Primary care physicians' willingness to disclose oncology errors involving multiple providers to patients.

PubMed

Mazor, Kathleen; Roblin, Douglas W; Greene, Sarah M; Fouayzi, Hassan; Gallagher, Thomas H

2016-10-01

Full disclosure of harmful errors to patients, including a statement of regret, an explanation, acceptance of responsibility and commitment to prevent recurrences is the current standard for physicians in the USA. To examine the extent to which primary care physicians' perceptions of event-level, physician-level and organisation-level factors influence intent to disclose a medical error in challenging situations. Cross-sectional survey containing two hypothetical vignettes: (1) delayed diagnosis of breast cancer, and (2) care coordination breakdown causing a delayed response to patient symptoms. In both cases, multiple physicians shared responsibility for the error, and both involved oncology diagnoses. The study was conducted in the context of the HMO Cancer Research Network Cancer Communication Research Center. Primary care physicians from three integrated healthcare delivery systems located in Washington, Massachusetts and Georgia; responses from 297 participants were included in these analyses. The dependent variable intent to disclose included intent to provide an apology, an explanation, information about the cause and plans for preventing recurrences. Independent variables included event-level factors (responsibility for the event, perceived seriousness of the event, predictions about a lawsuit); physician-level factors (value of patient-centred communication, communication self-efficacy and feelings about practice); organisation-level factors included perceived support for communication and time constraints. A majority of respondents would not fully disclose in either situation. The strongest predictors of disclosure were perceived personal responsibility, perceived seriousness of the event and perceived value of patient-centred communication. These variables were consistently associated with intent to disclose. To make meaningful progress towards improving disclosure; physicians, risk managers, organisational leaders, professional organisations and accreditation bodies need to understand the factors which influence disclosure. Such an understanding is required to inform institutional policies and provider training. 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/

Analysis of cellular and humoral immune responses against cytomegalovirus in patients with autoimmune Addison's disease.

PubMed

Edvardsen, Kine; Hellesen, Alexander; Husebye, Eystein S; Bratland, Eirik

2016-03-09

Autoimmune Addison's disease (AAD) is caused by multiple genetic and environmental factors. Variants of genes encoding immunologically important proteins such as the HLA molecules are strongly associated with AAD, but any environmental risk factors have yet to be defined. We hypothesized that primary or reactivating infections with cytomegalovirus (CMV) could represent an environmental risk factor in AAD, and that CMV specific CD8(+) T cell responses may be dysregulated, possibly leading to a suboptimal control of CMV. In particular, the objective was to assess the HLA-B8 restricted CD8(+) T cell response to CMV since this HLA class I variant is a genetic risk factor for AAD. To examine the CD8(+) T cell response in detail, we analyzed the HLA-A2 and HLA-B8 restricted responses in AAD patients and healthy controls seropositive for CMV antibodies using HLA multimer technology, IFN-γ ELISpot and a CD107a based degranulation assay. No differences between patients and controls were found in functions or frequencies of CMV-specific T cells, regardless if the analyses were performed ex vivo or after in vitro stimulation and expansion. However, individual patients showed signs of reactivating CMV infection correlating with poor CD8(+) T cell responses to the virus, and a concomitant upregulation of interferon regulated genes in peripheral blood cells. Several recently diagnosed AAD patients also showed serological signs of ongoing primary CMV infection. CMV infection does not appear to be a major environmental risk factor in AAD, but may represent a precipitating factor in individual patients.

A DELPHI STUDY OF RISK FACTORS FOR ACHILLES TENDINOPATHY- OPINIONS OF WORLD TENDON EXPERTS

PubMed Central

Watson, Paul J.; Barry, Simon

2016-01-01

Background and Purpose Achilles tendinopathy can be a debilitating chronic condition for both active and inactive individuals. The identification of risk facors is important both in preventing but also treating tendinopathy, many factors have been proposed but there is a lack of primary epidemiological data. The purpose of this study was to develop a statement of expert consensus on risk factors for Achilles tendinopathy in active and sedentary patient populations to inform a primary epidemiological study. Study design Delphi study Methods and Measures An online Delphi study was completed inviting participation from world tendon experts. The consensus was developed using three rounds of the Delphi technique. The first round developed a complete list of potential risk factors, the second round refined this list but also separated the factors into two population groups – active/athletic and inactive/sedentary. The third round ranked this list in order of perceived importance. Results Forty-four experts were invited to participate, 16 participated in the first round (response rate 40%) and two dropped out in the second round (resulting in a response rate of 35%). A total of 27 intrinsic and eight extrinsic risk factors were identified during round one. During round two only 12 intrinsic and five extrinsic risk factors were identified as important in active/athletic tendinopathy while 14 intrinsic and three extrinsic factors were identified as important for inactive/sedentary tendinopathy. Conclusions Risk factors for Achilles tendinopathy were identified based on expert consensus, and these factors provide a basis for primary epidemiological studies. Plantarflexor strength was identified as the primary modifiable factor in the active/athletic group while systemic factors were identified as important in the inactive/sedentary group, many of the potential factors suggested for either group were non-modifiable. Non-modifiable factors include: previous tendinopathy, previous injury, advancing age, sex, steroid exposure, and antibiotic treatment. Level of evidence Level V PMID:27757281

Institutional Dynamics of Education Reforms and Quality of Primary Education in Uganda

ERIC Educational Resources Information Center

Nyenje, Aida; James, Nkata L.

2016-01-01

This article scans Uganda's topical responsibility to transformation of the country's primary school education arrangement with attention to the institutional dynamics that constitute school factors such as the curriculum, assessment methods, course content, subject composition, teaching methods, and instructional materials; among others that…

Four Factors of Clinical Decision Making: A Teaching Model.

ERIC Educational Resources Information Center

Leist, James C.; Konen, Joseph C.

1996-01-01

Four factors of clinical decision making identified by medical students include quality of care, cost, ethics, and legal concerns. This paper argues that physicians have two responsibilities in the clinical decision-making model: to be the primary advocate for quality health care and to ensure balance among the four factors, working in partnership…

Risk factors for inadequate antibody response to primary rabies vaccination in dogs under one year of age

PubMed Central

Wallace, Ryan M.; Pees, Anna; Blanton, Jesse B.

2017-01-01

Ensuring the adequacy of response to rabies vaccination in dogs is important, particularly in the context of pet travel. Few studies have examined the factors associated with dogs’ failure to achieve an adequate antibody titer after vaccination (0.5 IU/ml). This study evaluated rabies antibody titers in dogs after primary vaccination. Dogs under one year of age whose serum was submitted to a reference laboratory for routine diagnostics, and which had no prior documented history of vaccination were enrolled (n = 8,011). Geometric mean titers (GMT) were calculated and univariate analysis was performed to assess factors associated with failure to achieve 0.5 IU/mL. Dogs vaccinated at >16 weeks of age had a significantly higher GMT compared to dogs vaccinated at a younger age (1.64 IU/ml, 1.57–1.72, ANOVA p < 0.01). There was no statistical difference in GMT between dogs vaccinated <12 weeks and dogs vaccinated 12–16 weeks (1.22 IU/ml and 1.21 IU/ml). The majority of dogs failed to reach an adequate titer within the first 3 days of primary vaccination; failure rates were also high if the interval from vaccination to titer check was greater than 90 days. Over 90% of dogs that failed primary vaccination were able to achieve adequate titers after booster vaccination. The ideal timing for blood draw is 8–30 days after primary vaccination. In the event of a failure, most dogs will achieve an adequate serologic response upon a repeat titer (in the absence of booster vaccination). Booster vaccination after failure provided the highest probability of an acceptable titer. PMID:28759602

Risk factors for inadequate antibody response to primary rabies vaccination in dogs under one year of age.

PubMed

Wallace, Ryan M; Pees, Anna; Blanton, Jesse B; Moore, Susan M

2017-07-01

Ensuring the adequacy of response to rabies vaccination in dogs is important, particularly in the context of pet travel. Few studies have examined the factors associated with dogs' failure to achieve an adequate antibody titer after vaccination (0.5 IU/ml). This study evaluated rabies antibody titers in dogs after primary vaccination. Dogs under one year of age whose serum was submitted to a reference laboratory for routine diagnostics, and which had no prior documented history of vaccination were enrolled (n = 8,011). Geometric mean titers (GMT) were calculated and univariate analysis was performed to assess factors associated with failure to achieve 0.5 IU/mL. Dogs vaccinated at >16 weeks of age had a significantly higher GMT compared to dogs vaccinated at a younger age (1.64 IU/ml, 1.57-1.72, ANOVA p < 0.01). There was no statistical difference in GMT between dogs vaccinated <12 weeks and dogs vaccinated 12-16 weeks (1.22 IU/ml and 1.21 IU/ml). The majority of dogs failed to reach an adequate titer within the first 3 days of primary vaccination; failure rates were also high if the interval from vaccination to titer check was greater than 90 days. Over 90% of dogs that failed primary vaccination were able to achieve adequate titers after booster vaccination. The ideal timing for blood draw is 8-30 days after primary vaccination. In the event of a failure, most dogs will achieve an adequate serologic response upon a repeat titer (in the absence of booster vaccination). Booster vaccination after failure provided the highest probability of an acceptable titer.

Pupil size directly modulates the feedforward response in human primary visual cortex independently of attention.

PubMed

Bombeke, Klaas; Duthoo, Wout; Mueller, Sven C; Hopf, Jens-Max; Boehler, C Nico

2016-02-15

Controversy revolves around the question of whether psychological factors like attention and emotion can influence the initial feedforward response in primary visual cortex (V1). Although traditionally, the electrophysiological correlate of this response in humans (the C1 component) has been found to be unaltered by psychological influences, a number of recent studies have described attentional and emotional modulations. Yet, research into psychological effects on the feedforward V1 response has neglected possible direct contributions of concomitant pupil-size modulations, which are known to also occur under various conditions of attentional load and emotional state. Here we tested the hypothesis that such pupil-size differences themselves directly affect the feedforward V1 response. We report data from two complementary experiments, in which we used procedures that modulate pupil size without differences in attentional load or emotion while simultaneously recording pupil-size and EEG data. Our results confirm that pupil size indeed directly influences the feedforward V1 response, showing an inverse relationship between pupil size and early V1 activity. While it is unclear in how far this effect represents a functionally-relevant adaptation, it identifies pupil-size differences as an important modulating factor of the feedforward response of V1 and could hence represent a confounding variable in research investigating the neural influence of psychological factors on early visual processing. Copyright © 2015 Elsevier Inc. All rights reserved.

Dinoflagellate Toxins Responsible for Ciguatera Food Poisoning

DTIC Science & Technology

1991-03-30

primary toxin causing the ciguatera syndrome,f 15, 161 while Banner et al.,l171 argued that ciguatoxili was the principal factor. Nevertheless, later...product of primary conisumers. These authors reported that an analysis of gut contents of Ctenochaetus striatus (a detrital feeder, exclusively) revealed a...the ileum preparation, placed doubt on this interpretation. Later work has indicated that MTX may secondarily affect channels by a primary affect upon

A Typology of Adult Literacy Instructional Approaches

ERIC Educational Resources Information Center

Beder, Hal; Lipnevich, Anastasiya; Robinson-Geller, Perrine

2007-01-01

This study addresses the primary question, "What instructional approaches typify adult literacy education in the United States?" as well as several secondary questions. To address the primary question, a survey was developed and responses were received from 598 adult literacy teachers in 12 states. When the data were subjected to factor analysis,…

The Nature of Institutional Heteronormativity in Primary Schools and Practice-Based Responses

ERIC Educational Resources Information Center

DePalma, Renee; Atkinson, Elizabeth

2010-01-01

Concern for school-based homophobia is increasing, yet there is a tendency to focus on individual incidents of homophobic bullying rather than the cultural and institutional factors supporting them. We analyse ways in which institutional heteronormativity operates in primary schools and report results from our research in UK schools that…

Developing a Scale for Culturally Responsive Practice: Validation, Relationship with School Organizational Factors, and Application

ERIC Educational Resources Information Center

Han, Jae-Bum

2017-01-01

The primary goal of this dissertation is to develop and provide preliminary validation for a new measure of culturally responsive practice. This instrument, which is called the Culturally Responsive Practice Scale (CRPS), includes items that reflect ways that teachers teach multicultural students in their classrooms. To accomplish the goal, three…

The knowledge, attitude and behavior about public health emergencies and the response capacity of primary care medical staffs of Guangdong Province, China.

PubMed

Zhiheng, Zhou; Caixia, Wang; Jiaji, Wang; Huajie, Yang; Chao, Wang; Wannian, Liang

2012-09-25

Primary care medical staffs' knowledge, attitude and behavior about health emergency and the response capacity are directly related to the control and prevention of public health emergencies. Therefore, it is of great significance for improving primary care to gain in-depth knowledge about knowledge, attitude and behavior and the response capacity of primary care medical staffs. The main objective of this study is to explore knowledge, attitude and behavior, and the response capacity of primary care medical staffs of Guangdong Province, China. Stratified clustered sample method was used in the anonymous questionnaire investigation about knowledge, attitude and behavior, and the response capacity of 3410 primary care medical staffs in 15 cities of Guangdong Province, China from July, 2010 to October 2010. The emergency response capacity was evaluated by 33 questions. The highest score of the response capacity was 100 points (full score), score of 70 was a standard. 62.4% primary care medical staffs believed that public health emergencies would happen. Influenza (3.86 ± 0.88), food poisoning (3.35 ± 0.75), and environmental pollution events (3.23 ± 0.80) (the total score was 5) were considered most likely to occur. Among the 7 public health emergency skills, the highest self-assessment score is "public health emergency prevention skills" (2.90 ± 0.68), the lowest is "public health emergency risk management (the total score was 5)" (1.81 ± 0.40). Attitude evaluation showed 66.1% of the medical staffs believed that the community awareness of risk management were ordinary. Evaluation of response capacity of health emergency showed that the score of primary care medical staffs was 67.23 ± 10.61, and the response capacity of senior physicians, public health physicians and physicians with relatively long-term practice were significantly better (P <0.05). Multiple linear stepwise regression analysis showed gender, title, position, type of work, work experience and whether to participate relative training were the main factors affecting the health emergency response capacity. The knowledge, attitude and behavior about public health emergencies and the response capacity of primary care medical staffs of Guangdong Province (China) were poor. Health administrative departments should strengthen the training of health emergency knowledge and skills of the primary care medical staffs to enhance their health emergency response capabilities.

Correlation Factors Describing Primary and Spatial Sensations of Sound Fields

NASA Astrophysics Data System (ADS)

ANDO, Y.

2002-11-01

The theory of subjective preference of the sound field in a concert hall is established based on the model of human auditory-brain system. The model consists of the autocorrelation function (ACF) mechanism and the interaural crosscorrelation function (IACF) mechanism for signals arriving at two ear entrances, and the specialization of human cerebral hemispheres. This theory can be developed to describe primary sensations such as pitch or missing fundamental, loudness, timbre and, in addition, duration sensation which is introduced here as a fourth. These four primary sensations may be formulated by the temporal factors extracted from the ACF associated with the left hemisphere and, spatial sensations such as localization in the horizontal plane, apparent source width and subjective diffuseness are described by the spatial factors extracted from the IACF associated with the right hemisphere. Any important subjective responses of sound fields may be described by both temporal and spatial factors.

Sources of Motivation for Work in Gerontology: The Ethnic Factor among Students of Social Work in Israel.

ERIC Educational Resources Information Center

Litwin, Howard

1994-01-01

Responses from 93 of 100 Arab and Jewish social work students in Israel identified ethnicity as the primary factor in motivation for working with elderly people. Arab students had a significantly higher degree of motivation. A secondary factor was a venerating or modernist attitude toward the aged. (SK)

Primary care physicians’ perspectives on the prescription opioid epidemic*

PubMed Central

Kennedy-Hendricks, Alene; Busch, Susan H.; McGinty, Emma E.; Bachhuber, Marcus A.; Niederdeppe, Jeff; Gollust, Sarah E.; Webster, Daniel W.; Fiellin, David A.; Barry, Colleen L.

2016-01-01

Background Prescription opioid use disorder and overdose have risen substantially in the U.S. Primary care physicians are critical to many ongoing and proposed efforts to address the prescription opioid epidemic. Yet, little is known about their attitudes and beliefs surrounding this issue. This study aimed to determine primary care physicians’ perceptions of the seriousness of the problem, its causes, groups responsible for addressing it, attitudes toward individuals with prescription opioid use disorder, beliefs about the effectiveness of addiction treatments, and support for various policies. Methods We conducted a national web-based survey in 2014 among 1,010 primary care physicians. We gauged responses to attitude and belief items on 7-point Likert scales. We examined the proportion agreeing with each statement, and whether responses differed among physicians prescribing higher and lower volumes of opioids. Results Respondents largely attributed the causes of prescription opioid use disorder to individual-oriented factors and certain physician-oriented factors, and believed that individuals with prescription opioid use disorder and physicians were primarily responsible for addressing the problem. Negative attitudes toward people with prescription opioid use disorder were prevalent, but a majority believed that treatment could be effective. There was majority support for all measured policies, with the highest levels of support for policies to monitor prescribing among patients potentially at risk for an opioid use disorder and to improve physician education and training. Conclusions Given strong endorsement of recommended policies, physician support could be leveraged to advance efforts to curb prescription opioid use disorder and overdose. PMID:27261154

Time-lag effects of global vegetation responses to climate change.

PubMed

Wu, Donghai; Zhao, Xiang; Liang, Shunlin; Zhou, Tao; Huang, Kaicheng; Tang, Bijian; Zhao, Wenqian

2015-09-01

Climate conditions significantly affect vegetation growth in terrestrial ecosystems. Due to the spatial heterogeneity of ecosystems, the vegetation responses to climate vary considerably with the diverse spatial patterns and the time-lag effects, which are the most important mechanism of climate-vegetation interactive effects. Extensive studies focused on large-scale vegetation-climate interactions use the simultaneous meteorological and vegetation indicators to develop models; however, the time-lag effects are less considered, which tends to increase uncertainty. In this study, we aim to quantitatively determine the time-lag effects of global vegetation responses to different climatic factors using the GIMMS3g NDVI time series and the CRU temperature, precipitation, and solar radiation datasets. First, this study analyzed the time-lag effects of global vegetation responses to different climatic factors. Then, a multiple linear regression model and partial correlation model were established to statistically analyze the roles of different climatic factors on vegetation responses, from which the primary climate-driving factors for different vegetation types were determined. The results showed that (i) both the time-lag effects of the vegetation responses and the major climate-driving factors that significantly affect vegetation growth varied significantly at the global scale, which was related to the diverse vegetation and climate characteristics; (ii) regarding the time-lag effects, the climatic factors explained 64% variation of the global vegetation growth, which was 11% relatively higher than the model ignoring the time-lag effects; (iii) for the area with a significant change trend (for the period 1982-2008) in the global GIMMS3g NDVI (P < 0.05), the primary driving factor was temperature; and (iv) at the regional scale, the variation in vegetation growth was also related to human activities and natural disturbances. Considering the time-lag effects is quite important for better predicting and evaluating the vegetation dynamics under the background of global climate change. © 2015 John Wiley & Sons Ltd.

Biotic regulation of CO2 uptake-climate responses: Links to vegetation properties

USDA-ARS?s Scientific Manuscript database

Background/Question/Methods Primary productivity is regulated by climatic factors, but also depends on which plant species are present and, more specifically, on how plant traits that control photosynthesis and its response to the environment are distributed in the community. We used remotely-sense...

Response of Southern Ocean Phytoplankton Communities to Trace Metal (including Iron) and Light Availability

NASA Astrophysics Data System (ADS)

Fietz, S.; Roychoudhury, A. N.; Thomalla, S.; Mtshali, T. N.; Philibert, R.; Van Horsten, N.; Loock, J. C.; Cloete, R.

2016-02-01

Phytoplankton primary productivity depends on macro- and micronutrient availability and in turn plays a key role in the marine biogeochemical cycles. The role of iron in regulating phytoplankton primary production and thus biogeochemical cycles in the Southern Ocean has been widely recognized; however, it also became obvious that iron is not the sole factor limiting primary production in the Southern Ocean and that light, for instance, might aggravate or relief trace nutrient limitation. We conducted a suite of ship-board incubation experiments in austral summer 2013/14, 2014/15 and winter 2015 to shed light on the complex interplay between trace metal and light limitation. We observed a strong difference in acclimation and photophysiological response depending on the environmental conditions of the in-situ communities prior to the experiment. The differences in acclimation and photophysiological responses resulted in different growth and macronutrient uptake rates. Revisited stations did, however, not always show the same responses. At at least one station we will link the incubation experiments to the in-situ vertical profiles of trace metals, macronutrients and primary productivity.

Complementation of a mutant cell line: central role of the 91 kDa polypeptide of ISGF3 in the interferon-alpha and -gamma signal transduction pathways.

PubMed Central

Müller, M; Laxton, C; Briscoe, J; Schindler, C; Improta, T; Darnell, J E; Stark, G R; Kerr, I M

1993-01-01

Mutants in complementation group U3, completely defective in the response of all genes tested to interferons (IFNs) alpha and gamma, do not express the 91 and 84 kDa polypeptide components of interferon-stimulated gene factor 3 (ISGF3), a transcription factor known to play a primary role in the IFN-alpha response pathway. The 91 and 84 kDa polypeptides are products of a single gene. They result from differential splicing and differ only in a 38 amino acid extension at the C-terminus of the 91 kDa polypeptide. Complementation of U3 mutants with cDNA constructs expressing the 91 kDa product at levels comparable to those observed in induced wild-type cells completely restored the response to both IFN-alpha and -gamma and the ability to form ISGF3. Complementation with the 84 kDa component similarly restored the ability to form ISGF3 and, albeit to a lower level, the IFN-alpha response of all genes tested so far. It failed, however, to restore the IFN-gamma response of any gene analysed. The precise nature of the DNA motifs and combination of factors required for the transcriptional response of all genes inducible by IFN-alpha and -gamma remains to be established. The results presented here, however, emphasize the apparent general requirement of the 91 kDa polypeptide in the primary transcriptional response to both types of IFN. Images PMID:7693454

Use of a safety climate questionnaire in UK health care: factor structure, reliability and usability.

PubMed

Hutchinson, A; Cooper, K L; Dean, J E; McIntosh, A; Patterson, M; Stride, C B; Laurence, B E; Smith, C M

2006-10-01

To explore the factor structure, reliability, and potential usefulness of a patient safety climate questionnaire in UK health care. Four acute hospital trusts and nine primary care trusts in England. The questionnaire used was the 27 item Teamwork and Safety Climate Survey. Thirty three healthcare staff commented on the wording and relevance. The questionnaire was then sent to 3650 staff within the 13 NHS trusts, seeking to achieve at least 600 responses as the basis for the factor analysis. 1307 questionnaires were returned (36% response). Factor analyses and reliability analyses were carried out on 897 responses from staff involved in direct patient care, to explore how consistently the questions measured the underlying constructs of safety climate and teamwork. Some questionnaire items related to multiple factors or did not relate strongly to any factor. Five items were discarded. Two teamwork factors were derived from the remaining 11 teamwork items and three safety climate factors were derived from the remaining 11 safety items. Internal consistency reliabilities were satisfactory to good (Cronbach's alpha > or =0.69 for all five factors). This is one of the few studies to undertake a detailed evaluation of a patient safety climate questionnaire in UK health care and possibly the first to do so in primary as well as secondary care. The results indicate that a 22 item version of this safety climate questionnaire is useable as a research instrument in both settings, but also demonstrates a more general need for thorough validation of safety climate questionnaires before widespread usage.

Economic expenditures associated with instrumental caregiving roles of adult siblings of persons with severe mental illness.

PubMed

Lohrer, Steven P; Lukens, Ellen P; Thorning, Helle

2007-04-01

Siblings of persons with mental illness who assume primary caregiving roles experience substantial and tangible economic impacts associated with this responsibility. This study investigated mailed survey responses collected from 156 adult siblings of persons with mental illness from New York State to examine instrumental costs associated with providing support to siblings with illness. Genders of both siblings, severity of the relatives' mental illness, and number of surviving parents in the family distinguished those occupying primary caregiving responsibility from those not in primary roles. Current caregivers incurred greater instrumental costs in the form of financial expenses, time spent in care activities, and crisis involvement than did those who were not primary care providers. Additional demographic and behavioral factors related to siblings with and without illness were associated with specific dimensions of instrumental expenditure. As siblings become increasingly engaged in caregiving, social service professionals must assume leadership in promoting programs and policies that meaningfully support family involvement for relatives with mental illness.

Scrutinizing screening: a critical interpretive review of primary care provider perspectives on mammography decision-making with average-risk women.

PubMed

Siedlikowski, Sophia; Ells, Carolyn; Bartlett, Gillian

2018-01-01

A decision to undertake screening for breast cancer often takes place within the primary care setting, but current controversies such as overdiagnosis and inconsistent screening recommendations based on evolving evidence render this a challenging process, particularly for average-risk women. Given the responsibility of primary care providers in counseling women in this decision-making process, it is important to understand their thoughts on these controversies and how they manage uncertainty in their practice. To review the perspectives and approaches of primary care providers regarding mammography decision-making with average-risk women. This study is a critical interpretive review of peer-review literature that reports primary care provider perspectives on mammography screening decision-making. Ovid MEDLINE®, Ovid PsycInfo, and Scopus databases were searched with dates from 2002 to 2017 using search terms related to mammography screening, uncertainty, counseling, decision-making, and primary health care providers. Nine articles were included following a review process involving the three authors. Using an inductive and iterative approach, data were grouped into four thematic categories: (1) perceptions on the effectiveness of screening, screening initiation age, and screening frequency; (2) factors guiding primary care providers in the screening decision-making process, including both provider and patient-related factors, (3) uncertainty faced by primary care providers regarding guidelines and screening discussions with their patients; and (4) informed decision-making with average-risk women, including factors that facilitate and hinder this process. The discussion of results addresses several factors about the diversity of perspectives and practices of physicians counseling average-risk women regarding breast cancer screening. This has implications for the challenge of understanding and explaining evidence, what should be shared with average-risk women considering screening, the forms of knowledge that physicians value to guide screening decision-making, and the consent process for population-based screening initiatives. Within the data, there was little attention placed on how physicians coped with uncertainty in practice. Given the dual responsibility of physicians in caring for both individuals and the larger population, further research should probe more deeply into how they balance their duties to individual patients with those to the larger population they serve.

Characteristics of dislocation structure in creep deformed lamellar tial alloy within primary regime

NASA Astrophysics Data System (ADS)

Cho, H. S.; Nam, Soo W.

1999-06-01

In this investigation, dislocations of a lamellar TiAl alloy are analyzed after creeping in the primary range at 800°C/200MPa in order to interpret their mobility It was found that the dislocation density in γ-laths decreased as the creep deformation proceeds within primary creep regime Schmid factor analysis suggests that the creep deformation in the early stage of the primary creep regime is controlled by the gliding of some of the initial dislocations which have a high enough Schmid factor As the creep deformation progressed, those dislocations with high Schmid factors slip preferentially to be annihilated at the α-γ interface For further continuous deformation, dislocation generation is required, and for this, α-phase is transformed to γ-phase in order to generate new dislocations A slow dislocation generation process by phase transformation of α-phase compared with the absorbing rate to sinks is responsible for the decreasing dislocation density as the creep strain increases

Human adipocytes are highly sensitive to intermittent hypoxia induced NF-kappaB activity and subsequent inflammatory gene expression

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

Taylor, Cormac T.; Kent, Brian D.; Crinion, Sophie J.

Highlights: • Intermittent hypoxia (IH) leads to NF-κB activation in human primary adipocytes. • Adipocytes bear higher pro-inflammatory potential than other human primary cells. • IH leads to upregulation of multiple pro-inflammatory genes in human adipocytes. - Abstract: Introduction: Intermittent hypoxia (IH)-induced activation of pro-inflammatory pathways is a major contributing factor to the cardiovascular pathophysiology associated with obstructive sleep apnea (OSA). Obesity is commonly associated with OSA although it remains unknown whether adipose tissue is a major source of inflammatory mediators in response to IH. The aim of this study was to test the hypothesis that IH leads to augmentedmore » inflammatory responses in human adipocytes when compared to cells of non-adipocyte lineages. Methods and results: Human primary subcutaneous and visceral adipocytes, human primary microvascular pulmonary endothelial cells (HUMEC-L) and human primary small airway epithelial cells (SAEC) were exposed to 0, 6 or 12 cycles of IH or stimulated with tumor necrosis factor (TNF)-α. IH led to a robust increase in NF-κB DNA-binding activity in adipocytes compared with normoxic controls regardless of whether the source of adipocytes was visceral or subcutaneous. Notably, the NF-κB response of adipocytes to both IH and TNF-α was significantly greater than that in HUMEC-L and SAEC. Western blotting confirmed enhanced nuclear translocation of p65 in adipocytes in response to IH, accompanied by phosphorylation of I-κB. Parallel to p65 activation, we observed a significant increase in secretion of the adipokines interleukin (IL)-8, IL-6 and TNF-α with IH in adipocytes accompanied by significant upregulation of mRNA expression. PCR-array suggested profound influence of IH on pro-inflammatory gene expression in adipocytes. Conclusion: Human adipocytes demonstrate strong sensitivity to inflammatory gene expression in response to acute IH and hence, adipose tissue may be a key source of inflammatory mediators in OSA.« less

Participatory Action Research in Two Primary Schools in a Rural Tanzanian Village: An Exploration of Factors to Cultivate Changes in Teaching and Learning

ERIC Educational Resources Information Center

Roberts, Daniel M.; Brown, Alisha M. B.; Edwards, Laura

2015-01-01

Access to primary and secondary education in Tanzania has drastically expanded in the past two decades. In response to this success, its ministry is now targeting improvements in educational quality through additional reform. Yet teacher absenteeism, physical abuse, overcrowding, lecture-based pedagogy and a system of accountability based…

The knowledge, attitude and behavior about public health emergencies and the response capacity of primary care medical staffs of Guangdong Province, China

PubMed Central

2012-01-01

Background Primary care medical staffs’ knowledge, attitude and behavior about health emergency and the response capacity are directly related to the control and prevention of public health emergencies. Therefore, it is of great significance for improving primary care to gain in-depth knowledge about knowledge, attitude and behavior and the response capacity of primary care medical staffs. The main objective of this study is to explore knowledge, attitude and behavior, and the response capacity of primary care medical staffs of Guangdong Province, China. Methods Stratified clustered sample method was used in the anonymous questionnaire investigation about knowledge, attitude and behavior, and the response capacity of 3410 primary care medical staffs in 15 cities of Guangdong Province, China from July, 2010 to October 2010. The emergency response capacity was evaluated by 33 questions. The highest score of the response capacity was 100 points (full score), score of 70 was a standard. Results 62.4% primary care medical staffs believed that public health emergencies would happen. Influenza (3.86 ± 0.88), food poisoning (3.35 ± 0.75), and environmental pollution events (3.23 ± 0.80) (the total score was 5) were considered most likely to occur. Among the 7 public health emergency skills, the highest self-assessment score is “public health emergency prevention skills” (2.90 ± 0.68), the lowest is “public health emergency risk management (the total score was 5)” (1.81 ± 0.40). Attitude evaluation showed 66.1% of the medical staffs believed that the community awareness of risk management were ordinary. Evaluation of response capacity of health emergency showed that the score of primary care medical staffs was 67.23 ± 10.61, and the response capacity of senior physicians, public health physicians and physicians with relatively long-term practice were significantly better (P <0.05). Multiple linear stepwise regression analysis showed gender, title, position, type of work, work experience and whether to participate relative training were the main factors affecting the health emergency response capacity. Conclusions The knowledge, attitude and behavior about public health emergencies and the response capacity of primary care medical staffs of Guangdong Province (China) were poor. Health administrative departments should strengthen the training of health emergency knowledge and skills of the primary care medical staffs to enhance their health emergency response capabilities. PMID:23009075

Source-specific pollution exposure and associations with pulmonary response in the Atlanta Commuters Exposure Studies.

PubMed

Krall, Jenna R; Ladva, Chandresh N; Russell, Armistead G; Golan, Rachel; Peng, Xing; Shi, Guoliang; Greenwald, Roby; Raysoni, Amit U; Waller, Lance A; Sarnat, Jeremy A

2018-06-01

Concentrations of traffic-related air pollutants are frequently higher within commuting vehicles than in ambient air. Pollutants found within vehicles may include those generated by tailpipe exhaust, brake wear, and road dust sources, as well as pollutants from in-cabin sources. Source-specific pollution, compared to total pollution, may represent regulation targets that can better protect human health. We estimated source-specific pollution exposures and corresponding pulmonary response in a panel study of commuters. We used constrained positive matrix factorization to estimate source-specific pollution factors and, subsequently, mixed effects models to estimate associations between source-specific pollution and pulmonary response. We identified four pollution factors that we named: crustal, primary tailpipe traffic, non-tailpipe traffic, and secondary. Among asthmatic subjects (N = 48), interquartile range increases in crustal and secondary pollution were associated with changes in lung function of -1.33% (95% confidence interval (CI): -2.45, -0.22) and -2.19% (95% CI: -3.46, -0.92) relative to baseline, respectively. Among non-asthmatic subjects (N = 51), non-tailpipe pollution was associated with pulmonary response only at 2.5 h post-commute. We found no significant associations between pulmonary response and primary tailpipe pollution. Health effects associated with traffic-related pollution may vary by source, and therefore some traffic pollution sources may require targeted interventions to protect health.

Purification and growth of melanocortin 1 receptor (Mc1r)-defective primary murine melanocytes is dependent on stem cell factor from keratinocyte-conditioned media

PubMed Central

Scott, Timothy L.; Wakamatsu, Kazumasa; Ito, Shosuke; D’Orazio, John A.

2015-01-01

Summary The melanocortin 1 receptor (MC1R) is a transmembrane Gs-coupled surface protein found on melanocytes that binds melanocyte stimulating hormone (MSH) and mediates activation of adenylyl cyclase and generation of the second messenger cAMP. MC1R regulates growth and differentiation of melanocytes and protects against carcinogenesis. Persons with loss-of-function polymorphisms of MC1R tend to be UV-sensitive (fair-skinned and with a poor tanning response) and are at high risk for melanoma. Mechanistic studies of the role of MC1R in melanocytic UV responses, however, have been hindered in part because Mc1r-defective primary murine melanocytes have been difficult to culture in vitro. Until now, effective growth of murine melanocytes has depended on cAMP stimulation with adenylyl cyclase activating or phosphodiesterase inhibiting agents. However, rescuing cAMP in the setting of defective MC1R signaling would be expected to confound experiments directly testing MC1R function on melanocytic UV responses. Here we report a novel method of culturing primary murine melanocytes in the absence of pharmacologic cAMP stimulation by incorporating conditioned supernatants containing stem cell factor (SCF) derived from primary keratinocytes. Importantly, this method seems to permit similar pigment expression by cultured melanocytes as that found in the skin of their parental murine strains. This novel approach will allow mechanistic investigation into MC1R’s role in protection against UV-mediated carcinogenesis and determination of the role of melanin pigment subtypes on UV-mediated melanocyte responses. PMID:19633898

Screening for increased cardiometabolic risk in primary care: a systematic review

PubMed Central

den Engelsen, Corine; Koekkoek, Paula S; Godefrooij, Merijn B; Spigt, Mark G; Rutten, Guy E

2014-01-01

Background Many programmes to detect and prevent cardiovascular disease (CVD) have been performed, but the optimal strategy is not yet clear. Aim To present a systematic review of cardiometabolic screening programmes performed among apparently healthy people (not yet known to have CVD, diabetes, or cardiometabolic risk factors) and mixed populations (apparently healthy people and people diagnosed with risk factor or disease) to define the optimal screening strategy. Design and setting Systematic review of studies performed in primary care in Western countries. Method MEDLINE, Embase, and CINAHL databases were searched for studies screening for increased cardiometabolic risk. Exclusion criteria were studies designed to assess prevalence of risk factors without follow-up or treatment; without involving a GP; when fewer than two risk factors were considered as the primary outcome; and studies constrained to ethnic minorities. Results The search strategy yielded 11 445 hits; 26 met the inclusion criteria. Five studies (1995–2012) were conducted in apparently healthy populations: three used a stepwise method. Response rates varied from 24% to 79%. Twenty-one studies (1967–2012) were performed in mixed populations; one used a stepwise method. Response rates varied from 50% to 75%. Prevalence rates could not be compared because of heterogeneity of used thresholds and eligible populations. Observed time trends were a shift from mixed to apparently healthy populations, increasing use of risk scores, and increasing use of stepwise screening methods. Conclusion The optimal screening strategy in primary care is likely stepwise, in apparently healthy people, with the use of risk scores. Increasing public awareness and actively involving GPs might facilitate screening efficiency and uptake. PMID:25267047

Cadmium, cobalt and lead cause stress response, cell cycle deregulation and increased steroid as well as xenobiotic metabolism in primary normal human bronchial epithelial cells which is coordinated by at least nine transcription factors.

PubMed

Glahn, Felix; Schmidt-Heck, Wolfgang; Zellmer, Sebastian; Guthke, Reinhard; Wiese, Jan; Golka, Klaus; Hergenröder, Roland; Degen, Gisela H; Lehmann, Thomas; Hermes, Matthias; Schormann, Wiebke; Brulport, Marc; Bauer, Alexander; Bedawy, Essam; Gebhardt, Rolf; Hengstler, Jan G; Foth, Heidi

2008-08-01

Workers occupationally exposed to cadmium, cobalt and lead have been reported to have increased levels of DNA damage. To analyze whether in vivo relevant concentrations of heavy metals cause systematic alterations in RNA expression patterns, we performed a gene array study using primary normal human bronchial epithelial cells. Cells were incubated with 15 microg/l Cd(II), 25 microg/l Co(II) and 550 microg/l Pb(II) either with individual substances or in combination. Differentially expressed genes were filtered out and used to identify enriched GO categories as well as KEGG pathways and to identify transcription factors whose binding sites are enriched in a given set of promoters. Interestingly, combined exposure to Cd(II), Co(II) and Pb(II) caused a coordinated response of at least seven stress response-related transcription factors, namely Oct-1, HIC1, TGIF, CREB, ATF4, SRF and YY1. A stress response was further corroborated by up regulation of genes involved in glutathione metabolism. A second major response to heavy metal exposure was deregulation of the cell cycle as evidenced by down regulation of the transcription factors ELK-1 and the Ets transcription factor GABP, as well as deregulation of genes involved in purine and pyrimidine metabolism. A third and surprising response was up regulation of genes involved in steroid metabolism, whereby promoter analysis identified up regulation of SRY that is known to play a role in sex determination. A forth response was up regulation of xenobiotic metabolising enzymes, particularly of dihydrodiol dehydrogenases 1 and 2 (AKR1C1, AKR1C2). Incubations with individual heavy metals showed that the response of AKR1C1 and AKR1C2 was predominantly caused by lead. In conclusion, we have shown that in vivo relevant concentrations of Cd(II), Co(II) and Pb(II) cause a complex and coordinated response in normal human bronchial epithelial cells. This study gives an overview of the most responsive genes.

Efficacy and Biomarker Study of Bevacizumab for Hearing Loss Resulting From Neurofibromatosis Type 2–Associated Vestibular Schwannomas

PubMed Central

Ye, Xiaobu; Duda, Dan G.; Halpin, Chris F.; Bergner, Amanda L.; Muzikansky, Alona; Merker, Vanessa L.; Gerstner, Elizabeth R.; Fayad, Laura M.; Ahlawat, Shivani; Jacobs, Michael A.; Jain, Rakesh K.; Zalewski, Christopher; Dombi, Eva; Widemann, Brigitte C.; Plotkin, Scott R.

2016-01-01

Purpose Neurofibromatosis type 2 (NF2) is a tumor predisposition syndrome characterized by bilateral vestibular schwannomas (VSs) resulting in deafness and brainstem compression. This study evaluated efficacy and biomarkers of bevacizumab activity for NF2-associated progressive and symptomatic VSs. Patients and Methods Bevacizumab 7.5 mg/kg was administered every 3 weeks for 46 weeks, followed by 24 weeks of surveillance after treatment with the drug. The primary end point was hearing response defined by word recognition score (WRS). Secondary end points included toxicity, tolerability, imaging response using volumetric magnetic resonance imaging analysis, durability of response, and imaging and blood biomarkers. Results Fourteen patients (estimated to yield > 90% power to detect an alternative response rate of 50% at alpha level of 0.05) with NF2, with a median age of 30 years (range, 14 to 79 years) and progressive hearing loss in the target ear (median baseline WRS, 60%; range 13% to 82%), were enrolled. The primary end point, confirmed hearing response (improvement maintained ≥ 3 months), occurred in five (36%) of 14 patients (95% CI, 13% to 65%; P < .001). Eight (57%) of 14 patients had transient hearing improvement above the 95% CI for WRS. No patients experienced hearing decline. Radiographic response was seen in six (43%) of 14 target VSs. Three grade 3 adverse events, hypertension (n = 2) and immune-mediated thrombocytopenic purpura (n = 1), were possibly related to bevacizumab. Bevacizumab treatment was associated with decreased free vascular endothelial growth factor (not bound to bevacizumab) and increased placental growth factor in plasma. Hearing responses were inversely associated with baseline plasma hepatocyte growth factor (P = .019). Imaging responses were associated with high baseline tumor vessel permeability and elevated blood levels of vascular endothelial growth factor D and stromal cell–derived factor 1α (P = .037 and .025, respectively). Conclusion Bevacizumab treatment resulted in durable hearing response in 36% of patients with NF2 and confirmed progressive VS-associated hearing loss. Imaging and plasma biomarkers showed promising associations with response that should be validated in larger studies. PMID:26976425

Bacteria-Triggered Systemic Immunity in Barley Is Associated with WRKY and ETHYLENE RESPONSIVE FACTORs But Not with Salicylic Acid1[C][W

PubMed Central

Dey, Sanjukta; Wenig, Marion; Langen, Gregor; Sharma, Sapna; Kugler, Karl G.; Knappe, Claudia; Hause, Bettina; Bichlmeier, Marlies; Babaeizad, Valiollah; Imani, Jafargholi; Janzik, Ingar; Stempfl, Thomas; Hückelhoven, Ralph; Kogel, Karl-Heinz; Mayer, Klaus F.X.

2014-01-01

Leaf-to-leaf systemic immune signaling known as systemic acquired resistance is poorly understood in monocotyledonous plants. Here, we characterize systemic immunity in barley (Hordeum vulgare) triggered after primary leaf infection with either Pseudomonas syringae pathovar japonica (Psj) or Xanthomonas translucens pathovar cerealis (Xtc). Both pathogens induced resistance in systemic, uninfected leaves against a subsequent challenge infection with Xtc. In contrast to systemic acquired resistance in Arabidopsis (Arabidopsis thaliana), systemic immunity in barley was not associated with NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 or the local or systemic accumulation of salicylic acid. Instead, we documented a moderate local but not systemic induction of abscisic acid after infection of leaves with Psj. In contrast to salicylic acid or its functional analog benzothiadiazole, local applications of the jasmonic acid methyl ester or abscisic acid triggered systemic immunity to Xtc. RNA sequencing analysis of local and systemic transcript accumulation revealed unique gene expression changes in response to both Psj and Xtc and a clear separation of local from systemic responses. The systemic response appeared relatively modest, and quantitative reverse transcription-polymerase chain reaction associated systemic immunity with the local and systemic induction of two WRKY and two ETHYLENE RESPONSIVE FACTOR (ERF)-like transcription factors. Systemic immunity against Xtc was further associated with transcriptional changes after a secondary/systemic Xtc challenge infection; these changes were dependent on the primary treatment. Taken together, bacteria-induced systemic immunity in barley may be mediated in part by WRKY and ERF-like transcription factors, possibly facilitating transcriptional reprogramming to potentiate immunity. PMID:25332505

Depression screening and management among adolescents in primary care: factors associated with best practice.

PubMed

Taliaferro, Lindsay A; Hetler, Joel; Edwall, Glenace; Wright, Catherine; Edwards, Anne R; Borowsky, Iris W

2013-06-01

To compare depression identification and management perceptions and practices between professions and disciplines in primary care and examine factors that increase the likelihood of administering a standardized depression screening instrument, asking about patients' depressive symptoms, and using best practice when managing depressed adolescents. Data came from an online survey of clinicians in Minnesota (20% response rate). Analyses involved bivariate tests and linear regressions. The analytic sample comprised 260 family medicine physicians, 127 pediatricians, 96 family nurse practitioners, and 54 pediatric nurse practitioners. Overall, few differences emerged between physicians and nurse practitioners or family and pediatric clinicians regarding addressing depression among adolescents. Two factors associated with administering a standardized instrument included having clear protocols for follow-up after depression screening and feeling better prepared to address depression among adolescents. Enhancing clinicians' competence to address depression and developing postscreening protocols could help providers implement universal screening in primary care.

Rheumatoid Arthritis Risk Allele PTPRC Is Also Associated With Response to Anti–Tumor Necrosis Factor α Therapy

PubMed Central

Cui, Jing; Saevarsdottir, Saedis; Thomson, Brian; Padyukov, Leonid; van der Helm-van Mil, Annette H. M.; Nititham, Joanne; Hughes, Laura B.; de Vries, Niek; Raychaudhuri, Soumya; Alfredsson, Lars; Askling, Johan; Wedrén, Sara; Ding, Bo; Guiducci, Candace; Wolbink, Gert Jan; Crusius, J. Bart A.; van der Horst-Bruinsma, Irene E.; Herenius, Marieke; Weinblatt, Michael E.; Shadick, Nancy A.; Worthington, Jane; Batliwalla, Franak; Kern, Marlena; Morgan, Ann W.; Wilson, Anthony G.; Isaacs, John D.; Hyrich, Kimme; Seldin, Michael F.; Moreland, Larry W.; Behrens, Timothy W.; Allaart, Cornelia F.; Criswell, Lindsey A.; Huizinga, Tom W. J.; Tak, Paul P.; Bridges, S. Louis; Toes, Rene E. M.; Barton, Anne; Klareskog, Lars; Gregersen, Peter K.; Karlson, Elizabeth W.; Plenge, Robert M.

2013-01-01

Objective Anti–tumor necrosis factor α (anti-TNF) therapy is a mainstay of treatment in rheumatoid arthritis (RA). The aim of the present study was to test established RA genetic risk factors to determine whether the same alleles also influence the response to anti-TNF therapy. Methods A total of 1,283 RA patients receiving etanercept, infliximab, or adalimumab therapy were studied from among an international collaborative consortium of 9 different RA cohorts. The primary end point compared RA patients with a good treatment response according to the European League Against Rheumatism (EULAR) response criteria (n = 505) with RA patients considered to be nonresponders (n = 316). The secondary end point was the change from baseline in the level of disease activity according to the Disease Activity Score in 28 joints (ΔDAS28). Clinical factors such as age, sex, and concomitant medications were tested as possible correlates of treatment response. Thirty-one single-nucleotide polymorphisms (SNPs) associated with the risk of RA were genotyped and tested for any association with treatment response, using univariate and multivariate logistic regression models. Results Of the 31 RA-associated risk alleles, a SNP at the PTPRC (also known as CD45) gene locus (rs10919563) was associated with the primary end point, a EULAR good response versus no response (odds ratio [OR] 0.55, P = 0.0001 in the multivariate model). Similar results were obtained using the secondary end point, the ΔDAS28 (P = 0.0002). There was suggestive evidence of a stronger association in autoantibody-positive patients with RA (OR 0.55, 95% confidence interval [95% CI] 0.39–0.76) as compared with autoantibody-negative patients (OR 0.90, 95% CI 0.41–1.99). Conclusion Statistically significant associations were observed between the response to anti-TNF therapy and an RA risk allele at the PTPRC gene locus. Additional studies will be required to replicate this finding in additional patient collections. PMID:20309874

Systematic review: predicting and optimising response to anti-TNF therapy in Crohn's disease - algorithm for practical management.

PubMed

Ding, N S; Hart, A; De Cruz, P

2016-01-01

Nonresponse and loss of response to anti-TNF therapies in Crohn's disease represent significant clinical problems for which clear management guidelines are lacking. To review the incidence, mechanisms and predictors of primary nonresponse and secondary loss of response to formulate practical clinical algorithms to guide management. Through a systematic literature review, 503 articles were identified which fit the inclusion criteria. Primary nonresponse to anti-TNF treatment affects 13-40% of patients. Secondary loss of response to anti-TNF occurs in 23-46% of patients when determined according to dose intensification, and 5-13% of patients when gauged by drug discontinuation rates. Recent evidence suggests that the mechanisms underlying primary nonresponse and secondary loss of response are multifactorial and include disease characteristics (phenotype, location, severity); drug (pharmacokinetic, pharmacodynamic or immunogenicity) and treatment strategy (dosing regimen) related factors. Clinical algorithms that employ therapeutic drug monitoring (using anti-TNF tough levels and anti-drug antibody levels) may be used to determine the underlying cause of primary nonresponse and secondary loss of response respectively and guide clinicians as to which patients are most likely to respond to anti-TNF therapy and help optimise drug therapy for those who are losing response to anti-TNF therapy. Nonresponse or loss of response to anti-TNF occurs commonly in Crohn's disease. Clinical algorithms utilising therapeutic drug monitoring may establish the mechanisms for treatment failure and help guide the subsequent therapeutic approach. © 2015 John Wiley & Sons Ltd.

Preoperative predictors of returning to work following primary total knee arthroplasty.

PubMed

Styron, Joseph F; Barsoum, Wael K; Smyth, Kathleen A; Singer, Mendel E

2011-01-05

There is little in the literature to guide clinicians in advising patients regarding their return to work following a primary total knee arthroplasty. In this study, we aimed to identify which factors are important in estimating a patient's time to return to work following primary total knee arthroplasty, how long patients can anticipate being off from work, and the types of jobs to which patients are able to return following primary total knee arthroplasty. A prospective cohort study was performed in which patients scheduled for a primary total knee arthroplasty completed a validated questionnaire preoperatively and at four to six weeks, three months, and six months postoperatively. The questionnaire assessed the patient's occupational physical demands, ability to perform job responsibilities, physical status, and motivation to return to work as well as factors that may impact his or her recovery and other workplace characteristics. Two survival analysis models were constructed to evaluate the time to return to work either at least part-time or full-time. Acceleration factors were calculated to indicate the relative percentage of time until the patient returned to work. The median time to return to work was 8.9 weeks. Patients who reported a sense of urgency about returning to work were found to return in half the time taken by other employees (acceleration factor = 0.468; p < 0.001). Other preoperative factors associated with a faster return to work included being female (acceleration factor = 0.783), self-employment (acceleration factor = 0.792), higher mental health scores (acceleration factor = 0.891), higher physical function scores (acceleration factor = 0.809), higher Functional Comorbidity Index scores (acceleration factor = 0.914), and a handicap accessible workplace (acceleration factor = 0.736). A slower return to work was associated with having less pain preoperatively (acceleration factor = 1.132), having a more physically demanding job (acceleration factor = 1.116), and receiving Workers' Compensation (acceleration factor = 4.360). Although the physical demands of a patient's job have a moderate influence on the patient's ability to return to work following a primary total knee arthroplasty, the patient's characteristics, particularly motivation, play a more important role.

Educators' Challenge: Healthy Mothers, Healthy Babies. A Framework for Curriculum Development in Responsible Childbearing, Pre-school through High School.

ERIC Educational Resources Information Center

Zeyen, Dorothy Dolph

A framework of concepts in nutrition, environmental factors, genetics, and human growth and development is presented as a background for developing elementary and secondary curricula on responsible childbearing. Aspects of the four subject areas are outlined for instruction at five education levels: preschool through kindergarten, primary, upper…

Understanding Classroom Feedback Practices: A Study of New Zealand Student Experiences, Perceptions, and Emotional Responses

ERIC Educational Resources Information Center

Harris, Lois R.; Brown, Gavin T.; Harnett, Jennifer A.

2014-01-01

While feedback is a key factor for improving student learning, little is known about how students understand and experience feedback within the classroom. This study analysed 193 New Zealand primary and secondary students' survey responses alongside drawings of their understandings and experiences of feedback to examine how they experience,…

HEALTHY study rationale, design and methods: Moderating risk of type 2 diabetes in multi-ethnic middle school students

USDA-ARS?s Scientific Manuscript database

The HEALTHY primary prevention trial was designed and implemented in response to the growing numbers of children and adolescents being diagnosed with type 2 diabetes. The objective was to moderate risk factors for type 2 diabetes. Modifiable risk factors measured were indicators of adiposity and gly...

Posttraumatic Stress Disorder's Frequency and Intensity Ratings Are Associated with Factor Structure Differences in Military Veterans

ERIC Educational Resources Information Center

Elhai, Jon D.; Palmieri, Patrick A.; Biehn, Tracey L.; Frueh, B. Christopher; Magruder, Kathryn M.

2010-01-01

We examined possible differences in the factor structure of posttraumatic stress disorder (PTSD) on the basis of whether frequency or intensity symptom response formats were used to assess PTSD. Participants included 669 veterans recruited from an epidemiological study of four Veterans Affairs Medical Centers' primary care clinics in the…

Delayed antibiotic prescription for upper respiratory tract infections in children under primary care: Physicians' views.

PubMed

Raft, Camilla Flintholm; Bjerrum, Lars; Arpi, Magnus; Jarløv, Jens Otto; Jensen, Jette Nygaard

2017-12-01

Overprescribing antibiotics for common or inaccurately diagnosed childhood infections is a frequent problem in primary healthcare in most countries. Delayed antibiotic prescriptions have been shown to reduce the use of antibiotics in primary healthcare. The aim was to examine primary care physicians' views on delayed antibiotic prescriptions to preschool children with symptoms of upper respiratory tract infections (URTIs). A questionnaire was sent to 1180 physicians working in general practice in the Capital Region of Denmark, between January and March 2015. The questions focused on physicians' attitude and use of delayed antibiotic prescriptions to children with URTIs. The response rate was 49% (n = 574). Seven per cent of the physicians often used delayed prescriptions to children with symptoms of URTI, but 46% believed that delayed prescription could reduce antibiotic use. The physicians' views on delayed antibiotic prescription were significantly associated with their number of years working in general practice. Parents' willingness to wait-and-see, need for reassurance, and knowledge about antibiotics influenced the physicians' views. Also, clinical symptoms and signs, parents' willingness to shoulder the responsibility, the capability of observation without antibiotic treatment, and structural factors like out-of-hour services were relevant factors in the decision. Most physicians, especially those with fewer years of practice, had a positive attitude towards delayed antibiotic prescription. Several factors influence the views of the physicians-from perceptions of parents to larger structural elements and years of experience.

Do primary care professionals agree about progress with implementation of primary care teams: results from a cross sectional study.

PubMed

Tierney, E; O'Sullivan, M; Hickey, L; Hannigan, A; May, C; Cullen, W; Kennedy, N; Kineen, L; MacFarlane, A

2016-11-22

Primary care is the cornerstone of healthcare reform with policies across jurisdictions promoting interdisciplinary team working. The effective implementation of such health policies requires understanding the perspectives of all actors. However, there is a lack of research about health professionals' views of this process. This study compares Primary Healthcare Professionals' perceptions of the effectiveness of the Primary Care Strategy and Primary Care Team (PCT) implementation in Ireland. Design and Setting: e-survey of (1) General Practitioners (GPs) associated with a Graduate Medical School (N = 100) and (2) Primary Care Professionals in 3 of 4 Health Service Executive (HSE) regions (N = 2309). After piloting, snowball sampling was used to administer the survey. Descriptive analysis was carried out using SPSS. Ratings across groups were compared using non-parametric tests. There were 569 responses. Response rates varied across disciplines (71 % for GPs, 22 % for other Primary Healthcare Professionals (PCPs). Respondents across all disciplines viewed interdisciplinary working as important. Respondents agreed on lack of progress of implementation of formal PCTs (median rating of 2, where 1 is no progress at all and 5 is complete implementation). GPs were more negative about the effectiveness of the Strategy to promote different disciplines to work together (median rating of 2 compared to 3 for clinical therapists and 3.5 for nurses, P = 0.001). Respondents identified resources and GP participation as most important for effective team working. Protected time for meetings and capacity to manage workload for meetings were rated as very important factors for effective team working by GPs, clinical therapists and nurses. A building for co-location of teams was rated as an important factor by nurses and clinical therapists though GPs rated it as less important. Payment to attend meetings and contractual arrangements were considered important factors by GPs but not by nurses or clinical therapists. PCPs and GPs agree there is limited PCT implementation. GPs are most negative about this implementation. There is some disagreement about which resources are most important for effective PCT working. These findings provide valuable data for clinicians and policy makers about implementation of interdisciplinary teams in primary care.

Family physicians' perspectives on interprofessional teamwork: Findings from a qualitative study.

PubMed

Szafran, Olga; Torti, Jacqueline M I; Kennett, Sandra L; Bell, Neil R

2018-03-01

The aim of this study was to describe family physicians' perspectives of their role in the primary care team and factors that facilitate and hinder teamwork. A qualitative study was conducted employing individual interviews with 19 academic/community-based family physicians who were part of interprofessional primary care teams in Edmonton, Alberta, Canada. Professional responsibilities and roles of physicians within the team and the facilitators and barriers to teamwork were investigated. Interviews were audiotaped, transcribed and analysed for emerging themes. The study findings revealed that family physicians consistently perceived themselves as having the leadership role on in the primary care team. Facilitators of teamwork included: communication; trust and respect; defined roles/responsibilities of team members; co-location; task shifting to other health professionals; and appropriate payment mechanisms. Barriers to teamwork included: undefined roles/responsibilities; lack of space; frequent staff turnover; network boundaries; and a culture of power and control. The findings suggest that moving family physicians toward more integrative and interdependent functioning within the primary care team will require overcoming the culture of traditional professional roles, addressing facilitators and barriers to teamwork, and providing training in teamwork.

Short-term to seasonal variability in factors driving primary productivity in a shallow estuary: Implications for modeling production

NASA Astrophysics Data System (ADS)

Canion, Andy; MacIntyre, Hugh L.; Phipps, Scott

2013-10-01

The inputs of primary productivity models may be highly variable on short timescales (hourly to daily) in turbid estuaries, but modeling of productivity in these environments is often implemented with data collected over longer timescales. Daily, seasonal, and spatial variability in primary productivity model parameters: chlorophyll a concentration (Chla), the downwelling light attenuation coefficient (kd), and photosynthesis-irradiance response parameters (Pmchl, αChl) were characterized in Weeks Bay, a nitrogen-impacted shallow estuary in the northern Gulf of Mexico. Variability in primary productivity model parameters in response to environmental forcing, nutrients, and microalgal taxonomic marker pigments were analysed in monthly and short-term datasets. Microalgal biomass (as Chla) was strongly related to total phosphorus concentration on seasonal scales. Hourly data support wind-driven resuspension as a major source of short-term variability in Chla and light attenuation (kd). The empirical relationship between areal primary productivity and a combined variable of biomass and light attenuation showed that variability in the photosynthesis-irradiance response contributed little to the overall variability in primary productivity, and Chla alone could account for 53-86% of the variability in primary productivity. Efforts to model productivity in similar shallow systems with highly variable microalgal biomass may benefit the most by investing resources in improving spatial and temporal resolution of chlorophyll a measurements before increasing the complexity of models used in productivity modeling.

Anti-Ig autoantibody and complement-mediated destruction of neoplastic cells

NASA Technical Reports Server (NTRS)

Towmey, J. J.

1976-01-01

Some immune response are effected through immunoglobulins (Ig), of which five classes have been recognized, namely, IgA, IgD, IgE, IgG, and IgM. Auto-antibodies associated with rheumatoid arthritis, termed rheumatoid factors (RF) react with antigenic determinants on IgG heavy chains. RF has predominant but not complete IgM specificity. This auto-antibody response was not detected in treated patients with primary brain tumors (where tissue is sequestered from the immune system by an intact bloodbrain barrier) or with multiple myeloma where humoral immunity is usually impaired. In addition, the prevalence of RF is not increased with solid tumors prior to initiation of chemotherapy or radiotherapy. It is proposed that RF is related to prior chemotherapy or radiotherapy of tumors anatomically accessible to immunologic tissues capable of antibody responses. A primary IgG response occurs, antigen-antibody complexes form, complexed IgG becomes immunologic, and an RF response results.

The Jerusalem Experience: Three Decades of Service, Research, and Training in Community-Oriented Primary Care

PubMed Central

Epstein, Leon; Gofin, Jaime; Gofin, Rosa; Neumark, Yehuda

2002-01-01

Community-oriented primary care (COPC) developed and was tested over nearly 3 decades in the Hadassah Community Health Center in Jerusalem, Israel. Integration of public health responsibility with individual-based clinical management of patients formed the cornerstone of the COPC approach. A family medicine practice and a mother and child preventive service provided the frameworks for this development. The health needs of the community were assessed, priorities determined, and intervention programs developed and implemented on the basis of detailed analysis of the factors responsible for defined health states. Ongoing health surveillance facilitated evaluation, and the effectiveness of interventions in different population groups was illustrated. The center’s international COPC involvement has had effects on primary health care policy worldwide. PMID:12406791

High Prevalence of Insecure Attachment in Patients with Primary Hypertension

PubMed Central

Balint, Elisabeth M.; Gander, Manuela; Pokorny, Dan; Funk, Alexandra; Waller, Christiane; Buchheim, Anna

2016-01-01

Hypertension is a major cardiovascular (CV) risk factor and is predicted by heightened CV reactivity to stress in healthy individuals. Patients with hypertension also show an altered stress response, while insecure attachment is linked to a heightened stress reactivity as well. This is the first study aiming to assess attachment representations in patients with primary hypertension and to investigate their CV responses when their attachment system is activated. We studied 50 patients (38 men, 12 women) with primary hypertension. The Adult Attachment Projective Picture System (AAP), a widely used and validated interview, was performed to measure the patients' attachment representations, and to activate their attachment system. Blood pressure and heart rate were measured after 10 min at rest prior to and directly after the AAP interview. Mood and state anxiety were assessed using the Multidimensional Mood State Questionnaire (MDBF) and the State Trait Anxiety Inventory-State (STAI-S) before and after the experiment. The prevalence of insecure attachment (dismissing, preoccupied, unresolved) in hypertensive patients was predominant (88%), while in non-clinical populations, only about 50% of individuals had insecure attachment patterns. Blood pressure (p < 0.001), heart rate (p = 0.016), and rate pressure product (p < 0.001) significantly increased in response to the attachment interview. Secure attached patients showed the highest rise in systolic blood pressure (p = 0.020) and the lowest heart rate compared to the other attachment groups (p = 0.043). However, attachment representation showed no significant group or interaction effects on diastolic blood pressure (DBP) and rate pressure product. Insecure attachment was highly over-represented in our sample of patients with primary hypertension. Additionally, a robust CV response to the attachment-activating stimulus was observed. Our data suggest that insecure attachment is significantly linked to primary hypertension, which implies the need for further investigations to evaluate attachment insecurity as a possible risk factor for hypertension. PMID:27536255

Effectiveness and efficiencies in police traffic services programs

DOT National Transportation Integrated Search

1982-03-01

Traffic law violations were causative factors in about 90 percent of all motor vehicle crashes. Primary responsibility for deterring traffic law violations and for apprehending violators of these laws rest with State, county and municipal police agen...

Persistence of hepatitis A virus antibodies after primary immunization and response to revaccination in children and adolescents with perinatal HIV exposure

PubMed Central

Gouvêa, Aída de Fátima Thomé Barbosa; Pinto, Maria Isabel de Moraes; Miyamoto, Maristela; Machado, Daisy Maria; Pessoa, Silvana Duarte; do Carmo, Fabiana Bononi; Beltrão, Suênia Cordeiro de Vasconcelos; Succi, Regina Célia de Menezes

2015-01-01

OBJECTIVE: To assess possible factors associated with the loss of antibodies to hepatitis A 7 years after the primary immunization in children of HIV-infected mothers and the response to revaccination in patients seronegative for hepatitis A. METHODS: Quantification of HAV antibodies by electrochemiluminescence was performed in 39 adolescents followed up at the Pediatric Aids Clinic of Federal University of São Paulo (Unifesp): 29 HIV-infected (HIV group) (median age: 12.8 years) and 10 HIV-exposed but non-infected (ENI group) (median age: 13.4 years). All of them received two doses of HAV vaccine (Havrix(r)) in 2002. RESULTS: The median age at primary immunization (PI) was 5.4 years for HIV group and 6.5 years for ENI group. All children, from both groups, had antibodies to HAV >20 mIU/mL after PI. Seven years later, the ENI group showed a median concentration of antibodies = 253.5 mIU/mL, while the HIV group = 113.0 mIU/mL (Mann-Whitney test, p=0.085). All ENI group and 23/29 (79.3%) from HIV group mantained HAV antibodies 7 years after PI. The levels of hepatitis A antibodies in the primary vaccination were the only factor independently associated with maintaining these antibodies for 7 years. The group that lost HAV seropositivity was revaccinated and 83.3% (5/6) responded with antibodies >20 mUI/mL. CONCLUSIONS: The antibodies levels acquired in the primary vaccination in the HIV group were the main factor associated with antibodies loss after HAV immunization. PMID:25918013

[Persistence of hepatitis A virus antibodies after primary immunization and response to revaccination in children and adolescents with perinatal HIV exposure].

PubMed

Gouvêa, Aída de Fátima Thomé Barbosa; Pinto, Maria Isabel de Moraes; Miyamoto, Maristela; Machado, Daisy Maria; Pessoa, Silvana Duarte; Carmo, Fabiana Bononi do; Beltrão, Suênia Cordeiro de Vasconcelos; Succi, Regina Célia de Menezes

2015-01-01

To assess possible factors associated with the loss of antibodies to hepatitis A 7 years after the primary immunization in children of HIV-infected mothers and the response to revaccination in patients seronegative for hepatitis A. Quantification of HAV antibodies by electrochemiluminescence was performed in 39 adolescents followed up at the Pediatric Aids Clinic of Federal University of São Paulo (Unifesp): 29 HIV-infected (HIVgroup) (median age: 12.8 years) and 10 HIV-exposed but non-infected (ENI group) (median age: 13.4 years). All of them received two doses of HAV vaccine (Havrix(®)) in 2002. The median age at primary immunization (PI) was 5.4 years for HIV group and 6.5 years for ENI group. All children, from both groups, had antibodies to HAV >20 mIU/mL after PI. Seven years later, the ENI group showed a median concentration of antibodies = 253.5 mIU/mL, while the HIV group = 113.0 mIU/mL (Mann-Whitney test, p=0.085). All ENI group and 23/29 (79.3%) from HIV group mantained HAV antibodies 7 years after PI. The levels of hepatitis A antibodies in the primary vaccination were the only factor independently associated with maintaining these antibodies for 7 years. The group that lost HAV seropositivity was revaccinated and 83.3% (5/6) responded with antibodies >20 mUI/mL. The antibodies levels acquired in the primary vaccination in the HIV group were the main factor associated with antibodies loss after HAV immunization. Copyright © 2015 Associação de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

Therapygenetics: Using genetic markers to predict response to psychological treatment for mood and anxiety disorders

PubMed Central

2013-01-01

Considerable variation is evident in response to psychological therapies for mood and anxiety disorders. Genetic factors alongside environmental variables and gene-environment interactions are implicated in the etiology of these disorders and it is plausible that these same factors may also be important in predicting individual differences in response to psychological treatment. In this article, we review the evidence that genetic variation influences psychological treatment outcomes with a primary focus on mood and anxiety disorders. Unlike most past work, which has considered prediction of response to pharmacotherapy, this article reviews recent work in the field of therapygenetics, namely the role of genes in predicting psychological treatment response. As this is a field in its infancy, methodological recommendations are made and opportunities for future research are identified. PMID:23388219

Structure activity relationship of phenolic diterpenes from Salvia officinalis as activators of the nuclear factor E2-related factor 2 pathway

PubMed Central

Fischedick, Justin T; Standiford, Miranda; Johnson, Delinda A.; Johnson, Jeffrey A.

2013-01-01

Nuclear factor E2-related factor 2 (Nrf2) is a transcription factor known to activate cytoprotective genes which may be useful in the treatment of neurodegenerative disease. In order to better understand the structure activity relationship of phenolic diterpenes from Salvia officinalis L., we isolated carnosic acid, carnosol, epirosmanol, rosmanol, 12-methoxy-carnosic acid, sageone, and carnosaldehyde using polyamide column, centrifugal partition chromatography, and semi-preparative high performance liquid chromatography. Isolated compounds were screened in-vitro for their ability to active the Nrf2 and general cellular toxicity using mouse primary cortical cultures. All compounds except 12-methoxy-carnosic acid were able to activate the antioxidant response element. Furthermore both carnosol and carnoasldehyde were able to induce Nrf2-dependent gene expression as well as protect mouse primary cortical neuronal cultures from H2O2 induced cell death. PMID:23507152

[Nerve growth factor and the physiology of pain: the relationships among interoception, sympathetic neurons and the emotional response indicated by the molecular pathophysiology of congenital insensitivity to pain with anhidrosis].

PubMed

Indo, Yasuhiro

2015-05-01

Nerve growth factor (NGF) is a neurotrophic factor essential for the survival and maintenance of neurons. Congenital insensitivity to pain with anhidrosis (CIPA) is caused by loss-of-function mutations in NTRK1, which encodes a receptor tyrosine kinase, TrkA, for NGF. Mutations in NTRK1 cause the selective loss of NGF-dependent neurons, including both NGF-dependent primary afferents and sympathetic postganglionic neurons, in otherwise intact systems. The NGF-dependent primary afferents are thinly myelinated AΔ or unmyelinated C-fibers that are dependent on the NGF-TrkA system during development. NGF-dependent primary afferents are not only nociceptive neurons that transmit pain and temperature sensation, but also are polymodal receptors that play essential roles for interoception by monitoring various changes in the physiological status of all tissues in the body. In addition, they contribute to various inflammatory processes in acute, chronic and allergic inflammation. Together with sympathetic postganglionic neurons, they maintain the homeostasis of the body and emotional responses via interactions with the brain, immune and endocrine systems. Pain is closely related to emotions that accompany physical responses induced by systemic activation of the sympathetic nervous system. In contrast to a negative image of emotions in daily life, Antonio Damasio proposed the 'Somatic Marker Hypothesis', wherein emotions play critical roles in the decision-making and reasoning processes. According to this hypothesis, reciprocal communication between the brain and the body-proper are essential for emotional responses. Using the pathophysiology of CIPA as a foundation, this article suggests that NGF-dependent neurons constitute a part of the neuronal network required for homeostasis and emotional responses, and indicates that this network plays important roles in mediating the reciprocal communication between the brain and the body-proper.

The Actin Depolymerizing Factor (ADF)/Cofilin Signaling Pathway and DNA Damage Responses in Cancer

PubMed Central

Chang, Chun-Yuan; Leu, Jyh-Der; Lee, Yi-Jang

2015-01-01

The actin depolymerizing factor (ADF)/cofilin protein family is essential for actin dynamics, cell division, chemotaxis and tumor metastasis. Cofilin-1 (CFL-1) is a primary non-muscle isoform of the ADF/cofilin protein family accelerating the actin filamental turnover in vitro and in vivo. In response to environmental stimulation, CFL-1 enters the nucleus to regulate the actin dynamics. Although the purpose of this cytoplasm-nucleus transition remains unclear, it is speculated that the interaction between CFL-1 and DNA may influence various biological responses, including DNA damage repair. In this review, we will discuss the possible involvement of CFL-1 in DNA damage responses (DDR) induced by ionizing radiation (IR), and the implications for cancer radiotherapy. PMID:25689427

Assessment and management of risk factors for the prevention of lifestyle-related disease: a cross-sectional survey of current activities, barriers and perceived training needs of primary care physiotherapists in the Republic of Ireland.

PubMed

O'Donoghue, G; Cunningham, C; Murphy, F; Woods, C; Aagaard-Hansen, J

2014-06-01

To provide a snapshot of current activities, barriers and perceived training needs for the assessment and management of behavioural risk factors in physiotherapy practice in primary care settings in the Republic of Ireland. Cross-sectional survey of primary care physiotherapists. Two hundred and twenty primary care physiotherapists were invited to participate. Each received a questionnaire, consisting of 23 questions, within five key sections. Its main focus was the risk factor management practices of physiotherapists. Descriptive statistics and frequencies were used to analyse the data. A response rate of 74% (163/220) was achieved. Level of physical activity was the most common risk factor assessed at initial and follow-up visits (78%, 127/163), followed by dietary status (55%, 90/163). Few respondents included smoking status and alcohol consumption in their assessment; however, the majority considered them as risk factors that should be addressed. The main reasons why smoking status and alcohol consumption were not assessed were lack of time, limited knowledge and expertise, not traditionally viewed as the physiotherapist's role, and patient's lack of interest in changing their unhealthy behaviour. The findings highlight an untapped potential in relation to physiotherapists addressing lifestyle-related risk factors. A number of strategies are required to improve the systematic assessment and management of these risk factors. Copyright © 2014 Chartered Society of Physiotherapy. Published by Elsevier Ltd. All rights reserved.

A Qualitative Study of Systemic Factors Contributing to Successful Implementation of Response to Intervention Programs in Elementary Schools

ERIC Educational Resources Information Center

White, Sheila B.

2017-01-01

Response to intervention (RTI), an educational reform effort designed to meet the needs of struggling learners, has been adopted by an increasing number of states as a primary component of their educational service delivery model for low-achieving students (Burns et al., 2013; Castillo & Batsche, 2012). RTI models are multi-tiered…

Bacteria-triggered systemic immunity in barley is associated with WRKY and ETHYLENE RESPONSIVE FACTORs but not with salicylic acid.

PubMed

Dey, Sanjukta; Wenig, Marion; Langen, Gregor; Sharma, Sapna; Kugler, Karl G; Knappe, Claudia; Hause, Bettina; Bichlmeier, Marlies; Babaeizad, Valiollah; Imani, Jafargholi; Janzik, Ingar; Stempfl, Thomas; Hückelhoven, Ralph; Kogel, Karl-Heinz; Mayer, Klaus F X; Vlot, A Corina

2014-12-01

Leaf-to-leaf systemic immune signaling known as systemic acquired resistance is poorly understood in monocotyledonous plants. Here, we characterize systemic immunity in barley (Hordeum vulgare) triggered after primary leaf infection with either Pseudomonas syringae pathovar japonica (Psj) or Xanthomonas translucens pathovar cerealis (Xtc). Both pathogens induced resistance in systemic, uninfected leaves against a subsequent challenge infection with Xtc. In contrast to systemic acquired resistance in Arabidopsis (Arabidopsis thaliana), systemic immunity in barley was not associated with NONEXPRESSOR OF PATHOGENESIS-RELATED GENES1 or the local or systemic accumulation of salicylic acid. Instead, we documented a moderate local but not systemic induction of abscisic acid after infection of leaves with Psj. In contrast to salicylic acid or its functional analog benzothiadiazole, local applications of the jasmonic acid methyl ester or abscisic acid triggered systemic immunity to Xtc. RNA sequencing analysis of local and systemic transcript accumulation revealed unique gene expression changes in response to both Psj and Xtc and a clear separation of local from systemic responses. The systemic response appeared relatively modest, and quantitative reverse transcription-polymerase chain reaction associated systemic immunity with the local and systemic induction of two WRKY and two ETHYLENE RESPONSIVE FACTOR (ERF)-like transcription factors. Systemic immunity against Xtc was further associated with transcriptional changes after a secondary/systemic Xtc challenge infection; these changes were dependent on the primary treatment. Taken together, bacteria-induced systemic immunity in barley may be mediated in part by WRKY and ERF-like transcription factors, possibly facilitating transcriptional reprogramming to potentiate immunity. © 2014 American Society of Plant Biologists. All Rights Reserved.

Research needs for an improved primary care response to chronic non-communicable diseases in Africa.

PubMed

Maher, D; Sekajugo, J; Harries, A D; Grosskurth, H

2010-02-01

With non-communicable diseases (NCDs) projected to become leading causes of morbidity and mortality in developing countries, research is needed to improve the primary care response, especially in sub-Saharan Africa. This region has a particularly high double burden of communicable diseases and NCDs and the least resources for an effective response. There is a lack of good quality epidemiological data from diverse settings on chronic NCD burden in sub-Saharan Africa, and the approach to primary care of people with chronic NCDs is currently often unstructured. The main primary care research needs are therefore firstly, epidemiological research to document the burden of chronic NCDs, and secondly, health system research to deliver the structured, programmatic, public health approach that has been proposed for the primary care of people with chronic NCDs. Documentation of the burden and trends of chronic NCDs and associated risk factors in different settings and different population groups is needed to enable health system planning for an improved primary care response. Key research issues in implementing the programmatic framework for an improved primary care response are how to (i) integrate screening and prevention within health delivery; (ii) validate the use of standard diagnostic protocols for NCD case-finding among patients presenting to the local health facilities; (iii) improve the procurement and provision of standardised treatment and (iv) develop and implement a data collection system for standardised monitoring and evaluation of patient outcomes. Important research considerations include the following: selection of research sites and the particular NCDs targeted; research methodology; local research capacity; research collaborations; ethical issues; translating research findings into policy and practice and funding. Meeting the research needs for an improved health system response is crucial to deliver effective, affordable and equitable care for the millions of people with chronic NCDs in developing countries in Africa.

Job satisfaction: rural versus urban primary health care workers' perception in Ogun State of Nigeria.

PubMed

Campbell, P C; Ebuehi, O M

2011-01-01

Job satisfaction implies doing a job one enjoys, doing it well, and being suitably rewarded for one' efforts. Several factors affect job satisfaction. To compare factors influencing job satisfaction amongst rural and urban primary health care workers in southwestern Nigeria. A cross sectional comparative study recruited qualified health workers selected by multi stage sampling technique from rural and urban health facilities in four local government areas (LGAs) of Ogun State in Southwestern Nigeria. Data were collected and analysed using Epi info V 3.5.1 RESULTS: The response rates were 88(88%) and 91(91%) respectively in the rural and urban areas. While urban workers derived satisfaction from availability of career development opportunities, materials and equipment, in their current job, rural workers derived satisfaction from community recognition of their work and improved staff relationship. Major de-motivating factors common to both groups were lack of supportive supervision, client-provider relationship and lack of in-service training. However more rural 74(84.1%) than urban 62(68.1%) health workers would prefer to continue working in their present health facilities (p=0.04). There was a statistically significant difference between the two groups in job satisfaction with respect to tools availability and career development opportunities (p<0.05). There is dissimilarity in factors influencing job satisfaction between rural and urban healthcare workers. There is need for human resource policy to be responsive to the diverse needs of health workers particularly at the primary level.

