulation of the ERK signaling pathway. Finally, knockdown of vimentin in HPSE expressing MM cells resulted in significantly attenuated MM cell dissemination and tumor growth in vivo. Collectively, these data demonstrate that the mesenchymal features induced by HPSE in MM cells contribute to enhanced tumor cell motility and bone-dissemination.

Id1 suppresses anti-tumour immune responses and promotes tumour progression by impairing myeloid cell maturation.

PubMed

Papaspyridonos, Marianna; Matei, Irina; Huang, Yujie; do Rosario Andre, Maria; Brazier-Mitouart, Helene; Waite, Janelle C; Chan, April S; Kalter, Julie; Ramos, Ilyssa; Wu, Qi; Williams, Caitlin; Wolchok, Jedd D; Chapman, Paul B; Peinado, Hector; Anandasabapathy, Niroshana; Ocean, Allyson J; Kaplan, Rosandra N; Greenfield, Jeffrey P; Bromberg, Jacqueline; Skokos, Dimitris; Lyden, David

2015-04-29

A central mechanism of tumour progression and metastasis involves the generation of an immunosuppressive 'macroenvironment' mediated in part through tumour-secreted factors. Here we demonstrate that upregulation of the Inhibitor of Differentiation 1 (Id1), in response to tumour-derived factors, such as TGFβ, is responsible for the switch from dendritic cell (DC) differentiation to myeloid-derived suppressor cell expansion during tumour progression. Genetic inactivation of Id1 largely corrects the myeloid imbalance, whereas Id1 overexpression in the absence of tumour-derived factors re-creates it. Id1 overexpression leads to systemic immunosuppression by downregulation of key molecules involved in DC differentiation and suppression of CD8 T-cell proliferation, thus promoting primary tumour growth and metastatic progression. Furthermore, advanced melanoma patients have increased plasma TGFβ levels and express higher levels of ID1 in myeloid peripheral blood cells. This study reveals a critical role for Id1 in suppressing the anti-tumour immune response during tumour progression and metastasis.

Promotion Models and Achievements of New-energy Automobiles in Shenzhen

NASA Astrophysics Data System (ADS)

Cai, Yu; Xiong, Siqin; Bai, Bo; Ma, Xiaoming

2017-08-01

As one of the pilot cities in China for demonstration and promotion of new-energy automobiles, Shenzhen, driven by the “two engines” of the government and the market, has made swift progress in promotion of its new-energy automobiles. This paper analyses Shenzhen’s governmental promotion policy concerning new-energy automobiles, summarizes Shenzhen’s commercial models for promoting new-energy automobiles, and is expected to provide reference for other provinces and cities to promote new-energy automobiles.

p65 down-regulates DEPTOR expression in response to LPS stimulation in hepatocytes.

PubMed

Yu, Xiaoling; Jin, Dan; Yu, An; Sun, Jun; Chen, Xiaodong; Yang, Zaiqing

2016-09-01

DEPTOR, a novel endogenous inhibitor of mTOR, plays an important role in regulating the inflammatory response in vascular endothelial cells (ECs) and in mouse skeletal muscle. However, the regulatory mechanism of DEPTOR transcription and its effects on liver inflammation are unknown presently. Here we reported the role of DEPTOR in regulating inflammatory response in mouse liver-derived Hepa1-6 cells and in a mouse model with LPS-induced hepatic inflammation. The results revealed that DEPTOR over-expression in Hepa1-6 liver cells increased the mRNA levels of the pro-inflammatory cytokines interleukin-6 (IL-6) and monocyte chemotactic protein-1 (MCP-1). Contrasting results were observed in Hepa1-6 cells with DEPTOR interference. Treatment Hepa1-6 cells with rapamycin, a specific inhibitor of mTORC1, increased MCP-1 mRNA, but have no significant effect on IL-6 mRNA. DEPTOR expression was down-regulated in Hepa1-6 cells with the treatment of inflammatory stimuli LPS or the over-expression of p65/NF-κB, a key inflammatory transcription factor. NF-κB antagonist (PDTC) and inhibitor (IκBα) blocked the effect of LPS on DEPTOR expression. The study in vivo showed that DEPTOR mRNA and protein were significantly reduced in a mouse model with LPS-induced hepatic inflammation, which was accompanied by a concurrent activation of the mTOR signaling pathway. Further, the transcriptional regulation of DEPTOR was explored, which revealed that DEPTOR promoter activity was significantly down-regulated by NF-κB. The progressive deletions and mutations demonstrated that the NF-κB binding motif situated at -145/-127 region is an essential component required for the DEPTOR promoter activity. Chromatin immunoprecipitation (ChIP) assays determined that p65 can directly interact with the DEPTOR promoter DNA. Those results indicate DEPTOR regulates liver inflammation at least partially via mTORC1 pathway, and is down-regulated by LPS through p65. Copyright © 2016 Elsevier B.V. All rights reserved.

CDKL2 promotes epithelial-mesenchymal transition and breast cancer progression

PubMed Central

Li, Linna; Liu, Chunping; Amato, Robert J.; Chang, Jeffrey T.; Du, Guangwei; Li, Wenliang

2014-01-01

The epithelial–mesenchymal transition (EMT) confers mesenchymal properties on epithelial cells and has been closely associated with the acquisition of aggressive traits by epithelial cancer cells. To identify novel regulators of EMT, we carried out cDNA screens that covered 500 human kinases. Subsequent characterization of candidate kinases led us to uncover cyclin-dependent kinase-like 2 (CDKL2) as a novel potent promoter for EMT and breast cancer progression. CDKL2-expressing human mammary gland epithelial cells displayed enhanced mesenchymal traits and stem cell-like phenotypes, which was acquired through activating a ZEB1/E-cadherin/β-catenin positive feedback loop and regulating CD44 mRNA alternative splicing to promote conversion of CD24high cells to CD44high cells. Furthermore, CDKL2 enhanced primary tumor formation and metastasis in a breast cancer xenograft model. Notably, CDKL2 is expressed significantly higher in mesenchymal human breast cancer cell lines than in epithelial lines, and its over-expression/amplification in human breast cancers is associated with shorter disease-free survival. Taken together, our study uncovered a major role for CDKL2 in promoting EMT and breast cancer progression. PMID:25333262

Human papillomavirus 16 E5 oncogene contributes to two stages of skin carcinogenesis.

PubMed

Maufort, John P; Williams, Sybil M Genther; Pitot, Henry C; Lambert, Paul F

2007-07-01

High-risk human papillomaviruses (HPVs), which cause the vast majority of cervical cancer, other anogenital cancers, and a subset of head and neck squamous cell carcinomas, encode three oncogenes: E5, E6, and E7. To determine the oncogenic properties of HPV16 E5 in vivo, we previously generated K14E5 transgenic mice, in which expression of E5 was directed to the basal compartment of stratified squamous epithelia. In these mice, E5 induced epidermal hyperplasia and spontaneous skin tumors. In the current study, we determined how E5 contributes to tumor formation in the skin using a multistage model for skin carcinogenesis that specifies the role of genes in three stages: initiation, promotion, and malignant progression. Both initiation and promotion are required steps for papilloma formation. K14E5 mice treated with the initiating agent 7,12-dimethylbenz(a)anthracene (DMBA) developed more papillomas than like-treated nontransgenic mice, whereas neither K14E5 nor nontransgenic mice treated with the promoting agent 12-O-tetradecanoylphorbol-13-acetate (TPA) developed papillomas. K14E5 mice treated with both DMBA and TPA to induce large numbers of papillomas had a higher incidence and earlier onset of carcinoma progression compared with like-treated nontransgenic mice. Thus, HPV16 E5 contributes to two stages of skin carcinogenesis: promotion and progression. The progressive neoplastic disease in K14E5 mice differed from that in nontransgenic mice in that benign tumors converted from exophytic to endophytic papillomas before progressing to carcinomas. Initial genetic and immunohistopathologic analyses did not determine the underlying basis for this distinct morphology, which correlates with a highly penetrant neoplastic phenotype.

Predicting Outcomes to Optimize Disease Management in Inflammatory Bowel Diseases.

PubMed

Torres, Joana; Caprioli, Flavio; Katsanos, Konstantinos H; Lobatón, Triana; Micic, Dejan; Zerôncio, Marco; Van Assche, Gert; Lee, James C; Lindsay, James O; Rubin, David T; Panaccione, Remo; Colombel, Jean-Frédéric

2016-12-01

Efforts to slow or prevent the progressive course of inflammatory bowel diseases [IBD] include early and intensive monitoring and treatment of patients at higher risk for complications. It is therefore essential to identify high-risk patients - both at diagnosis and throughout disease course. As a part of an IBD Ahead initiative, we conducted a comprehensive literature review to identify predictors of long-term IBD prognosis and generate draft expert summary statements. Statements were refined at national meetings of IBD experts in 32 countries and were finalized at an international meeting in November 2014. Patients with Crohn's disease presenting at a young age or with extensive anatomical involvement, deep ulcerations, ileal/ileocolonic involvement, perianal and/or severe rectal disease or penetrating/stenosing behaviour should be regarded as high risk for complications. Patients with ulcerative colitis presenting at young age, with extensive colitis and frequent flare-ups needing steroids or hospitalization present increased risk for colectomy or future hospitalization. Smoking status, concurrent primary sclerosing cholangitis and concurrent infections may impact the course of disease. Current genetic and serological markers lack accuracy for clinical use. Simple demographic and clinical features can guide the clinician in identifying patients at higher risk for disease complications at diagnosis and throughout disease course. However, many of these risk factors have been identified retrospectively and lack validation. Appropriately powered prospective studies are required to inform algorithms that can truly predict the risk for disease progression in the individual patient. © European Crohn’s and Colitis Organisation 2016.

Identification of surrogate endpoints in patients with locoregionally advanced nasopharyngeal carcinoma receiving neoadjuvant chemotherapy plus concurrent chemoradiotherapy versus concurrent chemoradiotherapy alone.

PubMed

Chen, Yu-Pei; Zhang, Wen-Na; Tang, Ling-Long; Mao, Yan-Ping; Liu, Xu; Chen, Lei; Zhou, Guan-Qun; Mai, Hai-Qiang; Shao, Jian-Yong; Jia, Wei-Hua; Kang, Tie-Bang; Zeng, Mu-Sheng; Sun, Ying; Ma, Jun

2015-11-24

In the era of intensity-modulated radiotherapy (IMRT), the efficacy of additional neoadjuvant chemotherapy (NACT) to concurrent chemoradiotherapy (CCRT) in locoregionally advanced nasopharyngeal carcinoma (NPC) is currently being investigated in ongoing trials. Overall survival (OS) is the gold standard endpoint in NPC trials. We performed this analysis to identify surrogate endpoints for OS, which could shorten follow-up duration and speed up assessment of treatment effects. We retrospectively analysed 208 matched-pair patients with locoregionally advanced NPC receiving NACT+CCRT or CCRT. Progression-free survival (PFS), failure-free survival (FFS), distant failure-free survival (D-FFS) and locoregional failure-free survival (LR-FFS) at 2 and 3 years were assessed as surrogates for 5-year OS according to Prentice's criteria. The strength of the associations were assessed using Spearman's rank correlation coefficient. No significant differences were observed between treatment arms for any surrogate endpoint at 2 years, which rejected Prentice's second criterion. In contrast, 3-year LR-FFS, PFS, FFS and D-FFS were consistent with all four of Prentice's criteria; the rank correlation coefficient (0.730) between 3-year PFS and 5-year OS was highest. 3-year PFS, FFS and D-FFS could be valid surrogate endpoints for 5-year OS; 3-year PFS may be the most accurate.

Induction gemcitabine and oxaliplatin therapy followed by a twice-weekly infusion of gemcitabine and concurrent external-beam radiation for neoadjuvant treatment of locally advanced pancreatic cancer: a single institutional experience.

PubMed

Leone, Francesco; Gatti, Marco; Massucco, Paolo; Colombi, Federica; Sperti, Elisa; Campanella, Delia; Regge, Daniele; Gabriele, Pietro; Capussotti, Lorenzo; Aglietta, Massimo

2013-01-15

Chemoradiotherapy (CRT) may render curative resection feasible in patients with locally advanced pancreatic carcinoma (LAPC). The authors previously demonstrated the achievement of significant disease control and a median survival of 14 months by CRT in patients with LAPC. In this study, they evaluated the use of induction chemotherapy followed by a CRT neoadjuvant protocol. Patients first received induction gemcitabine and oxaliplatin (GEMOX) (gemcitabine 1000 mg/m(2), oxaliplatin 100 mg/m(2)). Patients without disease progression then received gemcitabine twice weekly (50 mg/m(2) daily) concurrent with radiotherapy (50.4 grays) and were re-evaluated for resectability. Thirty-nine patients (15 with borderline resectable disease and 24 with unresectable disease) entered the study. The treatment was well tolerated. Disease control was obtained in 29 of 39 patients. Two patients progressed after GEMOX, and 7 progressed after CRT. After a median follow-up of 13 months, the median progression-free survival (PFS) was 10.2 months. The median PFS of patients with borderline resectable and unresectable disease was 16.6 and 9.1 months, respectively (P = .056). For the whole group, the median overall survival (OS) was 16.7 months (27.8 months for patients with borderline resectable disease, 13.3 for patients with unresectable disease; P = .045). Eleven patients (9 with borderline resectable disease and 2 with unresectable disease at diagnosis) underwent successful resection. Patients who underwent resection had a significantly longer median PFS compared with nonresected patients (19.7 months vs 7.6 months, respectively). The median OS among resected and nonresected patients was 31.5 months and 12.3 months, respectively (P < .001). The current results indicated that induction GEMOX followed by CRT is feasible in patients with LAPC. Both those with borderline resectable disease and those with unresectable disease received clinical benefit, a chance to obtain resectability, and improved survival. The authors concluded that this protocol warrants further evaluation. Copyright © 2012 American Cancer Society.

A Prospective Phase 2 Trial of Reirradiation With Stereotactic Body Radiation Therapy Plus Cetuximab in Patients With Previously Irradiated Recurrent Squamous Cell Carcinoma of the Head and Neck

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

Vargo, John A.; Ferris, Robert L.; Department of Otolaryngology, Head and Neck Surgery, University of Pittsburgh, Pittsburgh, Pennsylvania

Purpose: Salvage options for unresectable locally recurrent, previously irradiated squamous cell carcinoma of the head and neck (rSCCHN) are limited. Although the addition of reirradiation may improve outcomes compared to chemotherapy alone, significant toxicities limit salvage reirradiation strategies, leading to suboptimal outcomes. We therefore designed a phase 2 protocol to evaluate the efficacy of stereotactic body radiation therapy (SBRT) plus cetuximab for rSCCHN. Methods and Materials: From July 2007 to March 2013, 50 patients >18 years of age with inoperable locoregionally confined rSCCHN within a previously irradiated field receiving ≥60 Gy, with a Zubrod performance status of 0 to 2, and normalmore » hepatic and renal function were enrolled. Patients received concurrent cetuximab (400 mg/m{sup 2} on day −7 and then 250 mg/m{sup 2} on days 0 and +8) plus SBRT (40-44 Gy in 5 fractions on alternating days over 1-2 weeks). Primary endpoints were 1-year locoregional progression-free survival and National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 graded toxicity. Results: Median follow-up for surviving patients was 18 months (range: 10-70). The 1-year local PFS rate was 60% (95% confidence interval [CI]: 44%-75%), locoregional PFS was 37% (95% CI: 23%-53%), distant PFS was 71% (95% CI: 54%-85%), and PFS was 33% (95% CI: 20%-49%). The median overall survival was 10 months (95% CI: 7-16), with a 1-year overall survival of 40% (95% CI: 26%-54%). At last follow-up, 69% died of disease, 4% died with disease, 15% died without progression, 10% were alive without progression, and 2% were alive with progression. Acute and late grade 3 toxicity was observed in 6% of patients respectively. Conclusions: SBRT with concurrent cetuximab appears to be a safe salvage treatment for rSCCHN of short overall treatment time.« less

Oral kanglaite injection (KLTI) attenuates the lung cancer-promoting effect of high-fat diet (HFD)-induced obesity.

PubMed

Cao, Ning; Ma, Xiaofang; Guo, Zhenzhen; Zheng, Yaqiu; Geng, Shengnan; Meng, Mingjing; Du, Zhenhua; Lin, Haihong; Duan, Yongjian; Du, Gangjun

2016-09-20

Obesity is a risk factor for cancer and cancer-related mortality, however, its role in lung cancer progression remains controversial. This study aimed to assess whether high-fat diet (HFD)-induced obesity promotes lung cancer progression and whether the promotion can be decreased by Kanglaite injection (KLTI). In vivo, HFD-induced overweight or obesity increases the lung carcinoma incidence and multiplicity in a urethane-induced lung carcinogenic model and cancer-related mortality in a LLC allograft model by increasing oxidative stress and cellular signaling molecules including JAK, STAT3, Akt, mTOR, NF-κB and cyclin D1. These changes resulted in increases in vascular disruption and the lung water content, thereby promoting lung epithelial proliferation and the epithelial-mesenchymal transition (EMT) during carcinogenesis. Chronic KLTI treatment substantially prevented the weight gain resulting from HFD consumption, thereby reversing the metabolic dysfunction-related physiological changes and reducing susceptibility to lung carcinogenesis. In vitro, KLTI significantly suppressed the proliferation and induced apoptosis and differentiation in 3T3-L1 preadipocyte cells and attenuated endothelial cell permeability in HUVECs. Our study indicates that there is a potential relationship between obesity and lung cancer. This is the first study to show that obesity can directly accelerate carcinogen-induced lung cancer progression and that KLTI can decrease the lung cancer-promoting effect of HFD-induced obesity.

Gastric cancer-derived MSC-secreted PDGF-DD promotes gastric cancer progression.

PubMed

Huang, Feng; Wang, Mei; Yang, Tingting; Cai, Jie; Zhang, Qiang; Sun, Zixuan; Wu, Xiaodan; Zhang, Xu; Zhu, Wei; Qian, Hui; Xu, Wenrong

2014-11-01

This study was designed to investigate the role of PDGF-DD secreted by gastric cancer-derived mesenchymal stem cells (GC-MSCs) in human gastric cancer progression. Gastric cancer cells were indirectly co-cultured with GC-MSCs in a transwell system. The growth and migration of gastric cancer cells were evaluated by cell colony formation assay and transwell migration assay, respectively. The production of PDGF-DD in GC-MSCs was determined by using Luminex and ELISA. Neutralization of PDGFR-β by su16f and siRNA interference of PDGF-DD in GC-MSCs was used to demonstrate the role of PDGF-DD produced by GC-MSCs in gastric cancer progression. GC-MSC conditioned medium promoted gastric cancer cell proliferation and migration in vitro and in vivo. Co-culture with GC-MSCs increased the phosphorylation of PDGFR-β in SGC-7901 cells. Neutralization of PDGFR-β by su16f blocked the promoting role of GC-MSC conditioned medium in gastric cancer cell proliferation and migration. Recombinant PDGF-DD duplicated the effects of GC-MSC conditioned medium on gastric cancer cells. Knockdown of PDGF-DD in GC-MSCs abolished its effects on gastric cancer cells in vitro and in vivo. PDGF-DD secreted by GC-MSCs is capable of promoting gastric cancer cell progression in vitro and in vivo. Targeting the PDGF-DD/PDGFR-β interaction between MSCs and gastric cancer cells may represent a novel strategy for gastric cancer therapy.

Temporal Associations Between Social Activity and Mood, Fatigue, and Pain in Older Adults With HIV: An Ecological Momentary Assessment Study.

PubMed

Paolillo, Emily W; Tang, Bin; Depp, Colin A; Rooney, Alexandra S; Vaida, Florin; Kaufmann, Christopher N; Mausbach, Brent T; Moore, David J; Moore, Raeanne C

2018-05-14

Social isolation is associated with an increased risk for mental and physical health problems, especially among older persons living with HIV (PLWH). Thus, there is a need to better understand real-time temporal associations between social activity and mood- and health-related factors in this population to inform possible future interventions. This study aims to examine real-time relationships between social activity and mood, fatigue, and pain in a sample of older PLWH. A total of 20 older PLWH, recruited from the University of California, San Diego HIV Neurobehavioral Research Program in 2016, completed smartphone-based ecological momentary assessment (EMA) surveys 5 times per day for 1 week. Participants reported their current social activity (alone vs not alone and number of social interactions) and levels of mood (sadness, happiness, and stress), fatigue, and pain. Mixed-effects regression models were used to analyze concurrent and lagged associations among social activity, mood, fatigue, and pain. Participants (mean age 58.8, SD 4.3 years) reported being alone 63% of the time, on average, (SD 31.5%) during waking hours. Being alone was related to lower concurrent happiness (beta=-.300; 95% CI -.525 to -.079; P=.008). In lagged analyses, social activity predicted higher levels of fatigue later in the day (beta=-1.089; 95% CI -1.780 to -0.396; P=.002), and higher pain levels predicted being alone in the morning with a reduced likelihood of being alone as the day progressed (odds ratio 0.945, 95% CI 0.901-0.992; P=.02). The use of EMA elucidated a high rate of time spent alone among older PLWH. Promoting social activity despite the presence of pain or fatigue may improve happiness and psychological well-being in this population. ©Emily W Paolillo, Bin Tang, Colin A Depp, Alexandra S Rooney, Florin Vaida, Christopher N Kaufmann, Brent T Mausbach, David J Moore, Raeanne C Moore. Originally published in JMIR Mental Health (http://mental.jmir.org), 14.05.2018.

Reinforcement of smoking and drinking: tobacco marketing strategies linked with alcohol in the United States.

PubMed

Jiang, Nan; Ling, Pamela M

2011-10-01

We investigated tobacco companies' knowledge about concurrent use of tobacco and alcohol, their marketing strategies linking cigarettes with alcohol, and the benefits tobacco companies sought from these marketing activities. We performed systematic searches on previously secret tobacco industry documents, and we summarized the themes and contexts of relevant search results. Tobacco company research confirmed the association between tobacco use and alcohol use. Tobacco companies explored promotional strategies linking cigarettes and alcohol, such as jointly sponsoring special events with alcohol companies to lower the cost of sponsorships, increase consumer appeal, reinforce brand identity, and generate increased cigarette sales. They also pursued promotions that tied cigarette sales to alcohol purchases, and cigarette promotional events frequently featured alcohol discounts or encouraged alcohol use. Tobacco companies' numerous marketing strategies linking cigarettes with alcohol may have reinforced the use of both substances. Because using tobacco and alcohol together makes it harder to quit smoking, policies prohibiting tobacco sales and promotion in establishments where alcohol is served and sold might mitigate this effect. Smoking cessation programs should address the effect that alcohol consumption has on tobacco use.

Alternative promoter usage generates novel shorter MAPT mRNA transcripts in Alzheimer's disease and progressive supranuclear palsy brains.

PubMed

Huin, Vincent; Buée, Luc; Behal, Hélène; Labreuche, Julien; Sablonnière, Bernard; Dhaenens, Claire-Marie

2017-10-03

Alternative promoter usage is an important mechanism for transcriptome diversity and the regulation of gene expression. Indeed, this alternative usage may influence tissue/subcellular specificity, protein translation and function of the proteins. The existence of an alternative promoter for MAPT gene was considered for a long time to explain differential tissue specificity and differential response to transcription and growth factors between mRNA transcripts. The alternative promoter usage could explain partly the different tau proteins expression patterns observed in tauopathies. Here, we report on our discovery of a functional alternative promoter for MAPT, located upstream of the gene's second exon (exon 1). By analyzing genome databases and brain tissue from control individuals and patients with Alzheimer's disease or progressive supranuclear palsy, we identified novel shorter transcripts derived from this alternative promoter. These transcripts are increased in patients' brain tissue as assessed by 5'RACE-PCR and qPCR. We suggest that these new MAPT isoforms can be translated into normal or amino-terminal-truncated tau proteins. We further suggest that activation of MAPT's alternative promoter under pathological conditions leads to the production of truncated proteins, changes in protein localization and function, and thus neurodegeneration.

Campaign To Reduce Child Poverty. Progress Report [and] Policy Briefs 1-5.

ERIC Educational Resources Information Center

New Mexico Advocates for Children & Families, Albuquerque.

This document is comprised of a progress report and five policy briefs related to the New Mexico Advocates for Children and Families' Campaign To Reduce Child Poverty. This multi-year initiative educates the public and policymakers about child poverty and promotes public policy changes that would reduce poverty. The progress report presents…

Army National Guard and U.S. Army Reserve: Promotion of Commissioned Officers and Warrant Officers Other Than General Officers

DTIC Science & Technology

2001-10-24

Notification of Selection for Promotion—Officers Assigned to Control Group (Dual Component), page 57 Figure 4–15: Memorandum Format for Notification of... Group Standby Reserve (Active Status List) officers. (3) USAR officers released from AD in the grade of COL and below, and not under the jurisdiction...Control Group (Officer Active Duty Obligor) (OADO) or under administrative control of the Control Group (OADO) with concurrent assignment to a Reserve

Report of the third session of the West African Monsoon Experiment (WAMEX) scientific regional committee

NASA Astrophysics Data System (ADS)

After completion of the field phase of WAMEX, operations were assessed, further planning of data management activities was reviewed, and plans for the research and evaluation phase were coordinated. The WAMEX project was conducted concurrently with the first GARP Global Experiment. Impending data collection and processing activities are stressed in plans to promote the timely and complete analysis of the present situation. The advantages to be gained through international cooperation among scientists are emphasized.

Examine How Botswana Defense Force in Concurrence with Other Instruments of National Power, Promote Botwana’s National Interests in a Multifarious International Security Environment Regionally

DTIC Science & Technology

2016-06-10

national objectives that will be pursued through the implementation of the NSS. It is now prudent to focus arguments on the NDS. Formulating the...interests through foreign policy development ) in the region and abroad. 83 The fundamental purpose of Botswana’s NSS is principally based on a...notion. This will also be shown in subsequent arguments when discussing the Foreign Policy; Formulation and Implementation Model . But it is equally

Intramolecular Redox-Mannich Reactions: Facile Access to the Tetrahydroprotoberberine Core.

PubMed

Ma, Longle; Seidel, Daniel

2015-09-07

Cyclic amines such as pyrrolidine undergo redox-annulations with 2-formylaryl malonates. Concurrent oxidative amine α-CH bond functionalization and reductive N-alkylation render this transformation redox-neutral. This redox-Mannich process provides regioisomers of classic Reinhoudt reaction products as an entry to the tetrahydroprotoberberine core, enabling the synthesis of (±)-thalictricavine and its epimer. An unusually mild amine-promoted dealkoxycarbonylation was discovered in the course of these studies. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Content and concurrent validity of the motivation for change questionnaire.

PubMed

Grahn, Birgitta; Gard, Gunvor

2008-03-01

Musculoskeletal disorders (MSD) are nowadays seen within a biopsychosocial framework, including salutogenic factors, motivation factors, and coping ability. Such a framework recognizes the importance of motivational factors in health promotion and in rehabilitation. The Motivation for Change Questionnaire (MCQ) has been developed to measure the strength of individuals' motivation for change in life, MCQ part 1, and work situation, MCQ part 2. The purpose of the study was to test the content and concurrent validity of the MCQ on patients with prolonged musculoskeletal disorders referred to interdisciplinary rehabilitation as a basis for use in medical and occupational rehabilitation. Content validity was studied among an expert group of 20 rehabilitation professionals at a rehabilitation centre, and with 10 individuals suffering from prolonged MSD in the south of Sweden. The experts evaluated the clinical relevance of each question in MCQ. Concurrent validity was studied on 58 patients with prolonged MSD at an interdisciplinary rehabilitation centre in the south of Sweden. They answered MCQ, QPS Nordic questionnaire, KASAM and the Action theory questionnaire. Spearman's rank correlation coefficient was used in the analyses. The MCQ covered and measured areas of relevance according to content validity. No floor effects in any of the subscales of MCQ part 1 were seen. In MCQ part 2, floor effects were seen in two sub indexes. As for concurrent validity subscales of MCQ correlated significantly with QPS Nordic questionnaire and KASAM. Findings so far indicate the instrument to be valid for use within the present patient group. The questionnaire can be used to identify patient's motivating factors for change in life and work, as a basis for motivational work within rehabilitation.

Combined Diet and Physical Activity Promotion Programs for Prevention of Diabetes: Community Preventive Services Task Force Recommendation Statement.

PubMed

Pronk, Nicolaas P; Remington, Patrick L

2015-09-15

Community Preventive Services Task Force recommendation on the use of combined diet and physical activity promotion programs to reduce progression to type 2 diabetes in persons at increased risk. The Task Force commissioned an evidence review that assessed the benefits and harms of programs to promote and support individual improvements in diet, exercise, and weight and supervised a review on the economic efficiency of these programs in clinical trial, primary care, and primary care-referable settings. Adolescents and adults at increased risk for progression to type 2 diabetes. The Task Force recommends the use of combined diet and physical activity promotion programs by health care systems, communities, and other implementers to provide counseling and support to clients identified as being at increased risk for type 2 diabetes. Economic evidence indicates that these programs are cost-effective.

Research on Data Mining of the Internet of Things Based on Cloud Computing Platform

NASA Astrophysics Data System (ADS)

Zhang, Wenqing

2018-02-01

Based on the development of society and the progress of information technology, China’s information industry has made great progress and has gradually become an important pillar of national economic development. In this context, the gradual integration of information technology had promoted the construction of the Internet of Things system, so as to promote the human life developed in the direction of modernization intelligently. At present, in the process of forming the development of the Internet of Things the first need to fully tap the data, which thus provide users with better service, for the development of large-scale development of the Internet. This paper analyzes the meaning of Internet of things, and discusses the characteristics of Internet of things and data mining, hoping to promote the improvement on the Internet of Things system in China, and thus promote the realization of higher efficiency.

Concurrent Overexpression of Arabidopsis thaliana Cystathionine γ-Synthase and Silencing of Endogenous Methionine γ-Lyase Enhance Tuber Methionine Content in Solanum tuberosum.

PubMed

Kumar, Pavan; Jander, Georg

2017-04-05

Potatoes (Solanum tuberosum) are deficient in methionine, an essential amino acid in human and animal diets. Higher methionine levels increase the nutritional quality and promote the typically pleasant aroma associated with baked and fried potatoes. Several attempts have been made to elevate tuber methionine levels by genetic engineering of methionine biosynthesis and catabolism. Overexpressing Arabidopsis thaliana cystathionine γ-synthase (AtCGS) in S. tuberosum up-regulates a rate-limiting step of methionine biosynthesis and increases tuber methionine levels. Alternatively, silencing S. tuberosum methionine γ-lyase (StMGL), which causes decreased degradation of methionine into 2-ketobutyrate, also increases methionine levels. Concurrently enhancing biosynthesis and reducing degradation were predicted to provide further increases in tuber methionine content. Here we report that S. tuberosum cv. Désirée plants with AtCGS overexpression and StMGL silenced by RNA interference are morphologically normal and accumulate higher free methionine levels than either single-transgenic line.