Comparison of Factor Simplicity Indices for Dichotomous Data: DETECT R, Bentler's Simplicity Index, and the Loading Simplicity Index

ERIC Educational Resources Information Center

Finch, Holmes; Stage, Alan Kirk; Monahan, Patrick

2008-01-01

A primary assumption underlying several of the common methods for modeling item response data is unidimensionality, that is, test items tap into only one latent trait. This assumption can be assessed several ways, using nonlinear factor analysis and DETECT, a method based on the item conditional covariances. When multidimensionality is identified,…

Granulocyte-macrophage colony-stimulating factor responses of oral epithelial cells to Candida albicans.

PubMed

Dongari-Bagtzoglou, A; Kashleva, H

2003-06-01

Candida albicans is the principal fungal species responsible for oropharyngeal candidiasis, the most frequent opportunistic infection associated with immune deficiencies. Cytokines, such as granulocyte-macrophage colony-stimulating factor (GM-CSF), are important in the generation of effective immunity to C. albicans. The purposes of this investigation were to determine whether C. albicans triggers secretion of GM-CSF by oral epithelial cells in vitro and to investigate mechanisms of host cell-fungal interactions that trigger such responses. Oral epithelial cell lines as well as primary oral mucosal epithelial cells were challenged with stationary phase viable C. albicans, added to human cell cultures at varying yeast:oral cell ratios. Yeast were allowed to germinate for up to 48 h and supernatants were analyzed for GM-CSF by ELISA. Fixed organisms, germination-deficient mutants and separation of yeast from epithelial cells using cell culture inserts were used to assess the effects of viability, germination and physical contact, respectively, on the GM-CSF responses of these cells. Two out of three cell lines and three out of six primary cultures responded to C. albicans with an increase in GM-CSF secretion. GM-CSF responses were contact-dependent, strain-dependent, required yeast viability and were optimal when the yeast germinated into hyphae.

Management of Patients With Adenocarcinoma or Squamous Cancer of the Esophagus.

PubMed

Ilson, David H; van Hillegersberg, Richard

2018-01-01

Esophageal cancer is characterized by early and frequent metastasis. Surgery is the primary treatment for early-stage disease, whereas patients with patients with locally advanced disease receive perioperative chemotherapy or chemoradiotherapy. Squamous cancers can be treated with primary chemoradiotherapy without surgery, depending on their response to therapy and patient tolerance for subsequent surgery. Chemotherapy with a fluorinated pyrimidine and a platinum agent, followed by later treatment with taxanes and irinotecan, provides some benefit. Agents that inhibit the erb-b2 receptor tyrosine kinase 2 (ERBB2 or HER2), or vascular endothelial growth factor, including trastuzumab, ramucirumab, and apatinib, increase response and survival times. Esophageal adenocarcinomas have mutations in tumor protein p53 and mutations that activate receptor-associated tyrosine kinase, vascular endothelial growth factor, and cell cycle pathways, whereas esophageal squamous tumors have a distinct set of mutations. Esophageal cancers develop systems to evade anti-tumor immune responses, but studies are needed to determine how immune checkpoint modification contributes to esophageal tumor development. Copyright © 2018 AGA Institute. Published by Elsevier Inc. All rights reserved.

Effects of long-term nutrient additions on Arctic tundra, stream, and lake ecosystems: beyond NPP.

PubMed

Gough, Laura; Bettez, Neil D; Slavik, Karie A; Bowden, William B; Giblin, Anne E; Kling, George W; Laundre, James A; Shaver, Gaius R

2016-11-01

Primary producers form the base of food webs but also affect other ecosystem characteristics, such as habitat structure, light availability, and microclimate. Here, we examine changes caused by 5-30+ years of nutrient addition and resulting increases in net primary productivity (NPP) in tundra, streams, and lakes in northern Alaska. The Arctic provides an important opportunity to examine how ecosystems characterized by low diversity and low productivity respond to release from nutrient limitation. We review how responses of algae and plants affect light availability, perennial biotic structures available for consumers, oxygen levels, and temperature. Sometimes, responses were similar across all three ecosystems; e.g., increased NPP significantly reduced light to the substrate following fertilization. Perennial biotic structures increased in tundra and streams but not in lakes, and provided important new habitat niches for consumers as well as other producers. Oxygen and temperature responses also differed. Life history traits (e.g., longevity) of the primary producers along with the fate of detritus drove the responses and recovery. As global change persists and nutrients become more available in the Arctic and elsewhere, incorporating these factors as response variables will enable better prediction of ecosystem changes and feedbacks in this biome and others.

ZBTB32 restricts the duration of memory B cell recall responses1

PubMed Central

Jash, Arijita; Wang, Yinan; Weisel, Florian J.; Scharer, Christopher D.; Boss, Jeremy M.; Shlomchik, Mark J.; Bhattacharya, Deepta

2016-01-01

Memory B cell responses are more rapid and of greater magnitude than are primary antibody responses. The mechanisms by which these secondary responses are eventually attenuated remain unknown. We demonstrate that the transcription factor ZBTB32 limits the rapidity and duration of antibody recall responses. ZBTB32 is highly expressed by mouse and human memory B cells, but not by their naïve counterparts. Zbtb32−/− mice mount normal primary antibody responses to T-dependent antigens. However, Zbtb32−/− memory B cell-mediated recall responses occur more rapidly and persist longer than do control responses. Microarray analyses demonstrate that Zbtb32−/− secondary bone marrow plasma cells display elevated expression of genes that promote cell cycle progression and mitochondrial function relative to wild-type controls. BrdU labeling and adoptive transfer experiments confirm more rapid production and a cell-intrinsic survival advantage of Zbtb32−/− secondary plasma cells relative to wild-type counterparts. ZBTB32 is therefore a novel negative regulator of antibody recall responses. PMID:27357154

Region 4 of Rhizobium etli Primary Sigma Factor (SigA) Confers Transcriptional Laxity in Escherichia coli.

PubMed

Santillán, Orlando; Ramírez-Romero, Miguel A; Lozano, Luis; Checa, Alberto; Encarnación, Sergio M; Dávila, Guillermo

2016-01-01

Sigma factors are RNA polymerase subunits engaged in promoter recognition and DNA strand separation during transcription initiation in bacteria. Primary sigma factors are responsible for the expression of housekeeping genes and are essential for survival. RpoD, the primary sigma factor of Escherichia coli, a γ-proteobacteria, recognizes consensus promoter sequences highly similar to those of some α-proteobacteria species. Despite this resemblance, RpoD is unable to sustain transcription from most of the α-proteobacterial promoters tested so far. In contrast, we have found that SigA, the primary sigma factor of Rhizobium etli, an α-proteobacteria, is able to transcribe E. coli promoters, although it exhibits only 48% identity (98% coverage) to RpoD. We have called this the transcriptional laxity phenomenon. Here, we show that SigA partially complements the thermo-sensitive deficiency of RpoD285 from E. coli strain UQ285 and that the SigA region σ4 is responsible for this phenotype. Sixteen out of 74 residues (21.6%) within region σ4 are variable between RpoD and SigA. Mutating these residues significantly improves SigA ability to complement E. coli UQ285. Only six of these residues fall into positions already known to interact with promoter DNA and to comprise a helix-turn-helix motif. The remaining variable positions are located on previously unexplored sites inside region σ4, specifically into the first two α-helices of the region. Neither of the variable positions confined to these helices seem to interact directly with promoter sequence; instead, we adduce that these residues participate allosterically by contributing to correct region folding and/or positioning of the HTH motif. We propose that transcriptional laxity is a mechanism for ensuring transcription in spite of naturally occurring mutations from endogenous promoters and/or horizontally transferred DNA sequences, allowing survival and fast environmental adaptation of α-proteobacteria.

Region 4 of Rhizobium etli Primary Sigma Factor (SigA) Confers Transcriptional Laxity in Escherichia coli

PubMed Central

Santillán, Orlando; Ramírez-Romero, Miguel A.; Lozano, Luis; Checa, Alberto; Encarnación, Sergio M.; Dávila, Guillermo

2016-01-01

Sigma factors are RNA polymerase subunits engaged in promoter recognition and DNA strand separation during transcription initiation in bacteria. Primary sigma factors are responsible for the expression of housekeeping genes and are essential for survival. RpoD, the primary sigma factor of Escherichia coli, a γ-proteobacteria, recognizes consensus promoter sequences highly similar to those of some α-proteobacteria species. Despite this resemblance, RpoD is unable to sustain transcription from most of the α-proteobacterial promoters tested so far. In contrast, we have found that SigA, the primary sigma factor of Rhizobium etli, an α-proteobacteria, is able to transcribe E. coli promoters, although it exhibits only 48% identity (98% coverage) to RpoD. We have called this the transcriptional laxity phenomenon. Here, we show that SigA partially complements the thermo-sensitive deficiency of RpoD285 from E. coli strain UQ285 and that the SigA region σ4 is responsible for this phenotype. Sixteen out of 74 residues (21.6%) within region σ4 are variable between RpoD and SigA. Mutating these residues significantly improves SigA ability to complement E. coli UQ285. Only six of these residues fall into positions already known to interact with promoter DNA and to comprise a helix-turn-helix motif. The remaining variable positions are located on previously unexplored sites inside region σ4, specifically into the first two α-helices of the region. Neither of the variable positions confined to these helices seem to interact directly with promoter sequence; instead, we adduce that these residues participate allosterically by contributing to correct region folding and/or positioning of the HTH motif. We propose that transcriptional laxity is a mechanism for ensuring transcription in spite of naturally occurring mutations from endogenous promoters and/or horizontally transferred DNA sequences, allowing survival and fast environmental adaptation of α-proteobacteria. PMID:27468278

Career Choice and Primary Care in the United Arab Emirates

PubMed Central

Schiess, Nicoline; Ibrahim, Halah; Shaban, Sami; Perez, Maria Nichole; Nair, Satish Chandrasekhar

2015-01-01

Background  The low number of medical trainees entering primary care is contributing to the lack of access to primary care services in many countries. Despite the need for primary care physicians in the Middle East, there is limited information regarding trainees' career choices, a critical determinant in the supply of primary care physicians. Objective  We analyzed the career choices of medical students in the United Arab Emirates (UAE), with a larger goal of reforming postgraduate training in the region and enhancing the focus on primary care. Methods  We conducted a cross-sectional survey of applicants to a large established internal medicine residency program in the UAE. We calculated data for demographics, subspecialty choice, and factors affecting subspecialty choice, and we also reported descriptive statistics. Results  Our response rate was 86% (183 of 212). Only 25% of applicants (n = 46) were interested in general internal medicine. The majority of respondents (n = 126, 69%) indicated a desire to pursue subspecialty training, and the remainder chose careers in research or administration. A majority of respondents (73%) were women, unmarried, and childless. Educational debt or lifestyle were not indicated as important factors in career choice. Conclusions  Low interest in primary care was similar to that in many Western countries, despite a much higher percentage of female applicants and a reduced emphasis on lifestyle or income factors in career decisions. Reasons for the reduced interest in primary care deserve further exploration, as do tests of interventions to increase interest, such as improving the primary care clerkship experience. PMID:26692983

[Response rates in three opinion surveys performed through online questionnaires in the health setting].

PubMed

Aerny Perreten, Nicole; Domínguez-Berjón, Ma Felicitas; Astray Mochales, Jenaro; Esteban-Vasallo, María D; Blanco Ancos, Luis Miguel; Lópaz Pérez, Ma Ángeles

2012-01-01

The main advantages of online questionnaires are the speed of data collection and cost savings, but response rates are usually low. This study analyzed response rates and associated factors among health professionals in three opinion surveys in the autonomous region of Madrid. The participants, length of the questionnaire and topic differed among the three surveys. The surveys were conducted by using paid Internet software. The institutional e-mail addresses of distinct groups of health professionals were used. Response rates were highest in hospitals (up to 63%) and administrative services and were lowest in primary care (less than 33%). The differences in response rates were analyzed in primary care professionals according to age, sex and professional category and only the association with age was statistically significant. None of the surveys achieved a response rate of 60%. Differences were observed according to workplace, patterns of Internet usage, and interest in the subject. Copyright © 2011 SESPAS. Published by Elsevier Espana. All rights reserved.

Comprehensiveness of care from the patient perspective: comparison of primary healthcare evaluation instruments.

PubMed

Haggerty, Jeannie L; Beaulieu, Marie-Dominique; Pineault, Raynald; Burge, Frederick; Lévesque, Jean-Frédéric; Santor, Darcy A; Bouharaoui, Fatima; Beaulieu, Christine

2011-12-01

Comprehensiveness relates both to scope of services offered and to a whole-person clinical approach. Comprehensive services are defined as "the provision, either directly or indirectly, of a full range of services to meet most patients' healthcare needs"; whole-person care is "the extent to which a provider elicits and considers the physical, emotional and social aspects of a patient's health and considers the community context in their care." Among instruments that evaluate primary healthcare, two had subscales that mapped to comprehensive services and to the community component of whole-person care: the Primary Care Assessment Tool - Short Form (PCAT-S) and the Components of Primary Care Index (CPCI, a limited measure of whole-person care). To examine how well comprehensiveness is captured in validated instruments that evaluate primary healthcare from the patient's perspective. 645 adults with at least one healthcare contact in the previous 12 months responded to six instruments that evaluate primary healthcare. Scores were normalized for descriptive comparison. Exploratory and confirmatory (structural equation modelling) factor analysis examined fit to operational definition, and item response theory analysis examined item performance on common constructs. Over one-quarter of respondents had missing responses on services offered or doctor's knowledge of the community. The subscales did not load on a single factor; comprehensive services and community orientation were examined separately. The community orientation subscales did not perform satisfactorily. The three comprehensive services subscales fit very modestly onto two factors: (1) most healthcare needs (from one provider) (CPCI Comprehensive Care, PCAT-S First-Contact Utilization) and (2) range of services (PCAT-S Comprehensive Services Available). Individual item performance revealed several problems. Measurement of comprehensiveness is problematic, making this attribute a priority for measure development. Range of services offered is best obtained from providers. Whole-person care is not addressed as a separate construct, but some dimensions are covered by attributes such as interpersonal communication and relational continuity.

Prevention of coronary heart disease in people with severe mental illnesses: a qualitative study of patient and professionals' preferences for care

PubMed Central

Wright, Christine A; Osborn, David PJ; Nazareth, Irwin; King, Michael B

2006-01-01

Background People with severe mental illness (SMI) are at increased risk of developing coronary heart disease (CHD) and there is growing emphasis on the need to monitor their physical health. However, there is little consensus on how services for the primary prevention of CHD should be organised for this patient group. We explored the views of people with SMI and health professionals from primary care and community mental health teams (CMHTs) on how best to provide these services. Methods In-depth interviews were conducted with a purposive sample of patients with SMI (n = 31) and staff from primary care (n = 10) and community mental health teams (n = 25) in North Central London. Transcripts of the qualitative interviews were analysed using a 'framework' approach to identify the main themes in opinions regarding various service models. Results Cardiovascular risk factors in people with SMI were of concern to participants. However, there was some disagreement about the best way to deliver appropriate care. Although staff felt that primary care should take responsibility for risk factor screening and management, patients favoured CHD screening in their CMHT. Problems with both approaches were identified. These included a lack of familiarity in general practice with SMI and antipsychotic side effects and poor communication of physical health issues to the CMHT. Lack of knowledge regarding CHD risk factor screening and difficulties in interpreting screening results and implementing appropriate interventions exist in secondary care. Conclusion Management of physical health care for people with SMI requires complex solutions that cross the primary-secondary care interface. The views expressed by our participants suggest that neither primary nor secondary care services on their own can provide a comprehensive service for all patients. The increased risk of CHD associated with SMI and antipsychotic medications requires flexible solutions with clear lines of responsibility for assessing, communicating and managing CHD risks. PMID:16630335

Evaluation and optimization of hepatocyte culture media factors by design of experiments (DoE) methodology

PubMed Central

Dong, Jia; Lübberstedt, Marc; Urbaniak, Thomas; Nüssler, Andreas K.N.; Knobeloch, Daniel; Gerlach, Jörg C.; Zeilinger, Katrin

2008-01-01

Optimization of cell culture media based on statistical experimental design methodology is a widely used approach for improving cultivation conditions. We applied this methodology to refine the composition of an established culture medium for growth of a human hepatoma cell line, C3A. A selection of growth factors and nutrient supplements were systematically screened according to standard design of experiments (DoE) procedures. The results of the screening indicated that the medium additives hepatocyte growth factor, oncostatin M, and fibroblast growth factor 4 significantly influenced the metabolic activities of the C3A cell line. Surface response methodology revealed that the optimum levels for these factors were 30 ng/ml for hepatocyte growth factor and 35 ng/ml for oncostatin M. Additional experiments on primary human hepatocyte cultures showed high variance in metabolic activities between cells from different individuals, making determination of optimal levels of factors more difficult. Still, it was possible to conclude that hepatocyte growth factor, epidermal growth factor, and oncostatin M had decisive effects on the metabolic functions of primary human hepatocytes. PMID:19003182

Evaluation and optimization of hepatocyte culture media factors by design of experiments (DoE) methodology.

PubMed

Dong, Jia; Mandenius, Carl-Fredrik; Lübberstedt, Marc; Urbaniak, Thomas; Nüssler, Andreas K N; Knobeloch, Daniel; Gerlach, Jörg C; Zeilinger, Katrin

2008-07-01

Optimization of cell culture media based on statistical experimental design methodology is a widely used approach for improving cultivation conditions. We applied this methodology to refine the composition of an established culture medium for growth of a human hepatoma cell line, C3A. A selection of growth factors and nutrient supplements were systematically screened according to standard design of experiments (DoE) procedures. The results of the screening indicated that the medium additives hepatocyte growth factor, oncostatin M, and fibroblast growth factor 4 significantly influenced the metabolic activities of the C3A cell line. Surface response methodology revealed that the optimum levels for these factors were 30 ng/ml for hepatocyte growth factor and 35 ng/ml for oncostatin M. Additional experiments on primary human hepatocyte cultures showed high variance in metabolic activities between cells from different individuals, making determination of optimal levels of factors more difficult. Still, it was possible to conclude that hepatocyte growth factor, epidermal growth factor, and oncostatin M had decisive effects on the metabolic functions of primary human hepatocytes.

The Serum Response Factor and a Putative Novel Transcription Factor Regulate Expression of the Immediate-Early Gene Arc/Arg3.1 in Cultured Cortical Neurons

PubMed Central

Pintchovski, Sean A.; Peebles, Carol L.; Kim, Hong Joo; Verdin, Eric; Finkbeiner, Steven

2010-01-01

The immediate-early effector gene Arc/Arg3.1 is robustly upregulated by synaptic activity associated with learning and memory. Here we show in primary cortical neuron culture that diverse stimuli induce Arc expression through new transcription. Searching for regulatory regions important for Arc transcription, we found nine DNaseI-sensitive nucleosome-depleted sites at this genomic locus. A reporter gene encompassing these sites responded to synaptic activity in an NMDA receptor–dependent manner, consistent with endogenous Arc mRNA. Responsiveness mapped to two enhancer regions ∼6.5 kb and ∼1.4 kb upstream of Arc. We dissected these regions further and found that the proximal enhancer contains a functional and conserved “Zeste-like” response element that binds a putative novel nuclear protein in neurons. Therefore, activity regulates Arc transcription partly by a novel signaling pathway. We also found that the distal enhancer has a functional and highly conserved serum response element. This element binds serum response factor, which is recruited by synaptic activity to regulate Arc. Thus, Arc is the first target of serum response factor that functions at synapses to mediate plasticity. PMID:19193899

[Factors associated with primary care professionals' readiness to respond to intimate partner violence in Spain].

PubMed

Murillo, Pilar; Sebastián, Miguel San; Vives-Cases, Carmen; Goicolea, Isabel

2017-05-22

To analyse the Spanish primary care professionals' readiness to respond to intimate partner violence (IPV) in primary care and identify possible determinants that could facilitate a better response. A cross-sectional study with a non-probabilistic sampling by convenience was performed among healthcare professionals working in 15 primary care centres in Spain. The Physician Readiness to Manage Intimate Partner Violence Survey (PREMIS), the version validated and translated into Spanish, was the instrument used to collect information about knowledge, opinions and practices regarding intimate partner violence. Descriptive analysis and, simple and multiple linear regression analysis were performed. A total of 265 completed questionnaires were received, with a response rate of 80.3%. An exposure-response effect was observed, where at higher hours of training a higher score was obtained on the questionnaire sections (p <0.05). Age, type of profession, years of experience in primary care, hours of IPV training and reading the protocol showed positive association with knowledge (perceived preparation, perceived knowledge, actual knowledge), opinions (staff preparation, legal requirements, self-efficacy, workplace issues, constraints, understanding of the victim) and practice of healthcare professionals. Reading the regional/national protocol for action and receiving training in IPV were the most important interventions associated to a better primary care professionals' readiness to respond to IPV in Spanish primary care settings. Copyright © 2017 SESPAS. Publicado por Elsevier España, S.L.U. All rights reserved.

Primary vaccine failure to routine vaccines: Why and what to do?

PubMed

Wiedermann, Ursula; Garner-Spitzer, Erika; Wagner, Angelika

2016-01-01

There are 2 major factors responsible for vaccine failures, the first is vaccine-related such as failures in vaccine attenuation, vaccination regimes or administration. The other is host-related, of which host genetics, immune status, age, health or nutritional status can be associated with primary or secondary vaccine failures. The first describes the inability to respond to primary vaccination, the latter is characterized by a loss of protection after initial effectiveness. Our studies concentrate on the evaluation of immunological characteristics responsible for primary vaccine failures in different (risk) populations for which the underlying mechanisms are currently unknown. Here we summarise current knowledge and findings from our studies. About 2-10% of healthy individuals fail to mount antibody levels to routine vaccines. Comparing the immune responses to different vaccines in non-responder and high-responder vaccinees revealed that hypo-responsiveness is antigen/vaccine-specific at the humoral but not at the cellular level. We found that T-regulatory as well as B-regulatory cells and the production of IL-10 are involved in non/hypo-responsiveness. Non-responsiveness increases with age and in particular vaccination to a novel vaccine in persons > 65 years is associated with a high low/non-responder rate, indicating that vaccine schedules and doses (at least for primary vaccination) should be adapted according to age. In light of the growing number of allergic but also obese people, our current studies concentrate on these risk groups to reveal whether different vaccination approaches are necessary for optimal protection compared to healthy individuals. These studies are in line with the significant paradigm shift taking place in many fields of medical research and care, and will extend the concept of personalised medicine into the field of vaccinology.

A narrative systematic review of factors affecting diabetes prevention in primary care settings

PubMed Central

Eyles, Emily

2017-01-01

Background Type 2 diabetes is impacting millions of people globally; however, many future cases can be prevented through lifestyle changes and interventions. Primary care is an important setting for diabetes prevention, for at-risk populations, because it is a patient’s primary point of contact with the health care system and professionals can provide lifestyle counselling and support, as well as monitoring health outcomes. These are all essential elements for diabetes prevention for at-risk adults. Aim To understand the factors related to the delivery and uptake of type 2 diabetes prevention interventions within primary care in higher income countries. Methods For this narrative systematic review, we combined qualitative and quantitative studies of diabetes prevention within a primary care setting for patients at-risk of developing the condition. We used an iterative approach for evidence collection, which included using several databases (MEDLINE, Embase, Pysch info, BNI, SSCI, CINAHL, ASSIA), where we combined diabetes terms with primary care terms. Narrative and thematic synthesis were utilised to identify the prominent themes emerging from the data. Results A database of 6646 records was screened by the research team, and 18 papers were included. Three major themes were identified in this review. The first theme of context and setting of diabetes progression includes the risk and progression of diabetes, primary care as a setting, and where the responsibility for change is thought to lie. This review also found mixed views on the value of preventative services within primary care. The second theme focused on the various patient factors associated with diabetes prevention such as a patient’s motivation to modify their current lifestyle, perceptions and knowledge (or lack thereof) of the impacts of diabetes, lack of follow-up in healthcare settings, and trust in healthcare professionals. The third theme was centred on professional factors impacting on diabetes prevention which included workload, time constraints, resources, self-efficacy and knowledge as well as professionals’ perception of patient motivations towards change. Conclusion This review explored the factors influencing diabetes prevention in primary care, and identified the context of prevention, as well as patient and professional factors related to preventative services being offered in primary care. This systematic review complements previous reviews of real-world settings by exploring the significant factors in prevention, and the findings are relevant to academics, policymakers, patients and practitioners interested in understanding the factors associated with the delivery and uptake of diabetes prevention interventions. PMID:28531197

Factors Influencing Medical School Graduates Toward a Career in Psychiatry: Analysis from the 2011-2013 Association of American Medical Colleges Graduation Questionnaire.

PubMed

Wilbanks, Lindsey; Spollen, John; Messias, Erick

2016-04-01

Various factors influence choice of medical specialty. Previous research grouped specialties into controllable lifestyle, primary care, and surgical. This study compared factors influencing individuals to choose psychiatry versus other specialties. Data came from the 2011-2013 Association of American Medical Colleges Graduation Questionnaire. The authors grouped responses, ranging from no influence to minor, moderate, and strong influence, into psychiatry and controllable lifestyle, primary care, and surgical specialties and analyzed the data using one-way analysis of variance. The analyses included 29,227 students, of which 1329 (4.5%) elected psychiatry; 10,998 (37.6%), controllable lifestyle specialties; 12,320 (42.2%), primary care specialties; and 4580 (15.7%), surgical specialties. Students choosing psychiatry reported less influence of competitiveness, student debt, and salary expectations than those choosing controllable lifestyle and surgical specialties (p < 0.0001) and more influence of work/life balance than those choosing primary care and surgical specialties (p < 0.0001). They reported less influence of family expectations than those choosing controllable lifestyle specialties (p < 0.0001). They reported more influence of fit with personality than controllable lifestyle, primary care, and surgical specialties (p < 0.004). Students entering psychiatry do not fit the traditional categories of controllable lifestyle, primary care, and surgical profiles, but fall between controllable lifestyle and primary care specialties. Recruitment efforts may need to address this different pattern of influences.

Characterization and response of newly developed high-grade glioma cultures to the tyrosine kinase inhibitors, erlotinib, gefitinib and imatinib

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

Kinsella, Paula, E-mail: paula.kinsella@dcu.ie; Howley, Rachel, E-mail: rhowley@rcsi.ie; Doolan, Padraig, E-mail: padraig.doolan@dcu.ie

2012-03-10

High-grade gliomas (HGG), are the most common aggressive brain tumours in adults. Inhibitors targeting growth factor signalling pathways in glioma have shown a low clinical response rate. To accurately evaluate response to targeted therapies further in vitro studies are necessary. Growth factor pathway expression using epidermal growth factor receptor (EGFR), mutant EGFR (EGFRvIII), platelet derived growth factor receptor (PDGFR), C-Kit and C-Abl together with phosphatase and tensin homolog (PTEN) expression and downstream activation of AKT and phosphorylated ribosomal protein S6 (P70S6K) was analysed in 26 primary glioma cultures treated with the tyrosine kinase inhibitors (TKIs) erlotinib, gefitinib and imatinib. Responsemore » to TKIs was assessed using 50% inhibitory concentrations (IC{sub 50}). Response for each culture was compared with the EGFR/PDGFR immunocytochemical pathway profile using hierarchical cluster analysis (HCA) and principal component analysis (PCA). Erlotinib response was not strongly associated with high expression of the growth factor pathway components. PTEN expression did not correlate with response to any of the three TKIs. Increased EGFR expression was associated with gefitinib response; increased PDGFR-{alpha} expression was associated with imatinib response. The results of this in vitro study suggest gefitinib and imatinib may have therapeutic potential in HGG tumours with a corresponding growth factor receptor expression profile. -- Highlights: Black-Right-Pointing-Pointer Non-responders had low EGFR expression, high PDGFR-{beta}, and a low proliferation rate. Black-Right-Pointing-Pointer PTEN is not indicative of response to a TKI. Black-Right-Pointing-Pointer Erlotinib response was not associated with expression of the proteins examined. Black-Right-Pointing-Pointer Imatinib-response correlated with expression of PDGFR-{alpha}. Black-Right-Pointing-Pointer Gefitinib response correlated with increased expression of EGFR.« less

Managing an Online Survey about Influenza Vaccination in Primary Healthcare Workers

PubMed Central

Toledo, Diana; Aerny, Nicole; Soldevila, Núria; Baricot, Maretva; Godoy, Pere; Castilla, Jesús; García-Gutierrez, Susana; Torner, Núria; Astray, Jenaro; Mayoral, José María; Tamames, Sonia; González-Candelas, Fernando; Martín, Vicente; Díaz, José; Domíguez, Angela

2015-01-01

Online surveys are increasingly used due to their speed and efficiency. The aim of this study was to analyze factors that may have contributed to the quality and speed of response of an online survey on influenza vaccination in primary healthcare workers. A multicenter study including family physicians, nurses and pediatricians from primary healthcare teams from seven Spanish Autonomous Communities was designed. The centers were selected by simple random sampling. The survey remained active and accessible for 56 days and four reminders were sent. The odds ratios (OR) and their 95% confidence intervals (CI) were calculated to assess the association of sociodemographic variables and responding to the survey before the second reminder. Complete, validated information was obtained from 1965 primary healthcare workers. The total response rate was 36.2%. More nurses (46.3%) responded before the second reminder and more family physicians (52.8%) after the second reminder. The adjusted OR shows that family physicians responded later (AOR 1.46, 95% CI 1.2–1.8) than nurses. The responses obtained in the first 24 h after the initial sending and the reminders accounted for 41.7% of the completed surveys, indicating the importance of reminders. PMID:25584421

Factors influencing nurse and pharmacist willingness to take or not take responsibility for non-medical prescribing.

PubMed

Maddox, C; Halsall, D; Hall, J; Tully, M P

2016-01-01

In the UK, the majority of non-medical prescribers (NMPs) are nurses or pharmacists working in community or primary care. However, little is known about what influences their decisions to prescribe, unlike with medical prescribing. It is also unclear whether the medical findings can be extrapolated, given their very different prescribing training. To explore the factors influencing whether nurse and pharmacist NMPs in community and primary care settings take responsibility for prescribing. Initially, 20 NMPs (15 nurses and 5 pharmacists) were purposively selected and interviewed using the critical incident technique about situations where they felt it was inappropriate for them to take responsibility for prescribing or where they were uneasy about doing so. In addition, more general factors influencing their decision to take or not take prescribing responsibility were discussed. Subsequently, the themes from the interview analysis were validated in three focus groups with a total of 10 nurse NMPs. All data were analyzed using a constant comparison approach. Fifty-two critical incidents were recorded--12 from pharmacist NMPs and 40 from nurse NMPs. Participants experienced situations where they were reluctant to accept responsibility for prescribing. Perceptions of competency, role and risk influenced their decision to prescribe. Workarounds such as delaying the prescribing decision or refer the patient to a doctor were used. For NMPs to feel more confident about taking responsibility for prescribing, these issues of competency, role and perceived risk need to be addressed. Roles of NMPs must be clear to colleagues, doctors and patients. Training and support must be provided to enable professional development and increasing competence of NMPs. Copyright © 2016 Elsevier Inc. All rights reserved.

Seasonal and Inter-Annual Variations in Carbon Dioxide Exchange over an Alpine Grassland in the Eastern Qinghai-Tibetan Plateau.

PubMed

Shang, Lunyu; Zhang, Yu; Lyu, Shihua; Wang, Shaoying

2016-01-01

This work analyzed carbon dioxide exchange and its controlling factors over an alpine grassland on the eastern Qinghai-Tibetan Plateau. The main results show that air temperature and photosynthetically active radiation are two dominant factors controlling daily gross primary production. Soil temperature and soil water content are the main factors controlling ecosystem respiration. Canopy photosynthetic activity is also responsible for the variation of daily ecosystem respiration other than environmental factors. No clear correlation between net ecosystem exchange and environmental factors was observed at daily scale. Temperature sensitive coefficient was observed to increase with larger soil water content. High values of temperature sensitive coefficient occurred during the periods when soil water content was high and grass was active. Annual integrated net ecosystem exchange, gross primary production and ecosystem respiration were -191, 1145 and 954 g C m-2 for 2010, and -250, 975 and 725 g C m-2 for 2011, respectively. Thus, this alpine grassland was a moderate carbon sink in both of the two years. Compared to alpine grasslands on the Qinghai-Tibetan Plateau, this alpine grassland demonstrated a much greater potential for carbon sequestration than others. Annual precipitation is a dominant factor controlling the variation of annual net ecosystem exchange over this grassland. The difference in gross primary production between the two years was not caused by the variation in annual precipitation. Instead, air temperature and the length of growing season had an important impact on annual gross primary production. Variation of annual ecosystem respiration was closely related to annual gross primary production and soil water content during the growing season.

Seasonal and Inter-Annual Variations in Carbon Dioxide Exchange over an Alpine Grassland in the Eastern Qinghai-Tibetan Plateau

PubMed Central

Shang, Lunyu; Zhang, Yu; Lyu, Shihua; Wang, Shaoying

2016-01-01

This work analyzed carbon dioxide exchange and its controlling factors over an alpine grassland on the eastern Qinghai-Tibetan Plateau. The main results show that air temperature and photosynthetically active radiation are two dominant factors controlling daily gross primary production. Soil temperature and soil water content are the main factors controlling ecosystem respiration. Canopy photosynthetic activity is also responsible for the variation of daily ecosystem respiration other than environmental factors. No clear correlation between net ecosystem exchange and environmental factors was observed at daily scale. Temperature sensitive coefficient was observed to increase with larger soil water content. High values of temperature sensitive coefficient occurred during the periods when soil water content was high and grass was active. Annual integrated net ecosystem exchange, gross primary production and ecosystem respiration were -191, 1145 and 954 g C m-2 for 2010, and -250, 975 and 725 g C m-2 for 2011, respectively. Thus, this alpine grassland was a moderate carbon sink in both of the two years. Compared to alpine grasslands on the Qinghai-Tibetan Plateau, this alpine grassland demonstrated a much greater potential for carbon sequestration than others. Annual precipitation is a dominant factor controlling the variation of annual net ecosystem exchange over this grassland. The difference in gross primary production between the two years was not caused by the variation in annual precipitation. Instead, air temperature and the length of growing season had an important impact on annual gross primary production. Variation of annual ecosystem respiration was closely related to annual gross primary production and soil water content during the growing season. PMID:27861616

Do the conventional clinicopathologic parameters predict for response and survival in head and neck cancer patients undergoing neoadjuvant chemotherapy?

PubMed

Fonseca, E; Cruz, J J; Dueñas, A; Gómez, A; Sánchez, P; Martín, G; Nieto, A; Soria, P; Muñoz, A; Gómez, J L; Pardal, J L

1996-01-01

Neoadjuvant chemotherapy for head and neck carcinoma is still an important treatment modality. The prognostic value of patient and tumor parameters has been extensively evaluated in several trials, yielding mixed results. We report the prognostic factors emerging from a group of patients undergoing neoadjuvant chemotherapy. From April 1986 to June 1992, 149 consecutive patients received cisplatin-5-fluorouracil-based neoadjuvant chemotherapy. After four courses of chemotherapy, patients underwent local-regional treatment with surgery, radiation or both. A variety of patient and tumor characteristics were evaluated as predictors for response to chemotherapy and survival. The complete response, partial response and no response rates to NAC were 52%, 33% and 15%, respectively. No parameters predicted response to chemotherapy. At a maximum follow-up of 87 months, overall survival was 39% and disease-free survival was 49%. Variables shown to be predictors of survival in univariate analyses were age, performance status, histology, site, T, N, stage, and response to chemotherapy. Using the Cox regression analysis, only complete response to induction chemotherapy (P = 0.0006), performance status (P = 0.03), stage (P = 0.01), age (P = 0.03) and primary tumor site (P = 0.04) emerged as independent prognostic factors for survival. Complete response to chemotherapy was confirmed as the strongest prognostic factor influencing survival. However, conventional clinicopathologic factors did not predict response, hence, potential prognostic biologic and molecular factors for response must be sought. At present, much effort must be made for the improvement of the complete response rate, which seems to be a requisite to prolong survival.

Towards rational therapy with monoamine oxidase inhibitors.

PubMed

Tyrer, P

1976-04-01

A rational approach to the use of monoamine oxidase inhibitors (MAOIs) is outlined. Patients suitable for treatment cannot be classified adequately using conventional diagnostic labels. They include those with primary symptoms of hypochondriasis, agoraphobia and social phobias, irritability, somatic anxiety and anergia; those with primary depressed mood, guilt, ideas of reference and personality disorders seldom respond. There is great variation in the interval between the first administration of these drugs and clinical response, and this may account for the inconsistencies in published trials. The type of drug and its dose may affect rate of response, as may biochemical factors, including acetylator and monoamine oxidase status. To obtain maximum benefit, a course of therapy with MAOIs should last for several months.

Neurotrophic factor intervention restores auditory function in deafened animals

NASA Astrophysics Data System (ADS)

Shinohara, Takayuki; Bredberg, Göran; Ulfendahl, Mats; Pyykkö, Ilmari; Petri Olivius, N.; Kaksonen, Risto; Lindström, Bo; Altschuler, Richard; Miller, Josef M.

2002-02-01

A primary cause of deafness is damage of receptor cells in the inner ear. Clinically, it has been demonstrated that effective functionality can be provided by electrical stimulation of the auditory nerve, thus bypassing damaged receptor cells. However, subsequent to sensory cell loss there is a secondary degeneration of the afferent nerve fibers, resulting in reduced effectiveness of such cochlear prostheses. The effects of neurotrophic factors were tested in a guinea pig cochlear prosthesis model. After chemical deafening to mimic the clinical situation, the neurotrophic factors brain-derived neurotrophic factor and an analogue of ciliary neurotrophic factor were infused directly into the cochlea of the inner ear for 26 days by using an osmotic pump system. An electrode introduced into the cochlea was used to elicit auditory responses just as in patients implanted with cochlear prostheses. Intervention with brain-derived neurotrophic factor and the ciliary neurotrophic factor analogue not only increased the survival of auditory spiral ganglion neurons, but significantly enhanced the functional responsiveness of the auditory system as measured by using electrically evoked auditory brainstem responses. This demonstration that neurotrophin intervention enhances threshold sensitivity within the auditory system will have great clinical importance for the treatment of deaf patients with cochlear prostheses. The findings have direct implications for the enhancement of responsiveness in deafferented peripheral nerves.

A role for granulocyte-macrophage colony-stimulating factor in the regulation of CD8{sup +} T cell responses to rabies virus

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

Wanjalla, Celestine N.; Goldstein, Elizabeth F.; Wirblich, Christoph

2012-05-10

Inflammatory cytokines have a significant role in altering the innate and adaptive arms of immune responses. Here, we analyzed the effect of GM-CSF on a RABV-vaccine vector co-expressing HIV-1 Gag. To this end, we immunized mice with RABV expressing HIV-1 Gag and GM-CSF and analyzed the primary and recall CD8{sup +} T cell responses. We observed a statistically significant increase in antigen presenting cells (APCs) in the spleen and draining lymph nodes in response to GM-CSF. Despite the increase in APCs, the primary and memory anti HIV-1 CD8{sup +} T cell response was significantly lower. This was partly likely duemore » to lower levels of proliferation in the spleen. Animals treated with GM-CSF neutralizing antibodies restored the CD8{sup +} T cell response. These data define a role of GM-CSF expression, in the regulation of the CD8{sup +} T cell immune responses against RABV and has implications in the use of GM-CSF as a molecular adjuvant in vaccine development.« less

A prospective study of primary care patients with musculoskeletal pain: the identification of predictive factors for chronicity.

PubMed Central

Potter, R G; Jones, J M; Boardman, A P

2000-01-01

Primary care faces the challenge of reducing the proportion of patients continuing with musculoskeletal pain beyond the acute phase. This study assessed patients presenting in general practice with a four- to 12-week history of pain and re-assessed them 12 weeks later. Patients whose pain was described as 'none' or 'slight' were allocated to the 'acute group', and those whose pain continued to be 'moderate' or 'severe' were allocated to the 'chronic group'. Comparative analysis of the two groups' responses at initial assessment identified pain intensity, active coping score, and previous pain episode to be factors independently predictive of chronicity. PMID:10750237

Asymmetric cellular responses in primary human myoblasts using sera of different origin and specification

PubMed Central

Rullman, Eric; Lilja, Mats; Mandić, Mirko; Melin, Michael; Olsson, Karl; Gustafsson, Thomas

2018-01-01

For successful growth and maintenance of primary myogenic cells in vitro, culture medium and addition of sera are the most important factors. At present it is not established as to what extent sera of different origin and composition, supplemented in media or serum-free media conditions influence myoblast function and responses to different stimuli. By assessing markers of proliferation, differentiation/fusion, quiescence, apoptosis and protein synthesis the aim of the current study was to elucidate how primary human myoblasts and myotubes are modulated by different commonly used serum using FCS (foetal calf serum), (CS-FCS charcoal-stripped FCS, a manufacturing process to remove hormones and growth factors from sera), HS (horse serum) as well as in serum free conditions (DMEM). To characterise the biological impact of the different serum, myoblasts were stimulated with Insulin (100 nM) and Vitamin D (100 nM; 1α,25(OH)2D3, 1α,25-Dihydroxycholecalciferol, Calcitriol), two factors with characterised effects on promoting fusion and protein synthesis or quiescence, respectively in human myoblasts/myotubes. We demonstrate that sera of different origin/formulation differentially affect myoblast proliferation and myotube protein synthesis. Importantly, we showed that quantifying the extent to which Insulin effects myoblasts in vitro is highly dependent upon serum addition and which type is present in the media. Upregulation of mRNA markers for myogenic fusion, Myogenin, with Insulin stimulation, relative to DMEM, appeared dampened at varying degrees with serum addition and effects on p70S6K phosphorylation as a marker of protein synthesis could not be identified unless serum was removed from media. We propose that these asymmetric molecular and biochemical responses in human myoblasts reflect the variable composition of mitogenic and anabolic factors in each of the sera. The results have implications for both the reproducibility and interpretation of results from experimental models in myoblast cells/myotubes. PMID:29401478

Intravascular ATP and the regulation of blood flow and oxygen delivery in humans.

PubMed

Crecelius, Anne R; Kirby, Brett S; Dinenno, Frank A

2015-01-01

Regulation of vascular tone is a complex response that integrates multiple signals that allow for blood flow and oxygen supply to match oxygen demand appropriately. Here, we discuss the potential role of intravascular adenosine triphosphate (ATP) as a primary factor in these responses and put forth the hypothesis that deficient ATP release contributes to impairments in vascular control exhibited in aged and diseased populations.

A clinician's perspective on memory reconsolidation as the primary basis for psychotherapeutic change in posttraumatic stress disorder (PTSD).

PubMed

Kimbrel, Nathan A; Meyer, Eric C; Beckham, Jean C

2015-01-01

Lane et al.'s proposal that psychotherapeutic change comes about through memory reconsolidation is compelling; however, the model would be strengthened by the inclusion of predictions regarding additional factors that might influence treatment response, predictions for improving outcomes for non-responsive patients, and a discussion of how the proposed model might explain individual differences in vulnerability for mental health problems.

Exosomes in fetal bovine serum dampen primary macrophage IL-1β response to lipopolysaccharide (LPS) challenge.

PubMed

Beninson, Lida A; Fleshner, Monika

2015-02-01

This study identifies a previously unknown immunological function of exosomes present in fetal bovine serum (FBS). Exosomes are small (40-100 nm), biologically active nanoparticles released from cells that associate with a variety of proteins and miRNA. Exosomes are present in nearly all biological fluids, including FBS, a common supplement to cell culture media. While there are a growing number of studies examining cellular responses to exosomes, there is no assessment of how FBS exosomes impact cellular responses to immunological challenges. Our results demonstrate that primary macrophages from Fisher 344 rats cultured with lipopolysaccharide (LPS) in the presence of FBS exosomes exhibit a dose-dependent reduction in IL-1β compared to macrophages cultured in medium supplemented with exosome-depleted FBS. The addition of fetal bovine exosomes also reduced macrophage tumor necrosis factor-alpha (TNF-α) and IL-6, but not IL-10, monocyte chemotactic factor-1 (MCP-1), nitric oxide (NO), or lactose dehydrogenase (LDH) response to LPS. The selectivity of exosomal impact on macrophage IL-1β and pro-inflammatory protein responses may implicate the potential role of exosome-inflammasome interactions. These findings suggest that researchers should consider the immunological influence of FBS exosomes, particularly on IL-1β activity, when studying cells in culture. Copyright © 2015. Published by Elsevier B.V.

Leadership in primary health care: an international perspective.

PubMed

McMurray, Anne

2007-08-01

A primary health care approach is essential to contemporary nursing roles such as practice nursing. This paper examines the evolution of primary health care as a global strategy for responding to the social determinants of health. Primary health care roles require knowledge of, and a focus on social determinants of health, particularly the societal factors that allow and perpetuate inequities and disadvantage. They also require a depth and breadth of leadership skills that are responsive to health needs, appropriate in the social and regulatory context, and visionary in balancing both workforce and client needs. The key to succeeding in working with communities and groups under a primary health care umbrella is to balance the big picture of comprehensive primary health care with operational strategies for selective primary health care. The other essential element involves using leadership skills to promote inclusiveness, empowerment and health literacy, and ultimately, better health.

Sorting nexin 9 differentiates ligand-activated Smad3 from Smad2 for nuclear import and transforming growth factor β signaling

PubMed Central

Wilkes, Mark C.; Repellin, Claire E.; Kang, Jeong-Han; Andrianifahanana, Mahefatiana; Yin, Xueqian; Leof, Edward B.

2015-01-01

Transforming growth factor β (TGFβ) is a pleiotropic protein secreted from essentially all cell types and primary tissues. While TGFβ’s actions reflect the activity of a number of signaling networks, the primary mediator of TGFβ responses are the Smad proteins. Following receptor activation, these cytoplasmic proteins form hetero-oligomeric complexes that translocate to the nucleus and affect gene transcription. Here, through biological, biochemical, and immunofluorescence approaches, sorting nexin 9 (SNX9) is identified as being required for Smad3-dependent responses. SNX9 interacts with phosphorylated (p) Smad3 independent of Smad2 or Smad4 and promotes more rapid nuclear delivery than that observed independent of ligand. Although SNX9 does not bind nucleoporins Nup153 or Nup214 or some β importins (Imp7 or Impβ), it mediates the association of pSmad3 with Imp8 and the nuclear membrane. This facilitates nuclear translocation of pSmad3 but not SNX9. PMID:26337383

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.

[Effect of occupational stress on cardiovascular function of different vocational population].

PubMed

Yao, San-qiao; Fan, Xue-yun; Jin, Yu-lan; Bai, Yu-ping; Qu, Yin-e; Zhou, Yuan

2003-02-01

To study the effect of occupational stress on cardiovascular function of different vocational population. The occupational stressors, risk factors of cardiovascular diseases were investigated by questionnaire in 839 people with 4 kinds of jobs. Blood pressure, sugar, and lipid were detected at the same time. Blood pressure were higher in the groups of old age, long standing and teachers, and the abnormal rate of blood pressure was 21.69%. There was no difference in abnormal ECG among ages, standing and occupation, and the abnormal rate of ECG was 19.07%. Job control, job demands, job responsibility, role in a job and shift work were the main stress factors affecting systolic and diastolic blood pressure. More conflict in job, less chance of participation, severe job loads were the risk factors of primary hypertension. Accident due to job responsibility, job responsibility, role in a job were the main risk factors of abnormal electrocardiograph. Self-respect and activity beyond work were the good modifiers of heart function. Occupational stress has certain effect on cardiovascular function.

Prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy for locally advanced breast carcinoma.

PubMed

Machiavelli, M R; Romero, A O; Pérez, J E; Lacava, J A; Domínguez, M E; Rodríguez, R; Barbieri, M R; Romero Acuña, L A; Romero Acuña, J M; Langhi, M J; Amato, S; Ortiz, E H; Vallejo, C T; Leone, B A

1998-01-01

The prognostic significance of pathological response of primary tumor and metastatic axillary lymph nodes after neoadjuvant chemotherapy was assessed in patients with noninflammatory locally advanced breast carcinoma. Between January 1989 and April 1995, 148 consecutive patients with locally advanced breast carcinoma participated in the study. Of these, 140 fully evaluable patients (67, stage IIIA; 73, stage IIIB) were treated with three courses of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC), followed by modified radical mastectomy when technically feasible or definitive radiation therapy. The median age was 53 years (range, 26 to 75 years); 55% of patients were postmenopausal. Objective response was recorded in 99 of 140 patients (71%; 95% confidence interval, 63% to 79%). Complete response occurred in 11 patients (8%), and partial response occurred in 88 patients (63%). No change was recorded in 37 patients (26%), and progressive disease occurred in 4 patients (3%). One hundred and thirty-six patients underwent the planned surgery. Maximal pathological response of the primary tumor (in situ carcinoma or minimal microscopic residual tumor) was observed in 24 (18%); 112 patients (82%) presented minimal pathological response of the primary tumor (gross residual tumor). The number of metastatic axillary nodes after neoadjuvant chemotherapy was as follows: N0, 39 patients (29%); N1-N3, 35 patients (26%); > N3, 62 patients (45%). Considering the initial TNM status, 75% of the patients had decreases in tumor compartment after neoadjuvant chemotherapy. Also, 31% and 23% of patients with clinical N1 and N2, respectively, showed uninvolved axillary lymph nodes. A significant correlation was noted between pathological response of primary tumor and the number of metastatic axillary lymph nodes. Median disease-free survival was 34 months, whereas median overall survival was 66 months. Pathological responses of both primary tumor and metastatic axillary lymph nodes were strongly correlated with disease-free survival and overall survival in univariate analyses. Additionally, in a proportional hazard regression model and in an accelerated failure time model, metastatic axillary lymph nodes significantly influenced both disease-free survival and overall survival, whereas pathological response of primary tumor did so on disease-free survival only. After neoadjuvant chemotherapy, pathological responses of both primary tumor and metastatic axillary lymph nodes had a marked prognostic significance and influenced outcome for patients with locally advanced breast carcinoma. Our results suggest that maximal tumor shrinkage and sterilization of potentially involved axillary nodes may represent a major goal of neoadjuvant chemotherapy. Further studies are warranted to clarify whether these results reflect the therapeutic effect or intrinsic biologic factors of the tumor.

Characterization of primary standards for use in the HPLC analysis of the procyanidin content of cocoa and chocolate containing products.

PubMed

Hurst, William J; Stanley, Bruce; Glinski, Jan A; Davey, Matthew; Payne, Mark J; Stuart, David A

2009-10-15

This report describes the characterization of a series of commercially available procyanidin standards ranging from dimers DP = 2 to decamers DP = 10 for the determination of procyanidins from cocoa and chocolate. Using a combination of HPLC with fluorescence detection and MALDI-TOF mass spectrometry, the purity of each standard was determined and these data were used to determine relative response factors. These response factors were compared with other response factors obtained from published methods. Data comparing the procyanidin analysis of a commercially available US dark chocolate calculated using each of the calibration methods indicates divergent results and demonstrate that previous methods may significantly underreport the procyanidins in cocoa-containing products. These results have far reaching implications because the previous calibration methods have been used to develop data for a variety of scientific reports, including food databases and clinical studies.

Predictive factors and outcomes for ibrutinib therapy in relapsed/refractory mantle cell lymphoma-a "real world" study.

PubMed

Epperla, Narendranath; Hamadani, Mehdi; Cashen, Amanda F; Ahn, Kwang W; Oak, Eunhye; Kanate, Abraham S; Calzada, Oscar; Cohen, Jonathon B; Farmer, Luke; Ghosh, Nilanjan; Tallarico, Michael; Nabhan, Chadi; Costa, Luciano J; Kenkre, Vaishalee P; Hari, Parameswaran N; Fenske, Timothy S

2017-12-01

Ibrutinib has demonstrated significant activity in relapsed/refractory mantle cell lymphoma (MCL) in clinical trials. However, the impact of hematopoietic cell transplantation on the outcomes of ibrutinib and the predictive factors for ibrutinib response has not been well studied. Hence, we conducted a multicenter retrospective study of MCL patients who received ibrutinib to (1) determine the overall response rate (ORR), duration of response (DOR), progression-free survival (PFS), and overall survival (OS) of ibrutinib in routine clinical practice, (2) examine characteristics predictive of response to ibrutinib therapy, and (3) describe the outcomes of patients failing ibrutinib. Ninety-seven patients met the eligibility criteria. Overall response rate and median DOR to ibrutinib were 65% and 17 months, respectively. Only lack of primary refractory disease was predictive of ibrutinib response on multivariate analysis. Twenty-nine patients received postibrutinib therapies, with an ORR of 48% and a median DOR of 3 months. The median OS and PFS for the entire group (n = 97) was 22 and 15 months, respectively. On multivariate analysis, ibrutinib response, low MCL international prognostic index, and absence of primary refractory disease were predictors of better PFS, while ibrutinib response and Eastern Cooperative Oncology Group performance status ≤1 were predictors of better OS. The median OS postibrutinib failure was 2.5 months. Our results confirm the high ORR and DOR of ibrutinib in MCL and that prior hematopoietic cell transplantation does not negatively influence ibrutinib outcomes. Survival following ibrutinib failure is poor with no specific subsequent therapy showing superior activity in this setting. As a result, for select (transplant eligible) patients, allogeneic transplant should be strongly considered soon after ibrutinib response is documented to provide durable responses. Copyright © 2017 John Wiley & Sons, Ltd.

Neuromyelitis optica IgG stimulates an immunological response in rat astrocyte cultures.

PubMed

Howe, Charles L; Kaptzan, Tatiana; Magaña, Setty M; Ayers-Ringler, Jennifer R; LaFrance-Corey, Reghann G; Lucchinetti, Claudia F

2014-05-01

Neuromyelitis optica (NMO) is a primary astrocyte disease associated with central nervous system inflammation, demyelination, and tissue injury. Brain lesions are frequently observed in regions enriched in expression of the aquaporin-4 (AQP4) water channel, an antigenic target of the NMO IgG serologic marker. Based on observations of disease reversibility and careful characterization of NMO lesion development, we propose that the NMO IgG may induce a dynamic immunological response in astrocytes. Using primary rat astrocyte-enriched cultures and treatment with NMO patient-derived serum or purified IgG, we observed a robust pattern of gene expression changes consistent with the induction of a reactive and inflammatory phenotype in astrocytes. The reactive astrocyte factor lipocalin-2 and a broad spectrum of chemokines, cytokines, and stress response factors were induced by either NMO patient serum or purified IgG. Treatment with IgG from healthy controls had no effect. The effect is disease-specific, as serum from patients with relapsing-remitting multiple sclerosis, Sjögren's, or systemic lupus erythematosus did not induce a response in the cultures. We hypothesize that binding of the NMO IgG to AQP4 induces a cellular response that results in transcriptional and translational events within the astrocyte that are consistent with a reactive and inflammatory phenotype. Strategies aimed at reducing the inflammatory response of astrocytes may short circuit an amplification loop associated with NMO lesion development. Copyright © 2014 Wiley Periodicals, Inc.

Radiation Therapy for Primary Cutaneous Anaplastic Large Cell Lymphoma: An International Lymphoma Radiation Oncology Group Multi-institutional Experience

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

Million, Lynn, E-mail: lmillion@stanford.edu; Yi, Esther J.; Wu, Frank

Purpose: To collect response rates of primary cutaneous anaplastic large cell lymphoma, a rare cutaneous T-cell lymphoma, to radiation therapy (RT), and to determine potential prognostic factors predictive of outcome. Methods and Materials: The study was a retrospective analysis of patients with primary cutaneous anaplastic large cell lymphoma who received RT as primary therapy or after surgical excision. Data collected include initial stage of disease, RT modality (electron/photon), total dose, fractionation, response to treatment, and local recurrence. Radiation therapy was delivered at 8 participating International Lymphoma Radiation Oncology Group institutions worldwide. Results: Fifty-six patients met the eligibility criteria, and 63 tumorsmore » were treated: head and neck (27%), trunk (14%), upper extremities (27%), and lower extremities (32%). Median tumor size was 2.25 cm (range, 0.6-12 cm). T classification included T1, 40 patients (71%); T2, 12 patients (21%); and T3, 4 patients (7%). The median radiation dose was 35 Gy (range, 6-45 Gy). Complete clinical response (CCR) was achieved in 60 of 63 tumors (95%) and partial response in 3 tumors (5%). After CCR, 1 tumor recurred locally (1.7%) after 36 Gy and 7 months after RT. This was the only patient to die of disease. Conclusions: Primary cutaneous anaplastic large cell lymphoma is a rare, indolent cutaneous lymphoma with a low death rate. This analysis, which was restricted to patients selected for treatment with radiation, indicates that achieving CCR was independent of radiation dose. Because there were too few failures (<2%) for statistical analysis on dose response, 30 Gy seems to be adequate for local control, and even lower doses may suffice.« less

Characterization of low phosphorus insensitive Mutants Reveals a Crosstalk between Low Phosphorus-Induced Determinate Root Development and the Activation of Genes Involved in the Adaptation of Arabidopsis to Phosphorus Deficiency1

PubMed Central

Sánchez-Calderón, Lenin; López-Bucio, José; Chacón-López, Alejandra; Gutiérrez-Ortega, Abel; Hernández-Abreu, Esmeralda; Herrera-Estrella, Luis

2006-01-01

Low phosphorus (P) availability is one of the most limiting factors for plant productivity in many natural and agricultural ecosystems. Plants display a wide range of adaptive responses to cope with low P stress, which generally serve to enhance P availability in the soil and to increase its uptake by roots. In Arabidopsis (Arabidopsis thaliana), primary root growth inhibition and increased lateral root formation have been reported to occur in response to P limitation. To gain knowledge of the genetic mechanisms that regulate root architectural responses to P availability, we designed a screen for identifying Arabidopsis mutants that fail to arrest primary root growth when grown under low P conditions. Eleven low phosphorus insensitive (lpi) mutants that define at least four different complementation groups involved in primary root growth responses to P availability were identified. The lpi mutants do not show the typical determinate developmental program induced by P stress in the primary root. Other root developmental aspects of the low P rescue system, including increased root hair elongation and anthocyanin accumulation, remained unaltered in lpi mutants. In addition to the insensitivity of primary root growth inhibition, when subjected to P deprivation, lpi mutants show a reduced induction in the expression of several genes involved in the P starvation rescue system (PHOSPHATE TRANSPORTER 1 and 2, PURPLE ACID PHOSPHATASE 1, ACID PHOSPHATASE 5, and INDUCED BY PHOSPHATE STARVATION 1). Our results provide genetic support for the role of P as an important signal for postembryonic root development and root meristem maintenance and show a crosstalk in developmental and biochemical responses to P deprivation. PMID:16443695

Differential Activation of CD8+ Tumor-Specific Tc1 and Tc2 Cells by an IL-10-Producing Murine Plasmacytoma

PubMed Central

Pauels, Hans-Gerd; Becker, Christian; Kölsch, Eckehart

1998-01-01

The involvement of counteractive CD8+ T-cell subsets during tumor-specific immune responses was analyzed in a syngeneic murine plasmacytoma model. CD8+ Tc cells against the immunogenic IL-10-producing BALB/c plasmacytoma ADJ-PC-5 can be easily induced by immunization of BALB/c mice with X-irradiated ADJ-PC-5 tumor cells in vivo and in vitro. However, the failure of recipient mice to mount a protective Tc response against the tumor during early stages of a real or simulated tumor growth is not due to immunological ignorance, but depends on the induction of tumor-specific tolerance, involving a population of tumorinduced CD8+ T cells that are able to inhibit the generation of tumor-specific Tc cells in a primary ADJ-PC-5-specific MLTC, using IFN-γ as a suppressive factor. Whereas most longterm cultivated CD8+ ADJ-PC-5-specific Tc lines produce type-1 cytokines on stimulation, at least two of them, which were derived from a primary MLTC, display a type-2 cytokine spectrum. Furthermore, the primary in vitro Tc response against ADJ-PC-5 cells shows characteristics of a Tc2 response. The Tc response is strictly depending on tumor-derived IL-10. CD8+ Tc cells that are induced in a primary MLTC do not produce IFN-γ, and the tumor-specific Tc response is enhanced by IL-4 but suppressed by IFN-γ or IL-12. In contrast, ADJ-PC- 5-specific CD8+ Tc cells from immunized mice are IFN-γ producing Tc1 cells. Since the primary in vitro Tc response against the tumor is suppressed even by the smallest numbers of irradiated ADJ-PC-5-specific Tc1 cells via IFN-γ these Tc1 cells behave similar to the suppressive CD8+ T cells that are induced during early stages of ADJ-PC-5 tumorigenesis. PMID:9814607

Factors associated with the number of lesions excised for each skin cancer: a study of primary care physicians in Queensland, Australia.

PubMed

Baade, Peter D; Youl, Philippa H; Janda, Monika; Whiteman, David C; Del Mar, Christopher B; Aitken, Joanne F

2008-11-01

To assess physician, patient, and skin lesion characteristics that affect the number of benign skin lesions excised by primary care physicians for each skin cancer. Prospective study collecting clinical, patient, and histopathologic details of excisions or biopsies of skin lesions by random samples of primary care physicians. Southeast Queensland involving traditional family medicine physicians (n = 104; response rate, 53.9%) and family medicine physicians working in 27 primary care skin cancer clinics (n = 50; response rate, 75.0%). Of 28 755 skin examinations recorded during the study, 11 403 skin lesions were excised or biopsied; 97.5% of the excised lesions had clinical and histologic diagnoses recorded. Number of lesions needed to excise or biopsy (NNE) for 1 melanoma (pigmented lesions only) and NNE for 1 nonmelanoma skin cancer (nonpigmented lesions only). The NNE for nonpigmented lesions (n = 8139) was 1.5 (95% confidence interval, 1.4-1.6) and for pigmented lesions (n = 2977) was 19.6 (16.2-22.9). The NNE estimates were up to 8 times lower if the physician thought the lesion was likely to be malignant and up to 2.5 times higher if there was strong patient pressure to excise. The NNE estimates varied by other physician-, patient-, and lesion-related variables. Clinical impressions of excised skin lesions were strongly associated with NNE estimates. By focusing on pigmented skin lesions and by addressing the physician- and patient-specific factors identified, the effectiveness of future training for primary care physicians in the clinical management of skin cancer could be improved.

Current practice of preconception care by primary caregivers in the Netherlands.

PubMed

van Voorst, Sabine; Plasschaert, Sophie; de Jong-Potjer, Lieke; Steegers, Eric; Denktaş, Semiha

2016-06-01

Over the past decade the value of preconception care (PCC) consultations has been acknowledged. Investments have been made to promote delivery and uptake of PCC consultations in the Dutch primary care setting. We assessed current activities, perceptions and prerequisites for delivery of PCC in primary care. A questionnaire was compiled and distributed by mail or e-mail among 1682 general practitioners (GPs) and 746 midwives in the Netherlands between 2013 and 2014. The questionnaire was completed by 449 GPs and 250 midwives. While GPs and midwives were frequently asked about preconception risks, explicit requests by patients for a PCC consultation were less frequent. Although caregivers gave information on preconception risk factors, only a minority recommended PCC in the form of a dedicated consultation. Such consultations occurred infrequently. Risk factor assessment varied between GPs and midwives. Respondents' perceptions of PCC consultations, however, were generally positive. A small proportion believed that PCC medicalised pregnancy, and recognised barriers in actively raising the topic of patients' pregnancy wishes. More training, staff, promotion of PCC and adequate reimbursement were prerequisites for future delivery. GPs differed in their opinion of whether they or midwives were primarily responsible for PCC consultations. Midwives, however, saw themselves as responsible for providing PCC consultations. Primary care is underserving prospective parents with regards to PCC consultations. Targets to increase delivery of systematic PCC are: (1) promotion during routine care; (2) increased use of tools; (3) increased collaboration among primary caregivers; (4) reduction of caregivers' negative perceptions; and (5) tailoring PCC consultations to suit women's preferences.

Degraded Auditory Processing in a Rat Model of Autism Limits the Speech Representation in Non-primary Auditory Cortex

PubMed Central

Engineer, C.T.; Centanni, T.M.; Im, K.W.; Borland, M.S.; Moreno, N.A.; Carraway, R.S.; Wilson, L.G.; Kilgard, M.P.

2014-01-01

Although individuals with autism are known to have significant communication problems, the cellular mechanisms responsible for impaired communication are poorly understood. Valproic acid (VPA) is an anticonvulsant that is a known risk factor for autism in prenatally exposed children. Prenatal VPA exposure in rats causes numerous neural and behavioral abnormalities that mimic autism. We predicted that VPA exposure may lead to auditory processing impairments which may contribute to the deficits in communication observed in individuals with autism. In this study, we document auditory cortex responses in rats prenatally exposed to VPA. We recorded local field potentials and multiunit responses to speech sounds in primary auditory cortex, anterior auditory field, ventral auditory field. and posterior auditory field in VPA exposed and control rats. Prenatal VPA exposure severely degrades the precise spatiotemporal patterns evoked by speech sounds in secondary, but not primary auditory cortex. This result parallels findings in humans and suggests that secondary auditory fields may be more sensitive to environmental disturbances and may provide insight into possible mechanisms related to auditory deficits in individuals with autism. PMID:24639033

Long-term maintenance of luteinizing hormone-responsive testosterone formation by primary rat Leydig cells in vitro.

PubMed

Wang, Yiyan; Huang, Shengsong; Wang, Zhao; Chen, Fenfen; Chen, Panpan; Zhao, Xingxing; Lin, Han; Ge, Renshan; Zirkin, Barry; Chen, Haolin

2018-04-24

The inability of cultured primary Leydig cells to maintain luteinizing hormone (LH)-responsive testosterone formation in vitro for more than 3-5 days has presented a major challenge in testing trophic effects of regulatory factors or environmental toxicants. Our primary objective was to establish culture conditions sufficient to maintain LH-responsive testosterone formation by Leydig cells for at least a month. When isolated rat adult Leydig cells were cultured in DMEM/F12 and M199 culture medium containing insulin (10μg/ml), PDGFAA (10 ng/ml), lipoprotein (0.25 mg/ml), horse serum (1%) and a submaximal concentration of LH (0.2 ng/ml), the cells retained the ability to produce testosterone in vitro for at least 4 weeks. By using the longer-term culture conditions of this system, we were able to detect suppressive effects on testosterone production by low levels of the toxicant MEHP (mono-(2-ethylhexyl) phthalate), an active metabolite of the plasticizer DEHP, that were not detected by short-term culture. Copyright © 2018 Elsevier B.V. All rights reserved.

Developing a programme theory to explain how primary health care teams learn to respond to intimate partner violence: a realist case-study.

PubMed

Goicolea, Isabel; Hurtig, Anna-Karin; San Sebastian, Miguel; Vives-Cases, Carmen; Marchal, Bruno

2015-06-09

Despite the progress made on policies and programmes to strengthen primary health care teams' response to Intimate Partner Violence, the literature shows that encounters between women exposed to IPV and health-care providers are not always satisfactory, and a number of barriers that prevent individual health-care providers from responding to IPV have been identified. We carried out a realist case study, for which we developed and tested a programme theory that seeks to explain how, why and under which circumstances a primary health care team in Spain learned to respond to IPV. A realist case study design was chosen to allow for an in-depth exploration of the linkages between context, intervention, mechanisms and outcomes as they happen in their natural setting. The first author collected data at the primary health care center La Virgen (pseudonym) through the review of documents, observation and interviews with health systems' managers, team members, women patients, and members of external services. The quality of the IPV case management was assessed with the PREMIS tool. This study found that the health care team at La Virgen has managed 1) to engage a number of staff members in actively responding to IPV, 2) to establish good coordination, mutual support and continuous learning processes related to IPV, 3) to establish adequate internal referrals within La Virgen, and 4) to establish good coordination and referral systems with other services. Team and individual level factors have triggered the capacity and interest in creating spaces for team leaning, team work and therapeutic responses to IPV in La Virgen, although individual motivation strongly affected this mechanism. Regional interventions did not trigger individual and/ or team responses but legitimated the workings of motivated professionals. The primary health care team of La Virgen is involved in a continuous learning process, even as participation in the process varies between professionals. This process has been supported, but not caused, by a favourable policy for integration of a health care response to IPV. Specific contextual factors of La Virgen facilitated the uptake of the policy. To some extent, the performance of La Virgen has the potential to shape the IPV learning processes of other primary health care teams in Murcia.

5 CFR 950.104 - Local Federal Coordinating Committee responsibilities.

Code of Federal Regulations, 2010 CFR

2010-01-01

.... CFC loaned executives' time should be charged to regular working hours. It is not appropriate to place... not use the services of consulting firms, advertising firms or similar business organizations to... accuracy in solicitations, and sound governance and fiscal management practices as the primary factors in...

5 CFR 950.104 - Local Federal Coordinating Committee responsibilities.

Code of Federal Regulations, 2011 CFR

2011-01-01

.... CFC loaned executives' time should be charged to regular working hours. It is not appropriate to place... not use the services of consulting firms, advertising firms or similar business organizations to... accuracy in solicitations, and sound governance and fiscal management practices as the primary factors in...

Evidence for xylem embolism as a primary factor in dehydration-induced declines in leaf hydraulic conductance

Treesearch

Daniel M. Johnson; Katherine A. McCulloh; David R. Woodruff; Frederick C. Meinzer

2012-01-01

Hydraulic conductance of leaves (Kleaf) typically decreases with increasing water stress and recent studies have proposed different mechanisms responsible for decreasing Kleaf. We measured Kleaf concurrently with ultrasonic acoustic emissions (UAEs) in dehydrating leaves of several species to...

A New Paradigm: Moving toward Comprehensive Services.

ERIC Educational Resources Information Center

Illinois Initiative for Comprehensive Children and Family Services.

In order to better serve Illinois individuals and schools, human service organizations must pursue collaboration among and within state agencies, community organizations and resources, and families. Families have the primary responsibility for raising their children, but economic and social factors make it increasingly harder for families to do…

Hepatic TRAF2 Regulates Glucose Metabolism Through Enhancing Glucagon Responses

PubMed Central

Chen, Zheng; Sheng, Liang; Shen, Hong; Zhao, Yujun; Wang, Shaomeng; Brink, Robert; Rui, Liangyou

2012-01-01

Obesity is associated with intrahepatic inflammation that promotes insulin resistance and type 2 diabetes. Tumor necrosis factor receptor–associated factor (TRAF)2 is a key adaptor molecule that is known to mediate proinflammatory cytokine signaling in immune cells; however, its metabolic function remains unclear. We examined the role of hepatic TRAF2 in the regulation of insulin sensitivity and glucose metabolism. TRAF2 was deleted specifically in hepatocytes using the Cre/loxP system. The mutant mice were fed a high-fat diet (HFD) to induce insulin resistance and hyperglycemia. Hepatic glucose production (HGP) was examined using pyruvate tolerance tests, 2H nuclear magnetic resonance spectroscopy, and in vitro HGP assays. The expression of gluconeogenic genes was measured by quantitative real-time PCR. Insulin sensitivity was analyzed using insulin tolerance tests and insulin-stimulated phosphorylation of insulin receptors and Akt. Glucagon action was examined using glucagon tolerance tests and glucagon-stimulated HGP, cAMP-responsive element–binding (CREB) phosphorylation, and expression of gluconeogenic genes in the liver and primary hepatocytes. Hepatocyte-specific TRAF2 knockout (HKO) mice exhibited normal body weight, blood glucose levels, and insulin sensitivity. Under HFD conditions, blood glucose levels were significantly lower (by >30%) in HKO than in control mice. Both insulin signaling and the hypoglycemic response to insulin were similar between HKO and control mice. In contrast, glucagon signaling and the hyperglycemic response to glucagon were severely impaired in HKO mice. In addition, TRAF2 overexpression significantly increased the ability of glucagon or a cAMP analog to stimulate CREB phosphorylation, gluconeogenic gene expression, and HGP in primary hepatocytes. These results suggest that the hepatic TRAF2 cell autonomously promotes hepatic gluconeogenesis by enhancing the hyperglycemic response to glucagon and other factors that increase cAMP levels, thus contributing to hyperglycemia in obesity. PMID:22315325

An overview of transcriptional regulation in response to toxicological insult.

PubMed

Jennings, Paul; Limonciel, Alice; Felice, Luca; Leonard, Martin O

2013-01-01

The completion of the human genome project and the subsequent advent of DNA microarray and high-throughput sequencing technologies have led to a renaissance in molecular toxicology. Toxicogenomic data sets, from both in vivo and in vitro studies, are growing exponentially, providing a wealth of information on regulation of stress pathways at the transcriptome level. Through such studies, we are now beginning to appreciate the diversity and complexity of biological responses to xenobiotics. In this review, we aim to consolidate and summarise the major toxicologically relevant transcription factor-governed molecular pathways. It is becoming clear that different chemical entities can cause oxidative, genotoxic and proteotoxic stress, which induce cellular responses in an effort to restore homoeostasis. Primary among the response pathways involved are NFE2L2 (Nrf2), NFE2L1 (Nrf1), p53, heat shock factor and the unfolded protein response. Additionally, more specific mechanisms exist where xenobiotics act as ligands, including the aryl hydrocarbon receptor, metal-responsive transcription factor-1 and the nuclear receptor family of transcription factors. Other pathways including the immunomodulatory transcription factors NF-κB and STAT together with the hypoxia-inducible transcription factor HIF are also implicated in cellular responses to xenobiotic exposure. A less specific but equally important aspect to cellular injury controlled by transcriptional activity is loss of tissue-specific gene expression, resulting in dedifferentiation of target cells and compromise of tissue function. Here, we review these pathways and the genes they regulate in order to provide an overview of this growing field of molecular toxicology.

Psychological Factors and Conditioned Pain Modulation: A Meta-Analysis.

PubMed

Nahman-Averbuch, Hadas; Nir, Rony-Reuven; Sprecher, Elliot; Yarnitsky, David

2016-06-01

Conditioned pain modulation (CPM) responses may be affected by psychological factors such as anxiety, depression, and pain catastrophizing; however, most studies on CPM do not address these relations as their primary outcome. The aim of this meta-analysis was to analyze the findings regarding the associations between CPM responses and psychological factors in both pain-free individuals and pain patients. After a comprehensive PubMed search, 37 articles were found to be suitable for inclusion. Analyses used DerSimonian and Laird's random-effects model on Fisher's z-transforms of correlations; potential publication bias was tested using funnel plots and Egger's regression test for funnel plot asymmetry. Six meta-analyses were performed examining the correlations between anxiety, depression, and pain catastrophizing, and CPM responses in healthy individuals and pain patients. No significant correlations between CPM responses and any of the examined psychological factors were found. However, a secondary analysis, comparing modality-specific CPM responses and psychological factors in healthy individuals, revealed the following: (1) pressure-based CPM responses were correlated with anxiety (grand mean correlation in original units r=-0.1087; 95% confidence limits, -0.1752 to -0.0411); (2) heat-based CPM was correlated with depression (r=0.2443; 95% confidence limits, 0.0150 to 0.4492); and (3) electrical-based CPM was correlated with pain catastrophizing levels (r=-0.1501; 95% confidence limits, -0.2403 to -0.0574). Certain psychological factors seem to be associated with modality-specific CPM responses in healthy individuals. This potentially supports the notion that CPM paradigms evoked by different stimulation modalities represent different underlying mechanisms.

Comparison of the number of supervisors on medical student satisfaction during a child and adolescent psychiatry rotation.

PubMed

Mascioli, Kelly J; Robertson, Catharine J; Douglass, Alan B

2016-01-01

Traditionally, third-year medical students are assigned to one supervisor during their 1-week rotation in child and adolescent psychiatry. However, the majority of supervisory staff in the Division of Child and Adolescent Psychiatry opted to switch the supervision schedule to one in which some medical students are assigned to two primary supervisors. The aim of the study was to determine if students assigned to two primary supervisors had greater rotation satisfaction compared with students assigned to one primary supervisor during a 1-week clerkship rotation in child and adolescent psychiatry. A satisfaction questionnaire was sent to 110 third-year medical students who completed their child and adolescent clerkship rotation. Based on the responses, students were divided into groups depending on their number of supervisors. Questionnaire responses were compared between the groups using independent t-tests. When students who had one primary supervisor were compared to students who had two primary supervisors, the lone item showing a statistically significant difference was regarding improvement of assessment reports/progress notes. The number of supervisors does not significantly affect the satisfaction of students during a 1-week clerkship rotation in child and adolescent psychiatry. Other factors are important in rotation satisfaction.

CD70-deficiency impairs effector CD8 T cell generation and viral clearance but is dispensable for the recall response to LCMV

PubMed Central

Munitic, Ivana; Kuka, Mirela; Allam, Atef; Scoville, Jonathan P.; Ashwell, Jonathan D.

2012-01-01

CD27 interactions with its ligand, CD70, are thought to be necessary for optimal primary and memory adaptive immune responses to a variety of pathogens. Thus far all studies addressing the function of the CD27-CD70 axis have been performed either in mice lacking CD27, overexpressing CD70, or in which these receptors were blocked or mimicked by antibodies or recombinant soluble CD70. Because these methods have in some cases led to divergent results, we generated CD70-deficient mice to directly assess its role in vivo. We find that lack of CD70-mediated stimulation during primary responses to LCMV lowered the magnitude of CD8 antigen-specific T cell response, resulting in impaired viral clearance, without affecting CD4 T cell responses. Unexpectedly, CD70-CD27 costimulation was not needed for memory CD8 T cell generation or the ability to mount a recall response to LCMV. Adoptive transfers of wild type (WT) memory T cells into CD70−/− or WT hosts also showed no need for CD70-mediated stimulation during the course of the recall response. Moreover, CD70-expression by CD8 T cells could not rescue endogenous CD70−/− cells from defective expansion, arguing against a role for CD70-mediated T:T help in this model. Therefore, CD70 appears to be an important factor in the initiation of a robust and effective primary response but dispensable for CD8 T cell memory responses. PMID:23269247

Job Stressors, Personality and Burnout in Primary School Teachers

ERIC Educational Resources Information Center

Kokkinos, Constantinos M.

2007-01-01

Background: Teaching is considered a highly stressful occupation. Burnout is a negative affective response occurring as a result of chronic work stress. While the early theories of burnout focused exclusively on work-related stressors, recent research adopts a more integrative approach where both environmental and individual factors are studied.…

Response of the ascorbate-glutathione cycle to storage temperature in carambola fruit

USDA-ARS?s Scientific Manuscript database

The generation of reactive oxygen species (ROS) is considered to be a primary event under a variety of stress conditions. It has been generally accepted that reactive oxygen produced under stress is a detrimental factor, which causes lipid peroxidation, enzyme inactivation, and oxidative damage to D...

EFFECT OF AROCLOR 1254 ON THE TRANSCRIPTION FACTOR CREB AND CELL VIABILITY IN A PRIMARY CULTURE OF IMMATURE CORTICAL CELLS.