Synthetic cascades are enabled by combining biocatalysts with artificial metalloenzymes

NASA Astrophysics Data System (ADS)

Köhler, V.; Wilson, Y. M.; Dürrenberger, M.; Ghislieri, D.; Churakova, E.; Quinto, T.; Knörr, L.; Häussinger, D.; Hollmann, F.; Turner, N. J.; Ward, T. R.

2013-02-01

Enzymatic catalysis and homogeneous catalysis offer complementary means to address synthetic challenges, both in chemistry and in biology. Despite its attractiveness, the implementation of concurrent cascade reactions that combine an organometallic catalyst with an enzyme has proven challenging because of the mutual inactivation of both catalysts. To address this, we show that incorporation of a d6-piano stool complex within a host protein affords an artificial transfer hydrogenase (ATHase) that is fully compatible with and complementary to natural enzymes, thus enabling efficient concurrent tandem catalysis. To illustrate the generality of the approach, the ATHase was combined with various NADH-, FAD- and haem-dependent enzymes, resulting in orthogonal redox cascades. Up to three enzymes were integrated in the cascade and combined with the ATHase with a view to achieving (i) a double stereoselective amine deracemization, (ii) a horseradish peroxidase-coupled readout of the transfer hydrogenase activity towards its genetic optimization, (iii) the formation of L-pipecolic acid from L-lysine and (iv) regeneration of NADH to promote a monooxygenase-catalysed oxyfunctionalization reaction.

Substance use disorders, anorexia, bulimia, and concurrent disorders.

PubMed

Courbasson, Christine M A; Smith, Patrick D; Cleland, Patricia A

2005-01-01

While the co-prevalence of eating disorders (ED) has been documented in individuals with substance use disorders (SUD), little is known about the co-occurrence of other disorders in this population. Examining this issue is critical for public health policy and treatment success. To identify and evaluate the co-occurrence of ED and other psychiatric disorders in men and women with SUD. The sample consisted of individuals seeking treatment for substance use. Semi-structured interviews and the CAMH Concurrent Disorders Screener were completed to assess DSM-IV psychopathology. Chi-square analyses suggested that more women scored positive for ED than men, EDs were more prevalent in both genders than in the general population, and the co-occurrence of other disorders was higher for clients with both SUD and ED than with SUD. Individuals with both SUD and ED appear to have multiple needs that may not be readily assessed by existing addiction treatment programs. Assessment issues, treatment, potential prevention and health promotion implications are addressed.

[Concepts of development of the neurosurgical operative environment in the 21st century].

PubMed

Apuzzo, M; Liu, C

2002-01-01

The operative environment has to a large extent defines the "state of the art and science" of neurosurgery, which is now undergoing rapid reinvention. In order to remain current, each neurosurgeon should periodically reconsider their personal operative environment and its functional design with reference to modernity of practice as currently defined. Historical trends and their analysis offer predictive guides for development of such settings with an eye toward the future. Examination of technical developments in decade timeframes defines the progress in capability and need. Progressive minimalism of manipulation and the presence of operative definition with increasing precision are evident, with concurrent miniaturization of attendant computerized support systems, sensors, robotic interfaces, and imaging devices. These trends and developments offer the opportunity for simplificity of setting design with higher functionality as the desired endpoint.

Manganese intoxication: the cause of an inexplicable epileptic syndrome in a 3 year old child.

PubMed

Herrero Hernandez, Elena; Discalzi, Gianluigi; Dassi, Patrizia; Jarre, Laura; Pira, Enrico

2003-08-01

Excess manganese (Mn) can cause several neurotoxic effects, however only a few studies have reported epileptic syndromes related to manganese intoxication. We describe an epileptic syndrome due to manganese intoxication in a 3 year old male child. His blood manganese was elevated, but no other abnormal values or toxic substances were found in blood or urine. The electroencephalogram (EEG) showed a picture of progressive encephalopathy, while brain magnetic resonance was normal. The patient's conditions rapidly worsened to epileptic status despite the use of antiepileptic drugs. Chelating treatment with CaNa(2)EDTA was initiated to remove excess manganese and promptly succeeded in reverting epileptic symptoms. Concurrently, manganese blood levels and electroencephalogram progressively normalized. Thereafter it has been possible to discontinue antiepileptic treatment, and the patient remains in excellent conditions without any treatment.

From Scribbles to Scrabble: Preschool Children’s Developing Knowledge of Written Language

PubMed Central

Puranik, Cynthia S.; Lonigan, Christopher J.

2011-01-01

The purpose of this study was to concurrently examine the development of written language across several writing tasks and to investigate how writing features develop in preschool children. Emergent written language knowledge of 372 preschoolers was assessed using numerous writing tasks. The findings from this study indicate that children possess a great deal of writing knowledge before beginning school. Children appear to progress along a continuum from scribbling to conventional spelling, and this progression is linear and task dependent. There was clear evidence to support the claim that universal writing features develop before language-specific features. Children as young as 3 years possess knowledge regarding universal and language-specific writing features. There is substantial developmental continuity in literacy skills from the preschool period into early elementary grades. Implications of these findings on writing development are discussed. PMID:22448101

Targeting gene expression selectively in cancer cells by using the progression-elevated gene-3 promoter.

PubMed

Su, Zhao-Zhong; Sarkar, Devanand; Emdad, Luni; Duigou, Gregory J; Young, Charles S H; Ware, Joy; Randolph, Aaron; Valerie, Kristoffer; Fisher, Paul B

2005-01-25

One impediment to effective cancer-specific gene therapy is the rarity of regulatory sequences targeting gene expression selectively in tumor cells. Although many tissue-specific promoters are recognized, few cancer-selective gene promoters are available. Progression-elevated gene-3 (PEG-3) is a rodent gene identified by subtraction hybridization that displays elevated expression as a function of transformation by diversely acting oncogenes, DNA damage, and cancer cell progression. The promoter of PEG-3, PEG-Prom, displays robust expression in a broad spectrum of human cancer cell lines with marginal expression in normal cellular counterparts. Whereas GFP expression, when under the control of a CMV promoter, is detected in both normal and cancer cells, when GFP is expressed under the control of the PEG-Prom, cancer-selective expression is evident. Mutational analysis identifies the AP-1 and PEA-3 transcription factors as primary mediators of selective, cancer-specific expression of the PEG-Prom. Synthesis of apoptosis-inducing genes, under the control of the CMV promoter, inhibits the growth of both normal and cancer cells, whereas PEG-Prom-mediated expression of these genes kills only cancer cells and spares normal cells. The efficacy of the PEG-Prom as part of a cancer gene therapeutic regimen is further documented by in vivo experiments in which PEG-Prom-controlled expression of an apoptosis-inducing gene completely inhibited prostate cancer xenograft growth in nude mice. These compelling observations indicate that the PEG-Prom, with its cancer-specific expression, provides a means of selectively delivering genes to cancer cells, thereby providing a crucial component in developing effective cancer gene therapies.

Chronic alcohol intake promotes tumor growth in a diethylnitrosamine-induced hepatocarcinogenesis mouse model through increased Wnt/Beta-catenin signaling

USDA-ARS?s Scientific Manuscript database

Ethanol (EtOH) metabolism is involved in both initiating and promoting mechanisms in hepatocellular carcinoma progression in chronic alcoholics. In this study, we developed a mouse model to test the hypothesis that chronic EtOH consumption promotes tumor growth irrespective of EtOH-related initiati...

Nonrandomized Trial of Feasibility and Acceptability of Strategies for Promotion of Soapy Water as a Handwashing Agent in Rural Bangladesh.

PubMed

Ashraf, Sania; Nizame, Fosiul A; Islam, Mahfuza; Dutta, Notan C; Yeasmin, Dalia; Akhter, Sadika; Abedin, Jaynal; Winch, Peter J; Ram, Pavani K; Unicomb, Leanne; Leontsini, Elli; Luby, Stephen P

2017-02-08

We conducted a nonrandomized trial of strategies to promote soapy water for handwashing in rural Bangladesh and measured uptake. We enrolled households with children < 3 years for three progressively intensive study arms: promotion of soapy water ( N = 120), soapy water promotion plus handwashing stations ( N = 103), and soapy water promotion, stations plus detergent refills ( N = 90); we also enrolled control households ( N = 72). Our handwashing stations included tap-fitted buckets and soapy water bottles. Community promoters visited households and held community meetings to demonstrate soapy water preparation and promote handwashing at key times. Field workers measured uptake 4 months later. In-depth interviews and focus group discussions assessed factors associated with uptake. More households had soapy water at the handwashing place in progressively intensive arms: 18% (promotion), 60% (promotion plus station), and 71% (promotion, station with refills). Compared with the promotion-only arm, more households that received stations had soapy water at the primary handwashing station (44%, P ≤ 0.001; 71%, P < 0.001 with station plus detergent refill). Qualitative findings highlighted several dimensions that affected use: contextual (shared courtyard), psychosocial (perceived value), and technology dimensions (ease of use, convenience). Soapy water may increase habitual handwashing by addressing barriers of cost and availability of handwashing agents near water sources. Further research should inform optimal strategies to scale-up soapy water as a handwashing agent to study health impact. © The American Society of Tropical Medicine and Hygiene.

Nonrandomized Trial of Feasibility and Acceptability of Strategies for Promotion of Soapy Water as a Handwashing Agent in Rural Bangladesh

PubMed Central

Ashraf, Sania; Nizame, Fosiul A.; Islam, Mahfuza; Dutta, Notan C.; Yeasmin, Dalia; Akhter, Sadika; Abedin, Jaynal; Winch, Peter J.; Ram, Pavani K.; Unicomb, Leanne; Leontsini, Elli; Luby, Stephen P.

2017-01-01

We conducted a nonrandomized trial of strategies to promote soapy water for handwashing in rural Bangladesh and measured uptake. We enrolled households with children < 3 years for three progressively intensive study arms: promotion of soapy water (N = 120), soapy water promotion plus handwashing stations (N = 103), and soapy water promotion, stations plus detergent refills (N = 90); we also enrolled control households (N = 72). Our handwashing stations included tap-fitted buckets and soapy water bottles. Community promoters visited households and held community meetings to demonstrate soapy water preparation and promote handwashing at key times. Field workers measured uptake 4 months later. In-depth interviews and focus group discussions assessed factors associated with uptake. More households had soapy water at the handwashing place in progressively intensive arms: 18% (promotion), 60% (promotion plus station), and 71% (promotion, station with refills). Compared with the promotion-only arm, more households that received stations had soapy water at the primary handwashing station (44%, P ≤ 0.001; 71%, P < 0.001 with station plus detergent refill). Qualitative findings highlighted several dimensions that affected use: contextual (shared courtyard), psychosocial (perceived value), and technology dimensions (ease of use, convenience). Soapy water may increase habitual handwashing by addressing barriers of cost and availability of handwashing agents near water sources. Further research should inform optimal strategies to scale-up soapy water as a handwashing agent to study health impact. PMID:28025233

Promoting excellence in care.

PubMed

2004-07-01

Welcome to Nurse Researcher. This year's annual RCN International Nursing Research Conference was held recently in Cambridge, UK. The event, which attracted over 500 delegates from a range of diverse and academic settings across the world, brought together nurses and other healthcare professionals to promote and develop nursing knowledge. Over 200 papers and poster presentations covered a wide range of topics in nursing and healthcare research, including: issues in research methodology; education; theoretical perspectives; transcultural nursing; evidence-based practice; employment issues; and research governance. In addition to concurrent sessions and posters, many symposia, workshops and other fringe and networking events offered opportunities for sharing good practice and research collaboration. Next year's conference will be held in Belfast, Northern Ireland, UK from Tuesday 8 to Friday 11 March 2005. For more information visit: www.man.ac.uk/rcn/research2005.

The Kidney in Aging: Physiological Changes and Pathological Implications.

PubMed

Sobamowo, H; Prabhakar, S S

2017-01-01

Aging is associated with progressive decline in renal function along with concurrent morphological changes that ultimately lead to glomerulosclerosis. The mechanisms leading to such changes in the kidney with age as well as the basis of controversies that surround the physiological basis vs pathological nature of aging kidney are the focus of this in-depth review. In addition, the renal functional defects of acid-base homeostasis and electrolyte disturbances in elderly and the physiological basis of such disorders are also discussed. © 2017 Elsevier Inc. All rights reserved.

Parenting Predictors of Cognitive Skills and Emotion Knowledge in Socioeconomically Disadvantaged Preschoolers

PubMed Central

Merz, Emily C.; Zucker, Tricia A.; Landry, Susan H.; Williams, Jeffrey M.; Assel, Michael; Taylor, Heather B.; Lonigan, Christopher J.; Phillips, Beth M.; Clancy-Menchetti, Jeanine; Barnes, Marcia A.; Eisenberg, Nancy; de Villiers, Jill

2014-01-01

This study examined the concurrent and longitudinal associations of parental responsiveness and inferential language input with cognitive skills and emotion knowledge among socioeconomically disadvantaged preschoolers. Parents and 2- to 4-year-old children (mean age = 3.21 years; N=284) participated in a parent-child free play session, and children completed cognitive (language, early literacy, early mathematics) and emotion knowledge assessments. One year later, children completed the same assessment battery. Parental responsiveness was coded from the videotaped parent-child free play sessions, and parental inferential language input was coded from transcripts of a subset of 127 of these sessions. All analyses controlled for child age, gender, and parental education, and longitudinal analyses controlled for initial skill level. Parental responsiveness significantly predicted all concurrent cognitive skills as well as literacy, math, and emotion knowledge one year later. Parental inferential language input was significantly positively associated with children's concurrent emotion knowledge. In longitudinal analyses, an interaction was found such that for children with stronger initial language skills, higher levels of parental inferential language input facilitated greater vocabulary development, whereas for children with weaker initial language skills, there was no association between parental inferential language input and change in children's vocabulary skills. These findings further our understanding of the roles of parental responsiveness and inferential language input in promoting children's school readiness skills. PMID:25576967

Induction chemotherapy selects patients with locally advanced, unresectable pancreatic cancer for optimal benefit from consolidative chemoradiation therapy.

PubMed

Krishnan, Sunil; Rana, Vishal; Janjan, Nora A; Varadhachary, Gauri R; Abbruzzese, James L; Das, Prajnan; Delclos, Marc E; Gould, Morris S; Evans, Douglas B; Wolff, Robert A; Crane, Christopher H

2007-07-01

The current study was conducted to determine whether there were differences in outcome for patients with unresectable locally advanced pancreatic cancer (LAPC) who received treatment with chemoradiation therapy (CR) versus induction chemotherapy followed by CR (CCR). Between December 1993 and July 2005, 323 consecutive patients with LAPC were treated at the authors' institution with radiotherapy and concurrent gemcitabine or fluoropyrimidine chemotherapy. Two hundred forty-seven patients received CR as initial treatment, and 76 patients received a median of 2.5 months of gemcitabine-based induction chemotherapy prior to CR. Most patients received a radiation dose of 30 grays in 10 fractions (85%) concurrently with infusional 5-fluorouracil (41%), gemcitabine (39%), or capecitabine (20%). The median follow-up was 5.5 months (range, 1-63 months). For all patients, the median overall survival (OS) and progression-free survival (PFS) were 9 months and 5 months, respectively, and the 2-year estimated OS and PFS rates were 9% and 5%, respectively. The median OS and PFS were 8.5 months and 4.2 months, respectively, in the CR group and 11.9 months and 6.4 months, respectively, in the CCR group (both P < .001). The median times to local and distant progression were 6.0 months and 5.6 months, respectively, in the CR group and 8.9 and 9.5 months, respectively, in the CCR group (P = .003 and P = .007, respectively). There was no significant difference in the patterns of failure with the use of induction chemotherapy. The results from this analysis indicated that, by excluding patients with rapid distant progression, induction chemotherapy may select patients with LAPC for optimal benefit from consolidative CR. The authors believe that this strategy of enriching the population of patients who receive a locoregional treatment modality merits prospective randomized evaluation. Copyright (c) 2007 American Cancer Society.

Early diagnostic of concurrent gear degradation processes progressing under time-varying loads

NASA Astrophysics Data System (ADS)

Guilbault, Raynald; Lalonde, Sébastien

2016-08-01

This study develops a gear diagnostic procedure for the detection of multi- and concurrent degradation processes evolving under time-varying loads. Instead of a conventional comparison between a descriptor and an alarm level, this procedure bases its detection strategy on a descriptor evolution tracking; a lasting descriptor increase denotes the presence of ongoing degradation mechanisms. The procedure works from time domain residual signals prepared in the frequency domain, and accepts any gear conditions as reference signature. To extract the load fluctuation repercussions, the procedure integrates a scaling factor. The investigation first examines a simplification assuming a linear connection between the load and the dynamic response amplitudes. However, while generally valuable, the precision losses associated with large load variations may mask the contribution of tiny flaws. To better reflect the real non-linear relation, the paper reformulates the scaling factor; a power law with an exponent value of 0.85 produces noticeable improvements of the load effect extraction. To reduce the consequences of remaining oscillations, the procedure also includes a filtering phase. During the validation program, a synthetic wear progression assuming a commensurate relation between the wear depth and friction assured controlled evolutions of the surface degradation influence, whereas the fillet crack growth remained entirely determined by the operation conditions. Globally, the tested conditions attest that the final strategy provides accurate monitoring of coexisting isolated damages and general surface deterioration, and that its tracking-detection capacities are unaffected by severe time variations of external loads. The procedure promptly detects the presence of evolving abnormal phenomena. The tests show that the descriptor curve shapes virtually describe the constant wear progression superimposed on the crack length evolution. At the tooth fracture, the mean values of the residual signal evince strong perturbations, while after this episode, the monitoring curves continue signaling the ongoing wear process.

Phase II randomized trial of radiation therapy, cetuximab, and pemetrexed with or without bevacizumab in patients with locally advanced head and neck cancer.

PubMed

Argiris, A; Bauman, J E; Ohr, J; Gooding, W E; Heron, D E; Duvvuri, U; Kubicek, G J; Posluszny, D M; Vassilakopoulou, M; Kim, S; Grandis, J R; Johnson, J T; Gibson, M K; Clump, D A; Flaherty, J T; Chiosea, S I; Branstetter, B; Ferris, R L

2016-08-01

We previously reported the safety of concurrent cetuximab, an antibody against epidermal growth factor receptor (EGFR), pemetrexed, and radiation therapy (RT) in patients with locally advanced squamous cell carcinoma of the head and neck (SCCHN). In this non-comparative phase II randomized trial, we evaluated this non-platinum combination with or without bevacizumab, an inhibitor of vascular endothelial growth factor (VEGF). Patients with previously untreated stage III-IVB SCCHN were randomized to receive: conventionally fractionated radiation (70 Gy), concurrent cetuximab, and concurrent pemetrexed (arm A); or the identical regimen plus concurrent bevacizumab followed by bevacizumab maintenance for 24 weeks (arm B). The primary end point was 2-year progression-free survival (PFS), with each arm compared with historical control. Exploratory analyses included the relationship of established prognostic factors to PFS and quality of life (QoL). Seventy-eight patients were randomized: 66 oropharynx (42 HPV-positive, 15 HPV-negative, 9 unknown) and 12 larynx; 38 (49%) had heavy tobacco exposure. Two-year PFS was 79% [90% confidence interval (CI) 0.69-0.92; P < 0.0001] for arm A and 75% (90% CI 0.64-0.88; P < 0.0001) for arm B, both higher than historical control. No differences in PFS were observed for stage, tobacco history, HPV status, or type of center (community versus academic). A significantly increased rate of hemorrhage occurred in arm B. SCCHN-specific QoL declined acutely, with marked improvement but residual symptom burden 1 year post-treatment. RT with a concurrent non-platinum regimen of cetuximab and pemetrexed is feasible in academic and community settings, demonstrating expected toxicities and promising efficacy. Adding bevacizumab increased toxicity without apparent improvement in efficacy, countering the hypothesis that dual EGFR-VEGF targeting would overcome radiation resistance, and enhance clinical benefit. Further development of cetuximab, pemetrexed, and RT will require additional prospective study in defined, high-risk populations where treatment intensification is justified. © The Author 2016. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

Septic arthritis associated with systemic sepsis.

PubMed

Jung, Sung-Weon; Kim, Dong-Hee; Shin, Sung-Jin; Kang, Byoung-Youl; Eho, Yil-Ju; Yang, Seong-Wook

2018-01-01

Septic arthritis presents with good joint function, but sometimes leads to poor outcomes. Concurrent systemic sepsis has been regarded as the poor outcome, and the exact cause remains unclear. This paper was performed to identify factors associated with concurrent systemic sepsis and to research results to predict poor outcomes in patients with septic arthritis. Laboratory and medical data were reviewed for 137 adults with acute septic arthritis who underwent open or arthroscopic surgical debridement at our institution between January 2005 and December 2014. The patients were divided according to whether they had septic arthritis alone (Group A) or in combination with systemic sepsis (Group B). Systemic sepsis was defined as two more systemic inflammatory signs in response to an infectious process. Patient characteristics, laboratory findings, synovial fluid findings and cultures, and surgical results were compared between two groups. Of the 137 patients, 41 (29.9%) had initial systemic sepsis at the diagnosis of septic arthritis. Independent t test revealed that duration of prodromal symptom (p = 0.012), serum neutrophil percent (p = 0.008), C-reactive protein (p = 0.001), Charlson comorbidity index (p = 0.001), positive culture in synovial fluid (p = 0.001), and methicillin-sensitive Staphylococcus aureus (MSSA) isolate in synovial fluid (p = 0.001) had significant correlations with the group B. Repeated debridement was performed for those who had recurrence of infection, and this procedure was more often in group B (23 versus 21 joints, 23.9 versus 51.2%, p = 0.012). Progression of arthritis occurred more often in group B (16 versus 17 joints, 16.7 versus 41.5%, p = 0.001). Septic arthritis combined with systemic sepsis was related to duration of prodromal symptom, serum neutrophil percent, C-reactive protein, Charlson comorbidity index, positive culture in synovial fluid, and a MSSA isolate in synovial fluid. Concurrent systemic sepsis led to poor outcomes in patients with septic arthritis in terms of recurrence of infection and progression of arthritis. III Case control study.

Continuous-Course Reirradiation With Concurrent Carboplatin and Paclitaxel for Locally Recurrent, Nonmetastatic Squamous Cell Carcinoma of the Head-and-Neck

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

Kharofa, Jordan; Choong, Nicholas; Wang, Dian

Purpose: To examine the efficacy and toxicity of continuous-course, conformal reirradiation with weekly paclitaxel and carboplatin for the treatment of locally recurrent, nonmetastatic squamous cell carcinoma of the head and neck (SCCHN) in a previously irradiated field. Methods and Materials: Patients treated with continuous course-reirradiation with concurrent carboplatin and paclitaxel at the Medical College of Wisconsin and the Clement J. Zablocki VA from 2001 through 2009 were retrospectively reviewed. Patients included in the analysis had prior radiation at the site of recurrence of at least 45 Gy. The analysis included patients who received either intensity-modulated radiotherapy (RT) or three-dimensional conformalmore » RT techniques. All patients received weekly concurrent carboplatin (AUC2) and paclitaxel (30-50 mg/m{sup 2}). Results: Thirty-eight patients with nonmetastatic SCCHN met the entry criteria for analysis. The primary sites at initial diagnosis were oropharyngeal or laryngeal in most patients (66%). Median reirradiation dose was 60 Gy (range, 54-70 Gy). Acute toxicity included Grade 2 neutropenia (5%), Grade 3 neutropenia (15%), and Grade 1/2 thrombocytopenia (8%). No deaths occurred from hematologic toxicity. Chemotherapy doses held (50%) was more prevalent than radiation treatment break (8%). Sixty-eight percent of patients required a gastrostomy tube in follow-up. Significant late toxicity was experienced in 6 patients (16%): 1 tracheoesophageal fistula, 1 pharyngocutaneous fistula, 3 with osteoradionecrosis, and 1 patient with a lingual artery bleed. Patients treated with three-dimensional conformal RT had more frequent significant late toxicites than patients treated with intensity-modulated RT (44% and 7% respectively, p < 0.05). The median time to progression was 7 months and progression-free rates at 1, 2, and 5 years was 44%, 34%, and 29% respectively. The median overall survival was 16 months. Overall survival at 1, 3, and 5 years was 54%, 31%, and 20% respectively. Conclusions: Continuous-course, conformal reirradiation with weekly paclitaxel and carboplatin has an acceptable toxicity profile and offers a potentially curative option in a subset of patients with few other options.« less

TOO MANY MOUTHS promotes cell fate progression in stomatal development of Arabidopsis stems.

PubMed

Bhave, Neela S; Veley, Kira M; Nadeau, Jeanette A; Lucas, Jessica R; Bhave, Sanjay L; Sack, Fred D

2009-01-01

Mutations in TOO MANY MOUTHS (TMM), which encodes a receptor-like protein, cause stomatal patterning defects in Arabidopsis leaves but eliminate stomatal formation in stems. Stomatal development in wild-type and tmm stems was analyzed to define TMM function. Epidermal cells in young tmm stems underwent many asymmetric divisions characteristic of entry into the stomatal pathway. The resulting precursor cells, meristemoids, appropriately expressed cell fate markers such as pTMM:GFP. However, instead of progressing developmentally by forming a guard mother cell, the meristemoids arrested, dedifferentiated, and enlarged. Thus asymmetric divisions are necessary but not sufficient for stomatal formation in stems, and TMM promotes the fate and developmental progression of early precursor cells. Comparable developmental and mature stomatal phenotypes were also found in tmm hypocotyls and in the proximal flower stalk. TMM is also a positive regulator of meristemoid division in leaves suggesting that TMM generally promotes meristemoid activity. Our results are consistent with a model in which TMM interacts with other proteins to modulate precursor cell fate and progression in an organ and domain-specific manner. Finally, the consistent presence of a small number of dedifferentiated meristemoids in mature wild-type stems suggests that precursor cell arrest is a normal feature of Arabidopsis stem development.

Stress-resistant Translation of Cathepsin L mRNA in Breast Cancer Progression*

PubMed Central

Tholen, Martina; Wolanski, Julia; Stolze, Britta; Chiabudini, Marco; Gajda, Mieczyslaw; Bronsert, Peter; Stickeler, Elmar; Rospert, Sabine; Reinheckel, Thomas

2015-01-01

The cysteine protease cathepsin L (CTSL) is often thought to act as a tumor promoter by enhancing tumor progression and metastasis. This goes along with increased CTSL activity in various tumor entities; however, the mechanisms leading to high CTSL levels are incompletely understood. With the help of the polyoma middle T oncogene driven breast cancer mouse model expressing a human CTSL genomic transgene, we show that CTSL indeed promotes breast cancer metastasis to the lung. During tumor formation and progression high expression levels of CTSL are maintained by enduring translation of CTSL mRNA. Interestingly, human breast cancer specimens expressed the same pattern of 5′ untranslated region (UTR) splice variants as the transgenic mice and the human cancer cell line MDA-MB 321. By polyribosome profiling of tumor tissues and human breast cancer cells, we observe an intrinsic resistance of CTSL to stress-induced shutdown of translation. This ability can be attributed to all 5′ UTR variants of CTSL and is not dependent on a previously described internal ribosomal entry site motif. In conclusion, we provide in vivo functional evidence for overexpressed CTSL as a promoter of lung metastasis, whereas high CTSL levels are maintained during tumor progression due to stress-resistant mRNA translation. PMID:25957406

Ultrasonic Monitoring of the Progress of Lactic Acid Fermentation

NASA Astrophysics Data System (ADS)

Masuzawa, Nobuyoshi; Kimura, Akihiro; Ohdaira, Etsuzo

2003-05-01

Promotion of lactic acid fermentation by ultrasonic irradiation has been attempted. It is possible to determine the progress of fermentation and production of a curd, i.e., yoghurt and or kefir, by measuring acidity using a pH meter. However, this method is inconvenient and indirect for the evaluation of the progress of lactic acid fermentation under anaerobic condition. In this study, an ultrasonic monitoring method for evaluating the progress of lactic acid fermentation was examined.

Regulation of Tumor Progression by Programmed Necrosis

PubMed Central

Jeon, Hyun Min; Jeong, Eui Kyong; Lee, Yig Ji; Kim, Cho Hee; Park, Hye Gyeong

2018-01-01

Rapidly growing malignant tumors frequently encounter hypoxia and nutrient (e.g., glucose) deprivation, which occurs because of insufficient blood supply. This results in necrotic cell death in the core region of solid tumors. Necrotic cells release their cellular cytoplasmic contents into the extracellular space, such as high mobility group box 1 (HMGB1), which is a nonhistone nuclear protein, but acts as a proinflammatory and tumor-promoting cytokine when released by necrotic cells. These released molecules recruit immune and inflammatory cells, which exert tumor-promoting activity by inducing angiogenesis, proliferation, and invasion. Development of a necrotic core in cancer patients is also associated with poor prognosis. Conventionally, necrosis has been thought of as an unregulated process, unlike programmed cell death processes like apoptosis and autophagy. Recently, necrosis has been recognized as a programmed cell death, encompassing processes such as oncosis, necroptosis, and others. Metabolic stress-induced necrosis and its regulatory mechanisms have been poorly investigated until recently. Snail and Dlx-2, EMT-inducing transcription factors, are responsible for metabolic stress-induced necrosis in tumors. Snail and Dlx-2 contribute to tumor progression by promoting necrosis and inducing EMT and oncogenic metabolism. Oncogenic metabolism has been shown to play a role(s) in initiating necrosis. Here, we discuss the molecular mechanisms underlying metabolic stress-induced programmed necrosis that promote tumor progression and aggressiveness. PMID:29636841

The perioperative period and promotion of cancer metastasis: New outlooks on mediating mechanisms and immune involvement

PubMed Central

Neeman, Elad; Ben-Eliyahu, Shamgar

2012-01-01

Surgery for the removal of a primary tumor presents an opportunity to eradicate cancer or arrest its progression, but is also believed to promote the outbreak of pre-existing micrometastases and the initiation of new metastases. These deleterious effects of surgery are mediated through various mechanisms, including psychological and physiological neuroendocrine and paracrine stress responses elicited by surgery. In this review we (i) describe the many risk factors that arise during the perioperative period, acting synergistically to make this short timeframe critical for determining long-term cancer recurrence, (ii) present newly identified potent immunocyte populations that can destroy autologous tumor cells that were traditionally considered immune-resistant, thus invigorating the notion of immune-surveillance against cancer metastasis, (iii) describe in vivo evidence in cancer patients that support a role for anti-cancer immunity, (iv) indicate neuroendocrine and paracrine mediating mechanisms of stress- and surgery-induced promotion of cancer progression, focusing on the prominent role of catecholamines and prostaglandins through their impact on anti-cancer immunity, and through direct effects on the malignant tissue and its surrounding, (v) discuss the impact of different anesthetic approaches and other intra-operative procedures on immunity and cancer progression, and (vi) suggest prophylactic measures against the immunosuppressive and cancer promoting effects of surgery. PMID:22504092

Melanoma cell-derived exosomes promote epithelial-mesenchymal transition in primary melanocytes through paracrine/autocrine signaling in the tumor microenvironment

PubMed Central

Xiao, Deyi; Barry, Samantha; Kmetz, Daniel; Egger, Michael; Pan, Jianmin; Rai, Shesh N; Qu, Jifu; McMasters, Kelly M.; Hao, Hongying

2016-01-01

The tumor microenvironment is abundant with exosomes that are secreted by the cancer cells themselves. Exosomes are nanosized, organelle-like membranous structures that are increasingly being recognized as major contributors in the progression of malignant neoplasms. A critical element in melanoma progression is its propensity to metastasize, but little is known about how melanoma cell-derived exosomes modulate the microenvironment to optimize conditions for tumor progression and metastasis. Here, we provide evidence that melanoma cell-derived exosomes promote phenotype switching in primary melanocytes through paracrine/autocrine signaling. We found that the mitogen-activated protein kinase (MAPK) signaling pathway was activated during the exosome-mediated epithelial-to-mesenchymal transition (EMT)-resembling process, which promotes metastasis. Let-7i, an miRNA modulator of EMT, was also involved in this process. We further defined two other miRNA modulators of EMT (miR-191 and let-7a) in serum exosomes for differentiating stage I melanoma patients from non-melanoma subjects. These results provide the first strong molecular evidence that melanoma cell-derived exosomes promote the EMT-resembling process in the tumor microenvironment. Thus, novel strategies targeting EMT and modulating the tumor microenvironment may emerge as important approaches for the treatment of metastatic melanoma. PMID:27063098

Exosomes derived from gastric cancer cells activate NF-κB pathway in macrophages to promote cancer progression.

PubMed

Wu, Lijun; Zhang, Xu; Zhang, Bin; Shi, Hui; Yuan, Xiao; Sun, Yaoxiang; Pan, Zhaoji; Qian, Hui; Xu, Wenrong

2016-09-01

Exosomes are nano-sized membrane vesicles secreted by both normal and cancer cells. Emerging evidence indicates that cancer cells derived exosomes contribute to cancer progression through the modulation of tumor microenvironment. However, the effects of exosomes derived from gastric cancer cells on macrophages are not well understood. In this study, we investigated the biological role of gastric cancer cells derived exosomes in the activation of macrophages. We demonstrated that gastric cancer cells derived exosomes activated macrophages to express increased levels of proinflammatory factors, which in turn promoted tumor cell proliferation and migration. In addition, gastric cancer cells derived exosomes remarkably upregulated the phosphorylation of NF-κB in macrophages. Inhibiting the activation of NF-κB reversed the upregulation of proinflammatory factors in macrophages and blocked their promoting effects on gastric cancer cells. Moreover, we found that gastric cancer cells derived exosomes could also activate macrophages from human peripheral blood monocytes through the activation of NF-κB. In conclusion, our results suggest that gastric cancer cells derived exosomes stimulate the activation of NF-κB pathway in macrophages to promote cancer progression, which provides a potential therapeutic approach for gastric cancer by interfering with the interaction between exosomes and macrophages in tumor microenvironment.

Astrocyte Elevated Gene 1 Interacts with Acetyltransferase p300 and c-Jun To Promote Tumor Aggressiveness

PubMed Central

Liu, Liping; Guan, Hongyu; Li, Yun; Ying, Zhe; Wu, Jueheng; Zhu, Xun; Song, Libing

2016-01-01

ABSTRACT Astrocyte elevated gene 1 (AEG-1) is an oncoprotein that strongly promotes the development and progression of cancers. However, the detailed underlying mechanisms through which AEG-1 enhances tumor development and progression remain to be determined. In this study, we identified c-Jun and p300 to be novel interacting partners of AEG-1 in gliomas. AEG-1 promoted c-Jun transcriptional activity by interacting with the c-Jun/p300 complex and inducing c-Jun acetylation. Furthermore, the AEG-1/c-Jun/p300 complex was found to bind the promoter of c-Jun downstream targeted genes, consequently establishing an acetylated chromatin state that favors transcriptional activation. Importantly, AEG-1/p300-mediated c-Jun acetylation resulted in the development of a more aggressive malignant phenotype in gliomas through a drastic increase in glioma cell proliferation and angiogenesis in vitro and in vivo. Consistently, the AEG-1 expression levels in clinical glioma specimens correlated with the status of c-Jun activation. Taken together, our results suggest that AEG-1 mediates a novel epigenetic mechanism that enhances c-Jun transcriptional activity to induce glioma progression and that AEG-1 might be a novel, potential target for the treatment of gliomas. PMID:27956703

Chk1 promotes replication fork progression by controlling replication initiation

PubMed Central

Petermann, Eva; Woodcock, Mick; Helleday, Thomas

2010-01-01

DNA replication starts at initiation sites termed replication origins. Metazoan cells contain many more potential origins than are activated (fired) during each S phase. Origin activation is controlled by the ATR checkpoint kinase and its downstream effector kinase Chk1, which suppresses origin firing in response to replication blocks and during normal S phase by inhibiting the cyclin-dependent kinase Cdk2. In addition to increased origin activation, cells deficient in Chk1 activity display reduced rates of replication fork progression. Here we investigate the causal relationship between increased origin firing and reduced replication fork progression. We use the Cdk inhibitor roscovitine or RNAi depletion of Cdc7 to inhibit origin firing in Chk1-inhibited or RNAi-depleted cells. We report that Cdk inhibition and depletion of Cdc7 can alleviate the slow replication fork speeds in Chk1-deficient cells. Our data suggest that increased replication initiation leads to slow replication fork progression and that Chk1 promotes replication fork progression during normal S phase by controlling replication origin activity. PMID:20805465

Aberrant Receptor Internalization and Enhanced FRS2-dependent Signaling Contribute to the Transforming Activity of the Fibroblast Growth Factor Receptor 2 IIIb C3 Isoform*

PubMed Central

Cha, Jiyoung Y.; Maddileti, Savitri; Mitin, Natalia; Harden, T. Kendall; Der, Channing J.

2009-01-01

Alternative splice variants of fibroblast growth factor receptor 2 (FGFR2) IIIb, designated C1, C2, and C3, possess progressive reduction in their cytoplasmic carboxyl termini (822, 788, and 769 residues, respectively), with preferential expression of the C2 and C3 isoforms in human cancers. We determined that the progressive deletion of carboxyl-terminal sequences correlated with increasing transforming potency. The highly transforming C3 variant lacks five tyrosine residues present in C1, and we determined that the loss of Tyr-770 alone enhanced FGFR2 IIIb C1 transforming activity. Because Tyr-770 may compose a putative YXXL sorting motif, we hypothesized that loss of Tyr-770 in the 770YXXL motif may cause disruption of FGFR2 IIIb C1 internalization and enhance transforming activity. Surprisingly, we found that mutation of Leu-773 but not Tyr-770 impaired receptor internalization and increased receptor stability and activation. Interestingly, concurrent mutations of Tyr-770 and Leu-773 caused 2-fold higher transforming activity than caused by the Y770F or L773A single mutations, suggesting loss of Tyr and Leu residues of the 770YXXL773 motif enhances FGFR2 IIIb transforming activity by distinct mechanisms. We also determined that loss of Tyr-770 caused persistent activation of FRS2 by enhancing FRS2 binding to FGFR2 IIIb. Furthermore, we found that FRS2 binding to FGFR2 IIIb is required for increased FRS2 tyrosine phosphorylation and enhanced transforming activity by Y770F mutation. Our data support a dual mechanism where deletion of the 770YXXL773 motif promotes FGFR2 IIIb C3 transforming activity by causing aberrant receptor recycling and stability and persistent FRS2-dependent signaling. PMID:19103595

Rethinking the cognitive revolution from a neural perspective: how overuse/misuse of the term 'cognition' and the neglect of affective controls in behavioral neuroscience could be delaying progress in understanding the BrainMind.

PubMed

Cromwell, Howard Casey; Panksepp, Jaak

2011-10-01

Words such as cognition, motivation and emotion powerfully guide theory development and the overall aims and goals of behavioral neuroscience research. Once such concepts are accepted generally as natural aspects of the brain, their influence can be pervasive and long lasting. Importantly, the choice of conceptual terms used to describe and study mental/neural functions can also constrain research by forcing the results into seemingly useful 'conceptual' categories that have no discrete reality in the brain. Since the popularly named 'cognitive revolution' in psychological science came to fruition in the early 1970s, the term cognitive or cognition has been perhaps the most widely used conceptual term in behavioral neuroscience. These terms, similar to other conceptual terms, have potential value if utilized appropriately. We argue that recently the term cognition has been both overused and misused. This has led to problems in developing a usable shared definition for the term and to promotion of possible misdirections in research within behavioral neuroscience. In addition, we argue that cognitive-guided research influenced primarily by top-down (cortical toward subcortical) perspectives without concurrent non-cognitive modes of bottom-up developmental thinking, could hinder progress in the search for new treatments and medications for psychiatric illnesses and neurobehavioral disorders. Overall, linkages of animal research insights to human psychology may be better served by bottom-up (subcortical to cortical) affective and motivational 'state-control' perspectives, simply because the lower networks of the brain are foundational for the construction of higher 'information-processing' aspects of mind. Moving forward, rapidly expanding new techniques and creative methods in neuroscience along with more accurate brain concepts, may help guide the development of new therapeutics and hopefully more accurate ways to describe and explain brain-behavior relationships. Copyright © 2011 Elsevier Ltd. All rights reserved.

Limited role for extended maintenance temozolomide for newly diagnosed glioblastoma.

PubMed

Gramatzki, Dorothee; Kickingereder, Philipp; Hentschel, Bettina; Felsberg, Jörg; Herrlinger, Ulrich; Schackert, Gabriele; Tonn, Jörg-Christian; Westphal, Manfred; Sabel, Michael; Schlegel, Uwe; Wick, Wolfgang; Pietsch, Torsten; Reifenberger, Guido; Loeffler, Markus; Bendszus, Martin; Weller, Michael

2017-04-11

To explore an association with survival of modifying the current standard of care for patients with newly diagnosed glioblastoma of surgery followed by radiotherapy plus concurrent and 6 cycles of maintenance temozolomide chemotherapy (TMZ/RT → TMZ) by extending TMZ beyond 6 cycles. The German Glioma Network cohort was screened for patients with newly diagnosed glioblastoma who received TMZ/RT → TMZ and completed ≥6 cycles of maintenance chemotherapy without progression. Associations of clinical patient characteristics, molecular markers, and residual tumor determined by magnetic resonance imaging after 6 cycles of TMZ with progression-free survival (PFS) and overall survival (OS) were analyzed with the log-rank test. Multivariate analyses using the Cox proportional hazards model were performed to assess associations of prolonged TMZ use with outcome. Sixty-one of 142 identified patients received at least 7 maintenance TMZ cycles (median 11, range 7-20). Patients with extended maintenance TMZ treatment had better PFS (20.5 months, 95% confidence interval [CI] 17.7-23.3, vs 17.2 months, 95% CI 10.2-24.2, p = 0.035) but not OS (32.6 months, 95% CI 28.9-36.4, vs 33.2 months, 95% CI 25.3-41.0, p = 0.126). However, there was no significant association of prolonged TMZ chemotherapy with PFS (hazard ratio [HR] = 0.8, 95% CI 0.4-1.6, p = 0.559) or OS (HR = 1.6, 95% CI 0.8-3.3, p = 0.218) adjusted for age, extent of resection, Karnofsky performance score, presence of residual tumor, O 6 -methylguanine DNA methyltransferase (MGMT) promoter methylation status, or isocitrate dehydrogenase ( IDH ) mutation status. These data may not support the practice of prolonging maintenance TMZ chemotherapy beyond 6 cycles. This study provides Class III evidence that in patients with newly diagnosed glioblastoma, prolonged TMZ chemotherapy does not significantly increase PFS or OS. © 2017 American Academy of Neurology.

Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with Barrett's oesophagus.

PubMed

Kastelein, Florine; Biermann, Katharina; Steyerberg, Ewout W; Verheij, Joanne; Kalisvaart, Marit; Looijenga, Leendert H J; Stoop, Hans A; Walter, Laurens; Kuipers, Ernst J; Spaander, Manon C W; Bruno, Marco J

2013-12-01

The value of surveillance for patients with Barrett's oesophagus (BO) is under discussion given the overall low incidence of neoplastic progression and lack of discriminative tests for risk stratification. Histological diagnosis of low-grade dysplasia (LGD) is the only accepted predictor for progression to date, but has a low predictive value. The aim of this study was therefore to evaluate the value of p53 immunohistochemistry for predicting neoplastic progression in patients with BO. We conducted a case-control study within a prospective cohort of 720 patients with BO. Patients who developed high-grade dysplasia (HGD) or oesophageal adenocarcinoma (OAC) were classified as cases and patients without neoplastic progression were classified as controls. P53 protein expression was determined by immunohistochemistry in more than 12 000 biopsies from 635 patients and was scored independently by two expert pathologists who were blinded to long-term outcome. During follow-up, 49 (8%) patients developed HGD or OAC. P53 overexpression was associated with an increased risk of neoplastic progression in patients with BO after adjusting for age, gender, Barrett length and oesophagitis (adjusted relative risks (RR(a)) 5.6; 95% CI 3.1 to 10.3), but the risk was even higher with loss of p53 expression (RR(a) 14.0; 95% CI 5.3 to 37.2). The positive predictive value for neoplastic progression increased from 15% with histological diagnosis of LGD to 33% with LGD and concurrent aberrant p53 expression. Aberrant p53 protein expression is associated with an increased risk of neoplastic progression in patients with BO and appears to be a more powerful predictor of neoplastic progression than histological diagnosis of LGD.

A comparison of Omaha worksite health promotion activities to the 1992 national survey with a special perspective on program intervention.

PubMed

Eickhoff-Shemek, J M; Ryan, K F

1995-01-01

The purpose of this study was to compare the results from a survey of Omaha worksite health promotion activities with the results of a 1992 national survey. Comparisons were made on: (1) the kinds of health promotion activities offered, (2) progress toward the Healthy People 2000 worksite objectives, (3) types of program intervention offered, and (4) administrative factors. A one-time, written, mail-out/mail-back survey design was used. The study took place in Omaha, Nebraska. All area public and private worksites with 250 or more employees were sent surveys. Individuals who were preselected and identified as the best qualified within the company completed the survey instrument. Of the 176 worksites surveyed, 86 completed the survey (49%). Descriptive statistics (percentages) were used to compare the two surveys on kinds of programs offered, progress toward Healthy People 2000 related to worksite health promotion, the types of program intervention offered, and administrative factors. Generally, a greater percentage of respondent worksites from the national survey are offering more health promotion activities and have made more progress toward the Healthy People 2000 worksite objectives than the Omaha worksites. Results from both surveys showed that low levels of intervention are more prevalent than high levels of intervention, and that health promotion activities in most worksites are coordinated by human resources departments and not by someone professionally prepared in health education. Traditionally, major goals of worksite health promotion programs have focused on important organizational outcomes such as improved productivity/morale, reduction in absenteeism, and health care cost-containment. It is important to recognize, however, that low levels of intervention have less impact than more intensive programs on these desired outcomes. Future goals for local and national worksite health promotion programs may need to encourage implementation of more intensive intervention programs.

OSD1 promotes meiotic progression via APC/C inhibition and forms a regulatory network with TDM and CYCA1;2/TAM.

PubMed

Cromer, Laurence; Heyman, Jefri; Touati, Sandra; Harashima, Hirofumi; Araou, Emilie; Girard, Chloe; Horlow, Christine; Wassmann, Katja; Schnittger, Arp; De Veylder, Lieven; Mercier, Raphael

2012-01-01

Cell cycle control is modified at meiosis compared to mitosis, because two divisions follow a single DNA replication event. Cyclin-dependent kinases (CDKs) promote progression through both meiosis and mitosis, and a central regulator of their activity is the APC/C (Anaphase Promoting Complex/Cyclosome) that is especially required for exit from mitosis. We have shown previously that OSD1 is involved in entry into both meiosis I and meiosis II in Arabidopsis thaliana; however, the molecular mechanism by which OSD1 controls these transitions has remained unclear. Here we show that OSD1 promotes meiotic progression through APC/C inhibition. Next, we explored the functional relationships between OSD1 and the genes known to control meiotic cell cycle transitions in Arabidopsis. Like osd1, cyca1;2/tam mutation leads to a premature exit from meiosis after the first division, while tdm mutants perform an aberrant third meiotic division after normal meiosis I and II. Remarkably, while tdm is epistatic to tam, osd1 is epistatic to tdm. We further show that the expression of a non-destructible CYCA1;2/TAM provokes, like tdm, the entry into a third meiotic division. Finally, we show that CYCA1;2/TAM forms an active complex with CDKA;1 that can phosphorylate OSD1 in vitro. We thus propose that a functional network composed of OSD1, CYCA1;2/TAM, and TDM controls three key steps of meiotic progression, in which OSD1 is a meiotic APC/C inhibitor.

Infiltrating T cells promote renal cell carcinoma (RCC) progression via altering the estrogen receptor β-DAB2IP signals.

PubMed

Yeh, Chiuan-Ren; Ou, Zheng-Yu; Xiao, Guang-Qian; Guancial, Elizabeth; Yeh, Shuyuan

2015-12-29

Previous studies indicated the T cells, one of the most common types of immune cells existing in the microenvironment of renal cell carcinoma (RCC), may influence the progression of RCC. The potential linkage of T cells and the estrogen receptor beta (ERβ), a key player to impact RCC progression, however, remains unclear. Our results demonstrate that RCC cells can recruit more T cells than non-malignant kidney cells. Using an in vitro matrigel invasion system, we found infiltrating T cells could promote RCC cells invasion via increasing ERβ expression and transcriptional activity. Mechanism dissection suggested that co-culturing T cells with RCC cells released more T cell attraction factors, including IFN-γ, CCL3 and CCL5, suggesting a positive regulatory feed-back mechanism. Meanwhile, infiltrating T cells may also promote RCC cell invasion via increased ERβ and decreased DAB2IP expressions, and knocking down DAB2IP can then reverse the T cells-promoted RCC cell invasion. Together, our results suggest that infiltrating T cells may promote RCC cell invasion via increasing the RCC cell ERβ expression to inhibit the tumor suppressor DAB2IP signals. Further mechanism dissection showed that co-culturing T cells with RCC cells could produce more IGF-1 and FGF-7, which may enhance the ERβ transcriptional activity. The newly identified relationship between infiltrating T cells/ERβ/DAB2IP signals may provide a novel therapeutic target in the development of agents against RCC.

Heterogeneous effects of M-CSF isoforms on the progression of MLL-AF9 leukemia.

PubMed

Wang, Rong; Feng, Wenli; Yang, Feifei; Yang, Xiao; Wang, Lina; Chen, Chong; Hu, Yuting; Ren, Qian; Zheng, Guoguang

2018-02-01

Macrophage colony-stimulating factor (M-CSF) regulates both malignant cells and microenvironmental cells. Its splicing isoforms show functional heterogeneity. However, their roles on leukemia have not been well established. Here, the expression of total M-CSF in patients with hematopoietic malignancies was analyzed. The roles of M-CSF isoforms on the progression of acute myeloid leukemia (AML) were studied by establishing MLL-AF9-induced mouse AML models with high level membrane-bound M-CSF (mM-CSF) or soluble M-CSF (sM-CSF). Total M-CSF was highly expressed in myeloid leukemia patients. Furthermore, mM-CSF but not sM-CSF prolonged the survival of leukemia mice. While sM-CSF was more potent to promote proliferation and self-renew, mM-CSF was more potent to promote differentiation. Moreover, isoforms had different effects on leukemia-associated macrophages (LAMs) though they both increase monocytes/macrophages by growth-promoting and recruitment effects. In addition, mM-CSF promoted specific phagocytosis of leukemia cells by LAMs. RNA-seq analysis revealed that mM-CSF enhanced phagocytosis-associated genes and activated oxidative phosphorylation and metabolism pathway. These results highlight heterogeneous effects of M-CSF isoforms on AML progression and the mechanisms of mM-CSF, that is, intrinsically promoting AML cell differentiation and extrinsically enhancing infiltration of macrophages and phagocytosis by macrophages, which may provide potential clues for clinical diagnosis and therapy. © 2017 Australasian Society for Immunology Inc.

Id-1 promotes osteosarcoma cell growth and inhibits cell apoptosis via PI3K/AKT signaling pathway

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

Hao, Liang; Liao, Qi; Tang, Qiang

2016-02-12

Accumulating evidence reveals that Id-1 is upregulated and functions as a potential tumor promoter in several human cancer types. However, the role of Id-1 in osteosarcoma (OS) is unknown. In present study, we found that Id-1 expression was elevated in OS tissues than adjacent normal bone tissues. More importantly, we demonstrated that overexpression of Id-1 is significantly correlated with tumor progression and poor survival in OS patients. Furthermore, increased expression of Id-1 was observed in OS cell lines and ectopic expression of Id-1 significantly enhanced in vitro cell proliferation and promoted in vivo tumor growth, whereas knockdown of Id-1 suppressed OS cellsmore » growth. Moreover, our experimental data revealed that Id-1 promotes cell proliferation by facilitating cell cycle progression and inhibits cell apoptosis. Mechanistically, the effects of Id-1 in OS cells is at least partly through activation of PI3K/Akt signaling pathway. Therefore, we identified a tumorigenic role of Id-1 in OS and suggested a potential therapeutic target for OS patients. - Highlights: • Id-1 expression is positively correlated in OS patients with poor prognosis. • Overexpression of Id-1 promotes OS cell growth in vitro and in vivo. • Id-1induces cell cycle progression and inhibits cell apoptosis. • PI3K/Akt signaling pathway contributed to the oncogenic effects of Id-1 in OS cells.« less

Progress in Teachers' Readiness to Promote Positive Youth Development among Students during the Lions Quest Teaching Workshop

ERIC Educational Resources Information Center

Talvio, Markus; Berg, Minna; Ketonen, Elina; Komulainen, Erkki; Lonka, Kirsti

2015-01-01

Modern learning psychology places an emphasis on the ability of teachers to promote their students' social and emotional learning (SEL) and living a good life. Research on precisely how teachers promote SEL and well-being among their students, however, remains scarce. This study focused on evaluating the Lions Quest teaching workshop (LQ), which…

The dark side of hippo signaling: A cancer promoter role.

PubMed

Dunn, Brandon; Ma, Xianjue

2017-10-02

The Hippo signaling pathway regulates organ size and tissue homeostasis. Given this role it is unsurprising that dysregulation of this pathway has implications for cancer progression. A convincing body of literature shows that the Hippo pathway serves a tumor suppressive function with its inactivation leading to massive overgrowth. However, additional studies have also shown that activation of Hippo signaling can promote tumor progression. It remains unknown how a single pathway can produce such diametrically opposed effects. This lack of knowledge is in part due to our inability to make meaningful comparisons from studies which have taken place in a variety of cell types, tissues, and organisms. Recently however, we have published 2 studies using the Drosophila wing disk to study the Hippo pathway and have found that Hippo pathway activation can promote cell migration and invasion while Hippo pathway inactivation leads to overgrowth. Thus we propose here that Drosophila can provide a research platform with which to begin addressing how the Hippo pathway can both enhance and suppress tumor progression due to published pro- and anti-tumor functionalities of the Hippo pathway in the same tissue.

RUNX3 methylation in normal surrounding urothelium of patients with non-muscle-invasive bladder cancer: potential role in the prediction of tumor progression.

PubMed

Jeong, P; Min, B D; Ha, Y S; Song, P H; Kim, I Y; Ryu, K H; Kim, J H; Yun, S J; Kim, W J

2012-11-01

Previously, we reported a causal relationship between RUNX3 methylation and bladder tumor development. Thus, in order to clarify its role in tumorigenesis, this study aims to identify the function of RUNX3 methylation in normal adjacent urothelium of patients with non-muscle invasive bladder cancer (NMIBC). Tumor tissue and donor-matched normal adjacent tissue from 55 patients who underwent transurethral resection (TUR) were selected for the study, and RUNX3 promoter methylation was assessed using methylation-specific polymerase chain reaction (MS-PCR). RUNX3 promoter methylation occurred more frequently in tumor samples than in histologically normal urothelium in patients with NMIBC (P = 0.02). The methylation rates for the RUNX3 promoter in normal adjacent urothelium and tumor tissue were 47% and 69%, respectively. Interestingly, RUNX3 methylation in normal adjacent urothelium was associated with tumor number (P = 0.022) and progression (P = 0.035). Kaplan-Meier estimates revealed that RUNX3 methylation in normal urothelium showed a significant association with time to progression (P = 0.017) in NMIBC patients. Stratifying the patients into 'both methylation', 'one methylation' and 'no methylation' groups for tumors and normal urothelium revealed that no progression occurred in the 'no methylation' group during follow-up. Multivariate Cox regression analysis demonstrated that RUNX3 methylation in normal urothelium [hazards ratio (HR): 5.692, P = 0.042] was an independent predictor of progression. RUNX3 methylation was associated with transition from normal urothelium to bladder tumor. More importantly, RUNX3 methylation in normal adjacent urothelium may predict progression in NMIBC patients who have undergone TUR. Copyright © 2012 Elsevier Ltd. All rights reserved.

PlGF/VEGFR-1 Signaling Promotes Macrophage Polarization and Accelerated Tumor Progression in Obesity.

PubMed

Incio, Joao; Tam, Josh; Rahbari, Nuh N; Suboj, Priya; McManus, Dan T; Chin, Shan M; Vardam, Trupti D; Batista, Ana; Babykutty, Suboj; Jung, Keehoon; Khachatryan, Anna; Hato, Tai; Ligibel, Jennifer A; Krop, Ian E; Puchner, Stefan B; Schlett, Christopher L; Hoffmman, Udo; Ancukiewicz, Marek; Shibuya, Masabumi; Carmeliet, Peter; Soares, Raquel; Duda, Dan G; Jain, Rakesh K; Fukumura, Dai

2016-06-15

Obesity promotes pancreatic and breast cancer progression via mechanisms that are poorly understood. Although obesity is associated with increased systemic levels of placental growth factor (PlGF), the role of PlGF in obesity-induced tumor progression is not known. PlGF and its receptor VEGFR-1 have been shown to modulate tumor angiogenesis and promote tumor-associated macrophage (TAM) recruitment and activity. Here, we hypothesized that increased activity of PlGF/VEGFR-1 signaling mediates obesity-induced tumor progression by augmenting tumor angiogenesis and TAM recruitment/activity. We established diet-induced obese mouse models of wild-type C57BL/6, VEGFR-1 tyrosine kinase (TK)-null, or PlGF-null mice, and evaluated the role of PlGF/VEGFR-1 signaling in pancreatic and breast cancer mouse models and in human samples. We found that obesity increased TAM infiltration, tumor growth, and metastasis in pancreatic cancers, without affecting vessel density. Ablation of VEGFR-1 signaling prevented obesity-induced tumor progression and shifted the tumor immune environment toward an antitumor phenotype. Similar findings were observed in a breast cancer model. Obesity was associated with increased systemic PlGF, but not VEGF-A or VEGF-B, in pancreatic and breast cancer patients and in various mouse models of these cancers. Ablation of PlGF phenocopied the effects of VEGFR-1-TK deletion on tumors in obese mice. PlGF/VEGFR-1-TK deletion prevented weight gain in mice fed a high-fat diet, but exacerbated hyperinsulinemia. Addition of metformin not only normalized insulin levels but also enhanced antitumor immunity. Targeting PlGF/VEGFR-1 signaling reprograms the tumor immune microenvironment and inhibits obesity-induced acceleration of tumor progression. Clin Cancer Res; 22(12); 2993-3004. ©2016 AACR. ©2016 American Association for Cancer Research.

SIRT1 overexpression protects non-small cell lung cancer cells against osteopontin-induced epithelial-mesenchymal transition by suppressing NF-κB signaling.

PubMed

Li, Xuejiao; Jiang, Zhongxiu; Li, Xiangmin; Zhang, Xiaoye

2018-01-01

Osteopontin (OPN) is a promoter for tumor progression. It has been reported to promote non-small cell lung cancer (NSCLC) progression via the activation of nuclear factor-κB (NF-κB) signaling. As the increased acetylation of NF-κB p65 is linked to NF-κB activation, the regulation of NF-κB p65 acetylation could be a potential treatment target for OPN-induced NSCLC progression. Sirtuin 1 (SIRT1) is a deacetylase, and the role of SIRT1 in tumor progression is still controversial. The effect and mechanism of SIRT1 on OPN-induced tumor progression remains unknown. The results presented in this research demonstrated that OPN inhibited SIRT1 expression and promoted NF-κB p65 acetylation in NSCLC cell lines (A549 and NCI-H358). In this article, overexpression of SIRT1 was induced by infection of SIRT1-overexpressing lentiviral vectors. The overexpression of SIRT1 protected NSCLC cells against OPN-induced NF-κB p65 acetylation and epithelial-mesenchymal transition (EMT), as indicated by the reduction of OPN-induced changes in the expression levels of EMT-related markers and cellular morphology. Furthermore, SIRT1 overexpression significantly attenuated OPN-induced cell proliferation, migration and invasion. Moreover, overexpression of SIRT1 inhibited OPN-induced NF-κB activation. As OPN induced NSCLC cell EMT through activation of NF-κB signaling, OPN-induced SIRT1 downregulation may play an important role in NSCLC cell EMT via NF-κB signaling. The results suggest that SIRT1 could be a tumor suppressor to attenuate OPN-induced NSCLC progression through the regulation of NF-κB signaling.

MicroRNA-495-3p functions as a tumor suppressor by regulating multiple epigenetic modifiers in gastric carcinogenesis.