EPA Science Inventory

Considerable work indicates that elevations in Ca2+ levels and kinase activity are sensitive responses to polychlorinated biphenyls (PCBs), which are developmental neurotoxicants. In cortical cells in vitro the PCB mixture Aroclor 1254 (A1254) induces temporally and mechanistica...

Effect of blueberries and insulin on glucose induced neurotoxicity in brain cells in vitro

USDA-ARS?s Scientific Manuscript database

Introduction Literature had shown that disruption in glucose metabolism seen in metabolic syndrome maybe responsible for neuronal cell-death. Oxidative stress (OS) and inflammation (INF) triggered by the impaired metabolic process are considered to be the primary factors for the toxic neuronal atmos...

Oak Decline

Treesearch

Vernon Ammon; T. Evan Nebeker; Ted H. Filer; Francis I. McCracken; J. D. Solomon; H. E. Kennedy

1989-01-01

Occurrence of decline and mortality in this nation's hardwood forests has been documented in reports for the past 130 years. From 1856 through 1981, more than 26 decline events were reported from eight eastern states affecting almost all species of oaks. Fourteen factors have been implicated as either primary or secondary agents responsible for decline and...

Measurements of intracellular calcium signals in polarized primary cultures of normal and cystic fibrosis human airway epithelia.

PubMed

Ribeiro, Carla M P

2011-01-01

The airways are continuously challenged by a variety of stimuli including bacteria, viruses, allergens, and inflammatory factors that act as agonists for G protein-coupled receptors (GPCR). Intracellular calcium (Ca(2+) (i)) mobilization in airway epithelia in response to extracellular stimuli regulates key airway innate defense functions, e.g., Ca(2+)-activated Cl(-) secretion, ciliary beating, mucin secretion, and inflammatory responses. Because Ca(2+) (i) mobilization in response to luminal stimuli is larger in CF vs. normal human airway epithelia, alterations in Ca(2+) (i) signals have been associated with the pathogenesis of CF airway disease. Hence, assessment of Ca(2+) (i) signaling has become an important area of CF research. This chapter will focus on measurements of cytoplasmic and mitochondrial Ca(2+) signals resulting from GPCR activation in polarized primary cultures of normal and CF human bronchial epithelia (HBE).

Transcriptional regulation of PIN genes by FOUR LIPS and MYB88 during Arabidopsis root gravitropism.

PubMed

Wang, Hong-Zhe; Yang, Ke-Zhen; Zou, Jun-Jie; Zhu, Ling-Ling; Xie, Zi Dian; Morita, Miyo Terao; Tasaka, Masao; Friml, Jiří; Grotewold, Erich; Beeckman, Tom; Vanneste, Steffen; Sack, Fred; Le, Jie

2015-11-18

PIN proteins are auxin export carriers that direct intercellular auxin flow and in turn regulate many aspects of plant growth and development including responses to environmental changes. The Arabidopsis R2R3-MYB transcription factor FOUR LIPS (FLP) and its paralogue MYB88 regulate terminal divisions during stomatal development, as well as female reproductive development and stress responses. Here we show that FLP and MYB88 act redundantly but differentially in regulating the transcription of PIN3 and PIN7 in gravity-sensing cells of primary and lateral roots. On the one hand, FLP is involved in responses to gravity stimulation in primary roots, whereas on the other, FLP and MYB88 function complementarily in establishing the gravitropic set-point angles of lateral roots. Our results support a model in which FLP and MYB88 expression specifically determines the temporal-spatial patterns of PIN3 and PIN7 transcription that are closely associated with their preferential functions during root responses to gravity.

Direct calibration of a reference standard against the air kerma strength primary standard, at 192Ir HDR energy.

PubMed

Rajan, K N Govinda; Selvam, T Palani; Bhatt, B C; Vijayam, M; Patki, V S; Vinatha; Pendse, A M; Kannan, V

2002-04-07

The primary standard of low air kerma rate sources or beams, maintained at the Radiological Standards Laboratory (RSL) of the Bhabha Atomic Research Centre (BARC), is a 60 cm3 spherical graphite ionization chamber. A 192Ir HDR source was standardized at the hospital site in units of air kerma strength (AKS) using this primary standard. A 400 cm3 bakelite chamber, functioning as a reference standard at the RSL for a long period, at low air kerma rates (compared to external beam dose rates), was calibrated against the primary standard. It was seen that the primary standard and the reference standard, both being of low Z, showed roughly the same scatter response and yielded the same calibration factor for the 400 cm3 reference chamber, with or without room scatter. However, any likelihood of change in the reference chamber calibration factor would necessitate the re-transport of the primary standard to the hospital site for re-calibration. Frequent transport of the primary standard can affect the long-term stability of the primary standard, due to its movement or other extraneous causes. The calibration of the reference standard against the primary standard at the RSL, for an industrial type 192Ir source maintained at the laboratory, showed excellent agreement with the hospital calibration, making it possible to check the reference chamber calibration at RSL itself. Further calibration procedures have been developed to offer traceable calibration of the hospital well ionization chambers.

Colorectal cancer screening practices of primary care providers: results of a national survey in Malaysia.

PubMed

Norwati, Daud; Harmy, Mohamed Yusoff; Norhayati, Mohd Noor; Amry, Abdul Rahim

2014-01-01

The incidence of colorectal cancer has been increasing in many Asian countries including Malaysia during the past few decades. A physician recommendation has been shown to be a major factor that motivates patients to undergo screening. The present study objectives were to describe the practice of colorectal cancer screening by primary care providers in Malaysia and to determine the barriers for not following recommendations. In this cross sectional study involving 132 primary care providers from 44 Primary Care clinics in West Malaysia, self-administered questionnaires which consisted of demographic data, qualification, background on the primary care clinic, practices on colorectal cancer screening and barriers to colorectal cancer screening were distributed. A total of 116 primary care providers responded making a response rate of 87.9%. About 21% recommended faecal occult blood test (FOBT) in more than 50% of their patients who were eligible. The most common barrier was "unavailability of the test". The two most common patient factors are "patient in a hurry" and "poor patient awareness". This study indicates that colorectal cancer preventive activities among primary care providers are still poor in Malaysia. This may be related to the low availability of the test in the primary care setting and poor awareness and understanding of the importance of colorectal cancer screening among patients. More awareness programmes are required for the public. In addition, primary care providers should be kept abreast with the latest recommendations and policy makers need to improve colorectal cancer screening services in health clinics.

Patient safety in primary care: a survey of general practitioners in The Netherlands.

PubMed

Gaal, Sander; Verstappen, Wim; Wensing, Michel

2010-01-21

Primary care encompasses many different clinical domains and patient groups, which means that patient safety in primary care may be equally broad. Previous research on safety in primary care has focused on medication safety and incident reporting. In this study, the views of general practitioners (GPs) on patient safety were examined. A web-based survey of a sample of GPs was undertaken. The items were derived from aspects of patient safety issues identified in a prior interview study. The questionnaire used 10 clinical cases and 15 potential risk factors to explore GPs' views on patient safety. A total of 68 GPs responded (51.5% response rate). None of the clinical cases was uniformly judged as particularly safe or unsafe by the GPs. Cases judged to be unsafe by a majority of the GPs concerned either the maintenance of medical records or prescription and monitoring of medication. Cases which only a few GPs judged as unsafe concerned hygiene, the diagnostic process, prevention and communication. The risk factors most frequently judged to constitute a threat to patient safety were a poor doctor-patient relationship, insufficient continuing education on the part of the GP and a patient age over 75 years. Language barriers and polypharmacy also scored high. Deviation from evidence-based guidelines and patient privacy in the reception/waiting room were not perceived as risk factors by most of the GPs. The views of GPs on safety and risk in primary care did not completely match those presented in published papers and policy documents. The GPs in the present study judged a broader range of factors than in previously published research on patient safety in primary care, including a poor doctor-patient relationship, to pose a potential threat to patient safety. Other risk factors such as infection prevention, deviation from guidelines and incident reporting were judged to be less relevant than by policy makers.

Primary health care reform, dilemmatic space and risk of burnout among health workers.

PubMed

Freeman, Toby; Baum, Fran; Labonté, Ronald; Javanparast, Sara; Lawless, Angela

2018-05-01

Health system changes may increase primary health care workers' dilemmatic space, created when reforms contravene professional values. Dilemmatic space may be a risk factor for burnout. This study partnered with six Australian primary health care services (in South Australia: four state government-managed services including one Aboriginal health team and one non-government organisation and in Northern Territory: one Aboriginal community-controlled service) during a period of change and examined workers' dilemmatic space and incidence of burnout. Dilemmatic space and burnout were assessed in a survey of 130 staff across the six services (58% response rate). Additionally, 63 interviews were conducted with practitioners, managers, regional executives and health department staff. Dilemmatic space occurred across all services and was associated with higher rates of self-reported burnout. Three conditions associated with dilemmatic space were (1) conditions inherent in comprehensive primary health care, (2) stemming from service provision for Aboriginal and Torres Strait Islander peoples and (3) changes wrought by reorientation to selective primary health care in South Australia. Responses to dilemmatic space included ignoring directives or doing work 'under the radar', undertaking alternative work congruent with primary health care values outside of hours, or leaving the organisation. The findings show that comprehensive primary health care was contested and political. Future health reform processes would benefit from considering alignment of changes with staff values to reduce negative effects of the reform and safeguard worker wellbeing.

North Atlantic right whales (Eubalaena glacialis) ignore ships but respond to alerting stimuli.

PubMed Central

Nowacek, Douglas P.; Johnson, Mark P.; Tyack, Peter L.

2004-01-01

North Atlantic right whales were extensively hunted during the whaling era and have not recovered. One of the primary factors inhibiting their recovery is anthropogenic mortality caused by ship strikes. To assess risk factors involved in ship strikes, we used a multi-sensor acoustic recording tag to measure the responses of whales to passing ships and experimentally tested their responses to controlled sound exposures, which included recordings of ship noise, the social sounds of conspecifics and a signal designed to alert the whales. The whales reacted strongly to the alert signal, they reacted mildly to the social sounds of conspecifics, but they showed no such responses to the sounds of approaching vessels as well as actual vessels. Whales responded to the alert by swimming strongly to the surface, a response likely to increase rather than decrease the risk of collision. PMID:15058431

Laparoscopic evaluation of female factors in infertility.

PubMed

Aziz, Nousheen

2010-10-01

To find out different causes of female infertility with diagnostic laparoscopy and their comparative frequency in primary and secondary infertility. A case series. Department of Obstetric and Gynaecology, Liaquat University Hospital (LUH), Hyderabad, rom January 2006 to December 2007. All infertile women underwent diagnostic laparoscopy for primary and secondary infertility during the study period were included. Couples who had not lived together for at least 12 months, and those with male factor infertility were excluded. Data were collected on a proforma, and analysed on SPSS package for windows version 10. Frequencies were calculated for laparoscopic findings regarding primary and secondary infertility. Fifty infertile women underwent laparoscopy during the study period, 32 (64%) had primary infertility while 18 (36%) secondary infertility. Eight (25.0%) patients with primary and 2 (11.1%) patients with secondary infertility had no visible abnormality. The common finding was tubal blockage in 7 (21.9%) and 6 (33.3%) cases of primary and secondary infertility respectively. Five (15.6%) cases of primary infertility were detected as polycystic ovaries (PCO) which was not found in cases of secondary infertility. Endometriosis was found in 4 (12.5%) cases with primary infertility and 2 (11.1%) cases with secondary infertility. Pelvic inflammatory disease (PID) was found in 1 (3.1%) and 2 (16.7%) cases of primary and secondary infertility respectively. Peritubal and periovarian adhesions were detected in 2 (6.3%) cases with primary infertility and 4 (22.2%) cases with secondary infertility. Fibriod was found in 2 (6.3%) and 1 (5.6%) cases of primary and secondary infertility respectively. Ovarian cyst detected in 2 (6.3%) cases with primary infertility while none was found in cases of secondary infertility. Most common causes responsible for infertility were tubal occlusion, endometriosis, peritubal and periovarian adhesions. Ovarian causes were seen in primary infertility only.

MECHANISMS OF HYPNOSIS:

PubMed Central

Jensen, Mark P.; Adachi, Tomonori; Tomé-Pires, Catarina; Lee, Jikwan; Osman, Zubaidah Jamil; Miró, Jordi

2014-01-01

Evidence supports the efficacy of hypnotic treatments, but there remain many unresolved questions regarding how hypnosis produces its beneficial effects. Most theoretical models focus more or less on biological, psychological, and social factors. This scoping review summarizes the empirical findings regarding the associations between specific factors in each of these domains and response to hypnosis. The findings indicate that: (1) no single factor appears primary; (2) different factors may contribute more or less to outcomes in different subsets of individuals or for different conditions; and (3) comprehensive models of hypnosis that incorporate factors from all 3 domains may ultimately prove to be more useful than more restrictive models that focus on 1 or a very few factors. PMID:25365127

A three dimensional in vitro glial scar model to investigate the local strain effects from micromotion around neural implants.

PubMed

Spencer, Kevin C; Sy, Jay C; Falcón-Banchs, Roberto; Cima, Michael J

2017-02-28

Glial scar formation remains a significant barrier to the long term success of neural probes. Micromotion coupled with mechanical mismatch between the probe and tissue is believed to be a key driver of the inflammatory response. In vitro glial scar models present an intermediate step prior to conventional in vivo histology experiments as they enable cell-device interactions to be tested on a shorter timescale, with the ability to conduct broader biochemical assays. No established in vitro models have incorporated methods to assess device performance with respect to mechanical factors. In this study, we describe an in vitro glial scar model that combines high-precision linear actuators to simulate axial micromotion around neural implants with a 3D primary neural cell culture in a collagen gel. Strain field measurements were conducted to visualize the local displacement within the gel in response to micromotion. Primary brain cell cultures were found to be mechanically responsive to micromotion after one week in culture. Astrocytes, as determined by immunohistochemical staining, were found to have significantly increased in cell areas and perimeters in response to micromotion compared to static control wells. These results demonstrate the importance of micromotion when considering the chronic response to neural implants. Going forward, this model provides advantages over existing in vitro models as it will enable critical mechanical design factors of neural implants to be evaluated prior to in vivo testing.

Behaviors Influencing Human Immunodeficiency Virus Transmission in the Context of Positive Prevention among People Living with HIV/Acquired Immunodeficiency Syndrome in Iran: A Qualitative Study.

PubMed

Radfar, Seyed Ramin; Sedaghat, Abbas; Banihashemi, Arash Tehrani; Gouya, Mohammadmehdi; Rawson, Richard A

2014-08-01

Identifying factors, which influence health behaviors is critical to designing appropriate and effective preventive programs. Human immunodeficiency virus (HIV) transmission is highly related to people behaviors and understanding factors influencing healthy behaviors among Iranian people living with HIVs (PLHIVs)/acquired immunodeficiency syndrome (AIDS) is very important to tailor an effective response to HIV/AIDS epidemic. This study was conducted as a qualitative study by methods of focus group discussion and in-depth interview in six provinces of Iran with 64 PLHIVs to determine factors influence engagement in positive prevention. Knowledge and education, feelings of responsibility and positive prevention practices were identified as the primary domains of engagement. These domains were found to be influenced by feelings of ostracism and frustration, poverty, barriers to disclosure of HIV status, access to and utilization of drug abuse treatment services and antiretroviral therapy, adherence to treatment, age, religiousness, sex work, singleness, and incarceration. Designing new interventions and updating current interventions directed toward the aforementioned factors should be addressed by responsible Iranian authorities in order to have a national effective response on the HIV/AIDS epidemic.

Parallel studies of His-DTrp-Ala-Trp-DPhe-Lys-NH2 and human pancreatic growth hormone-releasing factor-44-NH2 in rat primary pituitary cell monolayer culture.

PubMed

Sartor, O; Bowers, C Y; Chang, D

1985-03-01

His-DTrp-Ala-Trp-DPhe-Lys-NH2 (GH-RP-6) is a synthetic hexapeptide that specifically releases GH both in vivo and in vitro in pituitary incubates. In this study, for the first time, GH-RP-6 was studied in primary pituitary cell monolayer culture. Parallel studies were performed with human pancreatic GH-releasing factor-44 (hpGRF-44). Culture conditions optimal for GH-RP-6 were not optimal for hpGRF-44. Both peptides released GH in a dose- and time-dependent manner. In this assay system, the ED50 for GH-RP-6 was 9 nM, and the ED50 for hp-GRF-44 was 1.6 nM. Calcium-blocking agents inhibited the GH responses of both peptides as well as basal GH release. Pretreatment with GH-RP-6 decreased the subsequent response to both GH-RP-6 and hpGRF-44. hpGRF-44 down regulated itself but not GH-RP-6. Rat sera potentiated the GH response of hpGRF-44 but not that of GH-RP-6. GH-RP-6 and hpGRF-44 GH responses were additive. These results suggest that GH-RP-6 and hpGRF-44 stimulate GH release via different somatotroph receptors.

PDC-E3BP is not a dominant T-cell autoantigen in primary biliary cirrhosis.

PubMed

McHugh, Anna; Robe, Amanda J; Palmer, Jeremy M; Jones, David E J

2006-05-01

Autoantibody responses reactive with the E2 and E3BP components of pyruvate dehydrogenase complex (PDC), which characterise primary biliary cirrhosis (PBC) crossreact, precluding the identification, from serological studies, of the antigen to which the principal breakdown of tolerance occurs. Although autoreactive T-cell responses to PDC-E2 have been well characterised it is, at present, unclear whether T-cell tolerance breakdown also occurs to PDC-E3BP. The aims of this study were to characterise autoreactive T-cell responses to PDC-E3BP in PBC and potential factors regulating their expression. Peripheral blood T-cell proliferative responses to purified recombinant human PDC-E2 and PDC-E3BP at a range of concentrations were characterised in PBC patients and control subjects. T-cell proliferative responses to both E2 and E3BP were absent from control subjects (median peak stimulation index (SI) to PDC-E2 1.2 [range 0.3-1.9], 0/10 positive (SI>2.32), median peak SI to PDC-E3BP 1.1 [0.7-2.1

IL-2 infusion abrogates humoral immune responses in humans.

PubMed Central

Gottlieb, D J; Prentice, H G; Heslop, H E; Bello, C; Brenner, M K

1992-01-01

Although IL-2 infusion enhances cell-mediated cytotoxicity in patients with neoplastic disease, administration is paradoxically associated with a modest fall in total serum IgG and an increased risk of infection. We now show that the adverse effects of IL-2 infusion on the humoral immune system are substantial. Although IL-2 induces the B cell growth and differentiating factors IL-4 and IL-6, infusion abrogates primary antibody responses entirely and reduces secondary antibody responses 50-fold following antigen challenge. There is no evidence of the generation of cells with suppressive activity on B cells but IL-2 increases the ratio of circulating virgin:memory cells. These results may help to explain the increased rate of bacterial infection in patients receiving IL-2. As IL-2 plays a central role in the generation of an immune response, the finding that it is also sufficiently immunosuppressive to inhibit primary- and secondary-type antibody responses suggests that exploration of the underlying mechanisms may provide insights into immune system homeostasis and may offer new approaches to therapeutic immunosuppression. Images Fig. 1 PMID:1544235

Antibody responses to bacteriophage phi X-174 in human subjects exposed to the antarctic winter-over model of spaceflight

NASA Technical Reports Server (NTRS)

Shearer, W. T.; Lugg, D. J.; Rosenblatt, H. M.; Nickolls, P. M.; Sharp, R. M.; Reuben, J. M.; Ochs, H. D.

2001-01-01

BACKGROUND: It has been proposed that exposure to long-term spaceflight conditions (stress, isolation, sleep disruption, containment, microbial contamination, and solar radiation) or to ground-based models of spaceflight will alter human immune responses, but specific antibody responses have not been fully evaluated. OBJECTIVE: We sought to determine whether exposure to the 8-month Antarctic winter-over model of spaceflight would alter human antibody responses. METHODS: During the 1999 Australian National Antarctic Research Expeditions, 11 adult study subjects at Casey, Antarctica, and 7 control subjects at Macquarie Island, sub-Antarctica, received primary and secondary immunizations with the T cell-dependent neoantigen bacteriophage phi X-174. Periodic plasma samples were analyzed for specific antibody function. RESULTS: All of the subjects from Casey, Antarctica, cleared bacteriophage phi X-174 normally by 1 week after primary immunization, and all had normal primary and secondary antibody responses, including immunologic memory amplification and switch from IgM to IgG antibody production. One subject showed a high normal pattern, and one subject had a low normal pattern. The control subjects from Macquarie Island also had normal immune responses to bacteriophage phi X-174. CONCLUSIONS: These data do not support the hypothesis that de novo specific antibody responses of subjects become defective during the conditions of the Antarctic winter-over. Because the Antarctic winter-over model of spaceflight lacks the important factors of microgravity and solar radiation, caution must be used in interpreting these data to anticipate normal antibody responses in long-term spaceflight.

Genetic Variants Within Molecular Targets of Antipsychotic Treatment: Effects on Treatment Response, Schizophrenia Risk, and Psychopathological Features.

PubMed

Calabrò, Marco; Porcelli, Stefano; Crisafulli, Concetta; Wang, Sheng-Min; Lee, Soo-Jung; Han, Changsu; Patkar, Ashwin A; Masand, Prakash S; Albani, Diego; Raimondi, Ilaria; Forloni, Gianluigi; Bin, Sofia; Cristalli, Carlotta; Mantovani, Vilma; Pae, Chi-Un; Serretti, Alessandro

2018-01-01

Schizophrenia (SCZ) is a common and severe mental disorder. Genetic factors likely play a role in its pathophysiology as well as in treatment response. In the present study, we investigated the effects of several single nucleotide polymorphisms (SNPs) within 9 genes involved with antipsychotic (AP) mechanisms of action. Two independent samples were recruited. The Korean sample included 176 subjects diagnosed with SCZ and 326 healthy controls, while the Italian sample included 83 subjects and 194 controls. AP response as measured by the positive and negative syndrome scale (PANSS) was the primary outcome, while the secondary outcome was the SCZ risk. Exploratory analyses were performed on (1) symptom clusters response (as measured by PANSS subscales); (2) age of onset; (3) family history; and (4) suicide history. Associations evidenced in the primary analyses did not survive to the FDR correction. Concerning SCZ risk, we partially confirmed the associations among COMT and MAPK1 genetic variants and SCZ. Finally, our exploratory analysis suggested that CHRNA7 and HTR2A genes may modulate both positive and negative symptoms responses, while PLA2G4A and SIGMAR1 may modulate respectively positive and negative symptoms responses. Moreover, GSK3B, HTR2A, PLA2G4A, and S100B variants may determine an anticipation of SCZ age of onset. Our results did not support a primary role for the genes investigated in AP response as a whole. However, our exploratory findings suggested that these genes may be involved in symptom clusters response.

Breed-specific incidence rates of canine primary bone tumors — A population based survey of dogs in Norway

PubMed Central

Anfinsen, Kristin P.; Grotmol, Tom; Bruland, Oyvind S.; Jonasdottir, Thora J.

2011-01-01

This is one of few published population-based studies describing breed specific rates of canine primary bone tumors. Incidence rates related to dog breeds could help clarify the impact of etiological factors such as birth weight, growth rate, and adult body weight/height on development of these tumors. The study population consisted of dogs within 4 large/giant breeds; Irish wolfhound (IW), Leonberger (LB), Newfoundland (NF), and Labrador retriever (LR), born between January 1st 1989 and December 31st 1998. Questionnaires distributed to owners of randomly selected dogs — fulfilling the criteria of breed, year of birth, and registration in the Norwegian Kennel Club — constituted the basis for this retrospective, population-based survey. Of the 3748 questionnaires received by owners, 1915 were completed, giving a response rate of 51%. Forty-three dogs had been diagnosed with primary bone tumors, based upon clinical examination and x-rays. The breeds IW and LB, with 126 and 72 cases per 10 000 dog years at risk (DYAR), respectively, had significantly higher incidence rates of primary bone tumors than NF and LR (P < 0.0001). Incidence rates for the latter were 11 and 2 cases per 10 000 DYAR, respectively. Pursuing a search for risk factors other than body size/weight is supported by the significantly different risks of developing primary bone tumors between similarly statured dogs, like NF and LB, observed in this study. Defining these breed-specific incidence rates enables subsequent case control studies, ultimately aiming to identify specific etiological factors for developing primary bone tumors. PMID:22210997

Identification of the cAMP response element that controls transcriptional activation of the insulin-like growth factor-I gene by prostaglandin E2 in osteoblasts

NASA Technical Reports Server (NTRS)

Thomas, M. J.; Umayahara, Y.; Shu, H.; Centrella, M.; Rotwein, P.; McCarthy, T. L.

1996-01-01

Insulin-like growth factor-I (IGF-I), a multifunctional growth factor, plays a key role in skeletal growth and can enhance bone cell replication and differentiation. We previously showed that prostaglandin E2 (PGE2) and other agents that increase cAMP activated IGF-I gene transcription in primary rat osteoblast cultures through promoter 1 (P1), the major IGF-I promoter, and found that transcriptional induction was mediated by protein kinase A. We now have identified a short segment of P1 that is essential for full hormonal regulation and have characterized inducible DNA-protein interactions involving this site. Transient transfections of IGF-I P1 reporter genes into primary rat osteoblasts showed that the 328-base pair untranslated region of exon 1 was required for a full 5.3-fold response to PGE2; mutation in a previously footprinted site, HS3D (base pairs +193 to +215), reduced induction by 65%. PGE2 stimulated nuclear protein binding to HS3D. Binding, as determined by gel mobility shift assay, was not seen in nuclear extracts from untreated osteoblast cultures, was detected within 2 h of PGE2 treatment, and was maximal by 4 h. This DNA-protein interaction was not observed in cytoplasmic extracts from PGE2-treated cultures, indicating nuclear localization of the protein kinase A-activated factor(s). Activation of this factor was not blocked by cycloheximide (Chx), and Chx did not impair stimulation of IGF-I gene expression by PGE2. In contrast, binding to a consensus cAMP response element (CRE; 5'-TGACGTCA-3') from the rat somatostatin gene was not modulated by PGE2 or Chx. Competition gel mobility shift analysis using mutated DNA probes identified 5'-CGCAATCG-3' as the minimal sequence needed for inducible binding. All modified IGF-I P1 promoterreporter genes with mutations within this CRE sequence also showed a diminished functional response to PGE2. These results identify the CRE within the 5'-untranslated region of IGF-I exon 1 that is required for hormonal activation of IGF-I gene transcription by cAMP in osteoblasts.

Impact of socioeconomic factors on nutritional status in primary school children.

PubMed

Babar, Nabeela Fazal; Muzaffar, Rizwana; Khan, Muhammad Athar; Imdad, Seema

2010-01-01

Child malnutrition is a major public health and development concern in most of the poor communities leading to high morbidity and mortality. Various studies have highlighted the factors involved. The present study focuses on socioeconomic inequality resulting in malnutrition. Objectives of the Study were to find the Impact of socio-economic factors on nutritional status in primary school children. It was a cross sectional survey conducted at Lahore from February to August 2005 among primary schools from public and private sectors to assess the nutritional status of primary school going children age 5-11 years belonging to different socio economic classes of the society. Systematic random sampling technique was applied to collect the sample. Body Mass Index in relation to NHANES reference population was used for assessing nutritional status. The nutritional status of children from lower socio economic class was poor as compared to their counter parts in upper socio economic class. Children with BMI < 5th percentile were 41% in lower class while in upper class it was 19.28%. Prevalence of malnutrition was 42.3% among children of illiterate mothers as compare to 20% in those of literate mothers. Poverty, low literacy rate, large families, food insecurity, food safety, women's education appears to be the important underlying factors responsible for poor health status of children from low socioeconomic class. It requires economic, political and social changes as well as changes for personal advancement mainly through educational opportunities to improve the nutritional status of the children.

Accurate and reproducible measurements of RhoA activation in small samples of primary cells.

PubMed

Nini, Lylia; Dagnino, Lina

2010-03-01

Rho GTPase activation is essential in a wide variety of cellular processes. Measurement of Rho GTPase activation is difficult with limited material, such as tissues or primary cells that exhibit stringent culture requirements for growth and survival. We defined parameters to accurately and reproducibly measure RhoA activation (i.e., RhoA-GTP) in cultured primary keratinocytes in response to serum and growth factor stimulation using enzyme-linked immunosorbent assay (ELISA)-based G-LISA assays. We also established conditions that minimize RhoA-GTP in unstimulated cells without affecting viability, allowing accurate measurements of RhoA activation on stimulation or induction of exogenous GTPase expression. Copyright 2009 Elsevier Inc. All rights reserved.

Lipopolysaccharide and hypoxia significantly alters interleukin-8 and macrophage chemoattractant protein-1 production by human fibroblasts but not fibrosis related factors.

PubMed

Eleftheriadis, T; Liakopoulos, V; Lawson, B; Antoniadi, G; Stefanidis, I; Galaktidou, G

2011-07-01

Besides extracellular matrix production, fibroblasts are able to produce various cytokines. Their ubiquitous position makes fibroblasts appropriate cells for sensing various noxious stimuli and for attracting immune cells in the affected area. In the present study the effect of lipopolysaccharide (LPS) and cobalt chloride (CoCl(2)) on the above fibroblasts functions were evaluated in primary human skin fibroblasts cultures. Collagen, matrix metalloproteinase-1, tissue inhibitor of metalloproteinases-1, transforming growth factor-β1, interleukin-8 (IL-8) and macrophage chemoattractant protein-1 (MCP-1) were measured in fibroblasts culture supernatants. Fibroblasts proliferation and viability were assessed as well. Hypoxia inducible factor-1α and the phosphorylated p65 portion of NF-κB were assessed in fibroblasts protein extracts. LPS and CoCl(2) had a minor effect on fibrosis related factors in human primary fibroblasts, possibly due to the absence of interplay with other cell types in the used experimental system. On the contrary both LPS and CoCl(2) increased significantly IL-8. LPS also increased considerably MCP-1, but CoCl(2) decreased it. Thus LPS and CoCl(2) induce a sentinel, nevertheless not identical, phenotype in primary human fibroblasts. The last disparity could result in different body response to infectious or hypoxic noxious stimuli.

Influence of socio-demographic, labour and professional factors on nursing perception concerning practice environment in Primary Health Care.

PubMed

Parro Moreno, Ana; Serrano Gallardo, Pilar; Ferrer Arnedo, Carmen; Serrano Molina, Lucía; de la Puerta Calatayud, M Luisa; Barberá Martín, Aurora; Morales Asencio, José Miguel; de Pedro Gómez, Joan

2013-11-01

To analyze the perception of nursing professionals of the Madrid Primary Health Care environment in which they practice, as well as its relationship with socio-demographic, work-related and professional factors. Cross-sectional, analytical, observational study. Questionnaire sent to a total of 475 nurses in Primary Health Care in Madrid (former Health Care Areas 6 and 9), in 2010. Perception of the practice environment using the Practice Environment Scale of the Nursing Work Index (PES-NWI) questionnaire, as well as; age; sex; years of professional experience; professional category; Health Care Area; employment status and education level. There was a response rate of 69.7% (331). The raw score for the PES-NWI was: 81.04 [95%CI: 79.18-82.91]. The factor with the highest score was "Support from Managers" (2.9 [95%CI: 2.8-3]) and the lowest "Workforce adequacy" (2.3 [95%CI: 2.2-2.4]). In the regression model (dependent variable: raw score in PES-NWI), adjusted by age, sex, employment status, professional category (coefficient B=6.586), and years worked at the centre (coefficient B=2.139, for a time of 0-2 years; coefficient B=7.482, for 3-10 years; coefficient B=7.867, for over 20 years) remained at p≤0.05. The support provided by nurse managers is the most highly valued factor in this practice environment, while workforce adequacy is perceived as the lowest. Nurses in posts of responsibility and those possessing a higher degree of training perceive their practice environment more favourably. Knowledge of the factors in the practice environment is a key element for health care organizations to optimize provision of care and to improve health care results. Copyright © 2012 Elsevier España, S.L. All rights reserved.

Masculinity, Femininity and Androgyny: A Methodological and Theoretical Critique.

ERIC Educational Resources Information Center

Marsh, Herbert W.; Myers, Margaret

The three primary purposes of this investigation were: (1) to apply confirmatory factor analysis (CFA) to responses from three instruments--Bem Sex Role Inventory (BSRI), Comrey Personality Scales (CPS), and Australian Sex-Role Scale (ASRS)--designed to measure masculinity (M) and femininity (F); (2) to determine the correlation between M and F on…

Celebrating Musical Diversity: Training Culturally Responsive Music Educators in Multiracial Singapore

ERIC Educational Resources Information Center

Cain, Melissa

2015-01-01

This article explores outcomes of research into the role and place of cultural diversity in primary music classes at five government schools in Singapore. The study highlights the ways in which a variety of factors such as specialist music training, government policy, curriculum documents, and professional development influence teacher practice.…

Calcium homeostasis and bone metabolic responses to protein diets and energy restriction: a randomized control trial

USDA-ARS?s Scientific Manuscript database

Despite some beneficial effects on bone, high protein diets are conventionally considered a primary dietary risk factor for osteoporosis and bone fracture due to the acid load associated with protein catabolism. To test the hypothesis that high dietary protein diets do not negatively affect calcium ...

Teachers' Choice of Using Practical Activities--A Hierarchical Classification Attempt

ERIC Educational Resources Information Center

Haara, Frode Olav

2015-01-01

From a system theoretically grounded point of view, a hierarchy of primary and secondary impact factors influencing the mathematics teacher's choice to use practical activities in mathematics teaching is suggested initially in the article. A study, based on qualitative responses from mathematics teachers, then gives grounds for suggesting that a…

Transcription factor regulation and cytokine expression following in vitro infection of primary chicken cell culture with low pathogenic avian influenza virus

USDA-ARS?s Scientific Manuscript database

Avian influenza virus (AIV) induced proinflammatory cytokine expression is believed to contribute to the disease pathogenesis following infection. However, there is limited information on the avian immune response to infection with low pathogenic avian influenza virus (LPAIV). To gain a better under...

Food Production in Africa: The Ignored Role of Women.

ERIC Educational Resources Information Center

Otieno, Tabitha N.

Whereas women carry the primary responsibility for food production in Africa, development agencies have devoted minimal resources to researching the impact of their policies and new techniques on the well-being of Africa's women farmers. C. K. Eicher (1995) and M. Smale (1995) call this the invisible factor because the gender-related constraints…

Factors Contributing to the Subjective Career Success among Islamic Educators in Primary Schools

ERIC Educational Resources Information Center

Supa'ad, Mesnan; Wahat, Nor Wahiza Abd; Fakhruddin, Fathiyah Mohd; Suandi, Turiman

2013-01-01

A very limited research has been done in the field of career development among Islamic education teachers. Most of the previous researches showed an improvement in terms of grades, positions, and responsibilities of their previous routines as an indicator of their career advancement. However, this conceptual (concept paper) discusses how…

Climate change and stream temperature projections in the Columbia River Basin: biological implications of spatial variation in hydrologic drivers

USDA-ARS?s Scientific Manuscript database

Water temperature is a primary physical factor affecting aquatic organisms. Assessment of suitable thermal habitat in freshwater systems is critical for predicting aquatic species responses to changes in climate and for guiding adaptation strategies. We use a hydrologic model coupled with a stream t...

Anticipating students' reasoning and planning prompts in structured problem-solving lessons

NASA Astrophysics Data System (ADS)

Vale, Colleen; Widjaja, Wanty; Doig, Brian; Groves, Susie

2018-02-01

Structured problem-solving lessons are used to explore mathematical concepts such as pattern and relationships in early algebra, and regularly used in Japanese Lesson Study research lessons. However, enactment of structured problem-solving lessons which involves detailed planning, anticipation of student solutions and orchestration of whole-class discussion of solutions is an ongoing challenge for many teachers. Moreover, primary teachers have limited experience in teaching early algebra or mathematical reasoning actions such as generalising. In this study, the critical factors of enacting the structured problem-solving lessons used in Japanese Lesson Study to elicit and develop primary students' capacity to generalise are explored. Teachers from three primary schools participated in two Japanese Lesson Study teams for this study. The lesson plans and video recordings of teaching and post-lesson discussion of the two research lessons along with students' responses and learning are compared to identify critical factors. The anticipation of students' reasoning together with preparation of supporting and challenging prompts was critical for scaffolding students' capacity to grasp and communicate generality.

The dual-specificity phosphatase MKP-1 limits the cardiac hypertrophic response in vitro and in vivo.

PubMed

Bueno, O F; De Windt, L J; Lim, H W; Tymitz, K M; Witt, S A; Kimball, T R; Molkentin, J D

2001-01-19

Mitogen-activated protein kinase (MAPK) signaling pathways are important regulators of cell growth, proliferation, and stress responsiveness. A family of dual-specificity MAP kinase phosphatases (MKPs) act as critical counteracting factors that directly regulate the magnitude and duration of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK) activation. Here we show that constitutive expression of MKP-1 in cultured primary cardiomyocytes using adenovirus-mediated gene transfer blocked the activation of p38, JNK1/2, and ERK1/2 and prevented agonist-induced hypertrophy. Transgenic mice expressing physiological levels of MKP-1 in the heart showed (1) no activation of p38, JNK1/2, or ERK1/2; (2) diminished developmental myocardial growth; and (3) attenuated hypertrophy in response to aortic banding and catecholamine infusion. These results provide further evidence implicating MAPK signaling factors as obligate regulators of cardiac growth and hypertrophy and demonstrate the importance of dual-specificity phosphatases as counterbalancing regulatory factors in the heart.

Nonlinear, interacting responses to climate limit grassland production under global change.

PubMed

Zhu, Kai; Chiariello, Nona R; Tobeck, Todd; Fukami, Tadashi; Field, Christopher B

2016-09-20

Global changes in climate, atmospheric composition, and pollutants are altering ecosystems and the goods and services they provide. Among approaches for predicting ecosystem responses, long-term observations and manipulative experiments can be powerful approaches for resolving single-factor and interactive effects of global changes on key metrics such as net primary production (NPP). Here we combine both approaches, developing multidimensional response surfaces for NPP based on the longest-running, best-replicated, most-multifactor global-change experiment at the ecosystem scale-a 17-y study of California grassland exposed to full-factorial warming, added precipitation, elevated CO2, and nitrogen deposition. Single-factor and interactive effects were not time-dependent, enabling us to analyze each year as a separate realization of the experiment and extract NPP as a continuous function of global-change factors. We found a ridge-shaped response surface in which NPP is humped (unimodal) in response to temperature and precipitation when CO2 and nitrogen are ambient, with peak NPP rising under elevated CO2 or nitrogen but also shifting to lower temperatures. Our results suggest that future climate change will push this ecosystem away from conditions that maximize NPP, but with large year-to-year variability.

Transcription factor Stat5a/b as a therapeutic target protein for prostate cancer

PubMed Central

Liao, Zhiyong; Lutz, Jacqueline; Nevalainen, Marja T.

2009-01-01

Prostate cancer is the most common non-cutaneous cancer in Western males. The majority of prostate cancer fatalities are caused by development of castration-resistant growth and metastatic spread of the primary tumor. The average duration of the response of primary prostate cancer to hormonal ablation is less than 3 years, and 75% of prostate cancers in the United States progress to hormone-refractory disease. The existing pharmacological therapies for metastatic and/or hormone-refractory prostate cancer do not provide significant survival benefit. This review summarizes the importance of transcription factor Stat5 signaling in the pathogenesis of prostate cancer and discusses the molecular basis why inhibition of Stat5a/b could be used as a therapeutic strategy for prostate cancer. PMID:19914392

Utilization of Rural Primary Care Physicians' Visit Services for Diabetes Management of Public Health in Southwestern China: A Cross-Sectional Study from Patients' View.

PubMed

Miao, Yudong; Ye, Ting; Qian, Dongfu; Li, Jinlong; Zhang, Liang

2014-06-01

Primary care physicians' visit services for diabetes management are now widely delivered in China's rural public health care. Current studies mainly focus on supply but risk factors from patients' view have not been previously explored. This study aims to present the utilization of rural primary care physicians' visit services for diabetes management in the last 12 months in southwestern China, and to explore risk factors from patients' view. This cross sectional study selected six towns at random and all 385 diabetics managed by primary care physicians were potential participants. Basing on the inclusion and exclusion criteria, 374 diabetics were taken as valid subjects and their survey responses formed the data resource of analyses. Descriptive indicators, χ2 contingency table analyses and Logistic regression were used. 54.8% respondents reported the utilization of visit services. According to the multivariate analysis, the positive factors mainly associated with utilization of visit services include disease duration (OR=1.654), use of diabetic drugs (OR=1.869), consulting diabetes care knowledge (OR=1.602), recognition of diabetic complications (OR=1.662), needs of visit services (OR=2.338). The utilization of rural primary care physicians' visit services still remains unsatisfactory. Mass rural health policy awareness, support, and emphasis are in urgent need and possible risk factors including disease duration, use of diabetic drugs, consulting diabetes care knowledge, recognition of diabetic complications and needs of visit services should be taken into account when making rural health policy of visit services for diabetes management in China and many other low- and middle-income countries.

Growth factor independence-1 antagonizes a p53-induced DNA damage response pathway in lymphoblastic leukemia

PubMed Central

Khandanpour, Cyrus; Phelan, James D.; Vassen, Lothar; Schütte, Judith; Chen, Riyan; Horman, Shane R.; Gaudreau, Marie-Claude; Krongold, Joseph; Zhu, Jinfang; Paul, William E.; Dührsen, Ulrich; Göttgens, Bertie; Grimes, H. Leighton; Möröy, Tarik

2013-01-01

Summary Most patients with acute lymphoblastic leukemia (ALL) fail current treatments highlighting the need for better therapies. Since oncogenic signaling activates a p53-dependent DNA-damage response and apoptosis, leukemic cells must devise appropriate countermeasures. We show here that growth factor independence 1 (Gfi1) can serve such a function, since Gfi1 ablation exacerbates p53 responses, and lowers the threshold for p53-induced cell death. Specifically, Gfi1 restricts p53 activity and expression of pro-apoptotic p53 targets such as Bax, Noxa (Pmaip1) and Puma (Bbc3). Subsequently, Gfi1 ablation cures mice from leukemia and limits the expansion of primary human T-ALL xenografts in mice. This suggests that targeting Gfi1 could improve the prognosis of patients with T-ALL or other lymphoid leukemias. PMID:23410974

Long-distance communication and signal amplification in systemic acquired resistance

PubMed Central

Shah, Jyoti; Zeier, Jürgen

2013-01-01

Systemic acquired resistance (SAR) is an inducible defense mechanism in plants that confers enhanced resistance against a variety of pathogens. SAR is activated in the uninfected systemic (distal) organs in response to a prior (primary) infection elsewhere in the plant. SAR is associated with the activation of salicylic acid (SA) signaling and the priming of defense responses for robust activation in response to subsequent infections. The activation of SAR requires communication by the primary infected tissues with the distal organs. The vasculature functions as a conduit for the translocation of factors that facilitate long-distance intra-plant communication. In recent years, several metabolites putatively involved in long-distance signaling have been identified. These include the methyl ester of SA (MeSA), the abietane diterpenoid dehydroabietinal (DA), the dicarboxylic acid azelaic acid (AzA), and a glycerol-3-phosphate (G3P)-dependent factor. Long-distance signaling by some of these metabolites also requires the lipid-transfer protein DIR1 (DEFECTIVE IN INDUCED RESISTANCE 1). The relative contribution of these factors in long-distance signaling is likely influenced by environmental conditions, for example light. In the systemic leaves, the AGD2-LIKE DEFENSE RESPONSE PROTEIN1 (ALD1)-dependent production of the lysine catabolite pipecolic acid (Pip), FLAVIN-DEPENDENT MONOOXYGENASE1 (FMO1) signaling, as well as SA synthesis and downstream signaling are required for the activation of SAR. This review summarizes the involvement and interaction between long-distance SAR signals and details the recently discovered role of Pip in defense amplification and priming that allows plants to acquire immunity at the systemic level. Recent advances in SA signaling and perception are also highlighted. PMID:23440336

Evidence for the association between IgG-antimitochondrial antibody and biochemical response to ursodeoxycholic acid treatment in primary biliary cholangitis.

PubMed

Tang, Libo; Zhong, Ruihua; He, Xuanqiu; Wang, Weibin; Liu, Jinhong; Zhu, Youfu; Li, Yongyin; Hou, Jinlin

2017-03-01

Antimitochondrial antibody (AMA) is considered the serological hallmark of primary biliary cholangitis (PBC), while data regarding the profile of AMA during ursodeoxycholic acid (UDCA) treatment are scarce. Here, we assessed the influence of UDCA treatment on titers of AMA and factors relevant to its production. Serum IgA-AMA, IgM-AMA, IgG-AMA, B cell-activating factor of the tumor necrosis factor family (BAFF), and the frequency of circulating plasmablasts were detected in PBC patients, including those who received UDCA therapy for 24 weeks, healthy controls, chronic hepatitis B patients, and autoimmune hepatitis patients. Consecutive liver sections from controls and PBC patients were stained by immunohistochemistry for detection of intrahepatic CD38 + , IgA + , IgM + , and IgG + cells. Significant decrease in titers of IgG-AMA was found only confined to PBC patients with biochemical response to UDCA treatment (P = 0.005), and similar pattern was also observed at week 24 in quantifying circulating plasmablasts (P = 0.025) and serum BAFF (P = 0.013). Notably, positive correlation between serum BAFF levels and titers of IgG-AMA, and the frequency of circulating plasmablasts were observed in PBC patients (r = 0.464, P = 0.034 and r = 0.700, P < 0.001, respectively). Additionally, in situ staining revealed significant accumulation of CD38 + and IgG + cells within the portal tracts of PBC liver. Decreased titers of serum IgG-AMA are associated with biochemical response to UDCA treatment, implicating the potentiality of this hallmark in therapeutic response evaluation and the beneficial effect of UDCA on humoral immunity in PBC patients. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.

Geriatric neuro-oncology: from mythology to biology.

PubMed

Weller, Michael; Platten, Michael; Roth, Patrick; Wick, Wolfgang

2011-12-01

Age has remained one of the most important determinants of risk for the development of certain brain tumors, of benefit from and tolerance of brain tumor treatment, and overall outcome. Regarding these three aspects, there are major differences across the spectrum of primary brain tumors depending on specific histology. Here, we review recent advances in understanding the biological basis of the prognostic marker 'age' in neuro-oncology. Contemporary population-based studies confirm the strong prognostic impact of age in many brain tumors. Elderly patients continue to be treated less aggressively than younger patients with the same tumors. However, biological factors may contribute to the negative prognostic impact of age. For instance, among gliomas, mutations of the isocitrate dehydrogenase genes, which are prognostically favorable, are much more common in younger patients. Moreover, complete responses defined by neuroimaging were much less durable in elderly as opposed to younger patients with primary central nervous system lymphoma in the German Primary Central Nervous System Lymphoma Study Group trial. A combination of age-adapted patterns of care and treatment-independent, tumor-intrinsic factors contributes to the poorer outcome of elderly patients with brain tumors. These factors need to be better distinguished and understood in order to improve outcome in elderly brain tumor patients.

Climate-mediated nitrogen and carbon dynamics in a tropical watershed

NASA Astrophysics Data System (ADS)

Ballantyne, A. P.; Baker, P. A.; Fritz, S. C.; Poulter, B.

2011-06-01

Climate variability affects the capacity of the biosphere to assimilate and store important elements, such as nitrogen and carbon. Here we present biogeochemical evidence from the sediments of tropical Lake Titicaca indicating that large hydrologic changes in response to global glacial cycles during the Quaternary were accompanied by major shifts in ecosystem state. During prolonged glacial intervals, lake level was high and the lake was in a stable nitrogen-limited state. In contrast, during warm dry interglacials lake level fell and rates of nitrogen concentrations increased by a factor of 4-12, resulting in a fivefold to 24-fold increase in organic carbon concentrations in the sediments due to increased primary productivity. Observed periods of increased primary productivity were also associated with an apparent increase in denitrification. However, the net accumulation of nitrogen during interglacial intervals indicates that increased nitrogen supply exceeded nitrogen losses due to denitrification, thereby causing increases in primary productivity. Although primary productivity in tropical ecosystems, especially freshwater ecosystems, tends to be nitrogen limited, our results indicate that climate variability may lead to changes in nitrogen availability and thus changes in primary productivity. Therefore some tropical ecosystems may shift between a stable state of nitrogen limitation and a stable state of nitrogen saturation in response to varying climatic conditions.

Human physiological responses to cold exposure: Acute responses and acclimatization to prolonged exposure.

PubMed

Castellani, John W; Young, Andrew J

2016-04-01

Cold exposure in humans causes specific acute and chronic physiological responses. This paper will review both the acute and long-term physiological responses and external factors that impact these physiological responses. Acute physiological responses to cold exposure include cutaneous vasoconstriction and shivering thermogenesis which, respectively, decrease heat loss and increase metabolic heat production. Vasoconstriction is elicited through reflex and local cooling. In combination, vasoconstriction and shivering operate to maintain thermal balance when the body is losing heat. Factors (anthropometry, sex, race, fitness, thermoregulatory fatigue) that influence the acute physiological responses to cold exposure are also reviewed. The physiological responses to chronic cold exposure, also known as cold acclimation/acclimatization, are also presented. Three primary patterns of cold acclimatization have been observed, a) habituation, b) metabolic adjustment, and c) insulative adjustment. Habituation is characterized by physiological adjustments in which the response is attenuated compared to an unacclimatized state. Metabolic acclimatization is characterized by an increased thermogenesis, whereas insulative acclimatization is characterized by enhancing the mechanisms that conserve body heat. The pattern of acclimatization is dependent on changes in skin and core temperature and the exposure duration. Published by Elsevier B.V.

Cross-sectional survey on awareness of colorectal cancer and a screening programme for primary health care professionals in Catalonia, Spain.

PubMed

Benito, L; García, M; Binefa, G; Mila, N; Vidal, C; Lluch, M T; Puig, M

2016-11-01

This study aimed to assess whether primary health care professionals have accurate information regarding colorectal cancer (CRC) screening procedures, surveillance recommendations and referral strategies. This cross-sectional descriptive study was based on a survey conducted among primary health care professionals in Barcelona, Spain. The questionnaire was used to gather information regarding CRC screening procedures as well as demographic and professional characteristics of the study subjects. A CRC and screening awareness score (ranging from 0 to 12) was created based on the survey questions. The response rate was 58.9% (206/305). The estimated mean score (standard deviation) was 8.43 (SD: 1.30). For four questions, more than 60% of the answers were incorrect: one related to risk factors, two concerning follow-up colonoscopy, and one related to surveillance. Only 30.8% of the participants believed that they were responsible for determining the appropriate surveillance intervals and for scheduling colonoscopies. Although the professionals had sufficient knowledge of CRC screening, professional knowledge of some aspects related to the major non-modifiable risk factors for the disease and surveillance colonoscopy procedures could be improved. Frequent communication with professionals is necessary to maintain updated screening-related information. Possible methods for facilitating communication could include continuous briefings, regular message reminders or educational websites. © 2016 John Wiley & Sons Ltd.

Factors associated with student learning processes in primary health care units: a questionnaire study.

PubMed

Bos, Elisabeth; Alinaghizadeh, Hassan; Saarikoski, Mikko; Kaila, Päivi

2015-01-01

Clinical placement plays a key role in education intended to develop nursing and caregiving skills. Studies of nursing students' clinical learning experiences show that these dimensions affect learning processes: (i) supervisory relationship, (ii) pedagogical atmosphere, (iii) management leadership style, (iv) premises of nursing care on the ward, and (v) nursing teachers' roles. Few empirical studies address the probability of an association between these dimensions and factors such as student (a) motivation, (b) satisfaction with clinical placement, and (c) experiences with professional role models. The study aimed to investigate factors associated with the five dimensions in clinical learning environments within primary health care units. The Swedish version of Clinical Learning Environment, Supervision and Teacher, a validated evaluation scale, was administered to 356 graduating nursing students after four or five weeks clinical placement in primary health care units. Response rate was 84%. Multivariate analysis of variance is determined if the five dimensions are associated with factors a, b, and c above. The analysis revealed a statistically significant association with the five dimensions and two factors: students' motivation and experiences with professional role models. The satisfaction factor had a statistically significant association (effect size was high) with all dimensions; this clearly indicates that students experienced satisfaction. These questionnaire results show that a good clinical learning experience constitutes a complex whole (totality) that involves several interacting factors. Supervisory relationship and pedagogical atmosphere particularly influenced students' satisfaction and motivation. These results provide valuable decision-support material for clinical education planning, implementation, and management. Copyright © 2014 Elsevier Ltd. All rights reserved.

Development of an efficient, non-viral transfection method for studying gene function and bone growth in human primary cranial suture mesenchymal cells reveals that the cells respond to BMP2 and BMP3.

PubMed

Dwivedi, Prem P; Anderson, Peter J; Powell, Barry C

2012-08-03

Achieving efficient introduction of plasmid DNA into primary cultures of mammalian cells is a common problem in biomedical research. Human primary cranial suture cells are derived from the connective mesenchymal tissue between the bone forming regions at the edges of the calvarial plates of the skull. Typically they are referred to as suture mesenchymal cells and are a heterogeneous population responsible for driving the rapid skull growth that occurs in utero and postnatally. To better understand the molecular mechanisms involved in skull growth, and in abnormal growth conditions, such as craniosynostosis, caused by premature bony fusion, it is essential to be able to easily introduce genes into primary bone forming cells to study their function. A comparison of several lipid-based techniques with two electroporation-based techniques demonstrated that the electroporation method known as nucleofection produced the best transfection efficiency. The parameters of nucleofection, including cell number, amount of DNA and nucleofection program, were optimized for transfection efficiency and cell survival. Two different genes and two promoter reporter vectors were used to validate the nucleofection method and the responses of human primary suture mesenchymal cells by fluorescence microscopy, RT-PCR and the dual luciferase assay. Quantification of bone morphogenetic protein (BMP) signalling using luciferase reporters demonstrated robust responses of the cells to both osteogenic BMP2 and to the anti-osteogenic BMP3. A nucleofection protocol has been developed that provides a simple and efficient, non-viral alternative method for in vitro studies of gene and protein function in human skull growth. Human primary suture mesenchymal cells exhibit robust responses to BMP2 and BMP3, and thus nucleofection can be a valuable method for studying the potential competing action of these two bone growth factors in a model system of cranial bone growth.

Development and Validation of the Primary Care Team Dynamics Survey

PubMed Central

Song, Hummy; Chien, Alyna T; Fisher, Josephine; Martin, Julia; Peters, Antoinette S; Hacker, Karen; Rosenthal, Meredith B; Singer, Sara J

2015-01-01

Objective To develop and validate a survey instrument designed to measure team dynamics in primary care. Data Sources/Study Setting We studied 1,080 physician and nonphysician health care professionals working at 18 primary care practices participating in a learning collaborative aimed at improving team-based care. Study Design We developed a conceptual model and administered a cross-sectional survey addressing team dynamics, and we assessed reliability and discriminant validity of survey factors and the overall survey's goodness-of-fit using structural equation modeling. Data Collection We administered the survey between September 2012 and March 2013. Principal Findings Overall response rate was 68 percent (732 respondents). Results support a seven-factor model of team dynamics, suggesting that conditions for team effectiveness, shared understanding, and three supportive processes are associated with acting and feeling like a team and, in turn, perceived team effectiveness. This model demonstrated adequate fit (goodness-of-fit index: 0.91), scale reliability (Cronbach's alphas: 0.71–0.91), and discriminant validity (average factor correlations: 0.49). Conclusions It is possible to measure primary care team dynamics reliably using a 29-item survey. This survey may be used in ambulatory settings to study teamwork and explore the effect of efforts to improve team-based care. Future studies should demonstrate the importance of team dynamics for markers of team effectiveness (e.g., work satisfaction, care quality, clinical outcomes). PMID:25423886

Development and validation of the primary care team dynamics survey.

PubMed

Song, Hummy; Chien, Alyna T; Fisher, Josephine; Martin, Julia; Peters, Antoinette S; Hacker, Karen; Rosenthal, Meredith B; Singer, Sara J

2015-06-01

To develop and validate a survey instrument designed to measure team dynamics in primary care. We studied 1,080 physician and nonphysician health care professionals working at 18 primary care practices participating in a learning collaborative aimed at improving team-based care. We developed a conceptual model and administered a cross-sectional survey addressing team dynamics, and we assessed reliability and discriminant validity of survey factors and the overall survey's goodness-of-fit using structural equation modeling. We administered the survey between September 2012 and March 2013. Overall response rate was 68 percent (732 respondents). Results support a seven-factor model of team dynamics, suggesting that conditions for team effectiveness, shared understanding, and three supportive processes are associated with acting and feeling like a team and, in turn, perceived team effectiveness. This model demonstrated adequate fit (goodness-of-fit index: 0.91), scale reliability (Cronbach's alphas: 0.71-0.91), and discriminant validity (average factor correlations: 0.49). It is possible to measure primary care team dynamics reliably using a 29-item survey. This survey may be used in ambulatory settings to study teamwork and explore the effect of efforts to improve team-based care. Future studies should demonstrate the importance of team dynamics for markers of team effectiveness (e.g., work satisfaction, care quality, clinical outcomes). © Health Research and Educational Trust.

Community participation in health service reform: the development of an innovative remote Aboriginal primary health-care service.

PubMed

Reeve, Carole; Humphreys, John; Wakerman, John; Carroll, Vicki; Carter, Maureen; O'Brien, Tim; Erlank, Carol; Mansour, Rafik; Smith, Bec

2015-01-01

The aim of this study was to describe the reorientation of a remote primary health-care service, in the Kimberley region of Australia, its impact on access to services and the factors instrumental in bringing about change. A unique community-initiated health service partnership was developed between a community-controlled Aboriginal health organisation, a government hospital and a population health unit, in order to overcome the challenges of delivering primary health care to a dispersed, highly disadvantaged Aboriginal population in a very remote area. The shared goals and clear delineation of responsibilities achieved through the partnership reoriented an essentially acute hospital-based service to a prevention-focussed comprehensive primary health-care service, with a focus on systematic screening for chronic disease, interdisciplinary follow up, health promotion, community advocacy and primary prevention. This formal partnership enabled the primary health-care service to meet the major challenges of providing a sustainable, prevention-focussed service in a very remote and socially disadvantaged area.

Pathways to ambulatory sensitive hospitalisations for Māori in the Auckland and Waitemata regions.

PubMed

Barker, Carol; Crengle, Sue; Bramley, Dale; Bartholomew, Karen; Bolton, Patricia; Walsh, Michael; Wignall, Jean

2016-10-28

Ambulatory Sensitive Hospitalisations (ASH) are a group of conditions potentially preventable through interventions delivered in the primary health care setting. ASH rates are consistently higher for Māori compared with non-Māori. This study aimed to establish Māori experience of factors driving the use of hospital services for ASH conditions, including barriers to accessing primary care. A telephone questionnaire exploring pathways to ASH was administered to Māori (n=150) admitted to Auckland and Waitemata District Health Board (DHB) hospitals with an ASH condition between January 1st-June 30th 2015. A cohort of 1,013 participants were identified; 842 (83.1%) were unable to be contacted. Of the 171 people contactable, 150 agreed to participate, giving an overall response rate of 14.8% and response rate of contactable patients of 87.7%. Results demonstrated high rates of self-reported enrolment, utilisation and preference for primary care. Many participants demonstrated appropriate health seeking behaviour and accurate recall of diagnoses. While financial barriers to accessing primary care were reported, non-financial barriers including lack of after-hours provision (12.6% adults, 37.7% children), appointment availability (7.4% adults, 17.0% children) and lack of transport (13.7% adults, 20.8% children) also featured in participant responses. Interventions to reduce Māori ASH include: timely access to primary care through electronic communications, increased appointment availability, extended opening hours, low cost after-hours care and consistent best management of ASH conditions in general practice through clinical pathways. Facilitated enrolment of ASH patients with no general practitioner could also reduce ASH. Research into transport barriers and enablers for Māori accessing primary care is required to support future interventions.

What does it take to set goals for self-management in primary care? A qualitative study.

PubMed

Lenzen, Stephanie Anna; van Dongen, Jerôme Jean Jacques; Daniëls, Ramon; van Bokhoven, Marloes Amantia; van der Weijden, Trudy; Beurskens, Anna

2016-12-01

There is an increasing number of patients with a chronic illness demanding primary care services. This demands for effective self-management support, including collaborative goal setting. Despite the fact that primary care professionals seem to have difficulties implementing goal setting, little information is available about the factors influencing the complexity of this process in primary care. The aim of this study was to contribute to an understanding of the complexity of self-management goal setting in primary care by exploring experts' and primary care professionals' experiences with self-management goal setting and viewpoints regarding influencing factors. A descriptive qualitative research methodology was adopted. Two focus groups and three individual interviews were conducted (total participants n = 17). Thematic content analysis was used to analyse the data. The findings were categorized into four main themes with subordinated subthemes. The themes focus around the complexity of setting non-medical goals and around professionals' skills and attitudes to negotiate and decide about goals with patients. Furthermore, patients' skills and attitudes for goal setting and the integration of goal setting in the time available were formulated as themes. Setting self-management goals in primary care, especially in family medicine, might require a shift from a medical perspective to a biopsychosocial perspective, with an increasing role set aside for the professional to coach the patient in expressing his self-management goals and to take responsibility for these goals. © The Author 2016. Published by Oxford University Press.

Does the primary site of colorectal cancer impact outcomes for patients with metastatic disease?

PubMed

Price, Timothy J; Beeke, Carol; Ullah, Shahid; Padbury, Robert; Maddern, Guy; Roder, David; Townsend, Amanda R; Moore, James; Roy, Amitesh; Tomita, Yoko; Karapetis, Christos

2015-03-15

Previous reports have described differences in biology and outcome for colorectal cancer based on whether the primary is right or left sided. Further division by right, left, and rectum or even exact primary site has also been explored. Possible differences in response to biological agents have also been reported based on side of primary lesion. We explored the South Australian registry for metastatic colorectal cancer to assess if there were any differences in patient characteristics, prognostic markers, and treatment received and outcomes based on whether the primary was right or left sided. We also explored if differences exist based on left colon and rectum and by exact primary site. Two thousand nine hundred seventy-two patients were analyzed. Thirty-five percent had a right-sided primary. The median overall survival for the entire group right versus left was 9.6 versus 20.3 months (P < .001). Multivariate analysis confirmed side of primary as an independent prognostic factor. For the group that had active therapy, defined as chemotherapy (± metastasis resection), median overall survival was right, 18.2 months; and left, 29.4 months (P < .001). Importantly, we found no suggestion of major differences if left side was divided by left colon and rectum, and trends by individual site still supported a left and right division. Patients with a right-sided primary have more negative prognostic factors and indeed have inferior outcomes compared with those with a left-sided primary. Our data with further breakdown by exact site still favor a simple left-versus-right division moving forward for metastatic colorectal cancer. © 2014 American Cancer Society.

Click or Clique? Using Educational Technology to Address Students' Anxieties about Peer Evaluation

ERIC Educational Resources Information Center

Walker, Ruth; Barwell, Graham

2009-01-01

Peer bias is recognised as a primary factor in negative student perceptions of peer assessment strategies. This study trialled the use of classroom response systems, widely known as clickers, in small seminar classes in order to actively engage students in their subject's assessment process while providing the anonymity that would lessen the…

Ozone Induces a Proinflammatory Response in Primary Human Bronchial Epithelial Cells Through Mitogen-Activated Protein Kinase Activation Without Nuclear Factor-kB Activation

EPA Science Inventory

Ground-level ozone (O3) is a ubiquitous environmental air pollutant that is a potent inducer of airway inflammation and has been linked with both respiratory and cardiovascular morbidity and mortality. Some studies using transformed or immortalized cells have attributed O3-medi...

Serum Hepatocyte Growth Factor Is Probably Associated With 3-Month Prognosis of Acute Ischemic Stroke.

PubMed

Zhu, Zhengbao; Xu, Tan; Guo, Daoxia; Huangfu, Xinfeng; Zhong, Chongke; Yang, Jingyuan; Wang, Aili; Chen, Chung-Shiuan; Peng, Yanbo; Xu, Tian; Wang, Jinchao; Sun, Yingxian; Peng, Hao; Li, Qunwei; Ju, Zhong; Geng, Deqin; Chen, Jing; Zhang, Yonghong; He, Jiang

2018-02-01

Serum hepatocyte growth factor (HGF) is positively associated with poor prognosis of heart failure and myocardial infarction, and it can also predict the risk of ischemic stroke in population. The goal of this study was to investigate the association between serum HGF and prognosis of ischemic stroke. A total of 3027 acute ischemic stroke patients were included in this post hoc analysis of the CATIS (China Antihypertensive Trial in Acute Ischemic Stroke). The primary outcome was composite outcome of death or major disability (modified Rankin Scale score ≥3) within 3 months. After multivariate adjustment, elevated HGF levels were associated with an increased risk of primary outcome (odds ratio, 1.50; 95% confidence interval, 1.10-2.03; P trend =0.015) when 2 extreme quartiles were compared. Each SD increase of log-transformed HGF was associated with 14% (95% confidence interval, 2%-27%) increased risk of primary outcome. Adding HGF quartiles to a model containing conventional risk factors improved the predictive power for primary outcome (net reclassification improvement: 17.50%, P <0.001; integrated discrimination index: 0.23%, P =0.022). The association between serum HGF and primary outcome could be modified by heparin pre-treatment ( P interaction =0.001), and a positive linear dose-response relationship between HGF and primary outcome was observed in patients without heparin pre-treatment ( P linearity <0.001) but not in those with heparin pre-treatment. Serum HGF levels were higher in the more severe stroke at baseline, and elevated HGF levels were probably associated with 3-month poor prognosis independently of stroke severity among ischemic stroke patients, especially in those without heparin pre-treatment. Further studies from other samples of ischemic stroke patients are needed to validate our findings. © 2018 American Heart Association, Inc.

Effectiveness of adalimumab for the treatment of ulcerative colitis in clinical practice: comparison between anti-tumour necrosis factor-naïve and non-naïve patients.

PubMed

Iborra, Marisa; Pérez-Gisbert, Javier; Bosca-Watts, Marta Maia; López-García, Alicia; García-Sánchez, Valle; López-Sanromán, Antonio; Hinojosa, Esther; Márquez, Lucía; García-López, Santiago; Chaparro, María; Aceituno, Montserrat; Calafat, Margalida; Guardiola, Jordi; Belloc, Blanca; Ber, Yolanda; Bujanda, Luis; Beltrán, Belén; Rodríguez-Gutiérrez, Cristina; Barrio, Jesús; Cabriada, José Luis; Rivero, Montserrat; Camargo, Raquel; van Domselaar, Manuel; Villoria, Albert; Schuterman, Hugo Salata; Hervás, David; Nos, Pilar

2017-07-01

Ulcerative colitis (UC) treatment is focused to achieve mucosal healing, avoiding disease progression. The study aimed to evaluate the real-world effectiveness of adalimumab (ADA) in UC and to identify predictors of remission to ADA. This cohort study used data from the ENEIDA registry. Clinical response, clinical remission, endoscopic remission, adverse events (AE), colectomy, and hospitalisations were evaluated; baseline characteristics and biological parameters were compared to determine predictors of response. We included 263 patients (87 naïve and 176 previously exposed to anti-tumour necrosis factor alpha, TNF). After 12 weeks, clinical response, clinical remission, and endoscopic remission rates were 51, 26, and 14 %, respectively. The naïve group demonstrated better response to treatment than the anti-TNF-exposed group at short-term. Clinical and endoscopic remission within 1 year of treatment was better in the naïve group (65 vs. 49 and 50 vs. 35 %, respectively). The rates of AE, dose-escalation, hospitalisations, and colectomy during the first year were higher in anti-TNF-exposed patients (40, 43, and 27 % vs. 26, 21, and 11 %, respectively). Patients with primary failure and intolerance to the first anti-TNF and severe disease were associated with worse clinical response. Primary non-response to prior anti-TNF treatment and severe disease were predictive of poorer clinical remission. Low levels of C-reactive protein (CRP) and faecal calprotectin (FC) at baseline were predictors of clinical remission. In clinical practice, ADA was effective in UC, especially in anti-TNF naïve patients. FC and CRP could be predictors of treatment effectiveness.

Clinical factors affecting physicians' management decisions in cases of female partner abuse.

PubMed

Ferris, L E; Norton, P; Dunn, E V; Gort, E H

1999-06-01

This study determined which clinical factors influence Canadian primary care physicians' management decisions in cases of female partner abuse. We used a cross-sectional survey design and randomly sampled (n = 2,014) English-speaking Canadian physicians with a primary interest in family or general practice who were practicing in any of the 12 provinces and territories in Canada and who were active in private practice and registered to prescribe. Respondents completed a questionnaire that required them to score management decision plans in response to case scenarios illustrating typical office-based situations that might involve domestic violence. The response rate was 50.7% (n = 1,022). Using forward stepwise regression analysis, the strongest predictor of whether a physician endorsed a management plan in response to violence was whether the woman acknowledged or revealed the abuse. Male physicians were more likely than females to endorse talking with the suspected abuser if he was known to them, regardless of the quality of this patient-physician relationship with the abuser. Decisions about whether to deal with the abuse or the selection of a management plan are not dependent on the severity of the physical abuse and the emotional consequences. Whether a woman acknowledges or reveals the abuse, as well as whether both the male and female patients are in the physician's practice, are predictive of whether a physician's response to a case scenario involves dealing with spousal abuse and how he/she will address it.

Why Aren't More Primary Care Residents Going into Primary Care? A Qualitative Study.

PubMed

Long, Theodore; Chaiyachati, Krisda; Bosu, Olatunde; Sircar, Sohini; Richards, Bradley; Garg, Megha; McGarry, Kelly; Solomon, Sonja; Berman, Rebecca; Curry, Leslie; Moriarty, John; Huot, Stephen

2016-12-01

Workforce projections indicate a potential shortage of up to 31,000 adult primary care providers by the year 2025. Approximately 80 % of internal medicine residents and nearly two-thirds of primary care internal medicine residents do not plan to have a career in primary care or general internal medicine. We aimed to explore contextual and programmatic factors within primary care residency training environments that may influence career choices. This was a qualitative study based on semi-structured, in-person interviews. Three primary care internal medicine residency programs were purposefully selected to represent a diversity of training environments. Second and third year residents were interviewed. We used a survey guide developed from pilot interviews and existing literature. Three members of the research team independently coded the transcripts and developed the code structure based on the constant comparative method. The research team identified emerging themes and refined codes. ATLAS.ti was used for the analysis. We completed 24 interviews (12 second-year residents, and 12 third-year residents). The age range was 27-39 years. Four recurrent themes characterized contextual and programmatic factors contributing to residents' decision-making: resident expectations of a career in primary care, navigation of the boundary between social needs and medical needs, mentorship and perceptions of primary care, and structural features of the training program. Addressing aspects of training that may discourage residents from careers in primary care such as lack of diversity in outpatient experiences and resident frustration with their inability to address social needs of patients, and strengthening aspects of training that may encourage interests in careers in primary care such as mentorship and protected time away from inpatient responsibilities during primary care rotations, may increase the proportion of residents enrolled in primary care training programs who pursue a career in primary care.

Identification of influencing factors and strategies to improve communication between general practitioners and community nurses: a qualitative focus group study.

PubMed

Nieuwboer, Minke S; Perry, Marieke; van der Sande, Rob; Maassen, Irma T H M; Olde Rikkert, Marcel G M; van der Marck, Marjolein A

2018-02-26

As the number of patients with complex healthcare needs grows, inter-professional collaboration between primary care professionals must be constantly optimized. General practitioners (GPs) and community nurses (CNs) are key professions in primary care; however, poor GP-CN communication is common, and research into the factors influencing its quality is limited. To explore patient-related GP-CN communication and facilitating and hindering factors, and to identify strategies to enhance this communication. A qualitative focus group design was used to identify the facilitating and hindering factors and strategies for improvement. In a Dutch primary care setting, 6 mono-professional focus group interviews (3 meetings of 13 GPs; 3 meetings of 18 CNs) were organized between June 2015 and April 2016, recorded and transcribed verbatim. Two independent researchers performed the coding of these interviews, identifying their categories and themes. Results show that, despite the regular contact between GPs and CNs, communication was generally perceived as poor in effectiveness and efficiency by both professions. Mutual trust was considered the most important facilitating factor for effective communication. Profession-specific factors (e.g. differences in responsibility and profession-specific language) and organizational factors (e.g. lack of shared care plans, no in-person communication, lack of time) may be of influence on communication. Participants' suggestions for improvement included organizing well-structured and reimbursed team meetings and facilitating face-to-face contact. GP-CN patient-related communication benefits most from trusting inter-personal relationships. Inter-professional training programmes should address both professional and organizational factors and should be evaluated for their effect on quality of care.

Frequency and prioritization of patient health risks from a structured health risk assessment.

PubMed

Phillips, Siobhan M; Glasgow, Russell E; Bello, Ghalib; Ory, Marcia G; Glenn, Beth A; Sheinfeld-Gorin, Sherri N; Sabo, Roy T; Heurtin-Roberts, Suzanne; Johnson, Sallie Beth; Krist, Alex H

2014-01-01

To describe the frequency and patient-reported readiness to change, desire to discuss, and perceived importance of 13 health risk factors in a diverse range of primary care practices. Patients (n = 1,707) in 9 primary care practices in the My Own Health Report (MOHR) trial reported general, behavioral, and psychosocial risk factors (body mass index [BMI], health status, diet, physical activity, sleep, drug use, stress, anxiety or worry, and depression). We classified responses as "at risk" or "healthy" for each factor, and patients indicated their readiness to change and/or desire to discuss identified risk factors with providers. Patients also selected 1 of the factors they were ready to change as most important. We then calculated frequencies within and across these factors and examined variation by patient characteristics and across practices. On average, patients had 5.8 (SD = 2.12; range, 0-13) unhealthy behaviors and mental health risk factors. About 55% of patients had more than 6 risk factors. On average, patients wanted to change 1.2 and discuss 0.7 risks. The most common risks were inadequate fruit/vegetable consumption (84.5%) and overweight/obesity (79.6%). Patients were most ready to change BMI (33.3%) and depression (30.7%), and most wanted to discuss depression (41.9%) and anxiety or worry (35.2%). Overall, patients rated health status as most important. Implementing routine comprehensive health risk assessments in primary care will likely identify a high number of behavioral and psychosocial health risks. By soliciting patient priorities, providers and patients can better manage counseling and behavior change. © 2014 Annals of Family Medicine, Inc.

Capacity, responsibility, and motivation: a critical qualitative evaluation of patient and practitioner views about barriers to self-management in people with multimorbidity.

PubMed

Coventry, Peter A; Fisher, Louise; Kenning, Cassandra; Bee, Penny; Bower, Peter

2014-10-31

Primary care is increasingly focussed on the care of people with two or more long-term conditions (multimorbidity). The UK Department of Health strategy for long term conditions is to use self-management support for the majority of patients but there is evidence of limited engagement among primary care professionals and patients with multimorbidity. Furthermore, multimorbidity is more common in areas of socioeconomic deprivation but deprivation may act as a barrier to patient engagement in self-management practices. Effective self-management is considered critical to meet the needs of people living with long term conditions but achieving this is a significant challenge in patients with multimorbidity. This study aimed to explore patient and practitioner views on factors influencing engagement in self-management in the context of multimorbidity. A qualitative study using individual semi-structured interviews with 20 patients and 20 practitioners drawn from four general practices in Greater Manchester situated in areas of high and low social deprivation. Three main factors were identified as influencing patient engagement in self-management: capacity (access and availability of socio-economic resources and time; knowledge; and emotional and physical energy), responsibility (the degree to which patients and practitioners agreed about the division of labour about chronic disease management, including self-management) and motivation (willingness to take-up types of self-management practices). Socioeconomic deprivation negatively impacted on all three factors. Motivation was especially reduced in the presence of mental and physical multimorbidity. Full engagement in self-management practices in multimorbidity was only present where patients' articulated a sense of capacity, responsibility, and motivation. Patient 'know-how' or interpretive capacity to self-manage multimorbidity is potentially an important precursor to responsibility and motivation, and might be a critical target for intervention. However, individual and social resources are needed to generate capacity, responsibility, and motivation for self-management, pointing to a balanced role for health services and wider enabling networks.

Aspergillus vertebral osteomyelitis in a child with a primary monocyte killing defect: response to GM-CSF therapy.

PubMed

Abu Jawdeh, L; Haidar, R; Bitar, F; Mroueh, S; Akel, S; Nuwayri-Salti, N; Dbaibo, G S

2000-07-01

We report the first case of vertebral aspergillosis in a child with a primary defect in monocyte killing, an extremely rare immunodeficiency The diagnosis of defective monocyte killing was made by an in vitro assay that showed normal killing of Staphylococcus aureus by the patient's neutrophils but impaired killing by his monocytes. Importantly, the extensive granulomatous infection that involved the vertebral column, posterior mediastinum, pleura, and lung was not responsive to aggressive treatment with a combination of liposomal amphotericin B. intralesional amphotericin B. itraconazole, and granulocyte transfusions. Dramatic clinical and radiological improvement was only seen after the addition of granulocyte macrophage-colony stimulating factor (GM-CSF) to his treatment regimen. The use of GM-CSF in the treatment of invasive aspergillosis in immunocompromised patients requires further evaluation.

Exploratory Cross-Sectional Study of Factors Associated with the Healthfulness of Parental Responses to Child Food Purchasing Requests.

PubMed

Calloway, Eric E; Ranjit, Nalini; Sweitzer, Sara J; Roberts-Gray, Cindy; Romo-Palafox, Maria J; McInnis, Katie A; Briley, Margaret E

2016-08-01

Objective The main objective of this study was to investigate the relationship between various factors (e.g., sociodemographic, child, and parental factors) and the healthfulness of parental responses to child in-store food purchasing requests. Additionally, a secondary objective is to describe "resist strategies" used by parents to respond to child food-purchasing requests and their efficacy in avoiding conflict. Methods Parent-child dyads (children aged 2-6 years) completed an audio-/visual-recoded food shopping trip at their usual grocery store and time. Recordings of trips were coded for behavioral and environmental factors. Parental healthful response rate (i.e., percent of responses that were healthful) was the primary outcome variable. A healthful response occurred when a parent yielded to a healthful child request, or resisted a non-healthful request. Parents also completed a questionnaire. Kruskal-Wallis tests were used to assess the relationship between the main outcome variable and sociodemographic, child, and parent factors. Results Parents (n = 39) responded healthfully to 62.9 % (±26.7 %) of child food purchasing requests. Low- and middle-income parents, and black and white parents, had significantly higher healthful response rates compared to high-income parents (p = 0.03) and Hispanic/Indian-descent parents (p = 0.02), respectively. Using the "ignore" strategy proved an effective resist strategy in this study, leading to no parent-child conflicts. Conclusions Programming that seeks to improve the healthfulness of food purchasing in families with young children should address unhealthful response behaviors in Hispanic/Indian-descent parents and high-income parents; although, the needs of these groups are different. Further research is needed to confirm and expand on these findings.

18F-FDG PET/CT Imaging of Primary Gastric Lymphoma.

PubMed

Davis, Brady S; Thompson, Trevor A; Wolin, Ely A

2016-12-01

Primary gastric lymphoma (PGL) accounts for less than 4% of gastric neoplasms. 18 F-FDG PET with simultaneously acquired CT ( 18 F-FDG PET/CT) allows for staging and differentiation from other gastric cancers. Rapid diagnosis and staging are important because chemotherapeutic response is generally favorable. We describe a case of an 83-y-old woman with stage II 1 PGL. 18 F-FDG PET/CT can be helpful to differentiate various gastric masses and is an important factor in the staging of PGL. © 2016 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Analysis of early mesothelial cell responses to Staphylococcus epidermidis isolated from patients with peritoneal dialysis-associated peritonitis.

PubMed

McGuire, Amanda L; Mulroney, Kieran T; Carson, Christine F; Ram, Ramesh; Morahan, Grant; Chakera, Aron

2017-01-01

The major complication of peritoneal dialysis (PD) is the development of peritonitis, an infection within the abdominal cavity, primarily caused by bacteria. PD peritonitis is associated with significant morbidity, mortality and health care costs. Staphylococcus epidermidis is the most frequently isolated cause of PD-associated peritonitis. Mesothelial cells are integral to the host response to peritonitis, and subsequent clinical outcomes, yet the effects of infection on mesothelial cells are not well characterised. We systematically investigated the early mesothelial cell response to clinical and reference isolates of S. epidermidis using primary mesothelial cells and the mesothelial cell line Met-5A. Using an unbiased whole genome microarray, followed by a targeted panel of genes known to be involved in the human antibacterial response, we identified 38 differentially regulated genes (adj. p-value < 0.05) representing 35 canonical pathways after 1 hour exposure to S. epidermidis. The top 3 canonical pathways were TNFR2 signaling, IL-17A signaling, and TNFR1 signaling (adj. p-values of 0.0012, 0.0012 and 0.0019, respectively). Subsequent qPCR validation confirmed significant differences in gene expression in a number of genes not previously described in mesothelial cell responses to infection, with heterogeneity observed between clinical isolates of S. epidermidis, and between Met-5A and primary mesothelial cells. Heterogeneity between different S. epidermidis isolates suggests that specific virulence factors may play critical roles in influencing outcomes from peritonitis. This study provides new insights into early mesothelial cell responses to infection with S. epidermidis, and confirms the importance of validating findings in primary mesothelial cells.

Contrasting effect of Saharan dust and UVR on autotrophic picoplankton in nearshore versus offshore waters of Mediterranean Sea

NASA Astrophysics Data System (ADS)

González-Olalla, J. M.; Medina-Sánchez, J. M.; Cabrerizo, M. J.; Villar-Argáiz, Manuel; Sánchez-Castillo, Pedro M.; Carrillo, Presentación

2017-08-01

Autotrophic picoplankton (APP) is responsible for the vast majority of primary production in oligotrophic marine areas, such as the Alboran Sea. The increase in atmospheric dust deposition (e.g., from Sahara Desert) associated with global warming, together with the high UV radiation (UVR) on these ecosystems, may generate effects on APP hitherto unknown. We performed an observational study across the Alboran Sea to establish which factors control the abundance and distribution of APP, and we made a microcosm experiment in two distinct areas, nearshore and offshore, to predict the joint UVR × dust impact on APP at midterm scales. Our observational study showed that temperature (T) was the main factor explaining the APP distribution whereas total dissolved nitrogen positively correlated with APP abundance. Our experimental study revealed that Saharan dust inputs reduced or inverted the UVR damage on the photosynthetic quantum yield (ΦPSII) and picoplanktonic primary production (PPP) in the nearshore area but accentuated it in the offshore. This contrasting effect is partially explained by the nonphotochemical quenching, acting as a photorepair mechanism. Picoeukaryotes reflected the observed effects on the physiological and metabolic variables, and Synechococcus was the only picoprokaryotic group that showed a positive response under UVR × dust conditions. Our study highlights a dual sensitivity of nearshore versus offshore picoplankton to dust inputs and UVR fluxes, just at the time in which these two global-change factors show their highest intensities and may recreate a potential future response of the microbial food web under global-change conditions.

Factors influencing motivation and retention of primary healthcare workers in the rural areas of Oyo State, Nigeria.

PubMed

Jegede, Ayodele S; Adejumo, Prisca; Ushie, Boniface Ayanbekongshie

2013-01-01

Limited data exist on retention of primary healthcare (PHC) staff in rural areas, crippling the already fragile healthcare systems in Nigeria. This study investigated why PHC staff would or would not want to work in rural areas and how they could be retained. Four hundred and twelve (412) health workers and caregivers, and 21 key informants were interviewed in Ona-Ara LGA. Logistic regression statistics was used to analyse quantitative data and narrative for qualitative data. There was no significant factor influencing health workers' unwillingness to work in rural areas and, relationship between their demographic characteristics and perceived reasons to do so. Combined factors influencing PHC workers' willingness to work in rural areas influenced use of PHC. Financial and non-financial incentives are responsible for workers' motivation to work in rural areas. The mal-distribution of health facilities and health workers between urban and rural areas must be addressed. Copyright © 2013 Longwoods Publishing.

Salvage therapy for CLL and the role of stem cell transplantation.

PubMed

Gribben, John G

2005-01-01

Chronic lymphocytic leukaemia (CLL) remains an incurable disease and, notwithstanding the excellent remission rates now achieved with purine analogs and monoclonal antibodies, the vast majority of patients with CLL are destined to relapse after primary treatment. The management of relapsed CLL patients is then dependent upon a number of factors, most importantly age, performance status, previous therapy administered, the response and duration of response to such therapy, and time from last therapy. Although prior therapy and response to such therapy are important factors in determining next therapy, it is often difficult to determine their importance from published studies. Furthermore, the goal of therapy, whether palliative or aggressive, must also be weighed into the decision when deciding on the next line of treatment. With many potential treatments available, the sequence of treatments and the timing of procedures such as stem cell transplantation remain controversial and are the focus of ongoing clinical trials.

PROGNOSTIC FACTORS FOR PRIMARY CENTRAL NERVOUS SYSTEM LYMPHOMAS TREATED WITH HIGH-DOSE METHOTREXATE-BASED CHEMO-RADIOTHERAPY

PubMed Central

Nagane, Motoo; Lee, Jeunghun; Shishido-Hara, Yukiko; Suzuki, Kaori; Shimizu, Saki; Umino, Michiru; Kobayashi, Keiichi; Shiokawa, Yoshiaki

2014-01-01

BACKGROUND: Chemotherapy with high-dose methotrexate (HD-MTX) followed by whole brain radiotherapy (WBRT) is a conventional approach to treat primary central nervous system lymphomas (PCNSL), but some tumors relapse early leading to unfavorable outcome. Several biomarkers have been identified as prognostic factors in PCNSL, however, the correlation of both clinical factors including those related to MTX metabolism and B-cell differentiation and oncogenic biomarkers with response to and outcome by therapy is yet unclear. METHODS: We investigated 32 immunocompetent patients (19 males, 13 females) with PCNSL (all diffuse large B-cell type) treated with HD-MTX based therapy with or without WBRT since 2000 in our institution. Paraffin-embedded formalin-fixed tumor tissue sections were stained immunohistochemically with antibodies against following factors: B-cell differentiation markers (CD10, Bcl-6, Mum-1, CD138); MTX metabolism-related (MRP family, LRP, DHFR); cell cycle-related (p27KIP1, MIB-1); drug resistance-related (MGMT, MLH1, MSH2, MSH6, PMS2); and oncogenes (Myc, Bcl-2). Correlation between positivity of these factors and clinical outcomes were evaluated using logrank test and cox regression analysis. RESULTS: Among these factors, complete response to HD-MTX was significantly associated with longer progression-free survival (PFS)(P = 0.0012), while Bcl-6 expression as well as histological subtype (non-germinal center B-cell, non-GCB) was closely correlated with shorter PFS. Age (>60) (P = 0.006) and MSH2 expression (P = 0.017) were found to be better predictor for overall survival (OS), but in multivariate analysis, they were no longer significant. Other factors involved in MTX metabolism, DNA repair enzymes, and oncogenes did not affect outcome. CONCLUSIONS: Non-GCB subtype and Bcl-6 expression may be associated with worse outcome in patients with PCNSL treated with HD-MTX, while MTX-metabolism related factors did not influence prognosis. Further investigation is needed to assess Bcl-6 as a potential prognostic factor in PCNSL. SECONDARY CATEGORY: Clinical Neuro-Oncology.

The structure of evaluative anxiety among children differing in socioeconomic status, ethnicity, and sex.

PubMed

Rhine, W R; Spaner, S D

1983-11-01

Following Anastasi and Thurstone, the factor structure of evaluative anxiety was examined among six groups of primary age boys and girls (N = 8064). A factor matching technique was used to study hypotheses about the effects of group differences in socioeconomic status (SES), ethnicity, and sex on the pattern of the children's responses to the Test Anxiety Scale for Children (TASC). Hypotheses about the congruence of factor patterns were based on both demographic differences and results of developmental research. The hypothesis of an SES X ethnicity X sex interaction was strongly supported. Implications for comparing factor structures, measuring evaluative anxiety, and future research of evaluative anxiety are discussed.

Neurotrophic Factors NGF, GDNF and NTN Selectively Modulate HSV1 and HSV2 Lytic Infection and Reactivation in Primary Adult Sensory and Autonomic Neurons

PubMed Central

Yanez, Andy A.; Harrell, Telvin; Sriranganathan, Heather J.; Ives, Angela M.; Bertke, Andrea S.

2017-01-01

Herpes simplex viruses (HSV1 and HSV2) establish latency in peripheral ganglia after ocular or genital infection, and can reactivate to produce different patterns and frequencies of recurrent disease. Previous studies showed that nerve growth factor (NGF) maintains HSV1 latency in embryonic sympathetic and sensory neurons. However, adult sensory neurons are no longer dependent on NGF for survival, some populations cease expression of NGF receptors postnatally, and the viruses preferentially establish latency in different populations of sensory neurons responsive to other neurotrophic factors (NTFs). Thus, NGF may not maintain latency in adult sensory neurons. To identify NTFs important for maintaining HSV1 and HSV2 latency in adult neurons, we investigated acute and latently-infected primary adult sensory trigeminal (TG) and sympathetic superior cervical ganglia (SCG) after NTF removal. NGF and glial cell line-derived neurotrophic factor (GDNF) deprivation induced HSV1 reactivation in adult sympathetic neurons. In adult sensory neurons, however, neurturin (NTN) and GDNF deprivation induced HSV1 and HSV2 reactivation, respectively, while NGF deprivation had no effects. Furthermore, HSV1 and HSV2 preferentially reactivated from neurons expressing GFRα2 and GFRα1, the high affinity receptors for NTN and GDNF, respectively. Thus, NTN and GDNF play a critical role in selective maintenance of HSV1 and HSV2 latency in primary adult sensory neurons. PMID:28178213

Neurotrophic Factors NGF, GDNF and NTN Selectively Modulate HSV1 and HSV2 Lytic Infection and Reactivation in Primary Adult Sensory and Autonomic Neurons.

PubMed

Yanez, Andy A; Harrell, Telvin; Sriranganathan, Heather J; Ives, Angela M; Bertke, Andrea S

2017-02-07

Herpes simplex viruses (HSV1 and HSV2) establish latency in peripheral ganglia after ocular or genital infection, and can reactivate to produce different patterns and frequencies of recurrent disease. Previous studies showed that nerve growth factor (NGF) maintains HSV1 latency in embryonic sympathetic and sensory neurons. However, adult sensory neurons are no longer dependent on NGF for survival, some populations cease expression of NGF receptors postnatally, and the viruses preferentially establish latency in different populations of sensory neurons responsive to other neurotrophic factors (NTFs). Thus, NGF may not maintain latency in adult sensory neurons. To identify NTFs important for maintaining HSV1 and HSV2 latency in adult neurons, we investigated acute and latently-infected primary adult sensory trigeminal (TG) and sympathetic superior cervical ganglia (SCG) after NTF removal. NGF and glial cell line-derived neurotrophic factor (GDNF) deprivation induced HSV1 reactivation in adult sympathetic neurons. In adult sensory neurons, however, neurturin (NTN) and GDNF deprivation induced HSV1 and HSV2 reactivation, respectively, while NGF deprivation had no effects. Furthermore, HSV1 and HSV2 preferentially reactivated from neurons expressing GFRα2 and GFRα1, the high affinity receptors for NTN and GDNF, respectively. Thus, NTN and GDNF play a critical role in selective maintenance of HSV1 and HSV2 latency in primary adult sensory neurons.

Dentists' training and willingness to treat adolescents with learning disabilities: the mediating role of social and clinical factors.

PubMed

Coyle, C F; Humphris, G M; Freeman, R

2013-12-01

To test a theoretical model based on Cohen's dental profession factors (training; practitioner attitudes; geography) to investigate practitioners' willingness to treat adolescents with learning disabilities (LD) in primary dental care. A sample of all 537 primary care dentists working in a mainly urban area of Northern Ireland and a more rural area of Scotland. Willingness to treat adolescents with LD. Questionnaire survey of demographic profile, undergraduate education, current knowledge, attitudes towards individuals with LD and willingness to treat this patient group. A path analytical approach (multiple meditational model) was used. Three hundred dentists participated giving a valid response rate of 61%. Undergraduate education and current knowledge (training) strengthened a social model perspective promoting positive attitudes and willingness to treat adolescents with LD. Undergraduate education and current knowledge about disability did not significantly contribute to dentists whose attitudes were underpinned by the medical model of disability. Therefore geography (rural or urban location) was not an influential factor in willingness to treat adolescents with LD. This does not exclude the possibility that area of work may have an influence as a consequence of undergraduate university attended. This model identifies the importance of undergraduate and continuing dental education with regard to modifying professional attitudes (social and clinical factors) to assist practitioners treat adolescents with LD and provide them with inclusive dental services in primary dental care.

A model for evolution and regulation of nicotine biosynthesis regulon in tobacco.

PubMed

Kajikawa, Masataka; Sierro, Nicolas; Hashimoto, Takashi; Shoji, Tsubasa

2017-06-03

In tobacco, the defense alkaloid nicotine is produced in roots and accumulates mainly in leaves. Signaling mediated by jasmonates (JAs) induces the formation of nicotine via a series of structural genes that constitute a regulon and are coordinated by JA-responsive transcription factors of the ethylene response factor (ERF) family. Early steps in the pyrrolidine and pyridine biosynthesis pathways likely arose through duplication of the polyamine and nicotinamide adenine dinucleotide (NAD) biosynthetic pathways, respectively, followed by recruitment of duplicated primary metabolic genes into the nicotine biosynthesis regulon. Transcriptional regulation of nicotine biosynthesis by ERF and cooperatively-acting MYC2 transcription factors is implied by the frequency of cognate cis-regulatory elements for these factors in the promoter regions of the downstream structural genes. Indeed, a mutant tobacco with low nicotine content was found to have a large chromosomal deletion in a cluster of closely related ERF genes at the nicotine-controlling NICOTINE2 (NIC2) locus.

First Spanish version of the Memorial Delirium Assessment Scale: psychometric properties, responsiveness, and factor loadings.

PubMed

Noguera, Antonio; Carvajal, Ana; Alonso-Babarro, Alberto; Chisholm, Gary; Bruera, Eduardo; Centeno, Carlos

2014-01-01

The Memorial Delirium Assessment Scale (MDAS) is a reliable and validated instrument with which to assess delirium. However, MDAS responsiveness has only been investigated in an indirect way. Also, neurobehavioral and global cognitive factors seem to be the MDAS main factor loads. The primary objective of this study was to evaluate MDAS responsiveness and analyze individual factors on this scale. The secondary objective was to confirm concurrent validity and reliability of the Spanish version of the MDAS. The translation-back translation method was used to obtain the Spanish version of the MDAS. Delirium diagnosis was determined by the clinical Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision criteria and with the Confusion Assessment Method. Responsiveness and factor loadings were determined with the Delirium Rating Scale-Revised-98, the Mini-Mental State Examination (MMSE), and the MDAS at baseline (0 hours) and at 72 hours. Variation in the scores of the Delirium Rating Scale-Revised-98 shows a correlation of r = 0.93, with variation in MDAS scores at P < 0.001. Variation in MMSE scores shows a correlation of r = -0.84, with variation in MDAS scores at P = 0.015. Factor I, neurobehavioral (reduced awareness, reduced attention, perceptual disturbance, delusions, altered psychomotor activity, and sleep-wake cycle disturbance), correlated moderately with the MMSE at -0.56. Factor II, global cognitive (disorientation, short-term memory impairment, impaired digit span, and disorganized thinking), correlated strongly with the MMSE at -0.81. Factor II was significantly more reliable than Factor I, rho = 0.7, P = 0.01. The high responsiveness confirms the value of the MDAS for ongoing delirium assessment. Two differentiated factor loadings point to a potential future need for MDAS subscales. Copyright © 2014 U.S. Cancer Pain Relief Committee. All rights reserved.

Enhanced innate immune responsiveness and intolerance to intestinal endotoxins in human biliary epithelial cells contributes to chronic cholangitis.

PubMed

Mueller, Tobias; Beutler, Claudia; Picó, Almudena Hurtado; Shibolet, Oren; Pratt, Daniel S; Pascher, Andreas; Neuhaus, Peter; Wiedenmann, Bertram; Berg, Thomas; Podolsky, Daniel K

2011-11-01

Pattern recognition receptors (PRRs) orchestrate the innate immune defence in human biliary epithelial cells (BECs). Tight control of PRR signalling provides tolerance to physiological amounts of intestinal endotoxins in human bile to avoid constant innate immune activation in BECs. We wanted to determine whether inappropriate innate immune responses to intestinal endotoxins contribute to the development and perpetuation of chronic biliary inflammation. We examined PRR-mediated innate immune responses and protective endotoxin tolerance in primary BECs isolated from patients with primary sclerosing cholangitis (PSC), alcoholic liver disease and patients without chronic liver disease. Expression studies comprised northern blots, RT-PCR, Western blots and immunocytochemistry. Functional studies comprised immuno-precipitation Western blots, FACS for endotoxin uptake, and NF-κB activation assays and ELISA for secreted IL-8 and tumour necrosis factor (TNF)-α. Primary BECs from explanted PSC livers showed reversibly increased TLR and NOD protein expression and activation of the MyD88/IRAK signalling complex. Consecutively, PSC BECs exhibited inappropriate innate immune responses to endotoxins and did not develop immune tolerance after repeated endotoxin exposures. This endotoxin hyper-responsiveness was probably because of the stimulatory effect of abundantly expressed IFN-γ and TNF-α in PSC livers, which stimulated TLR4-mediated endotoxin signalling in BECs, leading to increased TLR4-mediated endotoxin incorporation and impaired inactivation of the TLR4 signalling cascade. As TNF-α inhibition partly restored protective innate immune tolerance, endogenous TNF-α secretion probably contributed to inappropriate endotoxin responses in BECs. Inappropriate innate immune responses to intestinal endotoxins and subsequent endotoxin intolerance because of enhanced PRR signalling in BECs probably contribute to chronic cholangitis. © 2011 John Wiley & Sons A/S.

Characterization of the Phospholipid Platelet-Activating Factor As a Mediator of Inflammation in Chickens

PubMed Central

Garrido, Damien; Chanteloup, Nathalie K.; Trotereau, Angélina; Lion, Adrien; Bailleul, Geoffrey; Esnault, Evelyne; Trapp, Sascha; Quéré, Pascale; Schouler, Catherine; Guabiraba, Rodrigo

2017-01-01

Lipid mediators are known to play important roles in the onset and resolution phases of the inflammatory response in mammals. The phospholipid platelet-activating factor (PAF) is a pro-inflammatory lipid mediator which participates in vascular- and innate immunity-associated processes by increasing vascular permeability, by facilitating leukocyte adhesion to the endothelium, and by contributing to phagocyte activation. PAF exerts its function upon binding to its specific receptor, PAF receptor (PAFR), which is abundantly expressed in leukocytes and endothelial cells (ECs). In chickens, lipid mediators and their functions are still poorly characterized, and the role of PAF as an inflammatory mediator has not yet been investigated. In the present study we demonstrate that primary chicken macrophages express PAFR and lysophosphatidylcholine acyltransferase 2 (LPCAT2), the latter being essential to PAF biosynthesis during inflammation. Also, exogenous PAF treatment induces intracellular calcium increase, reactive oxygen species release, and increased phagocytosis by primary chicken macrophages in a PAFR-dependent manner. We also show that PAF contributes to the Escherichia coli lipopolysaccharide (LPS)-induced pro-inflammatory response and boosts the macrophage response to E. coli LPS via phosphatidylinositol 3-kinase/Akt- and calmodulin kinase II-mediated intracellular signaling pathways. Exogenous PAF treatment also increases avian pathogenic E. coli intracellular killing by chicken macrophages, and PAFR and LPCAT2 are upregulated in chicken lungs and liver during experimental pulmonary colibacillosis. Finally, exogenous PAF treatment increases cell permeability and upregulates the expression of genes coding for proteins involved in leukocyte adhesion to the endothelium in primary chicken endothelial cells (chAEC). In addition to these vascular phenomena, PAF boosts the chAEC inflammatory response to bacteria-associated molecular patterns in a PAFR-dependent manner. In conclusion, we identified PAF as an inflammation amplifier in chicken macrophages and ECs, which suggests that PAF could play important roles in the endothelium-innate immunity interface in birds during major bacterial infectious diseases such as colibacillosis. PMID:29326957

Protective factors for child development at age 2 in the presence of poor maternal mental health: results from the All Our Babies (AOB) pregnancy cohort

PubMed Central

McDonald, Sheila W; Kehler, Heather L; Tough, Suzanne C

2016-01-01

Objective To identify the combination of factors most protective of developmental delay at age 2 among children exposed to poor maternal mental health. Design Observational cohort study. Setting Pregnant women were recruited from primary healthcare offices, the public health laboratory service and community posters in Calgary, Alberta, Canada. Participants 1596 mother–child dyads who participated in the All Our Babies study and who completed a follow-up questionnaire when their child was 2 years old. Among participants who completed the 2-year questionnaire and had complete mental health data (n=1146), 305 women (27%) were classified as high maternal mental health risk. Primary measures Child development at age 2 was described and a resilience analysis was performed among a subgroup of families at maternal mental health risk. The primary outcome was child development problems. Protective factors were identified among families at risk, defined as maternal mental health risk, a composite measure created from participants’ responses to mental health life course questions and standardised mental health measures. Results At age 2, 18% of children were classified as having development problems, 15% with behavioural problems and 13% with delayed social–emotional competencies. Among children living in a family with maternal mental health risk, protective factors against development problems included higher social support, higher optimism, more relationship happiness, less difficulty balancing work and family responsibilities, limiting the child's screen time to <1 hour per day and the child being able to fall asleep in <30 min and sleeping through the night by age 2. Conclusions Among families where the mother has poor mental health, public health and early intervention strategies that support interpersonal relationships, social support, optimism, work–life balance, limiting children's screen time and establishing good sleep habits in the child's first 2 years show promise to positively influence early child development. PMID:28186930

Bone morphogenetic protein 15 and growth differentiation factor 9 expression in the ovary of European sea bass (Dicentrarchus labrax): cellular localization, developmental profiles, and response to unilateral ovariectomy.

PubMed

García-López, Ángel; Sánchez-Amaya, María Isabel; Halm, Silke; Astola, Antonio; Prat, Francisco

2011-12-01

Vertebrate oocytes actively contribute to follicle development by secreting a variety of growth factors, among which bone morphogenetic protein 15 (BMP15/Bmp15) and growth differentiation factor 9 (GDF9/Gdf9) have been paid particular attention. In the present study, we describe the cellular localization, the developmental profiles, and the response to unilateral ovariectomy (a procedure implying the surgical removal of one of the ovaries) of protein and mRNA steady-state levels of Bmp15 and Gdf9 in the ovary of European sea bass, an important fish species for marine aquaculture industry. In situ hybridization and immunohistochemistry demonstrated that the oocyte is the main production site of Bmp15 and Gdf9 in European sea bass ovary. During oocyte development, Bmp15 protein expression started to be detected only from the lipid vesicle stage onwards but not in primary pre-vitellogenic (i.e. perinucleolar) oocytes as the bmp15 mRNA already did. Gdf9 protein and gdf9 mRNA expression were both detected in primary perinucleolar oocytes and followed similar decreasing patterns thereafter. Unilateral ovariectomy induced a full compensatory growth of the remaining ovary in the 2-month period following surgery (Á. García-López, M.I. Sánchez-Amaya, C.R. Tyler, F. Prat 2011). The compensatory growth elicited different changes in the expression levels of mRNA and protein of both factors, although the involvement of Bmp15 and Gdf9 in the regulatory network orchestrating such process remains unclear at present. Altogether, our results establish a solid base for further studies focused on elucidating the specific functions of Bmp15 and Gdf9 during primary and secondary oocyte growth in European sea bass. Copyright © 2011 Elsevier Inc. All rights reserved.

Human Physiological Responses to Acute and Chronic Cold Exposure

NASA Technical Reports Server (NTRS)

Stocks, Jodie M.; Taylor, Nigel A. S.; Tipton, Michael J.; Greenleaf, John E.

2001-01-01

When inadequately protected humans are exposed to acute cold, excessive body heat is lost to the environment and unless heat production is increased and heat loss attenuated, body temperature will decrease. The primary physiological responses to counter the reduction in body temperature include marked cutaneous vasoconstriction and increased metabolism. These responses, and the hazards associated with such exposure, are mediated by a number of factors which contribute to heat production and loss. These include the severity and duration of the cold stimulus; exercise intensity; the magnitude of the metabolic response; and individual characteristics such as body composition, age, and gender. Chronic exposure to a cold environment, both natural and artificial, results in physiological alterations leading to adaptation. Three quite different, but not necessarily exclusive, patterns of human cold adaptation have been reported: metabolic, hypothermic, and insulative. Cold adaptation has also been associated with an habituation response, in which there is a desensitization, or damping, of the normal response to a cold stress. This review provides a comprehensive analysis of the human physiological and pathological responses to cold exposure. Particular attention is directed to the factors contributing to heat production and heat loss during acute cold stress, and the ability of humans to adapt to cold environments.

Innate immune response to Burkholderia mallei.

PubMed

Saikh, Kamal U; Mott, Tiffany M

2017-06-01

Burkholderia mallei is a facultative intracellular pathogen that causes the highly contagious and often the fatal disease, glanders. With its high rate of infectivity via aerosol and recalcitrance toward antibiotics, this pathogen is considered a potential biological threat agent. This review focuses on the most recent literature highlighting host innate immune response to B. mallei. Recent studies focused on elucidating host innate immune responses to the novel mechanisms and virulence factors employed by B. mallei for survival. Studies suggest that pathogen proteins manipulate various cellular processes, including host ubiquitination pathways, phagosomal escape, and actin-cytoskeleton rearrangement. Immune-signaling molecules such as Toll-like receptors, nucleotode-binding oligomerization domain, myeloid differentiation primary response protein 88, and proinflammatory cytokines such as interferon-gamma and tumor necrosis factor-α, play key roles in the induction of innate immune responses. Modifications in B. mallei lipopolysaccharide, in particular, the lipid A acyl groups, stimulate immune responses via Toll-like receptor4 activation that may contribute to persistent infection. Mortality is high because of septicemia and immune pathogenesis with B. mallei exposure. An effective innate immune response is critical to controlling the acute phase of the infection. Both vaccination and therapeutic approaches are necessary for complete protection against B. mallei.

Heterogeneous Molecular Catalysis of Electrochemical Reactions: Volcano Plots and Catalytic Tafel Plots.

PubMed

Costentin, Cyrille; Savéant, Jean-Michel

2017-06-14

We analyze here, in the framework of heterogeneous molecular catalysis, the reasons for the occurrence or nonoccurrence of volcanoes upon plotting the kinetics of the catalytic reaction versus the stabilization free energy of the primary intermediate of the catalytic process. As in the case of homogeneous molecular catalysis or catalysis by surface-active metallic sites, a strong motivation of such studies relates to modern energy challenges, particularly those involving small molecules, such as water, hydrogen, oxygen, proton, and carbon dioxide. This motivation is particularly pertinent for what concerns heterogeneous molecular catalysis, since it is commonly preferred to homogeneous molecular catalysis by the same molecules if only for chemical separation purposes and electrolytic cell architecture. As with the two other catalysis modes, the main drawback of the volcano plot approach is the basic assumption that the kinetic responses depend on a single descriptor, viz., the stabilization free energy of the primary intermediate. More comprehensive approaches, investigating the responses to the maximal number of experimental factors, and conveniently expressed as catalytic Tafel plots, should clearly be preferred. This is more so in the case of heterogeneous molecular catalysis in that additional transport factors in the supporting film may additionally affect the current-potential responses. This is attested by the noteworthy presence of maxima in catalytic Tafel plots as well as their dependence upon the cyclic voltammetric scan rate.

The Response of a Mechanical Oscillator Due to Swept and Dithered Excitation

NASA Technical Reports Server (NTRS)

Davis, R. Benjamin; Durham, R. Caitlyn; Brown, Andrew M.

2010-01-01

A single degree-of-freedom oscillator subject to linearly swept and/or dithered excitation is considered. Dither refers to the variation of an excitation frequency about a given nominal, or primary, frequency. Dither in rocket engine turbopump shaft speeds can be an important consideration when analyzing the dynamic response of turbomachinery components such as turbine blades. Results indicate that the incorporation of dithered excitation into a fatigue analysis may extend the predicted fatigue life of the structure by a factor of two or more.

Commander Naval Air Forces (CNAF) Flight Hour Program: Budgeting and Execution Response to the Implementation of the Fleet Response Plan and OP-20 Pricing Model Changes

DTIC Science & Technology

2005-06-01

seat ratio ( CSR ). The wartime CSR is the result of wartime manning levels divided by Primary Aircraft Authorized (PAA). The Aircrew Manning Factor...justifies the FHP.59 As ADM Mallon suggested, let us look at two simple examples of today’s best business practices with Starbucks and Southwest Airlines...focusing on efforts to achieve optimal efficiency in routine tasks of their operation. The Starbucks example involves redesigning ice scoops and

Using vignettes to assess contributions to the work of addressing child mental health problems in primary care.

PubMed

Wissow, Lawrence S; Zafar, Waleed; Fothergill, Kate; Ruble, Anne; Slade, Eric

2016-01-22

To further efforts to integrate mental health and primary care, this study develops a novel approach to quantifying the amount and sources of work involved in shifting care for common mental health problems to pediatric primary care providers. Email/web-based survey of a convenience sample (n = 58) of Maryland pediatricians (77% female, 58% at their site 10 or more years; 44% in private practice, 52 % urban, 48 % practicing with a co-located mental health provider). Participants were asked to review 11 vignettes, which described primary care management of child/youth mental health problems, and rate them on an integer-based ordinal scale for the overall amount of work involved compared to a 12th reference vignette describing an uncomplicated case of ADHD. Respondents were also asked to indicate factors (time, effort, stress) accounting for their ratings. Vignettes presented combinations of three diagnoses (ADHD, anxiety, and depression) and three factors (medical co-morbidity, psychiatric co-morbidity, and difficult families) reported to complicate mental health care. The reference case was pre-assigned a work value of 2. Estimates of the relationship of diagnosis and complicating factors with workload were obtained using linear regression, with random effects at the respondent level. The 58 pediatricians gave 593 vignette responses. Depression was associated with a 1.09 unit (about 50%) increase in work (95% CL .94, 1.25), while anxiety did not differ significantly from the reference case of uncomplicated ADHD (p = .28). Although all three complicating factors increased work ratings compared with the reference case, family complexity and psychiatric co-morbidity did so the most (.87 and 1.07 units, respectively, P < .001) while medical co-morbidity increased it the least (.44 units, p < .001). Factors most strongly associated with increased overall work were physician time, physician mental effort, and stress; those least strongly associated were staff time, physician physical effort, and malpractice risk. Pediatricians working with co-located mental health providers gave higher work ratings than did those without co-located staff. Both diagnosis and cross-diagnosis complicating factors contribute to the work involved in providing mental health services in primary care. Vignette studies may facilitate understanding which mental health services can be most readily incorporated into primary care as it is presently structured and help guide the design of training programs and other implementation strategies.

Activated stress response pathways within multicellular aggregates utilize an autocrine component.

PubMed

Jack, Graham D; Cabrera, M Carla; Manning, Michael L; Slaughter, Stephen M; Potts, Malcolm; Helm, Richard F

2007-04-01

Multicellular aggregates (spheroids) of primary human foreskin fibroblasts (HFF-2) and a glioblastoma cell line (T98G) entered and exited from long term (2 weeks) metabolic arrest utilizing an autocrine response. Cytokine production (specifically IFN-gamma) activated a Gadd45alpha/p38 pathway that led to increased AP-1 (c-jun and ATF3) transcription factor levels, augmenting cytokine production in an autocrine fashion. Whereas HFF-2 aggregates were capable of surviving long term arrest and recovery during NF-kappaB inhibition independent of JNK activation, T98G aggregates were not. Such endogenous processes are not easily observed with adherent monolayer cell culturing systems, strongly suggesting that more emphasis needs to be placed on determining the operational signal transduction cascades within multicellular aggregates. Extracellular inputs such as spheroid formation, arrest, and regrowth as monolayers invoke intracellular signaling responses converging at the AP-1 transcription factor level. Variations in responses are both cell type and transformation state dependent and require an autocrine cytokine component. The data are discussed in relation to the wounding response and avascular tumor growth mechanisms.

Unconventional imaging with contained granular media

NASA Astrophysics Data System (ADS)

Quadrelli, Marco B.; Basinger, Scott; Sidick, Erkin

2017-09-01

Typically, the cost of a space-borne imaging system is driven by the size and mass of the primary aperture. The solution that we propose uses a method to construct an imaging system in space in which the nonlinear optical properties of a cloud of micron-sized particles, shaped into a specific surface by electromagnetic means, and allows one to form a very large and lightweight aperture of an optical system, hence reducing overall mass and cost. Recent work at JPL has investigated the feasibility of a granular imaging system, concluding that such a system could be built and controlled in orbit. We conducted experiments and simulation of the optical response of a granular lens. In all cases, the optical response, measured by the Modulation Transfer Function, of hexagonal reflectors was closely comparable to that of a conventional spherical mirror. We conducted some further analyses by evaluating the sensitivity to fill factor and grain shape, and found a marked sensitivity to fill factor but no sensitivity to grain shape. We have also found that at fill factors as low as 30%, the reflection from a granular lens is still excellent. Furthermore, we replaced the monolithic primary mirror in an existing integrated model of an optical system (WFIRST Coronagraph) with a granular lens, and found that the granular lens that can be useful for exoplanet detection provides excellent contrast levels. We will present our testbed and simulation results in this paper.

Generation of an immortalized mouse embryonic palatal mesenchyme cell line

PubMed Central

Soriano, Philippe

2017-01-01

Palatogenesis is a complex morphogenetic process, disruptions in which result in highly prevalent birth defects in humans. In recent decades, the use of model systems such as genetically-modified mice, mouse palatal organ cultures and primary mouse embryonic palatal mesenchyme (MEPM) cultures has provided significant insight into the molecular and cellular defects underlying cleft palate. However, drawbacks in each of these systems have prevented high-throughput, large-scale studies of palatogenesis in vitro. Here, we report the generation of an immortalized MEPM cell line that maintains the morphology, migration ability, transcript expression and responsiveness to exogenous growth factors of primary MEPM cells, with increased proliferative potential over primary cultures. The immortalization method described in this study will facilitate the generation of palatal mesenchyme cells with an unlimited capacity for expansion from a single genetically-modified mouse embryo and enable mechanistic studies of palatogenesis that have not been possible using primary culture. PMID:28582446

The Noggin Factor in Survey Research: Developing New Techniques for Assessing Nonresponse Bias.

ERIC Educational Resources Information Center

Clark, Sheldon B.

The primary objective of this paper is to encourage survey researchers not to become overly reliant on the literature for generic solutions to non-response bias problems. In addition, the paper recounts an example of how a non-traditional approach was used to maximize the usefulness of data collected under unusual constraints and with an a priori…

Response of Scots pine stand vitality to changes in environmental factors in Poland, 1991-1995

Treesearch

Jerzy Wawrzoniak

1998-01-01

Vitality inventories of Scots pine stands, the most common species in Poland, have been done since 1991 by using the ICP-Forest methodology. In Scots pine stands older than 40 years, 1,040 observation plots were established. Defoliation was used as the primary indicator of stand vitality. During 1991 to 1995, SO2 and NOx...

Resin flow responses to fertilization, wounding and fungal inoculation in loblolly pine (Pinus taeda) in North Carolina

Treesearch

Larissa Knebel; Daniel J. Robinson; Thomas R. Wentworth; Kier D. Klepzig

2009-01-01

Resin flow is the primary means of natural defense against southern pine beetle (Dendroctonus frontalis Zimm.), the most important insect pest of Pinus spp. in the southern United States. As a result, factors affecting resin flowa are of interest to researchers and forest managers. We examined the influence of fertilization, artificial...

Organisational Learning Approaches to School Leadership and Management: Teachers' Values and Perceptions of Practice

ERIC Educational Resources Information Center

Pedder, David; MacBeath, John

2008-01-01

In this article, we report results of a survey of 1,397 teachers in 26 primary and 17 secondary schools in England as part of the Learning How to Learn project. We consider how school self-evaluation can be understood within an organisational learning frame. Factor analysis of teachers' responses helped us identify 4 dimensions of organisational…

Nrf2-dependent induction of innate host defense via heme oxygenase-1 inhibits Zika virus replication

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

Huang, Hanxia; Falgout, Barry; Takeda, Kazuyo

We identified primary human monocyte-derived macrophages (MDM) as vulnerable target cells for Zika virus (ZIKV) infection. We demonstrate dramatic effects of hemin, the natural inducer of the heme catabolic enzyme heme oxygenase-1 (HO-1), in the reduction of ZIKV replication in vitro. Both LLC-MK2 monkey kidney cells and primary MDM exhibited hemin-induced HO-1 expression with major reductions of >90% in ZIKV replication, with little toxicity to infected cells. Silencing expression of HO-1 or its upstream regulatory gene, nuclear factor erythroid-related factor 2 (Nrf2), attenuated hemin-induced suppression of ZIKV infection, suggesting an important role for induction of these intracellular mediators in retardingmore » ZIKV replication. The inverse correlation between hemin-induced HO-1 levels and ZIKV replication provides a potentially useful therapeutic modality based on stimulation of an innate cellular response against Zika virus infection. - Highlights: •Hemin treatment protected monocyte-derived macrophages against Zika virus (ZIKV) infection. •Innate cellular protection against ZIKV infection correlated with Nrf2-dependent HO-1 expression. •Stimulation of innate cellular responses may provide a therapeutic strategy against ZIKV infection.« less

Crucial Dimensions of Human Altruism. Affective vs. Conceptual Factors Leading to Helping or Reinforcing Others

PubMed Central

Szuster, Anna

2016-01-01

The aim of this article is to identify factors leading to favorable attitudes toward other people from different social categories. The parts of article reflect diverse levels of altruism regulation from primary affective responses to the environment, through social norms, to abstract moral concepts related to good and evil. The latter allow understanding of the perspective of other people (including those belonging to out-groups), acceptance of their values and engagement not only in helping behavior but also in supporting the development of others. PMID:27148127

The impact of temperament and character on the efficacy of nonpharmacologic treatment of primary insomnia.

PubMed

An, Hoyoung; Park, Jangho; Jang, Eun-Sook; Chung, Seockhoon

2012-02-01

Nonpharmacologic treatment, also known as cognitive behavioral treatment, is a first-line treatment of primary insomnia. We aimed to assess factors, including temperament and character, that were associated with responses to nonpharmacologic treatments of primary insomnia, that may assist physicians to recommend appropriate treatment. Outpatients diagnosed with psychophysiological insomnia (n = 99) were recruited between May 2009 and January 2010. Among 69 patients who consented to participate, 44 completed treatment and all assessment measures. In addition, 37 normal control subjects were also recruited. Baseline characteristics were assessed using the Temperament and Character Inventory, the Insomnia Severity Index, the Pittsburgh Sleep Quality Index, the Epworth Sleepiness Scale, the Dysfunctional Beliefs and Attitudes about Sleep scale, and the Hospital Anxiety and Depression Scale. After treatment, all assessment scales excluding the Temperament and Character Inventory were repeated. All patients received nonpharmacologic treatments, including sleep restriction, cognitive therapy, and sleep hygiene education. Novelty seeking, harm avoidance, reward dependence, cooperativeness, and self-transcendence scores were significantly different between normal controls and study subjects. Participants were divided into treatment responders (n = 23) and nonresponders (n = 21). Responders were significantly younger (50.3 ± 12.8 vs 58.7 ± 9.6 years, P = .02) and had significantly higher reward dependence scores (51.7 ± 5.9 vs 42.9 ± 6.9, P < .01) compared with nonresponders. The difference in reward dependence scores remained significant after controlling for other factors (odds ratio, 1.23; 95% confidence interval, 1.08-1.40; P = .01). Among personality dimensions, reward dependence was significantly associated with response to nonpharmacologic treatment in patients with primary insomnia. Copyright © 2012 Elsevier Inc. All rights reserved.

Treatment for liver metastases from breast cancer: Results and prognostic factors

PubMed Central

Li, Xiao-Ping; Meng, Zhi-Qiang; Guo, Wei-Jian; Li, Jie

2005-01-01

AIM: Liver metastases from breast cancer (BCLM) are associated with poor prognosis. Cytotoxic chemotherapy can result in regression of tumor lesions and a decrease in symptoms. Available data, in the literature, also suggest a subgroup of patients may benefit from surgery, but few talked about transcatheter arterial chemoembolization (TACE). We report the results of TACE and systemic chemotherapy for patients with liver metastases from breast cancer and evaluate the prognostic factors. METHODS: Forty-eight patients with liver metastases, from proved breast primary cancer were treated with TACE or systemic chemotherapy between January 1995 and December 2000. Treatment results were assessed according to WHO criteria, along with analysis of prognostic factors for survival using Cox regression model. RESULTS: The median follow-up was 28 mo (1-72 mo). Response rates were calculated for the TACE group and chemotherapy group, being 35.7% and 7.1%, respectively. The difference was significant. The one-, two- and three-year Survival rates for the TACE group were 63.04%, 30.35%, and 13.01%, and those for the systemic chemotherapy group were 33.88%, 11.29%, and 0%. According to univariate analysis, variables significantly associated with survival were the lymph node status of the primary cancer, the clinical stage of liver metastases, the Child-Pugh grade, loss of weight. Other factors such as age, the intervals between the primary to the metastases, the maximal diameter of the liver metastases, the number of liver metastases, extrahepatic metastasis showed no prognostic significances. These factors mentioned above such as the lymph node status of the primary cancer, the clinical stage of liver metastases, the Child-Pugh grade, loss of weight were also independent factors in multivariate analysis. CONCLUSION: TACE treatment of liver metastases from breast cancer may prolong survival in certain patients. This approach offers new promise for the curative treatment of the patients with metastatic breast cancer. PMID:15968739

CDX2 expression is concordant between primary colorectal cancer lesions and corresponding liver metastases independent of chemotherapy: a single-center retrospective study in Japan.

PubMed

Shigematsu, Yasuyuki; Inamura, Kentaro; Mise, Yoshihiro; Saiura, Akio; Rehnberg, Emil; Yamamoto, Noriko; Ishikawa, Yuichi; Takahashi, Shunji; Kanda, Hiroaki

2018-03-30

Loss of caudal-type homeobox transcription factor 2 (CDX2) expression in colorectal cancers (CRCs) has recently been proposed as a promising predictive biomarker for not only prognosis but also response to chemotherapy. However, the relationship between alterations in CDX2 expression during cancer progression and response to chemotherapy remains unclear. We herein aimed to determine the concordance of CDX2 expression between primary CRCs and corresponding liver metastases, in association with chemotherapy. Primary CRCs exhibited heterogeneous CDX2 expression. Seven of the 144 CRCs in the cohort (4.9%, 95% confidential interval, 2.0%-9.8%) were CDX2-negative. The concordance rate of the CDX2 expression status in patients who did not receive chemotherapy was 100% ( P = 0.041), whereas the concordance rate among patients who received chemotherapy only after primary resection was 96.3% ( P = 0.005). Moreover, the concordance rate in patients who received chemotherapy before both primary resection and liver metastasectomy was 100% ( P < 0.001). CDX2 expression status was highly concordant between primary CRCs and corresponding liver metastases, independent of chemotherapy, suggesting that the CDX2 expression status in CRCs was not affected by metastasis or chemotherapy. A total of 144 consecutive patients with CRC who were treated at a single center in Japan between 2006 and 2014 were included. Formalin-fixed paraffin-embedded whole sections of surgically resected primary CRCs and corresponding liver metastases were assessed for CDX2 expression by immunohistochemistry.

Prevalence of anxiety among women attending a primary care clinic in Malaysia

PubMed Central

Sidik, Sherina Mohd; Arroll, Bruce; Goodyear-Smith, Felicity

2011-01-01

Background This is the first study investigating anxiety among women attending a primary care clinic in Malaysia. Aim The objective was to determine the factors associated with anxiety among these women. Design This cross-sectional study was conducted in a government-funded primary care clinic in Malaysia. Consecutive female patients attending the clinic during the data-collection period were invited to participate in the study. Method Participants were given self-administered questionnaires, which included the validated Generalised Anxiety Disorder-7 questionnaire (GAD-7) Malay version to detect anxiety. Results Of the 1023 patients who were invited, 895 agreed to participate (response rate 87.5%). The prevalence of anxiety in this study was 7.8%, based on the GAD-7 (score ≥8). Multiple logistic regression analysis found that certain stressful life events and the emotional aspect of domestic violence were significantly associated with anxiety (P<0.05). Conclusion The prevalence of anxiety among women in this study is similar to that found in other countries. Factors found to be associated with anxiety, especially issues on domestic violence, need to be addressed and managed appropriately. PMID:21801511

CMX-8933, a peptide fragment of the glycoprotein ependymin, promotes activation of AP-1 transcription factor in mouse neuroblastoma and rat cortical cell cultures.

PubMed

Shashoua, V E; Adams, D; Boyer-Boiteau, A

2001-10-19

An 8-amino acid peptide fragment (CMX-8933) of Ependymin, a glycoprotein component of the extracellular fluid and cerebrospinal fluid of goldfish brain, was synthesized and tested for its capacity to activate AP-1 transcription factor in cell cultures. Dose-response and time-course studies of AP-1's binding to DNA were carried out in neuroblastoma (NB2a/dl) and primary rat brain cortical cultures using an electrophoretic mobility shift assay (EMSA). A 13-14-fold increase in AP-1's DNA binding was obtained when NB2a cells were incubated for 4 h with 6-10 microg/ml CMX-8933. Primary rat brain cortical cultures were much more sensitive to the effects of CMX-8933 than transformed (NB2a) cultures; here a 26.7+/-5.2-fold increase in binding was observed following a 3-h treatment with as little as 10 ng/ml peptide. These findings are consistent with an activation of this transcription factor, a characteristic that has been previously correlated with functional aspects of full-sized neurotrophic factors (nerve growth factor and brain-derived nerve growth factor) in neuronal differentiation and regeneration. Such data suggest a role for Ependymin in transcriptional control.

Primary Vaginal Melanoma, A Rare and Aggressive Entity. A Case Report and Review of the Literature

PubMed Central

KALAMPOKAS, EMMANOUIL; KALAMPOKAS, THEODOROS; DAMASKOS, CHRISTOS

2017-01-01

Malignant melanoma of the vagina is a rare, aggressive malignancy of poor prognosis. It principally affects post-menopausal women, with a mean age of 57 years, and the factors that contribute to its appearance are not well known. The first case of primary malignant vaginal melanoma was reported in 1887 and modern literature has noted about 500 cases, globally. Vaginal melanomas constitute 0.3% of all malignant melanomas and fewer than 3% of all vaginal carcinomas. To date there is no clear consensus regarding treatment. An early, accurate diagnosis and prompt investigation is essential in reaching appropriate treatment decisions. We present a clinical case of primary vaginal melanoma and review the literature briefly, presenting the current treatment plans and updates of this rare gynecological malignancy. Considerations, epidemiology, associated risk factors, response to therapy and expected outcome are also discussed. Conclusion: Primary malignant vaginal melanoma is a rare but aggressive melanoma that affects women in their 6th and 7th decade of life. The tumor appears as a dark node or spindle but can also be amelanotic. The size of the tumor is indicative of the prognostic factors. Surgery seems to be the only efficient treatment. Postoperative adjuvant therapy might help in preventing recurrence of the tumor. The survival rate is largely dependent on nodal and distant metastasis of the disease after initial tumor resection. There is a dire need to form a proper therapeutic regime to control this disease. PMID:28064232

Primary Care Outcomes Questionnaire: psychometric testing of a new instrument.

PubMed

Murphy, Mairead; Hollinghurst, Sandra; Cowlishaw, Sean; Salisbury, Chris

2018-06-01

Patients attend primary care for many reasons and to achieve a range of possible outcomes. There is currently no Patient Reported Outcome Measure (PROM) designed to capture these diverse outcomes, and trials of interventions in primary care may thus fail to detect beneficial effects. This study describes the psychometric testing of the Primary Care Outcomes Questionnaire (PCOQ), which was designed to capture a broad range of outcomes relevant to primary care. Questionnaires were administered in primary care in South West England. Patients completed the PCOQ in GP waiting rooms before a consultation, and a second questionnaire, including the PCOQ and seven comparator PROMs, after 1 week. Psychometric testing included exploratory factor analysis on the PCOQ, internal consistency, correlation coefficients between domain scores and comparator measures, and repeated measures effect sizes indicating change across 1 week. In total, 602 patients completed the PCOQ at baseline, and 264 (44%) returned the follow-up questionnaire. Exploratory factor analysis suggested four dimensions underlying the PCOQ items: health and wellbeing, health knowledge and self-care, confidence in health provision, and confidence in health plan. Each dimension was internally consistent and correlated as expected with comparator PROMs, providing evidence of construct validity. Patients reporting an improvement in their main problem exhibited small to moderate improvements in relevant domain scores on the PCOQ. The PCOQ was acceptable, feasible, showed strong psychometric properties, and was responsive to change. It is a promising new tool for assessment of outcomes of primary care interventions from a patient perspective. © British Journal of General Practice 2018.

Net primary productivity of China's terrestrial ecosystems from a process model driven by remote sensing.

PubMed

Feng, X; Liu, G; Chen, J M; Chen, M; Liu, J; Ju, W M; Sun, R; Zhou, W

2007-11-01

The terrestrial carbon cycle is one of the foci in global climate change research. Simulating net primary productivity (NPP) of terrestrial ecosystems is important for carbon cycle research. In this study, China's terrestrial NPP was simulated using the Boreal Ecosystem Productivity Simulator (BEPS), a carbon-water coupled process model based on remote sensing inputs. For these purposes, a national-wide database (including leaf area index, land cover, meteorology, vegetation and soil) at a 1 km resolution and a validation database were established. Using these databases and BEPS, daily maps of NPP for the entire China's landmass in 2001 were produced, and gross primary productivity (GPP) and autotrophic respiration (RA) were estimated. Using the simulated results, we explore temporal-spatial patterns of China's terrestrial NPP and the mechanisms of its responses to various environmental factors. The total NPP and mean NPP of China's landmass were 2.235 GtC and 235.2 gCm(-2)yr(-1), respectively; the total GPP and mean GPP were 4.418 GtC and 465 gCm(-2)yr(-1); and the total RA and mean RA were 2.227 GtC and 234 gCm(-2)yr(-1), respectively. On average, NPP was 50.6% of GPP. In addition, statistical analysis of NPP of different land cover types was conducted, and spatiotemporal patterns of NPP were investigated. The response of NPP to changes in some key factors such as LAI, precipitation, temperature, solar radiation, VPD and AWC are evaluated and discussed.

Satisfaction With Knee Function After Primary Anterior Cruciate Ligament Reconstruction Is Associated With Self-Efficacy, Quality of Life, and Returning to the Preinjury Physical Activity.

PubMed

Ardern, Clare L; Österberg, Annika; Sonesson, Sofi; Gauffin, Håkan; Webster, Kate E; Kvist, Joanna

2016-08-01

To assess whether patient-reported outcomes (psychological factors, appraisals of knee function, and physical activity participation) were associated with satisfaction with knee function after anterior cruciate ligament (ACL) reconstruction. Participants who were aged 18 to 45 years and a minimum 12 months post primary ACL reconstruction completed a questionnaire battery evaluating knee self-efficacy, knee-related quality of life, self-reported function, and physical activity participation. Participants' responses to the question "If you were to spend the rest of your life with your knee just the way it has been in the last week, would you feel . . . (7-point ordinal scale; 1 = happy, 7 = unhappy)" were categorized as satisfied, mostly satisfied, or dissatisfied and used as the primary outcome. Ordinal regression was used to examine associations between independent variables and the primary outcome. A total of 177 participants were included at an average of 3 years after primary ACL reconstruction. At follow-up, 44% reported they would be satisfied, 28% mostly satisfied, and 28% dissatisfied with the outcome of ACL reconstruction. There were significant differences in psychological responses and appraisal of knee function between the 3 groups (P = .001), and significantly more people in the satisfied group had returned to their preinjury activity (58%) than in the mostly satisfied (28%) and dissatisfied (26%) groups (P = .001). Multivariable analysis demonstrated that the odds of being satisfied increased by a factor of 3 with higher self-efficacy, greater knee-related quality of life, and returning to the preinjury activity. People who had returned to their preinjury physical activity and who reported higher knee-related self-efficacy and quality of life were more likely to be satisfied with the outcome of ACL reconstruction. Level IV, prognostic case series. Copyright © 2016 Arthroscopy Association of North America. Published by Elsevier Inc. All rights reserved.

Emotion processing in the criminal psychopath: the role of attention in emotion-facilitated memory.

PubMed

Glass, Samantha J; Newman, Joseph P

2009-02-01

The response modulation hypothesis specifies that low-anxious psychopathic individuals have difficulty processing information outside their primary attentional focus. To evaluate the applicability of this model to affective processing, the authors had 239 offenders, classified with the Psychopathy Checklist--Revised (R. D. Hare, 2003) and the Welsh Anxiety Scale (G. Welsh, 1956), perform 1 of 3 emotion memory tasks that examined the effects of emotion on memory for primary and contextual information. Regardless of anxiety level, psychopathic and control offenders demonstrated a significant and comparable memory bias for emotional over neutral words in the primary conditions. However, psychopathic individuals showed significantly less memory bias than did controls in the contextual conditions. Results indicate that the impact of emotion on memory is moderated by attentional factors.

The bZIP Transcription Factor Fgap1 Mediates Oxidative Stress Response and Trichothecene Biosynthesis But Not Virulence in Fusarium graminearum

PubMed Central

Montibus, Mathilde; Ducos, Christine; Bonnin-Verdal, Marie-Noelle; Bormann, Jorg; Ponts, Nadia; Richard-Forget, Florence; Barreau, Christian

2013-01-01

Redox sensing is of primary importance for fungi to cope with oxidant compounds found in their environment. Plant pathogens are particularly subject to the oxidative burst during the primary steps of infection. In the budding yeast Saccharomyces cerevisiae, it is the transcription factor Yap1 that mediates the response to oxidative stress via activation of genes coding for detoxification enzymes. In the cereal pathogen Fusarium graminearum, Fgap1 a homologue of Yap1 was identified and its role was investigated. During infection, this pathogen produces mycotoxins belonging to the trichothecenes family that accumulate in the grains. The global regulation of toxin biosynthesis is not completely understood. However, it is now clearly established that an oxidative stress activates the production of toxins by F. graminearum. The involvement of Fgap1 in this activation was investigated. A deleted mutant and a strain expressing a truncated constitutive form of Fgap1 were constructed. None of the mutants was affected in pathogenicity. The deleted mutant showed higher level of trichothecenes production associated with overexpression of Tri genes. Moreover activation of toxin accumulation in response to oxidative stress was no longer observed. Regarding the mutant with the truncated constitutive form of Fgap1, toxin production was strongly reduced. Expression of oxidative stress response genes was not activated in the deleted mutant and expression of the gene encoding the mitochondrial superoxide dismutase MnSOD1 was up-regulated in the mutant with the truncated constitutive form of Fgap1. Our results demonstrate that Fgap1 plays a key role in the link between oxidative stress response and F. graminearum secondary metabolism. PMID:24349499

Lysophosphatidic acid signaling through its receptor initiates profibrotic epithelial cell fibroblast communication mediated by epithelial cell derived connective tissue growth factor.

PubMed

Sakai, Norihiko; Chun, Jerold; Duffield, Jeremy S; Lagares, David; Wada, Takashi; Luster, Andrew D; Tager, Andrew M

2017-03-01

The expansion of the fibroblast pool is a critical step in organ fibrosis, but the mechanisms driving expansion remain to be fully clarified. We previously showed that lysophosphatidic acid (LPA) signaling through its receptor LPA 1 expressed on fibroblasts directly induces the recruitment of these cells. Here we tested whether LPA-LPA 1 signaling drives fibroblast proliferation and activation during the development of renal fibrosis. LPA 1 -deficient (LPA 1 -/- ) or -sufficient (LPA 1 +/+ ) mice were crossed to mice with green fluorescent protein expression (GFP) driven by the type I procollagen promoter (Col-GFP) to identify fibroblasts. Unilateral ureteral obstruction-induced increases in renal collagen were significantly, though not completely, attenuated in LPA 1 -/- Col-GFP mice, as were the accumulations of both fibroblasts and myofibroblasts. Connective tissue growth factor was detected mainly in tubular epithelial cells, and its levels were suppressed in LPA 1 -/- Col-GFP mice. LPA-LPA 1 signaling directly induced connective tissue growth factor expression in primary proximal tubular epithelial cells, through a myocardin-related transcription factor-serum response factor pathway. Proximal tubular epithelial cell-derived connective tissue growth factor mediated renal fibroblast proliferation and myofibroblast differentiation. Administration of an inhibitor of myocardin-related transcription factor/serum response factor suppressed obstruction-induced renal fibrosis. Thus, targeting LPA-LPA 1 signaling and/or myocardin-related transcription factor/serum response factor-induced transcription could be promising therapeutic strategies for renal fibrosis. Copyright © 2016 International Society of Nephrology. Published by Elsevier Inc. All rights reserved.

Toxic hepatitis in occupational exposure to solvents

PubMed Central

Malaguarnera, Giulia; Cataudella, Emanuela; Giordano, Maria; Nunnari, Giuseppe; Chisari, Giuseppe; Malaguarnera, Mariano

2012-01-01

The liver is the main organ responsible for the metabolism of drugs and toxic chemicals, and so is the primary target organ for many organic solvents. Work activities with hepatotoxins exposures are numerous and, moreover, organic solvents are used in various industrial processes. Organic solvents used in different industrial processes may be associated with hepatotoxicity. Several factors contribute to liver toxicity; among these are: species differences, nutritional condition, genetic factors, interaction with medications in use, alcohol abuse and interaction, and age. This review addresses the mechanisms of hepatotoxicity. The main pathogenic mechanisms responsible for functional and organic damage caused by solvents are: inflammation, dysfunction of cytochrome P450, mitochondrial dysfunction and oxidative stress. The health impact of exposure to solvents in the workplace remains an interesting and worrying question for professional health work. PMID:22719183

Frequency domain analysis of the random loading of cracked panels

NASA Technical Reports Server (NTRS)

Doyle, James F.

1994-01-01

The primary effort concerned the development of analytical methods for the accurate prediction of the effect of random loading on a panel with a crack. Of particular concern was the influence of frequency on the stress intensity factor behavior. Many modern structures, such as those found in advanced aircraft, are lightweight and susceptible to critical vibrations, and consequently dynamic response plays a very important role in their analysis. The presence of flaws and cracks can have catastrophic consequences. The stress intensity factor, K, emerges as a very significant parameter that characterizes the crack behavior. In analyzing the dynamic response of panels that contain cracks, the finite element method is used, but because this type of problem is inherently computationally intensive, a number of ways of calculating K more efficiently are explored.

Tumor Necrosis Factor Inhibitor Primary Failure Predicts Decreased Ustekinumab Efficacy in Psoriasis Patients.

PubMed

Sorensen, Eric P; Fanucci, Kristina A; Saraiya, Ami; Volf, Eva; Au, Shiu-chung; Argobi, Yahya; Mansfield, Ryan; Gottlieb, Alice B

2015-08-01

Additional studies are needed to examine the efficacy of ustekinumab in psoriasis patients who have previously been exposed to tumor necrosis factor inhibitors (TNFi). To examine the predictive effect of TNFi primary failure and the number of TNFi exposures on the efficacy of ustekinumab in psoriasis treatment. This retrospective study examined 44 psoriasis patients treated at the Tufts Medical Center Department of Dermatology between January 2008 and July 2014. Patients were selected if they were treated with ustekinumab and had ≥ 1 previous TNFi exposure. The following subgroups were compared: patients with vs without a previous TNFi primary failure, and patients with one vs multiple previous TNFi exposures. The efficacy measure used was the previously validated Simple Measure for Assessing Psoriasis Activity (S-MAPA), which is calculated by the product of the body surface area and physician global assessment. The primary outcome was the percentage improvement S-MAPA from course baseline at week 12 of ustekinumab treatment. Secondary outcomes were the psoriasis clearance, primary failure, and secondary failure rates with ustekinumab treatment. Patients with a previous TNFi primary failure had a significantly lower percentage improvement in S-MAPA score at week 12 of ustekinumab treatment compared with patients without TNFi primary failure (36.2% vs 61.1%, P=.027). Multivariate analysis demonstrated that this relationship was independent of patient demographics and medical comorbidities. Patients with multiple TNFi exposures had a non-statistically significant lower percentage S-MAPA improvement at week 12 (40.5% vs 52.9%, P=.294) of ustekinumab treatment compared with patients with a single TNFi exposure. Among psoriasis patients previously exposed to TNFi, a history of a previous TNFi primary failure predicts a decreased response to ustekinumab independent of patient demographics and medical comorbidities.

Primary CNS Lymphoma in Children and Adolescents: A Descriptive Analysis from the International Primary CNS Lymphoma Collaborative Group (IPCG)

PubMed Central

Abla, Oussama; Weitzman, Sheila; Blay, Jean-Yves; O’Neill, Brian Patrick; Abrey, Lauren E.; Neuwelt, Edward; Doolittle, Nancy D.; Baehring, Joachim; Pradhan, Kamnesh; Martin, S. Eric; Guerrera, Michael; Shah, Shafqat; Ghesquieres, Hervé; Silver, Michael; Betensky, Rebecca A.; Batchelor, Tracy

2014-01-01

Purpose To describe the demographic and clinical features and outcomes for children and adolescents with primary CNS lymphoma (PCNSL). Experimental Design A retrospective series of children and adolescents with PCNSL was assembled from ten cancer centers in three countries. Results Twenty-nine patients with a median age of 14 years were identified. Sixteen (55%) had Eastern Cooperative Oncology Group (ECOG) performance status (PS) ≥ 1. Front line therapy consisted of chemotherapy (CT) only in twenty patients (69%), while 9 (31%) had CT plus cranial radiotherapy. Most patients received methotrexate (MTX)-based regimens. Overall response rate was 86% (CR 69%, PR 17%). The 2 year PFS and OS rates were 61% and 86%, respectively; the 3 year OS was 82%. Univariate analyses were conducted for age (≤ 14 vs > 14 years), PS (0 or 1 vs >1), deep brain lesions, MTX dose, primary treatment with CT alone, intrathecal chemotherapy and high-dose therapy. Primary treatment with CT alone was associated with better overall response rates with an OR of 0.125 (p=0.02). There was a marginally significant relationship between higher doses of MTX and response (OR =1.5, p = 0.06). ECOG-PS of 0–1 was the only factor associated with better outcome with hazard ratios of 0.136 (p = 0.017) and 0.073(p = 0.033) for PFS and OS, respectively. Conclusion This is the largest series collected of pediatric PCNSL. The outcome of children and adolescents appears to be better than in adults. PS of 0–1 is associated with better survival. PMID:21224370

[Control or involvement? Relationship between parenting style and adolescent depression].

PubMed

Pikó, Bettina; Balázs, Máté Ádám

2010-01-01

A number of studies have pointed out that parenting style has a longstanding impact on psychological health. Besides parental/familial risk factors certain aspects of the parent-adolescent relationship may serve as a protective factor and help prevent adolescent depression such as the authoritative parenting style. The aim of the present study has been to analyze interrelationships between adolescent depressive symptomatology, authoritative parenting style, negative and positive parental links. The study was carried out on in all primary and secondary schools in Mako and the surrounding region in the spring of 2010, students of grades 7-12 (N = 2072), 49.2% of the sample were males and 50.8% females; 38.1% primary school pupils and 61.9% high school students. Self-administered questionnaires contained items of measuring depressive symptoms (CDI) and parental variables beyond sociodemographics. After descripive statistics, correlation and multiple linear regression analyses have been used to detect interrelationships. Data support the protective effect of authoritative parenting style in relation to adolescent depression, particularly among girls. Among boys, only mother's responsive behavior proved to be a protective factor. Among girls, however, both elements of the father's authoritative parenting style were decisive; not only responsiveness but also demandingness. The parenting style of the opposite-sex parent was prevailing in both sexes. Negative family interactions served as a risk factor, whereas positive parental identification was a protective factor during adolescence as well. There is a need to strengthen the role of the authoritative parenting style and to guarantee the presence of the opposite-sex parents in the adolescents' lives. Nowadays there are family-oriented interventions which put forward the effectiveness of parenting and problem-solving and aiming at harmonizing the parent-adolescent relationship.

Confidential reporting of patient safety events in primary care: results from a multilevel classification of cognitive and system factors.

PubMed

Kostopoulou, Olga; Delaney, Brendan

2007-04-01

To classify events of actual or potential harm to primary care patients using a multilevel taxonomy of cognitive and system factors. Observational study of patient safety events obtained via a confidential but not anonymous reporting system. Reports were followed up with interviews where necessary. Events were analysed for their causes and contributing factors using causal trees and were classified using the taxonomy. Five general medical practices in the West Midlands were selected to represent a range of sizes and types of patient population. All practice staff were invited to report patient safety events. Main outcome measures were frequencies of clinical types of events reported, cognitive types of error, types of detection and contributing factors; and relationship between types of error, practice size, patient consequences and detection. 78 reports were relevant to patient safety and analysable. They included 21 (27%) adverse events and 50 (64%) near misses. 16.7% (13/71) had serious patient consequences, including one death. 75.7% (59/78) had the potential for serious patient harm. Most reports referred to administrative errors (25.6%, 20/78). 60% (47/78) of the reports contained sufficient information to characterise cognition: "situation assessment and response selection" was involved in 45% (21/47) of these reports and was often linked to serious potential consequences. The most frequent contributing factor was work organisation, identified in 71 events. This included excessive task demands (47%, 37/71) and fragmentation (28%, 22/71). Even though most reported events were near misses, events with serious patient consequences were also reported. Failures in situation assessment and response selection, a cognitive activity that occurs in both clinical and administrative tasks, was related to serious potential harm.

Confidential reporting of patient safety events in primary care: results from a multilevel classification of cognitive and system factors

PubMed Central

Kostopoulou, Olga; Delaney, Brendan

2007-01-01

Objective To classify events of actual or potential harm to primary care patients using a multilevel taxonomy of cognitive and system factors. Methods Observational study of patient safety events obtained via a confidential but not anonymous reporting system. Reports were followed up with interviews where necessary. Events were analysed for their causes and contributing factors using causal trees and were classified using the taxonomy. Five general medical practices in the West Midlands were selected to represent a range of sizes and types of patient population. All practice staff were invited to report patient safety events. Main outcome measures were frequencies of clinical types of events reported, cognitive types of error, types of detection and contributing factors; and relationship between types of error, practice size, patient consequences and detection. Results 78 reports were relevant to patient safety and analysable. They included 21 (27%) adverse events and 50 (64%) near misses. 16.7% (13/71) had serious patient consequences, including one death. 75.7% (59/78) had the potential for serious patient harm. Most reports referred to administrative errors (25.6%, 20/78). 60% (47/78) of the reports contained sufficient information to characterise cognition: “situation assessment and response selection” was involved in 45% (21/47) of these reports and was often linked to serious potential consequences. The most frequent contributing factor was work organisation, identified in 71 events. This included excessive task demands (47%, 37/71) and fragmentation (28%, 22/71). Conclusions Even though most reported events were near misses, events with serious patient consequences were also reported. Failures in situation assessment and response selection, a cognitive activity that occurs in both clinical and administrative tasks, was related to serious potential harm. PMID:17403753

Trophic strategies, animal diversity and body size

USGS Publications Warehouse

Lafferty, Kevin D.; Kuris, Armand M.

2002-01-01

A primary difference between predators and parasites is the number of victims that an individual attacks throughout a life-history stage. A key division within natural enemies is whether a successful attack eliminates the fitness of the prey or the host. A third distinctive axis for parasites is whether the host must die to further parasite development. The presence or absence of intensity-dependent pathology is a fourth factor that separates macroparasites from microparasites; this also distinguishes between social and solitary predators. Combining these four dichotomies defines seven types of parasitism, seven corresponding parasites, three forms of predation and, when one considers obligate and facultative combinations of these forms, four types of predator. Here, we argue that the energetics underlying the relative and absolute sizes of natural enemies and their victims is the primary selective factor responsible for the evolution of these different trophic strategies.

Non-melanoma Skin Cancer in Canada Chapter 2: Primary Prevention of Non-melanoma Skin Cancer.

PubMed

Barber, Kirk; Searles, Gordon E; Vender, Ronald; Teoh, Hwee; Ashkenas, John

2015-01-01

Non-melanoma skin cancer (NMSC), including basal and squamous cell carcinoma (BCC and SCC), represents the most common malignancy. To provide guidance to Canadian health care practitioners regarding primary prevention of NMSC. Structured literature searches were conducted, using search terms including prevention, sunscreen, and sun prevention factor. All recommendations concern guidance that physicians should regularly discuss with their patients to help establish photoprotection habits. The GRADE system was used to assign strength to each recommendation. Ultraviolet exposure is the major modifiable risk factor for NMSC. Aspects of photoprotection, including effective sunscreen use and avoidance of both the midday sun and artificial tanning, are discussed. Several widespread misunderstandings that undermine responsible public health measures related to sun safety are addressed. Photoprotection represents both an individual priority and a public health imperative. By providing accurate information during routine patient visits, physicians reinforce the need for ongoing skin cancer prevention. © The Author(s) 2015.

Natural genetic variation of freezing tolerance in Arabidopsis.

PubMed

Hannah, Matthew A; Wiese, Dana; Freund, Susanne; Fiehn, Oliver; Heyer, Arnd G; Hincha, Dirk K

2006-09-01

Low temperature is a primary determinant of plant growth and survival. Using accessions of Arabidopsis (Arabidopsis thaliana) originating from Scandinavia to the Cape Verde Islands, we show that freezing tolerance of natural accessions correlates with habitat winter temperatures, identifying low temperature as an important selective pressure for Arabidopsis. Combined metabolite and transcript profiling show that during cold exposure, global changes of transcripts, but not of metabolites, correlate with the ability of Arabidopsis to cold acclimate. There are, however, metabolites and transcripts, including several transcription factors, that correlate with freezing tolerance, indicating regulatory pathways that may be of primary importance for this trait. These data identify that enhanced freezing tolerance is associated with the down-regulation of photosynthesis and hormonal responses and the induction of flavonoid metabolism, provide evidence for naturally increased nonacclimated freezing tolerance due to the constitutive activation of the C-repeat binding factors pathway, and identify candidate transcriptional regulators that correlate with freezing tolerance.

Factors associated with elderly diabetic adherence to treatment in primary health care.

PubMed

Borba, Anna Karla de Oliveira Tito; Marques, Ana Paula de Oliveira; Ramos, Vânia Pinheiro; Leal, Márcia Carrera Campos; Arruda, Ilma Kruze Grande de; Ramos, Roberta Souza Pereira da Silva

2018-03-01

This study aimed to investigate factors associated with the treatment adherence of 150 elderly diabetics assisted in gerontogeriatric outpatient service in northeastern Brazil. Full adherence to therapy was self-reported by 27.3% of the elderly. In the bivariate analysis, adherence was associated with self-perceived health, beliefs in the use of medication, understanding explanations about diabetes and professional responsible for treatment guidance. After analysis adjustment, only beliefs in medicine were significant when comparing non-adherence with full adherence (OR = 9.65; CI95% 1.6; 56.6) and non-adherence with partial adherence (OR = 18.15; CI95% 3.5;95.4). It can be concluded that full adherence to diabetes treatment is low and is associated with beliefs in medications for disease control. It is necessary to develop additional studies to better define the role of health beliefs and practices of care among elderly assisted in primary health care.

Thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients.

PubMed

Paradiso, A; Simone, G; Petroni, S; Leone, B; Vallejo, C; Lacava, J; Romero, A; Machiavelli, M; De Lena, M; Allegra, C J; Johnston, P G

2000-02-01

The purpose of this work was to analyse the ability of p53 and thymidilate synthase (TS) primary tumour expression to retrospectively predict clinical response to chemotherapy and long-term prognosis in patients with advanced colorectal cancers homogeneously treated by methotrexate (MTX)-modulated-5-fluorouracil (5-FU-FA). A total of 108 advanced colorectal cancer patients entered the present retrospective study. Immunohistochemical p53 (pAb 1801 mAb) and TS (TS106 mAb) expression on formalin-fixed paraffin-embedded primary tumour specimens was related to probability of clinical response to chemotherapy, time to progression and overall survival. p53 was expressed in 53/108 (49%) tumours, while 54/108 (50%) showed TS immunostaining. No relationship was demonstrated between p53 positivity and clinical response to chemotherapy (objective response (OR): 20% vs 23%, in p53+ and p53- cases respectively) or overall survival. Percent of OR was significantly higher in TS-negative with respect to TS-positive tumours (30% vs 15% respectively; P < 0.04); simultaneous analysis of TS and p53 indicated 7% OR for p53-positive/TS-positive tumours vs 46% for p53-positive/TS-negative tumours (P < 0.03). Logistic regression analysis confirmed a significant association between TS tumour status and clinical response to chemotherapy (hazard ratio (HR): 2.91; 95% confidence interval (CI) 8.34-1.01; two-sided P < 0.05). A multivariate analysis of overall survival showed that only a small number of metastatic sites was statistically relevant (HR 1.89; 95% CI 2.85-1.26; two-sided P < 0.03). Our study suggests that immunohistochemical expression of p53 and TS could assist the clinician in predicting response of colorectal cancer patients to modulated MTX-5-FU therapy.

Obesity prevention in English primary schools: headteacher perspectives.

PubMed

Clarke, J L; Pallan, M J; Lancashire, E R; Adab, P

2017-06-01

Schools are seen as important contributors to obesity prevention, yet face barriers in fulfilling this function. This qualitative study investigates headteacher views on the primary school role in preventing obesity. Semi-structured interviews were held with 22 headteachers from ethnically and socio-economically diverse schools in the West Midlands, UK. Data analysis was conducted using the framework approach. Two over-arching categories were identified: 'School roles and responsibilities' and 'Influencing factors'. Participants agreed that although schools contribute towards obesity prevention in many ways, a moral responsibility to support children's holistic development was the principal motivator, rather than preventing obesity per se. The perceived impact on learning was a key driver for promoting health. Parents were believed to have the main responsibility for preventing obesity, but barriers were identified. Whilst headteachers recognized the advantageous position of schools in offering support to parents, opinion varied on the degree to which schools could and should take on this role. Headteachers serving more deprived areas reported adopting certain responsibilities that elsewhere were fulfilled by parents, and were more likely to view working with families on healthy lifestyles as an important school function. Several factors were perceived as barriers to schools doing more to prevent obesity, including academic pressure, access to expert support and space. In conclusion, school leaders need more support, through resources and government policy, to enable them to maximize their role in obesity prevention. Additionally, school-based obesity prevention should be an integral part of the education agenda rather than bolt-on initiatives. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Advanced chordoma treated by first-line molecular targeted therapies: Outcomes and prognostic factors. A retrospective study of the French Sarcoma Group (GSF/GETO) and the Association des Neuro-Oncologues d'Expression Française (ANOCEF).

PubMed

Lebellec, Loïc; Chauffert, Bruno; Blay, Jean-Yves; Le Cesne, Axel; Chevreau, Christine; Bompas, Emmanuelle; Bertucci, François; Cupissol, Didier; Fabbro, Michel; Saada-Bouzid, Esma; Duffaud, Florence; Feuvret, Loïc; Bonneville-Levard, Alice; Bay, Jacques-Olivier; Vauleon, Elodie; Vinceneux, Armelle; Noel, Georges; Penel, Nicolas; Mir, Olivier

2017-07-01

To assess the role of first-line Molecular Targeted Therapies (MTTs) in Advanced chordoma (AC) patients. Retrospective study of 80 patients treated between January 2004 and December 2015 at 15 major French Sarcoma or Neurooncology Centres. The sex ratio M/F was 46/34. The median age was 59 (6-86) years. The primary sites were the sacrum (50, 62.5%), mobile spine (12, 15.0%), and skull base (18, 22.5%). Metastases were present in 28 patients (36.0%). The first line of MTTs consisted of imatinib (62, 77.5%), sorafenib (11, 13.7%), erlotinib (5, 6.3%), sunitinib (1, 1.2%) and temsirolimus (1, 1.2%). The reported responses were: partial response (5, 6.3%), stable disease (58, 72.5%), or progressive disease (10, 12.5%). Symptomatic improvement was seen in 28/66 assessable patients (42.4%) and was associated with an objective response occurrence (p = 0.005), imatinib (p = 0.020) or erlotinib use (p = 0.028). The median progression-free survival (PFS) was 9.4°months (95% CI, [6.8-16.1]). Two independent factors of poor prognosis for PFS were identified: a skull-based primary location (HR = 2.5, p = 0.019), and the interval between diagnosis and MTT of <52months (HR = 2.8, p < 0.001). The median overall survival (OS) was 4.4°years (95% CI, [3.8-5.6]). Four independent factors of poor prognosis for OS were identified: the presence of liver metastases (HR = 13.2, p < 0.001), pain requiring opioids (HR = 2.9, p = 0.012), skull-based primary location (HR = 19.7, p < 0.001), and prior radiotherapy (photon alone) (HR = 2.5, p = 0.024). The PFS and OS did not significantly differ between the MTT. The prognostic factors identified require validation in an independent database but are potently useful to guide treatment decisions and design further clinical trials. Copyright © 2017 Elsevier Ltd. All rights reserved.