PubMed

Eun, Jung Woo; Kim, Hyung Seok; Shen, Qingyu; Yang, Hee Doo; Kim, Sang Yean; Yoon, Jung Hwan; Park, Won Sang; Lee, Jung Young; Nam, Suk Woo

2018-01-01

MicroRNAs (miRNAs) engage in complex interactions with the machinery that controls the transcriptome and concurrently target multiple mRNAs. Here, we demonstrate that microRNA-495-3p (miR-495-3p) functions as a potent tumor suppressor by governing ten oncogenic epigenetic modifiers (EMs) in gastric carcinogenesis. From the large cohort transcriptome datasets of gastric cancer (GC) patients available from The Cancer Genome Atlas (TCGA) and the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO), we were able to recapitulate 15 EMs as significantly overexpressed in GC among the 51 EMs that were previously reported to be involved in cancer progression. Computational target prediction yielded miR-495-3p, which targets as many as ten of the 15 candidate oncogenic EMs. Ectopic expression of miRNA mimics in GC cells caused miR-495-3p to suppress ten EMs, and inhibited tumor cell growth and proliferation via caspase-dependent and caspase-independent cell death processing. In addition, in vitro metastasis assays showed that miR-495-3p plays a role in the metastatic behavior of GC cells by regulating SLUG, vimentin, and N-cadherin. Furthermore, treatment of GC cells with 5-aza-2'-deoxcytidine restored miR-495-3p expression; sequence analysis revealed hypermethylation of the miR-495-3p promoter region in GC cells. A negative regulatory loop is proposed, whereby DNMT1, among ten oncogenic EMs, regulates miR-495-3p expression via hypermethylation of the miR-495-3p promoter. Our findings suggest that the functional loss or suppression of miR-495-3p triggers overexpression of multiple oncogenic EMs, and thereby contributes to malignant transformation and growth of gastric epithelial cells. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2017 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Can learning in informal settings mitigate disadvantage and promote urban sustainability? School gardens in Washington, DC

NASA Astrophysics Data System (ADS)

Fisher-Maltese, Carley; Fisher, Dana R.; Ray, Rashawn

2017-09-01

This article explores how school gardens provide learning opportunities for school-aged children while concurrently helping cities achieve sustainability. The authors analyse this process in Washington, DC, a particularly innovative metropolis in the United States. This national capital city boasts two of the most progressive examples of legislation aimed at improving environmental awareness and inciting citizens to engage in environmental stewardship, both of which focus on school-aged children: (1) the Healthy Schools Act of 2010 and (2) the Sustainable DC Act of 2012. Together these policies focus on bringing healthy lifestyles and environmental awareness, including meaningful outdoor learning experiences, to students and families in the District of Columbia. This article is organised into three parts. The first part discusses how Washington, DC became a sustainable learning city through the implementation of these specific policies. The next part presents the results of a pilot study conducted in one kindergarten to Grade 5 (K-5) elementary school located in Ward 8, the poorest part of the city. The authors' analysis considers the support and the obstacles teachers and principals in the District of Columbia (DC) are experiencing in their efforts to integrate school gardens into the curriculum and the culture of their schools. Exploring the impacts of the school garden on the students, the local community, and the inter-generational relationships at and beyond schools, the authors aim to shed light on the benefits and the challenges. While Washington, DC is fostering its hope that the benefits prevail as it provides a model for other cities to follow, the authors also candidly present the challenges of implementing these policies. In the final part, they discuss the implications of their findings for school gardens and sustainable learning cities more broadly. They encourage further research to gain more insights into effective ways of promoting environmental literacy and to consolidate the transferability of this model.

Graphene oxide sensitizes cancer cells to chemotherapeutics by inducing early autophagy events, promoting nuclear trafficking and necrosis

PubMed Central

Lin, Kuan-Chen; Lin, Mei-Wei; Hsu, Mu-Nung; Yu-Chen, Guan; Chao, Yu-Chan; Tuan, Hsing-Yu; Chiang, Chi-Shiun; Hu, Yu-Chen

2018-01-01

Rationale: Cisplatin (CDDP) is a broad-spectrum anticancer drug but chemoresistance to CDDP impedes its wide use for cancer therapy. Autophagy is an event occurring in the cytoplasm and cytoplasmic LC3 puncta formation is a hallmark of autophagy. Graphene oxide (GO) is a nanomaterial that provokes autophagy in CT26 colon cancer cells and confers antitumor effects. Here we aimed to evaluate whether combined use of GO with CDDP (GO/CDDP) overcomes chemoresistance in different cancer cells and uncover the underlying mechanism. Methods: We treated different cancer cells with GO/CDDP and evaluated the cytotoxicity, death mechanism, autophagy induction and nuclear entry of CDDP. We further knocked down genes essential for autophagic flux and deciphered which step is critical to nuclear import and cell death. Finally, we performed immunoprecipitation, mass spectrometry and immunofluorescence labeling to evaluate the association of LC3 and CDDP. Results: We uncovered that combination of GO and CDDP (GO/CDDP) promoted the killing of not only CT26 cells, but also ovarian, cervical and prostate cancer cells. In the highly chemosensitized Skov-3 cells, GO/CDDP significantly enhanced concurrent nuclear import of CDDP and autophagy marker LC3 and elevated cell necrosis, which required autophagy initiation and progression but did not necessitate late autophagy events (e.g., autophagosome completion and autolysosome formation). The GO/CDDP-elicited nuclear trafficking and cell death also required importin α/β, and LC3 also co-migrated with CDDP and histone H1/H4 into the nucleus. In particular, GO/CDDP triggered histone H4 acetylation in the nucleus, which could decondense the chromosome and enable CDDP to more effectively access chromosomal DNA to trigger cell death. Conclusion: These findings shed light on the mechanisms of GO/CDDP-induced chemosensitization and implicate the potential applications of GO/CDDP to treat multiple cancers. PMID:29721093

RIVER DELL CENTER FOR THE PROMOTION OF THE HUMANITIES. PROGRESS REPORT ON PRINTED INFORMATION, CONFERENCES AND VISITATIONS TO NOVEMBER 30, 1966. (TITLE SUPPLIED).

ERIC Educational Resources Information Center

River Dell Regional Schools, Oradell, NJ.

THIS REPORT CITES THE PROGRESS AND ACCOMPLISHMENTS OF THE RIVER DELL CENTER. INFORMATION IS PRESENTED OF (1) PRINTED RELEASES, (2) CONTACTS MADE, (3) ON INSERVICE COURSE OFFERED, (4) DISSEMINATION OF COURSE INFORMATION, (5) VISITATIONS, AND (6) IN-PROGRESS ACTIVITIES. TWO REGIONAL SCHOOL NEWSLETTERS ALONG WITH CORRESPONDENCE LETTERS TO THE NEW…

Profound hearing loss associated with hydrocodone/acetaminophen abuse.

PubMed

Friedman, R A; House, J W; Luxford, W M; Gherini, S; Mills, D

2000-03-01

To describe profound hearing loss associated with hydrocodone overuse and the successful rehabilitation of these patients with cochlear implantation. Retrospective review. A tertiary otologic referral center. Twelve patients with rapidly progressive hearing loss and a concurrent history of hydrocodone overuse. Comprehensive medical histories, physical findings, audiometric tests, and, in those patients undergoing cochlear implantation, postimplantation performance data were reviewed. Clinical characteristics of hydrocodone-related hearing loss and open set word and sentence performance in those patients undergoing cochlear implantation. Hydrocodone overuse was associated with rapidly progressive sensorineural hearing loss in 12 patients. In four patients the initial presentation was unilateral, and two of the patients experienced vestibular symptoms. None of the 12 patients experienced improved thresholds after high-dose prednisone. Seven of the eight patients undergoing cochlear implantation have demonstrated early success with their devices. Hydrocodone is frequently prescribed in combination with acetaminophen for the relief of pain and has a side effects profile similar to other medications in its class. Although not described previously, overuse or abuse can be associated with a rapidly progressive sensorineural hearing loss. These patients can be successfully rehabilitated with cochlear implantation.

Lymphoscintigraphy of draught horses with chronic progressive lymphoedema.

PubMed

de Cock, H E V; Affolter, V K; Wisner, E R; Larson, R F; Ferraro, G L

2006-03-01

Early diagnosis of chronic progressive lymphoedema (CPL) may result in more effective interventions and provide a basis for further investigation of whether early diagnosis could be used as a means of eliminating potential genetic influences by cessation of breeding from affected individuals. Lymphoscintigraphy may be useful in draught horses to differentiate early lesions of CPL from other conditions in the pastern region. Forelimbs of 2 normal and 5 CPL-affected draught horses were evaluated with lymphoscintigraphy. Lymphoscintigraphy showed clearly the presence of interstitial fluid stasis and delayed lymphatic drainage in the affected extremities of diseased animals in contrast to normal animals of these breeds. The rate of decreased clearance of a particulate radiopharmaceutical from the tissues was related positively to the severity of clinical signs. Our findings support the hypothesis that lymph stasis is probably responsible for the progressive swelling and concurrent skin lesions observed in association with CPL in draught horses. Lymphoscintigraphy should also prove useful in diagnosis of CPL in draught horses, even in the mild stages of the disease; such early diagnosis may result in more effective intervention.

Unravelling the progressive role of rattlers in thermoelectric clathrate and strategies for performance improvement: Concurrently enhancing electronic transport and blocking phononic transport

NASA Astrophysics Data System (ADS)

Yang, Jia-Yue; Cheng, Long; Hu, Ming

2017-12-01

Intermetallic clathrates, one class of guest-host systems with perfectly crystalline structures, hold great potential to be the "phonon glass - electron crystal" thermoelectric materials. Previous studies focus on revealing the atomistic origins of blocked phononic transport, yet little attention is drawn to the enhanced electronic transport. In this work, we investigate the binary type-I M8Si46 (M = Sr, Ba, Tl, and Pb) clathrates and unravel how rattlers concurrently block phononic transport and enhance electronic transport from first-principles. By comparing the empty and filled clathrates, the lattice thermal conductivity is greatly reduced by a factor of 21 due to the decrease in phonon relaxation time for propagative phonons over 0-6 THz by 1.5 orders of magnitude. On the other hand, rattlers bridge charge gaps among cages by donating electrons and thus drastically increase electrical conductivity. The concurrent realization of blocked phononic transport and enhanced electronic transport boosts the figure-of-merit (ZT) of empty clathrate by 4 orders of magnitude. Furthermore, by manipulating metallic rattlers and n-type doping, the power factor is markedly improved and ZT can reach 0.55 at 800 K. These results provide a quantitative description of the guest-host interaction and coupling dynamics from first-principles. The proposed strategy of manipulating ratting atoms and in-situ doping offers important guidance to engineer clathrates with high thermoelectric performance.

Apatinib concurrent gemcitabine for controlling malignant ascites in advanced pancreatic cancer patient: A case report.

PubMed

Liang, Lijun; Wang, Lei; Zhu, Panrong; Xia, Youyou; Qiao, Yun; Hui, Kaiyuan; Hu, Chenxi; Ren, Yan; Jiang, Xiaodong

2017-11-01

Malignant ascites (MA) is one of the poor prognostic factors for advanced pancreatic cancer and can bring about serious symptoms. The improvement of quality of life for patients is priority. However, there is no standard method for the treatment for pancreatic cancer-mediated MA. Apatinib is a novel and highly selective tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2. There are no reports of concurrent apatinib with gemcitabine in patients with pancreatic cancer-mediated MA. Herein, we presented a 64-year-old man patient who visited hospital due to abdominal pain for 1 month. He was initially diagnosed with pancreatic cancer and his first symptom was MA. After failing in tube drainage and gemcitabine therapy, the patient received gemcitabine combined apatinib orally and after administrated 1 month, the MA was evaluated as nearly clear response according to the RECIST 1.1 standard, and without further need of paracentesis. The CEA and CA199 reached the lowest level after administrating for 2.5 months during the treatment process. 10.5 months following apatinib administration, the patient achieved a progression-free survival for more than 11 months. Hypertension (grade IV), hand-foot syndrome (grade I) and proteinuria (grade II) were observed. It indicated that apatinib concurrent gemcitabine may be a superior choice for pancreatic cancer-mediated MA. Further clinical trials required to confirm its efficacy and safety. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Apatinib concurrent gemcitabine for controlling malignant ascites in advanced pancreatic cancer patient

PubMed Central

Liang, Lijun; Wang, Lei; Zhu, Panrong; Xia, Youyou; Qiao, Yun; Hui, Kaiyuan; Hu, Chenxi; Ren, Yan; Jiang, Xiaodong

2017-01-01

Abstract Rationale: Malignant ascites (MA) is one of the poor prognostic factors for advanced pancreatic cancer and can bring about serious symptoms. The improvement of quality of life for patients is priority. However, there is no standard method for the treatment for pancreatic cancer-mediated MA. Apatinib is a novel and highly selective tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2. There are no reports of concurrent apatinib with gemcitabine in patients with pancreatic cancer-mediated MA. Patient concerns: Herein, we presented a 64-year-old man patient who visited hospital due to abdominal pain for 1 month. Diagnoses: He was initially diagnosed with pancreatic cancer and his first symptom was MA. Interventions: After failing in tube drainage and gemcitabine therapy, the patient received gemcitabine combined apatinib orally and after administrated 1 month, the MA was evaluated as nearly clear response according to the RECIST 1.1 standard, and without further need of paracentesis. The CEA and CA199 reached the lowest level after administrating for 2.5 months during the treatment process. Outcomes: 10.5 months following apatinib administration, the patient achieved a progression-free survival for more than 11 months. Hypertension (grade IV), hand-foot syndrome (grade I) and proteinuria (grade II) were observed. Lessons: It indicated that apatinib concurrent gemcitabine may be a superior choice for pancreatic cancer-mediated MA. Further clinical trials required to confirm its efficacy and safety. PMID:29381963

Motivational changes that develop in a mouse model of inflammation-induced depression are independent of indoleamine 2,3 dioxygenase.

PubMed

Vichaya, Elisabeth G; Laumet, Geoffroy; Christian, Diana L; Grossberg, Aaron J; Estrada, Darlene J; Heijnen, Cobi J; Kavelaars, Annemieke; Robert Dantzer

2018-04-27

Despite years of research, our understanding of the mechanisms by which inflammation induces depression is still limited. As clinical data points to a strong association between depression and motivational alterations, we sought to (1) characterize the motivational changes that are associated with inflammation in mice, and (2) determine if they depend on inflammation-induced activation of indoleamine 2,3 dioxygenase-1 (IDO1). Lipopolysaccharide (LPS)-treated or spared nerve injured (SNI) wild type (WT) and Ido1 -/- mice underwent behavioral tests of antidepressant activity (e.g., forced swim test) and motivated behavior, including assessment of (1) reward expectancy using a food-related anticipatory activity task, (2) willingness to work for reward using a progressive ratio schedule of food reinforcement, (3) effort allocation using a concurrent choice task, and (4) ability to associate environmental cues with reward using conditioned place preference. LPS- and SNI-induced deficits in behavioral tests of antidepressant activity in WT but not Ido1 -/- mice. Further, LPS decreased food related-anticipatory activity, reduced performance in the progressive ratio task, and shifted effort toward the preferred reward in the concurrent choice task. These effects were observed in both WT and Ido1 -/- mice. Finally, SNI mice developed a conditioned place preference based on relief from pain in an IDO1-independent manner. These findings demonstrate that the motivational effects of inflammation do not require IDO1. Further, they indicate that the motivational component of inflammation-induced depression is mechanistically distinct from that measured by behavioral tests of antidepressant activity.

Phlpp1 facilitates post-traumatic osteoarthritis and is induced by inflammation and promoter demethylation in human osteoarthritis

PubMed Central

Bradley, Elizabeth W.; Carpio, Lomeli R.; McGee-Lawrence, Meghan E.; Becerra, Clara Castillejo; Amanatullah, Derek F.; Ta, Lauren E.; Otero, Miguel; Goldring, Mary B.; Kakar, Sanjeev; Westendorf, Jennifer J.

2016-01-01

OBJECTIVE Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability. OA is characterized by articular chondrocyte deterioration, subchondral bone changes and debilitating pain. One strategy to promote cartilage regeneration and repair is to accelerate proliferation and matrix production of articular chondrocytes. We previously reported that the protein phosphatase Phlpp1 controls chondrocyte differentiation by regulating the activities of anabolic kinases. Here we examined the role of Phlpp1 in osteoarthritis progression in a murine model. We also assessed PHLPP1 expression and promoter methylation. DESIGN Knee joints of WT and Phlpp1−/− mice were surgically destabilized by transection of the medial meniscal ligament (DMM). Mice were assessed for signs of OA progression via radiographic and histological analyses, and pain assessment for mechanical hypersensitivity using the von Frey assay. Methylation of the PHLPP1 promoter and PHLPP1 expression was evaluated in human articular cartilage and chondrocyte cell lines. RESULTS Following DMM surgeries, Phlpp1 deficient mice showed fewer signs of OA and cartilage degeneration. Mechanical allodynia associated with DMM surgeries was also attenuated in Phlpp1−/− mice. PHLPP1 was highly expressed in human articular cartilage from OA patients, but was undetectable in cartilage specimens from femoral neck fractures. Higher PHLPP1 levels correlated with less PHLPP1 promoter CpG methylation in cartilage from OA patients. Blocking cytosine methylation or treatment with inflammatory mediators enhanced PHLPP1 expression in human chondrocyte cell lines. CONCLUSION Phlpp1 deficiency protects against OA progression while CpG demethylation and inflammatory responses promote PHLPP1 expression. PMID:26746148

Three endocrine neoplasms: an unusual combination of pheochromocytoma, pituitary adenoma, and papillary thyroid carcinoma.

PubMed

Sisson, James C; Giordano, Thomas J; Avram, Anca M

2012-04-01

Three endocrine neoplasms-bilateral pheochromocytomas, somatotrophic pituitary adenoma inducing acromegaly, and papillary carcinoma of the thyroid-occurred concurrently in a patient. A genetic mutation was hypothesized. Possible previously described genetic mutations were explored. Clinical assessments, laboratory data, images of tumors, histopathology, and immunohistochemistry of excised tissues documented the three neoplasms. Clinical assessment of the patient, family history, and a review of the literature sought a familial basis for the disorders. The methods confirmed the presence of three endocrine neoplasms. Each neoplasm was surgically excised and histologically verified. Surgical and (131)I treatments reduced the papillary carcinoma, but eventually this tumor progressed to a lethal degree. History, including that of nine siblings, uncovered no familial neoplasms. No similar case was found in the literature, but possible associations with germline mutations were considered. The concurrent development of pheochromocytomas, pituitary somatotrophic adenoma, and papillary thyroid carcinoma appears to be unique. Nevertheless, such tumors, particularly bilateral pheochromocytomas, strongly suggest a de novo germline mutation in a gene not previously associated with multiple endocrine neoplasia syndromes.

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

Long noncoding RNA SOX2OT contributes to gastric cancer progression by sponging miR-194-5p from AKT2.

PubMed

Qu, Fei; Cao, Peilong

2018-05-18

Gastric cancer (GC) is a highly malignant cancer with poor prognosis. Long non-coding RNA (LncRNA) may play an important role in tumor progression. Our present study aimed to explore the effect of LncRNA SOX2OT on GC progression. We observed that SOX2OT was overexpressed in GC tissues and cell lines. Overexpressed SOX2OT promoted cell proliferation and metastasis of GC cells (SGC-7901, TMK-1) and the phosphorylation of AKT2 as well, while knockdown of SOX2OT reversed these effects. Besides that, miR-194-5p was predicted to be a target of SOX2OT and decreased expression of miR-194-5p was observed in GC tissues and cell lines. Overexpressed miR-194-5p counteracted the promoting role of SOX2OT on cell proliferation and invasion of GC cells. Moreover, AKT2 was predicted to be a target of miR-194-5p. The expression of AKT2 was negatively regulated by miR-194-5p while positively regulated by SOX2OT. Overexpressed AKT2 also promoted GC cell proliferation and invasion. Our in vitro experiments suggested that SOX2OT promoted cell proliferation and metastasis of GC cells via sponging miR-194-5p from AKT2. Finally, our in vivo experiments indicated that overexpressed SOX2OT promoted GC tumor growth and metastasis in nude mice. Taken together, our present study suggested that SOX2OT contributed to GC progression via sponging miR-194-5p from AKT2 both in vitro and in vivo. The SOX2OT-miR-194-5p-AKT2 axis may provide a new perspective for treatment of GC. Copyright © 2018. Published by Elsevier Inc.

[Prostate biopsy under magnetic resonance imaging guidance].

PubMed

Kuplevatskiy, V I; CherkashiN, M A; Roshchin, D A; Berezina, N A; Vorob'ev, N A

2016-01-01

Prostate cancer (PC) is one of the most important problems in modern oncology. According to statistical data, PC ranks second in the cancer morbidity structure in the Russian Federation and developed countries and its prevalence has been progressively increasing over the past decade. A need for early diagnosis and maximally accurate morphological verification of the diagnosis in difficult clinical cases (inconvenient tumor location for standard transrectal biopsy; gland scarring changes concurrent with prostatitis and hemorrhage; threshold values of prostate-specific antigen with unclear changes in its doubling per unit time; suspicion of biochemical recurrence or clinical tumor progression after special treatment) leads to revised diagnostic algorithms and clinically introduced new high-tech invasive diagnostic methods. This paper gives the first analysis of literature data on Russian practice using one of the new methods to verify prostate cancer (transrectal prostate cancer under magnetic resonance imaging (MRI) guidance). The have sought the 1995-2015 data in the MEDLINE and Pubmed.

A case of atypical progressive outer retinal necrosis after highly active antiretroviral therapy.

PubMed

Woo, Se Joon; Yu, Hyeong Gon; Chung, Hum

2004-06-01

This is a report of an atypical case of progressive outer retinal necrosis (PORN) and the effect of highly active antiretroviral therapy (HAART) on the clinical course of viral retinitis in an acquired immunodeficiency syndrome (AIDS) patient. A 22-year-old male patient infected with human immunodeficiency virus (HIV) presented with unilaterally reduced visual acuity and a dense cataract. After cataract extraction, retinal lesions involving the peripheral and macular areas were found with perivascular sparing and the mud-cracked, characteristic appearance of PORN. He was diagnosed as having PORN based on clinical features and was given combined antiviral treatment. With concurrent HAART, the retinal lesions regressed, with the regression being accelerated by further treatment with intravenous acyclovir and ganciclovir. This case suggests that HAART may change the clinical course of PORN in AIDS patients by improving host immunity. PORN should be included in the differential diagnosis of acute unilateral cataract in AIDS patients.

The Formation and Function of Plant Cuticles1

PubMed Central

Yeats, Trevor H.; Rose, Jocelyn K.C.

2013-01-01

The plant cuticle is an extracellular hydrophobic layer that covers the aerial epidermis of all land plants, providing protection against desiccation and external environmental stresses. The past decade has seen considerable progress in assembling models for the biosynthesis of its two major components, the polymer cutin and cuticular waxes. Most recently, two breakthroughs in the long-sought molecular bases of alkane formation and polyester synthesis have allowed construction of nearly complete biosynthetic pathways for both waxes and cutin. Concurrently, a complex regulatory network controlling the synthesis of the cuticle is emerging. It has also become clear that the physiological role of the cuticle extends well beyond its primary function as a transpiration barrier, playing important roles in processes ranging from development to interaction with microbes. Here, we review recent progress in the biochemistry and molecular biology of cuticle synthesis and function and highlight some of the major questions that will drive future research in this field. PMID:23893170

Does Employment during High School Impair Academic Progress?

ERIC Educational Resources Information Center

D'Amico, Ronald

1984-01-01

Research results that showed that high school employment may foster high school achievement is explained by a congruence hypothesis, which holds that there is a correspondence between the personality traits promoted and rewarded by employers and those traits promoted and rewarded by teachers. (Author/RM)

The Ties That Bind: Mapping the Dynamic Enhancer-Promoter Interactome

DOE PAGES

Spurrell, Cailyn H.; Dickel, Diane E.; Visel, Axel

2016-11-17

Coupling chromosome conformation capture to molecular enrichment for promoter-containing DNA fragments enables the systematic mapping of interactions between individual distal regulatory sequences and their target genes. Here in this Minireview, we describe recent progress in the application of this technique and related complementary approaches to gain insight into the lineage- and cell-type-specific dynamics of interactions between regulators and gene promoters.

Rapid promotion and progression of fibrovascular polyps by inflammation and/or hyperplasia in hamster check pouch: implications for carcinogenesis assay.

PubMed

McGaughey, C; Jensen, J L

1983-03-01

Tumor initiation by topical application of 7,12-dimethylbenz[a]anthracene (DMBA) in dimethyl sulfoxide (DMSO) followed by topical application of retinyl acetate (RA), ethylphenylpropiolate, or acetic acid in DMSO at inflammatory and hyperplasiogenic dose regimens caused the rapid promotion of fibrovascular polyps with dysplastic epithelium in hamster cheek pouch. Such lesions did not occur in control animals initiated with DMBA followed by application of DMSO only, where inflammation was also minimal. At the dose regimen employed, RA caused obvious cytotoxicity and tissue destruction. With EPP and AA, there was no histological evidence of tissue destruction. At dose regimens resulting in minimal inflammation and no apparent cytotoxicity, RA promoted almost no polyps, but a higher yield of other tumor types. Thus, inflammation and/or hyperplasia apparently exerted a strong polyp-promoting and progressive influence. This and other differences between the tumorigenic responses of hamster-pouch mucosa and mouse skin suggest that the former supplement the latter in carcinogenic risk assessment.

Additive manufacturing: Toward holistic design

DOE PAGES

Jared, Bradley H.; Aguilo, Miguel A.; Beghini, Lauren L.; ...

2017-03-18

Here, additive manufacturing offers unprecedented opportunities to design complex structures optimized for performance envelopes inaccessible under conventional manufacturing constraints. Additive processes also promote realization of engineered materials with microstructures and properties that are impossible via traditional synthesis techniques. Enthused by these capabilities, optimization design tools have experienced a recent revival. The current capabilities of additive processes and optimization tools are summarized briefly, while an emerging opportunity is discussed to achieve a holistic design paradigm whereby computational tools are integrated with stochastic process and material awareness to enable the concurrent optimization of design topologies, material constructs and fabrication processes.

[The implementation of innovations in public health].

PubMed

Systerova, A A; Totskaia, E G

2012-01-01

Nowadays, the innovative activities are considered as the mechanism of implementation of public policy to increase effectiveness of public health system on the basis of achievements of modern medicine and technical sciences. The development, elaboration and implementation of products being in line with corresponding to criteria of innovation, promote the concurrency of medical institutions at the medical services market. The administrators of health departments and medical science professionals are to become aware about the problems of implementation of innovations into medical practice to develop the mechanisms of overcoming these issues.

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

Jared, Bradley H.; Aguilo, Miguel A.; Beghini, Lauren L.

Here, additive manufacturing offers unprecedented opportunities to design complex structures optimized for performance envelopes inaccessible under conventional manufacturing constraints. Additive processes also promote realization of engineered materials with microstructures and properties that are impossible via traditional synthesis techniques. Enthused by these capabilities, optimization design tools have experienced a recent revival. The current capabilities of additive processes and optimization tools are summarized briefly, while an emerging opportunity is discussed to achieve a holistic design paradigm whereby computational tools are integrated with stochastic process and material awareness to enable the concurrent optimization of design topologies, material constructs and fabrication processes.

Progress in Education: A Deconstructionist View.

ERIC Educational Resources Information Center

Buck, George H.; Osborne, John

1990-01-01

Using the deconstructionist theories of Michel Foucault, argues that there are several perennial myths in educational thought (e.g., all change is progressive and what is promoted as change is novel). Finds support for this method of criticism in the work of Quintilian, Bloom, Elkind, and Popper. (DMM)

Alcohol consumption promotes mammary tumor growth and insulin sensitivity

PubMed Central

Hong, Jina; Holcomb, Valerie B.; Tekle, Samrawit A.; Fan, Betty; Núñez, Nomelí P.

2010-01-01

Epidemiological data show that in women, alcohol has a beneficial effect by increasing insulin sensitivity but also a deleterious effect by increasing breast cancer risk. These effects have not been shown concurrently in an animal model of breast cancer. Our objective is to identify a mouse model of breast cancer whereby alcohol increases insulin sensitivity and promotes mammary tumorigenesis. Our results from the glucose tolerance test and the homeostasis model assessment show that alcohol consumption improved insulin sensitivity. However, alcohol-consuming mice developed larger mammary tumors and developed them earlier than water-consuming mice. In vitro results showed that alcohol exposure increased the invasiveness of breast cancer cells in a dose-dependent manner. Thus, this animal model, an in vitro model of breast cancer, may be used to elucidate the mechanism(s) by which alcohol affects breast cancer. PMID:20202743

Gastric cancer-derived exosomes promote peritoneal metastasis by destroying the mesothelial barrier.

PubMed

Deng, Guang; Qu, Jinglei; Zhang, Ye; Che, Xiaofang; Cheng, Yu; Fan, Yibo; Zhang, Simeng; Na, Di; Liu, Yunpeng; Qu, Xiujuan

2017-07-01

An intact mesothelium serves as a protective barrier to inhibit peritoneal carcinomatosis. Cancer-derived exosomes can mediate directional tumor metastasis; however, little is known about whether gastric cancer-derived exosomes will destroy the mesothelial barrier and promote peritoneal dissemination. Here, we demonstrate that gastric cancer-derived exosomes facilitate peritoneal metastasis by causing mesothelial barrier disruption and peritoneal fibrosis. Injury of peritoneal mesothelial cells elicited by gastric cancer-derived exosomes is through concurrent apoptosis and mesothelial-to-mesenchymal transition (MMT). Additionally, upregulation of p-ERK in peritoneal mesothelial cells is primarily responsible for the MMT while contributing little to apoptosis. Together, these data support the concept that exosomes play a crucial role in remodeling the premetastatic microenvironment and identify a novel mechanism for peritoneal metastasis of gastric carcinoma. © 2017 Federation of European Biochemical Societies.

A randomized controlled trial of single versus multiple health behavior change: promoting physical activity and nutrition among adolescents.

PubMed

Prochaska, Judith J; Sallis, James F

2004-05-01

Targeting multiple behaviors for change may provide significant health benefits. This study compared interventions targeting physical activity and nutrition (PAN) concurrently versus physical activity (PA) alone. Adolescents (N=138) were randomized to the PAN or PA intervention or control condition (n=46 per group). Primary outcomes were change in PA accelerometer and 3-day dietary recording from baseline to 3-month follow-up. The PAN and PA interventions were efficacious in supporting boys' (p<.001) but not girls' (p=.663) PA relative to the control condition. Dietary change was minimal. Although the findings do not reveal a decrement to PA promotion when a nutrition intervention was added, neither do they reveal any additional benefit. More studies comparing single versus multibehavioral interventions are needed. ((c) 2004 APA, all rights reserved)

Iron overload accelerates neuronal amyloid-β production and cognitive impairment in transgenic mice model of Alzheimer's disease.