Genome-wide expression analysis of soybean NF-Y genes reveals potential function in development and drought response.

PubMed

Quach, Truyen N; Nguyen, Hanh T M; Valliyodan, Babu; Joshi, Trupti; Xu, Dong; Nguyen, Henry T

2015-06-01

Nuclear factor-Y (NF-Y), a heterotrimeric transcription factor, is composed of NF-YA, NF-YB and NF-YC proteins. In plants, there are usually more than 10 genes for each family and their members have been identified to be key regulators in many developmental and physiological processes controlling gametogenesis, embryogenesis, nodule development, seed development, abscisic acid (ABA) signaling, flowering time, primary root elongation, blue light responses, endoplasmic reticulum (ER) stress response and drought tolerance. Taking the advantages of the recent soybean genome draft and information on functional characterizations of nuclear factor Y (NF-Y) transcription factor family in plants, we identified 21 GmNF-YA, 32 GmNF-YB, and 15 GmNF-YC genes in the soybean (Glycine max) genome. Phylogenetic analyses show that soybean's proteins share strong homology to Arabidopsis and many of them are closely related to functionally characterized NF-Y in plants. Expression analysis in various tissues of flower, leaf, root, seeds of different developmental stages, root hairs under rhizobium inoculation, and drought-treated roots and leaves revealed that certain groups of soybean NF-Y are likely involved in specific developmental and stress responses. This study provides extensive evaluation of the soybean NF-Y family and is particularly useful for further functional characterization of GmNF-Y proteins in seed development, nodulation and drought adaptation of soybean.

[Appraisal of occupational stress and its influential factors in nurses].

PubMed

Yang, Xin-wei; Wang, Zhi-ming; Wang, Mian-zhen; Lan, Ya-jia

2004-04-01

To assess the occupational stress and its influential factors in nurses. A test of occupational stress, its influential factors, work ability were carried out for 248 nurses and 319 controls with revised occupational stress inventory (OSI-R) and work ability index (WAI). The scores of personal cope resource (131.266 +/- 17.176) and work ability index (32.581 +/- 3.158) in nurse group were significantly higher than those in control group (126.931 +/- 19.108, 31.840 +/- 4.069) (P < 0.05). The main occupational stressors scores (role insufficiency, role clash, and responsibility) in nurses were higher than those in controls (P < 0.05). The stress response of interpersonal relationship in nurses was also higher. The items of personal cope resource, such as recreation, self-care and social support of nurses were superior to those of controls (P < 0.05). Stress response was positively correlated with occupational role (r = 0.512, P < 0.01), and negatively correlated with the personal cope resource (r = -0.475, P < 0.01). The primary influential factors of personal stress were recreation, social support, rational conduct, role insufficiency, role clash, responsibility, and poor work environment. To strengthen social support, to improve work condition for nurses, so as to reduce the occupational stress and to enhance the work ability of nurses are important task in occupational health field.

Reinventing primary care: lessons from Canada for the United States.

PubMed

Starfield, Barbara

2010-05-01

Canada is, in many respects, culturally and economically similar to the United States, and until relatively recently, the two countries had similar health systems. However, since passage of the Canada Health Act in the 1970s, that nation's health statistics have become increasingly superior. Although the costs of Canada's health system are high by international standards, they are much lower than U.S. costs. This paper describes several factors likely to be responsible for Canada's better health at lower cost: universal financial coverage through a so-called single payer; features conducive to a strong primary care infrastructure; and provincial autonomy under general principles set by national law.

Substitution scenario in follow-up of chronic cancer patients in primary care: prevalence, disease duration and estimated extra consultation time.

PubMed

van Dipten, C; Olde Hartman, T C; Biermans, M C J; Assendelft, W J J

2016-02-01

The incidence of cancer as well as survival rates for it are increasing. It is debated whether care in the chronic phase of cancer can be positioned in primary care due to doubts about capacity and workload. To estimate GPs' extra consultation time if they assume responsibility for the care in the chronic phase of cancer. Retrospective cohort study. Estimation of extra consultation time by quantifying prevalence, incidence, survival, number of chronic cancer patients, current practice contacts and registration of risk factors in patients with all types of cancers. The most prevalent types of cancer (with 5-year survival rates) are as follows: breast cancer (91.5%), colorectal cancer (63.8%), prostate cancer (78.3%), melanoma (91.9%) and bladder and urinary tract cancer (77.3%). Primary care practices include ~32 chronic cancer patients, with a potential extra consultation time of ~19 hours per year per 1000 patients. One-third (35%) are already in a chronic disease management programme and 57% were diagnosed >5 years ago. Registration of risk factors for cancer is incomplete, but of better quality when comorbidity is present. Numbers of chronic cancer patients and possible time investment by primary care professionals in the case of a substitution scenario should not be a limiting factor for transition of follow-up from secondary to primary care, as most of the patients were diagnosed >5 years ago and a large proportion of these patients are already monitored in an existing chronic care programme. © The Author 2015. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Infant breast-feeding and childhood caries: a nine-year study.

PubMed

Hong, Liang; Levy, Steven M; Warren, John J; Broffitt, Barbara

2014-01-01

This study's purpose was to assess the association between infant breast-feeding and caries experience of primary second molars in a nine-year longitudinal cohort study. Study sample was 509 subjects recruited at birth. Information about breast-feeding duration and other factors was collected through parents' responses to periodic questionnaires. Primary teeth were examined for dental caries at five years old and nine years old by calibrated dentist examiners. Caries experience (yes/no) and number of decayed and/or filled surfaces (dfs) were determined for five- and nine-year-olds. For primary second molars at five years old, 18 percent of children who were breast-fed less than six months had caries (mean dfs=0.55) while only 9 percent of children who were breast-fed at least six months had caries (mean dfs=0.33). From five to nine years old, caries incidence was 32 percent and 31 percent, respectively, for children breast-fed less than six months and at least six months. In multivariable regression analyses, shorter breast-feeding duration was positively associated with caries experience of primary second molars at five years old (P=.005), both before and after controlling for other important factors. Shorter duration of breast-feeding is suggested to be associated with increased risk for early childhood caries, but its impact might diminish with age.

Assessing impacts of climate change on species range shifts and extirpation on the local scale through Late Pleistocene fossils of Sequoia sempervirens in the Los Angeles Basin.

NASA Astrophysics Data System (ADS)

George, J.; MacDonald, G. M.

2017-12-01

As the effects of climate change become more apparent, increased importance must be placed on species' response to changing environments for ecosystem management and threat mitigation. While many studies have focused on the response of ecosystem types, few venture to the species level, as true limiting factors of species can be difficult to discern. Paleoproxies provide a valuable resource for predicting responses to future change through observation of similar responses in the past. This study uses plant paleorecords of Sequoia sempervirens to more closely examine the relationship of local climate change and species response in the Los Angeles Basin during the Late Pleistocene. The modern distribution of S. sempervirens has a southern extent, today, reaching the south end of Monterey County, California. Fossilized material from the La Brea Tar Pits extends that range to the farthest known point south, 200 miles from the southernmost modern stands, and has previously not been dated. A coupled analysis of 8 S. sempervirens specimens preserved in asphalt using Accelerator Mass Spectrometry (AMS) dates paired with δC13 values will help to illuminate patterns of changing climate on a local scale, as well as provide valuable data on primary environmental factors in plant community change. Understanding the intricacies of species' range shifts and factors behind local extirpation on a local scale is necessary to interpret species response in the past as well as predicting response in the future.

RAGE-Specific Inhibitor FPS-ZM1 Attenuates AGEs-Induced Neuroinflammation and Oxidative Stress in Rat Primary Microglia.

PubMed

Shen, Chao; Ma, Yingjuan; Zeng, Ziling; Yin, Qingqing; Hong, Yan; Hou, Xunyao; Liu, Xueping

2017-10-01

Advanced glycation end products (AGEs) enhance microglial activation and intensify the inflammatory response and oxidative stress in the brain. This process may occur due to direct cytotoxicity or interacting with AGEs receptors (RAGE), which are expressed on the surface of microglia. FPS-ZM1 is a high-affinity but nontoxic RAGE-specific inhibitor that has been recently shown to attenuate the Aβ-induced inflammatory response by blocking the ligation of Aβ to RAGE. In this study, we further investigated the effect of FPS-ZM1 on the AGEs/RAGE interaction and downstream elevation of neuroinflammation and oxidative stress in primary microglia cells. The results suggested that FPS-ZM1 significantly suppressed AGEs-induced RAGE overexpression, RAGE-dependent microglial activation, nuclear translocation of nuclear factor kappaB p65 (NF-κB p65), and the expression of downstream inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), cyclooxygenase 2 (COX-2)/prostaglandin E2 (PGE2) and inducible nitric oxide synthase (iNOS)/nitric oxide (NO). Furthermore, FPS-ZM1 attenuated AGEs-stimulated NADPH oxidase (NOX) activation and reactive oxygen species (ROS) expression. Finally, FPS-ZM1 elevated the levels of transcription factors nuclear-factor (erythroid-derived 2)-like 2 (Nrf2) and heme oxygenase-1 (HO-1), as well as decreased antioxidant capacity and increased production of oxidative species. Our results suggest that FPS-ZM1 may be neuroprotective through attenuating microglial activation, oxidative stress and inflammation by blocking RAGE.

TU-H-CAMPUS-IeP1-01: Bias and Computational Efficiency of Variance Reduction Methods for the Monte Carlo Simulation of Imaging Detectors

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

Sharma, D; Badano, A; Sempau, J

Purpose: Variance reduction techniques (VRTs) are employed in Monte Carlo simulations to obtain estimates with reduced statistical uncertainty for a given simulation time. In this work, we study the bias and efficiency of a VRT for estimating the response of imaging detectors. Methods: We implemented Directed Sampling (DS), preferentially directing a fraction of emitted optical photons directly towards the detector by altering the isotropic model. The weight of each optical photon is appropriately modified to maintain simulation estimates unbiased. We use a Monte Carlo tool called fastDETECT2 (part of the hybridMANTIS open-source package) for optical transport, modified for VRT. Themore » weight of each photon is calculated as the ratio of original probability (no VRT) and the new probability for a particular direction. For our analysis of bias and efficiency, we use pulse height spectra, point response functions, and Swank factors. We obtain results for a variety of cases including analog (no VRT, isotropic distribution), and DS with 0.2 and 0.8 optical photons directed towards the sensor plane. We used 10,000, 25-keV primaries. Results: The Swank factor for all cases in our simplified model converged fast (within the first 100 primaries) to a stable value of 0.9. The root mean square error per pixel for DS VRT for the point response function between analog and VRT cases was approximately 5e-4. Conclusion: Our preliminary results suggest that DS VRT does not affect the estimate of the mean for the Swank factor. Our findings indicate that it may be possible to design VRTs for imaging detector simulations to increase computational efficiency without introducing bias.« less

Hepatitis C virus knowledge improves hepatitis C virus screening practices among primary care physicians.

PubMed

Samuel, Sandeep T; Martinez, Anthony D; Chen, Yang; Markatou, Marianthi; Talal, Andrew H

2018-02-27

To understand the role of knowledge as a promoter of hepatitis C virus (HCV) screening among primary care physicians (PCP). A 45-item online questionnaire assessing knowledge of HCV natural history, risk factors, and treatment was distributed to 163 PCP. Logistic regression, adjusted for survey responses, assessed associations between PCP knowledge of HCV natural history and treatment and birth cohort ( i.e ., birth between 1945 and 1965) screening. Response stratification and weighting were used to account for nonresponse and to permit extension of responses to the entire survey population. Associations between various predictors including demographic characteristics, level of training, and HCV treatment experience and HCV knowledge were assessed. Ninety-one individuals (55.8%) responded. Abnormal liver enzymes (49.4%), assessment of HCV-related risk factors (30.6%), and birth cohort membership (20%) were the leading HCV screening indications. Most PCP (64.7%) felt that the combination of risk-factor and birth cohort screening utilizing a self-administered survey while awaiting the physician (55.3%) were the most efficient screening practices. Implementation of birth cohort screening was associated with awareness of the recommendations ( P -value = 0.01), knowledge of HCV natural history ( P -value < 0.01), and prior management of HCV patients ( P -value < 0.01). PCP with knowledge of HCV treatment was also knowledgeable about HCV natural history ( P -value < 0.01). Similarly, awareness of age-based screening recommendations was associated with HCV treatment knowledge ( P -value = 0.03). Comprehensive knowledge of HCV is critical to motivate HCV screening. PCP-targeted educational interventions are required to expand the HCV workforce and linkage-to-care opportunities as we seek global HCV eradication.

Recruiting primary care physicians to qualitative research: Experiences and recommendations from a childhood cancer survivorship study.

PubMed

Signorelli, Christina; Wakefield, Claire E; Fardell, Joanna E; Thornton-Benko, Elysia; Emery, Jon; McLoone, Jordana K; Cohn, Richard J

2018-01-01

Primary care physicians (PCPs) are essential for healthcare delivery but can be difficult to recruit to health research. Low response rates may impact the quality and value of data collected. This paper outlines participant and study design factors associated with increased response rates among PCPs invited to participate in a qualitative study at Sydney Children's Hospital, Australia. We invited 160 PCPs by post, who were nominated by their childhood cancer patients in a survey study. We followed-up by telephone, email, or fax 2 weeks later. Without any follow-up, 32 PCPs opted in to the study. With follow-up, a further 42 PCPs opted in, with email appearing to be the most effective method, yielding a total of 74 PCPs opting in (46.3%). We reached data saturation after 51 interviews. On average, it took 34.6 days from mail-out to interview completion. Nonrespondents were more likely to be male (P = 0.013). No survivor-related factors significantly influenced PCPs' likelihood of participating. Almost double the number of interviews were successfully completed if scheduled via email versus phone. Those requiring no follow-up did not differ significantly to late respondents in demographic/survivor-related characteristics. PCP factors associated with higher opt in rates, and early responses, may be of interest to others considering engaging PCPs and/or their patients in cancer-related research, particularly qualitative or mixed-methods studies. Study resources may be best allocated to email follow-up, incentives, and personalization of study documents linking PCPs to patients. These efforts may improve PCP participation and the representativeness of study findings. © 2017 Wiley Periodicals, Inc.

Von Willebrand factor antigen predicts response to double dose of aspirin and clopidogrel by PFA-100 in patients undergoing primary angioplasty for ST elevation myocardial infarction.

PubMed

Gianetti, Jacopo; Parri, Maria Serena; Della Pina, Francesca; Marchi, Federica; Koni, Endrin; De Caterina, Alberto; Maffei, Stefano; Berti, Sergio

2013-01-01

Von Willebrand factor (VWF) is an emerging risk factor in acute coronary syndromes. Platelet Function Analyzer (PFA-100) with Collagen/Epinephrine (CEPI) is sensitive to functional alterations of VWF and also identifies patients with high on-treatment platelet reactivity (HPR). The objective of this study was to verify the effect of double dose (DD) of aspirin and clopidogrel on HPR detected by PFA-100 and its relation to VWF and to its regulatory metalloprotease ADAMTS-13. Between 2009 and 2011 we enrolled 116 consecutive patients with ST elevation myocardial infarction undergoing primary PCI with HPR at day 5 after PCI. Patients recruited were then randomized between a standard dose (SD, n = 58) or DD of aspirin and clopidogrel (DD, n = 58), maintained for 6 months follow-up. Blood samples for PFA-100, light transmittance aggregometry, and VWF/ADAMTS-13 analysis were collected after 5, 30, and 180 days (Times 0, 1, and 2). At Times 1 and 2 we observed a significantly higher CEPI closure times (CT) in DD as compared to SD (P < 0.001). Delta of CEPI-CT (T1 - T0) was significantly related to VWF (P < 0.001) and inversely related to ADAMTS-13 (0.01). Responders had a significantly higher level of VWF at T0. Finally, in a multivariate model analysis, VWF and ADAMTS-13 in resulted significant predictors of CEPI-CT response (P = 0.02). HRP detected by PFA-100 in acute myocardial infarction is reversible by DD of aspirin and clopidogrel; the response is predicted by basal levels of VWF and ADAMTS-13. PFA-100 may be a useful tool to risk stratification in acute coronary syndromes given its sensitivity to VWF.

Factors associated with consultation behaviour for primary symptoms potentially indicating colorectal cancer: A cross-sectional study on response to symptoms

PubMed Central

2012-01-01

Background Little data exists on the factors associated with health care seeking behaviour for primary symptoms of colorectal cancer (CRC). This study aimed to identify individual, provider and psychosocial factors associated with (i) ever seeking medical advice and (ii) seeking early medical advice for primary symptoms of colorectal cancer (CRC). Methods 1592 persons aged 56–88 years randomly selected from the Hunter Community Study (HCS) were sent a questionnaire. Results Males and those who had received screening advice from a doctor were at significantly higher odds of ever seeking medical advice for rectal bleeding. Persons who had private health coverage, consulted a doctor because the ‘symptom was serious’, or who did not wait to consult a doctor for another reason were at significantly higher odds of seeking early medical advice (< 2 weeks). For change in bowel habit, persons with lower income, within the healthy weight range, or who had discussed their family history of CRC irrespective of whether informed of ‘increased risk’ were at significantly higher odds of ever seeking medical advice. Persons frequenting their GP less often and seeing their doctor because the symptom persisted were at significantly higher odds of seeking early medical advice (< 2 weeks). Conclusions The seriousness of symptoms, importance of early detection, and prompt consultation must be articulated in health messages to at-risk persons. This study identified modifiable factors, both individual and provider-related to consultation behaviour. Effective health promotion efforts must heed these factors and target sub-groups less likely to seek early medical advice. PMID:22862960

Financial and Time Burdens for Medical Students Interviewing for Residency.

PubMed

Callaway, Paul; Melhado, Trisha; Walling, Anne; Groskurth, Jordan

2017-02-01

Interviewing for residency positions is increasingly stressful for students and challenging for programs. Little information is available about the costs and time invested by students in interviewing or about the key factors in decisions to accept interview offers. Our objective was to assess the time and financial costs of residency interviewing for an entire class at a regional campus and explore factors influencing student decisions to accept interviews. We used a 14-item survey administered electronically immediately following National Resident Matching Program results. The response rate was 75% (49 of 65 students). About half interviewed in primary care specialties. Thirty students (63%) applied to 20 or more programs, and 91% were offered multiple interviews out of state. Seventy percent limited interviews by time and cost. Other important factors included personal "fit," program reputation, and the quality of residents. About 50% of the students spent more than 20 days and $1,000-$5,000 interviewing; 29% reported spending over $5,000. Students used multiple funding sources, predominantly loans and savings. Primary care applicants applied to fewer out-of-state programs, reported fewer interview days and lower expenses, but received more financial support from programs. Students invested considerable time and resources in interviewing, and these factors significantly influenced their decisions about accepting interviews. The other major factors in interview decisions concerned personal comfort with the program, especially the residents. The costs and time reported in this study could be greater than other schools due to the regional campus location or lower due to the high proportion of students interviewing in primary care.

Participant recruitment to FiCTION, a primary dental care trial - survey of facilitators and barriers.

PubMed

Keightley, A; Clarkson, J; Maguire, A; Speed, C; Innes, N

2014-11-01

To identify reasons behind a lower than expected participant recruitment rate within the FiCTION trial, a multi-centre paediatric primary dental care randomised controlled trial (RCT). An online survey, based on a previously published tool, consisting of both quantitative and qualitative responses, completed by staff in dental practices recruiting to FiCTION. Ratings from quantitative responses were aggregated to give overall scores for factors related to participant recruitment. Qualitative responses were independently grouped into themes. Thirty-nine anonymous responses were received. Main facilitators related to the support received from the central research team and importance of the research question. The main barriers related to low child eligibility rates and the integration of trial processes within routine workloads. These findings have directed strategies for enhancing participant recruitment at existing practices and informed recruitment of further practices. The results help provide a profile of the features required of practices to successfully screen and recruit participants. Future trials in this setting should consider the level of interest in the research question within practices, and ensure trial processes are as streamlined as possible. Research teams should actively support practices with participant recruitment and maintain enthusiasm among the entire practice team.

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

Rau, E. I.; Orlikovskiy, N. A.; Ivanova, E. S.

A new highly efficient design for semiconductor detectors of intermediate-energy electrons (1-50 keV) for application in scanning electron microscopes is proposed. Calculations of the response function of advanced detectors and control experiments show that the efficiency of the developed devices increases on average twofold, which is a significant positive factor in the operation of modern electron microscopes in the mode of low currents and at low primary electron energies.

The Determinants of Labor Force Participation Rates, with Special Reference to the Ozark Low-Income Area. Final Report.

ERIC Educational Resources Information Center

Sandmeyer, Robert L.; Warner, Larkin B.

The study's primary purpose was to identify and evaluate the relative importance of factors responsible for the generally low labor force participation rates observable in the Ozark Low-Income Area, and variations in rates within the area itself. The study focused on 108 contiguous, rural-oriented, low-income counties in the states of Arkansas,…

SU-E-I-57: Estimating the Occupational Eye Lens Dose in Interventional Radiology Using Active Personal Dosimeters Worn On the Chest

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

Omar, A; Marteinsdottir, M; Kadesjo, N

Purpose: To provide a general formalism for determination of occupational eye lens dose based on the response of an active personal dosimeter (APD) worn at chest level above the radiation protection apron. Methods: The formalism consists of three factors: (1) APD conversion factor converting the reading at chest level (APDchest) to the corresponding personal dose equivalent at eye level, (2) Dose conversion factor transferring the measured dose quantity, Hp(10), into a dose quantity relevant for the eye lens dose, (3) Correction factor accounting for differences in exposure of the eye(s) compared to the exposure at chest level (e.g., due tomore » protective lead glasses).The different factors were investigated and evaluated based on phantom and clinical measurements performed in an x-ray angiography suite for interventional cardiology. Results: The eye lens dose can be conservatively estimated by assigning an appropriate numerical value to each factor entering the formalism that in most circumstances overestimates the dose. Doing so, the eye lens dose to the primary operator and assisting staff was estimated in this work as D-eye,primary = 2.0 APDchest and D-eye,assisting = 1.0 APDchest, respectively.The annual eye lens dose to three nurses and one cardiologist was estimated to be 2, 2, 2, and 13 mSv (Hp(0.07)), respectively, using a TLD dosimeter worn at eye level. In comparison, using the formalism and APDchest measurements, the respective doses were 2, 2, 2, and 16 mSv (Hp(3)). Conclusion: The formalism outlined in this work can be used to estimate the occupational eye lens dose from the response of an APD worn on the chest. The formalism is general and could be applied also to other types of dosimeters. However, the numerical value of the different factors may differ from those obtained with the APD’s used in this work due to differences in dosimeter properties.« less

Biobehavioral modulation of the exosome transcriptome in ovarian carcinoma.

PubMed

Lutgendorf, Susan K; Thaker, Premal H; Arevalo, Jesusa M; Goodheart, Michael J; Slavich, George M; Sood, Anil K; Cole, Steve W

2018-02-01

Social factors in the patient macroenvironment have been shown to influence molecular events in the tumor microenvironment and thereby influence cancer progression. However, biomarkers providing a window into the longitudinal effects of biobehavioral factors on tumor biology over time are lacking. Exosome analysis is a novel strategy for in vivo monitoring of dynamic changes in tumor cells. This study examined exosomal profiles from patients with low or high levels of social support for epithelial-mesenchymal transition (EMT) polarization and gene expression related to inflammation and β-adrenergic signaling. Exosomes were isolated from plasma sampled from a series of 40 women before primary surgical resection of advanced-stage, high-grade ovarian carcinoma. Samples were selected for analysis on the basis of extremes of low and high levels of social support. After exosomal isolation and RNA extraction, a microarray analysis of the transcriptome was performed. Primary analyses identified significant upregulation of 67 mesenchymal-characteristic gene transcripts and downregulation of 63 epithelial-characteristic transcripts in patients with low social support; this demonstrated increased EMT polarization (P = .0002). Secondary analyses using promoter sequence bioinformatics supported a priori hypotheses linking low social support to 1) increased activity of cyclic adenosine monophosphate response element binding protein (CREB)/activating transcription factor (ATF) family transcription factors that mediate the β-adrenergic response to catecholamines via the cyclic adenosine monophosphate/protein kinase A signaling pathway (mean fold change for CREB: 2.24 ± 0.65; P = .0019; mean fold change for ATF: 2.00 ± 0.55; P = .0049) and 2) increased activity of the proinflammatory nuclear factor κB/Rel family of transcription factors (mean fold change: 2.10 ± 0.70; P = .0109). These findings suggest the possibility of leveraging exosomes as a noninvasive assessment of biobehavioral factors to help to direct personalized treatment approaches. Cancer 2018;124:580-6. © 2017 American Cancer Society. © 2017 American Cancer Society.

Unique and shared inflammatory profiles of human brain endothelia and pericytes.

PubMed

Smyth, Leon C D; Rustenhoven, Justin; Park, Thomas I-H; Schweder, Patrick; Jansson, Deidre; Heppner, Peter A; O'Carroll, Simon J; Mee, Edward W; Faull, Richard L M; Curtis, Maurice; Dragunow, Mike

2018-05-11

Pericytes and endothelial cells are critical cellular components of the blood-brain barrier (BBB) and play an important role in neuroinflammation. To date, the majority of inflammation-related studies in endothelia and pericytes have been carried out using immortalised cell lines or non-human-derived cells. Whether these are representative of primary human cells is unclear and systematic comparisons of the inflammatory responses of primary human brain-derived pericytes and endothelia has yet to be performed. To study the effects of neuroinflammation at the BBB, primary brain endothelial cells and pericytes were isolated from human biopsy tissue. Culture purity was examined using qPCR and immunocytochemistry. Electrical cell-substrate impedance sensing (ECIS) was used to determine the barrier properties of endothelial and pericyte cultures. Using immunocytochemistry, cytometric bead array, and ECIS, we compared the responses of endothelia and pericytes to a panel of inflammatory stimuli (IL-1β, TNFα, LPS, IFN-γ, TGF-β 1 , IL-6, and IL-4). Secretome analysis was performed to identify unique secretions of endothelia and pericytes in response to IL-1β. Endothelial cells were pure, moderately proliferative, retained the expression of BBB-related junctional proteins and transporters, and generated robust TEER. Both endothelia and pericytes have the same pattern of transcription factor activation in response to inflammatory stimuli but respond differently at the secretion level. Secretome analysis confirmed that endothelia and pericytes have overlapping but distinct secretome profiles in response to IL-1β. We identified several cell-type specific responses, including G-CSF and GM-CSF (endothelial-specific), and IGFBP2 and IGFBP3 (pericyte-specific). Finally, we demonstrated that direct addition of IL-1β, TNFα, LPS, and IL-4 contributed to the loss of endothelial barrier integrity in vitro. Here, we identify important cell-type differences in the inflammatory response of brain pericytes and endothelia and provide, for the first time, a comprehensive profile of the secretions of primary human brain endothelia and pericytes which has implications for understanding how inflammation affects the cerebrovasculature.

Development and evaluation of a self-care assessment inventory for workers.

PubMed

Ogasawara, Eiko; Shiihara, Yasufumi; Ando, Michiyo

2013-06-01

To develop and evaluate a self-care assessment inventory for workers (SCAI-W). A study using a self-care assessment inventory for workers consisting of 27 self-care items, the Japanese version of the Beck Depression Inventory (BDI), and the Japanese version of the University of Wales Institute of Science and Technology Mood Adjective Checklist (JUMACL) was conducted. These questionnaires were distributed to 2297 workers. There were 893 valid responses (39.9%, 584 men and 309 women, mean age 37.2±10.2 years). Three primary and eight secondary factors were established for the conceptual structure of self-care and validated by structural equation modeling. "Positive attitude" comprised the secondary factors, "hope" and "sense of fulfillment", and was influenced by another secondary factor, "social support". "Positive attitude" contributed to "attitude toward health". "Attitude toward health" comprised the secondary factors, "care about one's health" and "correction of bad habits". "Attitude toward health" influenced a primary factor, "everyday behavior", comprised of "wakefulness", "eating in moderation", and "lack of self-control". The primary factors "positive attitude" and "everyday behavior" influenced the BDI scores. A multiple regression analysis indicated that JUMACL subscale scores (energetic arousal and tense arousal), demographic data (living alone, sex, and age) and health-related data (exercise, smoking, body mass index, drinking more than three alcoholic drinks/day, and gambling) predicted the scores of the self-care assessment inventory for workers. This assessment inventory could be a useful measure of workers' self-care because it establishes a relationship between psychological and behavioral concepts that are important for health promotion. © 2012 The Authors. Japan Journal of Nursing Science © 2012 Japan Academy of Nursing Science.

The disinhibitory zone of the striate neuron receptive field and its sensitivity to cross-like figures.

PubMed

Lazareva, N A; Shevelev, I A; Novikova, R V; Tikhomirov, A S; Sharaev, G A; Tsutskiridze, D Yu

2002-01-01

Acute experiments on immobilized anesthetized cats were used to confirm the suggestion that the sensitivity of many neurons on the primary visual cortex to cross-shaped, angular, and Y-shaped figures may be determined by the presence within their receptive fields of disinhibitory zones, which block end-stopping inhibition. A total of 55 neurons (84 functions, i.e.. on and off responses) were used for studies of sensitivity to crosses, and responses to single bars of different lengths were compared before and after stimulation of an additional lateral zone of the field (the presumptive disinhibitory zone), which was located in terms of responses to crosses. Seventeen of the 55 cells in which increases in the length of a single bar decreased responses, i.e., which demonstrated end-stopping inhibition, showed significant increases in responses (by an average factor of 2.06 +/- 0.16) during simultaneous stimulation of the lateral zone of the receptive field, which we interpreted as a disinhibitory effect on end-stopping inhibition. These data provide the first direct evidence for the role of end-stopping inhibition and its blockade by the disinhibitory zone of the receptive field in determining the sensitivity of some neurons in the primary visual cortex of the cat to cross-shaped figures.

Organizational commitment among general practitioners: a cross-sectional study of the role of psychosocial factors.

PubMed

Kuusio, Hannamaria; Heponiemi, Tarja; Sinervo, Timo; Elovainio, Marko

2010-06-01

To examine whether general practitioners (GP) working in primary health care have lower organizational commitment compared with physicians working in other health sectors. The authors also tested whether psychosocial factors (job demands, job control, and colleague consultation) explain these differences in commitment between GPs and other physicians. Cross-sectional postal questionnaire. Setting and participants. A postal questionnaire was sent to a random sample of physicians (n = 5000) drawn from the Finnish Association database in 2006. A total of 2841 physicians (response rate 57%) returned the questionnaire, of which 2657 (545 GPs and 2090 other physicians) fulfilled all the participant criteria. Organizational commitment was measured with two different indicators: intention to change jobs and low affective commitment. GPs were less committed to their organizations than other physicians. Work-related psychosocial factors (high job demands, low job control, and poor colleague consultation) were all significant risk factors for low organizational commitment. The evidence collected suggests that policies that reduce psychological demands, such as job demands and low control, may contribute to better organizational commitment and, thus, alleviate the shortages of physicians in primary care. Furthermore, giving GPs a stronger say in decisions concerning their work and providing them with more variety in work tasks may even improve the quality of primary care. The strategies for workplace development should focus on redesigning jobs and identifying GPs at higher risk, such as those with especially high job strain.

Factors associated with lip and oral cavity cancer.

PubMed

Ribeiro, Isabella Lima Arrais; de Medeiros, Júlia Julliêta; Rodrigues, Larycia Vicente; Valença, Ana Maria Gondim; Lima Neto, Eufrásio de Andrade

2015-01-01

This study aimed to identify factors associated with the occurrence of primary cancer of the lip and oral cavity regions compared to other types of head and neck cancers according to demographic, socioeconomic data and lifestyle, in Brazil, from 2000 to 2011. A study was conducted using Hospital Cancer Records (Instituto Nacional do Câncer), from 2000 to 2011, totaling 23,153 cases. Data were analyzed by binary logistic regression (response category: primary cancers located in the lip and oral cavity; comparison category; other types of primary cancer in the head and neck, which does not affect the lip and oral cavity) at a significance level α = 5%. The study showed factors associated with higher incidence of cancer in the lip and oral cavity: being of advanced age (OR = 1.16), not having a family history of cancer (OR = 2.38), alcohol consumption (OR = 1.17); former tobacco use (OR = 1.51) or current tobacco use (OR = 1.65); having a previous diagnosis of cancer without treatment (OR =1.66). Being female (OR = 0.92), having completed basic (OR = 0.71) and higher (OR = 0.46) education and having previous diagnosis of cancer with treatment (OR = 0.74) constituted factors associated with lower prevalence of cancer of the lip and oral cavity. Age, absence of family history of cancer, smoking habits and alcohol consumption, and previous diagnosis of cancer without treatment were associated with a higher incidence of cancer of the lip and oral cavity.

High Proliferation Predicts Pathological Complete Response to Neoadjuvant Chemotherapy in Early Breast Cancer

PubMed Central

Lluch, Ana; Ribelles, Nuria; Anton-Torres, Antonio; Sanchez-Rovira, Pedro; Albanell, Joan; Calvo, Lourdes; García-Asenjo, Jose Antonio Lopez; Palacios, Jose; Chacon, Jose Ignacio; Ruiz, Amparo; De la Haba-Rodriguez, Juan; Segui-Palmer, Miguel A.; Cirauqui, Beatriz; Margeli, Mireia; Plazaola, Arrate; Barnadas, Agusti; Casas, Maribel; Caballero, Rosalia; Carrasco, Eva; Rojo, Federico

2016-01-01

Background. In the neoadjuvant setting, changes in the proliferation marker Ki67 are associated with primary endocrine treatment efficacy, but its value as a predictor of response to chemotherapy is still controversial. Patients and Methods. We analyzed 262 patients with centralized basal Ki67 immunohistochemical evaluation derived from 4 GEICAM (Spanish Breast Cancer Group) clinical trials of neoadjuvant chemotherapy for breast cancer. The objective was to identify the optimal threshold for Ki67 using the receiver-operating characteristic curve method to maximize its predictive value for chemotherapy benefit. We also evaluated the predictive role of the defined Ki67 cutoffs for molecular subtypes defined by estrogen receptor (ER) and human epidermal growth factor receptor 2 (HER2). Results. A basal Ki67 cutpoint of 50% predicted pathological complete response (pCR). Patients with Ki67 >50% achieved a pCR rate of 40% (36 of 91) versus a pCR rate of 19% in patients with Ki67 ≤50% (33 of 171) (p = .0004). Ki67 predictive value was especially relevant in ER-HER2− and ER-HER2+ patients (pCR rates of 42% and 64%, respectively, in patients with Ki67 >50% versus 15% and 45%, respectively, in patients with Ki67 ≤50%; p = .0337 and .3238, respectively). Both multivariate analyses confirmed the independent predictive value of the Ki67 cutpoint of 50%. Conclusion. Basal Ki67 proliferation index >50% should be considered an independent predictive factor for pCR reached after neoadjuvant chemotherapy, suggesting that cell proliferation is a phenomenon closely related to chemosensitivity. These findings could help to identify a group of patients with a potentially favorable long-term prognosis. Implications for Practice: The use of basal Ki67 status as a predictive factor of chemotherapy benefit could facilitate the identification of a patient subpopulation with high probability of achieving pathological complete response when treated with primary chemotherapy, and thus with a potentially favorable long-term prognosis. PMID:26786263

40 CFR 142.10 - Requirements for a determination of primary enforcement responsibility.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS... enforcement responsibility. A State has primary enforcement responsibility for public water systems in the...: (a) Has adopted drinking water regulations which are no less stringent than the national primary...

40 CFR 142.10 - Requirements for a determination of primary enforcement responsibility.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS... enforcement responsibility. A State has primary enforcement responsibility for public water systems in the...: (a) Has adopted drinking water regulations which are no less stringent than the national primary...

40 CFR 142.10 - Requirements for a determination of primary enforcement responsibility.

Code of Federal Regulations, 2014 CFR

2014-07-01

... PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS... enforcement responsibility. A State has primary enforcement responsibility for public water systems in the...: (a) Has adopted drinking water regulations which are no less stringent than the national primary...

Crosstalk between Two bZIP Signaling Pathways Orchestrates Salt-Induced Metabolic Reprogramming in Arabidopsis Roots

PubMed Central

Hartmann, Laura; Pedrotti, Lorenzo; Weiste, Christoph; Fekete, Agnes; Schierstaedt, Jasper; Göttler, Jasmin; Kempa, Stefan; Krischke, Markus; Dietrich, Katrin; Mueller, Martin J.; Vicente-Carbajosa, Jesus; Hanson, Johannes; Dröge-Laser, Wolfgang

2015-01-01

Soil salinity increasingly causes crop losses worldwide. Although roots are the primary targets of salt stress, the signaling networks that facilitate metabolic reprogramming to induce stress tolerance are less understood than those in leaves. Here, a combination of transcriptomic and metabolic approaches was performed in salt-treated Arabidopsis thaliana roots, which revealed that the group S1 basic leucine zipper transcription factors bZIP1 and bZIP53 reprogram primary C- and N-metabolism. In particular, gluconeogenesis and amino acid catabolism are affected by these transcription factors. Importantly, bZIP1 expression reflects cellular stress and energy status in roots. In addition to the well-described abiotic stress response pathway initiated by the hormone abscisic acid (ABA) and executed by SnRK2 (Snf1-RELATED-PROTEIN-KINASE2) and AREB-like bZIP factors, we identify a structurally related ABA-independent signaling module consisting of SnRK1s and S1 bZIPs. Crosstalk between these signaling pathways recruits particular bZIP factor combinations to establish at least four distinct gene expression patterns. Understanding this signaling network provides a framework for securing future crop productivity. PMID:26276836

Ambient ultrafine particles activate human monocytes: Effect of dose, differentiation state and age of donors.

PubMed

Bliss, Bishop; Tran, Kevin Ivan; Sioutas, Constantinos; Campbell, Arezoo

2018-02-01

Exposure to ambient particulate matter (PM) has been linked to adverse pulmonary and cardiovascular health effects. Activation of both inflammatory and oxidative stress pathways has been observed and may be a probable cause of these outcomes. We tested the hypothesis that in human monocytes, PM-induced oxidative and inflammatory responses are interrelated. A human monocytic cell line (THP-1) was used to determine if dose and differentiation state plays a role in the cellular response after a 24hr exposure to particles. Primary human monocytes derived from eight female, non-smoker donors (aged: 21, 24, 27, 28, 48, 49, 54 & 60yo) were used to determine if the age of donors modulates the response. Cells were treated with aqueous suspensions of ambient ultrafine particles (UFP, defined as smaller than 0.2µm in size) or a media control for 24hr. After exposure, reactive oxygen species (ROS) formation was increased irrespective of dose or differentiation state of THP-1 cells. In the primary human monocytes, ROS formation was not significantly changed. The release of the proinflammatory cytokine, tumor necrosis factor alpha (TNF-α), was dose-dependent and greatest in differentiated compared to undifferentiated THP-1 cells exposed to UFP. In the Primary human monocytes, TNF-α secretion was increased irrespective of the age of the donor. Our results suggest that after a 24hr exposure to particles, general reactive oxygen species formation was nonspecific and uncorrelated to cytokine secretion which was consistently enhanced. Cytokines play an important role in orchestrating many immune responses and thus the ability of ambient particles to enhance robust secretion of a proinflammatory cytokine from primary human monocytes, and how this may influence the response to pathogens and alter disease states, needs to be further evaluated. Copyright © 2017 Elsevier Inc. All rights reserved.

Expression profiling and functional analysis of Toll-like receptors in primary healthy human nasal epithelial cells shows no correlation and a refractory LPS response.

PubMed

van Tongeren, J; Röschmann, K I L; Reinartz, S M; Luiten, S; Fokkens, W J; de Jong, E C; van Drunen, C M

2015-01-01

Innate immune recognition via Toll-like receptors (TLRs) on barrier cells like epithelial cells has been shown to influence the regulation of local immune responses. Here we determine expression level variations and functionality of TLRs in nasal epithelial cells from healthy donors. Expression levels of the different TLRs on primary nasal epithelial cells from healthy donors derived from inferior turbinates was determined by RT-PCR. Functionality of the TLRs was determined by stimulation with the respective ligand and evaluation of released mediators by Luminex ELISA. Primary nasal epithelial cells express different levels of TLR1-6 and TLR9. We were unable to detect mRNA of TLR7, TLR8 and TLR10. Stimulation with Poly(I:C) resulted in a significant increased secretion of IL-4, IL-6, RANTES, IP-10, MIP-1β, VEGF, FGF, IL-1RA, IL-2R and G-CSF. Stimulation with PGN only resulted in significant increased production of IL-6, VEGF and IL-1RA. Although the expression of TLR4 and co-stimulatory molecules could be confirmed, primary nasal epithelial cells appeared to be unresponsive to stimulation with LPS. Furthermore, we observed huge individual differences in TLR agonist-induced mediator release, which did not correlate with the respective expression of TLRs. Our data suggest that nasal epithelium seems to have developed a delicate system of discrimination and recognition of microbial patterns. Hypo-responsiveness to LPS could provide a mechanism to dampen the inflammatory response in the nasal mucosa in order to avoid a chronic inflammatory response. Individual, differential expression of TLRs on epithelial cells and functionality in terms of released mediators might be a crucial factor in explaining why some people develop allergies to common inhaled antigens, and others do not.

Prognostic Relevance of Lymph Node Regression After Neoadjuvant Chemoradiation for Esophageal Cancer.

PubMed

Philippron, Annouck; Bollschweiler, Elfriede; Kunikata, Ayumi; Plum, Patrick; Schmidt, Claudia; Favi, Francesco; Drebber, Uta; Hölscher, Arnulf H

2016-01-01

Prognostic factors after preoperative chemoradiation for patients with advanced esophageal cancer are under discussion. Treatment response measured in the primary tumor is a well-defined prognostic marker. The prognostic relevance of tumor regression in lymph nodes (LNs), eg, histomorphologic characteristics must be evaluated in a larger series of patients. From 1997-2010, 403 patients with cT3N×M0 esophageal cancer underwent preoperative chemoradiation followed by transthoracic esophagectomy. Histopathologic response of the primary tumor was graded in resected specimens as "minor" (≥10% vital residual tumor cells) or "major." The LNs of all patients without LN metastases (ypN0 n = 222, adenocarcinoma n = 129, squamous cell carcinoma n = 93) were reevaluated for central fibrosis. Univariate and multivariate analyses were performed on histomorphologic criteria of examined LNs and used to correlate these with tumor response and prognosis. The 5-year survival rate (5YSR) for all patients was 30%. Overall, 5480 LNs were reevaluated for the existence of central fibrosis in ypN0 cases. The prognostic relevance of the LN regression (LNR) grading system was confirmed for all patients with univariate (P < 0.001) and multivariate (P = 0.02) analyses. In results, the 5YSR for ypN0 patients overall was 37%, for patients with major response by the primary tumor was 42%, and for minor responders was 19% (P < 0.001). Analyzing LNR in major responders, the group with less than 3 LNs with central fibrosis (n = 52) showed significantly better prognosis (5YSR = 63%) compared to those with more (5YSR = 34%), (P = 0.016). Conclusion includes morphologic signs of metastatic LNR after chemoradiation, such as central fibrosis, are of prognostic relevance for patients with advanced esophageal cancer, especially for those with major response of the primary tumor. Copyright © 2016 Elsevier Inc. All rights reserved.

Neuropeptides activate human mast cell degranulation and chemokine production

PubMed Central

Kulka, Marianna; Sheen, Cecilia H; Tancowny, Brian P; Grammer, Leslie C; Schleimer, Robert P

2008-01-01

During neuronal-induced inflammation, mast cells may respond to stimuli such as neuropeptides in an FcεRI-independent manner. In this study, we characterized human mast cell responses to substance P (SP), nerve growth factor (NGF), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) and compared these responses to human mast cell responses to immunoglobulin E (IgE)/anti-IgE and compound 48/80. Primary cultured mast cells, generated from CD34+ progenitors in the presence of stem cell factor and interleukin-6 (IL-6), and human cultured mast cells (LAD2) were stimulated with these and other stimuli (gastrin, concanavalin A, radiocontrast media, and mannitol) and their degranulation and chemokine production was assessed. VIP and SP stimulated primary human mast cells and LAD cells to degranulate; gastrin, concanavalin A, radiocontrast media, mannitol, CGRP and NGF did not activate degranulation. While anti-IgE stimulation did not induce significant production of chemokines, stimulation with VIP, SP or compound 48/80 potently induced production of monocyte chemoattractant protein-1, inducible protein-10, monokine induced by interferon-γ (MIG), RANTES (regulated on activation, normal, T-cell expressed, and secreted) and IL-8. VIP, SP and compound 48/80 also activated release of tumour necrosis factor, IL-3 and granulocyte–macrophage colony-stimulating factor, but not IL-4, interferon-γ or eotaxin. Human mast cells expressed surface neurokinin 1 receptor (NK1R), NK2R, NK3R and VIP receptor type 2 (VPAC2) but not VPAC1 and activation of human mast cells by IgE/anti-IgE up-regulated expression of VPAC2, NK2R, and NK3R. These studies demonstrate the pattern of receptor expression and activation of mast cell by a host of G-protein coupled receptor ligands and suggest that SP and VIP activate a unique signalling pathway in human mast cells. These results are likely to have direct relevance to neuronally induced inflammatory diseases. PMID:17922833

Development and validation of a Malawian version of the primary care assessment tool.

PubMed

Dullie, Luckson; Meland, Eivind; Hetlevik, Øystein; Mildestvedt, Thomas; Gjesdal, Sturla

2018-05-16

Malawi does not have validated tools for assessing primary care performance from patients' experience. The aim of this study was to develop a Malawian version of Primary Care Assessment Tool (PCAT-Mw) and to evaluate its reliability and validity in the assessment of the core primary care dimensions from adult patients' perspective in Malawi. A team of experts assessed the South African version of the primary care assessment tool (ZA-PCAT) for face and content validity. The adapted questionnaire underwent forward and backward translation and a pilot study. The tool was then used in an interviewer administered cross-sectional survey in Neno district, Malawi, to test validity and reliability. Exploratory factor analysis was performed on a random half of the sample to evaluate internal consistency, reliability and construct validity of items and scales. The identified constructs were then tested with confirmatory factor analysis. Likert scale assumption testing and descriptive statistics were done on the final factor structure. The PCAT-Mw was further tested for intra-rater and inter-rater reliability. From the responses of 631 patients, a 29-item PCAT-Mw was constructed comprising seven multi-item scales, representing five primary care dimensions (first contact, continuity, comprehensiveness, coordination and community orientation). All the seven scales achieved good internal consistency, item-total correlations and construct validity. Cronbach's alpha coefficient ranged from 0.66 to 0.91. A satisfactory goodness of fit model was achieved (GFI = 0.90, CFI = 0.91, RMSEA = 0.05, PCLOSE = 0.65). The full range of possible scores was observed for all scales. Scaling assumptions tests were achieved for all except the two comprehensiveness scales. Intra-class correlation coefficient (ICC) was 0.90 (n = 44, 95% CI 0.81-0.94, p < 0.001) for intra-rater reliability and 0.84 (n = 42, 95% CI 0.71-0.96, p < 0.001) for inter-rater reliability. Comprehensive metric analyses supported the reliability and validity of PCAT-Mw in assessing the core concepts of primary care from adult patients' experience. This tool could be used for health service research in primary care in Malawi.

Innate immune responses induced by lipopolysaccharide and lipoteichoic acid in primary goat mammary epithelial cells.

PubMed

Bulgari, Omar; Dong, Xianwen; Roca, Alfred L; Caroli, Anna M; Loor, Juan J

2017-01-01

Innate immune responses induced by in vitro stimulation of primary mammary epithelial cells (MEC) using Gram-negative lipopolysaccharide (LPS) and Gram-positive lipoteichoic acid (LTA) bacterial cell wall components are well- characterized in bovine species. The objective of the current study was to characterize the downstream regulation of the inflammatory response induced by Toll-like receptors in primary goat MEC (pgMEC). We performed quantitative real-time RT-PCR (qPCR) to measure mRNA levels of 9 genes involved in transcriptional regulation or antibacterial activity: Toll-like receptor 2 ( TLR2 ), Toll-like receptor 4 ( TLR4 ), prostaglandin-endoperoxide synthase 2 ( PTGS2 ), interferon induced protein with tetratricopeptide repeats 3 ( IFIT3 ), interferon regulatory factor 3 ( IRF3 ), myeloid differentiation primary response 88 ( MYD88 ), nuclear factor of kappa light polypeptide gene enhancer in B-cells 1 ( NFKB1 ), Toll interacting protein ( TOLLIP ), and lactoferrin ( LTF ). Furthermore, we analyzed 7 cytokines involved in Toll-like receptor signaling pathways: C-C motif chemokine ligand 2 ( CCL2 ), C-C motif chemokine ligand 5 ( CCL5 ), C-X-C motif chemokine ligand 6 ( CXCL6 ), interleukin 8 ( CXCL8 ), interleukin 1 beta ( IL1B ), interleukin 6 ( IL6 ), and tumor necrosis factor alpha ( TNF ). Stimulation of pgMEC with LPS for 3 h led to an increase in expression of CCL2 , CXCL6 , IL6 , CXCL8 , PTGS2 , IFIT3 , MYD88 , NFKB1 , and TLR4 ( P  < 0.05). Except for IL6 , and PTGS2 , the same genes had greater expression than controls at 6 h post-LPS ( P  < 0.05). Expression of CCL5 , PTGS2 , IFIT3 , NFKB1 , TLR4 , and TOLLIP was greater than controls after 3 h of incubation with LTA ( P  < 0.05). Compared to controls, stimulation with LTA for 6 h led to greater expression of PTGS2 , IFIT3 , NFKB1 , and TOLLIP ( P  < 0.05) whereas the expression of CXCL6 , CXCL8 , and TLR4 was lower ( P  < 0.05). At 3 h incubation with both toxins compared to controls a greater expression ( P  < 0.05) of CCL2 , CCL5 , CXCL6 , CXCL8 , IL6 , PTGS2 , IFIT3 , IRF3 , MYD88 , and NFKB1 was detected. After 6 h of incubation with both toxins, the expression of CCL2 , CXCL6 , IFIT3 , MYD88 , NFKB1 , and TLR4 was higher than the controls ( P  < 0.05). Data indicate that in the goat MEC, LTA induces a weaker inflammatory response than LPS. This may be related to the observation that gram-positive bacteria cause chronic mastitis more often than gram-negative infections.

Types of social support and parental acceptance among transfemale youth and their impact on mental health, sexual debut, history of sex work and condomless anal intercourse.

PubMed

Le, Victory; Arayasirikul, Sean; Chen, Yea-Hung; Jin, Harry; Wilson, Erin C

2016-01-01

Transfemale youth (TFY) are an underserved and understudied population at risk for numerous poor physical and mental health outcomes, most notably HIV. Research suggests that parental acceptance and social support may serve as protective factors against HIV and other risks for TFY; however, it is unclear whether TFY receive primary social support from parents with or without parental acceptance of their gender identity. This study examines differences in parental acceptance, mental health and the HIV risk factors of history of sex work, age at sexual debut and engagement in condomless anal intercourse between TFY with two types of primary social support - non-parental primary social support (NPPSS) and parental primary social support (PPSS). Cross-sectional data collected from 301 TFY from 2012 to 2014 in the San Francisco Bay Area were analyzed to determine differences in parental acceptance, mental health and HIV risk factors between youth with and without PPSS. Univariate statistics and chi-squared tests were conducted to determine if parental acceptance and health outcomes were correlated with type of social support. Two-hundred fifty-one participants (83.7%) reported having NPPSS, and 49 (16.3%) reported PPSS. Significantly more youth with PPSS reported affirmative responses on parental acceptance items than their NPPSS counterparts. For example, 87.8% of youth with PPSS reported that their parents believed they could have a happy future as a trans adult, compared with 51.6% of youth with NPPSS (p<0.001). Fewer participants with PPSS reported symptoms of psychological distress (2.0% vs. 12.5%, p=0.057), though this finding was not statistically significant; no significant associations were found between primary social support type and HIV risk factors. These results suggest that TFY with parental acceptance of their gender identity may be more likely to reach out to their parents as their primary source of social support. Interventions focused on parental acceptance of their child's gender identity may have the most promise for creating parental social support systems in the lives of TFY.

Medulloblastoma in China: Clinicopathologic Analyses of SHH, WNT, and Non-SHH/WNT Molecular Subgroups Reveal Different Therapeutic Responses to Adjuvant Chemotherapy

PubMed Central

Ren, Yong; Yao, Yu; Li, Kay Ka-Wai; Ng, Ho-Keung; Mao, Ying; Zhou, Liang-Fu; Zhong, Ping

2014-01-01

Medulloblastoma (MB) is one of the most common primary central nervous system tumors in children. Data is lacking of a large cohort of medulloblastoma patients in China. Also, our knowledge on the sensitivity of different molecular subgroups of MB to adjuvant radiation therapy (RT) or chemotherapy (CHT) is still limited. The authors performed a retrospective study of 173 medulloblastoma patients treated at two institutions from 2002 to 2011. Formalin-fixed paraffin embedded (FFPE) tissues were available in all the cases and sections were stained to classify histological and molecular subgroups. Univariate and multivariate analyses were used to investigate prognostic factors. Of 173 patients, there were 118 children and 55 adults, 112 males and 61 females. Estimated 5-year overall survival (OS) rates for all patients, children and adults were 52%, 48% and 63%, respectively. After multivariate analysis, postoperative primary radiation therapy (RT) and chemotherapy (CHT) were revealed as favorable prognostic factors influencing OS and EFS. Postoperative primary chemotherapy (CHT) was found significantly improving the survival of children (p<0.001) while it was not a significant prognostic factor for adult patients. Moreover, patients in WNT subtype had better OS (p = 0.028) than others (SHH and Non-SHH/WNT subtypes) given postoperative adjuvant therapies. Postoperative primary RT was found to be a strong prognostic factor influencing the survival in all histological and molecular subgroups (p<0.001). Postoperative primary CHT was found significantly to influence the survival of classic medulloblastoma (CMB) (OS p<0.001, EFS p<0.001), SHH subgroup (OS p = 0.020, EFS p = 0.049) and WNT subgroup (OS p = 0.003, EFS p = 0.016) but not in desmoplastic/nodular medulloblastoma (DMB) (OS p = 0.361, EFS p = 0.834) and Non-SHH/WNT subgroup (OS p = 0.127, EFS p = 0.055). Our study showed postoperative primary CHT significantly influence the survival of CMB, SHH subgroup and WNT subgroup but not in DMB and Non-SHH/WNT subgroup of MB. PMID:24932704

Types of social support and parental acceptance among transfemale youth and their impact on mental health, sexual debut, history of sex work and condomless anal intercourse

PubMed Central

Le, Victory; Arayasirikul, Sean; Chen, Yea-Hung; Jin, Harry; Wilson, Erin C

2016-01-01

Introduction Transfemale youth (TFY) are an underserved and understudied population at risk for numerous poor physical and mental health outcomes, most notably HIV. Research suggests that parental acceptance and social support may serve as protective factors against HIV and other risks for TFY; however, it is unclear whether TFY receive primary social support from parents with or without parental acceptance of their gender identity. This study examines differences in parental acceptance, mental health and the HIV risk factors of history of sex work, age at sexual debut and engagement in condomless anal intercourse between TFY with two types of primary social support – non-parental primary social support (NPPSS) and parental primary social support (PPSS). Methods Cross-sectional data collected from 301 TFY from 2012 to 2014 in the San Francisco Bay Area were analyzed to determine differences in parental acceptance, mental health and HIV risk factors between youth with and without PPSS. Univariate statistics and chi-squared tests were conducted to determine if parental acceptance and health outcomes were correlated with type of social support. Results Two-hundred fifty-one participants (83.7%) reported having NPPSS, and 49 (16.3%) reported PPSS. Significantly more youth with PPSS reported affirmative responses on parental acceptance items than their NPPSS counterparts. For example, 87.8% of youth with PPSS reported that their parents believed they could have a happy future as a trans adult, compared with 51.6% of youth with NPPSS (p<0.001). Fewer participants with PPSS reported symptoms of psychological distress (2.0% vs. 12.5%, p=0.057), though this finding was not statistically significant; no significant associations were found between primary social support type and HIV risk factors. Conclusions These results suggest that TFY with parental acceptance of their gender identity may be more likely to reach out to their parents as their primary source of social support. Interventions focused on parental acceptance of their child's gender identity may have the most promise for creating parental social support systems in the lives of TFY. PMID:27431467

Phenylalanine Is Required to Promote Specific Developmental Responses and Prevents Cellular Damage in Response to Ultraviolet Light in Soybean (Glycine max) during the Seed-to-Seedling Transition

PubMed Central

Sullivan, Joe H.; Muhammad, DurreShahwar; Warpeha, Katherine M.

2014-01-01

UV-radiation elicits a suite of developmental (photomorphogenic) and protective responses in plants, but responses early post-germination have received little attention, particularly in intensively bred plants of economic importance. We examined germination, hypocotyl elongation, leaf pubescence and subcellular responses of germinating and/or etiolated soybean (Glycine max (L.) Merr.) seedlings in response to treatment with discrete wavelengths of UV-A or UV-B radiation. We demonstrate differential responses of germinating/young soybean seedlings to a range of UV wavelengths that indicate unique signal transduction mechanisms regulate UV-initiated responses. We have investigated how phenylalanine, a key substrate in the phenylpropanoid pathway, may be involved in these responses. Pubescence may be a key location for phenylalanine-derived protective compounds, as UV-B irradiation increased pubescence and accumulation of UV-absorbing compounds within primary leaf pubescence, visualized by microscopy and absorbance spectra. Mass spectrometry analysis of pubescence indicated that sinapic esters accumulate in the UV-irradiated hairs compared to unirradiated primary leaf tissue. Deleterious effects of some UV-B wavelengths on germination and seedling responses were reduced or entirely prevented by inclusion of phenylalanine in the growth media. Key effects of phenylalanine were not duplicated by tyrosine or tryptophan or sucrose, nor is the specificity of response due to the absorbance of phenylalanine itself. These results suggest that in the seed-to-seedling transition, phenylalanine may be a limiting factor in the development of initial mechanisms of UV protection in the developing leaf. PMID:25549094

Differentiation of Inflammation-Responsive Astrocytes from Glial Progenitors Generated from Human Induced Pluripotent Stem Cells.

PubMed

Santos, Renata; Vadodaria, Krishna C; Jaeger, Baptiste N; Mei, Arianna; Lefcochilos-Fogelquist, Sabrina; Mendes, Ana P D; Erikson, Galina; Shokhirev, Maxim; Randolph-Moore, Lynne; Fredlender, Callie; Dave, Sonia; Oefner, Ruth; Fitzpatrick, Conor; Pena, Monique; Barron, Jerika J; Ku, Manching; Denli, Ahmet M; Kerman, Bilal E; Charnay, Patrick; Kelsoe, John R; Marchetto, Maria C; Gage, Fred H

2017-06-06

Astrocyte dysfunction and neuroinflammation are detrimental features in multiple pathologies of the CNS. Therefore, the development of methods that produce functional human astrocytes represents an advance in the study of neurological diseases. Here we report an efficient method for inflammation-responsive astrocyte generation from induced pluripotent stem cells (iPSCs) and embryonic stem cells. This protocol uses an intermediate glial progenitor stage and generates functional astrocytes that show levels of glutamate uptake and calcium activation comparable with those observed in human primary astrocytes. Stimulation of stem cell-derived astrocytes with interleukin-1β or tumor necrosis factor α elicits a strong and rapid pro-inflammatory response. RNA-sequencing transcriptome profiling confirmed that similar gene expression changes occurred in iPSC-derived and primary astrocytes upon stimulation with interleukin-1β. This protocol represents an important tool for modeling in-a-dish neurological diseases with an inflammatory component, allowing for the investigation of the role of diseased astrocytes in neuronal degeneration. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Rising nutrient-pulse frequency and high UVR strengthen microbial interactions

PubMed Central

Cabrerizo, Marco J.; Medina-Sánchez, Juan Manuel; Dorado-García, Irene; Villar-Argaiz, Manuel; Carrillo, Presentación

2017-01-01

Solar radiation and nutrient pulses regulate the ecosystem’s functioning. However, little is known about how a greater frequency of pulsed nutrients under high ultraviolet radiation (UVR) levels, as expected in the near future, could alter the responses and interaction between primary producers and decomposers. In this report, we demonstrate through a mesocosm study in lake La Caldera (Spain) that a repeated (press) compared to a one-time (pulse) schedule under UVR prompted higher increases in primary (PP) than in bacterial production (BP) coupled with a replacement of photoautotrophs by mixotrophic nanoflagellates (MNFs). The mechanism underlying these amplified phytoplanktonic responses was a dual control by MNFs on bacteria through the excretion of organic carbon and an increased top-down control by bacterivory. We also show across a 6-year whole-lake study that the changes from photoautotrophs to MNFs were related mainly to the frequency of pulsed nutrients (e.g. desert dust inputs). Our results underscore how an improved understanding of the interaction between chronic and stochastic environmental factors is critical for predicting ongoing changes in ecosystem functioning and its responses to climatically driven changes. PMID:28252666

Rising nutrient-pulse frequency and high UVR strengthen microbial interactions

NASA Astrophysics Data System (ADS)

Cabrerizo, Marco J.; Medina-Sánchez, Juan Manuel; Dorado-García, Irene; Villar-Argaiz, Manuel; Carrillo, Presentación

2017-03-01

Solar radiation and nutrient pulses regulate the ecosystem’s functioning. However, little is known about how a greater frequency of pulsed nutrients under high ultraviolet radiation (UVR) levels, as expected in the near future, could alter the responses and interaction between primary producers and decomposers. In this report, we demonstrate through a mesocosm study in lake La Caldera (Spain) that a repeated (press) compared to a one-time (pulse) schedule under UVR prompted higher increases in primary (PP) than in bacterial production (BP) coupled with a replacement of photoautotrophs by mixotrophic nanoflagellates (MNFs). The mechanism underlying these amplified phytoplanktonic responses was a dual control by MNFs on bacteria through the excretion of organic carbon and an increased top-down control by bacterivory. We also show across a 6-year whole-lake study that the changes from photoautotrophs to MNFs were related mainly to the frequency of pulsed nutrients (e.g. desert dust inputs). Our results underscore how an improved understanding of the interaction between chronic and stochastic environmental factors is critical for predicting ongoing changes in ecosystem functioning and its responses to climatically driven changes.

Dissociation of Innate Immune Responses in Microglia Infected with Listeria monocytogenes

PubMed Central

Frande-Cabanes, Elisabet; Fernandez-Prieto, Lorena; Calderon-Gonzalez, Ricardo; Rodríguez-Del Río, Estela; Yañez-Diaz, Sonsoles; López-Fanarraga, Monica; Alvarez-Domínguez, Carmen

2014-01-01

Microglia, the innate immune cells of the brain, plays a central role in cerebral listeriosis. Here, we present evidence that microglia control Listeria infection differently than macrophages. Infection of primary microglial cultures and murine cell lines with Listeria resulted in a dual function of the two gene expression programmes involved in early and late immune responses in macrophages. Whereas the bacterial gene hly seems responsible for both transcriptional programmes in macrophages, Listeria induces in microglia only the tumor necrosis factor (TNF)-regulated transcriptional programme. Listeria also represses in microglia the late immune response gathered in two clusters, microbial degradation, and interferon (IFN)-inducible genes. The bacterial gene actA was required in microglia to induce TNF-regulated responses and to repress the late response. Isolation of microglial phagosomes revealed a phagosomal environment unable to destroy Listeria. Microglial phagosomes were also defective in several signaling and trafficking components reported as relevant for Listeria innate immune responses. This transcriptional strategy in microglia induced high levels of TNF-α and monocyte chemotactic protein-1 and low production of other neurotoxic compounds such as nitric oxide, hydrogen peroxide, and Type I IFNs. These cytokines and toxic microglial products are also released by primary microglia, and this cytokine and chemokine cocktail display a low potential to trigger neuronal apoptosis. This overall bacterial strategy strongly suggests that microglia limit Listeria inflammation pattern exclusively through TNF-mediated responses to preserve brain integrity. GLIA 2014;62:233–246 PMID:24311463

Infection with hepatitis C virus depends on TACSTD2, a regulator of claudin-1 and occludin highly downregulated in hepatocellular carcinoma

PubMed Central

Alayli, Farah; Melis, Marta; Kabat, Juraj; Pomerenke, Anna; Altan-Bonnet, Nihal; Zamboni, Fausto; Emerson, Suzanne U.

2018-01-01

Entry of hepatitis C virus (HCV) into hepatocytes is a complex process that involves numerous cellular factors, including the scavenger receptor class B type 1 (SR-B1), the tetraspanin CD81, and the tight junction (TJ) proteins claudin-1 (CLDN1) and occludin (OCLN). Despite expression of all known HCV-entry factors, in vitro models based on hepatoma cell lines do not fully reproduce the in vivo susceptibility of liver cells to primary HCV isolates, implying the existence of additional host factors which are critical for HCV entry and/or replication. Likewise, HCV replication is severely impaired within hepatocellular carcinoma (HCC) tissue in vivo, but the mechanisms responsible for this restriction are presently unknown. Here, we identify tumor-associated calcium signal transducer 2 (TACSTD2), one of the most downregulated genes in primary HCC tissue, as a host factor that interacts with CLDN1 and OCLN and regulates their cellular localization. TACSTD2 gene silencing disrupts the typical linear distribution of CLDN1 and OCLN along the cellular membrane in both hepatoma cells and primary human hepatocytes, recapitulating the pattern observed in vivo in primary HCC tissue. Mechanistic studies suggest that TACSTD2 is involved in the phosphorylation of CLDN1 and OCLN, which is required for their proper cellular localization. Silencing of TACSTD2 dramatically inhibits HCV infection with a pan-genotype effect that occurs at the level of viral entry. Our study identifies TACSTD2 as a novel regulator of two major HCV-entry factors, CLDN1 and OCLN, which is strongly downregulated in malignant hepatocytes. These results provide new insights into the complex process of HCV entry into hepatocytes and may assist in the development of more efficient cellular systems for HCV propagation in vitro. PMID:29538454

Early innate immune responses to Sin Nombre hantavirus occur independently of IFN regulatory factor 3, characterized pattern recognition receptors, and viral entry.

PubMed

Prescott, Joseph B; Hall, Pamela R; Bondu-Hawkins, Virginie S; Ye, Chunyan; Hjelle, Brian

2007-08-01

Sin Nombre virus (SNV) is a highly pathogenic New World virus and etiologic agent of hantavirus cardiopulmonary syndrome. We have previously shown that replication-defective virus particles are able to induce a strong IFN-stimulated gene (ISG) response in human primary cells. RNA viruses often stimulate the innate immune response by interactions between viral nucleic acids, acting as a pathogen-associated molecular pattern, and cellular pattern-recognition receptors (PRRs). Ligand binding to PRRs activates transcription factors which regulate the expression of antiviral genes, and in all systems examined thus far, IFN regulatory factor 3 (IRF3) has been described as an essential intermediate for induction of ISG expression. However, we now describe a model in which IRF3 is dispensable for the induction of ISG transcription in response to viral particles. IRF3-independent ISG transcription in human hepatoma cell lines is initiated early after exposure to SNV virus particles in an entry- and replication-independent fashion. Furthermore, using gene knockdown, we discovered that this activation is independent of the best-characterized RNA- and protein-sensing PRRs including the cytoplasmic caspase recruitment domain-containing RNA helicases and the TLRs. SNV particles engage a heretofore unrecognized PRR, likely located at the cell surface, and engage a novel IRF3-independent pathway that activates the innate immune response.

Antigen expression level threshold tunes the fate of CD8 T cells during primary hepatic immune responses.

PubMed

Tay, Szun Szun; Wong, Yik Chun; McDonald, David M; Wood, Nicole A W; Roediger, Ben; Sierro, Frederic; Mcguffog, Claire; Alexander, Ian E; Bishop, G Alex; Gamble, Jennifer R; Weninger, Wolfgang; McCaughan, Geoffrey W; Bertolino, Patrick; Bowen, David G

2014-06-24

CD8 T-cell responses to liver-expressed antigens range from deletional tolerance to full effector differentiation resulting in overt hepatotoxicity. The reasons for these heterogeneous outcomes are not well understood. To identify factors that govern the fate of CD8 T cells activated by hepatocyte-expressed antigen, we exploited recombinant adenoassociated viral vectors that enabled us to vary potential parameters determining these outcomes in vivo. Our findings reveal a threshold of antigen expression within the liver as the dominant factor determining T-cell fate, irrespective of T-cell receptor affinity or antigen cross-presentation. Thus, when a low percentage of hepatocytes expressed cognate antigen, high-affinity T cells developed and maintained effector function, whereas, at a high percentage, they became functionally exhausted and silenced. Exhaustion was not irreversibly determined by initial activation, but was maintained by high intrahepatic antigen load during the early phase of the response; cytolytic function was restored when T cells primed under high antigen load conditions were transferred into an environment of low-level antigen expression. Our study reveals a hierarchy of factors dictating the fate of CD8 T cells during hepatic immune responses, and provides an explanation for the different immune outcomes observed in a variety of immune-mediated liver pathologic conditions.

Petri Net computational modelling of Langerhans cell Interferon Regulatory Factor Network predicts their role in T cell activation.

PubMed

Polak, Marta E; Ung, Chuin Ying; Masapust, Joanna; Freeman, Tom C; Ardern-Jones, Michael R

2017-04-06

Langerhans cells (LCs) are able to orchestrate adaptive immune responses in the skin by interpreting the microenvironmental context in which they encounter foreign substances, but the regulatory basis for this has not been established. Utilising systems immunology approaches combining in silico modelling of a reconstructed gene regulatory network (GRN) with in vitro validation of the predictions, we sought to determine the mechanisms of regulation of immune responses in human primary LCs. The key role of Interferon regulatory factors (IRFs) as controllers of the human Langerhans cell response to epidermal cytokines was revealed by whole transcriptome analysis. Applying Boolean logic we assembled a Petri net-based model of the IRF-GRN which provides molecular pathway predictions for the induction of different transcriptional programmes in LCs. In silico simulations performed after model parameterisation with transcription factor expression values predicted that human LC activation of antigen-specific CD8 T cells would be differentially regulated by epidermal cytokine induction of specific IRF-controlled pathways. This was confirmed by in vitro measurement of IFN-γ production by activated T cells. As a proof of concept, this approach shows that stochastic modelling of a specific immune networks renders transcriptome data valuable for the prediction of functional outcomes of immune responses.

Innate immune response to Burkholderia mallei

PubMed Central

Saikh, Kamal U.; Mott, Tiffany M.

2017-01-01

Purpose of review Burkholderia mallei is a facultative intracellular pathogen that causes the highly contagious and often the fatal disease, glanders. With its high rate of infectivity via aerosol and recalcitrance toward antibiotics, this pathogen is considered a potential biological threat agent. This review focuses on the most recent literature highlighting host innate immune response to B. mallei. Recent findings Recent studies focused on elucidating host innate immune responses to the novel mechanisms and virulence factors employed by B. mallei for survival. Studies suggest that pathogen proteins manipulate various cellular processes, including host ubiquitination pathways, phagosomal escape, and actin–cytoskeleton rearrangement. Immune-signaling molecules such as Toll-like receptors, nucleotode-binding oligomerization domain, myeloid differentiation primary response protein 88, and proinflammatory cytokines such as interferon-gamma and tumor necrosis factor-α, play key roles in the induction of innate immune responses. Modifications in B. mallei lipopolysaccharide, in particular, the lipid A acyl groups, stimulate immune responses via Toll-like receptor4 activation that may contribute to persistent infection. Summary Mortality is high because of septicemia and immune pathogenesis with B. mallei exposure. An effective innate immune response is critical to controlling the acute phase of the infection. Both vaccination and therapeutic approaches are necessary for complete protection against B. mallei. PMID:28177960

Krüppel-like factors are effectors of nuclear receptor signaling

PubMed Central

Knoedler, Joseph R.; Denver, Robert J.

2015-01-01

Binding of steroid and thyroid hormones to their cognate nuclear receptors (NRs) impacts virtually every aspect of postembryonic development, physiology and behavior, and inappropriate signaling by NRs may contribute to disease. While NRs regulate genes by direct binding to hormone response elements in the genome, their actions may depend on the activity of other transcription factors (TFs) that may or may not bind DNA. The Krüppel-like family of transcription factors (KLF) is an evolutionarily conserved class of DNA-binding proteins that influence many aspects of development and physiology. Several members of this family have been shown to play diverse roles in NR signaling. For example, KLFs 1) act as accessory transcription factors for NR actions, 2) regulate expression of NR genes, and 3) as gene products of primary NR response genes function as key players in NR-dependent transcriptional networks. In mouse models, deletion of different KLFs leads to aberrant transcriptional and physiological responses to hormones, underscoring the importance of these proteins in the regulation of hormonal signaling. Understanding the functional relationships between NRs and KLFs will yield important insights into mechanisms of NR signaling. In this review we present a conceptual framework for understanding how KLFs participate in NR signaling, and we provide examples of how these proteins function to effect hormone action. PMID:24642391

Career retention in the dental hygiene workforce in Texas.

PubMed

Johns, G H; Gutmann, M E; DeWald, J P; Nunn, M E

2001-01-01

The purpose of this study was to determine the factors that influence the retention and attrition of dental hygienists within the workforce in Texas. Respondents' perception of the role of employee benefits and practice of dental hygiene on career retention were explored. Demographic descriptors, including educational level, marital status, age, employment setting, and practice statuses, were also examined. A questionnaire modified from the American Dental Hygienists' Association Extension Study: Retention of Dental Hygienists in the Workforce Final Report, April 1992, was mailed to a systematic sample of licensed Texas dental hygienists in March 1999. Descriptive statistics were computed for dental hygienists currently in practice in Texas and those not in practice at the time of the survey. Differences in demographics, benefits, and attitudes between dental hygienists currently in practice in Texas and dental hygienists not in practice at the time of the survey were tested using independent t-tests for interval data and chi-squared tests for categorical data. All statistical analyses were conducted using the Statistical Package for Social Scientists (SPSS v. 9, Chicago, Illinois). A response rate of 68.1% was obtained. Results revealed the primary reasons for remaining in the practice of dental hygiene were salary, family responsibility, professional collaboration, and variety of work. The primary reasons for leaving dental hygiene practice were family responsibility, boredom, salary, and lack of benefits. Secondary and tertiary reasons stated for staying in clinical practice revealed additional factors including benefits, participation in decision-making, and a safe environment. Dental hygienists in clinical practice were more likely to be employed by a dentist in a single practice and see more patients per day, have a certificate or associate's degree, be unmarried, have fewer children, and be younger than dental hygienists not in practice. The findings suggest that dental hygienists in Texas who remain in the workforce are positively influenced primarily by salary. Dental hygienists in Texas who had left the workforce were primarily influenced to leave practice because of family responsibility. Boredom and lack of benefits were also important factors in deciding to leave clinical practice. Employers of dental hygienists need to be aware of these factors in the hiring process. In addition, dental hygiene educators should prepare students in interviewing techniques for better communication regarding retention factors.

Primary care practitioner perceptions and attitudes of complementary medicine: a content analysis of free-text responses from a survey of non-metropolitan Australian general practitioners.

PubMed

Wardle, Jon L; Sibbritt, David W; Adams, Jon

2018-05-01

AimThis study examines GP perceptions, attitudes and knowledge of complementary medicine (CM), and to understand contextual factors that influence these perceptions, attitudes and knowledge. CM use is increasing, and its influence on primary care becoming increasingly significant. Although general practitioners (GPs) often have central primary care gate-keeper roles within health systems, few studies have looked specifically at GPs' perceptions, attitudes and knowledge of CM. A questionnaire was mailed to all 1486 GPs registered as practicing in non-metropolitan areas of New South Wales. The survey included one free-text qualitative question, where respondents were invited to highlight issues associated with CM in their own words. Free-text responses were analyzed qualitatively using thematic analysis.FindingsIn total, 585 GPs responded to the survey (adjusted response rate 40.1%), with 152 (26.0%) filling in the free-text question. Central themes which emerged were risk as a primary concern; opposition to, resistance to and the inappropriateness of complementary therapies; struggles with complexity and ambivalent tolerance. GPs in Australia have a wide variety of perceptions toward CM. A minority of GPs have absolute views on CM, with most GPs having numerous caveats and qualifications of individual CM. Efficacy is only one aspect of CM critically evaluated by GPs when gauging support for individual therapies - risk, alignment with medical principles and an openness to exploring new avenues of treatment where others have failed, all appear to be equally important considerations when GPs form their views around CM.

Prepared to react? Assessing the functional capacity of the primary health care system in rural Orissa, India to respond to the devastating flood of September 2008.

PubMed

Phalkey, Revati; Dash, Shisir R; Mukhopadhyay, Alok; Runge-Ranzinger, Silvia; Marx, Michael

2012-01-01

Early detection of an impending flood and the availability of countermeasures to deal with it can significantly reduce its health impacts. In developing countries like India, public primary health care facilities are frontline organizations that deal with disasters particularly in rural settings. For developing robust counter reacting systems evaluating preparedness capacities within existing systems becomes necessary. The objective of the study is to assess the functional capacity of the primary health care system in Jagatsinghpur district of rural Orissa in India to respond to the devastating flood of September 2008. An onsite survey was conducted in all 29 primary and secondary facilities in five rural blocks (administrative units) of Jagatsinghpur district in Orissa state. A pre-tested structured questionnaire was administered face to face in the facilities. The data was entered, processed and analyzed using STATA(®) 10. Data from our primary survey clearly shows that the healthcare facilities are ill prepared to handle the flood despite being faced by them annually. Basic utilities like electricity backup and essential medical supplies are lacking during floods. Lack of human resources along with missing standard operating procedures; pre-identified communication and incident command systems; effective leadership; and weak financial structures are the main hindering factors in mounting an adequate response to the floods. The 2008 flood challenged the primary curative and preventive health care services in Jagatsinghpur. Simple steps like developing facility specific preparedness plans which detail out standard operating procedures during floods and identify clear lines of command will go a long way in strengthening the response to future floods. Performance critiques provided by the grass roots workers, like this one, should be used for institutional learning and effective preparedness planning. Additionally each facility should maintain contingency funds for emergency response along with local vendor agreements to ensure stock supplies during floods. The facilities should ensure that baseline public health standards for health care delivery identified by the Government are met in non-flood periods in order to improve the response during floods. Building strong public primary health care systems is a development challenge. The recovery phases of disasters should be seen as an opportunity to expand and improve services and facilities.

Prepared to react? Assessing the functional capacity of the primary health care system in rural Orissa, India to respond to the devastating flood of September 2008

PubMed Central

Phalkey, Revati; Dash, Shisir R.; Mukhopadhyay, Alok; Runge-Ranzinger, Silvia; Marx, Michael

2012-01-01

Background Early detection of an impending flood and the availability of countermeasures to deal with it can significantly reduce its health impacts. In developing countries like India, public primary health care facilities are frontline organizations that deal with disasters particularly in rural settings. For developing robust counter reacting systems evaluating preparedness capacities within existing systems becomes necessary. Objective The objective of the study is to assess the functional capacity of the primary health care system in Jagatsinghpur district of rural Orissa in India to respond to the devastating flood of September 2008. Methods An onsite survey was conducted in all 29 primary and secondary facilities in five rural blocks (administrative units) of Jagatsinghpur district in Orissa state. A pre-tested structured questionnaire was administered face to face in the facilities. The data was entered, processed and analyzed using STATA® 10. Results Data from our primary survey clearly shows that the healthcare facilities are ill prepared to handle the flood despite being faced by them annually. Basic utilities like electricity backup and essential medical supplies are lacking during floods. Lack of human resources along with missing standard operating procedures; pre-identified communication and incident command systems; effective leadership; and weak financial structures are the main hindering factors in mounting an adequate response to the floods. Conclusion The 2008 flood challenged the primary curative and preventive health care services in Jagatsinghpur. Simple steps like developing facility specific preparedness plans which detail out standard operating procedures during floods and identify clear lines of command will go a long way in strengthening the response to future floods. Performance critiques provided by the grass roots workers, like this one, should be used for institutional learning and effective preparedness planning. Additionally each facility should maintain contingency funds for emergency response along with local vendor agreements to ensure stock supplies during floods. The facilities should ensure that baseline public health standards for health care delivery identified by the Government are met in non-flood periods in order to improve the response during floods. Building strong public primary health care systems is a development challenge. The recovery phases of disasters should be seen as an opportunity to expand and improve services and facilities. PMID:22435044

Mitigation of hard x-ray background in backlit pinhole imagers

DOE PAGES

Fein, J. R.; Keiter, P. A.; Holloway, J. P.; ...

2016-09-16

Experiments were performed to mitigate the hard x-ray background commonly observed in backlit pinhole imagers. The material of the scaffold holding the primary backlighter foil was varied to reduce the laser-plasma instabilities responsible for hot electrons and resulting hard x-ray background. Radiographic measurements with image plates showed a factor of >25 decrease in x-rays between 30 and 67 keV when going from a plastic to Al or V scaffold. Here, a potential design using V scaffold offers a signal-to-background ratio of 6:1, a factor of 2 greater than using the bare plastic scaffold.

Use of minocycline as systemic antimicrobial therapy in refractory periodontitis with chronic gingival enlargement.

PubMed

Khatri, Parag M; Kumar, Rajesh

2012-01-01

Periodontal disease is a multifactorial disease having various risk factors, but a dynamic interaction between bacterial products and host response in association with genetic and environmental factors is considered as the primary cause for periodontal tissue destruction in periodontitis. This bacterial-host interaction which is ever-so-present in periodontitis directs us toward utilizing antimicrobial agents along with the routine mechanical debridement. This case report present a case of a female patient with recurrent periodontal infections with gingival enlargement treated with systemic Minocycline in conjunction with the conventional non-surgical approach.

Utilization of Microgravity Bioreactor for Differentiation and Growth of Human Vascular Endothelial Cells

NASA Technical Reports Server (NTRS)

Chen, Chu-Huang; Pellis, Neal R.

1997-01-01

The goal was to delineate mechanisms of genetic responses to angiogenic stimulation of human coronary arterial and dermal microvascular endothelial cells during exposure to microgravity. The NASA-designed rotating-wall vessel was used to create a three-dimensional culture environment with low shear-stress and microgravity simulating that in space. The primary specific aim was to determine whether simulated microgravity enhances endothelial cell growth and whether the growth enhancement is associated by augmented expression of Basic Fibroblast Growth Factor (BFGF) and c-fos, an immediate early gene and component of the transcription factor AP-1.

The generation of NGF-secreting primary rat monocytes: a comparison of different transfer methods.

PubMed

Hohsfield, Lindsay A; Geley, Stephan; Reindl, Markus; Humpel, Christian

2013-05-31

Nerve growth factor (NGF), a member of the neurotrophin family, is responsible for the maintenance and survival of cholinergic neurons in the basal forebrain. The degeneration of cholinergic neurons and reduced acetycholine levels are hallmarks of Alzheimer's disease (AD) as well as associated with learning and memory deficits. Thus far, NGF has proven the most potent neuroprotective molecule against cholinergic neurodegeneration. However, delivery of this factor into the brain remains difficult. Recent studies have begun to elucidate the potential use of monocytes as vehicles for therapeutic delivery into the brain. In this study, we employed different transfection and transduction methods to generate NGF-secreting primary rat monocytes. Specifically, we compared five methods for generating NGF-secreting monocytes: (1) cationic lipid-mediated transfection (Effectene and FuGene), (2) classical electroporation, (3) nucleofection, (4) protein delivery (Bioporter) and (5) lentiviral vectors. Here, we report that classical transfection methods (lipid-mediated transfection, electroporation, nucleofection) are inefficient tools for proper gene transfer into primary rat monocytes. We demonstrate that lentiviral infection and Bioporter can successfully transduce/load primary rat monocytes and produce effective NGF secretion. Furthermore, our results indicate that NGF is bioactive and that Bioporter-loaded monocytes do not appear to exhibit any functional disruptions (i.e. in their ability to differentiate and phagocytose beta-amyloid). Taken together, our results show that primary monocytes can be effectively loaded or transduced with NGF and provides information on the most effective method for generating NGF-secreting primary rat monocytes. This study also provides a basis for further development of primary monocytes as therapeutic delivery vehicles to the diseased AD brain. Copyright © 2013 Elsevier B.V. All rights reserved.

Inflammation responses in patients with pulmonary tuberculosis in an intensive care unit

PubMed Central

Liu, Qiu-Yue; Han, Fen; Pan, Li-Ping; Jia, Hong-Yan; Li, Qi; Zhang, Zong-De

2018-01-01

Pulmonary tuberculosis caused by Mycobacterium tuberculosis remains a global problem. Inflammatory responses are the primary characteristics of patients with pulmonary tuberculosis in intensive care units (ICU). The aim of the present study was to investigate the clinical importance of inflammatory cells and factors for patients with pulmonary tuberculosis in ICU. A total of 124 patients with pulmonary tuberculosis in ICU were recruited for the present study. The inflammatory responses in patients with pulmonary tuberculosis in ICU were examined by changes in inflammatory cells and factors in the serum. The results indicated that serum levels of lymphocytes, plasma cells, granulocytes and monocytes were increased in patients with pulmonary tuberculosis in ICU compared with healthy controls. The serum levels of inflammatory factors interleukin (IL)-1, IL-6, IL-10, IL-12, and IL-4 were upregulated in patients with pulmonary tuberculosis in ICU. Lower plasma concentrations of IL-2, IL-15 and interferon-γ were detected in patients with pulmonary tuberculosis compared with healthy controls. It was demonstrated that high mobility group box-1 protein expression levels were higher in the serum of patients with pulmonary tuberculosis compared with healthy controls. Notably, an imbalance of T-helper cell (Th)1/Th2 cytokines was observed in patients with pulmonary tuberculosis. Pulmonary tuberculosis caused by M. tuberculosis also upregulated expression of matrix metalloproteinase (MMP)-1 and MMP-9 in hPMCs. In conclusion, these outcomes demonstrated that inflammatory responses and inflammatory factors are associated with the progression of pulmonary tuberculosis, suggesting that inhibition of inflammatory responses and inflammatory factors may be beneficial for the treatment of patients with pulmonary tuberculosis in ICU. PMID:29456674

Warming and Elevated CO2 Interact to Drive Rapid Shifts in Marine Community Production.

PubMed

Sorte, Cascade J B; Bracken, Matthew E S

2015-01-01

Predicting the outcome of future climate change requires an understanding of how alterations in multiple environmental factors manifest in natural communities and affect ecosystem functioning. We conducted an in situ, fully factorial field manipulation of CO2 and temperature on a rocky shoreline in southeastern Alaska, USA. Warming strongly impacted functioning of tide pool systems within one month, with the rate of net community production (NCP) more than doubling in warmed pools under ambient CO2 levels relative to initial NCP values. However, in pools with added CO2, NCP was unaffected by warming. Productivity responses paralleled changes in the carbon-to-nitrogen ratio of a red alga, the most abundant primary producer species in the system, highlighting the direct link between physiology and ecosystem functioning. These observed changes in algal physiology and community productivity in response to our manipulations indicate the potential for natural systems to shift rapidly in response to changing climatic conditions and for multiple environmental factors to act antagonistically.

Warming and Elevated CO2 Interact to Drive Rapid Shifts in Marine Community Production

PubMed Central

Sorte, Cascade J. B.; Bracken, Matthew E. S.

2015-01-01

Predicting the outcome of future climate change requires an understanding of how alterations in multiple environmental factors manifest in natural communities and affect ecosystem functioning. We conducted an in situ, fully factorial field manipulation of CO2 and temperature on a rocky shoreline in southeastern Alaska, USA. Warming strongly impacted functioning of tide pool systems within one month, with the rate of net community production (NCP) more than doubling in warmed pools under ambient CO2 levels relative to initial NCP values. However, in pools with added CO2, NCP was unaffected by warming. Productivity responses paralleled changes in the carbon-to-nitrogen ratio of a red alga, the most abundant primary producer species in the system, highlighting the direct link between physiology and ecosystem functioning. These observed changes in algal physiology and community productivity in response to our manipulations indicate the potential for natural systems to shift rapidly in response to changing climatic conditions and for multiple environmental factors to act antagonistically. PMID:26714167

Protein S is inducible by interleukin 4 in T cells and inhibits lymphoid cell procoagulant activity

PubMed Central

Smiley, Stephen T.; Boyer, Sarah N.; Heeb, Mary J.; Griffin, John H.; Grusby, Michael J.

1997-01-01

Extravascular procoagulant activity often accompanies cell-mediated immune responses and systemic administration of pharmacologic anticoagulants prevents cell-mediated delayed-type hypersensitivity reactions. These observations suggest a direct association between coagulation and cell-mediated immunity. The cytokine interleukin (IL)-4 potently suppresses cell-mediated immune responses, but its mechanism of action remains to be determined. Herein we demonstrate that the physiologic anticoagulant protein S is IL-4-inducible in primary T cells. Although protein S was known to inhibit the classic factor Va-dependent prothrombinase assembled by endothelial cells and platelets, we found that protein S also inhibits the factor Va-independent prothrombinase assembled by lymphoid cells. Thus, protein S-mediated down-regulation of lymphoid cell procoagulant activity may be one mechanism by which IL-4 antagonizes cell-mediated immunity. PMID:9326636

Naphthazarin protects against glutamate-induced neuronal death via activation of the Nrf2/ARE pathway

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

Son, Tae Gen; Kawamoto, Elisa M.; Yu, Qian-Sheng

2013-04-19

Highlights: •Naphthazarin activates the Nrf2/ARE pathway. •Naphthazarin induces Nrf2-driven genes in neurons and astrocytes. •Naphthazarin protects neurons against excitotoxicity. -- Abstract: Nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway is an important cellular stress response pathway involved in neuroprotection. We previously screened several natural phytochemicals and identified plumbagin as a novel activator of the Nrf2/ARE pathway that can protect neurons against ischemic injury. Here we extended our studies to natural and synthetic derivatives of plumbagin. We found that 5,8-dimethoxy-1,4-naphthoquinone (naphthazarin) is a potent activator of the Nrf2/ARE pathway, up-regulates the expression of Nrf2-driven genes in primary neuronal andmore » glial cultures, and protects neurons against glutamate-induced excitotoxicity.« less

Airway epithelial cell response to human metapneumovirus infection

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

Bao, X.; Liu, T.; Spetch, L.

2007-11-10

Human metapneumovirus (hMPV) is a major cause of lower respiratory tract infections (LRTIs) in infants, elderly and immunocompromised patients. In this study, we show that hMPV can infect in a similar manner epithelial cells representative of different tracts of the airways. hMPV-induced expression of chemokines IL-8 and RANTES in primary small alveolar epithelial cells (SAE) and in a human alveolar type II-like epithelial cell line (A549) was similar, suggesting that A549 cells can be used as a model to study lower airway epithelial cell responses to hMPV infection. A549 secreted a variety of CXC and CC chemokines, cytokines and typemore » I interferons, following hMPV infection. hMPV was also a strong inducer of transcription factors belonging to nuclear factor (NF)-{kappa}B, interferon regulatory factors (IRFs) and signal transducers and activators of transcription (STATs) families, which are known to orchestrate the expression of inflammatory and immunomodulatory mediators.« less

Factors associated with National Council Licensure Examination-Registered Nurse success.

PubMed

Arathuzik, D; Aber, C

1998-01-01

Identification of factors associated with National Council Licensure Examination-Registered Nurse (NCLEX-RN) success is critical at public colleges of nursing with diverse student populations. This issue was the purpose of this research study. A descriptive correlational research design was used. Seventy-nine generic senior students enrolled in an urban public university participated in the study. Several internal and external blocks to success were described by the students, including family responsibilities, emotional distress, fatigue, and financial and work burdens. Significant correlations were found between success in the NCLEX-RN and cumulative undergraduate nursing program grade point average, English as the primary language spoken at home, lack of family responsibilities or demands, lack of emotional distress, and sense of competency in critical thinking. Establishment of a comprehensive data base-including factors associated with success in the NCLEX-RN and programs of advisement, tutoring, and stress management as well as classes in study skills, test taking, and NCLEX preparation-are recommended for public colleges of nursing with diverse student populations.

Primary Care Parenting Intervention Effects on Use of Physical Punishment Among Low-Income Parents of Toddlers

PubMed Central

Canfield, Caitlin F.; Weisleder, Adriana; Cates, Carolyn Brockmeyer; Huberman, Harris S.; Dreyer, Benard P.; Legano, Lori A.; Johnson, Samantha Berkule; Seery, Anne; Mendelsohn, Alan L.

2015-01-01

Objectives As part of a large randomized controlled trial, we assessed the impact of two early primary care parenting interventions—the Video Interaction Project (VIP) and Building Blocks (BB)—on the use of physical punishment among low-income parents of toddlers. We also determined whether the impact was mediated through increases in responsive parenting and decreases in maternal psychosocial risk. Methods Four hundred thirty-eight mother-child dyads (161 VIP, 113 BB, 164 Control) were assessed when children were 14 and/or 24 months. Mothers were asked about their use of physical punishment as well as their responsive parenting behaviors, depressive symptoms, and parenting stress. Results VIP was associated with lower physical punishment scores at 24 months, as compared with BB and Controls. In addition, fewer VIP parents reported ever using physical punishment as a discipline strategy. Significant indirect effects were found for both responsive parenting and maternal psychosocial risk, indicating that VIP affects these behaviors and risk factors, and this is an important pathway through which VIP affects parents’ use of physical punishment. Conclusion The results support the efficacy of VIP, and the role of pediatric primary care, in reducing the use of physical punishment among low-income families by enhancing parent-child relationships. In this way, the findings support the potential of VIP to improve developmental outcomes for at-risk children. PMID:26375804

Primary Care Parenting Intervention and Its Effects on the Use of Physical Punishment Among Low-Income Parents of Toddlers.

PubMed

Canfield, Caitlin F; Weisleder, Adriana; Cates, Carolyn B; Huberman, Harris S; Dreyer, Benard P; Legano, Lori A; Johnson, Samantha Berkule; Seery, Anne; Mendelsohn, Alan L

2015-10-01

As part of a large randomized controlled trial, the authors assessed the impact of 2 early primary care parenting interventions-the Video Interaction Project (VIP) and Building Blocks (BB)-on the use of physical punishment among low-income parents of toddlers. They also determined whether the impact was mediated through increases in responsive parenting and decreases in maternal psychosocial risk. Four hundred thirty-eight mother-child dyads (161 VIP, 113 BB, 164 Control) were assessed when the children were 14 and/or 24 months old. Mothers were asked about their use of physical punishment and their responsive parenting behaviors, depressive symptoms, and parenting stress. The VIP was associated with lower physical punishment scores at 24 months, as compared to BB and controls. In addition, fewer VIP parents reported ever using physical punishment as a disciplinary strategy. Significant indirect effects were found for both responsive parenting and maternal psychosocial risk, indicating that the VIP affects these behaviors and risk factors, and that this is an important pathway through which the VIP affects the parents' use of physical punishment. The results support the efficacy of the VIP and the role of pediatric primary care, in reducing the use of physical punishment among low-income families by enhancing parent-child relationships. In this way, the findings support the potential of the VIP to improve developmental outcomes for at-risk children.

Krüppel–Like Factor 15 Mediates Glucocorticoid-Induced Restoration of Podocyte Differentiation Markers

PubMed Central

Guo, Yiqing; Revelo, Monica P.; Roa-Peña, Lucia; Miller, Timothy; Ling, Jason; Shankland, Stuart J.; Bialkowska, Agnieszka B.; Ly, Victoria; Estrada, Chelsea; Jain, Mukesh K.; Lu, Yuan; Ma’ayan, Avi; Mehrotra, Anita; Yacoub, Rabi; Nord, Edward P.; Woroniecki, Robert P.; Yang, Vincent W.; He, John C.

2017-01-01

Podocyte injury is the inciting event in primary glomerulopathies, such as minimal change disease and primary FSGS, and glucocorticoids remain the initial and often, the primary treatment of choice for these glomerulopathies. Because inflammation is not readily apparent in these diseases, understanding the direct effects of glucocorticoids on the podocyte, independent of the immunomodulatory effects, may lead to the identification of targets downstream of glucocorticoids that minimize toxicity without compromising efficacy. Several studies showed that treatment with glucocorticoids restores podocyte differentiation markers and normal ultrastructure and improves cell survival in murine podocytes. We previously determined that Krüppel–like factor 15 (KLF15), a kidney–enriched zinc finger transcription factor, is required for restoring podocyte differentiation markers in mice and human podocytes under cell stress. Here, we show that in vitro treatment with dexamethasone induced a rapid increase of KLF15 expression in human and murine podocytes and enhanced the affinity of glucocorticoid receptor binding to the promoter region of KLF15. In three independent proteinuric murine models, podocyte-specific loss of Klf15 abrogated dexamethasone–induced podocyte recovery. Furthermore, knockdown of KLF15 reduced cell survival and destabilized the actin cytoskeleton in differentiated human podocytes. Conversely, overexpression of KLF15 stabilized the actin cytoskeleton under cell stress in human podocytes. Finally, the level of KLF15 expression in the podocytes and glomeruli from human biopsy specimens correlated with glucocorticoid responsiveness in 35 patients with minimal change disease or primary FSGS. Thus, these studies identify the critical role of KLF15 in mediating the salutary effects of glucocorticoids in the podocyte. PMID:27288011

Primary Vaginal Melanoma, A Rare and Aggressive Entity. A Case Report and Review of the Literature.

PubMed

Kalampokas, Emmanouil; Kalampokas, Theodoros; Damaskos, Christos

2017-01-02

Malignant melanoma of the vagina is a rare, aggressive malignancy of poor prognosis. It principally affects post-menopausal women, with a mean age of 57 years, and the factors that contribute to its appearance are not well known. The first case of primary malignant vaginal melanoma was reported in 1887 and modern literature has noted about 500 cases, globally. Vaginal melanomas constitute 0.3% of all malignant melanomas and fewer than 3% of all vaginal carcinomas. To date there is no clear consensus regarding treatment. An early, accurate diagnosis and prompt investigation is essential in reaching appropriate treatment decisions. We present a clinical case of primary vaginal melanoma and review the literature briefly, presenting the current treatment plans and updates of this rare gynecological malignancy. Considerations, epidemiology, associated risk factors, response to therapy and expected outcome are also discussed. Primary malignant vaginal melanoma is a rare but aggressive melanoma that affects women in their 6th and 7th decade of life. The tumor appears as a dark node or spindle but can also be amelanotic. The size of the tumor is indicative of the prognostic factors. Surgery seems to be the only efficient treatment. Postoperative adjuvant therapy might help in preventing recurrence of the tumor. The survival rate is largely dependent on nodal and distant metastasis of the disease after initial tumor resection. There is a dire need to form a proper therapeutic regime to control this disease. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Prevalence of depression among women attending a primary urban care clinic in Malaysia.

PubMed

Sidik, Sherina Mohd; Arroll, Bruce; Goodyear-Smith, Felicity; Ahmad, Rozali

2012-07-01

Depression affects more women than men in Malaysia. The objective of this paper was to determine the prevalence of depression and its associated factors among women attending a government primary care clinic. A cross-sectional study was conducted in a government-funded primary care clinic in Malaysia. Consecutive adult female patients attending the clinic during the data collection period were invited to participate. The participants completed self-administered questionnaires (including the validated Patient Health Questionnaire [PHQ-9], which was translated into the Malay language). A total of 895 female patients participated in the study (response rate 87.5%). The prevalence of depression (PHQ-9 scores ≥ 10) was 12.1%. Based on multiple logistic regression analysis, certain stressful life events were found to be associated with depression (p < 0.05). These factors, arranged from highest to lowest risk, were financial problems (odds ratio [OR] 3.7, 95% confidence interval [CI] 2.2-6.2), unhappiness in the parent-child relationship (OR 3.0, 95% CI 1.2-7.5), history of serious illness (OR 2.4, 95% CI 1.1-5.2), unhappiness in family relationships (OR 2.3, 95% CI 1.1-4.7) and unhappiness at work (OR 2.2, 95% CI 1.1-4.3) (p < 0.05). The prevalence of depression among participants in this study was clinically significant and corresponded with the findings of other international studies. Factors associated with depression need to be highlighted and addressed accordingly. Clinicians in Malaysia should be aware of this prevalence when making diagnoses in primary care.

Frequency and predictive factors for overlap syndrome between autoimmune hepatitis and primary cholestatic liver disease.

PubMed

Gheorghe, Liana; Iacob, Speranta; Gheorghe, Cristian; Iacob, Razvan; Simionov, Iulia; Vadan, Roxana; Becheanu, Gabriel; Parvulescu, Iuliana; Toader, Cristina

2004-06-01

To evaluate the frequency of cholestatic pattern in patients with autoimmune hepatitis (AIH) and to identify predictive factors associated with the development of the overlap syndrome. Eighty-two consecutive patients diagnosed with AIH at the referral centre between January 1998 and June 2002 were included in the study. The new scoring system modified by the International Autoimmune Hepatitis Group was used to classify patients as definite/probable. Overlap syndrome was considered when the patient had clinical, serological and histological characteristics of two conditions: AIH and primary biliary cirrhosis (PBC) or AIH and primary sclerosing cholangitis (PSC). From the 82 AIH patients (76 female and six male), 84.1% presented definite AIH (> 15 points) and 15.9% probable AIH (10 - 15 points). The frequency of the overlap syndrome was 20%: 13% with PBC and 7% with PSC. In the univariate analysis the overlap syndrome was associated with male gender (P = 0.01), age < 35 years (P < 0.0001), histopathological aspect of cholestasis (P < 0.0001), suboptimal response to treatment (P < 0.0001) and probable AIH (P < 0.0001). Age < 35 years, probable AIH and the absence of anti-nuclear antibody (ANA) have been identified as independent indicators of the overlap diagnosis by the logistic regression analysis. Patients with overlap syndrome between AIH and primary cholestatic liver disease are frequently diagnosed in clinical practice, representing 20% of AIH cases in our study. The independent predictive factors associated with the diagnosis of overlap syndrome are young age, ANA(-) profile, and probable diagnosis according with the scoring system for AIH.

Diabetes knowledge of nurses providing community care for diabetes patients in Auckland, New Zealand.

PubMed

Daly, Barbara; Arroll, Bruce; Sheridan, Nicolette; Kenealy, Timothy; Scragg, Robert

2014-10-01

To quantify and compare knowledge of diabetes including risk factors for diabetes-related complications among the three main groups of primary health care nurses. In a cross-sectional survey of practice, district and specialist nurses (n=1091) in Auckland, New Zealand, 31% were randomly sampled to complete a self-administered questionnaire and telephone interview, designed to ascertain nurses' knowledge of diabetes and best practice, in 2006-2008. All 287 nurses (response rate 86%) completed the telephone interview and 284 the self-administered questionnaire. Major risk factors identified by nurses were excess body weight for type 2 diabetes (96%) and elevated plasma glucose levels or glycosylated haemoglobin (86%) for diabetes-related complications. In contrast, major cardiovascular risk factors were less well identified, particularly smoking, although by more specialist nurses (43%) than practice (14%) and district (12%) nurses (p=0.0005). Cardiovascular complications, particularly stroke, were less well known than microvascular complications, and by significantly fewer practice (13%) and district (8%) nurses than specialist nurses (36%, p=0.002). In general, nurses had better knowledge of overweight as a risk factor for type 2 diabetes mellitus and elevated plasma glucose levels as a risk factor for diabetes-related complications compared with knowledge of cardiovascular risk factors, particularly smoking. Copyright © 2014 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

BALKANS SECURITY. Current and Projected Factors Affecting Regional Stability

DTIC Science & Technology

2000-04-01

Security Briefing Section II Current Situation in Kosovo and Bosnia primary responsibility for public security in Kosovo. 6 According to a senior KFOR...Integrity * Reliability GAO/NSIAD-00-125BR „.c-miBUTION STATEMENT A ApSwed for Public Release Contents Letter Briefing Section Appendixes Tables...Figures Briefing Section I: Background Briefing Section II: Current Situation in Kosovo and Bosnia Briefing Section III: Projected Security Situation

The likely impact of elevated [CO2], nitrogen deposition, increased temperature and management on carbon sequestration in temperate and boreal forest ecosystems: a literature review

Treesearch

Riitta Hyvönen; Göran I. Ågren; Sune Linder; Tryggve Persson; M. Francesca Cotrufo; Alf Ekblad; Michael Freeman; Achim Grelle; Ivan A. Janssens; Paul G. Jarvis; Seppo Kellomäki; Anders Lindroth; Denis Loustau; Tomas Lundmark; Richard J. Norby; Ram Oren; Kim Pilegaard; Michael G. Ryan; Bjarni D. Sigurdsson; Monika Strömgren; Marcel van Oijen; Göran Wallin

2007-01-01

Temperate and boreal forest ecosystems contain a large part of the carbon stored on land, in the form of both biomass and soil organic matter. Increasing atmospheric [CO2], increasing temperature, elevated nitrogen deposition and intensified management will change this C store. Well documented single-factor responses of net primary production are: higher photosynthetic...

Repeated burning alters the structure and composition of hardwood regeneration in oak-dominated forests of eastern Kentucky, USA

Treesearch

Tara L. Keyser; Mary Arthur; David L. Loftis

2017-01-01

The exclusion of anthropogenic fire is a primary factor responsible for the ‘mesophication’ of eastern oak (Quercus) forests and resultant oak regeneration problems. Consequently, the reintroduction of fire is increasingly used to promote the establishment and growth of oak and hickory (Carya) and control competition from shade-tolerant species (e.g., red maple (Acer...

Understanding psychological stress, its biological processes, and impact on primary headache.

PubMed

Nash, Justin M; Thebarge, Ronald W

2006-10-01

Psychological stress is generally acknowledged to be a central contributor to primary headache. Stress results from any challenge or threat, either real or perceived, to normal functioning. The stress response is the body's activation of physiological systems, namely the hypothalamic-pituitary-adrenal axis, to protect and restore functioning. Chronic activation of the stress response can lead to wear and tear that eventually can predispose an individual to disease. There are multiple ways that stress and headache are closely related. Stress can (a) be a predisposing factor that contributes to headache disorder onset, (b) accelerate the progression of the headache disorder into a chronic condition, and (c) precipitate and exacerbate individual headache episodes. How stress impacts headache is not often understood. However, stress is assumed to affect primary headache by directly impacting pain production and modulation processes at both the peripheral and central levels. Stress can also independently worsen headache-related disability and quality of life. Finally, the headache experience itself can serve as a stressor that compromises an individual's health and well-being. With the prominent role that stress plays in headache, there are implications for the evaluation of stress and the use of stress reduction strategies at the various stages of headache disorder onset and progression. Future directions can help to develop a better empirical understanding of the pattern of the stress and headache connections and the mechanisms that explain the connections. Further research can also examine the interactive effects of stress and other factors that impact headache disorder onset, course, and adjustment.

The presence of resuscitation equipment and influencing factors at General Practitioners' offices in Denmark: a cross-sectional study.

PubMed

Niegsch, Mark L; Krarup, Nikolaj T; Clausen, Niels Erikstrup

2014-01-01

Automated external defibrillators (AEDs) have proven effective when used by GPs. Despite this and the latest guidelines from the European Resuscitation Council, there are no recommendations for Danish GPs regarding proper equipment to treat cardiac arrest. Currently, there are no published data on the distribution of AEDs among GPs in Denmark. To assess the prevalence of resuscitation equipment and educated staff among Danish GPs and the parameters influencing the absence of AEDs at GP offices. A cross-sectional questionnaire-based survey among the 2030 GPs registered in Denmark. Questions concerned demographics, occurrence of resuscitation equipment and attitude towards acquisition of an AED. With a response rate >70%, we found that the prevalence of AEDs in GP offices is low (31.7%). Limited financial possibilities and relevant treatment by ambulance personnel were stated as the primary causes for not having an AED. In general, Danish primary care physicians believe that AEDs should be governmentally sponsored. Positive influential factors on the acquisition of an AED were education, number of physicians in the GP office and previous experience of cardiac arrest. Danish primary care physicians are generally not equipped with AEDs despite the proven effect of AEDs in GP offices. The main reasons for not acquiring an AED are financial considerations and believing that response time by ambulance services and nearby health facilities are the optimal treatment. We recommend better education and information in order to facilitate future acquisition of AEDs among GPs. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The Transition of Primary Care Group Practices to Next Generation Models: Satisfaction of Staff, Clinicians, and Patients.

PubMed

Zink, Therese; Kralewski, John; Dowd, Bryan

Restructuring primary care is essential to achieve the triple aim. This case study examines the human factors of extensive redesign on 2 midsized primary care clinics (clinics A and B) in the Midwest United States that are owned by a large health care system. The transition occurred when while the principles for patient-centered medical home were being rolled out nationally, and before the Affordable Care Act. After the transition, interviews and discussions were conducted with 5 stakeholder groups: health system leaders, clinic managers, clinicians, nurses, and reception staff. Using a culture assessment instrument, the responses of personnel at clinics A and B were compared with comparison clinics from another health system that had not undergone transition. Patient satisfaction scores are presented. Clinics A and B were similar in size and staffing. Three human factor themes emerged from interviews: responses to change, professional and personal challenges due to role redefinition, and the importance of communication. The comparison clinics had an equal or higher mean culture scores compared with the transition clinics (A and B). Patient satisfaction in improved in Clinic A. The transition took more time than expected. Health system leaders underestimated the stress and the role adjustments for clinicians and nurses. Change leaders need to anticipate the challenge of role redefinition until health profession schools graduate trainees with more experience in new models of team-based care. Incorporating experience with team based, interprofessional care into training is essential to properly prepare future health professionals. © Copyright 2017 by the American Board of Family Medicine.

Recovery, work-life balance and work experiences important to self-rated health: A questionnaire study on salutogenic work factors among Swedish primary health care employees

PubMed Central

Ejlertsson, Lina; Heijbel, Bodil; Ejlertsson, Göran; Andersson, Ingemar

2018-01-01

BACKGROUND: There is a lack of information on positive work factors among health care workers. OBJECTIVE: To explore salutogenic work-related factors among primary health care employees. METHOD: Questionnaire to all employees (n = 599) from different professions in public and private primary health care centers in one health care district in Sweden. The questionnaire, which had a salutogenic perspective, included information on self-rated health from the previously validated SHIS (Salutogenic Health Indicator Scale), psychosocial work environment and experiences, recovery, leadership, social climate, reflection and work-life balance. RESULTS: The response rate was 84%. A multivariable linear regression model, with SHIS as the dependent variable, showed three significant predictors. Recovery had the highest relationship to SHIS (β= 0.34), followed by experience of work-life balance (β= 0.25) and work experiences (β= 0.20). Increased experience of recovery during working hours related to higher self-rated health independent of recovery outside work. CONCLUSION: Individual experiences of work, work-life balance and, most importantly, recovery seem to be essential areas for health promotion. Recovery outside the workplace has been studied previously, but since recovery during work was shown to be of great importance in relation to higher self-rated health, more research is needed to explore different recovery strategies in the workplace. PMID:29439377

Pirfenidone exerts antifibrotic effects through inhibition of GLI transcription factors.

PubMed

Didiasova, Miroslava; Singh, Rajeev; Wilhelm, Jochen; Kwapiszewska, Grazyna; Wujak, Lukasz; Zakrzewicz, Dariusz; Schaefer, Liliana; Markart, Philipp; Seeger, Werner; Lauth, Matthias; Wygrecka, Malgorzata

2017-05-01

Pirfenidone is an antifibrotic drug, recently approved for the treatment of patients with idiopathic pulmonary fibrosis (IPF). Although pirfenidone exhibits anti-inflammatory, antioxidant, and antifibrotic properties, the molecular mechanism underlying its protective effects remains unknown. Here, we link pirfenidone action with the regulation of the profibrotic hedgehog (Hh) signaling pathway. We demonstrate that pirfenidone selectively destabilizes the glioma-associated oncogene homolog (GLI)2 protein, the primary activator of Hh-mediated gene transcription. Consequently, pirfenidone decreases overall Hh pathway activity in patients with IPF and in patient-derived primary lung fibroblasts and leads to diminished levels of Hh target genes, such as GLI1, Hh receptor Patched-1, α-smooth muscle actin, and fibronectin, and to reduced cell migration and proliferation. Interestingly, Hh-triggered TGF-β1 expression potentiated Hh responsiveness of primary lung fibroblasts by elevating the available pool of glioma-associated oncogene homolog (GLI)1/GLI2, thus creating a vicious cycle of amplifying fibrotic processes. Because GLI transcription factors are not only crucial for Hh-mediated changes but are also required as mediators of TGF-β signaling, our findings suggest that pirfenidone exerts its clinically beneficial effects through dual Hh/TGF-β inhibition by targeting the GLI2 protein.-Didiasova, M., Singh, R., Wilhelm, J., Kwapiszewska, G., Wujak, L., Zakrzewicz, D., Schaefer, L., Markart, P., Seeger, W., Lauth, M., Wygrecka, M. Pirfenidone exerts antifibrotic effects through inhibition of GLI transcription factors. © FASEB.

Inhibition of GSK3 differentially modulates NF-{kappa}B, CREB, AP-1 and {beta}-catenin signaling in hepatocytes, but fails to promote TNF-{alpha}-induced apoptosis

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

Goetschel, Frank; Kern, Claudia; Lang, Simona

2008-04-01

Glycogen synthase kinase-3 (GSK-3) is known to modulate cell survival and apoptosis through multiple intracellular signaling pathways. However, its hepatoprotective function and its role in activation of NF-{kappa}B and anti-apoptotic factors are poorly understood and remain controversial. Here we investigated whether inhibition of GSK-3 could induce apoptosis in the presence of TNF-{alpha} in primary mouse hepatocytes. We show that pharmacological inhibition of GSK-3 in primary mouse hepatocytes does not lead to TNF-{alpha}-induced apoptosis despite reduced NF-{kappa}B activity. Enhanced stability of I{kappa}B-{alpha} appears to be responsible for lower levels of nuclear NF-{kappa}B and hence reduced transactivation. Additionally, inhibition of GSK-3 wasmore » accompanied by marked upregulation of {beta}-catenin, AP-1, and CREB transcription factors. Stimulation of canonical Wnt signaling and CREB activity led to elevated levels of anti-apoptotic factors. Hence, survival of primary mouse hepatocytes may be caused by the activation and/or upregulation of other key regulators of liver homeostasis and regeneration. These signaling molecules may compensate for the compromised anti-apoptotic function of NF-{kappa}B and allow survival of hepatocytes in the presence of TNF-{alpha} and GSK-3 inhibition.« less

Recovery, work-life balance and work experiences important to self-rated health: A questionnaire study on salutogenic work factors among Swedish primary health care employees.

PubMed

Ejlertsson, Lina; Heijbel, Bodil; Ejlertsson, Göran; Andersson, Ingemar

2018-01-01

There is a lack of information on positive work factors among health care workers. To explore salutogenic work-related factors among primary health care employees. Questionnaire to all employees (n = 599) from different professions in public and private primary health care centers in one health care district in Sweden. The questionnaire, which had a salutogenic perspective, included information on self-rated health from the previously validated SHIS (Salutogenic Health Indicator Scale), psychosocial work environment and experiences, recovery, leadership, social climate, reflection and work-life balance. The response rate was 84%. A multivariable linear regression model, with SHIS as the dependent variable, showed three significant predictors. Recovery had the highest relationship to SHIS (β= 0.34), followed by experience of work-life balance (β= 0.25) and work experiences (β= 0.20). Increased experience of recovery during working hours related to higher self-rated health independent of recovery outside work. Individual experiences of work, work-life balance and, most importantly, recovery seem to be essential areas for health promotion. Recovery outside the workplace has been studied previously, but since recovery during work was shown to be of great importance in relation to higher self-rated health, more research is needed to explore different recovery strategies in the workplace.

Targeting the Myofibroblast Genetic Switch: Inhibitors of Myocardin-Related Transcription Factor/Serum Response Factor–Regulated Gene Transcription Prevent Fibrosis in a Murine Model of Skin Injury

PubMed Central

Haak, Andrew J.; Tsou, Pei-Suen; Amin, Mohammad A.; Ruth, Jeffrey H.; Campbell, Phillip; Fox, David A.; Khanna, Dinesh; Larsen, Scott D.

2014-01-01

Systemic sclerosis (SSc), or scleroderma, similar to many fibrotic disorders, lacks effective therapies. Current trials focus on anti-inflammatory drugs or targeted approaches aimed at one of the many receptor mechanisms initiating fibrosis. In light of evidence that a myocardin-related transcription factor (MRTF)–and serum response factor (SRF)–regulated gene transcriptional program induced by Rho GTPases is essential for myofibroblast activation, we explored the hypothesis that inhibitors of this pathway may represent novel antifibrotics. MRTF/SRF-regulated genes show spontaneously increased expression in primary dermal fibroblasts from patients with diffuse cutaneous SSc. A novel small-molecule inhibitor of MRTF/SRF-regulated transcription (CCG-203971) inhibits expression of connective tissue growth factor (CTGF), α-smooth muscle actin (α-SMA), and collagen 1 (COL1A2) in both SSc fibroblasts and in lysophosphatidic acid (LPA)–and transforming growth factor β (TGFβ)–stimulated fibroblasts. In vivo treatment with CCG-203971 also prevented bleomycin-induced skin thickening and collagen deposition. Thus, targeting the MRTF/SRF gene transcription pathway could provide an efficacious new approach to therapy for SSc and other fibrotic disorders. PMID:24706986

Differential epigenetic and transcriptional response of the skeletal muscle carnitine palmitoyltransferase 1B (CPT1B) gene to lipid exposure with obesity

PubMed Central

Maples, Jill M.; Brault, Jeffrey J.; Witczak, Carol A.; Park, Sanghee; Hubal, Monica J.; Weber, Todd M.; Houmard, Joseph A.

2015-01-01

The ability to increase fatty acid oxidation (FAO) in response to dietary lipid is impaired in the skeletal muscle of obese individuals, which is associated with a failure to coordinately upregulate genes involved with FAO. While the molecular mechanisms contributing to this metabolic inflexibility are not evident, a possible candidate is carnitine palmitoyltransferase-1B (CPT1B), which is a rate-limiting step in FAO. The present study was undertaken to determine if the differential response of skeletal muscle CPT1B gene transcription to lipid between lean and severely obese subjects is linked to epigenetic modifications (DNA methylation and histone acetylation) that impact transcriptional activation. In primary human skeletal muscle cultures the expression of CPT1B was blunted in severely obese women compared with their lean counterparts in response to lipid, which was accompanied by changes in CpG methylation, H3/H4 histone acetylation, and peroxisome proliferator-activated receptor-δ and hepatocyte nuclear factor 4α transcription factor occupancy at the CPT1B promoter. Methylation of specific CpG sites in the CPT1B promoter that correlated with CPT1B transcript level blocked the binding of the transcription factor upstream stimulatory factor, suggesting a potential causal mechanism. These findings indicate that epigenetic modifications may play important roles in the regulation of CPT1B in response to a physiologically relevant lipid mixture in human skeletal muscle, a major site of fatty acid catabolism, and that differential DNA methylation may underlie the depressed expression of CPT1B in response to lipid, contributing to the metabolic inflexibility associated with severe obesity. PMID:26058865

BMI1 Is Expressed in Canine Osteosarcoma and Contributes to Cell Growth and Chemotherapy Resistance

PubMed Central

Gandour-Edwards, Regina; Withers, Sita S.; Holt, Roseline; Rebhun, Robert B.

2015-01-01

BMI1, a stem cell factor and member of the polycomb group of genes, has been shown to contribute to growth and chemoresistance of several human malignancies including primary osteosarcoma (OSA). Naturally occurring OSA in the dog represents a large animal model of human OSA, however the potential role of BMI1 in canine primary and metastatic OSA has not been examined. Immunohistochemical staining of canine primary and metastatic OSA tumors revealed strong nuclear expression of BMI1. An identical staining pattern was found in both primary and metastatic human OSA tissues. Canine OSA cell lines (Abrams, Moresco, and D17) expressed high levels of BMI1 compared with canine osteoblasts and knockdown or inhibition of BMI1 by siRNA or by small molecule BMI1-inhibitor PTC-209 demonstrated a role for BMI1 in canine OSA cell growth and resistance to carboplatin and doxorubicin chemotherapy. These findings suggest that inhibition of BMI1 in primary or metastatic OSA may improve response to chemotherapy and that the dog may serve as a large animal model to evaluate such therapy. PMID:26110620

Primary teachers' subject matter knowledge: decimals

NASA Astrophysics Data System (ADS)

Ubuz, Behiye; Yayan, Betül

2010-09-01

The main objective of this study was to investigate primary teachers' subject matter knowledge in the domain of decimals and more elaborately to investigate their performance and difficulties in reading scale, ordering numbers, finding the nearest decimal and doing operations, such as addition and subtraction. The difficulties in these particular areas are analysed and suggestions are made regarding their causes. Further, factors that influence this knowledge were explored. The sample of the study was 63 primary teachers. A decimal concepts test including 18 tasks was administered and the total scores for the 63 primary teachers ranged from 3 to 18 with a mean and median of 12. Fifty per cent of the teachers were above the mean score. The detailed investigation of the responses revealed that the primary teachers faced similar difficulties that students and pre-service teachers faced. Discrepancy on teachers' knowledge revealed important differences based on educational level attained, but not the number of years of teaching experience and experience in teaching decimals. Some suggestions have been made regarding the implications for pre- and in-service teacher training.

BMI1 is expressed in canine osteosarcoma and contributes to cell growth and chemotherapy resistance.

PubMed

Shahi, Mehdi Hayat; York, Daniel; Gandour-Edwards, Regina; Withers, Sita S; Holt, Roseline; Rebhun, Robert B

2015-01-01

BMI1, a stem cell factor and member of the polycomb group of genes, has been shown to contribute to growth and chemoresistance of several human malignancies including primary osteosarcoma (OSA). Naturally occurring OSA in the dog represents a large animal model of human OSA, however the potential role of BMI1 in canine primary and metastatic OSA has not been examined. Immunohistochemical staining of canine primary and metastatic OSA tumors revealed strong nuclear expression of BMI1. An identical staining pattern was found in both primary and metastatic human OSA tissues. Canine OSA cell lines (Abrams, Moresco, and D17) expressed high levels of BMI1 compared with canine osteoblasts and knockdown or inhibition of BMI1 by siRNA or by small molecule BMI1-inhibitor PTC-209 demonstrated a role for BMI1 in canine OSA cell growth and resistance to carboplatin and doxorubicin chemotherapy. These findings suggest that inhibition of BMI1 in primary or metastatic OSA may improve response to chemotherapy and that the dog may serve as a large animal model to evaluate such therapy.

Evaluation of cerebral maturation by visual and quantitative analysis of resting electroencephalography in children with primary nocturnal enuresis.

PubMed

Hallioğlu, O; Ozge, A; Comelekoglu, U; Topaloglu, A K; Kanik, A; Duzovali, O; Yilgor, E

2001-10-01

This study was undertaken to evaluate resting electroencephalographic (EEG) changes and their relations to cerebral maturation in children with primary nocturnal enuresis. Cerebral maturation is known to be important in the pathogenesis of this disorder. Twenty-five right-handed patients with primary nocturnal enuresis, aged 6 to 14 years, and 23 age- and sex-matched healthy children were included in this cross-sectional case-control study. The abnormalities detected using such techniques as hemispheral asymmetry, regional differences, and hyperventilation response in addition to visual and quantitative EEG analysis were examined statistically by multivariate analysis. A decrease in alpha activity in the left (dominant hemisphere) temporal lobe and in the frontal lobes bilaterally and an increase in delta activity in the right temporal region were observed. We concluded that insufficient cerebral maturation is an important factor in the pathogenesis of primary nocturnal enuresis, and EEG, as a noninvasive and inexpensive method, could be used in evaluating cerebral maturation.

The Adoption of Roles by Primary Care Providers during Implementation of the New Chronic Disease Guidelines in Urban Mongolia: A Qualitative Study.

PubMed

Chimeddamba, Oyun; Ayton, Darshini; Bazarragchaa, Nansalmaa; Dorjsuren, Bayarsaikhan; Peeters, Anna; Joyce, Catherine

2016-04-07

(1) BACKGROUND: In 2011, new chronic disease guidelines were introduced across Mongolia. No formal advice was provided regarding role delineation. This study aimed to analyse the roles that different primary care providers adopted, and the variations in these, in the implementation of the guidelines in urban Mongolia; (2) METHODS: Ten group interviews with nurses and ten individual interviews each with practice doctors and practice directors were conducted. Data was analysed using a thematic approach based on the identified themes relevant to role delineation; (3) RESULTS: There was some variability and flexibility in role delineation. Factors involving teamwork, task rotation and practice flexibility facilitated well the guideline implementation. However, factors including expectations and decision making, nursing shortage, and training gaps adversely influenced in the roles and responsibilities. Some role confusion and dissatisfaction was identified, often associated with a lack of training or staff turnover; (4) CONCLUSIONS: Findings suggest that adequate ongoing training is required to maximize the range of roles particular provider types, especially primary care nurses, are competent to perform. Ensuring that role delineation is specified in guidelines could remove confusion and enhance implementation of such guidelines.

Immunoglobulin M antibody response to measles virus following primary and secondary vaccination and natural virus infection.

PubMed

Erdman, D D; Heath, J L; Watson, J C; Markowitz, L E; Bellini, W J

1993-09-01

The use of IgM antibody detection for the classification of the primary and secondary measles antibody response in persons following primary and secondary vaccination and natural measles virus infection was examined. Of 32 nonimmune children receiving primary measles vaccination, 31 (97%) developed IgM antibodies, consistent with a primary antibody response. Of 21 previously vaccinated children with low levels of preexisting IgG antibodies who responded to revaccination, none developed detectable IgM antibodies, whereas 33 of 35 (94%) with no detectable preexisting IgG antibodies developed an IgM response. Of a sample of 57 measles cases with a prior history of vaccination, 55 (96%) had detectable IgM antibodies. Of these, 30 (55%) were classified as having a primary antibody response and 25 (45%) a secondary antibody response based on differences in their ratios of IgM to IgG antibodies. Differences in the severity of clinical symptoms between these 2 groups were consistent with this classification scheme. These findings suggest that 1) an IgM response follows primary measles vaccination in the immunologically naive, 2) an IgM response is absent on revaccination of those previously immunized, and 3) an IgM response may follow clinical measles virus infection independent of prior immunization status.

Breast cancer and gene testing: risk, rationale, and responsibilities of primary care providers.

PubMed

Wilcox-Honnold, P M

1998-01-01

Family history is one of the known risk factors for breast cancer. Breast cancer susceptibility genes, BRCA-1 and BRCA-2, have been identified as accountable for less than 10% of all cases of breast cancer. Certain populations however, including native Icelanders and Ashkenazi Jews have a higher incidence of BRCA mutations than the general population. Genetic testing for these mutations is now available. Many ethical issues remain regarding who should be tested and what interventions should be carried out with positive test results. This article describes the patient assessment and counseling process for breast cancer testing to improve the knowledge base and confidence of the primary care provider.

JC virus induces altered patterns of cellular gene expression: Interferon-inducible genes as major transcriptional targets

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

Verma, Saguna; Ziegler, Katja; Ananthula, Praveen

2006-02-20

Human polyomavirus JC (JCV) infects 80% of the population worldwide. Primary infection, typically occurring during childhood, is asymptomatic in immunocompetent individuals and results in lifelong latency and persistent infection. However, among the severely immunocompromised, JCV may cause a fatal demyelinating disease, progressive multifocal leukoencephalopathy (PML). Virus-host interactions influencing persistence and pathogenicity are not well understood, although significant regulation of JCV activity is thought to occur at the level of transcription. Regulation of the JCV early and late promoters during the lytic cycle is a complex event that requires participation of both viral and cellular factors. We have used cDNA microarraymore » technology to analyze global alterations in gene expression in JCV-permissive primary human fetal glial cells (PHFG). Expression of more than 400 cellular genes was altered, including many that influence cell proliferation, cell communication and interferon (IFN)-mediated host defense responses. Genes in the latter category included signal transducer and activator of transcription 1 (STAT1), interferon stimulating gene 56 (ISG56), myxovirus resistance 1 (MxA), 2'5'-oligoadenylate synthetase (OAS), and cig5. The expression of these genes was further confirmed in JCV-infected PHFG cells and the human glioblastoma cell line U87MG to ensure the specificity of JCV in inducing this strong antiviral response. Results obtained by real-time RT-PCR and Western blot analyses supported the microarray data and provide temporal information related to virus-induced changes in the IFN response pathway. Our data indicate that the induction of an antiviral response may be one of the cellular factors regulating/controlling JCV replication in immunocompetent hosts and therefore constraining the development of PML.« less

Development and Preliminary Validation of Chinese Preschoolers’ Eating Behavior Questionnaire

PubMed Central

Zhang, Yuhai; Wang, Baoxi; Sun, Lijun; Shang, Lei

2014-01-01

Background The objective of this study was to develop a questionnaire for caregivers to assess the eating behavior of Chinese preschoolers. Methods To assess children’s eating behaviors, 152 items were derived from a broad review of the literature related to epidemiology surveys and the assessment of children’s eating behaviors. All of these items were reviewed by 50 caregivers of preschoolers and 10 experienced pediatricians. Seventy-seven items were selected for use in a primary questionnaire. After conducting an exploratory factor analysis and a variability analysis on the data from 313 preschoolers used to evaluate this primary questionnaire, we deleted 39 of these 77 items. A Chinese Preschoolers’ Eating Behavior Questionnaire (CPEBQ) was finally established from the remaining 38 items. The structure of this questionnaire was explored by factor analysis, and its reliability, validity and discriminative ability were evaluated with data collected from caregivers of 603 preschoolers. Results The CPEBQ consisted of 7 dimensions and 38 items. The 7 dimensions were food fussiness, food responsiveness, eating habit, satiety responsiveness, exogenous eating, emotional eating and initiative eating. The Cronbach’s α coefficient for the questionnaire was 0.92, and the test-retest reliability was 0.72. There were significant differences between the scores of normal-weight, overweight and obese preschoolers when it was referred to food fussiness, food responsiveness, eating habits, satiety responsiveness and emotional eating (p<0.05). Differences in caregiver’s education levels also had significant effects on scores for food fussiness, eating habits and exogenous eating (p<0.05). Conclusions The CPEBQ satisfies the conditions of reliability and validity, in accordance with psychometric demands. The questionnaire can be employed to evaluate the characteristics of Chinese preschoolers’ eating behaviors; therefore, it can be used in child health care practice and research. PMID:24520359

FOXO3 Modulates Endothelial Gene Expression and Function by Classical and Alternative Mechanisms*

PubMed Central

Czymai, Tobias; Viemann, Dorothee; Sticht, Carsten; Molema, Grietje; Goebeler, Matthias; Schmidt, Marc

2010-01-01

FOXO transcription factors represent targets of the phosphatidylinositol 3-kinase/protein kinase B survival pathway controlling important biological processes, such as cell cycle progression, apoptosis, vascular remodeling, stress responses, and metabolism. Recent studies suggested the existence of alternative mechanisms of FOXO-dependent gene expression beyond classical binding to a FOXO-responsive DNA-binding element (FRE). Here we analyzed the relative contribution of those mechanisms to vascular function by comparing the transcriptional and cellular responses to conditional activation of FOXO3 and a corresponding FRE-binding mutant in human primary endothelial cells. We demonstrate that FOXO3 controls expression of vascular remodeling genes in an FRE-dependent manner. In contrast, FOXO3-induced cell cycle arrest and apoptosis occurs independently of FRE binding, albeit FRE-dependent gene expression augments the proapoptotic response. These findings are supported by bioinformatical analysis, which revealed a statistical overrepresentation of cell cycle regulators and apoptosis-related genes in the group of co-regulated genes. Molecular analysis of FOXO3-induced endothelial apoptosis excluded modulators of the extrinsic death receptor pathway and demonstrated important roles for the BCL-2 family members BIM and NOXA in this process. Although NOXA essentially contributed to FRE-dependent apoptosis, BIM was effectively induced in the absence of FRE-binding, and small interfering RNA-mediated BIM depletion could rescue apoptosis induced by both FOXO3 mutants. These data suggest BIM as a critical cell type-specific mediator of FOXO3-induced endothelial apoptosis, whereas NOXA functions as an amplifying factor. Our study provides the first comprehensive analysis of alternatively regulated FOXO3 targets in relevant primary cells and underscores the importance of such genes for endothelial function and integrity. PMID:20123982

Risk factors for perioperative hyperglycemia in primary hip and knee replacements

PubMed Central

Jämsen, Esa; Nevalainen, Pasi I; Eskelinen, Antti; Kalliovalkama, Jarkko; Moilanen, Teemu

2015-01-01

Background and purpose Background and purpose — Perioperative hyperglycemia has been associated with adverse outcomes in several fields of surgery. In this observational study, we identified factors associated with an increased risk of hyperglycemia following hip and knee replacement. Patients and methods Patients and methods — We prospectively monitored changes in glucose following primary hip and knee replacements in 191 patients with osteoarthritis. Possible associations of patient characteristics and operation-related factors with hyperglycemia (defined as glucose > 7.8 mmol/L in 2 consecutive measurements) and severe hyperglycemia (glucose > 10 mmol/L) were analyzed using binary logistic regression with adjustment for age, sex, operated joint, and anesthesiological risk score. Results Results — 76 patients (40%) developed hyperglycemia, and 48 of them (25% of the whole cohort) had severe hyperglycemia. Glycemic responses were similar following hip replacement and knee replacement. Previously diagnosed diabetes was associated with an increased risk of hyperglycemia and severe hyperglycemia, compared to patients with normal glucose metabolism, whereas newly diagnosed diabetes and milder glucose metabolism disorders had no effect. In patients without previously diagnosed diabetes, increased values of preoperative glycosylated hemoglobin (HbA1c) and fasting glucose on the day of operation were associated with hyperglycemia. Higher anesthesiological risk score—but none of the operation-related factors analyzed—was associated with an increased risk of hyperglycemia. Interpretation Interpretation — Perioperative hyperglycemia is common in primary hip and knee replacements. Previously diagnosed diabetes is the strongest risk factor for hyperglycemia. In patients with no history of diabetes, preoperative HbA1c and fasting glucose on the day of operation can be used to stratify the risk of hyperglycemia. PMID:25409255

Establishment of primary mixed cell cultures from spontaneous canine mammary tumors: Characterization of classic and new cancer-associated molecules

PubMed Central

Gentile, Luciana B.; Nagamine, Marcia K.; Biondi, Luiz R.; Sanches, Daniel S.; Toyota, Fábio; Giovani, Tatiane M.; de Jesus, Isis P.; da Fonseca, Ivone I. M.; Queiroz-Hazarbassanov, Nicolle; Diaz, Bruno L.; Salles Gomes, Cristina de O. Massoco

2017-01-01

There are many factors which make canine cancer like cancer in humans. The occurrence of spontaneous mammary tumors in pet dogs, tumor genetics, molecular targets and exposure to the same environmental risk factors are among these factors. Therefore, the study of canine cancer can provide useful information to the oncology field. This study aimed to establish and characterize a panel of primary mixed cell cultures obtained from spontaneous canine mammary tumors. Eight established cell cultures obtained from one normal mammary gland, one complex adenoma, one mixed adenoma, two complex carcinomas and two mixed carcinomas were analyzed. The gene expression levels of classic molecular cancer players such as fibroblast growth factor receptor (FGFR) 2, breast cancer (BRCA) 1, BRCA2 and estrogen receptor (ESR) 1 were evaluated. For the first time, three orphan nuclear receptors, estrogen-related receptors (ERRs) α, β and γ were studied in canine mammary cancer. The highest expression level of ERRα was observed in complex carcinoma-derived cell culture, while the highest levels of ERRβ and γ were observed in cells derived from a mixed carcinoma. Meanwhile, complex carcinomas presented the highest levels of expression of ESR1, BRCA1 and FGFR2 among all samples. BRCA2 was found exclusively in complex adenoma. The transcription factor GATA3 had its highest levels in mixed carcinoma samples and its lowest levels in complex adenoma. Proliferation assays were also performed to evaluate the mixed cell cultures response to ER ligands, genistein and DES, both in normoxia and hypoxic conditions. Our results demonstrate that morphological and functional studies of primary mixed cell cultures derived from spontaneous canine mammary tumors are possible and provide valuable tool for the study of various stages of mammary cancer development. PMID:28945747

Phosphoproteomics to Characterize Host Response During Influenza A Virus Infection of Human Macrophages.

PubMed

Söderholm, Sandra; Kainov, Denis E; Öhman, Tiina; Denisova, Oxana V; Schepens, Bert; Kulesskiy, Evgeny; Imanishi, Susumu Y; Corthals, Garry; Hintsanen, Petteri; Aittokallio, Tero; Saelens, Xavier; Matikainen, Sampsa; Nyman, Tuula A

2016-10-01

Influenza A viruses cause infections in the human respiratory tract and give rise to annual seasonal outbreaks, as well as more rarely dreaded pandemics. Influenza A viruses become quickly resistant to the virus-directed antiviral treatments, which are the current main treatment options. A promising alternative approach is to target host cell factors that are exploited by influenza viruses. To this end, we characterized the phosphoproteome of influenza A virus infected primary human macrophages to elucidate the intracellular signaling pathways and critical host factors activated upon influenza infection. We identified 1675 phosphoproteins, 4004 phosphopeptides and 4146 nonredundant phosphosites. The phosphorylation of 1113 proteins (66%) was regulated upon infection, highlighting the importance of such global phosphoproteomic profiling in primary cells. Notably, 285 of the identified phosphorylation sites have not been previously described in publicly available phosphorylation databases, despite many published large-scale phosphoproteome studies using human and mouse cell lines. Systematic bioinformatics analysis of the phosphoproteome data indicated that the phosphorylation of proteins involved in the ubiquitin/proteasome pathway (such as TRIM22 and TRIM25) and antiviral responses (such as MAVS) changed in infected macrophages. Proteins known to play roles in small GTPase-, mitogen-activated protein kinase-, and cyclin-dependent kinase- signaling were also regulated by phosphorylation upon infection. In particular, the influenza infection had a major influence on the phosphorylation profiles of a large number of cyclin-dependent kinase substrates. Functional studies using cyclin-dependent kinase inhibitors showed that the cyclin-dependent kinase activity is required for efficient viral replication and for activation of the host antiviral responses. In addition, we show that cyclin-dependent kinase inhibitors protect IAV-infected mice from death. In conclusion, we provide the first comprehensive phosphoproteome characterization of influenza A virus infection in primary human macrophages, and provide evidence that cyclin-dependent kinases represent potential therapeutic targets for more effective treatment of influenza infections. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Phosphoproteomics to Characterize Host Response During Influenza A Virus Infection of Human Macrophages*

PubMed Central

Söderholm, Sandra; Kainov, Denis E.; Öhman, Tiina; Denisova, Oxana V.; Schepens, Bert; Kulesskiy, Evgeny; Imanishi, Susumu Y.; Corthals, Garry; Hintsanen, Petteri; Aittokallio, Tero; Saelens, Xavier; Matikainen, Sampsa; Nyman, Tuula A.

2016-01-01

Influenza A viruses cause infections in the human respiratory tract and give rise to annual seasonal outbreaks, as well as more rarely dreaded pandemics. Influenza A viruses become quickly resistant to the virus-directed antiviral treatments, which are the current main treatment options. A promising alternative approach is to target host cell factors that are exploited by influenza viruses. To this end, we characterized the phosphoproteome of influenza A virus infected primary human macrophages to elucidate the intracellular signaling pathways and critical host factors activated upon influenza infection. We identified 1675 phosphoproteins, 4004 phosphopeptides and 4146 nonredundant phosphosites. The phosphorylation of 1113 proteins (66%) was regulated upon infection, highlighting the importance of such global phosphoproteomic profiling in primary cells. Notably, 285 of the identified phosphorylation sites have not been previously described in publicly available phosphorylation databases, despite many published large-scale phosphoproteome studies using human and mouse cell lines. Systematic bioinformatics analysis of the phosphoproteome data indicated that the phosphorylation of proteins involved in the ubiquitin/proteasome pathway (such as TRIM22 and TRIM25) and antiviral responses (such as MAVS) changed in infected macrophages. Proteins known to play roles in small GTPase–, mitogen-activated protein kinase–, and cyclin-dependent kinase- signaling were also regulated by phosphorylation upon infection. In particular, the influenza infection had a major influence on the phosphorylation profiles of a large number of cyclin-dependent kinase substrates. Functional studies using cyclin-dependent kinase inhibitors showed that the cyclin-dependent kinase activity is required for efficient viral replication and for activation of the host antiviral responses. In addition, we show that cyclin-dependent kinase inhibitors protect IAV-infected mice from death. In conclusion, we provide the first comprehensive phosphoproteome characterization of influenza A virus infection in primary human macrophages, and provide evidence that cyclin-dependent kinases represent potential therapeutic targets for more effective treatment of influenza infections. PMID:27486199

Signaling mechanisms coupled to tyrosines in the granulocyte colony-stimulating factor receptor orchestrate G-CSF-induced expansion of myeloid progenitor cells.

PubMed

Hermans, Mirjam H A; van de Geijn, Gert-Jan; Antonissen, Claudia; Gits, Judith; van Leeuwen, Daphne; Ward, Alister C; Touw, Ivo P

2003-04-01

Granulocyte colony-stimulating factor (G-CSF) is the major regulator of neutrophil production. Studies in cell lines have established that conserved tyrosines Tyr704, Tyr729, Tyr744, Tyr764 within the cytoplasmic domain of G-CSF receptor (G-CSF-R) contribute significantly to G-CSF-induced proliferation, differentiation, and cell survival. However, it is unclear whether these tyrosines are equally important under more physiologic conditions. Here, we investigated how individual G-CSF-R tyrosines affect G-CSF responses of primary myeloid progenitors. We generated G-CSF-R-deficient mice and transduced their bone marrow cells with tyrosine "null" mutant (m0), single tyrosine "add-back" mutants, or wild-type (WT) receptors. G-CSF-induced responses were determined in primary colony assays, serial replatings, and suspension cultures. We show that removal of all tyrosines had no major influence on primary colony growth. However, adding back Tyr764 strongly enhanced proliferative responses, which was reverted by inhibition of ERK activity. Tyr729, which we found to be associated with the suppressor of cytokine signaling, SOCS3, had a negative effect on colony formation. After repetitive replatings, the clonogenic capacities of cells expressing m0 gradually dropped compared with WT. The presence of Tyr729, but also Tyr704 and Tyr744, both involved in activation of signal transducer and activator of transcription 3 (STAT3), further reduced replating efficiencies. Conversely, Tyr764 greatly elevated the clonogenic abilities of myeloid progenitors, resulting in a more than 10(4)-fold increase of colony-forming cells over m0 after the fifth replating. These findings suggest that tyrosines in the cytoplasmic domain of G-CSF-R, although dispensable for G-CSF-induced colony growth, recruit signaling mechanisms that regulate the maintenance and outgrowth of myeloid progenitor cells.

Analysis and Validation of Contactless Time-Gated Interrogation Technique for Quartz Resonator Sensors

PubMed Central

Baù, Marco; Ferrari, Marco; Ferrari, Vittorio

2017-01-01

A technique for contactless electromagnetic interrogation of AT-cut quartz piezoelectric resonator sensors is proposed based on a primary coil electromagnetically air-coupled to a secondary coil connected to the electrodes of the resonator. The interrogation technique periodically switches between interleaved excitation and detection phases. During the excitation phase, the resonator is set into vibration by a driving voltage applied to the primary coil, whereas in the detection phase, the excitation signal is turned off and the transient decaying response of the resonator is sensed without contact by measuring the voltage induced back across the primary coil. This approach ensures that the readout frequency of the sensor signal is to a first order approximation independent of the interrogation distance between the primary and secondary coils. A detailed theoretical analysis of the interrogation principle based on a lumped-element equivalent circuit is presented. The analysis has been experimentally validated on a 4.432 MHz AT-cut quartz crystal resonator, demonstrating the accurate readout of the series resonant frequency and quality factor over an interrogation distance of up to 2 cm. As an application, the technique has been applied to the measurement of liquid microdroplets deposited on a 4.8 MHz AT-cut quartz crystal. More generally, the proposed technique can be exploited for the measurement of any physical or chemical quantities affecting the resonant response of quartz resonator sensors. PMID:28574459

Analysis and Validation of Contactless Time-Gated Interrogation Technique for Quartz Resonator Sensors.

PubMed

Baù, Marco; Ferrari, Marco; Ferrari, Vittorio

2017-06-02

A technique for contactless electromagnetic interrogation of AT-cut quartz piezoelectric resonator sensors is proposed based on a primary coil electromagnetically air-coupled to a secondary coil connected to the electrodes of the resonator. The interrogation technique periodically switches between interleaved excitation and detection phases. During the excitation phase, the resonator is set into vibration by a driving voltage applied to the primary coil, whereas in the detection phase, the excitation signal is turned off and the transient decaying response of the resonator is sensed without contact by measuring the voltage induced back across the primary coil. This approach ensures that the readout frequency of the sensor signal is to a first order approximation independent of the interrogation distance between the primary and secondary coils. A detailed theoretical analysis of the interrogation principle based on a lumped-element equivalent circuit is presented. The analysis has been experimentally validated on a 4.432 MHz AT-cut quartz crystal resonator, demonstrating the accurate readout of the series resonant frequency and quality factor over an interrogation distance of up to 2 cm. As an application, the technique has been applied to the measurement of liquid microdroplets deposited on a 4.8 MHz AT-cut quartz crystal. More generally, the proposed technique can be exploited for the measurement of any physical or chemical quantities affecting the resonant response of quartz resonator sensors.

Response of free-living nitrogen-fixing microorganisms to land use change in the Amazon rainforest.

PubMed

Mirza, Babur S; Potisap, Chotima; Nüsslein, Klaus; Bohannan, Brendan J M; Rodrigues, Jorge L M

2014-01-01

The Amazon rainforest, the largest equatorial forest in the world, is being cleared for pasture and agricultural use at alarming rates. Tropical deforestation is known to cause alterations in microbial communities at taxonomic and phylogenetic levels, but it is unclear whether microbial functional groups are altered. We asked whether free-living nitrogen-fixing microorganisms (diazotrophs) respond to deforestation in the Amazon rainforest, using analysis of the marker gene nifH. Clone libraries were generated from soil samples collected from a primary forest, a 5-year-old pasture originally converted from primary forest, and a secondary forest established after pasture abandonment. Although diazotroph richness did not significantly change among the three plots, diazotroph community composition was altered with forest-to-pasture conversion, and phylogenetic similarity was higher among pasture communities than among those in forests. There was also 10-fold increase in nifH gene abundance following conversion from primary forest to pasture. Three environmental factors were associated with the observed changes: soil acidity, total N concentration, and C/N ratio. Our results suggest a partial restoration to initial levels of abundance and community structure of diazotrophs following pasture abandonment, with primary and secondary forests sharing similar communities. We postulate that the response of diazotrophs to land use change is a direct consequence of changes in plant communities, particularly the higher N demand of pasture plant communities for supporting aboveground plant growth.

Using the Patient Health Questionnaire-9 to measure depression among racially and ethnically diverse primary care patients.

PubMed

Huang, Frederick Y; Chung, Henry; Kroenke, Kurt; Delucchi, Kevin L; Spitzer, Robert L

2006-06-01

The Patient Health Questionnaire depression scale (PHQ-9) is a well-validated, Diagnostic and Statistical Manual of Mental Disorders- Fourth Edition (DSM-IV) criterion-based measure for diagnosing depression, assessing severity and monitoring treatment response. The performance of most depression scales including the PHQ-9, however, has not been rigorously evaluated in different racial/ethnic populations. Therefore, we compared the factor structure of the PHQ-9 between different racial/ethnic groups as well as the rates of endorsement and differential item functioning (DIF) of the 9 items of the PHQ-9. The presence of DIF would indicate that responses to an individual item differ significantly between groups, controlling for the level of depression. A combined dataset from 2 separate studies of 5,053 primary care patients including non-Hispanic white (n=2,520), African American (n=598), Chinese American (n=941), and Latino (n=974) patients was used for our analysis. Exploratory principal components factor analysis was used to derive the factor structure of the PHQ-9 in each of the 4 racial/ethnic groups. A generalized Mantel-Haenszel statistic was used to test for DIF. One main factor that included all PHQ-9 items was found in each racial/ethnic group with alpha coefficients ranging from 0.79 to 0.89. Although endorsement rates of individual items were generally similar among the 4 groups, evidence of DIF was found for some items. Our analyses indicate that in African American, Chinese American, Latino, and non-Hispanic white patient groups the PHQ-9 measures a common concept of depression and can be effective for the detection and monitoring of depression in these diverse populations.

Natural Hemozoin Stimulates Syncytiotrophoblast to Secrete Chemokines and Recruit Peripheral Blood Mononuclear Cells

PubMed Central

Lucchi, Naomi W.; Sarr, Demba; Owino, Simon O.; Mwalimu, Stephen M.; Peterson, David S.; Moore, Julie M.

2011-01-01

Background Placental malaria is associated with local accumulation of parasitized erythrocytes, deposition of the parasite hemoglobin metabolite, hemozoin, and accumulation of mononuclear cells in the intervillous space. Fetal syncytiotrophoblast cells in contact with maternal blood are known to respond immunologically to cytoadherent Plasmodium falciparum-infected erythrocytes, but their responsiveness to hemozoin, a potent pro-inflammatory stimulator of monocytes, macrophages and dendritic cells, is not known. Methods The biochemical and immunological changes induced in primary syncytiotrophoblast by natural hemozoin was assessed. Changes in syncytiotrophoblast mitogen-activated protein kinase activation was assessed by immunoblotting and secreted cytokine and chemokine proteins were assayed by ELISA. Chemotaxis of peripheral blood mononuclear cells was assessed using a two-chamber assay system and flow cytometry was used to assess the activation of primary monocytes by hemozoin-stimulated syncytiotrophoblast conditioned medium. Results Hemozoin stimulation induced ERK1/2 phosphorylation. Treated cells secreted CXCL8, CCL3, CCL4, and tumor necrosis factor and released soluble intercellular adhesion molecule-1. Furthermore, the dependence of the hemozoin responses on ERK1/2 stimulation was confirmed by inhibition of chemokine release in syncytiotrophoblast treated with an ERK pathway inhibitor. Hemozoin-stimulated cells elicited the specific migration of PBMCs, and conditioned medium from the cells induced the upregulation of intercellular adhesion molecule-1 on primary monocytes. Conclusions These findings confirm an immunostimulatory role for hemozoin and expand the cell types known to be responsive to hemozoin to include fetal syncytiotrophoblast. The results provide further evidence that syncytiotrophoblast cells can influence the local maternal immune response to placental malaria. PMID:21632106

An analysis of hearing screening test results in 2291 premature infants of Chinese population.

PubMed

Huang, Lili; Xiong, Fei; Li, Jinrong; Yang, Fan

2017-04-01

The aim of this study was to analyze the hearing screening program among preterm infants as well as to identify risk factors associated with failing primary newborn hearing screening. The retrospectively selected population included all preterm infants who had primary hearing screening in a neonatal ward from January 1st, 2013 to December 31st, 2015 at West China Second University Hospital, Sichuan University. The newborn hearing screening (NHS) procedure was performed in all preterm infants by automated auditory brainstem response (AABR). Infants who failed the primary hearing screening received a second screening at 42 days after birth. Infants who failed both tests were referred to a tertiary audiology center for diagnostic confirmation and management before 6 months of age. The final diagnosis for referred infants was obtained by telephone follow-up. The risk factors associated with failure to pass the primary hearing screen were evaluated and analyzed for preterm infants. Among 2291 preterm infants recruited, 155 infants (6.8%) failed the primary hearing screening with an abnormal AABR. Of these 155 infants, 113 (72.9%) passed the secondary screening. At the end of the follow-up, 1 infant (0.04%) was diagnosed with hearing loss, 3 infants had delayed language development, and 40 infants were lost to follow up. Multivariate regression analysis revealed that gestational age ≤32 weeks (Odds ratio [OR] = 2.093, 95% confidence interval [CI] 1.370-3.196), super hyperbilirubinemia (≥25 mg/dl) (OR = 3.560, 95% CI 1.009-12.560), and respiratory failure (OR = 1.971, 95% CI 1.188-3.265) were associated with failure to pass newborn hearing screening. The prevalence of failure to pass primary hearing screening among preterm infants was 6.8% in our study, and we found a relatively low prevalence of hearing loss (0.04%). Super hyperbilirubinemia, gestational age ≤32weeks, and respiratory failure were risk factors associated with failure of preterm infants to pass the primary hearing screening. Our results suggest that preterm infants with hyperbilirubinemia, gestational age ≤32 weeks, and respiratory failure should be closely followed. Copyright © 2017 Elsevier B.V. All rights reserved.

Fibroblast growth factor 19 in patients with bile acid diarrhoea: a prospective comparison of FGF19 serum assay and SeHCAT retention.

PubMed

Pattni, S S; Brydon, W G; Dew, T; Johnston, I M; Nolan, J D; Srinivas, M; Basumani, P; Bardhan, K D; Walters, J R F

2013-10-01

Bile acid diarrhoea is a common, under-diagnosed cause of chronic watery diarrhoea, responding to specific treatment with bile acid sequestrants. We previously showed patients with bile acid diarrhoea have lower median levels compared with healthy controls, of the ileal hormone fibroblast growth factor 19 (FGF19), which regulates bile acid synthesis. To measure serum FGF19 and SeHCAT retention prospectively in patients with chronic diarrhoea. One hundred and fifty-two consecutive patients were grouped according to (75) Se-homocholic acid taurine (SeHCAT) 7-day retention: normal (>15%) in 72 (47%) diarrhoea controls; ≤15% in 54 (36%) with primary bile acid diarrhoea, and in 26 (17%) with secondary bile acid diarrhoea. Fasting blood was assayed for FGF19, 7α-hydroxy-4-cholesten-3-one (C4) and total bile acids. FGF19 was significantly lower in the primary bile acid diarrhoea group compared with the diarrhoea control group (median 147 vs. 225 pg/mL, P < 0.001), and also in the secondary group (P < 0.006). FGF19 and SeHCAT values were positively correlated (rs = 0.44, P < 0.001); both were inversely related to C4. Other significant relationships included SeHCAT and body mass index (BMI)(P = 0.02), and FGF19 with age (P < 0.01). The negative and positive predictive values of FGF19 ≤ 145 pg/mL for a SeHCAT <10% were 82% and 61%, respectively, and were generally improved in an index including BMI, age and C4. In a subset of 28 primary patients, limited data suggested that FGF19 could predict response to sequestrant therapy. Reduced fibroblast growth factor 19 is a feature of bile acid diarrhoea. Further studies will fully define its role in predicting the response of these patients to therapy. © 2013 John Wiley & Sons Ltd.

From concept to content: assessing the implementation fidelity of a chronic care model for frail, older people who live at home.

PubMed

Muntinga, Maaike E; Van Leeuwen, Karen M; Schellevis, François G; Nijpels, Giel; Jansen, Aaltje P D

2015-01-22

Implementation fidelity, the degree to which a care program is implemented as intended, can influence program impact. Since results of trials that aim to implement comprehensive care programs for frail, older people have been conflicting, assessing implementation fidelity alongside these trials is essential to differentiate between flaws inherent to the program and implementation issues. This study demonstrates how a theory-based assessment of fidelity can increase insight in the implementation process of a complex intervention in primary elderly care. The Geriatric Care Model was implemented among 35 primary care practices in the Netherlands. During home visits, practice nurses conducted a comprehensive geriatric assessment and wrote a tailored care plan. Multidisciplinary team consultations were organized with the aim to enhance the coordination between professionals caring for a single patient with complex needs. To assess fidelity, we identified 5 key intervention components and formulated corresponding research questions using Carroll's framework for fidelity. Adherence (coverage, frequency, duration, content) was assessed per intervention component during and at the end of the intervention period. Two moderating factors (participant responsiveness and facilitation strategies) were assessed at the end of the intervention. Adherence to the geriatric assessments and care plans was high, but decreased over time. Adherence to multidisciplinary consultations was initially poor, but increased over time. We found that individual differences in adherence between practice nurses and primary care physicians were moderate, while differences in participant responsiveness (satisfaction, involvement) were more distinct. Nurses deviated from protocol due to contextual factors and personal work routines. Adherence to the Geriatric Care Model was high for most of the essential intervention components. Study limitations include the limited number of assessed moderating factors. We argue that a longitudinal investigation of adherence per intervention component is essential for a complete understanding of the implementation process, but that such investigations may be complicated by practical and methodological challenges. The Netherlands National Trial Register (NTR). 2160 .

Use of selection indices to model the functional response of predators

USGS Publications Warehouse

Joly, D.O.; Patterson, B.R.