PubMed

Becerril-Ortega, Javier; Bordji, Karim; Fréret, Thomas; Rush, Travis; Buisson, Alain

2014-10-01

Iron dyshomeostasis is proving increasingly likely to be involved in the pathology of Alzheimer's disease (AD); yet, its mechanism is not well understood. Here, we investigated the AD-related mechanism(s) of iron-sulfate exposure in vitro and in vivo, using cultured primary cortical neurons and APP/PS1 AD-model mice, respectively. In both systems, we observed iron-induced disruptions of amyloid precursor protein (APP) processing, neuronal signaling, and cognitive behavior. Iron overload increased production of amyloidogenic KPI-APP and amyloid beta. Further, this APP misprocessing was blocked by MK-801 in vitro, suggesting the effect was N-methyl-D-aspartate receptor (NMDAR) dependent. Calcium imaging confirmed that 24 hours iron exposure led to disrupted synaptic signaling by augmenting GluN2B-containing NMDAR expression-GluN2B messenger RNA and protein levels were increased and promoting excessing extrasynaptic NMDAR signaling. The disrupted GluN2B expression was concurrent with diminished expression of the splicing factors, sc35 and hnRNPA1. In APP/PS1 mice, chronic iron treatment led to hastened progression of cognitive impairment with the novel object recognition discrimination index, revealing a deficit at the age of 4 months, concomitant with augmented GluN2B expression. Together, these data suggest iron-induced APP misprocessing and hastened cognitive decline occur through inordinate extrasynaptic NMDAR activation. Copyright © 2014 Elsevier Inc. All rights reserved.

Phytochemicals inhibit the immunosuppressive functions of myeloid-derived suppressor cells (MDSC): Impact on cancer and age-related chronic inflammatory disorders.

PubMed

Salminen, Antero; Kaarniranta, Kai; Kauppinen, Anu

2018-06-08

Traditional herbal medicine has provided natural remedies against cancers and many age-related inflammatory diseases for thousands of years. Modern drug discovery techniques have revealed several active ingredients and their medicinal targets have been characterized. Concurrently, there has been great progress in understanding the pathological mechanisms underpinning cancers and inflammatory diseases. These studies have demonstrated that immature myeloid-derived suppressor cells (MDSCs) have a crucial role in the immune escape of cancer cells thus promoting tumor growth. Inflammatory factors stimulate the recruitment, expansion, and activation of MDSCs in tumors and inflamed tissues. The immunosuppression generated by MDSCs has an important role in the resolution of acute inflammation but in chronic inflammatory disorders, the activation of MDSCs suppresses the innate and adaptive immune responses thus aggravating the disease processes in association with tumors, chronic infections, and many degenerative diseases. Currently, MDSCs are important drug discovery targets in cancers and chronic inflammatory diseases. Interestingly, there are promising reports that certain phytochemicals can function as potent inhibitors of the immunosuppressive MDSCs that could partially explain the therapeutic benefits of herbal medicine. We will briefly describe the immune suppressive functions of MDSCs in cancers and age-related inflammatory diseases and then review in detail the chemically characterized phytochemicals of different herbal categories, e.g. flavonoids, terpenoids, retinoids, curcumins, and β-glucans, which possess the MDSC-dependent antitumor and anti-inflammatory properties. Copyright © 2018 Elsevier B.V. All rights reserved.

Peroxisome proliferator-activated receptor δ (PPARδ) induces estrogen receptor-positive mammary neoplasia through an inflammatory and metabolic phenotype linked to mTor activation

PubMed Central

Yuan, Hongyan; Lu, Jin; Xiao, Junfeng; Upadhyay, Geeta; Umans, Rachel; Kallakury, Bhaskar; Yin, Yuhzi; Fant, Michael E.; Kopelovich, Levy; Glazer, Robert I.

2013-01-01

The peroxisome proliferator-activated receptor-δ (PPARδ) regulates a multitude of physiological processes associated with glucose and lipid metabolism, inflammation and proliferation. One or more of these processes are potential risk factors for the ability of PPARδ agonists to promote tumorigenesis in the mammary gland. In the present study, we describe a new transgenic mouse model in which activation of PPARδ in the mammary epithelium by endogenous or synthetic ligands resulted in progressive histopathological changes that culminated in the appearance of estrogen receptor- and progesterone receptor-positive and ErbB2-negative infiltrating ductal carcinomas. Multiparous mice presented with mammary carcinomas after a latency of 12 months, and administration of the PPARδ ligand GW501516 reduced tumor latency to five months. Histopathological changes occurred concurrently with an increase in an inflammatory, invasive, metabolic and proliferative gene signature, including expression of the trophoblast gene, Plac1, beginning one week after GW501516 treatment, and remained elevated throughout tumorigenesis. The appearance of malignant changes correlated with a pronounced increase in phosphatidylcholine and lysophosphatidic acid metabolites, which coincided with activation of Akt and mTor signaling that were attenuated by treatment with the mTor inhibitor everolimus. Our findings are the first to demonstrate a direct role of PPARδ in the pathogenesis of mammary tumorigenesis, and suggest a rationale for therapeutic approaches to prevent and treat this disease. PMID:23811944

Comparing the effects of entertainment media and tobacco marketing on youth smoking

PubMed Central

Sargent, J D; Gibson, J; Heatherton, T F

2009-01-01

Objectives To examine the concurrent effects of exposure to movie smoking and tobacco marketing receptivity on adolescent smoking onset and progression. Methods Cross-sectional study of 4524 northern New England adolescents aged 10–14 in 1999 with longitudinal follow-up of 2603 baseline never-smokers. Cross-sectional outcomes included ever tried smoking and higher level of lifetime smoking among 784 experimenters. The longitudinal outcome was onset of smoking among baseline never-smokers two years later. Movie smoking exposure was modelled as four population quartiles, tobacco marketing receptivity included two levels—having a favourite tobacco advert and wanting/owning tobacco promotional items. All analyses controlled for sociodemographics, other social influences, personality characteristics of the adolescent and parenting style. Results In the full cross-sectional sample, 17.5% had tried smoking; both exposure to movie smoking and receptivity to tobacco marketing were associated with having tried smoking. Among experimental smokers, the majority (64%) were receptive to tobacco marketing, which had a multivariate association with higher level of lifetime smoking (movie smoking did not). In the longitudinal study 9.5% of baseline never-smokers tried smoking at follow-up. Fewer never-smokers (18.5%) were receptive to tobacco marketing. Movie smoking had a multivariate association with trying smoking (receptivity to tobacco marketing did not). Conclusions The results suggest separate roles for entertainment media and tobacco marketing on adolescent smoking. Both exposures deserve equal emphasis from a policy standpoint. PMID:18948391

Brain interstitial fluid TNF-α after subarachnoid hemorrhage

PubMed Central

Hanafy, Khalid A.; Grobelny, Bartosz; Fernandez, Luis; Kurtz, Pedro; Connolly, ES; Mayer, Stephan A.; Schindler, Christian; Badjatia, Neeraj

2010-01-01

Objective: TNF-α is an inflammatory cytokine that plays a central role in promoting the cascade of events leading to an inflammatory response. Recent studies have suggested that TNF-α may play a key role in the formation and rupture of cerebral aneurysms, and that the underlying cerebral inflammatory response is a major determinate of outcome following subrarachnoid hemorrhage (SAH). Methods: We studied 14 comatose SAH patients who underwent multimodality neuromonitoring with intracranial pressure (ICP) and cerebral microdialysis as part of their clinical care. Continuous physiological variables were time-locked every 8 hours and recorded at the same point that brain interstitial fluid TNF-α was measured in brain microdialysis samples. Significant associations were determined using generalized estimation equations. Results: Each patient had a mean of 9 brain tissue TNF-α measurements obtained over an average of 72 hours of monitoring. TNF-α levels rose progressively over time. Predictors of elevated brain interstitial TNF-α included higher brain interstitial fluid glucose levels (β=0.066, P<0.02), intraventricular hemorrhage (β=0.085, P<0.021), and aneurysm size >6 mm (β=0.14, p<0.001). There was no relationship between TNF-α levels and the burden of cisternal SAH; concurrent measurements of serum glucose, or lactate-pyruvate ratio. Interpretation: Brain interstitial TNF-α levels are elevated after SAH, and are associated with large aneurysm size, the burden of intraventricular blood, and elevation brain interstitial glucose levels. PMID:20110094

Cancer-induced cardiac cachexia: Pathogenesis and impact of physical activity (Review).

PubMed

Belloum, Yassine; Rannou-Bekono, Françoise; Favier, François B

2017-05-01

Cachexia is a wasting syndrome observed in many patients suffering from several chronic diseases including cancer. In addition to the progressive loss of skeletal muscle mass, cancer cachexia results in cardiac function impairment. During the severe stage of the disease, patients as well as animals bearing cancer cells display cardiac atrophy. Cardiac energy metabolism is also impeded with disruption of mitochondrial homeostasis and reduced oxidative capacity, although the available data remain equivocal. The release of inflammatory cytokines by tumor is a key mechanism in the initiation of heart failure. Oxidative stress, which results from the combination of chemotherapy, inadequate antioxidant consumption and chronic inflammation, will further foster heart failure. Protein catabolism is due to the concomitant activation of proteolytic systems and inhibition of protein synthesis, both processes being triggered by the deactivation of the Akt/mammalian target of rapamycin pathway. The reduction in oxidative capacity involves AMP-activated protein kinase and peroxisome proliferator-activated receptor gamma coactivator 1α dysregulation. The nuclear factor-κB transcription factor plays a prominent role in the coordination of these alterations. Physical exercise appears as an interesting non-pharmaceutical way to counteract cancer cachexia-induced-heart failure. Indeed, aerobic training has anti-inflammatory effects, increases anti-oxidant defenses, prevents atrophy and promotes oxidative metabolism. The present review points out the importance of better understanding the concurrent structural and metabolic changes within the myocardium during cancer and the protective effects of exercise against cardiac cachexia.

Concurrent treatment with a macrocyclic lactone and benzimidazole provides season long performance advantages in grazing cattle harboring macrocyclic lactone resistant nematodes.

PubMed

Edmonds, M D; Vatta, A F; Marchiondo, A A; Vanimisetti, H B; Edmonds, J D

2018-03-15

In 2013, a 118-day study was initiated to investigate the efficacy of concurrent treatment at pasture turnout with an injectable macrocyclic lactone with activity up to 28 days and an oral benzimidazole, referred to as "conventional" anthelmintics, when compared to treatment with conventional macrocyclic lactone alone or an injectable macrocyclic lactone with extended activity of 100 days or longer. A group of 210 steers were obtained from a ranch in California and transported to Idaho, USA. A total of 176 steers with the highest fecal egg counts were blocked by pre-treatment body weights and pasture location. A total of 44 pasture paddocks were assigned with 4 steers per paddock with 12 paddocks per therapeutic treatment group and 8 paddocks per controls. The four treatments were injectable doramectin (Dectomax ® , Zoetis Inc., 0.2 mg kg -1 BW, SC), injectable doramectin concurrently with oral albendazole (Valbazen ® , Zoetis Inc., 10 mg kg -1 BW, PO), extended release injectable eprinomectin (LongRange™, Merial Limited, 1 mg kg -1 BW, SC) or saline. Cattle were individually weighed and sampled for fecal egg count on Days 0, 31/32, 61, 88, and 117/118 with an additional fecal sample on Day 14. At conclusion, one steer per paddock was euthanized for nematode recovery. The results from the first 32 days found evidence of macrocyclic lactone resistance against injectable doramectin and extended release eprinomectin. During this period the concurrent therapy provided nearly 100% efficacy based on fecal egg count reduction and a 19.98% improvement in total weight gain compared to controls (P = 0.039). At the conclusion of the 118-day study and past the approved efficacy for the conventional anthelmintics, the concurrent therapy with conventional anthelmintics provided a 22.98% improvement in total weight gain compared to controls (P = 0.004). The 118-day improvement in weight gain for the extended release eprinomectin group (29.06% compared to control) was not statistically different from the concurrent therapy with conventional anthelmintics. The results indicate that concurrent treatment with a conventional macrocyclic lactone and benzimidazole may provide production benefits early in the grazing period that continue throughout the entire period for cattle harboring macrocyclic lactone resistant nematodes. By using two different anthelmintic classes together, macrocyclic lactone resistant parasites were effectively controlled early in the period. Furthermore, the use of an effective conventional anthelmintic treatment regimen without an extended period of drug release may help to promote refugia and decrease the further selection for anthelmintic resistant parasites. Copyright © 2018 Elsevier B.V. All rights reserved.

Moving from idea to action: promoting physical activity by empowering adolescents.

PubMed

Lindqvist, Anna-Karin; Mikaelsson, Katarina; Westerberg, Mats; Gard, Gunvor; Kostenius, Catrine

2014-11-01

Physical activity provides fundamental health benefits for children and youth. The aim of the study was to explore the possibility of conducting an empowerment-inspired intervention and examine the impact of the intervention in promoting moderate and vigorous physical activity (MVPA) among adolescents. A nonrandomized trial with a concurrent control group was carried out. Physical activity data were collected before and after the intervention with daily questions by short message service. Self-efficacy, social support, and attitude were also measured before and after the intervention since they were possible mediators. The intervention was created by the students, the researchers, and the teachers using an empowerment-based approach. Students in the intervention group (n = 21) increased their MVPA on average by 4.9 (SD = 28.9) minutes per day, and students in the control group (n = 25) reduced their MVPA on average by 25.4 (SD = 23.0) minutes per day (p = .000). The intervention might have contributed to a promotion of physical activity among students in the intervention group. The most valuable contribution this study provides is the knowledge that it is possible to develop and conduct an empowerment-inspired intervention to promote adolescent physical activity. © 2014 Society for Public Health Education.

Reinforcement of Smoking and Drinking: Tobacco Marketing Strategies Linked With Alcohol in the United States

PubMed Central

Jiang, Nan

2011-01-01

Objectives. We investigated tobacco companies’ knowledge about concurrent use of tobacco and alcohol, their marketing strategies linking cigarettes with alcohol, and the benefits tobacco companies sought from these marketing activities. Methods. We performed systematic searches on previously secret tobacco industry documents, and we summarized the themes and contexts of relevant search results. Results. Tobacco company research confirmed the association between tobacco use and alcohol use. Tobacco companies explored promotional strategies linking cigarettes and alcohol, such as jointly sponsoring special events with alcohol companies to lower the cost of sponsorships, increase consumer appeal, reinforce brand identity, and generate increased cigarette sales. They also pursued promotions that tied cigarette sales to alcohol purchases, and cigarette promotional events frequently featured alcohol discounts or encouraged alcohol use. Conclusions. Tobacco companies’ numerous marketing strategies linking cigarettes with alcohol may have reinforced the use of both substances. Because using tobacco and alcohol together makes it harder to quit smoking, policies prohibiting tobacco sales and promotion in establishments where alcohol is served and sold might mitigate this effect. Smoking cessation programs should address the effect that alcohol consumption has on tobacco use. PMID:21852637

The Critical Role of Inflammation in the Pathogenesis and Progression of Myeloid Malignancies

PubMed Central

Craver, Brianna M.; El Alaoui, Kenza; Scherber, Robyn M.; Fleischman, Angela G.

2018-01-01

Hematopoietic stem cells (HSCs) maintain an organism’s immune system for a lifetime, and derangements in HSC proliferation and differentiation result in hematologic malignancies. Chronic inflammation plays a contributory if not causal role in HSC dysfunction. Inflammation induces HSC exhaustion, which promotes the emergence of mutant clones that may be resistant to an inflammatory microenvironment; this likely promotes the onset of a myeloid hematologic malignancy. Inflammatory cytokines are characteristically high in patients with myeloid malignancies and are linked to disease initiation, symptom burden, disease progression, and worsened prognostic survival. This review will cover our current understanding of the role of inflammation in the initiation, progression, and complications of myeloid hematologic malignancies, drawing from clinical studies as well as murine models. We will also highlight inflammation as a therapeutic target in hematologic malignancies. PMID:29614027

The Promotion of Girls' Education through Recruitment and Training of Female Teachers in Nepal (Phase I). Mid-Decade Review of Progress towards Education for All.

ERIC Educational Resources Information Center

Thapa, Bijaya; Bajracharya, Hridaya; Thapa, Renu; Chitrakar, Roshan; Lamichhane, Shreeram; Tuladhar, Sumon

In 1995, the International Consultative Forum on Education for All commissioned case studies in developing countries as part of a mid-decade review of progress in expanding access to basic education. This paper examines the progress of Nepal's Basic and Primary Education Master Plan (BPEP), which aims to increase female participation in formal and…

Synergistic Action of FOXP3 and TSC1 Pathways During Tumor Progression

DTIC Science & Technology

2015-10-01

invasive carcinoma and, ultimately, metastatic disease [1-3]. Mouse models of PIN (mPIN) generated by a single- mutant gene in prostate do not progress...downstream target) is sufficient to significantly reduce the initiation of prostate cancer in the Pten conditional knockout mouse model [19-21...the possibility that these two genetic hits cooperate to promote tumor progression, and mouse models show that this cooperation accelerates

Androgen receptor (AR) suppresses miRNA-145 to promote renal cell carcinoma (RCC) progression independent of VHL status

PubMed Central

Chen, Yuan; Sun, Yin; Rao, Qun; Xu, Hua; Li, Lei; Chang, Chawnshang

2015-01-01

Mutational inactivation of the VHL tumor suppressor plays key roles in the development of renal cell carcinoma (RCC), and mutated VHL-mediated VEGF induction has become the main target for the current RCC therapy. Here we identified a signal pathway of VEGF induction by androgen receptor (AR)/miRNA-145 as a new target to suppress RCC progression. Mechanism dissection revealed that AR might function through binding to the androgen receptor element (ARE) located on the promoter region of miRNA-145 to suppress p53's ability to induce expression of miRNA-145 that normally suppresses expression of HIF2α/VEGF/MMP9/CCND1. Suppressing AR with AR-shRNA or introducing exogenous miRNA-145 mimic can attenuate RCC progression independent of VHL status. MiR-145 mimic in preclinical RCC orthotopic xenograft mouse model revealed its efficacy in suppression of RCC progression. These results together identified signals by AR-suppressed miRNA-145 as a key player in the RCC progression via regulating HIF2α/VEGF/MMP9/CCND1 expression levels. Blockade of the newly identified signal by AR inhibition or miRNA-145 mimics has promising therapeutic benefit to suppress RCC progression. PMID:26304926

The p21-activated kinase 4-Slug transcription factor axis promotes epithelial-mesenchymal transition and worsens prognosis in prostate cancer.

PubMed

Park, Jung-Jin; Park, Mee-Hee; Oh, Eun Hye; Soung, Nak-Kyun; Lee, Soo Jae; Jung, Jae-Kyung; Lee, Ok-Jun; Yun, Seok Joong; Kim, Wun-Jae; Shin, Eun-Young; Kim, Eung-Gook

2018-05-30

Epithelial-mesenchymal transition (EMT) facilitates cancer invasion and metastasis and thus accelerates cancer progression. p21-activated kinase 4 (PAK4) is a critical regulator of prostate cancer (PC) progression. Here, we report that PAK4 activation promotes PC progression through the EMT regulator Slug. We find that phosphorylated PAK4 S474 (pPAK4) levels, an index of PAK4 activation, were tightly associated with Gleason score (p < 0.001), a clinical indicator of PC progression, but not with prostate serum antigen levels or tumor stage. Stable silencing of PAK4 in PC cells reduced their potential for EMT, cellular invasion, and metastasis in vivo. PAK4 bound and directly phosphorylated Slug at two previously unknown sites, S158 and S254, which resulted in its stabilization. The non-phosphorylatable form Slug S158A/S254A upregulated transcription of CDH1, which encodes E-cadherin, and thus suppressed EMT and invasion, to a greater extent than did wild-type Slug. The strong EMT inducer TGF-β elevated pPAK4 and pSlug S158 levels; PAK4 knockdown or introduction of a dominant-negative form of PAK4 inhibited both TGF-β-stimulated EMT and an increase in pSlug S158 levels. Finally, immunohistochemistry revealed a positive correlation between pPAK4 and pSlug S158 but an inverse correlation between pSlug S158 and E-cadherin. The results suggest that the PAK4-Slug axis represents a novel pathway that promotes PC progression.

Genistein versus ICI 182, 780: an ally or enemy in metastatic progression of prostate cancer.

PubMed

Nakamura, Hisae; Wang, Yuwei; Xue, Hui; Romanish, Mark T; Mager, Dixie L; Helgason, Cheryl D; Wang, Yuzhuo

2013-12-01

Androgen signalling through the androgen receptor (AR) plays a critical role in prostate cancer (PCa) initiation and progression. Estrogen in synergy with androgen is essential for cell growth of the normal and malignant prostate. However, the exact role that estrogen and the estrogen receptor play in prostate carcinogenesis remains unclear. We have previously demonstrated the metastasis-promoting effect of an estrogen receptor beta (ERβ) agonist (genistein) in a patient-derived PCa xenograft model mimicking localized and metastatic disease. To test the hypothesis that the tumor-promoting activity of genistein was due to its estrogenic properties, we treated the xenograft-bearing mice with genistein and an anti-estrogen compound (ICI 182, 780) and compared the differential gene expression using microarrays. Using a second xenograft model which was derived from another patient, we showed that genistein promoted disease progression in vivo and ICI 182, 780 inhibited metastatic spread. The microarray analysis revealed that the metallothionein (MT) gene family was differentially expressed in tumors treated by these compounds. Using qRT-PCR, the differences in expression levels were validated in the metastatic and non-metastatic LTL313 PCa xenograft tumor lines, both of which were originally derived from the same PCa patient. Together our data provide evidence that genistein stimulates and ICI 182, 780 inhibits metastatic progression, suggesting that these effects may be mediated by ERβ signalling. © 2013 Wiley Periodicals, Inc.

Kallikrein-related peptidase 4 induces cancer-associated fibroblast features in prostate-derived stromal cells.

PubMed

Kryza, Thomas; Silva, Lakmali M; Bock, Nathalie; Fuhrman-Luck, Ruth A; Stephens, Carson R; Gao, Jin; Samaratunga, Hema; Lawrence, Mitchell G; Hooper, John D; Dong, Ying; Risbridger, Gail P; Clements, Judith A

2017-10-01

The reciprocal communication between cancer cells and their microenvironment is critical in cancer progression. Although involvement of cancer-associated fibroblasts (CAF) in cancer progression is long established, the molecular mechanisms leading to differentiation of CAFs from normal fibroblasts are poorly understood. Here, we report that kallikrein-related peptidase-4 (KLK4) promotes CAF differentiation. KLK4 is highly expressed in prostate epithelial cells of premalignant (prostatic intraepithelial neoplasia) and malignant lesions compared to normal prostate epithelia, especially at the peristromal interface. KLK4 induced CAF-like features in the prostate-derived WPMY1 normal stromal cell line, including increased expression of alpha-smooth muscle actin, ESR1 and SFRP1. KLK4 activated protease-activated receptor-1 in WPMY1 cells increasing expression of several factors (FGF1, TAGLN, LOX, IL8, VEGFA) involved in prostate cancer progression. In addition, KLK4 induced WPMY1 cell proliferation and secretome changes, which in turn stimulated HUVEC cell proliferation that could be blocked by a VEGFA antibody. Importantly, the genes dysregulated by KLK4 treatment of WPMY1 cells were also differentially expressed between patient-derived CAFs compared to matched nonmalignant fibroblasts and were further increased by KLK4 treatment. Taken together, we propose that epithelial-derived KLK4 promotes tumour progression by actively promoting CAF differentiation in the prostate stromal microenvironment. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

APELA promotes tumour growth and cell migration in ovarian cancer in a p53-dependent manner.

PubMed

Yi, Yuyin; Tsai, Shu-Huei; Cheng, Jung-Chien; Wang, Evan Y; Anglesio, Michael S; Cochrane, Dawn R; Fuller, Megan; Gibb, Ewan A; Wei, Wei; Huntsman, David G; Karsan, Aly; Hoodless, Pamela A

2017-12-01

APELA is a small, secreted peptide that can function as a ligand for the G-protein coupled receptor, Apelin Receptor (APLNR, APJ). APELA plays an essential role in endoderm differentiation and cardiac development during embryogenesis. We investigated whether APELA exerts any functions in cancer progression. The Cancer Genome Atlas (TCGA) RNA sequencing datasets, microarray from an OCCC mouse model, and RNA isolated from fresh frozen and FFPE patient tissue were used to assess APELA expression. APELA knockout ovarian clear cell carcinoma (OCCC) cell lines were generated using CRISPR/Cas9. APELA was expressed in various ovarian cancer histotypes and was especially elevated in OCCC. Disruption of APELA expression in OCCC cell lines suppressed cell growth and migration, and altered cell-cycle progression. Moreover, addition of human recombinant APELA peptide to the OCCC cell line OVISE promoted cell growth and migration. Interestingly, OVISE cells do not express APLNR, suggesting that APELA can function through an APLNR-independent pathway. Furthermore, APELA affected cell growth and cell cycle progression in a p53-dependent manner. In addition, APELA knockdown induced p53 expression in cancer cell lines. Our findings uncover a potential oncogenic role for APELA in promoting ovarian tumour progression and provide a possible therapeutic strategy in ovarian cancer by targeting APELA. Copyright © 2017 Elsevier Inc. All rights reserved.

Hepatocellular carcinoma-associated mesenchymal stem cells promote hepatocarcinoma progression: role of the S100A4-miR155-SOCS1-MMP9 axis.

PubMed

Yan, Xin-Long; Jia, Ya-Li; Chen, Lin; Zeng, Quan; Zhou, Jun-Nian; Fu, Chun-Jiang; Chen, Hai-Xu; Yuan, Hong-Feng; Li, Zhi-Wei; Shi, Lei; Xu, Ying-Chen; Wang, Jing-Xue; Zhang, Xiao-Mei; He, Li-Juan; Zhai, Chao; Yue, Wen; Pei, Xue-Tao

2013-06-01

Cancer-associated mesenchymal stem cells (MSCs) play a pivotal role in modulating tumor progression. However, the interactions between liver cancer-associated MSCs (LC-MSCs) and hepatocellular carcinoma (HCC) remain unreported. Here, we identified the presence of MSCs in HCC tissues. We also showed that LC-MSCs significantly enhanced tumor growth in vivo and promoted tumor sphere formation in vitro. LC-MSCs also promoted HCC metastasis in an orthotopic liver transplantation model. Complementary DNA (cDNA) microarray analysis showed that S100A4 expression was significantly higher in LC-MSCs compared with liver normal MSCs (LN-MSCs) from adjacent cancer-free tissues. Importantly, the inhibition of S100A4 led to a reduction of proliferation and invasion of HCC cells, while exogenous S100A4 expression in HCC cells resulted in heavier tumors and more metastasis sites. Our results indicate that S100A4 secreted from LC-MSCs can promote HCC cell proliferation and invasion. We then found the expression of oncogenic microRNA (miR)-155 in HCC cells was significantly up-regulated by coculture with LC-MSCs and by S100A4 ectopic overexpression. The invasion-promoting effects of S100A4 were significantly attenuated by a miR-155 inhibitor. These results suggest that S100A4 exerts its effects through the regulation of miR-155 expression in HCC cells. We demonstrate that S100A4 secreted from LC-MSCs promotes the expression of miR-155, which mediates the down-regulation of suppressor of cytokine signaling 1, leading to the subsequent activation of STAT3 signaling. This promotes the expression of matrix metalloproteinases 9, which results in increased tumor invasiveness. S100A4 secreted from LC-MSCs is involved in the modulation of HCC progression, and may be a potential therapeutic target. (HEPATOLOGY 2013). Copyright © 2013 American Association for the Study of Liver Diseases.

Characterization of caries progression on dentin after irradiation with Nd:YAG laser by FTIR spectroscopy and fluorescence imaging

NASA Astrophysics Data System (ADS)

Ana, P. A.; Brito, A. M. M.; Zezell, D. M.; Lins, E. C. C. C.

2015-06-01

Considering the use of high intensity lasers for preventing dental caries, this blind in vitro study evaluated the compositional and fluorescence effects promoted by Nd:YAG laser (λ=1064 nm) when applied for prevention of progression of dentin caries, in association or not with topical application of acidulated phosphate fluoride (APF). Sixty bovine root dentin slabs were prepared and demineralized by 32h in order to create early caries lesions. After, the slabs were distributed into six experimental groups: G1- untreated and not submitted to a pH-cycling model; G2- untreated and submitted to a pH-cycling model; G3- acidulated phosphate fluoride application (APF); G4- Nd:YAG irradiation (84.9 J/cm2, 60 mJ/pulse); G5- treated with Nd:YAG+APF; G6- treated with APF+Nd:YAG. After treatments, the samples of groups G2 to G6 were submitted to a 4-day pH-cycling model in order to simulate the progression of early caries lesions. All samples were characterized by the micro-attenuated total reflection technique of Fourier transformed infrared spectroscopy (μATR-FTIR), using a diamond crystal, and by a fluorescence imaging system (FIS), in which it was used an illuminating system at λ= 405±30 nm. Demineralization promoted reduction in carbonate and phosphate contents, exposing the organic matter; as well, it was observed a significant reduction of fluorescence intensity. Nd:YAG laser promoted additional chemical changes, and increased the fluorescence intensity even with the development of caries lesions. It was concluded that the compositional changes promoted by Nd:YAG, when associated to APF, are responsible for the reduction of demineralization progression observed on root dentin.

TRIM24 promotes glioma progression and enhances chemoresistance through activation of the PI3K/Akt signaling pathway.

PubMed

Zhang, L-H; Yin, A-A; Cheng, J-X; Huang, H-Y; Li, X-M; Zhang, Y-Q; Han, N; Zhang, X

2015-01-29

The tripartite motif protein TRIM24 (tripartite motif-containing 24) has been found to play distinct roles in tumor development and progression, according to different tumor contexts. However, it remains elusive whether TRIM24 plays a role in malignant gliomas that are the most common and deadly primary brain tumors in adults. We report here that TRIM24 expression is positively correlated with glioma malignancy and is negatively associated with prognosis of patients with newly diagnosed glioblastoma, which is the most malignant form of gliomas but displays highly heterogeneous clinical outcome. The multivariate Cox regression analysis demonstrates the independent predictive value of TRIM24 expression level for overall and progression-free survival. Knockdown of TRIM24 suppresses cell proliferation, cell cycle progression, clone formation and in vivo tumor development, whereas overexpression of TRIM24 promotes cell growth. Chromatin immunoprecipitation, real-time reverse transcription-PCR and mutation analyses demonstrate that TRIM24 binds to the PIK3CA promoter via its PHD-Bromo domain to activate the transcription of PIK3CA gene, thus enhancing phosphatidylinositide 3-kinase (PI3K)/Akt signaling. The pan-PI3K inhibitor LY294002 and small interfering RNA targeting PIK3CA both abrogate the growth-promoting effect of TRIM24. Moreover, TRIM24 regulates the expression of DNA repair enzyme O(6)-methylguanine-DNA methyltransferase (MGMT) through PI3K/Akt/nuclear factor-κB signaling transduction and enhances resistance to temozolomide, the standard chemotherapeutic agent for glioblastoma. Finally, glioblastoma patients with low TRIM24 expression benefit from chemotherapy, whereas those with high TRIM24 expression do not have such benefit. Our results suggest that TRIM24 might serve as a potential prognostic marker and therapeutic target for the management of malignant gliomas.