2003-01-01

The functional response of a predator to changing prey density is an important determinant of stability of predatora??prey systems. We show how Manly's selection indices can be used to distinguish between hyperbolic and sigmoidal models of a predator functional response to primary prey density in the presence of alternative prey. Specifically, an inverse relationship between prey density and preference for that prey results in a hyperbolic functional response while a positive relationship can yield either a hyperbolic or sigmoidal functional response, depending on the form and relative magnitudes of the density-dependent preference model, attack rate, and handling time. As an example, we examine wolf (Canis lupus) functional response to moose (Alces alces) density in the presence of caribou (Rangifer tarandus). The use of selection indices to evaluate the form of the functional response has significant advantages over previous attempts to fit Holling's functional response curves to killing-rate data directly, including increased sensitivity, use of relatively easily collected data, and consideration of other explanatory factors (e.g., weather, seasons, productivity).

Infant Breast-feeding and Childhood Caries: A Nine-year Study

PubMed Central

Hong, Liang; Levy, Steven M.; Warren, John J.; Broffitt, Barbara

2017-01-01

Purpose This study’s purpose was to assess the association between infant breast-feeding and caries experience of primary second molars in a nine-year longitudinal cohort study. Methods Study sample was 509 subjects recruited at birth. Information about breast-feeding duration and other factors was collected through parents’ responses to periodic questionnaires. Primary teeth were examined for dental caries at five years old and nine years old by calibrated dentist examiners. Caries experience (yes/no) and number of decayed and/or filled surfaces (dfs) were determined for five- and nine-year-olds. Results For primary second molars at five years old, 18 percent of children who were breast-fed less than six months had caries (mean dfs=0.55) while only 9 percent of children who were breast-fed at least six months had caries (mean dfs=0.33). From five to nine years old, caries incidence was 32 percent and 31 percent, respectively, for children breast-fed less than six months and at least six months. In multivariable regression analyses, shorter breast-feeding duration was positively associated with caries experience of primary second molars at five years old (P=.005), both before and after controlling for other important factors. Conclusions Shorter duration of breast-feeding is suggested to be associated with increased risk for early childhood caries, but its impact might diminish with age. PMID:25198001

Understanding epigenetics of schizophrenia in the backdrop of its antipsychotic drug therapy.

PubMed

Swathy, Babu; Banerjee, Moinak

2017-05-01

The diatheses of gene and environment interaction in schizophrenia (SCZ) are becoming increasingly evident. Genetic and epigenetic backgrounds are being considered in stratifying and addressing phenotypic variation and drug response in SCZ. But how much of these epigenetic alterations are the primary contributing factor, toward disease pathogenesis and drug response, needs further clarity. Evidence indicates that antipsychotic drugs can also alter the epigenetic homeostasis thereby inducing pharmacoepigenomic effects. We re-examine the context of epigenetics in disease pathogenesis and antipsychotic drug therapy in SCZ to understand how much of these observations act as real indicators of the disease or therapeutic response. We propose that epigenetic viewpoint in SCZ needs to be critically examined under the genetic, epigenetic and pharmacoepigenetic background.

The impact of stress on body function: A review

PubMed Central

Yaribeygi, Habib; Panahi, Yunes; Sahraei, Hedayat; Johnston, Thomas P.; Sahebkar, Amirhossein

2017-01-01

Any intrinsic or extrinsic stimulus that evokes a biological response is known as stress. The compensatory responses to these stresses are known as stress responses. Based on the type, timing and severity of the applied stimulus, stress can exert various actions on the body ranging from alterations in homeostasis to life-threatening effects and death. In many cases, the pathophysiological complications of disease arise from stress and the subjects exposed to stress, e.g. those that work or live in stressful environments, have a higher likelihood of many disorders. Stress can be either a triggering or aggravating factor for many diseases and pathological conditions. In this study, we have reviewed some of the major effects of stress on the primary physiological systems of humans. PMID:28900385

Contextual Factors Related to Implementation and Reach of a Pragmatic Multisite Trial– The My Own Health Report (MOHR) Study

PubMed Central

Balasubramanian, Bijal A.; Heurtin-Roberts, Suzanne; Krasny, Sarah; Rohweder, Catherine; Fair, Kayla; Olmos, Tanya; Stange, Kurt C.; Gorin, Sherri Sheinfeld

2018-01-01

Background Contextual factors relevant to health care improvement studies are important for translating findings to other settings; however, these are rarely collected systematically and reported. This study articulates a prospective method for assessing contextual factors and describes factors related to implementation and patient reach of a pragmatic multisite trial conducted in nine primary care practices. Methods In a qualitative case-series, contextual factors were assessed from the My Own Health Report (MOHR) study, focused on systematically conducting health risk assessments and goal setting for unhealthy behaviors and behavioral health in primary care. Data were collected prospectively at baseline, mid-point, and end of intervention using a template that guided conduct of interviews and observations at practice sites. A multidisciplinary team used an iterative process to summarize themes describing contextual factors related to intervention implementation and patient reach, calculated by dividing the number of patients who completed the MOHR assessment by the number of patients offered MOHR. Results Contextual factors operational both within and external to the practice environment influenced implementation and patient reach over time. These included practice members’ motivations towards the MOHR intervention, practice staff capacity to take on additional responsibilities for implementation, practice information system capacity, external resources to support quality improvement, linkages with community resources, and fit of implementation strategy to patient populations. Conclusions Systematic assessment of contextual factors throughout implementation of quality improvement initiatives is needed to meaningfully interpret findings and translate lessons learned to other health care settings. Thus, knowledge of contextual factors is essential for scaling up of effective improvement strategies. PMID:28484066

A trust region-based approach to optimize triple response systems

NASA Astrophysics Data System (ADS)

Fan, Shu-Kai S.; Fan, Chihhao; Huang, Chia-Fen

2014-05-01

This article presents a new computing procedure for the global optimization of the triple response system (TRS) where the response functions are non-convex quadratics and the input factors satisfy a radial constrained region of interest. The TRS arising from response surface modelling can be approximated using a nonlinear mathematical program that considers one primary objective function and two secondary constraint functions. An optimization algorithm named the triple response surface algorithm (TRSALG) is proposed to determine the global optimum for the non-degenerate TRS. In TRSALG, the Lagrange multipliers of the secondary functions are determined using the Hooke-Jeeves search method and the Lagrange multiplier of the radial constraint is located using the trust region method within the global optimality space. The proposed algorithm is illustrated in terms of three examples appearing in the quality-control literature. The results of TRSALG compared to a gradient-based method are also presented.

Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells

PubMed Central

Lee, Jonghyeob; Sugiyama, Takuya; Liu, Yinghua; Wang, Jing; Gu, Xueying; Lei, Ji; Markmann, James F; Miyazaki, Satsuki; Miyazaki, Jun-ichi; Szot, Gregory L; Bottino, Rita; Kim, Seung K

2013-01-01

Pancreatic islet β-cell insufficiency underlies pathogenesis of diabetes mellitus; thus, functional β-cell replacement from renewable sources is the focus of intensive worldwide effort. However, in vitro production of progeny that secrete insulin in response to physiological cues from primary human cells has proven elusive. Here we describe fractionation, expansion and conversion of primary adult human pancreatic ductal cells into progeny resembling native β-cells. FACS-sorted adult human ductal cells clonally expanded as spheres in culture, while retaining ductal characteristics. Expression of the cardinal islet developmental regulators Neurog3, MafA, Pdx1 and Pax6 converted exocrine duct cells into endocrine progeny with hallmark β-cell properties, including the ability to synthesize, process and store insulin, and secrete it in response to glucose or other depolarizing stimuli. These studies provide evidence that genetic reprogramming of expandable human pancreatic cells with defined factors may serve as a general strategy for islet replacement in diabetes. DOI: http://dx.doi.org/10.7554/eLife.00940.001 PMID:24252877

Expansion and conversion of human pancreatic ductal cells into insulin-secreting endocrine cells.

PubMed

Lee, Jonghyeob; Sugiyama, Takuya; Liu, Yinghua; Wang, Jing; Gu, Xueying; Lei, Ji; Markmann, James F; Miyazaki, Satsuki; Miyazaki, Jun-Ichi; Szot, Gregory L; Bottino, Rita; Kim, Seung K

2013-11-19

Pancreatic islet β-cell insufficiency underlies pathogenesis of diabetes mellitus; thus, functional β-cell replacement from renewable sources is the focus of intensive worldwide effort. However, in vitro production of progeny that secrete insulin in response to physiological cues from primary human cells has proven elusive. Here we describe fractionation, expansion and conversion of primary adult human pancreatic ductal cells into progeny resembling native β-cells. FACS-sorted adult human ductal cells clonally expanded as spheres in culture, while retaining ductal characteristics. Expression of the cardinal islet developmental regulators Neurog3, MafA, Pdx1 and Pax6 converted exocrine duct cells into endocrine progeny with hallmark β-cell properties, including the ability to synthesize, process and store insulin, and secrete it in response to glucose or other depolarizing stimuli. These studies provide evidence that genetic reprogramming of expandable human pancreatic cells with defined factors may serve as a general strategy for islet replacement in diabetes. DOI: http://dx.doi.org/10.7554/eLife.00940.001.

Primary Biliary Cirrhosis Beyond Ursodeoxycholic Acid.

PubMed

Corpechot, Christophe

2016-02-01

Although ursodeoxycholic acid remains the only approved pharmacotherapy for patients with primary biliary cirrhosis, the better characterization of factors responsible for the poor response to this drug and the emergence of several new putative therapeutic targets now offer significant opportunities to improve the management of patients and our capacity to treat them more efficiently. The availability of novel treatment options, such as fibrates, budesonide, and obeticholic acid, all capable of improving prognostic markers, invites us to reconsider our management and treatment strategies. Early identification of high-risk patients should remain a priority to deliver adjunctive therapies to appropriately selected populations and increase their chances of success. Given the absence of comparative trials, the choice between second-line treatments should be dictated by the biochemical, histological, and expected tolerance profiles. Here the author presents a brief overview of what should be known in this field and proposes a practical approach to facilitate decision making. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

THE POPULATION OF COMPACT RADIO SOURCES IN THE ORION NEBULA CLUSTER

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

Forbrich, J.; Meingast, S.; Rivilla, V. M.

We present a deep centimeter-wavelength catalog of the Orion Nebula Cluster (ONC), based on a 30 hr single-pointing observation with the Karl G. Jansky Very Large Array in its high-resolution A-configuration using two 1 GHz bands centered at 4.7 and 7.3 GHz. A total of 556 compact sources were detected in a map with a nominal rms noise of 3 μ Jy bm{sup −1}, limited by complex source structure and the primary beam response. Compared to previous catalogs, our detections increase the sample of known compact radio sources in the ONC by more than a factor of seven. The newmore » data show complex emission on a wide range of spatial scales. Following a preliminary correction for the wideband primary-beam response, we determine radio spectral indices for 170 sources whose index uncertainties are less than ±0.5. We compare the radio to the X-ray and near-infrared point-source populations, noting similarities and differences.« less

Weekly irinotecan in patients with metastatic colorectal cancer failing 5-fluorouracil-based chemotherapy: efficacy and prognostic factors.

PubMed

Karaoğlu, Aziz; Yalcin, Suayib; Tekuzman, Gülten; Kars, Ayse; Celik, Ismail; Güler, Nilüfer; Ozişik, Yavuz; Türker, Alev; Barişta, Ibrahim; Güllü, Ibrahim

2003-01-01

We evaluated the efficacy and tolerability of weekly irinotecan as a second-line treatment in patients with colorectal cancer failing 5-fluorouracil-based chemotherapy and searched for predictive and prognostic factors. A total of 36 patients were included. Median age was 53 years (range, 33-72). One treatment cycle consisted of irinotecan, 100 mg/m2 weekly, for 4 weeks followed by a 2-week rest. Gender, age, primary site, number of metastatic sites, histologic subtype, differentiation, pretreatment CEA, CA 19-9 and lactate dehydrogenase levels and marker response to treatment were investigated as predictive factors for response to treatment and as prognostic factors in the overall survival and time to progression of the patients. A total of 120 cycles (median, 3 cycles) was delivered. An overall 14% objective response rate (1 complete and 4 partial responses) was achieved. The median response duration was 4 months (range, 2-7). Another 36% of the patients had stable disease for a median duration of 4 months (range, 2-8). Median time-to-disease progression was 4 months and overall median survival was 12 months (95% confidence interval, 9-15). Pretreatment serum CA 19-9 level and marker response to two courses of treatment were found to be clinically significant in time to progression and overall survival. Younger age (< or = 45 years) was a poor prognostic factor associated with a shorter time to progression. The major toxicity was grade 3-4 diarrhea, which occurred in 28% of the patients, and treatment was discontinued in 3 (8%) patients due to toxicity. Other hematological and non-hematological toxicities were mild and manageable. We concluded that weekly irinotecan at the dose of 100 mg/m2 is an effective and tolerable treatment option, with a 50% disease control rate, for patients with colorectal cancer failing previous 5-fluorouracil-based chemotherapy.

Utilization of the cellular stress response to sensitize cancer cells to TRAIL-mediated apoptosis.

PubMed

Siegelin, Markus David

2012-08-01

Tumor necrosis factor-related apoptosis inducing ligand (TRAIL) is a promising death ligand who has received significant attention due to its specific anti-cancer activity. Recently, a number of clinical trials involving either recombinant soluble TRAIL or agonistic death receptor (DR) antibodies have even been initiated. One major caveat in TRAIL-based anti-cancer therapies is that a considerable number of cancer cells are notorious resistant to apoptosis induction by TRAIL. Overcoming this primary or secondary evolved resistance is an utmost important goal of present cancer research. The current literature suggests that TRAIL resistance is mediated by a number of endogenous factors. According to recent research, stress-related transcription factors have acquired a pivotal role in the sensitization of highly resistant cancer cells, for example, pancreatic cancer and glioblastoma cells, to TRAIL-mediated cell death. Out of this transcription factor family, C/EBP-homologous protein (CHOP) is linked to the control of DR-mediated apoptosis by modulation of several apoptotic and anti-apoptotic factors. Stress responses in certain organelles, such as endoplasmic reticulum (ER) and mitochondria, are potent inductors of CHOP expression. This report focuses on the influence of stress responses on endogenous or acquired resistance to extrinsic apoptosis in tumor cells and summarizes recent findings and results. The Medline and ClinicalTrials database with key words were used for this review. A potential novel treatment strategy for highly treatment-resistant tumors is the induction of a cellular stress response in cancer cells. The induction of an organelle-related stress response, such as nuclear, ER and mitochondrial stress, leads to a dramatic sensitization of a broad variety of cancer cells of different tumor entities to the apoptotic ligand, TRAIL. Importantly, non-neoplastic cells are not sensitized to TRAIL-mediated cell death through the unfolded protein response in most instances, suggesting that this treatment is not only of high efficacy, but even more less of unwanted toxicity in patients.

Alterations in T lymphocytes and T-lymphocyte subpopulations in patients with syphilis.

PubMed Central

Jensen, J R; From, E

1982-01-01

The distribution of T-lymphocyte subpopulations was studied in 34 patients with primary or secondary syphilis before and after treatment. An absolute and relative T lymphopenia was found in all patients. In primary syphilis the concentration of helper cells--T cells with Fc receptors for IgM (T mu)--was low whereas in secondary syphilis the suppressor cell concentration--T cells with Fc receptors for IgG (T gamma)--was reduced. Using lymphocytes from healthy subjects this could be imitated in vitro by the addition of serum from patients with secondary syphilis. In many autoimmune diseases a low concentration of T gamma may be a primary factor in the production of autoantibodies. The occurrence of similar changes in patients with secondary syphilis, however, indicates that such fluctuations in the T-cell subpopulations may take place during a strong immune response. PMID:6459815

Effect of microstructural anisotropy on fracture toughness of hot rolled 13Cr ODS steel - The role of primary and secondary cracking

NASA Astrophysics Data System (ADS)

Das, A.; Viehrig, H. W.; Bergner, F.; Heintze, C.; Altstadt, E.; Hoffmann, J.

2017-08-01

ODS steels have been known to exhibit anisotropic fracture behaviour and form secondary cracks. In this work, the factors responsible for the anisotropic fracture behaviour have been investigated using scanning electron microscopy and electron backscatter microscopy. Fracture toughness of hot rolled 13Cr ODS steel was determined using unloading compliance method for L-T and T-L orientations at various temperatures. L-T orientation had higher fracture toughness than T-L orientation and also contained more pronounced secondary cracking. Secondary cracks appeared at lower loads than primary cracks in both orientations. Primary crack propagation was found to be preferentially through fine grains in a bimodal microstructure. Grains were aligned and elongated the most towards rolling direction followed by T and S directions resulting in fracture anisotropy. Crystallographic texture and preferential alignment of Ti enriched particles parallel to rolling direction also contributed towards fracture anisotropy.

40 CFR 173.3 - Initiation of rescission proceedings.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PROGRAMS PROCEDURES GOVERNING THE RESCISSION OF STATE PRIMARY ENFORCEMENT RESPONSIBILITY FOR PESTICIDE USE... State having primary enforcement responsibility for pesticide use violations is not carrying out such... Administrator shall notify the State in writing of his intent to rescind its primary enforcement responsibility...

Time-Series Transcriptomics Reveals That AGAMOUS-LIKE22 Affects Primary Metabolism and Developmental Processes in Drought-Stressed Arabidopsis[OPEN

PubMed Central

Penfold, Christopher A.; Jenkins, Dafyd J.; Legaie, Roxane; Lawson, Tracy; Vialet-Chabrand, Silvere R.M.; Subramaniam, Sunitha; Hickman, Richard; Feil, Regina; Bowden, Laura; Hill, Claire; Lunn, John E.; Finkenstädt, Bärbel; Buchanan-Wollaston, Vicky; Beynon, Jim; Wild, David L.; Ott, Sascha

2016-01-01

In Arabidopsis thaliana, changes in metabolism and gene expression drive increased drought tolerance and initiate diverse drought avoidance and escape responses. To address regulatory processes that link these responses, we set out to identify genes that govern early responses to drought. To do this, a high-resolution time series transcriptomics data set was produced, coupled with detailed physiological and metabolic analyses of plants subjected to a slow transition from well-watered to drought conditions. A total of 1815 drought-responsive differentially expressed genes were identified. The early changes in gene expression coincided with a drop in carbon assimilation, and only in the late stages with an increase in foliar abscisic acid content. To identify gene regulatory networks (GRNs) mediating the transition between the early and late stages of drought, we used Bayesian network modeling of differentially expressed transcription factor (TF) genes. This approach identified AGAMOUS-LIKE22 (AGL22), as key hub gene in a TF GRN. It has previously been shown that AGL22 is involved in the transition from vegetative state to flowering but here we show that AGL22 expression influences steady state photosynthetic rates and lifetime water use. This suggests that AGL22 uniquely regulates a transcriptional network during drought stress, linking changes in primary metabolism and the initiation of stress responses. PMID:26842464

Role of the myeloid differentiation primary response (MYD88) and TIR-domain-containing adapter-inducing interferon-β (TRIF) pathways in dengue.

PubMed

Duran, Anyelo; Valero, Nereida; Mosquera, Jesus; Delgado, Lineth; Alvarez-Mon, Melchor; Torres, Mariana

2016-10-01

Dengue disease courses with high viremia titers and high cytokine production suggesting viral replication and active immune response that could be related to viral evasion. One of the main targets of dengue virus (DENV) is monocyte/macrophage cells; however, little information regarding viral evasive mechanisms and pathway activation in monocytes infected by DENV is available. The aim of this study was to determine the role of myeloid differentiation primary response (MyD88), TIR-domain-containing adapter- inducing interferon-β (TRIF) and NF-kB pathways in viral replication and cytokine production in human monocyte cultures infected by DENV2. In this regard Pepinh- TRIF, Pepinh- MYD and pyrrolidine dithiocarbamate (PDTC) were used to inhibit TRIF, MYD88 and NF-kB pathways. Cytokine production was measured by ELISA. Increased DENV replication and IFNα/β, TNF-α, IL-12 and IL-18 in infected cultures at 24h were found. All of these parameters were significantly decreased after TRIF, MYD88 or NF-kB inhibition. Association analysis between viral replication and cytokine production showed high significant positive correlation in TRIF and MYD88 treated cultures. This study shows that DENV2 induces activation of innate-immune response and transcription factors to drive viral expression and replication in the face of pro-inflammatory antiviral responses in vitro. Copyright © 2016 Elsevier Inc. All rights reserved.

Environmental and biological context modulates the physiological stress response of bats to human disturbance.

PubMed

Phelps, Kendra L; Kingston, Tigga

2018-06-01

Environmental and biological context play significant roles in modulating physiological stress responses of individuals in wildlife populations yet are often overlooked when evaluating consequences of human disturbance on individual health and fitness. Furthermore, most studies gauge individual stress responses based on a single physiological biomarker, typically circulating glucocorticoid concentrations, which limits interpretation of the complex, multifaceted responses of individuals to stressors. We selected four physiological biomarkers to capture short-term and prolonged stress responses in a widespread cave-roosting bat, Hipposideros diadema, across multiple gradients of human disturbance in and around caves in the Philippines. We used conditional inference trees and random forest analysis to determine the role of environmental quality (cave complexity, available roosting area), assemblage composition (intra- and interspecific associations and species richness), and intrinsic characteristics of individuals (sex and reproductive status) in modulating responses to disturbance. Direct cave disturbance (hunting pressure and human visitation) was the primary driver of neutrophil-to-lymphocyte ratios, with lower ratios associated with increased disturbance, while context-specific factors were more important in explaining total leukocyte count, body condition, and ectoparasite load. Moreover, conditional inference trees revealed complex interactions among human disturbance and modulating factors. Cave complexity often ameliorated individual responses to human disturbance, whereas conspecific abundance often compounded responses. Our study demonstrates the importance of an integrated approach that incorporates environmental and biological context when identifying drivers of physiological responses, and that assesses responses to gradients of direct and indirect disturbance using multiple complementary biomarkers.

A Temperature-Responsive Network Links Cell Shape and Virulence Traits in a Primary Fungal Pathogen

PubMed Central

Beyhan, Sinem; Gutierrez, Matias; Voorhies, Mark; Sil, Anita

2013-01-01

Survival at host temperature is a critical trait for pathogenic microbes of humans. Thermally dimorphic fungal pathogens, including Histoplasma capsulatum, are soil fungi that undergo dramatic changes in cell shape and virulence gene expression in response to host temperature. How these organisms link changes in temperature to both morphologic development and expression of virulence traits is unknown. Here we elucidate a temperature-responsive transcriptional network in H. capsulatum, which switches from a filamentous form in the environment to a pathogenic yeast form at body temperature. The circuit is driven by three highly conserved factors, Ryp1, Ryp2, and Ryp3, that are required for yeast-phase growth at 37°C. Ryp factors belong to distinct families of proteins that control developmental transitions in fungi: Ryp1 is a member of the WOPR family of transcription factors, and Ryp2 and Ryp3 are both members of the Velvet family of proteins whose molecular function is unknown. Here we provide the first evidence that these WOPR and Velvet proteins interact, and that Velvet proteins associate with DNA to drive gene expression. Using genome-wide chromatin immunoprecipitation studies, we determine that Ryp1, Ryp2, and Ryp3 associate with a large common set of genomic loci that includes known virulence genes, indicating that the Ryp factors directly control genes required for pathogenicity in addition to their role in regulating cell morphology. We further dissect the Ryp regulatory circuit by determining that a fourth transcription factor, which we name Ryp4, is required for yeast-phase growth and gene expression, associates with DNA, and displays interdependent regulation with Ryp1, Ryp2, and Ryp3. Finally, we define cis-acting motifs that recruit the Ryp factors to their interwoven network of temperature-responsive target genes. Taken together, our results reveal a positive feedback circuit that directs a broad transcriptional switch between environmental and pathogenic states in response to temperature. PMID:23935449

High need patients receiving targeted entitlements: what responsibilities do they have in primary health care?

PubMed

Buetow, S

2005-05-01

Patient responsibilities in primary health care are controversial and, by comparison, the responsibilities of high need patients are less clear. This paper aims to suggest why high need patients receiving targeted entitlements in primary health care are free to have prima facie special responsibilities; why, given this freedom, these patients morally have special responsibilities; what these responsibilities are, and how publicly funded health systems ought to be able to respond when these remain unmet. It is suggested that the special responsibilities and their place in public policy acquire moral significance as a means to discharge a moral debt, share special knowledge, and produce desirable consequences in regard to personal and collective interests. Special responsibilities magnify ordinary patient responsibilities and require patients not to hesitate regarding attendance for primary health care. Persistent patient disregard of special responsibilities may necessitate limiting the scope of these responsibilities, removing system barriers, or respecifying special rights.

Modeling the growth of Listeria monocytogenes on the surface of smear- or mold-ripened cheese.

PubMed

Schvartzman, M Sol; Gonzalez-Barron, Ursula; Butler, Francis; Jordan, Kieran

2014-01-01

Surface-ripened cheeses are matured by means of manual or mechanical technologies posing a risk of cross-contamination, if any cheeses are contaminated with Listeria monocytogenes. In predictive microbiology, primary models are used to describe microbial responses, such as growth rate over time and secondary models explain how those responses change with environmental factors. In this way, primary models were used to assess the growth rate of L. monocytogenes during ripening of the cheeses and the secondary models to test how much the growth rate was affected by either the pH and/or the water activity (aw) of the cheeses. The two models combined can be used to predict outcomes. The purpose of these experiments was to test three primary (the modified Gompertz equation, the Baranyi and Roberts model, and the Logistic model) and three secondary (the Cardinal model, the Ratowski model, and the Presser model) mathematical models in order to define which combination of models would best predict the growth of L. monocytogenes on the surface of artificially contaminated surface-ripened cheeses. Growth on the surface of the cheese was assessed and modeled. The primary models were firstly fitted to the data and the effects of pH and aw on the growth rate (μmax) were incorporated and assessed one by one with the secondary models. The Logistic primary model by itself did not show a better fit of the data among the other primary models tested, but the inclusion of the Cardinal secondary model improved the final fit. The aw was not related to the growth of Listeria. This study suggests that surface-ripened cheese should be separately regulated within EU microbiological food legislation and results expressed as counts per surface area rather than per gram.

Recognition Memory for Braille or Spoken Words: An fMRI study in Early Blind

PubMed Central

Burton, Harold; Sinclair, Robert J.; Agato, Alvin

2012-01-01

We examined cortical activity in early blind during word recognition memory. Nine participants were blind at birth and one by 1.5 yrs. In an event-related design, we studied blood oxygen level-dependent responses to studied (“old”) compared to novel (“new”) words. Presentation mode was in Braille or spoken. Responses were larger for identified “new” words read with Braille in bilateral lower and higher tier visual areas and primary somatosensory cortex. Responses to spoken “new” words were larger in bilateral primary and accessory auditory cortex. Auditory cortex was unresponsive to Braille words and occipital cortex responded to spoken words but not differentially with “old”/“new” recognition. Left dorsolateral prefrontal cortex had larger responses to “old” words only with Braille. Larger occipital cortex responses to “new” Braille words suggested verbal memory based on the mechanism of recollection. A previous report in sighted noted larger responses for “new” words studied in association with pictures that created a distinctiveness heuristic source factor which enhanced recollection during remembering. Prior behavioral studies in early blind noted an exceptional ability to recall words. Utilization of this skill by participants in the current study possibly engendered recollection that augmented remembering “old” words. A larger response when identifying “new” words possibly resulted from exhaustive recollecting the sensory properties of “old” words in modality appropriate sensory cortices. The uniqueness of a memory role for occipital cortex is in its cross-modal responses to coding tactile properties of Braille. The latter possibly reflects a “sensory echo” that aids recollection. PMID:22251836

Recognition memory for Braille or spoken words: an fMRI study in early blind.

PubMed

Burton, Harold; Sinclair, Robert J; Agato, Alvin

2012-02-15

We examined cortical activity in early blind during word recognition memory. Nine participants were blind at birth and one by 1.5years. In an event-related design, we studied blood oxygen level-dependent responses to studied ("old") compared to novel ("new") words. Presentation mode was in Braille or spoken. Responses were larger for identified "new" words read with Braille in bilateral lower and higher tier visual areas and primary somatosensory cortex. Responses to spoken "new" words were larger in bilateral primary and accessory auditory cortex. Auditory cortex was unresponsive to Braille words and occipital cortex responded to spoken words but not differentially with "old"/"new" recognition. Left dorsolateral prefrontal cortex had larger responses to "old" words only with Braille. Larger occipital cortex responses to "new" Braille words suggested verbal memory based on the mechanism of recollection. A previous report in sighted noted larger responses for "new" words studied in association with pictures that created a distinctiveness heuristic source factor which enhanced recollection during remembering. Prior behavioral studies in early blind noted an exceptional ability to recall words. Utilization of this skill by participants in the current study possibly engendered recollection that augmented remembering "old" words. A larger response when identifying "new" words possibly resulted from exhaustive recollecting the sensory properties of "old" words in modality appropriate sensory cortices. The uniqueness of a memory role for occipital cortex is in its cross-modal responses to coding tactile properties of Braille. The latter possibly reflects a "sensory echo" that aids recollection. Copyright © 2011 Elsevier B.V. All rights reserved.

Barriers to primary care responsiveness to poverty as a risk factor for health.

PubMed

Bloch, Gary; Rozmovits, Linda; Giambrone, Broden

2011-06-29

Poverty is widely recognized as a major determinant of poor health, and this link has been extensively studied and verified. Despite the strong evidentiary link, little work has been done to determine what primary care health providers can do to address their patients' income as a risk to their health. This qualitative study explores the barriers to primary care responsiveness to poverty as a health issue in a well-resourced jurisdiction with near-universal health care insurance coverage. One to one interviews were conducted with twelve experts on poverty and health in primary care in Ontario, Canada. Participants included family physicians, specialist physicians, nurse practitioners, community workers, advocates, policy experts and researchers. The interviews were analysed for anticipated and emergent themes. This study reveals provider- and patient-centred structural, attitudinal, and knowledge-based barriers to addressing poverty as a risk to health. While many of its findings reinforce previous work in this area, this study's findings point to a number of areas front line primary care providers could target to address their patients' poverty. These include a lack of provider understanding of the lived reality of poverty, leading to a failure to collect adequate data about patients' social circumstances, and to the development of inappropriate care plans. Participants also pointed to prejudicial attitudes among providers, a failure of primary care disciplines to incorporate approaches to poverty as a standard of care, and a lack of knowledge of concrete steps providers can take to address patients' poverty. While this study reinforces, in a well-resourced jurisdiction such as Ontario, the previously reported existence of significant barriers to addressing income as a health issue within primary care, the findings point to the possibility of front line primary care providers taking direct steps to address the health risks posed by poverty. The consistent direction and replicability of these findings point to a refocusing of the research agenda toward an examination of interventions to decrease the health impacts of poverty.

A Demonstration of the Subversion Threat: Facing a Critical Responsibility in the Defense of Cyberspace

DTIC Science & Technology

2002-03-01

dependence upon the proper functioning of the system is crucial. Perhaps the closest relative to subversion is the Trojan Horse attack in which the...additional malicious function. There are three primary factors that distinguish this from subversion. First, the Trojan Horse requires a legitimate...user to run it while the artifice in subversion does not. Second, the Trojan Horse program exploits the level of privilege associated with the

Young Tanzanians and the Cinema: A Study of the Effects of Selected Basic Motion Picture Elements and Population Characteristics on Filmic Comprehension of Tanzanian Adolescent Primary School Children.

ERIC Educational Resources Information Center

Giltrow, David Roger

A study was conducted of Tanzanian adolescent school children's responses to filmic elements. The design included a very large sample in a complicated factorial design, varying such factors as color, type of action, background and sound of the film, and the demographic characteristics of the subjects. Results showed that of these variables,…

Using the Advanced Progressive Matrices (Set I) to Assess Fluid Ability in a Short Time Frame: An Item Response Theory-Based Analysis

ERIC Educational Resources Information Center

Chiesi, Francesca; Ciancaleoni, Matteo; Galli, Silvia; Primi, Caterina

2012-01-01

This article is aimed at evaluating the possibility that Set I of the Advanced Progressive Matrices (APM-Set I) can be employed to assess fluid ability in a short time frame. The APM-Set I was administered to a sample of 1,389 primary and secondary school students. Confirmatory factor analysis attested to the unidimensionality of the scale. Item…

IRREVERSIBLE HEMORRHAGIC SHOCK IN GERMFREE RATS

PubMed Central

Zweifach, B. W.; Gordon, H. A.; Wagner, M.; Reyniers, J. A.

1958-01-01

Evidence has been provided that a state of irreversible hemorrhagic shock can be induced in a bacteria-free environment in rats reared under germfree conditions. The response to bleeding, the duration of the hypotensive episode and the pathological changes were the same in the germfree and in normal stock rats. The findings are interpreted as evidence opposed to the concept that bacteria or bacterial products are implicated, as primary factors, in the pathogenicity of shock. PMID:13513911

A phase 1b trial of the combination of the antiangiogenic agent sunitinib and radiation therapy for patients with primary and metastatic central nervous system malignancies.

PubMed

Wuthrick, Evan J; Kamrava, Mitchell; Curran, Walter J; Werner-Wasik, Maria; Camphausen, Kevin A; Hyslop, Terry; Axelrod, Rita; Andrews, David W; Glass, Jon; Machtay, Mitchell; Dicker, Adam P

2011-12-15

In this phase 1 trial, the authors evaluated sunitinib combined with radiation therapy (RT) for the treatment of primary or metastatic central nervous system (CNS) malignancies. Eligible patients had CNS malignancies that required a (minimum) 2-week course of RT. Sunitinib (37.5 mg) was administered daily for the duration of RT with optional treatment extension of 1 month. Urine was collected at 3 time points for correlative biomarker studies. The primary endpoint was acute toxicity defined according to Common Toxicity Criteria version 3. Fifteen patients were enrolled (12 with CNS metastasis and 3 with primary tumors). RT doses ranged from 14 Gray (Gy) to 70 Gy (1.8-3.5 Gy per fraction). Acute toxicities included hematologic, nausea, hyperglycemia, fatigue, hypocalcemia, and diarrhea. Six patients (40%) developed grade ≤ 2 toxicities. Grade 3 toxicities occurred in 7 patients (47%) and included hematologic toxicity, fatigue, deep vein thrombosis, dysphasia, hyperglycemia, and hyponatremia. No grade 3 through 5 hypertensive events or intracerebral hemorrhages occurred. Two grade 5 adverse events attributed to disease progression occurred. The median follow-up was 34.2 months. Two patients (13%) achieved a partial response, 9 patients (60%) had stable disease, and 2 patients (13%) patients had progressive disease. The 6-month progression-free survival rate for patients who had brain metastasis was 58%. Grade 3 hematologic toxicity was correlated with greater changes in vascular endothelial growth factor levels changes between baseline and the completion of RT. Continuous 37.5-mg sunitinib combined with RT in patients who had CNS malignancies yielded acceptable toxicities and adverse events. The current results indicated that changes in urine vascular endothelial growth factor levels are associated with hematologic toxicity, and this association should be analyzed in a larger cohort. The feasibility, safety, and early response results warrant a phase 2 trial. Copyright © 2011 American Cancer Society.

Use of transcriptomics and co-expression networks to analyze the interconnections between nitrogen assimilation and photorespiratory metabolism

PubMed Central

Pérez-Delgado, Carmen M.; Moyano, Tomás C.; García-Calderón, Margarita; Canales, Javier; Gutiérrez, Rodrigo A.; Márquez, Antonio J.; Betti, Marco

2016-01-01

Nitrogen is one of the most important nutrients for plants and, in natural soils, its availability is often a major limiting factor for plant growth. Here we examine the effect of different forms of nitrogen nutrition and of photorespiration on gene expression in the model legume Lotus japonicus with the aim of identifying regulatory candidate genes co-ordinating primary nitrogen assimilation and photorespiration. The transcriptomic changes produced by the use of different nitrogen sources in leaves of L. japonicus plants combined with the transcriptomic changes produced in the same tissue by different photorespiratory conditions were examined. The results obtained provide novel information on the possible role of plastidic glutamine synthetase in the response to different nitrogen sources and in the C/N balance of L. japonicus plants. The use of gene co-expression networks establishes a clear relationship between photorespiration and primary nitrogen assimilation and identifies possible transcription factors connected to the genes of both routes. PMID:27117340

Prevention of Graves' ophthalmopathy.

PubMed

Bartalena, Luigi

2012-06-01

Smoking is the most important risk factor for the occurrence/progression of Graves' ophthalmopathy (GO), as well as for its lower/slower response to immunosuppression. Accordingly, refrain from smoking should be urged, both as primary prevention (removal of risk factors in Graves' patients without GO), secondary prevention (early detection and treatment of asymptomatic/very mild GO) and tertiary prevention (reduction of complications/disability of overt GO). A 6-month course of 200 μg/day sodium selenite can prevent progression of mild GO to more severe GO and is, therefore, a form of secondary prevention and, probably, primary prevention. Correction of thyroid dysfunction and stable maintenance of euthyroidism are important preventive measures. The optimal treatment for hyperthyroidism in patients with GO is uncertain, because evidence demonstrating the superiority of antithyroid drugs over thyroid ablation (radioiodine, thyroidectomy, or both) is lacking. If radioiodine is used, low-dose steroid prophylaxis is recommended, particularly in smokers, to prevent radioiodine-associated GO progression. Copyright © 2011 Elsevier Ltd. All rights reserved.

Binding and Translocation of Termination Factor Rho Studied at the Single-Molecule Level

PubMed Central

Koslover, Daniel J.; Fazal, Furqan M.; Mooney, Rachel A.; Landick, Robert; Block, Steven M.

2012-01-01

Rho termination factor is an essential hexameric helicase responsible for terminating 20–50% of all mRNA synthesis in E. coli. We used single- molecule force spectroscopy to investigate Rho-RNA binding interactions at the Rho- utilization (rut) site of the ? tR1 terminator. Our results are consistent with Rho complexes adopting two states, one that binds 57 ±2 nucleotides of RNA across all six of the Rho primary binding sites, and another that binds 85 ±2 nucleotides at the six primary sites plus a single secondary site situated at the center of the hexamer. The single-molecule data serve to establish that Rho translocates 5′-to-3′ towards RNA polymerase (RNAP) by a tethered-tracking mechanism, looping out the intervening RNA between the rut site and RNAP. These findings lead to a general model for Rho binding and translocation, and establish a novel experimental approach that should facilitate additional single- molecule studies of RNA-binding proteins. PMID:22885804

Caries prevalence in different racial groups of schoolchildren in West Malaysia.

PubMed

Yassin, I; Low, T

1975-08-01

A dental health survey of 15,197 schoolchildren age 6-18 years was conducted in West Malaysia. The caries experience in the permanent teeth of the three racial groups, namely Malay, Chinese and Indian/Pakistani, showed a distinct variation. The prevalence was highest among the Chinese children, being about twice that of the Malay and Indian/Pakistani children. In the primary dentition, however, the caries experience in the three racial groups was comparable. An analysis of the factors contributing to the racial variation showed that dietary influence was not the only factor responsible. The possibility of a racial variation in caries susceptibility has been postulated. In the primary dentition the similar caries experience observed in the three groups of children was most probably due to the widespread occurrence of rampant caries which would heavily weight the dift score of the children in all three groups. The need to fluoridate the public water supply as an effective preventive measure is emphasized.

A decade of insights into grassland ecosystem responses to global environmental change

USGS Publications Warehouse

Borer, Elizabeth T.; Grace, James B.; Harpole, W. Stanley; MacDougall, Andrew S.; Seabloom, Eric W.

2017-01-01

Earth’s biodiversity and carbon uptake by plants, or primary productivity, are intricately interlinked, underlie many essential ecosystem processes, and depend on the interplay among environmental factors, many of which are being changed by human activities. While ecological theory generalizes across taxa and environments, most empirical tests of factors controlling diversity and productivity have been observational, single-site experiments, or meta-analyses, limiting our understanding of variation among site-level responses and tests of general mechanisms. A synthesis of results from ten years of a globally distributed, coordinated experiment, the Nutrient Network (NutNet), demonstrates that species diversity promotes ecosystem productivity and stability, and that nutrient supply and herbivory control diversity via changes in composition, including invasions of non-native species and extinction of native species. Distributed experimental networks are a powerful tool for tests and integration of multiple theories and for generating multivariate predictions about the effects of global changes on future ecosystems.

Variations in brain defects result from cellular mosaicism in the activation of heat shock signalling.

PubMed

Ishii, Seiji; Torii, Masaaki; Son, Alexander I; Rajendraprasad, Meenu; Morozov, Yury M; Kawasawa, Yuka Imamura; Salzberg, Anna C; Fujimoto, Mitsuaki; Brennand, Kristen; Nakai, Akira; Mezger, Valerie; Gage, Fred H; Rakic, Pasko; Hashimoto-Torii, Kazue

2017-05-02

Repetitive prenatal exposure to identical or similar doses of harmful agents results in highly variable and unpredictable negative effects on fetal brain development ranging in severity from high to little or none. However, the molecular and cellular basis of this variability is not well understood. This study reports that exposure of mouse and human embryonic brain tissues to equal doses of harmful chemicals, such as ethanol, activates the primary stress response transcription factor heat shock factor 1 (Hsf1) in a highly variable and stochastic manner. While Hsf1 is essential for protecting the embryonic brain from environmental stress, excessive activation impairs critical developmental events such as neuronal migration. Our results suggest that mosaic activation of Hsf1 within the embryonic brain in response to prenatal environmental stress exposure may contribute to the resulting generation of phenotypic variations observed in complex congenital brain disorders.

Equine recurrent uveitis: Human and equine perspectives.

PubMed

Malalana, Fernando; Stylianides, Amira; McGowan, Catherine

2015-10-01

Equine recurrent uveitis (ERU) is a spontaneous disease characterised by repeated episodes of intraocular inflammation. The epidemiology of ERU has not been fully elucidated, but the condition appears to be much more common in horses than is recurrent uveitis in humans, especially in certain breeds and geographical regions. Both humans and horses show a similarly altered immune response and a marked autoimmune response as the primary disease pathophysiology. However, an inciting cause is not always clear. Potential inciting factors in horses include microbial agents such as Leptospira spp. Microbial factors and genetic predisposition to the disease may provide clues as to why the horse appears so susceptible to this disease. The aim of this review is to discuss the immunology and genetics of ERU, compare the disease in horses with autoimmune anterior uveitis in humans, and discuss potential reasons for the increased prevalence in the horse. Copyright © 2015 Elsevier Ltd. All rights reserved.

Regional versus local drivers of water quality in the Windermere catchment, Lake District, UK: the dominant influence of wastewater pollution over the past 200 years.

PubMed

Moorhouse, Heather L; McGowan, Suzanne; Taranu, Zofia E; Gregory-Eaves, Irene; Leavitt, Peter R; Jones, Matthew D; Barker, Philip; Brayshaw, Susan A

2018-05-10

Freshwater ecosystems are threatened by multiple anthropogenic stressors acting over different spatial and temporal scales, resulting in toxic algal blooms, reduced water quality, and hypoxia. However, while catchment characteristics act as a 'filter' modifying lake response to disturbance, little is known of the relative importance of different drivers and possible differentiation in the response of upland remote lakes in comparison to lowland, impacted lakes. Moreover, many studies have focussed on single lakes rather than looking at responses across a set of individual, yet connected lake basins. Here we used sedimentary algal pigments as an index of changes in primary producer assemblages over the last ~200 years in a northern temperate watershed consisting of 11 upland and lowland lakes within the Lake District, UK, to test our hypotheses about landscape drivers. Specifically, we expected that the magnitude of change in phototrophic assemblages would be greatest in lowland rather than upland lakes due to more intensive human activities in the watersheds of the former (agriculture, urbanization). Regional parameters, such as climate dynamics, would be the predominant factors regulating lake primary producers in remote upland lakes and thus, synchronize the dynamic of primary producer assemblages in these basins. We found broad support for the hypotheses pertaining to lowland sites as wastewater treatment was the main predictor of changes to primary producer assemblages in lowland lakes. In contrast, upland headwaters responded weakly to variation in atmospheric temperature, and dynamics in primary producers across upland lakes were asynchronous. Collectively, these findings show that nutrient inputs from point sources overwhelm climatic controls of algae and nuisance cyanobacteria, but highlights that large-scale stressors do not always initiate coherent regional lake response. Further, a lake's position in its landscape, its connectivity and proximity to point nutrients are important determinants of changes in production and composition of phototrophic assemblages. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Landscape level influence: aquatic primary production in the Colorado River of Glen and Grand canyons

NASA Astrophysics Data System (ADS)

Yard, M. D.; Kennedy, T.; Yackulic, C. B.; Bennett, G. E.

2012-12-01

Irregular features common to canyon-bound regions intercept solar incidence (photosynthetic photon flux density [PPFD: μmol m-2 s-1]) and can affect ecosystem energetics. The Colorado River in Grand Canyon is topographically complex, typical of most streams and rivers in the arid southwest. Dam-regulated systems like the Colorado River have reduced sediment loads, and consequently increased water transparency relative to unimpounded rivers; however, sediment supply from tributaries and flow regulation that affects erosion and subsequent sediment transport, interact to create spatial and temporal variation in optical conditions in this river network. Solar incidence and suspended sediment loads regulate the amount of underwater light available for aquatic photosynthesis in this regulated river. Since light availability is depth dependent (Beer's law), benthic algae is often exposed to varying levels of desiccation or reduced light conditions due to daily flow regulation, additional factors that further constrain aquatic primary production. Considerable evidence suggests that the Colorado River food web is now energetically dependent on autotrophic production, an unusual condition since large river foodwebs are typically supported by allochthonous carbon synthesized and transported from terrestrial environments. We developed a mechanistic model to account for these regulating factors to predict how primary production might be affected by observed and alternative flow regimes proposed as part of ongoing adaptive management experimentation. Inputs to our model include empirical data (suspended sediment and temperature), and predictive relationships: 1) solar incidence reaching the water surface (topographic complexity), 2) suspended sediment-light extinction relationships (optical properties), 3) unsteady flow routing model (stage-depth relationship), 4) channel morphology (photosynthetic area), and 5) photosynthetic-irradiant response for dominant algae (Cladophora glomerata and associated epiphytes). Initial findings suggest that aquatic primary production varies spatially and temporally in response to natural processes occurring at varying spatial scales and that flow regulation per se has only a minor effect on primary production. All of these physical drivers combined are likely to structure the abundance, distribution, and interaction of aquatic biota found in this ecosystem.

Urine epidermal growth factor, monocyte chemoattractant protein-1 or their ratio as predictors of complete remission in primary glomerulonephritis.

PubMed

Chanrat, Eakkapat; Worawichawong, Supanat; Radinahamed, Piyanuch; Sathirapongsasuti, Nuankanya; Nongnuch, Arkom; Assanatham, Montira; Udomsubpayakul, Umaporn; Kitiyakara, Chagriya

2018-04-01

The balance of several cytokines likely influences the resolution of glomerulonephritis. Monocyte chemoattractant protein-1(MCP-1) is a chemokine that promotes renal inflammation whereas epidermal growth factor (EGF) stimulates protective responses. Previously, high urine MCP-1(MCP-1) and low urine EGF (EGF) levels were found to be associated with tubulointerstitial fibrosis, but there is limited information on the value of these mediators as predictors of therapeutic responses or long term outcome in primary glomerulonephritis. To determine the performance of urine EGF, MCP-1 or their ratio at baseline as biomarkers to predict complete remission, and the relationship of these mediators with subsequent renal function 24 months later in primary glomerulonephritis. This is a prospective study of patients with biopsy-proven primary glomerulonephritis. Baseline urine samples were collected at biopsy before therapy. MCP-1 and EGF were analyzed by enzyme-linked immunosorbent assays and expressed as a ratio to urine creatinine (ng/mgCr) or as EGF/MCP-1 ratio (ng/ng). Proteinuria and estimated glomerular filtration rate (eGRF) were monitored after therapy. Complete remission (CR) was defined as proteinuria ≤ 0.3 g/gCr. Median follow-up was 20 months. Of all patients (n = 74), 38 patients (51.4%) subsequently achieved CR. Baseline urine EGF and EGF/MCP-1 levels were significantly higher in CR compared to Not CR. By contrast, MCP-1 was not different. High EGF (EGF > 75 ng/mgCr) was a significant predictor (OR 2.28) for CR by multivariate analysis after adjusting for proteinuria, blood pressure, baseline eGFR. In patients who completed 24 months follow-up (n = 43), baseline EGF correlated inversely with proteinuria and positively with eGFR at 24 months. High urine EGF level is a promising biomarker of CR. Baseline EGF levels correlated with kidney function at 2 years. EGF/MCP-1 was not superior to EGF alone. Further studies are necessary to determine the role of urine EGF as a guide to therapy in primary GN. Copyright © 2018 Elsevier Ltd. All rights reserved.

Altered Cytokine Gene Expression in Peripheral Blood Monocytes across the Menstrual Cycle in Primary Dysmenorrhea: A Case-Control Study

PubMed Central

Ma, Hongyue; Hong, Min; Duan, Jinao; Liu, Pei; Fan, Xinsheng; Shang, Erxin; Su, Shulan; Guo, Jianming; Qian, Dawei; Tang, Yuping

2013-01-01

Primary dysmenorrhea is one of the most common gynecological complaints in young women, but potential peripheral immunologic features underlying this condition remain undefined. In this paper, we compared 84 common cytokine gene expression profiles of peripheral blood mononuclear cells (PBMCs) from six primary dysmenorrheic young women and three unaffected controls on the seventh day before (secretory phase), and the first (menstrual phase) and the fifth (regenerative phase) days of menstruation, using a real-time PCR array assay combined with pattern recognition and gene function annotation methods. Comparisons between dysmenorrhea and normal control groups identified 11 (nine increased and two decreased), 14 (five increased and nine decreased), and 15 (seven increased and eight decreased) genes with ≥2-fold difference in expression (P<0.05) in the three phases of menstruation, respectively. In the menstrual phase, genes encoding pro-inflammatory cytokines (IL1B, TNF, IL6, and IL8) were up-regulated, and genes encoding TGF-β superfamily members (BMP4, BMP6, GDF5, GDF11, LEFTY2, NODAL, and MSTN) were down-regulated. Functional annotation revealed an excessive inflammatory response and insufficient TGF-β superfamily member signals with anti-inflammatory consequences, which may directly contribute to menstrual pain. In the secretory and regenerative phases, increased expression of pro-inflammatory cytokines and decreased expression of growth factors were also observed. These factors may be involved in the regulation of decidualization, endometrium breakdown and repair, and indirectly exacerbate primary dysmenorrhea. This first study of cytokine gene expression profiles in PBMCs from young primary dysmenorrheic women demonstrates a shift in the balance between expression patterns of pro-inflammatory cytokines and TGF-β superfamily members across the whole menstrual cycle, underlying the peripheral immunologic features of primary dysmenorrhea. PMID:23390521

Satisfaction of Patients Attending in Primary Healthcare Centers in Riyadh, Saudi Arabia: A Random Cross-Sectional Study.

PubMed

Almutairi, Khalid M

2017-06-01

This study aims to determine the level of satisfaction of patients who visit primary healthcare centers in Riyadh, Saudi Arabia. The investigation was a cross-sectional study conducted in twenty randomly selected primary healthcare centers in Riyadh, Saudi Arabia from October to December 2014. A descriptive data analysis was performed. Eligible participants had visited at least one of the selected primary healthcare centers within the past 12 months. A total of 1741 participants completed the survey, providing a response rate of 87 % (43 % male, 57 % female). The highest satisfaction rates were in the following areas: comprehensiveness and coordination 76.2 % (95 % CI 74.8 ± 77.5), communication 72.7 % (95 % CI 71.3 ± 74) and attitude of staff 73.4 % (95 % CI 72.1 ± 74.8) The areas of greatest concern expressed by the participants were the length of the wait and the quality of the facility 55.4 % (95 % CI 53.3 ± 57.5), 50.5 % (95 % CI 48.3 ± 52.7), respectively. The majority of the patients attending primary healthcare centers in Riyadh showed high levels of satisfaction; however, there are still some factors that need to be considered and improved upon. These include the accessibility of primary healthcare centers as well as waiting time of patients. The results of the current study showed relative improvement in other factors such as comprehensiveness and coordination, communication and attitude of staff. The level of satisfaction of patients and stakeholders shows the progress of the quality of care in healthcare facilities in Riyadh, Saudi Arabia.

Dynamic Analysis of Darrieus Vertical Axis Wind Turbine Rotors

NASA Technical Reports Server (NTRS)

Lobitz, D. W.

1981-01-01

The dynamic response characteristics of the vertical axis wind turbine (VAWT) rotor are important factors governing the safety and fatigue life of VAWT systems. The principal problems are the determination of critical rotor speeds (resonances) and the assessment of forced vibration response amplitudes. The solution to these problems is complicated by centrifugal and Coriolis effects which can have substantial influence on rotor resonant frequencies and mode shapes. The primary tools now in use for rotor analysis are described and discussed. These tools include a lumped spring mass model (VAWTDYN) and also finite-element based approaches. The accuracy and completeness of current capabilities are also discussed.

Effects of Corporate Social Responsibility and Governance on Its Credit Ratings

PubMed Central

Kim, Dong-young

2014-01-01

This study reviews the impact of corporate social responsibility (CSR) and corporate governance on its credit rating. The result of regression analysis to credit ratings with relevant primary independent variables shows that both factors have significant effects on it. As we have predicted, the signs of both regression coefficients have a positive sign (+) proving that corporates with excellent CSR and governance index (CGI) scores have higher credit ratings and vice versa. The results show nonfinancial information also may have effects on corporate credit rating. The investment on personal data protection could be an example of CSR/CGI activities which have positive effects on corporate credit ratings. PMID:25401134

Effects of corporate social responsibility and governance on its credit ratings.

PubMed

Kim, Dong-young; Kim, JeongYeon

2014-01-01

This study reviews the impact of corporate social responsibility (CSR) and corporate governance on its credit rating. The result of regression analysis to credit ratings with relevant primary independent variables shows that both factors have significant effects on it. As we have predicted, the signs of both regression coefficients have a positive sign (+) proving that corporates with excellent CSR and governance index (CGI) scores have higher credit ratings and vice versa. The results show nonfinancial information also may have effects on corporate credit rating. The investment on personal data protection could be an example of CSR/CGI activities which have positive effects on corporate credit ratings.

Simulator Investigations of the Problems of Flying a Swept-Wing Transport Aircraft in Heavy Turbulence

NASA Technical Reports Server (NTRS)

Bray, Richard S.; Larsen, William E.

1965-01-01

An investigation of several factors which may contribute to the problem of piloting jet transport aircraft in heavy turbulence was conducted by using a piloted simulator that included the most significant airplane response and cockpit vibrations induced by rough air. Results indicated that the primary fuselage structural frequency contributed significantly to a distracting cockpit environment, and there was obtained evidence of severely reduced instrument flight proficiency during simulated maneuvering flight in heavy turbulence. It is concluded that the addition of similar rough-air response capabilities to training simulators would be of value in pilot indoctrination in turbulent-flight procedures.

Root Bending Is Antagonistically Affected by Hypoxia and ERF-Mediated Transcription via Auxin Signaling1[OPEN

PubMed Central

Eysholdt-Derzsó, Emese

2017-01-01

When plants encounter soil water logging or flooding, roots are the first organs to be confronted with reduced gas diffusion resulting in limited oxygen supply. Since roots do not generate photosynthetic oxygen, they are rapidly faced with oxygen shortage rendering roots particularly prone to damage. While metabolic adaptations to low oxygen conditions, which ensure basic energy supply, have been well characterized, adaptation of root growth and development have received less attention. In this study, we show that hypoxic conditions cause the primary root to grow sidewise in a low oxygen environment, possibly to escape soil patches with reduced oxygen availability. This growth behavior is reversible in that gravitropic growth resumes when seedlings are returned to normoxic conditions. Hypoxic root bending is inhibited by the group VII ethylene response factor (ERFVII) RAP2.12, as rap2.12-1 seedlings show exaggerated primary root bending. Furthermore, overexpression of the ERFVII member HRE2 inhibits root bending, suggesting that primary root growth direction at hypoxic conditions is antagonistically regulated by hypoxia and hypoxia-activated ERFVIIs. Root bending is preceded by the establishment of an auxin gradient across the root tip as quantified with DII-VENUS and is synergistically enhanced by hypoxia and the auxin transport inhibitor naphthylphthalamic acid. The protein abundance of the auxin efflux carrier PIN2 is reduced at hypoxic conditions, a response that is suppressed by RAP2.12 overexpression, suggesting antagonistic control of auxin flux by hypoxia and ERFVII. Taken together, we show that hypoxia triggers an escape response of the primary root that is controlled by ERFVII activity and mediated by auxin signaling in the root tip. PMID:28698356

Systemic therapy of aggressive fibromatosis in children and adolescents: Report of the Cooperative Weichteilsarkom Studiengruppe (CWS).

PubMed

Sparber-Sauer, Monika; Seitz, Guido; von Kalle, Thekla; Vokuhl, Christian; Leuschner, Ivo; Scheer, Monika; Münter, Marc; Ljungman, Gustaf; Bielack, Stefan S; Niggli, Felix; Ladenstein, Ruth; Klingebiel, Thomas; Fuchs, Joerg; Koscielniak, Ewa

2018-05-01

Treatment algorithms for patients with aggressive fibromatosis (AF) are challenging. There are limited data available about the use of systemic therapy (ST) in pediatric patients with AF. Patient-, tumor-, and treatment-related factors of 90 children and adolescents with AF treated on multiple prospective trials of the Cooperative Weichteilsarkom Studiengruppe (1981-2015) were analyzed with focus on response and outcome of ST. Median age was 9.48 years (0.02-18.05). Primary resection was performed in 54 patients and ST was administered in 29 of 54 patients because of disease progression or relapse. In 35 patients, ST was the initial treatment modality. A secondary resection was performed in 21 of 35 patients after ST. A total of 64 patients received ST, mainly methotrexate and vinblastine (40%) with a median duration of 380 days. The most frequent radiological response to ST was stable disease at 3 months (39%) and partial response at 6 months (53%). Radiotherapy was administered to 15 of 90 patients. One patient remained on observation only. The 5-year overall survival was 100% and the 5-year event-free survival (EFS) was 44%. Patients who had a primary resection showed a 5-year EFS of 35% versus 59% in patients who had received primary ST (P = 0.08). Functional deficiencies as long-term sequelae following resection occurred in 11 patients. At a median follow-up of 5.05 years (0.25-14.88), complete remission was achieved in 51 patients and partial remission in 28 patients. ST seems appropriate if a primary complete resection is not feasible and at relapse/progression after resection. © 2018 Wiley Periodicals, Inc.

Epidermal growth factor receptor (EGFr) status associated with failure of primary endocrine therapy in elderly postmenopausal patients with breast cancer.

PubMed Central

Nicholson, S.; Halcrow, P.; Sainsbury, J. R.; Angus, B.; Chambers, P.; Farndon, J. R.; Harris, A. L.

1988-01-01

We have used primary endocrine therapy for 61 elderly women with operable breast cancer (median age 77 years). Eleven patients (18%) had complete and 24 (39%) partial tumour regression, 12 (20%) had stable disease for a minimum of six months and 14 (23%) no response. Salvage surgery was undertaken in the 14 with no response and 8/9 with progressive disease following initial response, thus samples were available from relapse patients only. Assays for EGFr (two point radioreceptor assay) and oestrogen receptors (ER) (dextran coated charcoal method and an immunohistochemical method) were performed on 20/22 patients. Ten of these 20 tumours were EGFr+ (greater than 10 fmol mg-1 binding) and 9/13 patients progressing within six months had EGFr+ tumours. 15/22 were available for ER evaluation and there was no such association with ER status. EGFr status was also associated with early recurrence after surgery and death in the endocrine failure group (P less than 0.005 and P less than 0.05 respectively). Of a control population of 33 patients (median age 72 years) treated by primary surgery, only 6 were EGFr+. In this group early relapse was predicted by EGFr status, but not by ER status (median disease free survival for EGFr+ patients 15 months, and for EGFr- patients 40 months, P less than 0.01, logrank test). There was a significantly higher proportion of EGFr+ tumours in the endocrine failure group compared with the control population (P less than 0.001). EGFr status is a marker for rapid early progression on primary endocrine therapy and the development of non-excisional methods of EGFr analysis would allow better directed therapeutic decisions. PMID:3224082

The Significance of the Stromal Response in Breast Cancer: An Immunohistochemical Study of Myofibroblasts in Primary and Metastatic Breast Cancer.

PubMed

Roozdar, Alale; Hayes, Malcolm M; Pourseyedei, Bahram; Zeinalinejad, Hamid; Shamsi Meymandi, Manzumeh; Dabiri, Bahram; Dabiri, Shahriar

2018-05-01

Gene expression profiling of breast cancer has demonstrated the importance of stromal response in determining the prognosis of invasive breast cancer. The host response to breast cancer is of increasing interest to pathologists and may be a future focus for novel pharmacological treatments. This study describes the pattern of distribution of stromal myofibroblasts using immunostains for CD10 and smooth muscle actin (SMA) in 50 primary breast cancers and their matched nodal metastases (68.6% nodes positive and 31.4% nodes negative). The stroma within the tumor (intratumoral) and at the advancing tumor edge (peri-tumoral) was studied in both primary and nodal sites. A simple quantitative scoring system was employed for both immunostains. The correlation between expression of these markers by stromal cells and standard pathological prognostic factors of stage, grade, hormone receptor and Her-2 status was analysed. SMA-positive stromal cells were more abundant in peri-tumoral stroma compared with intratumoral stroma in both primary and metastatic lesions. SMA expression in the lymph node metastases showed a significant correlation with tumor stage. SMA expression in peri-tumoral stroma correlated with Her-2 status. The results of this study suggest that myofibroblasts, particularly those expressing SMA, might potentiate the progression of the carcinomatous process especially in nodal metastases. Thus these cells may be a potential therapeutic target. © 2018 The Author(s). This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Factors affecting physicians' responses to patients' requests for antidepressants: focus group study.

PubMed

Tentler, Aleksey; Silberman, Jordan; Paterniti, Debora A; Kravitz, Richard L; Epstein, Ronald M

2008-01-01

The ways in which patients' requests for antidepressants affect physicians' prescribing behavior are poorly understood. To describe physicians' affective and cognitive responses to standardized patients' (SPs) requests for antidepressants, as well as the attitudinal and contextual factors influencing prescribing behavior. Focus group interviews and brief demographic questionnaires. Twenty-two primary care physicians in 6 focus groups; all had participated in a prior RCT of the influence of patients' requests on physicians' prescribing. Iterative review of interview transcripts, involving qualitative coding and thematic analysis. Physicians participating in the focus groups were frequently unaware of and denied the degree to which their thinking was biased by patient requests, but were able to recognize such biases after facilitated reflection. Common affective responses included annoyance and empathy. Common cognitive reactions resulted in further diagnostic inquiry or in acquiescing to the patient's demands to save time or build the patient-clinician relationship. Patients' requests for medication prompted the participants to err on the side of overtreating versus careful review of clinical indications. Lack of time and participants' attitudes--toward the role of the patient and the pharmaceutical ads--also influenced their responses, prompting them to interpret patient requests as diagnostic clues or opportunities for efficiency. This study provides a taxonomy of affective and cognitive responses to patients' requests for medications and the underlying attitudes and contextual factors influencing them. Improved capacity for moment-to-moment self-awareness during clinical reasoning processes may increase the appropriateness of prescribing.

Cytokinin induces genome-wide binding of the type-B response regulator ARR10 to regulate growth and development in Arabidopsis

PubMed Central

Zubo, Yan O.; Blakley, Ivory Clabaugh; Yamburenko, Maria V.; Worthen, Jennifer M.; Street, Ian H.; Franco-Zorrilla, José M.; Zhang, Wenjing; Raines, Tracy; Kieber, Joseph J.; Loraine, Ann E.

2017-01-01

The plant hormone cytokinin affects a diverse array of growth and development processes and responses to the environment. How a signaling molecule mediates such a diverse array of outputs and how these response pathways are integrated with other inputs remain fundamental questions in plant biology. To this end, we characterized the transcriptional network initiated by the type-B ARABIDOPSIS RESPONSE REGULATORs (ARRs) that mediate the cytokinin primary response, making use of chromatin immunoprecipitation sequencing (ChIP-seq), protein-binding microarrays, and transcriptomic approaches. By ectopic overexpression of ARR10, Arabidopsis lines hypersensitive to cytokinin were generated and used to clarify the role of cytokinin in regulation of various physiological responses. ChIP-seq was used to identify the cytokinin-dependent targets for ARR10, thereby defining a crucial link between the cytokinin primary-response pathway and the transcriptional changes that mediate physiological responses to this phytohormone. Binding of ARR10 was induced by cytokinin with binding sites enriched toward the transcriptional start sites for both induced and repressed genes. Three type-B ARR DNA-binding motifs, determined by use of protein-binding microarrays, were enriched at ARR10 binding sites, confirming their physiological relevance. WUSCHEL was identified as a direct target of ARR10, with its cytokinin-enhanced expression resulting in enhanced shooting in tissue culture. Results from our analyses shed light on the physiological role of the type-B ARRs in regulating the cytokinin response, mechanism of type-B ARR activation, and basis by which cytokinin regulates diverse aspects of growth and development as well as responses to biotic and abiotic factors. PMID:28673986

Use of a LiESP/QA-21 Vaccine (CaniLeish) Stimulates an Appropriate Th1-Dominated Cell-Mediated Immune Response in Dogs

PubMed Central

Moreno, Javier; Vouldoukis, Ioannis; Martin, Virginie; McGahie, David; Cuisinier, Anne-Marie; Gueguen, Sylvie

2012-01-01

Canine leishmaniasis is an important zoonotic disease of dogs. The clinical outcome of infection is variable, with the efficiency of the immune response being the key determining factor. There is now a general consensus that a predominant Th1 immune profile in an overall mixed Th1/Th2 response is associated with resistance in dogs, and the absence of a strong Th1 influence is associated with a progression to clinical disease. As a result, there has been a growing demand for vaccines that can induce a specific, strong Th1 response. In this study, we measured the impact of a primary course of a newly available LiESP/QA-21 vaccine on selected humoral and cellular markers of the canine immune response during the onset of immunity. All vaccinated dogs developed a humoral response characterised by IgG2 production. More importantly, vaccinated dogs developed significantly stronger cell-mediated immunity responses than did control dogs. Vaccination induced specific cellular reactivity to soluble Leishmania antigens, with a Leishmania-specific lymphoproliferation (p = 0.0072), characterised by an increased population of T lymphocytes producing IFN-γ (p = 0.0021) and a significant ability of macrophages to reduce intracellular parasite burdens in vitro after co-culture with autologous lymphocytes (p = 0.0014). These responses were correlated with induction of the NOS pathway and production of NO derivatives, which has been shown to be an important leishmanicidal mechanism. These results confirm that vaccination with LiESP/QA-21 induces an appropriate Th1-profile cell-mediated response within three weeks of completing the primary course, and that this response effectively reduces the parasite load in pre-infected macrophages in vitro. PMID:22724031

Simulated effects of existing and proposed surface-water impoundments and gas-well pads on streamflow and suspended sediment in the Cypress Creek watershed, Arkansas

USGS Publications Warehouse

Hart, Rheannon M.

2014-01-01

The Arkansas Natural Resources Commission and the Arkansas Department of Environmental Quality list suspended sediment from “poor pastures” as a primary source of nonpoint-source pollution in north-central Arkansas, but unpaved (gravel) roads are another important source of suspended sediment. Because of the high sediment-loading rates associated with gravel roads and the large amount of pasture within the watershed, the factors most responsible for suspended sediment within the Cypress Creek watershed are likely associated more with the pastureland and gravel roads, than factors associated with gas-well pads/pipelines.

Factors influencing the patient with rheumatoid arthritis in their decision to seek podiatry.

PubMed

Blake, A; Mandy, P J; Stew, G

2013-12-01

Despite the level of foot involvement in rheumatoid arthritis (RA), and the literature to support early assessment of foot care needs, local referral of patients to podiatry has been occurring too late to instigate certain preventative interventions. Preliminary fieldwork has highlighted that the primary responsibility for the instigation of this lies with the patient. The present study describes the factors that influence the patient with RA in their decision to self-report foot problems. A case study research strategy was employed. Nine patients attending the outpatient rheumatology department participated in the study and data were gathered through semi-structured interviews. This information was analysed using a framework approach. The key themes derived from the data suggested that there are a variety of factors influencing the patient's decision to self-report foot concerns. Some will act to encourage the action and others will act to oppose it. Other factors can influence the decision either way, depending on the individual patient (psychological state, previous experience, body image changes). In addition, age, gender, and cultural and social aspects are also significant. Due to the multitude of factors influencing the individual's decision to seek help, the patient cannot be given sole responsibility for their foot health if we wish to achieve timely and appropriate podiatry, as recommended in the literature. Responsibility should be three-way; the patient, the members of the rheumatology team and, once in the podiatry service, the podiatrist should maintain this. Copyright © 2013 John Wiley & Sons, Ltd.

Controls on Characteristics of Event-based Catchment Flood Response over Continental United States

NASA Astrophysics Data System (ADS)

Shen, X.; Mei, Y.; Nikolopoulos, E. I.; Anagnostou, E. N.

2017-12-01

Understanding the primary drivers of regional flood characteristics is of utmost importance for the development of flood early warning system. Many studies have dedicated their efforts on this topic, but the majority of these works is limited in terms of either the size of event population or the extent of their study domain. This prevents us from drawing a comprehensive understanding of the primary factors controlling the variability of catchment flood response across different hydroclimatic regimes and basin geomorphologies. In this study, we render an exhaustive analysis that includes the effect of climate, hydrometeorology, geomorphology, land cover and initial wetness conditions on the catchment's flood response for 318,000 flood events distributed across 5,900 catchments (basin scales ranging from 1 to 106 km2) of the Continental United States (CONUS) over a 10-year (2002 to 2013) period. Event runoff coefficients, response time lag and hydrograph shape are used as diagnostic variables to represent catchment flood response. Our results indicate different distributions of runoff coefficient over different climate regions and seasons. The magnitude of runoff coefficient increases as function of initial basin wetness condition and rainfall depth. Opposite patterns are found for the actual evapotranspiration rate and baseflow index. On the other hand, response time lag is controlled by the relief ratio of the basins and the mean flow length of the events; hydrograph shape reveals increasing trend with soil moisture condition and relief ratio.

Association Between Response to Acid-Suppression Therapy and Efficacy of Antireflux Surgery in Patients With Extraesophageal Reflux.

PubMed

Krill, Joseph T; Naik, Rishi D; Higginbotham, Tina; Slaughter, James C; Holzman, Michael D; Francis, David O; Garrett, C Gaelyn; Vaezi, Michael F

2017-05-01

The effectiveness of antireflux surgery (ARS) varies among patients with extraesophageal manifestations of gastroesophageal reflux disease (GERD). By studying a cohort of patients with primary extraesophageal symptoms and abnormal physiologic markers for GERD, we aimed to identify factors associated with positive outcomes from surgery, and compare outcomes to those with typical esophageal manifestations of GERD. We performed a retrospective cohort study to compare adult patients with extraesophageal and typical reflux symptoms who underwent de novo ARS from 2004 through 2012 at a tertiary care center. All 115 patients (79 with typical GERD and 36 with extraesophageal manifestations of GERD) had evidence of abnormal distal esophageal acid exposure based on pH testing or endoscopy. The principle outcome was time to primary symptom recurrence after surgery, based on patient reports of partial or total recurrence of symptoms at follow-up visits. Patients were followed up for a median duration of 66 months (interquartile range, 52-77 mo). The median time to recurrence of symptoms in the overall cohort was 68 months (11.5 months in the extraesophageal cohort vs >132 months in the typical cohort). Symptom recurrence after ARS was associated with having primarily extraesophageal symptoms (adjusted hazard ratio, 2.34; 95% confidence interval, 1.31-4.17) and poor preoperative symptom response to acid-suppression therapy (AST) (hazard ratio, 3.85; 95% confidence interval, 2.05-7.22). Patients with primary extraesophageal symptoms who had a full or partial preoperative AST response experienced lower rates of symptom recurrence compared to patients with poor AST response (P < .01). The rate of symptom recurrence was lowest among patients with primary typical reflux symptoms who had a partial or full symptom response to AST (P < .01). The severity of acid reflux on pH testing, symptom indices, severity of esophagitis, and hiatal hernia size were not associated with symptom response. In a retrospective study, we found the effectiveness of ARS to be less predictable in patients with extraesophageal symptoms of GERD than in patients with typical GERD. Response to AST before surgery was associated with ARS effectiveness in patients with extraesophageal reflux symptoms. Caution should be exercised when advocating ARS for patients with extraesophageal symptoms that do not respond to AST. Copyright © 2017 AGA Institute. Published by Elsevier Inc. All rights reserved.

The headache under-response to treatment (HURT) questionnaire, an outcome measure to guide follow-up in primary care: development, psychometric evaluation and assessment of utility.

PubMed

Steiner, T J; Buse, D C; Al Jumah, M; Westergaard, M L; Jensen, R H; Reed, M L; Prilipko, L; Mennini, F S; Láinez, M J A; Ravishankar, K; Sakai, F; Yu, S-Y; Fontebasso, M; Al Khathami, A; MacGregor, E A; Antonaci, F; Tassorelli, C; Lipton, R B

2018-02-14

Headache disorders are both common and burdensome but, given the many people affected, provision of health care to all is challenging. Structured headache services based in primary care are the most efficient, equitable and cost-effective solution but place responsibility for managing most patients on health-care providers with limited training in headache care. The development of practical management aids for primary care is therefore a purpose of the Global Campaign against Headache. This manuscript presents an outcome measure, the Headache Under-Response to Treatment (HURT) questionnaire, describing its purpose, development, psychometric evaluation and assessment for clinical utility. The objective was a simple-to-use instrument that would both assess outcome and provide guidance to improving outcome, having utility across the range of headache disorders, across clinical settings and across countries and cultures. After literature review, an expert consensus group drawn from all six world regions formulated HURT through item development and item reduction using item-response theory. Using the American Migraine Prevalence and Prevention Study's general-population respondent panel, two mailed surveys assessed the psychometric properties of HURT, comparing it with other instruments as external validators. Reliability was assessed in patients in two culturally-contrasting clinical settings: headache specialist centres in Europe (n = 159) and primary-care centres in Saudi Arabia (n = 40). Clinical utility was assessed in similar settings (Europe n = 201; Saudi Arabia n = 342). The final instrument, an 8-item self-administered questionnaire, addressed headache frequency, disability, medication use and effect, patients' perceptions of headache "control" and their understanding of their diagnoses. Psychometric evaluation revealed a two-factor model (headache frequency, disability and medication use; and medication efficacy and headache control), with scale properties apparently stable across disorders and correlating well and in the expected directions with external validators. The literature review found few instruments linking assessment to clinical advice or suggested actions: HURT appeared to fill this gap. In European specialist care, it showed utility as an outcome measure across headache disorders. In Saudi Arabian primary care, HURT (translated into Arabic) was reliable and responsive to clinical change. With demonstrated validity and clinical utility across disorders, cultures and settings, HURT is available for clinical and research purposes.

Dermatophytes activate skin keratinocytes via mitogen-activated protein kinase signaling and induce immune responses.

PubMed

Achterman, Rebecca R; Moyes, David L; Thavaraj, Selvam; Smith, Adam R; Blair, Kris M; White, Theodore C; Naglik, Julian R

2015-04-01

Dermatophytes cause superficial and cutaneous fungal infections in immunocompetent hosts and invasive disease in immunocompromised hosts. However, the host mechanisms that regulate innate immune responses against these fungi are largely unknown. Here, we utilized commercially available epidermal tissues and primary keratinocytes to assess (i) damage induction by anthropophilic, geophilic, and zoophilic dermatophyte strains and (ii) the keratinocyte signaling pathways, transcription factors, and proinflammatory responses induced by a representative dermatophyte, Trichophyton equinum. Initially, five dermatophyte species were tested for their ability to invade, cause tissue damage, and induce cytokines, with Microsporum gypseum inducing the greatest level of damage and cytokine release. Using T. equinum as a representative dermatophyte, we found that the mitogen-activated protein kinase (MAPK) pathways were predominantly affected, with increased levels of phospho-p38 and phospho-Jun N-terminal protein kinase (JNK) but decreased levels of phospho-extracellular signal-regulated kinases 1 and 2 (ERK1/2). Notably, the NF-κB and PI3K pathways were largely unaffected. T. equinum also significantly increased expression of the AP-1-associated transcription factor, c-Fos, and the MAPK regulatory phosphatase, MKP1. Importantly, the ability of T. equinum to invade, cause tissue damage, activate signaling and transcription factors, and induce proinflammatory responses correlated with germination, indicating that germination may be important for dermatophyte virulence and host immune activation. Copyright © 2015, Achterman et al.

Relative quantification of beta-casein expression in primary goat mammary epithelial cell lines.

PubMed

Ogorevc, J; Dovč, P

2015-04-15

Primary mammary epithelial cell cultures were established from mammary tissue of lactating and non-lactating goats to assess the expression of beta-casein (CSN2) in vitro. Primary cell cultures were established by enzymatic digestion of mammary tissue and characterized using antibodies against cytokeratin 14, cytokeratin 18, and vimentin. The established primary cell lines in the second passage were grown in basal medium on plastic and in hormone-supplemented (lactogenic) medium on plastic and on an extracellular matrix-covered surface, respectively. CSN2 gene expression was evaluated using quantitative reverse transcription PCR. The presence of CSN2 transcripts was detected in all samples, including cells originating from non-lactating goat, grown in basal medium. The presence of CSN2 protein was confirmed using immunofluorescence. Response to the hormonal treatment and cell morphology differed between the cell lines and treatments. In 2 cell lines supplemented with lactogenic hormones in the medium, CSN2 expression was increased, while CSN2 levels in one of the cell lines remained constant, regardless of the treatment. Addition of extracellular matrix showed positive effects on CSN2 transcription activity in 1 of the cell lines, while in the other 2 showed no statistically significant effects. CSN2 expression appeared to depend on subtle differences in physiological state of the starting tissue material, growth conditions, cell types present in the culture, and methods used for cell culture establishment. Further studies are necessary to identify factors that determine hormone-responsiveness and transcriptional activity of milk protein genes in goat primary mammary cell cultures.

Modulation of Lipopolysaccharide Stimulated Nuclear Factor kappa B Mediated iNOS/NO Production by Bromelain in Rat Primary Microglial Cells.