The utility and cost of routine follow-up procedures in the surveillance of ovarian and primary peritoneal carcinoma: a 16-year institutional review.

PubMed

Rettenmaier, N B; Rettenmaier, C R; Wojciechowski, T; Abaid, L N; Brown, J V; Micha, J P; Goldstein, B H

2010-11-23

The purpose of this study was to evaluate the number of ovarian cancer and primary peritoneal cancer (PPC) progressive disease cases identified via routine follow-up procedures and the corresponding cost throughout a 16-year period at a single medical institution. Previously undiagnosed epithelial ovarian (n=241), PPC (n=23), and concurrent ovarian and uterine (n=24) cancer patients were treated and then followed via CA-125, imaging (e.g., CT scan, chest X-ray), physical examination and vaginal cytology. In the group of 287 patients, there were 151 cases of disease progression. Serial imaging detected the highest number of progressive disease cases (66 initial and 45 confirmatory diagnoses), but the cost was rather high ($13,454 per patient recurrence), whereas CA-125 testing (74 initial and 20 corroborative diagnoses) was the least expensive ($3,924) per recurrent diagnosis. The total cost of surveillance during the 16-year period was nearly $2,400,000. Ultimately, serial imaging and the CA-125 assay detected the highest number of ovarian cancer and PCC progressive disease cases in comparison to physical examination and vaginal cytology, but nevertheless, all of the procedures were conducted at a considerable financial expense.

From conventionally fractionated radiation therapy to hyperfractionated radiation therapy alone and with concurrent chemotherapy in patients with early-stage nonsmall cell lung cancer.

PubMed

Jeremić, Branislav; Milicić, Biljana

2008-02-15

The authors' single-institution experience in patients with early-stage (I and II) nonsmall cell lung cancer (NSCLC) who were treated between 1980 and 1998 with either conventionally fractionated (CF) radiation therapy (RT), or hyperfractionated (HFX) RT, or HFX RT with concurrent paclitaxel/carboplatin (HFX RT-Pac/C) was reviewed. Seventy-eight patients received 60 grays (Gy) in 30 daily fractions (CF), 116 patients received 69.6 Gy (1.2 Gy twice daily), and 56 patients received 67.6 Gy (1.3 Gy twice daily) with concurrent, low-dose, daily C (25 mg/m2) and Pac (10 mg/m2). Biologically equivalent doses for the 3 groups were 72 Gy, 78 Gy, and 76 Gy, respectively, for acute effects (alpha/beta = 10 Gy) and 120 Gy, 111 Gy, and 111 Gy, respectively, for late effects (alpha/beta = 2 Gy). For all 250 patients, the overall median survival was 27 months, the cause-specific survival was 27 months, the local progression-free survival was 32 months, and distant metastasis-free survival was not achieved; and the respective 5-year survival rates were 27%, 32%, 45%, and 68%. CF achieved significantly inferior survival than either HFX RT alone or HFX RT-Pac/C (P = .0332 and P = .0013, respectively), and no difference was observed between the 2 HFX RT regimens (P = .1934). Only acute hematologic high-grade toxicity (grade >or=3) was more frequent with HFX RT-Pac/C than with either RT alone, whereas other toxicities were similar between the 3 treatment groups. HFX RT with or without concurrent chemotherapy may be better than CF in patients with early-stage NSCLC. The role of chemotherapy deserves further investigation, because the group that received chemotherapy in the current study had a higher incidence of acute high-grade hematologic toxicity. Cancer 2008. (c) 2008 American Cancer Society.

RTOG 0913: A Phase 1 Study of Daily Everolimus (RAD001) in Combination With Radiation Therapy and Temozolomide in Patients With Newly Diagnosed Glioblastoma

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

Chinnaiyan, Prakash, E-mail: prakash.chinnaiyan@moffitt.org; Won, Minhee; Wen, Patrick Y.

Purpose: To determine the safety of the mammalian target of rapamycin inhibitor everolimus (RAD001) administered daily with concurrent radiation and temozolomide in newly diagnosed glioblastoma patients. Methods and Materials: Everolimus was administered daily with concurrent radiation (60 Gy in 30 fractions) and temozolomide (75 mg/m{sup 2} per day). Everolimus was escalated from 2.5 mg/d (dose level 1) to 5 mg/d (dose level 2) to 10 mg/d (dose level 3). Adjuvant temozolomide was delivered at 150 to 200 mg/m{sup 2} on days 1 to 5, every 28 days, for up to 12 cycles, with concurrent everolimus at the previously established dailymore » dose of 10 mg/d. Dose escalation continued if a dose level produced dose-limiting toxicities (DLTs) in fewer than 3 of the first 6 evaluable patients. Results: Between October 28, 2010, and July 2, 2012, the Radiation Therapy Oncology Group 0913 protocol initially registered a total of 35 patients, with 25 patients successfully meeting enrollment criteria receiving the drug and evaluable for toxicity. Everolimus was successfully escalated to the predetermined maximum tolerated dose of 10 mg/d. Two of the first 6 eligible patients had a DLT at each dose level. DLTs included gait disturbance, febrile neutropenia, rash, fatigue, thrombocytopenia, hypoxia, ear pain, headache, and mucositis. Other common toxicities were grade 1 or 2 hypercholesterolemia and hypertriglyceridemia. At the time of analysis, there was 1 death reported, which was attributed to tumor progression. Conclusions: Daily oral everolimus (10 mg) combined with both concurrent radiation and temozolomide followed by adjuvant temozolomide is well tolerated, with an acceptable toxicity profile. A randomized phase 2 clinical trial with mandatory correlative biomarker analysis is currently under way, designed to both determine the efficacy of this regimen and identify molecular determinants of response.« less

Prospective Phase I-II Trial of Helical Tomotherapy With or Without Chemotherapy for Postoperative Cervical Cancer Patients

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

Schwarz, Julie K., E-mail: jschwarz@radonc.wustl.edu; Department of Cell Biology and Physiology, Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO; Alvin J. Siteman Cancer Center, Washington University School of Medicine, St. Louis, MO

2011-12-01

Purpose: To investigate, in a prospective trial, the acute and chronic toxicity of patients with cervical cancer treated with surgery and postoperative intensity-modulated radiotherapy (RT) delivered using helical tomotherapy, with or without the administration of concurrent chemotherapy. Patients and Methods: A total of 24 evaluable patients entered the study between March 2006 and August 2009. The indications for postoperative RT were tumor size, lymphovascular space invasion, and the depth of cervical stromal invasion in 15 patients; 9 patients underwent postoperative RT because of surgically positive lymph nodes. All patients underwent pelvic RT delivered with helical tomotherapy and intracavitary high-dose-rate brachytherapy.more » Treatment consisted of concurrent weekly platinum in 17, sequential carboplatin/Taxol in 1, and RT alone in 6. The patients were monitored for acute and chronic toxicity using the Common Toxicity Criteria, version 3.0. Results: The median follow-up was 24 months (range, 4-49). At the last follow-up visit, 23 patients were alive and disease free. Of the 24 patients, 12 (50%) experienced acute Grade 3 gastrointestinal toxicity (anorexia in 5, diarrhea in 4, and nausea in 3). One patient developed acute Grade 4 genitourinary toxicity (vesicovaginal fistula). For patients treated with concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 71% and 24%, respectively. For patients treated without concurrent chemotherapy, the incidence of acute Grade 3 and 4 hematologic toxicity was 29% and 14%, respectively. Two long-term toxicities occurred (vesicovaginal fistula at 25 months and small bowel obstruction at 30 months). The overall and progression-free survival rate at 3 years for all patients was 100% and 89%, respectively. Conclusion: The results of our study have shown that postoperative external RT for cervical cancer delivered with helical tomotherapy and high-dose-rate brachytherapy and with or without chemotherapy is feasible, with acceptable acute and chronic toxicity.« less

Impact of a comprehensive geriatric assessment to manage elderly patients with locally advanced non-small-cell lung cancers: An open phase II study using concurrent cisplatin-oral vinorelbine and radiotherapy (GFPC 08-06).

PubMed

Locher, Chrystèle; Pourel, Nicolas; Le Caer, Hervé; Berard, Henri; Auliac, Jean-Bernard; Monnet, Isabelle; Descourt, Renaud; Vergnenègre, Alain; Lafay, Isabelle Martel; Greillier, Laurent; Chouaïd, Christos

2018-07-01

Few data have been published on the optimal management of elderly patients with locally advanced non-small-cell lung cancers (La-NSCLC). This prospective, multicenter, phase II study was undertaken to evaluate the ability of a comprehensive geriatric assessment (CGA) to select the elderly La-NSCLC patients who potentially may benefit from concurrent radio-chemotherapy. The main inclusion criteria were: La-NSCLC, >70 years old, at least one measurable target, ECOG performance status (PS) 0/1 and normal CGA. Weekly cisplatin (30 mg/m 2 ) and oral vinorelbine (30 mg/m 2 ) were combined with standard thoracic radiotherapy (66 Gy, 33 fractions) for 6.5 weeks. The primary evaluation criterion was <15% clinically relevant grade >2 toxicity. Secondary criteria were response rates, overall survival (OS) and progression-free survival (PFS). Among the 49 patients screened, 40 were included: 87.5% men, median age: 75.1 (70-84) years, 67.5% with PS 0, 52.5% squamous cell carcinomas. The full concurrent regimen was administrated in 77.5% of the cases (chemotherapy: 85%, radiotherapy: 90%); 22.5% of the patients experienced toxicity grade >2 (with three treatment-imputed deaths), 15% when restricted to clinically relevant >2 grade toxicities. One (2.6%) patient achieved a complete response, 53.8% had partial responses and 35.9% stable disease. Median PFS was 15 (95%CI: 8,7-35,2) months, OS 21.8 (95%CI: 16-NR) months and 1-, 2- and 4-year survival rates were 77.5%, 45% and 34.8%. CGA was able to select fit elderly patients with La-NSCLCs eligible for concurrent chemoradiotherapy with a satisfactory risk/benefit ratio. Copyright © 2018 Elsevier B.V. All rights reserved.

Parents Exhibit Children's Progress at a Poster Session.

ERIC Educational Resources Information Center

Donley, Corrine R.; Williams, Gladys

1997-01-01

Describes a program of New York's Keller School (a school for toddlers and preschoolers with communication, cognitive, and emotional disorders), which promotes meaningful family involvement through parent education. Activities to promote parent participation are described, including an annual poster session to present the parents' own data on…

Oncogenic Properties of Apoptotic Tumor Cells in Aggressive B Cell Lymphoma

PubMed Central

Ford, Catriona A.; Petrova, Sofia; Pound, John D.; Voss, Jorine J.L.P.; Melville, Lynsey; Paterson, Margaret; Farnworth, Sarah L.; Gallimore, Awen M.; Cuff, Simone; Wheadon, Helen; Dobbin, Edwina; Ogden, Carol Anne; Dumitriu, Ingrid E.; Dunbar, Donald R.; Murray, Paul G.; Ruckerl, Dominik; Allen, Judith E.; Hume, David A.; van Rooijen, Nico; Goodlad, John R.; Freeman, Tom C.; Gregory, Christopher D.

2015-01-01

Summary Background Cells undergoing apoptosis are known to modulate their tissue microenvironments. By acting on phagocytes, notably macrophages, apoptotic cells inhibit immunological and inflammatory responses and promote trophic signaling pathways. Paradoxically, because of their potential to cause death of tumor cells and thereby militate against malignant disease progression, both apoptosis and tumor-associated macrophages (TAMs) are often associated with poor prognosis in cancer. We hypothesized that, in progression of malignant disease, constitutive loss of a fraction of the tumor cell population through apoptosis could yield tumor-promoting effects. Results Here, we demonstrate that apoptotic tumor cells promote coordinated tumor growth, angiogenesis, and accumulation of TAMs in aggressive B cell lymphomas. Through unbiased “in situ transcriptomics” analysis—gene expression profiling of laser-captured TAMs to establish their activation signature in situ—we show that these cells are activated to signal via multiple tumor-promoting reparatory, trophic, angiogenic, tissue remodeling, and anti-inflammatory pathways. Our results also suggest that apoptotic lymphoma cells help drive this signature. Furthermore, we demonstrate that, upon induction of apoptosis, lymphoma cells not only activate expression of the tumor-promoting matrix metalloproteinases MMP2 and MMP12 in macrophages but also express and process these MMPs directly. Finally, using a model of malignant melanoma, we show that the oncogenic potential of apoptotic tumor cells extends beyond lymphoma. Conclusions In addition to its profound tumor-suppressive role, apoptosis can potentiate cancer progression. These results have important implications for understanding the fundamental biology of cell death, its roles in malignant disease, and the broader consequences of apoptosis-inducing anti-cancer therapy. PMID:25702581

Cancer Stem-like Cells Act via Distinct Signaling Pathways in Promoting Late Stages of Malignant Progression.

PubMed

da Silva-Diz, Victoria; Simón-Extremera, Pilar; Bernat-Peguera, Adrià; de Sostoa, Jana; Urpí, Maria; Penín, Rosa M; Sidelnikova, Diana Pérez; Bermejo, Oriol; Viñals, Joan Maria; Rodolosse, Annie; González-Suárez, Eva; Moruno, Antonio Gómez; Pujana, Miguel Ángel; Esteller, Manel; Villanueva, Alberto; Viñals, Francesc; Muñoz, Purificación

2016-03-01

Cancer stem-like cells (CSC) play key roles in long-term tumor propagation and metastasis, but their dynamics during disease progression are not understood. Tumor relapse in patients with initially excised skin squamous cell carcinomas (SCC) is characterized by increased metastatic potential, and SCC progression is associated with an expansion of CSC. Here, we used genetically and chemically-induced mouse models of skin SCC to investigate the signaling pathways contributing to CSC function during disease progression. We found that CSC regulatory mechanisms change in advanced SCC, correlating with aggressive tumor growth and enhanced metastasis. β-Catenin and EGFR signaling, induced in early SCC CSC, were downregulated in advanced SCC. Instead, autocrine FGFR1 and PDGFRα signaling, which have not been previously associated with skin SCC CSC, were upregulated in late CSC and promoted tumor growth and metastasis, respectively. Finally, high-grade and recurrent human skin SCC recapitulated the signaling changes observed in advanced mouse SCC. Collectively, our findings suggest a stage-specific switch in CSC regulation during disease progression that could be therapeutically exploited by targeting the PDGFR and FGFR1 pathways to block relapse and metastasis of advanced human skin SCC. ©2015 American Association for Cancer Research.

Concurrent Hand and Penile Gangrene following Prolonged Warfarin Use; a Case Report.

PubMed

Mahdizadeh, Fatemeh; Safari, Saeed

2017-01-01

Warfarin induced skin necrosis (WISN) is a rare but important side effect of warfarin. Early diagnosis may lessen the amount of permanent tissue damage and can prevent progression to full thickness skin necrosis. So, physicians should be aware of such a complication. Screening for protein C or S or anti-thrombin deficiencies, or presence of anti-phospholipid antibodies before beginning warfarin therapy, could be helpful to avoid high levels of international normalized ratio (INR). Here, we report a 54-year-old man who presented to the emergency department with acral and penile gangrene following prolonged use of warfarin.

Intramedullary Percutaneous Fixation of Extra-Articular Proximal and Middle Phalanx Fractures.

PubMed

Jovanovic, Nebojsa; Aldlyami, Ehab; Saraj, Basem; Fm Seidam, Mohamed; Badawi, Hamed; Shaat, Ahmed; Alawadi, Khalid; Dodakundi, Chaitanya

2018-06-01

Multiple methods have been described for treating unstable proximal and middle phalangeal fractures. Irrespective of using an open or closed technique of fixation, stiffness and extensor lag at the proximal/distal interphalangeal joint almost always occur. This issue can be avoided by allowing the patients to mobilize the fingers out of plaster or splint as early as possible from the day of surgery. We describe a technique of intramedullary percutaneous fixation of extra-articular proximal and middle phalanx fractures allowing immediate mobilization of fingers, concurrent stabilization with progressive healing and thus preventing such complications.

Alternative chemotherapeutic agents: nitrosoureas, cisplatin, irinotecan.

PubMed

Carrillo, Jose A; Munoz, Claudia A

2012-04-01

Irinotecan, cisplatin, and nitrosoureas have a long history of use in brain tumors, with demonstrated efficacy in the adjuvant treatment of malignant gliomas. In the era of temozolomide with concurrent radiotherapy given as the standard of care, their use has shifted to treatment at progression or recurrence. Now with the widespread use of bevacizumab in the recurrent setting, irinotecan and other chemotherapies are seeing increased use in combination with bevacizumab and alone in the recurrent setting. The activity of these chemotherapeutic agents in brain tumors will likely ensure a place in the armamentarium of neuro-oncologists for many years. Published by Elsevier Inc.

Polycystic kidneys in the red panda (Ailurus fulgens).

PubMed

Makungu, Modesta; du Plessis, Wencke M; Barrows, Michelle; Koeppel, Katja N; Groenewald, Hermanus B

2013-09-01

An intact adult male 14.3-yr-old red panda (Ailurus fulgens) presented for health examination with a history of slowly progressing loss of body condition. Abdominal radiographs revealed a truncated abdomen with poor serosal abdominal detail and multiple areas of spondylosis with some collapsed intervertebral disc spaces. On computed tomography, multiple ovoid hypoattenuating lesions were seen in the left and right kidneys. Gross pathology and histopathology revealed multiple cystic lesions in the kidneys concurrent with pancreatic cysts on histopathology. To the best of the authors' knowledge, polycystic kidneys have not been reported in this species.

Diplopia as the primary presentation of foodborne botulism.

PubMed

Khakshoor, Hamid; Moghaddam, Ali Akbar Saber; Vejdani, Amir Hossein; Armstrong, Blair K; Moshirfar, Majid

2012-05-01

Foodborne botulism is a serious condition caused by Clostridium botulinum neurotoxin. Clinically, botulism presents as bilateral cranial nerve neuropathy and descending paralysis. We report a unique presentation of botulism to remind clinicians of this potentially fatal condition. In this observational case report initial evaluation showed only esodeviation. This progressed to unilateral cranial nerve six (CN VI) paresis along with systemic signs. Clinical diagnosis was made based on in-depth history and concurrent symptoms in three other patients. Foodborne botulism presenting as diplopia and unilateral motility deficits is rare and can represent a diagnostic and therapeutic challenge to the ophthalmologist.

Diplopia as the primary presentation of foodborne botulism

PubMed Central

Khakshoor, Hamid; Moghaddam, Ali Akbar Saber; Vejdani, Amir Hossein; Armstrong, Blair K.; Moshirfar, Majid

2012-01-01

Foodborne botulism is a serious condition caused by Clostridium botulinum neurotoxin. Clinically, botulism presents as bilateral cranial nerve neuropathy and descending paralysis. We report a unique presentation of botulism to remind clinicians of this potentially fatal condition. In this observational case report initial evaluation showed only esodeviation. This progressed to unilateral cranial nerve six (CN VI) paresis along with systemic signs. Clinical diagnosis was made based on in-depth history and concurrent symptoms in three other patients. Foodborne botulism presenting as diplopia and unilateral motility deficits is rare and can represent a diagnostic and therapeutic challenge to the ophthalmologist. PMID:22993467

Enabling Large-Scale Biomedical Analysis in the Cloud

PubMed Central

Lin, Ying-Chih; Yu, Chin-Sheng; Lin, Yen-Jen

2013-01-01

Recent progress in high-throughput instrumentations has led to an astonishing growth in both volume and complexity of biomedical data collected from various sources. The planet-size data brings serious challenges to the storage and computing technologies. Cloud computing is an alternative to crack the nut because it gives concurrent consideration to enable storage and high-performance computing on large-scale data. This work briefly introduces the data intensive computing system and summarizes existing cloud-based resources in bioinformatics. These developments and applications would facilitate biomedical research to make the vast amount of diversification data meaningful and usable. PMID:24288665

Multiple concurrent temporal recalibrations driven by audiovisual stimuli with apparent physical differences.

PubMed

Yuan, Xiangyong; Bi, Cuihua; Huang, Xiting

2015-05-01

Out-of-synchrony experiences can easily recalibrate one's subjective simultaneity point in the direction of the experienced asynchrony. Although temporal adjustment of multiple audiovisual stimuli has been recently demonstrated to be spatially specific, perceptual grouping processes that organize separate audiovisual stimuli into distinctive "objects" may play a more important role in forming the basis for subsequent multiple temporal recalibrations. We investigated whether apparent physical differences between audiovisual pairs that make them distinct from each other can independently drive multiple concurrent temporal recalibrations regardless of spatial overlap. Experiment 1 verified that reducing the physical difference between two audiovisual pairs diminishes the multiple temporal recalibrations by exposing observers to two utterances with opposing temporal relationships spoken by one single speaker rather than two distinct speakers at the same location. Experiment 2 found that increasing the physical difference between two stimuli pairs can promote multiple temporal recalibrations by complicating their non-temporal dimensions (e.g., disks composed of two rather than one attribute and tones generated by multiplying two frequencies); however, these recalibration aftereffects were subtle. Experiment 3 further revealed that making the two audiovisual pairs differ in temporal structures (one transient and one gradual) was sufficient to drive concurrent temporal recalibration. These results confirm that the more audiovisual pairs physically differ, especially in temporal profile, the more likely multiple temporal perception adjustments will be content-constrained regardless of spatial overlap. These results indicate that multiple temporal recalibrations are based secondarily on the outcome of perceptual grouping processes.

Harnessing the concurrent reaction dynamics in active Si and Ge to achieve high performance lithium-ion batteries

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

Zhang, Qiaobao; Chen, Huixin; Luo, Langli

Advanced composite electrodes containing multiple active components are often used in lithium-ion batteries for practical applications. The performance of such heterogeneous composite electrodes can in principle be enhanced by tailoring the concurrent reaction dynamics in multiple active components for promoting their collective beneficial effects. However, the potential of this design principle has remained uncharted to date. Here we develop a composite anode of Cu/Si/Ge nanowire arrays, where each nanowire consists of a core of Cu segments and a Si/Ge bilayer shell. This unique electrode architecture exhibited a markedly improved electrochemical performance over the reference Cu/Si systems, demonstrating a stable capacitymore » retention (81% after 3000 cycles at 2C) and doubled specific capacity at a rate of 16C (1C = 2 A g1). By using in situ transmission electron microscopy and electrochemical testing, we unravel a novel reaction mechanism of dynamic co-lithiation/co-delithiation in the active Si and Ge bilayer, which is shown to effectively alleviate the electrochemically induced mechanical degradation and thus greatly enhance the long-cycle stability of the electrode. Our findings offer insights into a rational design of high-performance lithium-ion batteries via exploiting the concurrent reaction dynamics in the multiple active components of composite electrodes.A composite anode of Cu/Si/Ge nanowire arrays grown on a porous Ni foam enables the outstanding capacity, rate capability and cycle stability of Li-ion batteries.« less

Renal failure and concurrent RAAS blockade in older CKD patients with renal artery stenosis: an extended Mayo Clinic prospective 63-month experience.

PubMed

Onuigbo, Macaulay A C; Onuigbo, Nnonyelum T C

2008-01-01

Concerns have been raised regarding a possible link between the increasing utilization of RAAS blocking strategies in the United States and the increasing ESRD epidemic. Most reports of accelerated renal failure in CKD patients with renal artery stenosis on RAAS blockade are retrospective. We hypothesized that this syndrome is therefore poorly understood, may be under-recognized, and demanded prospective analysis. As part of a larger cohort of 100 CKD patients on RAAS blockade presenting with worsening renal failure (>25% increased serum creatinine from baseline) while concurrently on an ACE inhibitor and/or an angiotensin receptor blocker, 26 patients (26%) enrolled between September 2002 and February 2005 had hemodynamically significant renal artery stenosis. RAAS blockade was discontinued, standard nephrology care applied, and eGFR by MDRD monitored. They consisted of 26 Caucasian patients, M:F = 10:16, age 75.3 +/- 6.4 (63-87) years. Mean follow-up was 26.4 +/- 16.4 (1-49) months. Duration of RAAS blockade prior to enrollment was 20.2 +/- 16.4 (0.5-48) months. Contrary to previous reports, precipitating factors were often absent (15/26), unilateral RAS lesions in patients with dual kidneys was common (19/26), and progression to ESRD was frequent (5/26). Four-fifths of the ESRD patients were dead after 5.5 +/- 4.1 (1-11) months. A fifth patient with improved eGFR died after 14 months from metastatic gastric cancer. Excluding five patients who progressed to ESRD and two patients lost early to follow-up, in 19 patients, eGFR increased from 27.8 +/- 9.5 (11-47) to 36.7 +/- 16 (14-68) mL/min/1.73 m(2) BSA (p = 0.014) after 34.8 +/- 10.1 (14-49) months of follow-up. This improvement in eGFR was evident after weeks to months of stopping RAAS blockade in these patients with and without renal PTA and stenting. Nevertheless, renal PTA/stenting further improved eGFR in selected patients. We conclude that renal failure/ESRD associated with concurrent RAAS blockade in older CKD patients with renal stenosis remains poorly understood and mostly unrecognized. Unilateral lesions in patients with dual kidneys, absent precipitating factors, and progression to ESRD with high mortality, despite discontinuation of RAAS blockade, are more common than previously thought. Lower baseline eGFR (<35) predicted ESRD. Our findings call for a larger prospective study, especially given growing concerns of iatrogenic renal failure from RAAS blockade in the aging U.S. population. An aging U.S. population further raises the probability of the presence of increasing and unrecognized renal artery stenosis in our CKD patient population.

[Charles Darwin and the problem of evolutionary progress].

PubMed

Iordanskiĭ, N N

2010-01-01

According to Ch. Darwin's evolutionary theory, evolutionary progress (interpreted as morpho-physiological progress or arogenesis in recent terminology) is one of logical results of natural selection. At the same time, natural selection does not hold any factors especially promoting evolutionary progress. Darwin emphasized that the pattern of evolutionary changes depends on organism nature more than on the pattern of environment changes. Arogenesis specificity is determined by organization of rigorous biological systems - integral organisms. Onward progressive development is determined by fundamental features of living organisms: metabolism and homeostasis. The concept of social Darwinism differs fundamentally from Darwin's ideas about the most important role of social instincts in progress of mankind. Competition and selection play secondary role in socio-cultural progress of human society.

From Charity School to Workhouse in the 1720's: The SPCK and Mr Marriott's Solution.

ERIC Educational Resources Information Center

Simon, Joan

1988-01-01

Traces the progress of the Society for Promoting Christian Knowledge's (England) charity school movement in the early eighteenth century and its shift from promotion of catechistical instruction to putting children to work in workhouses that served to banish idleness and beggary. (GEA)

The Salutogenic Wellness Promotion Scale for Older Adults

ERIC Educational Resources Information Center

Becker, Craig M.; Chaney, Beth H.; Shores, Kindal; Glascoff, Mary

2015-01-01

Background: From 1990 to 2050, the population aged 60 years and older will rise from 9% to 21%. Healthy aging initiatives are vital to promote individual, community, and global well-being during this transformation. Accurate health measurement tools are needed to successfully guide strategies and plot progress. The validated multi-dimensional…

Promoting Student Engagement in the Classroom

ERIC Educational Resources Information Center

Bundick, Matthew J.; Quaglia, Russell J.; Corso, Michael J.; Haywood, Dawn E.

2014-01-01

Background/Context: Much progress has been made toward a greater understanding of student engagement and its role in promoting a host of desirable outcomes, including academic outcomes such as higher achievement and reduced dropout, as well as various well-being and life outcomes. Nonetheless, disengagement in our schools is widespread. This may…

Strategies to Promote Lesson Study in Developing Countries

ERIC Educational Resources Information Center

Saito, Eisuke

2012-01-01

Purpose: The purpose of this paper is to discuss the developmental stages of lesson study for learning community (LSLC) and to clarify the measures necessary for promoting the progress of LSLC, targeting consultants working on educational development projects for developing countries. Design/methodology/approach: The paper is organised as a…

Investigation of Using Analytics in Promoting Mobile Learning Support

ERIC Educational Resources Information Center

Visali, Videhi; Swami, Niraj

2013-01-01

Learning analytics can promote pedagogically informed use of learner data, which can steer the progress of technology mediated learning across several learning contexts. This paper presents the application of analytics to a mobile learning solution and demonstrates how a pedagogical sense was inferred from the data. Further, this inference was…

THE TUMOR MACROENVIRONMENT: CANCER-PROMOTING NETWORKS BEYOND TUMOR BEDS

PubMed Central

Rutkowski, Melanie R.; Svoronos, Nikolaos; Puchalt, Alfredo Perales; Conejo-Garcia, Jose R.

2015-01-01

During tumor progression, alterations within the systemic tumor environment, or macroenvironment, result in the promotion of tumor growth, tumor invasion to distal organs, and eventual metastatic disease. Distally produced hormones, commensal microbiota residing within mucosal surfaces, and myeloid cells and even the bone marrow impact the systemic immune system, tumor growth, and metastatic spread. Understanding the reciprocal interactions between the cells and soluble factors within the macroenvironment and the primary tumor will enable the design of specific therapies that have the potential to prevent dissemination and metastatic spread. This chapter will summarize recent findings detailing how the primary tumor and systemic tumor macroenvironment coordinate malignant progression. PMID:26216635

Coexistence of BRAF V600E and TERT Promoter Mutations in Low-grade Serous Carcinoma of Ovary Recurring as Carcinosarcoma in a Lymph Node: Report of a Case.

PubMed

Tavallaee, Mahkam; Steiner, David F; Zehnder, James L; Folkins, Ann K; Karam, Amer K

2018-04-03

Low-grade serous carcinomas only rarely coexist with or progress to high-grade tumors. We present a case of low-grade serous carcinoma with transformation to carcinosarcoma on recurrence in the lymph node. Identical BRAF V600E and telomerase reverse transcriptase promoter mutations were identified in both the original and recurrent tumor. Given that telomerase reverse transcriptase promotor mutations are thought to play a role in progression of other tumor types, the function of telomerase reverse transcriptase mutations in BRAF mutated low-grade serous carcinoma deserves investigation.

Stepfamily Relationship Quality and Children's Internalizing and Externalizing Problems.

PubMed

Jensen, Todd M; Lippold, Melissa A; Mills-Koonce, Roger; Fosco, Gregory M

2017-03-07

The stepfamily literature is replete with between-group analyses by which youth residing in stepfamilies are compared to youth in other family structures across indicators of adjustment and well-being. Few longitudinal studies examine variation in stepfamily functioning to identify factors that promote the positive adjustment of stepchildren over time. Using a longitudinal sample of 191 stepchildren (56% female, mean age = 11.3 years), the current study examines the association between the relationship quality of three central stepfamily dyads (stepparent-child, parent-child, and stepcouple) and children's internalizing and externalizing problems concurrently and over time. Results from path analyses indicate that higher levels of parent-child affective quality are associated with lower levels of children's concurrent internalizing and externalizing problems at Wave 1. Higher levels of stepparent-child affective quality are associated with decreases in children's internalizing and externalizing problems at Wave 2 (6 months beyond baseline), even after controlling for children's internalizing and externalizing problems at Wave 1 and other covariates. The stepcouple relationship was not directly linked to youth outcomes. Our findings provide implications for future research and practice. © 2017 Family Process Institute.

The dawn of a new era in onco-cardiology: The Kumamoto Classification.

PubMed

Sueta, Daisuke; Tabata, Noriaki; Akasaka, Tomonori; Yamashita, Takayoshi; Ikemoto, Tomokazu; Hokimoto, Seiji

2016-10-01

The term "onco-cardiology" has been used in reference to cardiotoxicity in the treatment of malignant disease. In actual clinical situations, however, cardiovascular disease (CVD) associated with malignant disease and the concurrence of atherosclerotic disease with malignant disease are commonly observed, complicating the course of treatment. Patients with malignant disease associated with coronary artery disease often die from the cardiovascular disease, so it is essential to classify these disease states. Additionally, the prevalence of these classifications makes it easy to manage patients with malignant disease and coronary artery disease. We divided the broad field of onco-cardiology into 4 classifications based on clinical scenarios (CSs): CS1 represents the so-called paraneoplastic syndrome. CS2 represents cardiotoxicity during treatment of malignant diseases. CS3 represents the concurrence of atherosclerotic disease with malignant disease, and CS4 represents cardiovascular disease with benign tumors. This classification facilitates the management of patients with malignant disease and coronary artery disease by promoting not only the primary but also the secondary prevention of CVD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Anxiety and depression strongly associated with sexual risk behaviors among networks of young men in Dar es Salaam, Tanzania.

PubMed

Hill, Lauren M; Maman, Suzanne; Kilonzo, Mrema Noel; Kajula, Lusajo Joel

2017-02-01

This study tested the association between mental health scores and sexual risk behaviors among male members of social groups known as "camps" in Dar es Salaam, Tanzania. Anxiety and depression were measured using the HSCL-25 and condom use and sexual partner concurrency were assessed through self-report. A total of 1113 sexually active men with an average age of 27 years were included in the analyses. Higher anxiety and depression scores were significantly associated with both condom use (Anxiety AOR = 0.58, 95% CI: 0.44, 0.77; Depression AOR = 0.60, 95% CI: 0.47, 0.77) and concurrency (Anxiety AOR = 2.32, 95% CI: 1.73, 3.12; Depression AOR = 2.08, 95% CI: 1.60, 2.70). The results of this study provide information salient to the development of effective HIV prevention interventions targeting populations with high burdens of anxiety and depression. The feasibility and effect of integrating mental health promotion activities into HIV prevention interventions should be explored.

Using ecological momentary assessment to examine antecedents and correlates of physical activity bouts in adults age 50+ years: a pilot study.

PubMed

Dunton, Genevieve Fridlund; Atienza, Audie A; Castro, Cynthia M; King, Abby C

2009-12-01

National recommendations supporting the promotion of multiple short (10+ minute) physical activity bouts each day to increase overall physical activity levels in middle-aged and older adults underscore the need to identify antecedents and correlates of such daily physical activity episodes. This pilot study used Ecological Momentary Assessment to examine the time-lagged and concurrent effects of empirically supported social, cognitive, affective, and physiological factors on physical activity among adults age 50+ years. Participants (N = 23) responded to diary prompts on a handheld computer four times per day across a 2-week period. Moderate-to-vigorous physical activity (MVPA), self-efficacy, positive and negative affect, control, demand, fatigue, energy, social interactions, and stressful events were assessed during each sequence. Multivariate results showed that greater self-efficacy and control predicted greater MVPA at each subsequent assessment throughout the day (p < 0.05). Also, having a positive social interaction was concurrently related to higher levels of MVPA (p = 0.052). Time-varying multidimensional individual processes predict within daily physical activity levels.

An androgen receptor negatively induced long non-coding RNA ARNILA binding to miR-204 promotes the invasion and metastasis of triple-negative breast cancer.

PubMed

Yang, Fang; Shen, Yan; Zhang, Wenwen; Jin, Juan; Huang, Doudou; Fang, Hehui; Ji, Wenfei; Shi, Yaqin; Tang, Lin; Chen, Weiwei; Zhou, Guohua; Guan, Xiaoxiang

2018-05-29

Androgen receptor (AR) is emerging as a novel prognostic biomarker in triple-negative breast cancer (TNBC), but the underlying mechanisms remain unknown. As accumulating evidence has shown that long non-coding RNAs (lncRNAs) regulate important cancer hallmarks, we hypothesised that AR-regulated lncRNAs might play roles in TNBC progression. Here, we performed experiments with or without DHT treatment in three TNBC cell lines, and we identified an AR negatively induced lncRNA (ARNILA), which correlated with poor progression-free survival (PFS) in TNBC patients and promoted epithelial-mesenchymal transition (EMT), invasion and metastasis in vitro and in vivo. Subsequently, we demonstrated that ARNILA functioned as a competing endogenous RNA (ceRNA) for miR-204 to facilitate expression of its target gene Sox4, which is known to induce EMT and contribute to breast cancer progression, thereby promoting EMT, invasion and metastasis of TNBC. Our findings not only provide new insights into the mechanisms of lncRNA in regulating AR but also suggest ARNILA as an alternative therapeutic target to suppress metastasis of TNBC patients.

Substance P Promotes Wound Healing in Diabetes by Modulating Inflammation and Macrophage Phenotype

PubMed Central

Leal, Ermelindo C.; Carvalho, Eugénia; Tellechea, Ana; Kafanas, Antonios; Tecilazich, Francesco; Kearney, Cathal; Kuchibhotla, Sarada; Auster, Michael E.; Kokkotou, Efi; Mooney, David J.; LoGerfo, Frank W.; Pradhan-Nabzdyk, Leena; Veves, Aristidis

2016-01-01

Diabetic foot ulceration is a major complication of diabetes. Substance P (SP) is involved in wound healing, but its effect in diabetic skin wounds is unclear. We examined the effect of exogenous SP delivery on diabetic mouse and rabbit wounds. We also studied the impact of deficiency in SP or its receptor, neurokinin-1 receptor, on wound healing in mouse models. SP treatment improved wound healing in mice and rabbits, whereas the absence of SP or its receptor impaired wound progression in mice. Moreover, SP bioavailability in diabetic skin was reduced as SP gene expression was decreased, whereas the gene expression and protein levels of the enzyme that degrades SP, neutral endopeptidase, were increased. Diabetes and SP deficiency were associated with absence of an acute inflammatory response important for wound healing progression and instead revealed a persistent inflammation throughout the healing process. SP treatment induced an acute inflammatory response, which enabled the progression to the proliferative phase and modulated macrophage activation toward the M2 phenotype that promotes wound healing. In conclusion, SP treatment reverses the chronic proinflammatory state in diabetic skin and promotes healing of diabetic wounds. PMID:25871534

Long noncoding RNA LINC01296 promotes tumor growth and progression by sponging miR-5095 in human cholangiocarcinoma.

PubMed

Zhang, Dawei; Li, Haiyan; Xie, Juping; Jiang, Decan; Cao, Liangqi; Yang, Xuewei; Xue, Ping; Jiang, Xiaofeng

2018-06-01

The aim of the present study was to elucidate whether, and how, long intergenic non-protein coding RNA 1296 (LINC01296) is involved in the modulation of human cholangiocarcinoma (CCA) development and progression. Microarray data analysis and reverse transcription-quantitative polymerase chain reaction analysis demonstrated that LINC01296 was significantly upregulated in human CCA compared with nontumor tissues. Furthermore, the expression of LINC01296 in human CCA was positively associated with tumor severity and clinical stage. Knockdown of LINC01296 dramatically suppressed the viability, migration and invasion of RBE and CCLP1 cells, and promoted cell apoptosis in vitro. Furthermore, LINC01296 knockdown inhibited tumor growth in a xenograft model. Mechanistically, LINC01296 was demonstrated to sponge microRNA-5095 (miR-5095), which targets MYCN proto-oncogene bHLH transcription factor (MYCN) mRNA in human CCA. By inhibition of miR-5095, LINC01296 overexpression upregulated the expression of MYCN and promoted cell viability, migration and invasion in CCA cells. The results reveal that the axis of LINC01296/miR-5095/MYCN may be a mechanism to regulate CCA development and progression.

Targeting RhoA/Rho kinase and p21-activated kinase signaling to prevent cancer development and progression.

PubMed

Chang, Yu-Wen E; Bean, Ronald R; Jakobi, Rolf

2009-06-01

Elevated RhoA/Rho kinase and p21-activated kinase signaling have been shown to promote cancer development and metastasis and have drawn much attention as potential targets of anti-cancer therapy. Elevated RhoA and Rho kinase activity promote cancer cell invasion and eventually lead to metastasis by disrupting E-cadherin-mediated adherens junctions and degradation of the extracellular matrix. Elevated p21-activated kinase activity promotes invasion by stimulating cell motility but also promotes cancer cell survival and growth. In this review we describe normal functions of RhoA/Rho kinase and p21-activated kinase signaling, mechanisms that lead to constitutive activation of RhoA/Rho kinase and p21-activated kinase pathways, and processes by which constitutive RhoA/Rho kinase and p21-activated kinase activity promote cancer development and progression to more aggressive and metastatic phenotypes. In addition, we summarize relevant patents on RhoA/Rho kinase and p21-activated kinase as targets of anti-cancer therapy and discuss the clinical potential of different approaches to modulate RhoA/Rho kinase and p21-activated kinase signaling.

β4-Integrin/PI3K Signaling Promotes Tumor Progression through the Galectin-3-N-Glycan Complex.

PubMed

Kariya, Yukiko; Oyama, Midori; Hashimoto, Yasuhiro; Gu, Jianguo; Kariya, Yoshinobu

2018-06-01

Malignant transformation is associated with aberrant N -glycosylation, but the role of protein N -glycosylation in cancer progression remains poorly defined. β4-integrin is a major carrier of N -glycans and is associated with poor prognosis, tumorigenesis, and metastasis. Here, N -glycosylation of β4-integrin contributes to the activation of signaling pathways that promote β4-dependent tumor development and progression. Increased expression of β1,6GlcNAc-branched N -glycans was found to be colocalized with β4-integrin in human cutaneous squamous cell carcinoma tissues, and that the β1,6GlcNAc residue was abundant on β4-integrin in transformed keratinocytes. Interruption of β1,6GlcNAc-branching formation on β4-integrin with the introduction of bisecting GlcNAc by N -acetylglucosaminyltransferase III overexpression was correlated with suppression of cancer cell migration and tumorigenesis. N -Glycan deletion on β4-integrin impaired β4-dependent cancer cell migration, invasion, and growth in vitro and diminished tumorigenesis and proliferation in vivo The reduced abilities of β4-integrin were accompanied with decreased phosphoinositol-3 kinase (PI3K)/Akt signals and were restored by the overexpression of the constitutively active p110 PI3K subunit. Binding of galectin-3 to β4-integrin via β1,6GlcNAc-branched N -glycans promoted β4-integrin-mediated cancer cell adhesion and migration. In contrast, a neutralizing antibody against galectin-3 attenuated β4-integrin N -glycan-mediated PI3K activation and inhibited the ability of β4-integrin to promote cell motility. Furthermore, galectin-3 knockdown by shRNA suppressed β4-integrin N -glycan-mediated tumorigenesis. These findings provide a novel role for N -glycosylation of β4-integrin in tumor development and progression, and the regulatory mechanism for β4-integrin/PI3K signaling via the galectin-3- N -glycan complex. Implications: N -Glycosylation of β4-integrin plays a functional role in promoting tumor development and progression through PI3K activation via the galectin-3- N -glycan complex. Mol Cancer Res; 16(6); 1024-34. ©2018 AACR . ©2018 American Association for Cancer Research.

Progress in life's history: Linking Darwinism and palaeontology in Britain, 1860-1914.

PubMed

Manias, Chris

2017-12-01

This paper examines the tension between Darwinian evolution and palaeontological research in Britain in the 1860-1914 period, looking at how three key promoters of Darwinian thinking - Thomas Henry Huxley, Edwin Ray Lankester and Alfred Russell Wallace - integrated palaeontological ideas and narratives of life's history into their public presentations of evolutionary theory. It shows how engagement with palaeontological science was an important part of the promotion of evolutionary ideas in Britain, which often bolstered notions that evolution depended upon progress and development along a wider plan. While often critical of some of the non-Darwinian concepts of evolution professed by many contemporary palaeontologists, and frequently citing the 'imperfection' of the fossil record itself, Darwinian thinkers nevertheless engaged extensively with palaeontology to develop evolutionary narratives informed by notions of improvement and progress within the natural world. Crown Copyright © 2017. Published by Elsevier Ltd. All rights reserved.

DPPIV promotes endometrial carcinoma cell proliferation, invasion and tumorigenesis

PubMed Central

Yang, Xiaoqing; Zhang, Xinhua; Wu, Rongrong; Huang, Qicheng; Jiang, Yao; Qin, Jianbing; Yao, Feng; Jin, Guohua; Zhang, Yuquan

2017-01-01

Dipeptidyl peptidase IV (DPPIV), also known as CD26, is a 110-kDa cell surface glycoprotein expressed in various tissues. DPPIV reportedly plays a direct role in the progression of several human malignancies. DPPIV specific inhibitors are employed as antidiabetics and could potentially be repurposed to enhance anti-tumor immunotherapies. In the present study, we investigated the correlation between DPPIV expression and tumor progression in endometrial carcinoma (EC). DPPIV overexpression altered cell morphology and stimulated cell proliferation, invasion and tumorigenesis in vitro and in vivo. These effects were abrogated by DPPIV knockdown or pharmacological inhibition using sitagliptin. DPPIV overexpression increased hypoxia-inducible factor 1a (HIF-1a) and vascular endothelial growth factor A (VEGFA) expression to promote HIF-1a-VEGFA signaling. Our results indicated that DPPIV accelerated endometrial carcinoma progression and that sitagliptin may be an effective anti-EC therapeutic. PMID:28060721

DPPIV promotes endometrial carcinoma cell proliferation, invasion and tumorigenesis.

PubMed

Yang, Xiaoqing; Zhang, Xinhua; Wu, Rongrong; Huang, Qicheng; Jiang, Yao; Qin, Jianbing; Yao, Feng; Jin, Guohua; Zhang, Yuquan

2017-01-31

Dipeptidyl peptidase IV (DPPIV), also known as CD26, is a 110-kDa cell surface glycoprotein expressed in various tissues. DPPIV reportedly plays a direct role in the progression of several human malignancies. DPPIV specific inhibitors are employed as antidiabetics and could potentially be repurposed to enhance anti-tumor immunotherapies. In the present study, we investigated the correlation between DPPIV expression and tumor progression in endometrial carcinoma (EC). DPPIV overexpression altered cell morphology and stimulated cell proliferation, invasion and tumorigenesis in vitro and in vivo. These effects were abrogated by DPPIV knockdown or pharmacological inhibition using sitagliptin. DPPIV overexpression increased hypoxia-inducible factor 1a (HIF-1a) and vascular endothelial growth factor A (VEGFA) expression to promote HIF-1a-VEGFA signaling. Our results indicated that DPPIV accelerated endometrial carcinoma progression and that sitagliptin may be an effective anti-EC therapeutic.

Nuclear respiratory factor 2 regulates the expression of the same NMDA receptor subunit genes as NRF-1: both factors act by a concurrent and parallel mechanism to couple energy metabolism and synaptic transmission.

PubMed

Priya, Anusha; Johar, Kaid; Wong-Riley, Margaret T T

2013-01-01

Neuronal activity and energy metabolism are tightly coupled processes. Previously, we found that nuclear respiratory factor 1 (NRF-1) transcriptionally co-regulates energy metabolism and neuronal activity by regulating all 13 subunits of the critical energy generating enzyme, cytochrome c oxidase (COX), as well as N-methyl-d-aspartate (NMDA) receptor subunits 1 and 2B, GluN1 (Grin1) and GluN2B (Grin2b). We also found that another transcription factor, nuclear respiratory factor 2 (NRF-2 or GA-binding protein) regulates all subunits of COX as well. The goal of the present study was to test our hypothesis that NRF-2 also regulates specific subunits of NMDA receptors, and that it functions with NRF-1 via one of three mechanisms: complementary, concurrent and parallel, or a combination of complementary and concurrent/parallel. By means of multiple approaches, including in silico analysis, electrophoretic mobility shift and supershift assays, in vivo chromatin immunoprecipitation of mouse neuroblastoma cells and rat visual cortical tissue, promoter mutations, real-time quantitative PCR, and western blot analysis, NRF-2 was found to functionally regulate Grin1 and Grin2b genes, but not any other NMDA subunit genes. Grin1 and Grin2b transcripts were up-regulated by depolarizing KCl, but silencing of NRF-2 prevented this up-regulation. On the other hand, over-expression of NRF-2 rescued the down-regulation of these subunits by the impulse blocker TTX. NRF-2 binding sites on Grin1 and Grin2b are conserved among species. Our data indicate that NRF-2 and NRF-1 operate in a concurrent and parallel manner in mediating the tight coupling between energy metabolism and neuronal activity at the molecular level. Copyright © 2012 Elsevier B.V. All rights reserved.

Sphingosine-1-phosphate promotes erythrocyte glycolysis and oxygen release for adaptation to high-altitude hypoxia

PubMed Central

Sun, Kaiqi; Zhang, Yujin; D'Alessandro, Angelo; Nemkov, Travis; Song, Anren; Wu, Hongyu; Liu, Hong; Adebiyi, Morayo; Huang, Aji; Wen, Yuan E.; Bogdanov, Mikhail V.; Vila, Alejandro; O'Brien, John; Kellems, Rodney E.; Dowhan, William; Subudhi, Andrew W.; Jameson-Van Houten, Sonja; Julian, Colleen G.; Lovering, Andrew T.; Safo, Martin; Hansen, Kirk C.; Roach, Robert C.; Xia, Yang

2016-01-01

Sphingosine-1-phosphate (S1P) is a bioactive signalling lipid highly enriched in mature erythrocytes, with unknown functions pertaining to erythrocyte physiology. Here by employing nonbiased high-throughput metabolomic profiling, we show that erythrocyte S1P levels rapidly increase in 21 healthy lowland volunteers at 5,260 m altitude on day 1 and continue increasing to 16 days with concurrently elevated erythrocyte sphingonisne kinase 1 (Sphk1) activity and haemoglobin (Hb) oxygen (O2) release capacity. Mouse genetic studies show that elevated erythrocyte Sphk1-induced S1P protects against tissue hypoxia by inducing O2 release. Mechanistically, we show that intracellular S1P promotes deoxygenated Hb anchoring to the membrane, enhances the release of membrane-bound glycolytic enzymes to the cytosol, induces glycolysis and thus the production of 2,3-bisphosphoglycerate (2,3-BPG), an erythrocyte-specific glycolytic intermediate, which facilitates O2 release. Altogether, we reveal S1P as an intracellular hypoxia-responsive biolipid promoting erythrocyte glycolysis, O2 delivery and thus new therapeutic opportunities to counteract tissue hypoxia. PMID:27417539

Using the Framework for Health Promotion Action to address staff perceptions of occupational health and safety at a fly-in/fly-out mine in north-west Queensland.

PubMed

Devine, Susan G; Muller, Reinhold; Carter, Anthony

2008-12-01

An exploratory descriptive study was undertaken to identify staff perceptions of the types and sources of occupational health and safety hazards at a remote fly-in-fly-out minerals extraction and processing plant in northwest Queensland. Ongoing focus groups with all sectors of the operation were conducted concurrently with quantitative research studies from 2001 to 2005. Action research processes were used with management and staff to develop responses to identified issues. Staff identified and generated solutions to the core themes of: health and safety policies and procedures; chemical exposures; hydration and fatigue. The Framework for Health Promotion Action was applied to ensure a comprehensive and holistic response to identified issues. Participatory processes using an action research framework enabled a deep understanding of staff perceptions of occupational health and safety hazards in this setting. The Framework for Health Promotion provided a relevant and useful tool to engage with staff and develop solutions to perceived occupational health and safety issues in the workplace.

Placement, Progress, and Promotion: ESL Assessment in California's Adult Schools

ERIC Educational Resources Information Center

Gonzalves, Lisa

2017-01-01

In California adult schools, standardized language assessments are typically administered to adult English as a second language (ESL) students upon enrollment; students then take these same state-approved tests throughout the academic year to demonstrate progress. As these tests assess only listening and reading skills, schools may use their own…

Poverty Reduction and the World Bank. Progress in Fiscal 1996 and 1997.

ERIC Educational Resources Information Center

World Bank, Washington, DC.

This report reviews progress in implementation of the World Bank's poverty reduction strategy during fiscal 1996-97. Chapter 1, "The World Bank's Poverty Reduction Strategy and Future Directions," outlines elements in the poverty reduction strategy: policies to promote broad-based labor-demanding growth and increase the productivity and…

Reflective Practice in the Ballet Class: Bringing Progressive Pedagogy to the Classical Tradition

ERIC Educational Resources Information Center

Zeller, Jessica

2017-01-01

This research seeks to broaden the dialogue on progressive ballet pedagogy through an examination of reflective practices in the ballet class. Ballet's traditional model of instruction has long required students to quietly comply with the pedagogue's directives, and it has thus become notorious for promoting student passivity. Despite strong…

Recent Progress in Optical Chemical Sensors

PubMed Central

Qazi, Hummad Habib; Mohammad, Abu Bakar bin; Akram, Muhammad

2012-01-01

Optical chemical sensors have promoted escalating interest in the determination of various pollutants in the environment, which are creating toxicity and may cause serious health problems. This review paper focuses particularly on the recent progress and developments in this field; the working principles and basic classes of optical chemical sensors have been briefly described. PMID:23443392

A Letter to White Women Teachers: An Urgent Plea for Change

ERIC Educational Resources Information Center

Baker, Laura

2017-01-01

The new Progressive Education Network mission says that Progressive Education "promotes diversity, equity, and justice." These goals cannot be met unless there are substantial changes in the way the majority of teachers in the United States, white women teachers, think and operate. This open letter to that audience from a white woman…

Performance Plan: Progress Report 2nd Quarter Fiscal Year 2000.

ERIC Educational Resources Information Center

Department of Education, Washington, DC. Student Financial Assistance.

This document is progress report on the U.S. Department of Education's Student Financial Assistance (SFA) programs. Regarding its customer satisfaction objective, SFA notes that it looks to private sector leaders in e-commerce and promotes electronic services; offers electronic filing of the Free Application For Student Aid (FAFSA); offers most…

Promoting Learning and Achievement through Self-Assessment

ERIC Educational Resources Information Center

Andrade, Heidi; Valtcheva, Anna

2009-01-01

Criteria-referenced self-assessment is a process during which students collect information about their own performance or progress; compare it to explicitly stated criteria, goals, or standards; and revise accordingly. The authors argue that self-assessment must be a formative type of assessment, done on drafts of works in progress: It should not…

Factors that Promote Progression in Schools Functioning as Professional Learning Community

ERIC Educational Resources Information Center

Leclerc, Martine; Moreau, Andre C.; Dumouchel, Catherine; Sallafranque-St-Louis, Francois

2012-01-01

The purpose of this research is to identify factors that influence the functioning of a school working as a Professional Learning Community (PLC) and to analyze the links between these factors and the school's progression. This research was developed within the context of an interpretative research paradigm. The primary data collection tool…

Enhanced mammary progesterone receptor-A isoform activity in the promotion of mammary tumor progression by dietary soy in rats

USDA-ARS?s Scientific Manuscript database

Dietary contribution to breast cancer risk, recurrence, and progression remains incompletely understood. Increased consumption of soy and soy isoflavones is associated with reduced mammary cancer susceptibility in women and in rodent models of carcinogenesis. In rats treated with N-Methyl-N-Nitrosou...

Scholarly productivity for nursing clinical track faculty.

PubMed

Tschannen, Dana; Anderson, Christine; Strobbe, Stephen; Bay, Esther; Bigelow, April; Dahlem, Chin Hwa Gina Y; Gosselin, Ann K; Pollard, Jennifer; Seng, Julia S

2014-01-01

Recent years have yielded substantial advancement by clinical track faculty in cohort expansion and collective contributions to the discipline of nursing. As a result, standards for progression and promotion for clinical faculty need to be more fully developed, articulated, and disseminated. Our school formed a task force to examine benchmarks for the progression and promotion of clinical faculty across schools of nursing, with the goal of guiding faculty, reviewers, and decision makers about what constitutes excellence in scholarly productivity. Results from analyses of curriculum vitae of clinical professors or associate professors at six universities with high research activity revealed a variety of productivity among clinical track members, which included notable diversity in the types of scholarly products. Findings from this project help quantify types of scholarship for clinical faculty at the time of promotion. This work provides a springboard for greater understanding of the contributions of clinical track faculty to nursing practice. Copyright © 2014 Elsevier Inc. All rights reserved.

High-dependency care: experiences of the psychosocial work environment.

PubMed

Rahman, Hanif Abdul; Naing, Lin; Abdul-Mumin, Khadizah

2017-11-23

to explore high-dependency care nurses' experiences of their psychosocial work environment. four focus groups were conducted with 23 emergency and critical care hospital nurses in Brunei. All sessions were recorded, transcribed verbatim and analysed using inductive-approach thematic analysis. three major themes were identified. 'Specialisation/specific skills' explained a fundamental requirement for the high-dependency care nurses to work effectively and efficiently in their workplace. 'Task completion' narrated the pressure they experienced to complete their tasks within time constraints exacerbated by a reduced number of staff. 'Acknowledgement' signified their need for fair and adequate reward for their hard work through career progression and promotion. this study facilitates the design of future interventions and policies that promote a healthy psychosocial work environment by ensuring nurses working in these areas have the required specialisation skills, there is a balance of workload and nurse-to-patient ratios, and they are offered fairness and equity in career progression and promotion.

CD13-positive bone marrow-derived myeloid cells promote angiogenesis, tumor growth, and metastasis.

PubMed

Dondossola, Eleonora; Rangel, Roberto; Guzman-Rojas, Liliana; Barbu, Elena M; Hosoya, Hitomi; St John, Lisa S; Molldrem, Jeffrey J; Corti, Angelo; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

2013-12-17

Angiogenesis is fundamental to tumorigenesis and an attractive target for therapeutic intervention against cancer. We have recently demonstrated that CD13 (aminopeptidase N) expressed by nonmalignant host cells of unspecified types regulate tumor blood vessel development. Here, we compare CD13 wild-type and null bone marrow-transplanted tumor-bearing mice to show that host CD13(+) bone marrow-derived cells promote cancer progression via their effect on angiogenesis. Furthermore, we have identified CD11b(+)CD13(+) myeloid cells as the immune subpopulation directly regulating tumor blood vessel development. Finally, we show that these cells are specifically localized within the tumor microenvironment and produce proangiogenic soluble factors. Thus, CD11b(+)CD13(+) myeloid cells constitute a population of bone marrow-derived cells that promote tumor progression and metastasis and are potential candidates for the development of targeted antiangiogenic drugs.

Influences of innate immunity, autophagy, and fibroblast activation in the pathogenesis of lung fibrosis

PubMed Central

O'Dwyer, David N.; Ashley, Shanna L.

2016-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by accumulation of extracellular matrix (ECM) and impaired gas exchange. The pathobiological mechanisms that account for disease progression are poorly understood but likely involve alterations in innate inflammatory cells, epithelial cells, and fibroblasts. Thus we seek to review the most recent literature highlighting the complex roles of neutrophils and macrophages as both promoters of fibrosis and defenders against infection. With respect to epithelial cells and fibroblasts, we review the data suggesting that defective autophagy promotes the fibrogenic potential of both cell types and discuss new evidence related to matrix metalloproteinases, growth factors, and cellular metabolism in the form of lactic acid generation that may have consequences for promoting fibrogenesis. We discuss potential cross talk between innate and structural cell types and also highlight literature that may help explain the limitations of current IPF therapies. PMID:27474089

Influences of innate immunity, autophagy, and fibroblast activation in the pathogenesis of lung fibrosis.

PubMed

O'Dwyer, David N; Ashley, Shanna L; Moore, Bethany B

2016-09-01

Idiopathic pulmonary fibrosis (IPF) is a progressive interstitial lung disease characterized by accumulation of extracellular matrix (ECM) and impaired gas exchange. The pathobiological mechanisms that account for disease progression are poorly understood but likely involve alterations in innate inflammatory cells, epithelial cells, and fibroblasts. Thus we seek to review the most recent literature highlighting the complex roles of neutrophils and macrophages as both promoters of fibrosis and defenders against infection. With respect to epithelial cells and fibroblasts, we review the data suggesting that defective autophagy promotes the fibrogenic potential of both cell types and discuss new evidence related to matrix metalloproteinases, growth factors, and cellular metabolism in the form of lactic acid generation that may have consequences for promoting fibrogenesis. We discuss potential cross talk between innate and structural cell types and also highlight literature that may help explain the limitations of current IPF therapies. Copyright © 2016 the American Physiological Society.

Recent progress and future direction of cancer epidemiological research in Japan.

PubMed

Sobue, Tomotaka

2015-06-01

In 2006, the Cancer Control Act was approved and a Basic Plan, to Promote the Cancer Control Program at the national level, was developed in 2007. Cancer research is recognized as a fundamental component to provide evidence in cancer control program. Cancer epidemiology plays central role in connecting research and policy, since it directly deals with data from humans. Research for cancer epidemiology in Japan made substantial progress, in the field of descriptive studies, cohort studies, intervention studies and activities for summarizing evidences. In future, promoting high-quality large-scale intervention studies, individual-level linkage studies, simulation models and studies for elderly population will be of great importance, but at the same time research should be promoted in well-balanced fashion not placing too much emphasis on one particular research field. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Prognostic Value of Plasma Epstein-Barr Virus DNA for Local and Regionally Advanced Nasopharyngeal Carcinoma Treated With Cisplatin-Based Concurrent Chemoradiotherapy in Intensity-Modulated Radiotherapy Era.

PubMed

Chen, Wen-Hui; Tang, Lin-Quan; Guo, Shan-Shan; Chen, Qiu-Yan; Zhang, Lu; Liu, Li-Ting; Qian, Chao-Nan; Guo, Xiang; Xie, Dan; Zeng, Mu-Sheng; Mai, Hai-Qiang

2016-02-01

This study aimed to evaluate the prognostic value of plasma Epstein-Barr Virus DNA (EBV DNA) for local and regionally advanced nasopharyngeal carcinoma (NPC) patients treated with concurrent chemoradiotherapy in intensity-modulated radiotherapy (IMRT) era.In this observational study, 404 nonmetastatic local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy were recruited. Blood samples were collected before treatment for examination of plasma EBV DNA levels. We evaluated the association of pretreatment plasma EBV DNA levels with progression-free survival rate (PFS), distant metastasis-free survival rate (DMFS), and overall survival rate (OS).Compared to patients with an EBV DNA level < 4000  copies/mL, patients with an EBV DNA ≥ 4000  copies/mL had a lower rate of 3-year PFS (76%, 95% CI [68-84]) versus (93%, 95% CI [90-96], P < 0.001), DMFS (83%, 95% CI [76-89]) versus (97%, 95% CI [94-99], P < 0.001), and OS (85%, 95% CI [78-92]) versus (98%, 95% CI [95-100], P < 0.001). Multivariate analysis showed that pretreatment EBV DNA levels (HR = 3.324, 95% CI, 1.80-6.138, P < 0.001) and clinical stage (HR = 1.878, 95% CI, 1.036-3.404, P = 0.038) were the only independent factor associated with PFS, pretreatment EBV DNA level was the only significant factor to predict DMFS (HR = 6.292, 95% CI, 2.647-14.956, P < 0.001), and pretreatment EBV DNA levels (HR = 3.753, 95% CI, 1.701-8.284, P < 0.001) and clinical stage (HR = 2.577, 95% CI, 1.252-5.050, P = 0.010) were significantly associated with OS. In subgroup analysis, higher plasma EBV DNA levels still predicted a worse PFS, DMFS, and OS for the patients stage III or stage IVa-b, compared with those with low EBV DNA levels.Elevated plasma EBV DNA was still effective prognostic biomarker for local and regionally advanced NPC patients treated with IMRT and cisplatin-based concurrent chemotherapy. Future ramdomized clinical trials are needed to further evaluate whether plasma EBV DNA levels could be applied to guide concurrent chemotherapy regimen for local and regionally advanced NPC patients.

Extracellular Acidic pH Activates the Sterol Regulatory Element-Binding Protein 2 to Promote Tumor Progression.

PubMed

Kondo, Ayano; Yamamoto, Shogo; Nakaki, Ryo; Shimamura, Teppei; Hamakubo, Takao; Sakai, Juro; Kodama, Tatsuhiko; Yoshida, Tetsuo; Aburatani, Hiroyuki; Osawa, Tsuyoshi

2017-02-28

Conditions of the tumor microenvironment, such as hypoxia and nutrient starvation, play critical roles in cancer progression. However, the role of acidic extracellular pH in cancer progression is not studied as extensively as that of hypoxia. Here, we show that extracellular acidic pH (pH 6.8) triggered activation of sterol regulatory element-binding protein 2 (SREBP2) by stimulating nuclear translocation and promoter binding to its targets, along with intracellular acidification. Interestingly, inhibition of SREBP2, but not SREBP1, suppressed the upregulation of low pH-induced cholesterol biosynthesis-related genes. Moreover, acyl-CoA synthetase short-chain family member 2 (ACSS2), a direct SREBP2 target, provided a growth advantage to cancer cells under acidic pH. Furthermore, acidic pH-responsive SREBP2 target genes were associated with reduced overall survival of cancer patients. Thus, our findings show that SREBP2 is a key transcriptional regulator of metabolic genes and progression of cancer cells, partly in response to extracellular acidification. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

The Ties That Bind: Mapping the Dynamic Enhancer-Promoter Interactome.

PubMed

Spurrell, Cailyn H; Dickel, Diane E; Visel, Axel

2016-11-17

Coupling chromosome conformation capture to molecular enrichment for promoter-containing DNA fragments enables the systematic mapping of interactions between individual distal regulatory sequences and their target genes. In this Minireview, we describe recent progress in the application of this technique and related complementary approaches to gain insight into the lineage- and cell-type-specific dynamics of interactions between regulators and gene promoters. Copyright © 2016 Elsevier Inc. All rights reserved.

IL-7 splicing variant IL-7{delta}5 induces human breast cancer cell proliferation via activation of PI3K/Akt pathway

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

Pan, Deshun; Department of Pharmaceutical science, Guangdong Pharmaceutical University, Guangzhou, Guangdong; Liu, Bing

2012-06-15

Highlights: Black-Right-Pointing-Pointer This study confirms the role of IL-7{delta}5 in breast cancer cell proliferation. Black-Right-Pointing-Pointer IL-7{delta}5 promotes breast cancer cell proliferation and cell cycle progression. Black-Right-Pointing-Pointer IL-7{delta}5 promotes cell proliferation via activation of PI3K/Akt pathway. -- Abstract: Various tumor cells express interleukin 7 (IL-7) and IL-7 variants. IL-7 has been confirmed to stimulate solid tumor cell proliferation. However, the effect of IL-7 variants on tumor cell proliferation remains unclear. In this study, we evaluated the role of IL-7{delta}5 (an IL-7 variant lacking exon 5) on proliferation and cell cycle progression of human MDA-MB-231 and MCF-7 breast cancer cells. The resultsmore » showed that IL-7{delta}5 promoted cell proliferation and cell cycle progression from G1 phase to G2/M phase, associated with upregulation of cyclin D1 expression and the downregulation of p27{sup kip1} expression. Mechanistically, we found that IL-7{delta}5 induced the activation of Akt. Inhibition of PI3K/Akt pathway by LY294002 reversed the proliferation and cell cycle progression of MDA-MB-231 and MCF-7 cells induced by IL-7{delta}5. In conclusion, our findings demonstrate that IL-7{delta}5 variant induces human breast cancer cell proliferation and cell cycle progression via activation of PI3K/Akt pathway. Thus, IL-7{delta}5 may be a potential target for human breast cancer therapeutics intervention.« less

Recent advances in understanding vitiligo.

PubMed

Manga, Prashiela; Elbuluk, Nada; Orlow, Seth J

2016-01-01

Vitiligo, an acquired depigmentation disorder, manifests as white macules on the skin and can cause significant psychological stress and stigmatization. Recent advances have shed light on key components that drive disease onset and progression as well as therapeutic approaches. Vitiligo can be triggered by stress to the melanin pigment-producing cells of the skin, the melanocytes. The triggers, which range from sunburn to mechanical trauma and chemical exposures, ultimately cause an autoimmune response that targets melanocytes, driving progressive skin depigmentation. The most significant progress in our understanding of disease etiology has been made on three fronts: (1) identifying cellular responses to stress, including antioxidant pathways and the unfolded protein response (UPR), as key players in disease onset, (2) characterizing immune responses that target melanocytes and drive disease progression, and (3) identifying major susceptibility genes. The current model for vitiligo pathogenesis postulates that oxidative stress causes cellular disruptions, including interruption of protein maturation in the endoplasmic reticulum (ER), leading to the activation of the UPR and expression of UPR-regulated chemokines such as interleukin 6 (IL-6) and IL-8. These chemokines recruit immune components to the skin, causing melanocytes to be targeted for destruction. Oxidative stress can further increase melanocyte targeting by promoting antigen presentation. Two key components of the autoimmune response that promote disease progression are the interferon (IFN)-γ/CXCL10 axis and IL-17-mediated responses. Several genome-wide association studies support a role for these pathways, with the antioxidant gene NRF2, UPR gene XBP1, and numerous immune-related genes including class I and class II major histocompatibility genes associated with a risk for developing vitiligo. Novel approaches to promote repigmentation in vitiligo are being investigated and may yield effective, long-lasting therapies.

Phase II study. Concurrent chemotherapy and radiotherapy with nitroglycerin in locally advanced non-small cell lung cancer.

PubMed

Arrieta, Oscar; Blake, Mónika; de la Mata-Moya, María Dolores; Corona, Francisco; Turcott, Jenny; Orta, David; Alexander-Alatorre, Jorge; Gallardo-Rincón, Dolores

2014-05-01

Nitroglycerin, a nitric oxide donor agent, reduces the expression of hypoxia-inducible factor-1α (HIF-1α) and could be a normalizer of the tumor microenvironment. Both factors are associated with chemo-radio-resistance. The aim of this study was to determine the safety profile and efficacy of nitroglycerin administration with chemo-radiotherapy in patients with locally advanced non-small cell lung cancer (NSCLC). This is a phase II trial of locally advanced NSCLC patients treated with cisplatin and vinorelbine plus concurrent nitroglycerin with radiotherapy. A 25-mg NTG patch was administered to the patients for 5 days (1 day before and 4 days after chemotherapy induction and consolidation) and all day during chemo-radiotherapy. VEGF plasmatic level was determined before and after two cycles of chemotherapy. Thirty-five patients were enrolled in this trial. Sixty-three percent of patients achieved an overall response after induction of chemotherapy, and 75% achieved an overall response after chemo-radiotherapy. The median progression-free survival was 13.5 months (95% CI, 8.8-18.2), and the median overall survival was 26.9 months (95% CI, 15.3-38.5). Reduction of VEGF level was associated with better OS. The toxicity profile related to nitroglycerin included headache (20%) and hypotension (2.9%). The addition of nitroglycerin to induction chemotherapy and concurrent chemoradiotherapy in patients with locally advanced NSCLC has an acceptable toxicity profile and supports the possibility to add nitroglycerin to chemotherapy and radiotherapy. A randomized trial is warranted to confirm these findings. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

The Monkey game: A computerized verbal working memory task for self-reliant administration in primary school children.

PubMed

Van de Weijer-Bergsma, Eva; Kroesbergen, Evelyn H; Jolani, Shahab; Van Luit, Johannes E H

2016-06-01

In two studies, the psychometric properties of an online self-reliant verbal working memory task (the Monkey game) for primary school children (6-12 years of age) were examined. In Study 1, children (n = 5,203) from 31 primary schools participated. The participants completed computerized verbal and visual-spatial working memory tasks (i.e., the Monkey game and the Lion game) and a paper-and-pencil version of Raven's Standard Progressive Matrices. Reading comprehension and math achievement test scores were obtained from the schools. First, the internal consistency of the Monkey game was examined. Second, multilevel modeling was used to examine the effects of classroom membership. Multilevel multivariate regression analysis was used to examine the Monkey game's concurrent relationship with the Lion game and its predictive relationships with reading comprehension and math achievement. Also, age-related differences in performance were examined. In Study 2, the concurrent relationships between the Monkey game and two tester-led computerized working memory tasks were further examined (n = 140). Also, the 1- and 2-year stability of the Monkey game was investigated. The Monkey game showed excellent internal consistency, good concurrent relationships with the other working memory measures, and significant age differences in performance. Performance on the Monkey game was also predictive of subsequent reading comprehension and mathematics performance, even after controlling for individual differences in intelligence. Performance on the Monkey game was influenced by classroom membership. The Monkey game is a reliable and suitable instrument for the online computerized and self-reliant assessment of verbal working memory in primary school children.

Using the Statecharts paradigm for simulation of patient flow in surgical care.

PubMed

Sobolev, Boris; Harel, David; Vasilakis, Christos; Levy, Adrian

2008-03-01

Computer simulation of patient flow has been used extensively to assess the impacts of changes in the management of surgical care. However, little research is available on the utility of existing modeling techniques. The purpose of this paper is to examine the capacity of Statecharts, a system of graphical specification, for constructing a discrete-event simulation model of the perioperative process. The Statecharts specification paradigm was originally developed for representing reactive systems by extending the formalism of finite-state machines through notions of hierarchy, parallelism, and event broadcasting. Hierarchy permits subordination between states so that one state may contain other states. Parallelism permits more than one state to be active at any given time. Broadcasting of events allows one state to detect changes in another state. In the context of the peri-operative process, hierarchy provides the means to describe steps within activities and to cluster related activities, parallelism provides the means to specify concurrent activities, and event broadcasting provides the means to trigger a series of actions in one activity according to transitions that occur in another activity. Combined with hierarchy and parallelism, event broadcasting offers a convenient way to describe the interaction of concurrent activities. We applied the Statecharts formalism to describe the progress of individual patients through surgical care as a series of asynchronous updates in patient records generated in reaction to events produced by parallel finite-state machines representing concurrent clinical and managerial activities. We conclude that Statecharts capture successfully the behavioral aspects of surgical care delivery by specifying permissible chronology of events, conditions, and actions.

The extracellular matrix locally regulates asynchronous concurrent lactation in tammar wallaby (Macropus eugenii).

PubMed

Wanyonyi, Stephen S; Lefevre, Christophe; Sharp, Julie A; Nicholas, Kevin R

2013-08-08

Asynchronous concurrent lactation (ACL) is an extreme lactation strategy in macropod marsupials including the tammar wallaby, that may hold the key to understanding local control of mammary epithelial cell function. Marsupials have a short gestation and a long lactation consisting of three phases; P2A, P2B and P3, representing early, mid and late lactation respectively and characterised by profound changes in milk composition. A lactating tammar is able to concurrently produce phase 2A and 3 milk from adjacent glands in order to feed a young newborn and an older sibling at heel. Physiological effectors of ACL remain unknown and in this study the extracellular matrix (ECM) is investigated for its role in switching mammary phenotypes between phases of tammar wallaby lactation. Using the level of expression of the genes for the phase specific markers tELP, tWAP, and tLLP-B representing phases 2A, 2B and 3 respectively we show for the first time that tammar wallaby mammary epithelial cells (WallMECs) extracted from P2B acquire P3 phenotype when cultured on P3 ECM. Similarly P2A cells acquire P2B phenotype when cultured on P2B ECM. We further demonstrate that changes in phase phenotype correlate with phase-specific changes in ECM composition. This study shows that progressive changes in ECM composition in individual mammary glands provide a local regulatory mechanism for milk protein gene expression thereby enabling the mammary glands to lactate independently. Copyright © 2013. Published by Elsevier B.V.

Rapid Production of High-Purity Hydrogen Fuel through Microwave-Promoted Deep Catalytic Dehydrogenation of Liquid Alkanes with Abundant Metals.

PubMed

Jie, Xiangyu; Gonzalez-Cortes, Sergio; Xiao, Tiancun; Wang, Jiale; Yao, Benzhen; Slocombe, Daniel R; Al-Megren, Hamid A; Dilworth, Jonathan R; Thomas, John M; Edwards, Peter P

2017-08-14

Hydrogen as an energy carrier promises a sustainable energy revolution. However, one of the greatest challenges for any future hydrogen economy is the necessity for large scale hydrogen production not involving concurrent CO 2 production. The high intrinsic hydrogen content of liquid-range alkane hydrocarbons (including diesel) offers a potential route to CO 2 -free hydrogen production through their catalytic deep dehydrogenation. We report here a means of rapidly liberating high-purity hydrogen by microwave-promoted catalytic dehydrogenation of liquid alkanes using Fe and Ni particles supported on silicon carbide. A H 2 production selectivity from all evolved gases of some 98 %, is achieved with less than a fraction of a percent of adventitious CO and CO 2 . The major co-product is solid, elemental carbon. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

EAT-UP™ Family-Centered Feeding Intervention to Promote Food Acceptance and Decrease Challenging Behaviors: A Single-Case Experimental Design Replicated Across Three Families of Children with Autism Spectrum Disorder.

PubMed

Cosbey, Joanna; Muldoon, Deirdre

2017-03-01

This study evaluated the effectiveness of a family-centered feeding intervention, Easing Anxiety Together with Understanding and Perseverance (EAT-UP™), for promoting food acceptance of children with autism spectrum disorder at home. A concurrent multiple-baseline design was used with systematic replication across three families. Baseline was followed by an 'Intervention-Coaching' phase and then an 'Intervention-Independent' phase. Using direct observation and pre- and post-intervention questionnaires, data on acceptance of less preferred foods and challenging mealtime behaviors were collected. Procedural fidelity was monitored throughout all study phases. Data were analyzed using visual analysis and measures of effect size. All children demonstrated increases in food acceptance (effect size >0.90) and dietary diversity and decreased challenging behaviors. Implications for practice and research are discussed.

S100-A9 protein in exosomes from chronic lymphocytic leukemia cells promotes NF-κB activity during disease progression.

PubMed

Prieto, Daniel; Sotelo, Natalia; Seija, Noé; Sernbo, Sandra; Abreu, Cecilia; Durán, Rosario; Gil, Magdalena; Sicco, Estefanía; Irigoin, Victoria; Oliver, Carolina; Landoni, Ana Inés; Gabus, Raúl; Dighiero, Guillermo; Oppezzo, Pablo

2017-08-10

Chronic lymphocytic leukemia (CLL) is an incurable disease characterized by accumulation of clonal B lymphocytes, resulting from a complex balance between cell proliferation and apoptotic death. Continuous crosstalk between cancer cells and local/distant host environment is required for effective tumor growth. Among the main actors of this dynamic interplay between tumoral cells and their microenvironment are the nano-sized vesicles called exosomes. Emerging evidence indicates that secretion, composition, and functional capacity of exosomes are altered as tumors progress to an aggressive phenotype. In CLL, no data exist exploring the specific changes in the proteomic profile of plasma-derived exosomes from patients during disease evolution. We hereby report for the first time different proteomic profiles of plasma exosomes, both between indolent and progressive CLLs as well as within the individual patients at the onset of disease and during its progression. Next, we focus on the changes of the exosome protein cargoes, which are found exclusively in patients with progressive CLL after disease progression. The alterations in the proteomic cargoes underline different networks specific for leukemia progression related to inflammation, oxidative stress, and NF-κB and phosphatidylinositol 3-kinase/AKT pathway activation. Finally, our results suggest a preponderant role for the protein S100-A9 as an activator of the NFκB pathway during CLL progression and suggest that the leukemic clone can generate an autoactivation loop through S100-A9 expression, NF-κB activation, and exosome secretion. Collectively, our data propose a new pathway for NF-κB activation in CLL and highlight the importance of exosomes as extracellular mediators promoting tumor progression in CLL. © 2017 by The American Society of Hematology.

Immunological roulette: Luck or something more? Considering the connections between host and environment in TB.

PubMed

Pearl, John E; Das, Mrinal; Cooper, Andrea M

2018-03-01

Accurate prediction of which patient will progress from a sub-clinical Mycobacterium tuberculosis infection to active tuberculosis represents an elusive, yet critical, clinical research objective. From the individual perspective, progression can be considered to be the product of a series of unfortunate events or even a run of bad luck. Here, we identify the subtle physiological relationships that can influence the odds of progression to active TB and how this progression may reflect directed dysbiosis in a number of interrelated systems. Most infected individuals who progress to disease have apparently good immune responses, but these responses are, at times, compromised by either local or systemic environmental factors. Obvious disease promoting processes, such as tissue-damaging granulomata, usually manifest in the lung, but illness is systemic. This apparent dichotomy between local and systemic reflects a clear need to define the factors that promote progression to active disease within the context of the body as a physiological whole. We discuss aspects of the host environment that can impact expression of immunity, including the microbiome, glucocorticoid-mediated regulation, catecholamines and interaction between the gut, liver and lung. We suggest the importance of integrating precision medicine into our analyses of experimental outcomes such that apparently conflicting results are not contentious, but rather reflect the impact of these subtle relationships with our environment and microbiota.

PRL-3 Promotes the Malignant Progression of Melanoma via Triggering Dephosphorylation and Cytoplasmic Localization of NHERF1.

PubMed

Fang, Xian-Ying; Song, Ran; Chen, Wei; Yang, Yuan-Yuan; Gu, Yan-Hong; Shu, Yong-Qian; Wu, Xu-Dong; Wu, Xue-Feng; Sun, Yang; Shen, Yan; Xu, Qiang

2015-09-01

Phosphatase of regenerating liver-3 (PRL-3) has been reported to have a critical role in metastatic progression of cancers. Here, we investigate how PRL-3 increases the malignant degree of melanoma cells. The expression of PRL-3 increased gradually during the malignant progression of melanoma. The phosphorylation of Akt was elevated in highly malignant melanoma cells, which was accompanied by a decrease in nuclear phosphatase and tensin homolog (PTEN). The phosphorylation of NHERF1 in the serine site was regulated by PRL-3 and showed cytoplasmic translocation upon dephosphorylation, which resulted in a decrease in nuclear PTEN. The co-translocation of NHERF1 and PTEN from the nucleus to the cytoplasm was observed during the malignant progression of melanoma cells. Tumor growth was inhibited significantly, and the survival was prolonged upon knockdown of cytoplasmic NHERF1 in B16BL6 cells prior to the inoculation into mice. Taken together, to our knowledge previously unreported, we have identified NHERF1 as a potential substrate of PRL-3. Its phosphorylation status as well as its change in cellular localization and association with PTEN correlated with the malignant progression of melanoma. Our data provide an explanation for how PRL-3 promotes the malignant progression of melanoma, as well as a diagnostic marker or therapeutic target for malignant melanoma.

A phase I, dose-finding study of sorafenib in combination with gemcitabine and radiation therapy in patients with unresectable pancreatic adenocarcinoma: a Grupo Español Multidisciplinario en Cáncer Digestivo (GEMCAD) study.

PubMed

Aparicio, Jorge; García-Mora, Carmen; Martín, Marta; Petriz, Ma Lourdes; Feliu, Jaime; Sánchez-Santos, Ma Elena; Ayuso, Juan Ramón; Fuster, David; Conill, Carlos; Maurel, Joan

2014-01-01

Sorafenib, an oral inhibitor of B-raf, VEGFR2, and PDGFR2-beta, acts against pancreatic cancer in preclinical models. Due to the radio-sensitization activity of both sorafenib and gemcitabine, we designed a multicenter, phase I trial to evaluate the safety profile and the recommended dose of this combination used with concomitant radiation therapy. Patients with biopsy-proven, unresectable pancreatic adenocarcinoma (based on vascular invasion detected by computed tomography) were treated with gemcitabine (300 mg/m2 i.v. weekly ×5 weeks) concurrently with radiation therapy (45 Gy in 25 fractions) and sorafenib (escalated doses in a 3+3 design, from 200 to 800 mg/day). Radiation portals included the primary tumor but not the regional lymph nodes. Patients with planning target volumes (PTV) over 500 cc were excluded. Cases not progressing during chemoradiation were allowed to continue with sorafenib until disease progression. Twelve patients were included. Three patients received 200 mg/day, 6 received 400 mg/day, and 3 received 800 mg/day; PTVs ranged from 105 to 500 cc. No dose-limiting toxicities occurred. The most common grade 2 toxicities were fatigue, neutropenia, nausea, and raised serum transaminases. Treatment was discontinued in one patient because of a reversible posterior leukoencephalopathy. There were no treatment-related deaths. The addition of sorafenib to concurrent gemcitabine and radiation therapy showed a favorable safety profile in unresectable pancreatic adenocarcinoma. A dose of 800 mg/day is recommended for phase II evaluation. EudraCT 2007-003211-31 ClinicalTrials.gov 00789763.

Magnesium taurate prevents cataractogenesis via restoration of lenticular oxidative damage and ATPase function in cadmium chloride-induced hypertensive experimental animals.

PubMed

Choudhary, Rajesh; Bodakhe, Surendra H

2016-12-01

Previously we found that hypertension potentiates the risk the cataractogenesis. In the present study, we investigated the protective effects of magnesium taurate (MgT) on hypertension and associated lenticular damages against cadmium chloride (CdCl 2 )-induced hypertensive animals. Male Sprague-Dawley albino rats (150-180g) were assigned to five experimental groups (n=6). Among the five groups, normal group received 0.3% carboxymethyl cellulose (10ml/kg/day, p.o.). Hypertension control group received CdCl 2 (0.5mg/kg/day, i.p.). Tests and standard groups received MgT (3 and 6mg/kg/day, p.o.) and amlodipine (3mg/kg/day, p.o.) concurrently with CdCl 2 respectively , for six consecutive weeks. Blood pressure, heart rate, and eyes were examined biweekly, and pathophysiological parameters in serum and eye lenses were evaluated after six weeks of the experimental protocol. The chronic administration of MgT concurrently with CdCl 2 significantly restored the blood pressure, serum and lens antioxidants (CAT, SOD, GPx, and GSH), MDA level, and ions (Na + , K + , and Ca 2+ ). Additionally, MgT treatment led to significant increase in the lens proteins (total and soluble), Ca 2+ ATPase, and Na + K + ATPase activity as compared to hypertension control group. Ophthalmoscope observations indicated that MgT treatments delayed the progression of cataract against the hypertensive state. The study shows that MgT prevents the progression of cataractogenesis via restoration of blood pressure, lenticular oxidative damages, and lens ATPase functions in the hypertensive state. The results suggest that MgT supplement may play a beneficial role to manage hypertension and associated cataractogenesis. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

The clinical efficacy of consolidation chemotherapy for resectable esophageal squamous cell cancer after trimodality therapy.

PubMed

Sun, Yanan; Cheng, Siguo; Lu, Yufei; Zheng, Xiaoli; Ye, Ke; Ge, Hong

2016-01-01

We aimed to assess the clinical outcome of consolidation chemotherapy for resectable esophageal squamous cell cancer (ESCC) after trimodality therapy. From January 2005 to December 2012, a total of 192 consecutive locally advanced ESCC patients who underwent trimodality therapy successfully was included. Grouping was based on the degree of myelosuppression occurred during preoperative chemoradiotherapy. Of the 192 patients, 120 patients underwent trimodality therapy only (TT group), while 72 patients received consolidation chemotherapy additionally after trimodality therapy (TC group). Preoperative chemoradiotherapy included two cycles of chemotherapy concurrently with radiotherapy. The chemotherapy regimen consisted of cisplatin 20 mg/m2/day and fluorouracil 400 mg/m2/day administered intravenously infusion on days 1-5 of a 21 days cycle. Concurrent radiotherapy was delivered in a total of 40 Gy in 20 fractions. All patients underwent surgery successfully. For 72 patients in TC group, additional 1-4 cycles of consolidation chemotherapy were administered, and chemotherapy regimen was as before. The 5-year survival rate was 43.5% in TT group, as compared with 48.8% in TC group. (P = 0.238). The 5.year progression.free survival. (PFS) rates were 34.0% in TT group and 38.8% in TC group. (P = 0.049). Risk reduction in PFS was remarkable for males and those who did not achieve pathologic complete response. (pCR). The incidence rate of disease progression did not differ significantly. (P = 0.200). The addition of consolidation chemotherapy demonstrates no survival benefit for patients with locally advanced ESCC, but PFS is significantly improved, especially for males and those who did not achieve pCR.

Safety and pharmacokinetics of dose-intensive imatinib mesylate plus temozolomide: Phase 1 trial in adults with malignant glioma

PubMed Central

Reardon, David A.; Desjardins, Annick; Vredenburgh, James J.; Sathornsumetee, Sith; Rich, Jeremy N.; Quinn, Jennifer A.; Lagattuta, Theodore F.; Egorin, Merrill J.; Gururangan, Sridharan; McLendon, Roger; Herndon, James E.; Friedman, Allan H.; Salvado, August J.; Friedman, Henry S.

2008-01-01

We determined the maximum tolerated dose (MTD) and dose-limiting toxicity (DLT) of imatinib mesylate, an inhibitor of the receptor tyrosine kinases platelet-derived growth factor receptor (PDGFR), the proto-oncogene product c-kit, and the fusion protein Bcr-Abl, when administered for 8 days in combination with temozolomide (TMZ) to malignant glioma (MG) patients. MG patients who had not failed prior TMZ were eligible to receive TMZ at a dose of 150–200 mg/m2 per day on days 4–8 plus imatinib mesylate administered orally on days 1–8 of each 4-week cycle. Patients were stratified based on concurrent administration of CYP3A4-inducing antiepileptic drugs (EIAEDs). The imatinib dose was escalated in successive cohorts of patients independently for each stratum. Imatinib, at doses ranging from 400 mg to 1,200 mg, was administered with TMZ to 65 patients: 52 (80%) with glioblastoma multiforme (GBM) and 13 (20%) with grade III MG. At enrollment, 34 patients (52%) had stable disease, and 33 (48%) had progressive disease; 30 patients (46%) were on EIAEDs. The MTD of imatinib for patients concurrently receiving or not receiving EIAEDs was 1,000 mg. DLTs were hematologic, gastrointestinal, renal, and hepatic. Pharmacokinetic analyses revealed lowered exposures and enhanced clearance among patients on EIAEDs. Among GBM patients with stable disease at enrollment (n = 28), the median progression-free and overall survival times were 41.7 and 56.1 weeks, respectively. Imatinib doses up to 1,000 mg/day for 8 consecutive days are well tolerated when combined with standard TMZ dosing for MG patients. A subsequent phase 2 study is required to further evaluate the efficacy of this regimen for this patient population. PMID:18359865

Repeated nitrous oxide exposure in rats causes a thermoregulatory sign-reversal with concurrent activation of opposing thermoregulatory effectors

PubMed Central

Ramsay, Douglas S; Woods, Stephen C; Kaiyala, Karl J

2014-01-01

Initial administration of 60% nitrous oxide (N2O) to rats at an ambient temperature of 21°C decreases core temperature (Tc), primarily via increased heat loss (HL). Over repeated N2O administrations, rats first develop tolerance to this hypothermia and subsequently exhibit hyperthermia (a sign-reversal) due primarily to progressive increases in heat production (HP). When rats initially receive 60% N2O in a thermal gradient, they become hypothermic while selecting cooler ambient temperatures that facilitate HL. This study investigated whether rats repeatedly administered 60% N2O in a thermal gradient would use the gradient to behaviorally facilitate, or oppose, the development of chronic tolerance and a hyperthermic sign-reversal. Male Long-Evans rats (N = 16) received twelve 3-h administrations of 60% N2O in a gas-tight, live-in thermal gradient. Hypothermia (Sessions 1–3), complete chronic tolerance (Sessions 4–6), and a subsequent transient hyperthermic sign-reversal (Sessions 7–12) sequentially developed. Despite the progressive recovery and eventual hyperthermic sign-reversal of Tc, rats consistently selected cooler ambient temperatures during all N2O administrations. A final 60% N2O administration in a total calorimeter indicated that the hyperthermic sign-reversal resulted primarily from increased HP. Thus, rats did not facilitate chronic tolerance development by moving to warmer locations in the gradient, and instead selected cooler ambient temperatures while simultaneously increasing autonomic HP. The inefficient concurrent activation of opposing effectors and the development of a sign-reversal are incompatible with homeostatic models of drug-adaptation and may be better interpreted using a model of drug-induced allostasis. PMID:25938127