PubMed

Abbasi Habashi, Soraya; Sabouni, Farzaneh; Moghimi, Ali; Ansari Majd, Saeed

2016-01-01

Microglial cells act as the sentinel of the central nervous system .They are involved in neuroprotection but are highly implicated in neurodegeneration of the aging brain. When over-activated, microglia release pro-inflammatory factors, such as nitric oxide (NO) and cytokines, which are critical in eliciting neuroinflammatory responses associated with neurodegenerative diseases. This study examined whether bromelain, the pineapple-derived extract, may exert an anti-inflammatory effect in primary microglia and may be neuroprotective by regulating microglial activation. Following the isolation of neonatal rat primary microglial cells, the activation profile of microglia was investigated by studying the effects of bromelain (5, 10, 20, and 30 µg/ml) on the levels of NO, inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-κB) in microglia treated with lipopolysaccharide (LPS) (1 µg/ml). Data were analyzed using Student's t-test. P values less than 0.05 were considered to be statistically significant, compared with the LPS-treated group without bromelain. Results showed that pretreatment of rat primary microglia with bromelain, decreased the production of NO induced by LPS (1 µg/ml) treatment in a dose-dependent manner. Bromelain (30 µg/ml) also significantly reduced the expression of iNOS at mRNA level and NF-κB at protein level. Moreover, the study of mitochondrial activity in microglia indicated that bromelain had no cytotoxicity at any of the applied doses, suggesting that the anti-inflammatory effects of bromelain are not due to cell death. Bromelain can be of potential use as an agent for alleviation of symptoms in neurodegenerative diseases.

Modulation of Lipopolysaccharide Stimulated Nuclear Factor kappa B Mediated iNOS/NO Production by Bromelain in Rat Primary Microglial Cells

PubMed Central

Abbasi Habashi, Soraya; Sabouni, Farzaneh; Moghimi, Ali; Ansari Majd, Saeed

2016-01-01

Background: Microglial cells act as the sentinel of the central nervous system .They are involved in neuroprotection but are highly implicated in neurodegeneration of the aging brain. When over-activated, microglia release pro-inflammatory factors, such as nitric oxide (NO) and cytokines, which are critical in eliciting neuroinflammatory responses associated with neurodegenerative diseases. This study examined whether bromelain, the pineapple-derived extract, may exert an anti-inflammatory effect in primary microglia and may be neuroprotective by regulating microglial activation. Methods: Following the isolation of neonatal rat primary microglial cells, the activation profile of microglia was investigated by studying the effects of bromelain (5, 10, 20, and 30 µg/ml) on the levels of NO, inducible nitric oxide synthase (iNOS), and nuclear factor kappa B (NF-κB) in microglia treated with lipopolysaccharide (LPS) (1 µg/ml). Data were analyzed using Student's t-test. P values less than 0.05 were considered to be statistically significant, compared with the LPS-treated group without bromelain. Results: Results showed that pretreatment of rat primary microglia with bromelain, decreased the production of NO induced by LPS (1 µg/ml) treatment in a dose-dependent manner. Bromelain (30 µg/ml) also significantly reduced the expression of iNOS at mRNA level and NF-κB at protein level. Moreover, the study of mitochondrial activity in microglia indicated that bromelain had no cytotoxicity at any of the applied doses, suggesting that the anti-inflammatory effects of bromelain are not due to cell death. Conclusion: Bromelain can be of potential use as an agent for alleviation of symptoms in neurodegenerative diseases. PMID:26459398

Promoter-level expression clustering identifies time development of transcriptional regulatory cascades initiated by ErbB receptors in breast cancer cells.

PubMed

Mina, Marco; Magi, Shigeyuki; Jurman, Giuseppe; Itoh, Masayoshi; Kawaji, Hideya; Lassmann, Timo; Arner, Erik; Forrest, Alistair R R; Carninci, Piero; Hayashizaki, Yoshihide; Daub, Carsten O; Okada-Hatakeyama, Mariko; Furlanello, Cesare

2015-07-16

The analysis of CAGE (Cap Analysis of Gene Expression) time-course has been proposed by the FANTOM5 Consortium to extend the understanding of the sequence of events facilitating cell state transition at the level of promoter regulation. To identify the most prominent transcriptional regulations induced by growth factors in human breast cancer, we apply here the Complexity Invariant Dynamic Time Warping motif EnRichment (CIDER) analysis approach to the CAGE time-course datasets of MCF-7 cells stimulated by epidermal growth factor (EGF) or heregulin (HRG). We identify a multi-level cascade of regulations rooted by the Serum Response Factor (SRF) transcription factor, connecting the MAPK-mediated transduction of the HRG stimulus to the negative regulation of the MAPK pathway by the members of the DUSP family phosphatases. The finding confirms the known primary role of FOS and FOSL1, members of AP-1 family, in shaping gene expression in response to HRG induction. Moreover, we identify a new potential regulation of DUSP5 and RARA (known to antagonize the transcriptional regulation induced by the estrogen receptors) by the activity of the AP-1 complex, specific to HRG response. The results indicate that a divergence in AP-1 regulation determines cellular changes of breast cancer cells stimulated by ErbB receptors.

Under which climate and soil conditions the plant productivity-precipitation relationship is linear or nonlinear?

PubMed

Ye, Jian-Sheng; Pei, Jiu-Ying; Fang, Chao

2018-03-01

Understanding under which climate and soil conditions the plant productivity-precipitation relationship is linear or nonlinear is useful for accurately predicting the response of ecosystem function to global environmental change. Using long-term (2000-2016) net primary productivity (NPP)-precipitation datasets derived from satellite observations, we identify >5600pixels in the North Hemisphere landmass that fit either linear or nonlinear temporal NPP-precipitation relationships. Differences in climate (precipitation, radiation, ratio of actual to potential evapotranspiration, temperature) and soil factors (nitrogen, phosphorous, organic carbon, field capacity) between the linear and nonlinear types are evaluated. Our analysis shows that both linear and nonlinear types exhibit similar interannual precipitation variabilities and occurrences of extreme precipitation. Permutational multivariate analysis of variance suggests that linear and nonlinear types differ significantly regarding to radiation, ratio of actual to potential evapotranspiration, and soil factors. The nonlinear type possesses lower radiation and/or less soil nutrients than the linear type, thereby suggesting that nonlinear type features higher degree of limitation from resources other than precipitation. This study suggests several factors limiting the responses of plant productivity to changes in precipitation, thus causing nonlinear NPP-precipitation pattern. Precipitation manipulation and modeling experiments should combine with changes in other climate and soil factors to better predict the response of plant productivity under future climate. Copyright © 2017 Elsevier B.V. All rights reserved.

Are "Human Factors" the Primary Cause of Complications in the Field of Implant Dentistry?

PubMed

Renouard, Franck; Amalberti, René; Renouard, Erell

Complications in medicine and dentistry are usually analyzed from a purely technical point of view. Rarely is the role of human behavior or judgment considered as a reason for adverse outcomes. When the role of human factors is considered, these are usually described in general terms rather than specifically identifying the factors responsible for an adverse event. The impact of cognitive and behavioral factors in the explanation of adverse events has been studied in other high-stakes areas such as aviation and nuclear power. Specific protocols have been developed to reduce rates of human error, and, where human error is unavoidable, to lessen its impact. This approach has dramatically reduced the incidence of accidents in these fields. This article aims to review how a similar approach may prove valuable in the reduction of complications in implant dentistry.

The truth is out there: the structure of beliefs about extraterrestrial life among Austrian and British respondents.

PubMed

Swami, Viren; Furnham, Adrian; Haubner, Tanja; Stieger, Stefan; Voracek, Martin

2009-02-01

Previous investigators of extraterrestrial beliefs have relied on single-item scales, which limit the researchers' understanding of such beliefs. The present authors report responses to a 37-item scale about extraterrestrial beliefs from 320 participants in Austria and 257 participants in Britain. A factor analysis revealed 3 primary factors that were stable across sites: (a) belief that extraterrestrial life has visited Earth and that governmental agencies have knowledge of this fact, (b) scientific search for extraterrestrial life, and (c) general beliefs about the existence of extraterrestrial life. Participants rated only Factor 3 positively, suggesting that there is a distinction between paranormal-related beliefs and science-related beliefs. The authors found only political orientation and religiosity to be significantly correlated with factor scores. They discuss their results in relation to previous reports of extraterrestrial beliefs.

40 CFR 142.10 - Requirements for a determination of primary enforcement responsibility.

Code of Federal Regulations, 2011 CFR

2011-07-01

... drinking water regulations (NPDWRs) in effect under part 141 of this chapter; (b) Has adopted and is... PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS... enforcement responsibility. A State has primary enforcement responsibility for public water systems in the...

40 CFR 142.10 - Requirements for a determination of primary enforcement responsibility.

Code of Federal Regulations, 2012 CFR

2012-07-01

... drinking water regulations (NPDWRs) in effect under part 141 of this chapter; (b) Has adopted and is... PROTECTION AGENCY (CONTINUED) WATER PROGRAMS (CONTINUED) NATIONAL PRIMARY DRINKING WATER REGULATIONS... enforcement responsibility. A State has primary enforcement responsibility for public water systems in the...

Stress and visceral pain: from animal models to clinical therapies

PubMed Central

Larauche, Muriel; Mulak, Agata; Taché, Yvette

2011-01-01

Epidemiological studies have implicated stress (psychosocial and physical) as a trigger of first onset or exacerbation of irritable bowel syndrome (IBS) symptoms of which visceral pain is an integrant landmark. A number of experimental acute or chronic exteroceptive or interoceptive stressors induce visceral hyperalgesia in rodents although recent evidence also points to stress-related visceral analgesia as established in the somatic pain field. Underlying mechanisms of stress-related visceral hypersensitivity may involve a combination of sensitization of primary afferents, central sensitization in response to input from the viscera and dysregulation of descending pathways that modulate spinal nociceptive transmission or analgesic response. Biochemical coding of stress involves the recruitment of corticotropin releasing factor (CRF) signaling pathways. Experimental studies established that activation of brain and peripheral CRF receptor subtype 1 plays a primary role in the development of stress-related delayed visceral hyperalgesia while subtype 2 activation induces analgesic response. In line with stress pathways playing a role in IBS, non-pharmacologic and pharmacologic treatment modalities aimed at reducing stress perception using a broad range of evidence-based mind-body interventions and centrally-targeted medications to reduce anxiety impact on brain patterns activated by visceral stimuli and dampen visceral pain. PMID:21575632

Activation of Nrf2 is required for up-regulation of the π class of glutathione S-transferase in rat primary hepatocytes with L-methionine starvation.

PubMed

Lin, Ai-Hsuan; Chen, Haw-Wen; Liu, Cheng-Tze; Tsai, Chia-Wen; Lii, Chong-Kuei

2012-07-04

Numerous genes expression is regulated in response to amino acid shortage, which helps organisms adapt to amino acid limitation. The expression of the π class of glutathione (GSH) S-transferase (GSTP), a highly inducible phase II detoxification enzyme, is regulated mainly by activates activating protein 1 (AP-1) binding to the enhancer I of GSTP (GPEI). Here we show the critical role of nuclear factor erythroid-2-related factor 2 (Nrf2) in up-regulating GSTP gene transcription. Primary rat hepatocytes were cultured in a methionine-restricted medium, and immunoblotting and RT-PCR analyses showed that methionine restriction time-dependently increased GSTP protein and mRNA expression over a 48 h period. Nrf2 translocation to the nucleus, nuclear proteins binding to GPEI, and antioxidant response element (ARE) luciferase reporter activity were increased by methionine restriction as well as by l-buthionine sulfoximine (BSO), a GSH synthesis inhibitor. Transfection with Nrf2 siRNA knocked down Nrf2 expression and reversed the methionine-induced GSTP expression and GPEI binding activity. Chromatin immunoprecipitation assay confirmed the binding of Nrf2 to the GPEI. Phosphorylation of extracellular signal-regulated kinase 2 (ERK2) was increased in methionine-restricted and BSO-treated cells. ERK2 siRNA abolished methionine restriction-induced Nrf2 nuclear translocation, GPEI binding activity, ARE-luciferase reporter activity, and GSTP expression. Our results suggest that the up-regulation of GSTP gene transcription in response to methionine restriction likely occurs via the ERK-Nrf2-GPEI signaling pathway.

Paradoxical Regulation of Human FGF21 by Both Fasting and Feeding Signals: Is FGF21 a Nutritional Adaptation Factor?

PubMed Central

Uebanso, Takashi; Taketani, Yutaka; Yamamoto, Hironori; Amo, Kikuko; Ominami, Hirokazu; Arai, Hidekazu; Takei, Yuichiro; Masuda, Masashi; Tanimura, Ayako; Harada, Nagakatsu; Yamanaka-Okumura, Hisami; Takeda, Eiji

2011-01-01

Fibroblast growth factor 21 (FGF21) has recently emerged as a metabolic hormone involved in regulating glucose and lipid metabolism in mouse, but the regulatory mechanisms and actions of FGF21 in humans remain unclear. Here we have investigated the regulatory mechanisms of the human FGF21 gene at the transcriptional level. A deletion study of the human FGF21 promoter (−1672 to +230 bp) revealed two fasting signals, including peroxisome proliferator-activated receptor α (PPARα) and glucagon signals, that independently induced human FGF21 gene transcription in mouse primary hepatocytes. In addition, two feeding signals, glucose and xylitol, also dose-dependently induced human FGF21 gene transcription and mRNA expression in both human HepG2 cells and mouse primary hepatocytes. FGF21 protein expression and secretion were also induced by high glucose stimulation. The human FGF21 promoter (−1672 to +230 bp) was found to have a carbohydrate-responsive element at −380 to −366 bp, which is distinct from the PPAR response element (PPRE). Knock-down of the carbohydrate response element binding protein by RNAi diminished glucose-induced human FGF21 transcription. Moreover, we found that a region from −555 to −443 bp of the human FGF21 promoter region exerts an important role in the activation of basic transcription. In conclusion, human FGF21 gene expression is paradoxically and independently regulated by both fasting and feeding signals. These regulatory mechanisms suggest that human FGF21 is increased with nutritional crisis, including starvation and overfeeding. PMID:21829679

Mechanisms of resistance to anti-epidermal growth factor receptor inhibitors in metastatic colorectal cancer

PubMed Central

Sforza, Vincenzo; Martinelli, Erika; Ciardiello, Fortunato; Gambardella, Valentina; Napolitano, Stefania; Martini, Giulia; della Corte, Carminia; Cardone, Claudia; Ferrara, Marianna L; Reginelli, Alfonso; Liguori, Giuseppina; Belli, Giulio; Troiani, Teresa

2016-01-01

The prognosis of patients with metastatic colorectal cancer (mCRC) remain poor despite the impressive improvement of treatments observed over the last 20 years that led to an increase in median overall survival from 6 mo, with the only best supportive care, to approximately 30 mo with the introduction of active chemotherapy drugs and targeted agents. The monoclonal antibodies (moAbs) cetuximab and panitumumab, directed against the epidermal growth factor receptor (EGFR), undoubtedly represent a major step forward in the treatment of mCRC, given the relevant efficacy in terms of progression-free survival, overall survival, response rate, and quality of life observed in several phase III clinical trials among different lines of treatment. However, the anti-EGFR moAbs were shown only to be effective in a subset of patients. For instance, KRAS and NRAS mutations have been identified as biomarkers of resistance to these drugs, improving the selection of patients who might derive a benefit from these treatments. Nevertheless, several other alterations might affect the response to these drugs, and unfortunately, even the responders eventually become resistant by developing secondary (or acquired) resistance in approximately 13-18 mo. Several studies highlighted that the landscape of responsible alterations of both primary and acquired resistance to anti-EGFR drugs biochemically converge into MEK-ERK and PIK3CA-AKT pathways. In this review, we describe the currently known mechanisms of primary and acquired resistance to anti-EGFR moAbs together with the various strategies evaluated to prevent, overcame or revert them. PMID:27605871

Efficacy of switching between tumor necrosis factor-alfa inhibitors in psoriasis: results from the Italian Psocare registry.

PubMed

Piaserico, Stefano; Cazzaniga, Simone; Chimenti, Sergio; Giannetti, Alberto; Maccarone, Mara; Picardo, Mauro; Peserico, Andrea; Naldi, Luigi

2014-02-01

Some studies have shown that switching patients from one tumor necrosis factor (TNF)-alfa inhibitor to another may be beneficial when they have an inadequate response or an adverse event. We sought to assess the variables predicting the efficacy of the second TNF-alfa inhibitor in patients discontinuing the first TNF-alfa inhibitor. Data from all 5423 consecutive patients starting TNF-alfa inhibitor therapy for psoriasis between September 2005 and September 2010 who were included in the Italian Psocare registry were analyzed. In 105 patients who switched to a second TNF-alfa inhibitor who had complete follow-up data, 75% improvement in the Psoriasis Area Severity Index score (PASI 75) was reached by 29% after 16 weeks and by 45.6% after 24 weeks. Patients who switched because of secondary loss of efficacy (loss of initial PASI 75 response) or adverse events/intolerance were more likely to reach PASI 75 than those who switched as a result of primary inefficacy (PASI 75 never achieved) (hazard ratio 2.7, 95% confidence interval 1.3-5.5 vs hazard ratio 2.0, 95% confidence interval 1.0-3.9 and 1, respectively). There was a small number of patients with complete follow-up data. PASI 75 response in patients who switched from one anti-TNF-alfa agent to another was significantly reduced in patients who showed primary inefficacy of the first anti-TNF-alfa. Copyright © 2013 American Academy of Dermatology, Inc. Published by Mosby, Inc. All rights reserved.

High-dimensional gene expression profiling studies in high and low responders to primary smallpox vaccination.

PubMed

Haralambieva, Iana H; Oberg, Ann L; Dhiman, Neelam; Ovsyannikova, Inna G; Kennedy, Richard B; Grill, Diane E; Jacobson, Robert M; Poland, Gregory A

2012-11-15

The mechanisms underlying smallpox vaccine-induced variations in immune responses are not well understood, but are of considerable interest to a deeper understanding of poxvirus immunity and correlates of protection. We assessed transcriptional messenger RNA expression changes in 197 recipients of primary smallpox vaccination representing the extremes of humoral and cellular immune responses. The 20 most significant differentially expressed genes include a tumor necrosis factor-receptor superfamily member, an interferon (IFN) gene, a chemokine gene, zinc finger protein genes, nuclear factors, and histones (P ≤ 1.06E(-20), q ≤ 2.64E(-17)). A pathway analysis identified 4 enriched pathways with cytokine production by the T-helper 17 subset of CD4+ T cells being the most significant pathway (P = 3.42E(-05)). Two pathways (antiviral actions of IFNs, P = 8.95E(-05); and IFN-α/β signaling pathway, P = 2.92E(-04)), integral to innate immunity, were enriched when comparing high with low antibody responders (false discovery rate, < 0.05). Genes related to immune function and transcription (TLR8, P = .0002; DAPP1, P = .0003; LAMP3, P = 9.96E(-05); NR4A2, P ≤ .0002; EGR3, P = 4.52E(-05)), and other genes with a possible impact on immunity (LNPEP, P = 3.72E(-05); CAPRIN1, P = .0001; XRN1, P = .0001), were found to be expressed differentially in high versus low antibody responders. We identified novel and known immunity-related genes and pathways that may account for differences in immune response to smallpox vaccination.

Overview of the cellular and molecular basis of kidney fibrosis

PubMed Central

Eddy, Allison A

2014-01-01

The common pathogenetic pathway of progressive injury in patients with chronic kidney disease (CKD) is epitomized as normal kidney parenchymal destruction due to scarring (fibrosis). Understanding the fundamental pathways that lead to renal fibrosis is essential in order to develop better therapeutic options for human CKD. Although complex, four cellular responses are pivotal. (1) An interstitial inflammatory response that has multiple consequences—some harmful and others healing. (2) The appearance of a unique interstitial cell population of myofibroblasts, primarily derived from kidney stromal cells (fibroblasts and pericytes), that are the primary source of the various extracellular matrix proteins that form interstitial scars. (3) Tubular epithelial cells that have variable and time-dependent roles as early responders to injury and later as victims of fibrosis due to the loss of their regenerative abilities. (4) Loss of interstitial capillary integrity that compromises oxygen delivery and leads to a vicious cascade of hypoxia–oxidant stress that accentuates injury and fibrosis. In the absence of adequate angiogenic responses, a healthy interstitial capillary network is not maintained. The fibrotic ‘scar' that typifies CKD is an interesting consortium of multifunctional macromolecules that not only change in composition and structure over time, but can be degraded via extracellular and intracellular proteases. Although transforming growth factor beta appears to be the primary driver of kidney fibrosis, a vast array of additional molecules may have modulating roles. The importance of genetic and epigenetic factors is increasingly appreciated. An intriguing but incompletely understood cardiorenal syndrome underlies the high morbidity and mortality rates that develop in association with progressive kidney fibrosis. PMID:25401038

Approaches to Mitigate the Unwanted Immunogenicity of Therapeutic Proteins during Drug Development.

PubMed

Salazar-Fontana, Laura I; Desai, Dharmesh D; Khan, Tarik A; Pillutla, Renuka C; Prior, Sandra; Ramakrishnan, Radha; Schneider, Jennifer; Joseph, Alexandra

2017-03-01

All biotherapeutics have the potential to induce an immune response. This immunological response is complex and, in addition to antibody formation, involves T cell activation and innate immune responses that could contribute to adverse effects. Integrated immunogenicity data analysis is crucial to understanding the possible clinical consequences of anti-drug antibody (ADA) responses. Because patient- and product-related factors can influence the immunogenicity of a therapeutic protein, a risk-based approach is recommended and followed by most drug developers to provide insight over the potential harm of unwanted ADA responses. This paper examines mitigation strategies currently implemented and novel under investigation approaches used by drug developers. The review describes immunomodulatory regimens used in the clinic to mitigate deleterious ADA responses to replacement therapies for deficiency syndromes, such as hemophilia A and B, and high risk classical infantile Pompe patients (e.g., cyclophosphamide, methotrexate, rituximab); novel in silico and in vitro prediction tools used to select candidates based on their immunogenicity potential (e.g., anti-CD52 antibody primary sequence and IFN beta-1a formulation); in vitro generation of tolerogenic antigen-presenting cells (APCs) to reduce ADA responses to factor VIII and IX in murine models of hemophilia; and selection of novel delivery systems to reduce in vivo ADA responses to highly immunogenic biotherapeutics (e.g., asparaginase). We conclude that mitigation strategies should be considered early in development for biotherapeutics based on our knowledge of existing clinical data for biotherapeutics and the immune response involved in the generation of these ADAs.

Economies through Application of Nonmedical Primary-Preventative Health: Lessons from the Healthy Country Healthy People Experience of Australia’s Aboriginal People

PubMed Central

Campbell, David

2016-01-01

The World Health Organization reports noncommunicable disease as a global pandemic. While national and international health research/policy bodies, such as the World Health Organization and the Australian Institute of Health and Welfare, emphasize the importance of preventative health, there is a continuing distortion in the allocation of resources to curative health as a result of government failure. Government failure is, in part, the result of a political response to individual preference for certainty in receiving treatment for specific health conditions, rather than the uncertainty of population-based preventative intervention. This has led to a failure to engage with those primary causative factors affecting chronic disease, namely the psychosocial stressors, in which the socioeconomic determinants are an important component. Such causal factors are open to manipulation through government policies and joint government-government, government-private cooperation through application of nonmedical primary-preventative health policies. The health benefits of Aboriginal people in traditional land management, or caring-for-country, in remote to very remote Australia, is used to exemplify the social benefits of nonmedical primary-preventative health intervention. Such practices form part of the “healthy country, health people” concept that is traditionally relied upon by Indigenous peoples. Possible health and wider private good and public good social benefits are shown to occur across multiple disciplines and jurisdictions with the possibility of substantial economies. General principles in the application of nonmedical primary-preventative health activities are developed through consideration of the experience of Afboriginal people participation in traditional caring-for-country. PMID:27482574

Political economy of decentralising HIV and AIDS treatment services to primary healthcare facilities in three Nigerian states.

PubMed

Mbachu, Chinyere; Onwujekwe, Obinna; Ezumah, Nkoli; Ajayi, Olayinka; Sanwo, Olusola; Uzochukwu, Benjamin

2016-09-01

Decentralisation is defined as the dispersion, distribution or transfer of resources, functions and decision-making power from a central authority to regional and local authorities. It is usually accompanied by assignment of accountability and responsibility for results. Fundamental to understanding decentralisation is learning what motivates central governments to give up power and resources to local governments, and the practical significance of this on their positions regarding decentralisation. This study examined key political and institutional influences on role-players' capacity to support decentralisation of HIV and AIDS treatment services to primary healthcare facilities, and implications for sustainability. In-depth interviews were conducted with 55 purposively selected key informants, drawn from three Nigerian states that were at different stages of decentralising HIV and AIDS treatment services to primary care facilities. Key informants represented different categories of role-players involved in HIV and AIDS control programmes. Thematic framework analysis of data was done. Support for decentralisation of HIV and AIDS treatment services to primary healthcare facilities was substantial among different categories of actors. Political factors such as the local and global agenda for health, political tenure and party affiliations, and institutional factors such as consolidation of decision-making power and improvements in career trajectories, influenced role-players support for decentralisation of HIV and AIDS treatment services. It is feasible and acceptable to decentralise HIV and AIDS treatment services to primary healthcare facilities, to help improve coverage. However, role-players' support largely depends on how well the reform aligns with political structures and current institutional practices.

Lactoferrin promote primary rat osteoblast proliferation and differentiation via up-regulation of insulin-like growth factor-1 expression.

PubMed

Hou, Jian-ming; Wu, Man; Lin, Qing-ming; Lin, Fan; Xue, Ying; Lan, Xu-hua; Chen, En-yu; Wang, Mei-li; Yang, Hai-yan; Wang, Feng-xiong

2014-08-01

The aim of this study was to explore the effect of lactoferrin (LF) in primary fetal rat osteoblasts proliferation and differentiation and investigate the underlying molecular mechanisms. Primary rat osteoblasts were obtained from the calvarias of neonatal rats. Osteoblasts were treated with LF (0.1-1000 μg/mL), or OSI-906 [a selective inhibitor of insulin-like growth factor 1 (IGF-1) receptor and insulin receptor]. The IGF-1 was then knocked down by small hairpin RNA (shRNA) technology and then was treated with recombinant human IGF-1 or LF. Cell proliferation and differentiation were measured by MTT assay and alkaline phosphatase (ALP) assay, respectively. The expression of IGF-1 and IGF binding protein 2 (IGFBP2) mRNA were analyzed using real-time PCR. LF promotes the proliferation and differentiation of osteoblasts in a certain range (1-100 μg/mL) in time- and dose-dependent manner. The mRNA level of IGF-1 was significantly increased, while the expression of IGFBP2 was suppressed by LF treatment. Knockdown of IGF-1 by shRNA in primary rat osteoblast dramatically decreased the abilities of proliferation and differentiation of osteoblasts and blocked the proliferation and differentiation effect of LF in osteoblasts. OSI906 (5 μM) blocked the mitogenic and differentiation of LF in osteoblasts. Proliferation and differentiation of primary rat osteoblasts in response to LF are mediated in part by stimulating of IGF-1 gene expression and alterations in the gene expression of IGFBP2.

Thymidilate synthase and p53 primary tumour expression as predictive factors for advanced colorectal cancer patients

PubMed Central

Paradiso, A; Simone, G; Petroni, S; Leone, B; Vallejo, C; Lacava, J; Romero, A; Machiavelli, M; Lena, M De; Allegra, C J; Johnston, P G

2000-01-01

The purpose of this work was to analyse the ability of p53 and thymidilate synthase (TS) primary tumour expression to retrospectively predict clinical response to chemotherapy and long-term prognosis in patients with advanced colorectal cancers homogeneously treated by methotrexate (MTX)-modulated–5-fluorouracil (5-FU-FA). A total of 108 advanced colorectal cancer patients entered the present retrospective study. Immunohistochemical p53 (pAb 1801 mAb) and TS (TS106 mAb) expression on formalin-fixed paraffin-embedded primary tumour specimens was related to probability of clinical response to chemotherapy, time to progression and overall survival. p53 was expressed in 53/108 (49%) tumours, while 54/108 (50%) showed TS immunostaining. No relationship was demonstrated between p53 positivity and clinical response to chemotherapy (objective response (OR): 20% vs 23%, in p53+ and p53– cases respectively) or overall survival. Percent of OR was significantly higher in TS-negative with respect to TS-positive tumours (30% vs 15% respectively;P< 0.04); simultaneous analysis of TS and p53 indicated 7% OR for p53-positive/TS-positive tumours vs 46% for p53-positive/TS-negative tumours (P< 0.03). Logistic regression analysis confirmed a significant association between TS tumour status and clinical response to chemotherapy (hazard ratio (HR): 2.91; 95% confidence interval (CI) 8.34–1.01; two-sided P< 0.05). A multivariate analysis of overall survival showed that only a small number of metastatic sites was statistically relevant (HR 1.89; 95% CI 2.85–1.26; two-sided P< 0.03). Our study suggests that immunohistochemical expression of p53 and TS could assist the clinician in predicting response of colorectal cancer patients to modulated MTX-5-FU therapy. © 2000 Cancer Research Campaign PMID:10682666

Gamma Knife Radiosurgery for the Treatment of Cystic Cerebral Metastases

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

Ebinu, Julius O.; Lwu, Shelly; Monsalves, Eric

Purpose: To assess the role of Gamma Knife radiosurgery (GKRS) in the treatment of nonsurgical cystic brain metastasis, and to determine predictors of response to GKRS. Methods: We reviewed a prospectively maintained database of brain metastases patients treated at our institution between 2006 and 2010. All lesions with a cystic component were identified, and volumetric analysis was done to measure percentage of cystic volume on day of treatment and consecutive follow-up MRI scans. Clinical, radiologic, and dosimetry parameters were reviewed to establish the overall response of cystic metastases to GKRS as well as identify potential predictive factors of response. Results:more » A total of 111 lesions in 73 patients were analyzed; 57% of lesions received prior whole-brain radiation therapy (WBRT). Lung carcinoma was the primary cancer in 51% of patients, 10% breast, 10% colorectal, 4% melanoma, and 26% other. Fifty-seven percent of the patients were recursive partitioning analysis class 1, the remainder class 2. Mean target volume was 3.3 mL (range, 0.1-23 mL). Median prescription dose was 21 Gy (range, 15-24 Gy). Local control rates were 91%, 63%, and 37% at 6, 12, and 18 months, respectively. Local control was improved in lung primary and worse in patients with prior WBRT (univariate). Only lung primary predicted local control in multivariate analysis, whereas age and tumor volume did not. Lesions with a large cystic component did not show a poorer response compared with those with a small cystic component. Conclusions: This study supports the use of GKRS in the management of nonsurgical cystic metastases, despite a traditionally perceived poorer response. Our local control rates are comparable to a matched cohort of noncystic brain metastases, and therefore the presence of a large cystic component should not deter the use of GKRS. Predictors of response included tumor subtype. Prior WBRT decreased effectiveness of SRS for local control rates.« less

The intrahepatic signalling niche of hedgehog is defined by primary cilia positive cells during chronic liver injury.

PubMed

Grzelak, Candice Alexandra; Martelotto, Luciano Gastón; Sigglekow, Nicholas David; Patkunanathan, Bramilla; Ajami, Katerina; Calabro, Sarah Ruth; Dwyer, Benjamin James; Tirnitz-Parker, Janina Elke Eleonore; Watkins, D Neil; Warner, Fiona Jane; Shackel, Nicholas Adam; McCaughan, Geoffrey William

2014-01-01

In vertebrates, canonical Hedgehog (Hh) pathway activation requires Smoothened (SMO) translocation to the primary cilium (Pc), followed by a GLI-mediated transcriptional response. In addition, a similar gene regulation occurs in response to growth factors/cytokines, although independently of SMO signalling. The Hh pathway plays a critical role in liver fibrosis/regeneration, however, the mechanism of activation in chronic liver injury is poorly understood. This study aimed to characterise Hh pathway activation upon thioacetamide (TAA)-induced chronic liver injury in vivo by defining Hh-responsive cells, namely cells harbouring Pc and Pc-localised SMO. C57BL/6 mice (wild-type or Ptc1(+/-)) were TAA-treated. Liver injury and Hh ligand/pathway mRNA and protein expression were assessed in vivo. SMO/GLI manipulation and SMO-dependent/independent activation of GLI-mediated transcriptional response in Pc-positive (Pc(+)) cells were studied in vitro. In vivo, Hh activation was progressively induced following TAA. At the epithelial-mesenchymal interface, injured hepatocytes produced Hh ligands. Progenitors, myofibroblasts, leukocytes and hepatocytes were GLI2(+). Pc(+) cells increased following TAA, but only EpCAM(+)/GLI2(+) progenitors were Pc(+)/SMO(+). In vitro, SMO knockdown/hGli3-R overexpression reduced proliferation/viability in Pc(+) progenitors, whilst increased proliferation occurred with hGli1 overexpression. HGF induced GLI transcriptional activity independently of Pc/SMO. Ptc1(+/-) mice exhibited increased progenitor, myofibroblast and fibrosis responses. In chronic liver injury, Pc(+) progenitors receive Hh ligand signals and process it through Pc/SMO-dependent activation of GLI-mediated transcriptional response. Pc/SMO-independent GLI activation likely occurs in Pc(-)/GLI2(+) cells. Increased fibrosis in Hh gain-of-function mice likely occurs by primary progenitor expansion/proliferation and secondary fibrotic myofibroblast expansion, in close contact with progenitors. Copyright © 2013 European Association for the Study of the Liver. All rights reserved.

HIF1α regulated expression of XPA contributes to cisplatin resistance in lung cancer

PubMed Central

Liu, Yanbin; Bernauer, Amanda M.; Yingling, Christin M.; Belinsky, Steven A.

2012-01-01

Factors regulating nucleotide excision repair probably contribute to the heterogenous response of advanced stage lung cancer patients to drugs such as cisplatin. Studies to identify the genes in the nucleotide excision repair pathway most closely associated with resistance to cisplatin have not been conclusive. We hypothesized that Xeroderma pigmentosum complementation group A (XPA), because of its dual role in sensing and recruiting other DNA repair proteins to the damaged template, would be critical in defining sensitivity to cisplatin. Studies were conducted to identify factors regulating transcription of XPA, to assess its role in modulating sensitivity to cisplatin and its expression in primary lung tumors. Hypoxia-inducible factor 1 alpha (HIF1α) subunit was found to bind with strong affinity to a hypoxia response element sequence in the promoter of XPA. Modulating expression of HIF1α by small interfering RNA or cobalt chloride markedly reduced or increased transcription of XPA in lung cancer cell lines, respectively. Protein levels of XPA were strongly correlated with sensitivity to cisplatin (r = 0.88; P < 0.001) in cell lines and sensitivity could be increased by small interfering RNA depletion of XPA. Expression of XPA determined in 54 primary lung tumors was elevated on average 5.2-fold when compared with normal bronchial epithelial cells and correlated with levels of HIF1α (r = 0.58; P < 0.01). Together, these studies identify XPA as a novel target for regulation by HIF1α whose modulation could impact lung cancer therapy. PMID:22467238

Determination of the KQclinfclin,Qmsr fmsr correction factors for detectors used with an 800 MU/min CyberKnife(®) system equipped with fixed collimators and a study of detector response to small photon beams using a Monte Carlo method.

PubMed

Moignier, C; Huet, C; Makovicka, L

2014-07-01

In a previous work, output ratio (ORdet) measurements were performed for the 800 MU/min CyberKnife(®) at the Oscar Lambret Center (COL, France) using several commercially available detectors as well as using two passive dosimeters (EBT2 radiochromic film and micro-LiF TLD-700). The primary aim of the present work was to determine by Monte Carlo calculations the output factor in water (OFMC,w) and the [Formula: see text] correction factors. The secondary aim was to study the detector response in small beams using Monte Carlo simulation. The LINAC head of the CyberKnife(®) was modeled using the PENELOPE Monte Carlo code system. The primary electron beam was modeled using a monoenergetic source with a radial gaussian distribution. The model was adjusted by comparisons between calculated and measured lateral profiles and tissue-phantom ratios obtained with the largest field. In addition, the PTW 60016 and 60017 diodes, PTW 60003 diamond, and micro-LiF were modeled. Output ratios with modeled detectors (ORMC,det) and OFMC,w were calculated and compared to measurements, in order to validate the model for smallest fields and to calculate [Formula: see text] correction factors, respectively. For the study of the influence of detector characteristics on their response in small beams; first, the impact of the atomic composition and the mass density of silicon, LiF, and diamond materials were investigated; second, the material, the volume averaging, and the coating effects of detecting material on the detector responses were estimated. Finally, the influence of the size of silicon chip on diode response was investigated. Looking at measurement ratios (uncorrected output factors) compared to the OFMC,w, the PTW 60016, 60017 and Sun Nuclear EDGE diodes systematically over-responded (about +6% for the 5 mm field), whereas the PTW 31014 Pinpoint chamber systematically under-responded (about -12% for the 5 mm field). ORdet measured with the SFD diode and PTW 60003 diamond detectors were in good agreement with OFMC,w except for the 5 mm field size (about -7.5% for the diamond and +3% for the SFD). A good agreement with OFMC,w was obtained with the EBT2 film and micro-LiF dosimeters (deviation less than 1.4% for all fields investigated). [Formula: see text] correction factors for several detectors used in this work have been calculated. The impact of atomic composition on the dosimetric response of detectors was found to be insignificant, unlike the mass density and size of the detecting material. The results obtained with the passive dosimeters showed that they can be used for small beam OF measurements without correction factors. The study of detector response showed that ORdet is depending on the mass density, the volume averaging, and the coating effects of the detecting material. Each effect was quantified for the PTW 60016 and 60017 diodes, the micro-LiF, and the PTW 60003 diamond detectors. None of the active detectors used in this work can be recommended as a reference for small field dosimetry, but an improved diode detector with a smaller silicon chip coated with tissue-equivalent material is anticipated (by simulation) to be a reliable small field dosimetric detector in a nonequilibrium field.

Evidence-based practice among primary care physicians in Kuwait.

PubMed

Ahmad, Abeer S H; Al-Mutar, Nouf B E; Al-Hulabi, Fahad A S; Al-Rashidee, Eman S L; Doi, Suhail A R; Thalib, Lukman

2009-12-01

The level of evidence-based practice (EBP) and awareness has not been previously assessed among primary care physicians in Kuwait. The objectives of this study were to quantify the level of EBP and awareness in Kuwait and identify the factors related to EBP. We used a cross sectional study that enrolled 332 primary care physicians in 57 primary care centres randomly chosen in Kuwait. A self-administered questionnaire was used to collect the data with a response rate of about 93%. Although half of the physicians self reported that they use EBP most of the time, further analysis revealed that only about 24% of this group had a reasonable understanding of EBP. Most of the clinical practice in the Kuwaiti primary care system seems to be based on the clinician's own judgment or what they learned in the medical school and traditional text books, rather than evidence-based sources. None of the physicians had an Internet connection at their work place and a vast majority of them had no access to international journals nor were confident about critical appraisal of published evidence. Overall level of awareness of evidence-based medicine (EBM) among primary care physicians in Kuwait was considerably low. Training in the areas of EBM as well as making sure the Kuwaiti primary care centres have access to evidence-based sources are critically important if primary care in Kuwait were to become evidence based.

Pseudomonas aeruginosa LasB protease impairs innate immunity in mice and humans by targeting a lung epithelial cystic fibrosis transmembrane regulator–IL-6–antimicrobial–repair pathway

PubMed Central

Saint-Criq, Vinciane; Villeret, Bérengère; Bastaert, Fabien; Kheir, Saadé; Hatton, Aurélie; Cazes, Aurélie; Xing, Zhou; Sermet-Gaudelus, Isabelle; Garcia-Verdugo, Ignacio; Edelman, Aleksander

2018-01-01

Background Pseudomonas aeruginosa lung infections are a huge problem in ventilator-associated pneumonia, cystic fibrosis (CF) and in chronic obstructive pulmonary disease (COPD) exacerbations. This bacterium secretes virulence factors that may subvert host innate immunity. Objective We evaluated the effect of P. aeruginosa elastase LasB, an important virulence factor secreted by the type II secretion system, on ion transport, innate immune responses and epithelial repair, both in vitro and in vivo. Methods Wild-type (WT) or cystic fibrosis transmembrane conductance regulator (CFTR)-mutated epithelial cells (cell lines and primary cells from patients) were treated with WT or ΔLasB pseudomonas aeruginosa O1 (PAO1) secretomes. The effect of LasB and PAO1 infection was also assessed in vivo in murine models. Results We showed that LasB was the most abundant protein in WT PAO1 secretomes and that it decreased epithelial CFTR expression and activity. In airway epithelial cell lines and primary bronchial epithelial cells, LasB degraded the immune mediators interleukin (IL)-6 and trappin-2, an important epithelial-derived antimicrobial molecule. We further showed that an IL-6/STAT3 signalling pathway was downregulated by LasB, resulting in inhibition of epithelial cell repair. In mice, intranasally instillated LasB induced significant weight loss, inflammation, injury and death. By contrast, we showed that overexpression of IL-6 and trappin-2 protected mice against WT-PAO1-induced death, by upregulating IL-17/IL-22 antimicrobial and repair pathways. Conclusions Our data demonstrate that PAO1 LasB is a major P. aeruginosa secreted factor that modulates ion transport, immune response and tissue repair. Targeting this virulence factor or upregulating protective factors such as IL-6 or antimicrobial molecules such as trappin-2 could be beneficial in P. aeruginosa-infected individuals. PMID:28790180

Re-irradiation of recurrent gliomas: pooled analysis and validation of an established prognostic score-report of the Radiation Oncology Group (ROG) of the German Cancer Consortium (DKTK).

PubMed

Combs, Stephanie E; Niyazi, Maximilian; Adeberg, Sebastian; Bougatf, Nina; Kaul, David; Fleischmann, Daniel F; Gruen, Arne; Fokas, Emmanouil; Rödel, Claus M; Eckert, Franziska; Paulsen, Frank; Oehlke, Oliver; Grosu, Anca-Ligia; Seidlitz, Annekatrin; Lattermann, Annika; Krause, Mechthild; Baumann, Michael; Guberina, Maja; Stuschke, Martin; Budach, Volker; Belka, Claus; Debus, Jürgen; Kessel, Kerstin A

2018-05-01

The heterogeneity of high-grade glioma recurrences remains an ongoing challenge for the interdisciplinary neurooncology team. Response to re-irradiation (re-RT) is heterogeneous, and survival data depend on prognostic factors such as tumor volume, primary histology, age, the possibility of reresection, or time between primary diagnosis and initial RT and re-RT. In the present pooled analysis, we gathered data from radiooncology centers of the DKTK Consortium and used it to validate the established prognostic score by Combs et al. and its modification by Kessel et al. Data consisted of a large independent, multicenter cohort of 565 high-grade glioma patients treated with re-RT from 1997 to 2016 and a median dose of 36 Gy. Primary RT was between 1986 and 2015 with a median dose of 60 Gy. Median age was 54 years; median follow-up was 7.1 months. Median OS after re-RT was 7.5, 9.5, and 13.8 months for WHO IV, III, and I/II gliomas, respectively. All six prognostic factors were tested for their significance on OS. Aside from the time from primary RT to re-RT (P = 0.074) and the reresection status (P = 0.101), all factors (primary histology, age, KPS, and tumor volume) were significant. Both the original and new score showed a highly significant influence on survival with P < 0.001. Both prognostic scores successfully predict survival after re-RT and can easily be applied in the routine clinical workflow. Now, further prognostic features need to be found to even improve treatment decisions regarding neurooncological interventions for recurrent glioma patients. © 2018 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Stem cell factor and interleukin-2/15 combine to enhance MAPK-mediated proliferation of human natural killer cells

PubMed Central

Benson, Don M.; Yu, Jianhua; Becknell, Brian; Wei, Min; Freud, Aharon G.; Ferketich, Amy K.; Trotta, Rossana; Perrotti, Danilo; Briesewitz, Roger

2009-01-01

Stem cell factor (SCF) promotes synergistic cellular proliferation in combination with several growth factors, and appears important for normal natural killer (NK)–cell development. CD34+ hematopoietic precursor cells (HPCs) require interleukin-15 (IL-15) for differentiation into human NK cells, and this effect can be mimicked by IL-2. Culture of CD34+ HPCs or some primary human NK cells in IL-2/15 and SCF results in enhanced growth compared with either cytokine alone. The molecular mechanisms responsible for this are unknown and were investigated in the present work. Activation of NK cells by IL-2/15 increases expression of c-kit whose kinase activity is required for synergy with IL-2/15 signaling. Mitogen-activated protein kinase (MAPK) signaling intermediaries that are activated both by SCF and IL-2/15 are enhanced in combination to facilitate earlier cell-cycle entry. The effect results at least in part via enhanced MAPK-mediated modulation of p27 and CDK4. Collectively the data reveal a novel mechanism by which SCF enhances cellular proliferation in combination with IL-2/15 in primary human NK cells. PMID:19060242

Socio-economic and locational determinants of accessibility and utilization of primary health-care.

PubMed

Field, K S; Briggs, D J

2001-09-01

Differences in levels of utilization vary and are a function of socio-economic and geographical factors. This paper presents the results of a questionnaire study involving twelve GP practices in Northamptonshire, UK, of factors which affect access and utilization in asthmatics and diabetics; these groups were selected to control for differences in utilization behaviour, as a result of different aetiologies. The questionnaire sought data on: residential location of patients, utilization characteristics of primary health-care, personal circumstances and mobility and hindrances to access and utilization. Key themes were identified relating to age, gender, social class, employment, ethnicity and proximity to the GP surgery. The young, elderly and females report higher rates of utilization, as do nonmanual workers and those who are unemployed. However, accessibility and utilization vary greatly in response to mobility and locational characteristics; these variations tend to be masked by data on overall rates of usage. Optimal scaling techniques were used to investigate the interactions between the factors affecting accessibility and utilization, and to characterize patients in terms of their levels of utilization. Results confirmed that current service provision afforded a differential level of service to patients, which does not directly reflect their level of need.

Factors influencing law enforcement decisions to adopt an evidence-based robbery prevention program.

PubMed

Cabell, A; Casteel, C; Chronister, T; Nocera, M; Vladutiu, C J; Peek-Asa, C

2013-12-01

Homicide is the leading cause of workplace death among small retail and service businesses in the United States. Evidence-based programs have been shown to reduce robbery and robbery-related crimes in small retail businesses; however, reaching small businesses with programs has been difficult. As small businesses typically have no corporate backing or trade affiliation, police departments have been identified as potential vehicles for program dissemination. A national sample of 300 law enforcement agencies was surveyed to identify facilitators and barriers to adoption and sustainability of an evidence-based program. The questionnaire was developed using behavioral theory concepts and administered via telephone. Preliminary findings suggest the primary facilitators to program adoption included organizational capacity factors such as staff buy-in, dedicated personnel and financial support. Competing responsibilities was the primary barrier identified by agencies. Agency size and program complexity were identified as potential predictors of program adoption. Identifying agency and program-specific characteristics that influence program adoption by law enforcement agencies will be valuable for marketing programs to agencies that have the infrastructure to support and sustain program dissemination. Understanding these factors will optimize the reach of evidence-based strategies to small businesses.

Activation of the Nrf2-ARE pathway by siRNA knockdown of Keap1 reduces oxidative stress and provides partial protection from MPTP-mediated neurotoxicity.

PubMed

Williamson, Tracy P; Johnson, Delinda A; Johnson, Jeffrey A

2012-06-01

Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that binds to the antioxidant response element, a cis-acting regulatory element that increases expression of detoxifying enzymes and antioxidant proteins. Kelch-like ECH associating protein 1 (Keap1) protein is a negative regulator of Nrf2. Previous work has shown that genetic overexpression of Nrf2 is protective in vitro and in vivo. To modulate the Nrf2-ARE system without overexpressing Nrf2, we used short interfering RNA (siRNA) directed against Keap1. Keap1 siRNA administration in primary astrocytes increased the levels of Nrf2-ARE driven genes and protected against oxidative stress. Moreover, Keap1 siRNA resulted in a persistent upregulation of the Nrf2-ARE pathway and protection against oxidative stress in primary astrocytes. Keap1 siRNA injected into the striatum was also modestly protective against MPTP-induced dopaminergic terminal damage. These data indicate that activation of endogenous intracellular levels of Nrf2 is sufficient to protect in models of oxidative stress and Parkinson's disease. Copyright © 2012 Elsevier Inc. All rights reserved.

Factors Influencing Primary Students' Learning Achievement in Bangladesh

ERIC Educational Resources Information Center

Nath, Samir Ranjan

2012-01-01

Using "Education Watch" database of 2008, this article explores the factors associated with learning achievement of primary school students in Bangladesh. The sample consists of 7,093 fifth graders (final year of compulsory primary education) from 440 primary schools. Based on nationally adopted competencies for primary education, a…

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

Tan, Jin; Zhang, Yingchen; Krad, Ibrahim

Power system frequency needs to be maintained close to its nominal value at all times to avoid machine damage, under-frequency load-shedding and even blackouts. Adequate primary frequency response and secondary frequency response are the primary forces to correct an energy imbalance at the second to minute level. As wind energy becomes a larger portion of the world's energy portfolio, there are greater oppotunities for wind to provide frequency response services. This paper addresses one area of frequency control that has been missing in previous work - the reliabilty impacts and interactions between primary and secondary frequency control. The lack ofmore » a commercially available tools to simulate the interaction of these two responses has limited the energy industry's understanding of when the depletion of primary control reserve will impact the performance of secondary conrol response or vice versa. To investigate this issue, in this paper we develop a multi-area frequency response integration model with combined primary and secondary frequency control capabilities.« less

Teamwork in primary care: perspectives of general practitioners and community nurses in Lithuania

PubMed Central

2013-01-01

Background A team approach in primary care has proven benefits in achieving better outcomes, reducing health care costs, satisfying patient needs, ensuring continuity of care, increasing job satisfaction among health providers and using human health care resources more efficiently. However, some research indicates constraints in collaboration within primary health care (PHC) teams in Lithuania. The aim of this study was to gain a better understanding of the phenomenon of teamwork in Lithuania by exploring the experiences of teamwork by general practitioners (GPs) and community nurses (CNs) involved in PHC. Methods Six focus groups were formed with 29 GPs and 27 CNs from the Kaunas Region of Lithuania. Discussions were recorded and transcribed verbatim. A thematic analysis of these data was then performed. Results The analysis of focus group data identified six thematic categories related to teamwork in PHC: the structure of a PHC team, synergy among PHC team members, descriptions of roles and responsibilities of team members, competencies of PHC team members, communications between PHC team members and the organisational background for teamwork. These findings provide the basis for a discussion of a thematic model of teamwork that embraces formal, individual and organisational factors. Conclusions The need for effective teamwork in PHC is an issue receiving broad consensus; however, the process of teambuilding is often taken for granted in the PHC sector in Lithuania. This study suggests that both formal and individual behavioural factors should be targeted when aiming to strengthen PHC teams. Furthermore, this study underscores the need to provide explicit formal descriptions of the roles and responsibilities of PHC team members in Lithuania, which would include establishing clear professional boundaries. The training of team members is an essential component of the teambuilding process, but not sufficient by itself. PMID:23945286

α-Iso-cubebenol inhibits inflammation-mediated neurotoxicity and amyloid beta 1-42 fibril-induced microglial activation.

PubMed

Park, Sun Young; Park, Tae Gyeong; Lee, Sang-Joon; Bae, Yoe-Sik; Ko, Min J; Choi, Young-Whan

2014-01-01

To examine the antineuroinflammatory and neuroprotective activity of α-iso-cubebenol and its molecular mechanism of action in amyloid β (Aβ) 1-42 fibril-stimulated microglia. Aβ 1-42 fibrils were used to induce a neuroinflammatory response in murine primary microglia and BV-2 murine microglia cell lines. Cell viability was monitored by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, protein expression and phosphorylation were determined by Western blot analysis, and matrix metalloproteinase-9 (MMP-9) activity was determined by gelatin zymography assay. In addition, prostaglandin E2 (PGE2), pro-inflammatory cytokines and chemokines were measured by ELISA, and the transactivity of nuclear factor (NF)-κB was determined by a reporter assay. α-Iso-cubebenol significantly inhibited Aβ 1-42 fibril-induced MMP-9, inducible nitric oxide synthase and cyclooxygenase-2 expressions and activity, without affecting cell viability. α-Iso-cubebenol also suppressed the production of tumour necrosis factor-α, IL-1β, IL-6, monocyte chemoattractant protein-1 and reactive oxygen species in a dose-dependent manner, while decreasing the nuclear translocation and transactivity of NF-κB by inhibiting the phosphorylation and degradation of the inhibitor of κB (IκB)α. α-Iso-cubebenol suppressed the phosphorylation of mitogen-activated protein kinase (MAPK) in Aβ 1-42 fibril-stimulated microglia. Primary cortical neurons were protected by the inhibitory effect of α-iso-cubebenol on Aβ 1-42 fibril-induced neuroinflammatory response. α-Iso-cubebenol suppresses Aβ 1-42 fibril-induced neuroinflammatory molecules in primary microglia via the suppression of NF-κB/inhibitor of κBα and MAPK. Importantly, the antineuroinflammatory potential of α-iso-cubebenol is critical for neuroprotection. © 2013 Royal Pharmaceutical Society.

Evaluation of expression and function of vascular endothelial growth factor receptor 2, platelet derived growth factor receptors-alpha and -beta, KIT, and RET in canine apocrine gland anal sac adenocarcinoma and thyroid carcinoma.

PubMed

Urie, Bridget K; Russell, Duncan S; Kisseberth, William C; London, Cheryl A

2012-05-25

Toceranib phosphate (Palladia) has a reported objective response rate of 25% in both canine apocrine gland anal sac adenocarcinoma (AGASACA) and thyroid carcinoma (TC), with stable disease occurring in an additional 50-60% of dogs. The basis for the observed responses to toceranib is not known. The purpose of this study was to evaluate AGASACA and TC samples for the expression and activation of VEGFR2, PDGFRα, PDGFRβ, KIT and RET to assess whether dysregulation of these receptor tyrosine kinases (RTKs) may contribute to the biologic activity of toceranib. mRNA for VEGFR2, PDGFRα/β, KIT and RET was detected in all AGASACA samples. mRNA for VEGFR2, PDGFRα/β, and KIT was detected in all TC samples, while mRNA for RET was amplified in 10/15 samples. No phosphorylation of VEGFR2, PDGFRα/β, or KIT was observed on the arrays. However, phosphorylation of RET was detected in 54% of the primary AGASACA and 20% of TC. VEGFR2 was expressed in 19/24 primary and 6/10 metastatic AGASACA and 6/15 TC samples. KIT was present in 8/24 primary and 3/10 metastatic AGASACA and 9/15 TC samples. PDGFRα expression was noted in all tumor samples. In contrast PDGFRβ expression was found in only a few tumor samples but was evident in the stroma of all tumor specimens. Known targets of toceranib are expressed in both AGASAC and TC. Given the observed expression of VEGFR and PDGFRα/β and phosphorylation of RET, these RTKs merit investigation as to their roles in the biology of AGSACA and TC and their contribution to toceranib's activity.

Evaluation of expression and function of vascular endothelial growth factor receptor 2, platelet derived growth factor receptors-alpha and -beta, KIT, and RET in canine apocrine gland anal sac adenocarcinoma and thyroid carcinoma

PubMed Central

2012-01-01

Background Toceranib phosphate (Palladia) has a reported objective response rate of 25% in both canine apocrine gland anal sac adenocarcinoma (AGASACA) and thyroid carcinoma (TC), with stable disease occurring in an additional 50-60% of dogs. The basis for the observed responses to toceranib is not known. The purpose of this study was to evaluate AGASACA and TC samples for the expression and activation of VEGFR2, PDGFRα, PDGFRβ, KIT and RET to assess whether dysregulation of these receptor tyrosine kinases (RTKs) may contribute to the biologic activity of toceranib. Results mRNA for VEGFR2, PDGFRα/β, KIT and RET was detected in all AGASACA samples. mRNA for VEGFR2, PDGFRα/β, and KIT was detected in all TC samples, while mRNA for RET was amplified in 10/15 samples. No phosphorylation of VEGFR2, PDGFRα/β, or KIT was observed on the arrays. However, phosphorylation of RET was detected in 54% of the primary AGASACA and 20% of TC. VEGFR2 was expressed in 19/24 primary and 6/10 metastatic AGASACA and 6/15 TC samples. KIT was present in 8/24 primary and 3/10 metastatic AGASACA and 9/15 TC samples. PDGFRα expression was noted in all tumor samples. In contrast PDGFRβ expression was found in only a few tumor samples but was evident in the stroma of all tumor specimens. Conclusions Known targets of toceranib are expressed in both AGASAC and TC. Given the observed expression of VEGFR and PDGFRα/β and phosphorylation of RET, these RTKs merit investigation as to their roles in the biology of AGSACA and TC and their contribution to toceranib’s activity. PMID:22630170

Understanding flucloxacillin prescribing trends and treatment non-response in UK primary care: a Clinical Practice Research Datalink (CPRD) study

PubMed Central

Francis, Nick A.; Hood, Kerenza; Lyons, Ronan; Butler, Christopher C.

2016-01-01

Objectives The volume of prescribed antibiotics is associated with antimicrobial resistance and, unlike most other antibiotic classes, flucloxacillin prescribing has increased. We aimed to describe UK primary care flucloxacillin prescribing and factors associated with subsequent antibiotic prescribing as a proxy for non-response. Patients and methods Clinical Practice Research Datalink patients with acute prescriptions for oral flucloxacillin between January 2004 and December 2013, prescription details, associated Read codes and patient demographics were identified. Monthly prescribing rates were plotted and logistic regression identified factors associated with having a subsequent antibiotic prescription within 28 days. Results 3 031 179 acute prescriptions for 1 667 431 patients were included. Average monthly prescription rates increased from 4.74 prescriptions per 1000 patient-months in 2004 to 5.74 (increase of 21.1%) in 2013. The highest prescribing rates and the largest increases in rates were seen in older adults (70+ years), but the overall increase in prescribing was not accounted for by an ageing population. Prescribing 500 mg tablets/capsules rather than 250 mg became more common. Children were frequently prescribed low doses and small volumes (5 day course) and prescribing declined for children, including for impetigo. Only 4.2% of new prescriptions involved co-prescription of another antibiotic. Age (<5 and ≥60 years), diagnosis of ‘cellulitis or abscess’ or no associated code, and 500 mg dose were associated with a subsequent antibiotic prescription, which occurred after 17.6% of first prescriptions. Conclusions There is a need to understand better the reasons for increased prescribing of flucloxacillin in primary care, optimal dosing (and the need to co-prescribe other antibiotics) and the reasons why one in five patients are prescribed a further antibiotic within 4 weeks. PMID:27090629

[Autophagy modulates the levels of inflammatory cytokines in macrophages induced by lipopolysaccharide].

PubMed

Ren, Caiyuan; Zhang, Xiangying; Shi, Hongbo; Chen, Dexi; Duan, Zhongping; Zhang, Huanhu; Ren, Feng

2017-05-01

Objective To analyze the effect of autophagy on inflammatory response in macrophages induced by lipopolysaccharide (LPS) and investigate its molecular mechanism. Methods Bone marrow mesenchymal stem cells, which were separated from the femora of mice, were cultured and induced to differentiate into primary macrophages in vitro. The inflammatory cell model was established by stimulating the primary macrophages with LPS. Autophagy was inhibited by 3-methyladenine (3-MA) or promoted by rapamycin. Green fluorescent protein-microtubule associated protein 1 light chain 3 (GFP-LC3) plasmid was used to transfect primary macrophages and the percentage of cells with GFP-LC3 puncta were counted in the different groups. The mRNA levels of LC3B, tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), IL-6 and IL-12p40 were detected by real-time quantitative PCR, and the protein levels of LC3B, nuclear factor κB (NF-κB) and IκBα were determined by Western blotting. Results LC3B mRNA and protein expression levels were gradually up-regulated and the autophagosomes increased in the macrophages 2, 4 and 6 hours after treated by LPS. Compared with only LPS treatment group, autophagy inhibition by 3-MA pretreatment promoted the mRNA expressions of inflammatory cytokines including TNF-α, IL-1β, IL-6 and IL-12p40, and the autophagy induction by rapamycin pretreatment suppressed TNF-α, IL-1β, IL-6 and IL-12p40. Meanwhile, 3-MA or rapamycin pretreatment further regulated the protein expressions of IκBα and p-NF-kBp65 induced by LPS in macrophages. Conclusion Autophagy can suppress the LPS-induced inflammatory response in macrophages by regulating NF-κB signaling pathway.

c-MET Overexpression in Colorectal Cancer: A Poor Prognostic Factor for Survival.

PubMed

Lee, Su Jin; Lee, Jeeyun; Park, Se Hoon; Park, Joon Oh; Lim, Ho Yeong; Kang, Won Ki; Park, Young Suk; Kim, Seung Tae

2018-03-02

Increased mesenchymal-epithelial transition factor gene (c-MET) expression in several human malignancies is related to increased tumor progression and is a new potential drug target for several types of cancers. In the present study, we investigated the incidence of c-MET overexpression and its prognostic significance in patients with colorectal cancer (CRC). We retrospectively reviewed the data from 255 stage IV CRC patients who had results from a c-MET immunohistochemical test at Samsung Medical Center. We explored the relationships between c-MET overexpression and clinicopathological features and survival. Primary tumor sites were 67 right-sided colon, 98 left-sided colon, and 90 rectum. Forty-two patients (16.7%) had poorly differentiated or mucinous carcinoma. Among the 255 patients, 39 (15.3%) exhibited c-MET overexpression. There was no significant difference in the prevalence of c-MET overexpression according to primary site, histologic differentiation, molecular markers, or metastatic sites. In a comparison of the tumor response to first-line chemotherapy according to the level of c-MET expression, we found no significant difference in either partial response or disease control rate. In the survival analysis, patients with c-MET overexpression had significantly shorter overall survival (39 vs. 27 months; P = .018) and progression-free survival (PFS) during bevacizumab treatment (10 vs. 7 months; P = .024). c-MET overexpression, which was detected in 39 CRC patients (15.3%) irrespective of primary sites or molecular markers, indicated a poor survival prognosis and predicted shorter PFS during bevacizumab treatment in patients with CRC. Further studies are warranted to elucidate the value of c-MET-targeted therapy in CRC patients. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

What is the risk of urinary tract infection in children with antenatally presenting dilating vesico-ureteric reflux?

PubMed

Evans, Kathryn; Asimakadou, Maria; Nwankwo, Oluchi; Desai, Divyesh; Cherian, Abraham; Mushtaq, Imran; Cuckow, Peter; Duffy, Patrick; Smeulders, Naima

2015-04-01

The incidence of recurrent urinary tract infection (UTI) in children with primary vesico-ureteric reflux (VUR) presenting symptomatically is well documented. The risk of UTI in asymptomatic primary VUR diagnosed on investigation of antenatal hydronephrosis (ANH) is less clear. Paradoxically, several previous studies have suggested a lower risk (1-25%). We ascertain the incidence of UTI amongst antenatally-presenting primary VUR and explore risk factors. All patients <16 years managed for primary VUR between 1997 and 2013 were retrospectively reviewed. Patients were identified by searching 'VUR, vesicoureteric reflux' and 'vesico' in the clinical database. Sex, follow up, antibiotic prophylaxis, age at UTI, grade of VUR, radioisotope imaging findings (CRN-congenital reflux nephropathy, NRD-new renal defects), evidence of bladder dysfunction, surgical intervention and resolution were recorded. UTI diagnosis was based on positive urine culture with symptoms including fever. SPSS statistical package and Pearson's Chi-squared test were used to explore significance. Of 308 patients with primary VUR aged <16 years treated, 242 were diagnosed following presentation with UTI. The remaining 66 (21%) were initially asymptomatic, and VUR was diagnosed on investigation of ANH. All were given prophylaxis from birth. Six months to 16years (median 6years) follow-up was available for 54 (42 males, 12 females). All but two patients had grade III-V VUR (96%), bilaterally in 41 (76%). CRN was evident in 30 (56%; all male) and bladder dysfunction in 12 (22%; 10 males). Twenty-eight patients (52%) developed a UTI. The risk of UTI was 58% in girls, 33% in boys without CRN and 57% in boys with CRN (p = 0.17). Bladder dysfunction was a significant risk factor for UTI (p = 0.03). All 8 (15%; 7 males) with NRD had had a UTI. A single UTI appeared responsible for the majority of NRD (6/8; 75%). UTI occurred in 6/27 (22%) boys after circumcision compared to 17/25 (68%) prior/without circumcision (p < 0.05). The incidence of UTI in VUR detected after presentation with ANH was 52%. CRN and bladder dysfunction were risk factors for developing a UTI. Circumcision appears to significantly reduce the risk of infection. Antenatal presentation of primary VUR does not carry a reduced risk of UTI. A single UTI, in half before the age of six months, seemed responsible for the majority of NRD. In boys, the highest risk of UTI is in the first few months of infancy, despite antibiotic prophylaxis, and other interventions, particularly circumcision, should therefore be considered as early as possible. Copyright © 2015 Journal of Pediatric Urology Company. Published by Elsevier Ltd. All rights reserved.

Stress Sensors and Signal Transducers in Cyanobacteria

PubMed Central

Los, Dmitry A.; Zorina, Anna; Sinetova, Maria; Kryazhov, Sergey; Mironov, Kirill; Zinchenko, Vladislav V.

2010-01-01

In living cells, the perception of environmental stress and the subsequent transduction of stress signals are primary events in the acclimation to changes in the environment. Some molecular sensors and transducers of environmental stress cannot be identified by traditional and conventional methods. Based on genomic information, a systematic approach has been applied to the solution of this problem in cyanobacteria, involving mutagenesis of potential sensors and signal transducers in combination with DNA microarray analyses for the genome-wide expression of genes. Forty-five genes for the histidine kinases (Hiks), 12 genes for serine-threonine protein kinases (Spks), 42 genes for response regulators (Rres), seven genes for RNA polymerase sigma factors, and nearly 70 genes for transcription factors have been successfully inactivated by targeted mutagenesis in the unicellular cyanobacterium Synechocystis sp. PCC 6803. Screening of mutant libraries by genome-wide DNA microarray analysis under various stress and non-stress conditions has allowed identification of proteins that perceive and transduce signals of environmental stress. Here we summarize recent progress in the identification of sensory and regulatory systems, including Hiks, Rres, Spks, sigma factors, transcription factors, and the role of genomic DNA supercoiling in the regulation of the responses of cyanobacterial cells to various types of stress. PMID:22294932

Neutrophils differentially attenuate immune response to Aspergillus infection through complement receptor 3 and induction of myeloperoxidase.

PubMed

Goh, Jessamine G; Ravikumar, Sharada; Win, Mar Soe; Cao, Qiong; Tan, Ai Ling; Lim, Joan H J; Leong, Winnie; Herbrecht, Raoul; Troke, Peter F; Kullberg, Bart Jan; Netea, Mihai G; Chng, Wee Joo; Dan, Yock Young; Chai, Louis Y A

2018-03-01

Invasive aspergillosis (IA) remains a major cause of morbidity in immunocompromised hosts. This is due to the inability of the host immunity to respond appropriately to Aspergillus. An established risk factor for IA is neutropenia that is encountered by patients undergoing chemotherapy. Herein, we investigate the role of neutrophils in modulating host response to Aspergillus. We found that neutrophils had the propensity to suppress proinflammatory cytokine production but through different mechanisms for specific cytokines. Cellular contact was requisite for the modulation of interleukin-1 beta production by Aspergillus with the involvement of complement receptor 3. On the other hand, inhibition of tumour necrosis factor-alpha production (TNF-α) was cell contact-independent and mediated by secreted myeloperoxidase. Specifically, the inhibition of TNF-α by myeloperoxidase was through the TLR4 pathway and involved interference with the mRNA transcription of TNF receptor-associated factor 6/interferon regulatory factor 5. Our study illustrates the extended immune modulatory role of neutrophils beyond its primary phagocytic function. The absence of neutrophils and loss of its inhibitory effect on cytokine production explains the hypercytokinemia seen in neutropenic patients when infected with Aspergillus. © 2017 John Wiley & Sons Ltd.

Delayed recovery from anesthesia: A postgraduate educational review.

PubMed

Misal, Ullhas Sudhakarrao; Joshi, Suchita Annasaheb; Shaikh, Mudassir Mohd

2016-01-01

Delayed awakening from anesthesia remains one of the biggest challenges that involve an anesthesiologist. With the general use of fast-acting anesthetic agents, patients usually awaken quickly in the postoperative period. The time to emerge from anesthesia is affected by patient factors, anesthetic factors, duration of surgery, and painful stimulation. The principal factors responsible for delayed awakening following anesthesia are anesthetic agents and medications used in the perioperative period. Nonpharmacological causes may have a serious sequel, hence recognizing these organic conditions is important. Certain underlying metabolic disorders such as hypoglycemia, severe hyperglycemia, and electrolyte imbalance, especially hypernatremia, hypoxia, hypercapnia, central anticholinergic syndrome, chronic hypertension, liver disease, hypoalbuminemia, uremia, and severe hypothyroidism may also be responsible for delayed recovery following anesthesia. Unexpected delayed emergence after general anesthesia may also be due to intraoperative cerebral hypoxia, hemorrhage, embolism, or thrombosis. Accurate diagnosis of the underlying cause is the key for the institution of appropriate therapy, but primary management is to maintain airway, breathing, and circulation. This comprehensive review discusses the risk factors, causes, evaluation and management of delayed recovery based on our clinical experience, and literature search on the internet, supported by the standard textbooks of anesthesiology.

Impact of systemically active neurohumoral factors on the erectile response of the rat.

PubMed

MacKenzie, Lindsay D; Heaton, Jeremy P W; Adams, Michael A

2011-09-01

Mean arterial pressure (MAP) and specific regulation of penile blood flow are the primary determinants of an erection. While this concept is well recognized, the differential relationship between systemically acting vasoactive factors on arterial pressure and erectile responses is not well described. The aim of this study was to determine how the modification of systemic levels of neurohumoral factors impacts on the magnitude and efficiency of the erectile response. The main outcome measures for this study are changes in MAP and intracavernosal pressure (ICP) following electrostimulation of the cavernous nerve. Anesthetized adult, male Sprague-Dawley rats were catheterized for measuring MAP (carotid), ICP, and drug administration (vena cava). Erections were induced via cavernous nerve electrostimulation. Vasoactive drug infusions were used to produce changes in MAP levels including: hexamethonium, angiotensin II (ANGII)±hexamethonium, methoxamine±hexamethonium, losartan, MAHMA NONOate, and terbutaline. In general, ICP and MAP were linearly correlated regardless of treatment. Hexamethonium markedly dropped MAP and proportionately decreased the magnitude of the erectile response. ANGII or methoxamine given to hexamethonium-pretreated or untreated rats increased MAP similarly, but produced contrasting effects on erectile responses. ANGII-induced pressor responses were associated with increased erectile responses whereas all methoxamine treatments markedly decreased erectile responses. Depressor changes with losartan or terbutaline, but not MAHMA NONOate, also impacted negatively on the efficiency of the erectile responses at lower arterial pressures. In general, the magnitude of the erectile responses was found to be dependent upon the level of MAP, although the mechanism by which arterial pressure was changed impacted substantially on the characteristics of the relationship. The major finding was that circulation-wide α-adrenoceptor stimulation was extremely deleterious to erectile responses whereas global stimulation of ANG II receptors was actually proerectile. Overall, the results indicate that neurohumoral specificity in systemic hemodynamic control is also critical in establishing the optimal erectile environment in rats. © 2011 International Society for Sexual Medicine.

Is receptor oligomerization causally linked to activation of the EGF receptor kinase?

NASA Technical Reports Server (NTRS)

Rintoul, D. A.; Spooner, B. S. (Principal Investigator)

1992-01-01

Transduction of a signal from an extracellular peptide hormone to produce an intracellular response is often mediated by a cell surface receptor, which is usually a glycoprotein. The secondary intracellular signal(s) generated after hormone binding to the receptor have been intensively studied. The nature of the primary signal generated by ligand binding to the receptor is understood less well in most cases. The particular case of the epidermal growth factor (EGF) receptor is analyzed, and evidence for or against two dissimilar models of primary signal transduction is reviewed. Evidence for the most widely accepted current model is found to be unconvincing. Evidence for the other model is substantial but indirect; a direct test of this model remains to be done.

Predictors of response to anti-tumor necrosis factor therapy in ulcerative colitis.

PubMed

Zampeli, Evanthia; Gizis, Michalis; Siakavellas, Spyros I; Bamias, Giorgos

2014-08-15

Ulcerative colitis (UC) is an immune-mediated, chronic inflammatory disease of the large intestine. Its course is characterized by flares of acute inflammation and periods of low-grade chronic inflammatory activity or remission. Monoclonal antibodies against tumor necrosis factor (anti-TNF) are part of the therapeutic armamentarium and are used in cases of moderate to severe UC that is refractory to conventional treatment with corticosteroids and/or immunosuppressants. Therapeutic response to these agents is not uniform and a large percentage of patients either fail to improve (primary non-response) or lose response after a period of improvement (secondary non-response/loss of response). In addition, the use of anti-TNF agents has been related to uncommon but potentially serious adverse effects that preclude their administration or lead to their discontinuation. Finally, use of these medications is associated with a considerable cost for the health system. The identification of parameters that may predict response to anti-TNF drugs in UC would help to better select for patients with a high probability to respond and minimize risk and costs for those who will not respond. Analysis of the major clinical trials and the accumulated experience with the use of anti-TNF drugs in UC has resulted to the report of such prognostic factors. Included are clinical and epidemiological characteristics, laboratory markers, endoscopic indicators and molecular (immunological/genetic) signatures. Such predictive parameters of long-term outcomes may either be present at the commencement of treatment or determined during the early period of therapy. Validation of these prognostic markers in large cohorts of patients with variable characteristics will facilitate their introduction into clinical practice and the best selection of UC patients who will benefit from anti-TNF therapy.

Diversification, phylogeny and evolution of auxin response factor (ARF) family: insights gained from analyzing maize ARF genes.

PubMed

Wang, Yijun; Deng, Dexiang; Shi, Yating; Miao, Nan; Bian, Yunlong; Yin, Zhitong

2012-03-01

Auxin response factors (ARFs), member of the plant-specific B3 DNA binding superfamily, target specifically to auxin response elements (AuxREs) in promoters of primary auxin-responsive genes and heterodimerize with Aux/IAA proteins in auxin signaling transduction cascade. In previous research, we have isolated and characterized maize Aux/IAA genes in whole-genome scale. Here, we report the comprehensive analysis of ARF genes in maize. A total of 36 ARF genes were identified and validated from the B73 maize genome through an iterative strategy. Thirty-six maize ARF genes are distributed in all maize chromosomes except chromosome 7. Maize ARF genes expansion is mainly due to recent segmental duplications. Maize ARF proteins share one B3 DNA binding domain which consists of seven-stranded β sheets and two short α helixes. Twelve maize ARFs with glutamine-rich middle regions could be as activators in modulating expression of auxin-responsive genes. Eleven maize ARF proteins are lack of homo- and heterodimerization domains. Putative cis-elements involved in phytohormones and light signaling responses, biotic and abiotic stress adaption locate in promoters of maize ARF genes. Expression patterns vary greatly between clades and sister pairs of maize ARF genes. The B3 DNA binding and auxin response factor domains of maize ARF proteins are primarily subjected to negative selection during selective sweep. The mixed selective forces drive the diversification and evolution of genomic regions outside of B3 and ARF domains. Additionally, the dicot-specific proliferation of ARF genes was detected. Comparative genomics analysis indicated that maize, sorghum and rice duplicate chromosomal blocks containing ARF homologs are highly syntenic. This study provides insights into the distribution, phylogeny and evolution of ARF gene family.

Injury prevention in child and adolescent sport: whose responsibility is it?

PubMed

Emery, Carolyn A; Hagel, Brent; Morrongiello, Barbara A

2006-11-01

Sport and recreational injuries are a leading cause of morbidity in youth. There is a significant body of literature on risk factors for sport-related injuries and a growing body of research supporting the effectiveness of sport-specific prevention strategies in youth. Given the predictability and preventability of injuries in youth sport, the purpose of this article is to develop a model that considers societal responsibility for injury prevention in youth sport, and to discuss the evidence that supports this model. Previously published papers have provided a basis for expert opinion to discuss an approach to examining the shared societal responsibility for implementing countermeasures to reduce the risk of injury to youth during sports. Based on a historical perspective, broad conceptual framework, and specific evidence for prevention strategies in youth sport, the authors have developed and supported a theoretical model that defines a responsibility hierarchy in preventing injuries in youth sport. An argument has been made for a hierarchy of responsibility, with the lowest level of responsibility assigned to the child, and the highest level to those organizations or groups with the potential to effect the most change. The justification for this approach has been discussed in the context of the desirability of passive prevention strategies, the limited evidence for the effectiveness of strategies relying solely on behavior change in children and parents, and the level of perceptual and cognitive development in children that inadequately prepares them to take primary responsibility for their own safety in sport. The development of effective programs to reduce the burden of sport injury among youth necessitates a scientific approach, the identification of key risk factors for injury, a thorough examination of how factors interact to affect risk, and the identification of potential barriers to the effectiveness of injury-prevention programs.

Impaired Immune Response to Primary but Not to Booster Vaccination Against Hepatitis B in Older Adults.

PubMed

Weinberger, Birgit; Haks, Mariëlle C; de Paus, Roelof A; Ottenhoff, Tom H M; Bauer, Tanja; Grubeck-Loebenstein, Beatrix

2018-01-01

Many current vaccines are less immunogenic and less effective in elderly compared to younger adults due to age-related changes of the immune system. Most vaccines utilized in the elderly contain antigens, which the target population has had previous contact with due to previous vaccination or infection. Therefore, most studies investigating vaccine-induced immune responses in the elderly do not analyze responses to neo-antigens but rather booster responses. However, age-related differences in the immune response could differentially affect primary versus recall responses. We therefore investigated the impact of age on primary and recall antibody responses following hepatitis B vaccination in young and older adults. Focused gene expression profiling was performed before and 1 day after the vaccination in order to identify gene signatures predicting antibody responses. Young (20-40 years; n  = 24) and elderly (>60 years; n  = 17) healthy volunteers received either a primary series (no prior vaccination) or a single booster shot (documented primary vaccination more than 10 years ago). Antibody titers were determined at days 0, 7, and 28, as well as 6 months after the vaccination. After primary vaccination, antibody responses were lower and delayed in the elderly compared to young adults. Non-responders after the three-dose primary series were only observed in the elderly group. Maximum antibody concentrations after booster vaccination were similar in both age groups. Focused gene expression profiling identified 29 transcripts that correlated with age at baseline and clustered in a network centered around type I interferons and pro-inflammatory cytokines. In addition, smaller 8- and 6-gene signatures were identified at baseline that associated with vaccine responsiveness during primary and booster vaccination, respectively. When evaluating the kinetic changes in gene expression profiles before and after primary vaccination, a 33-gene signature, dominated by IFN-signaling, pro-inflammatory cytokines, inflammasome components, and immune cell subset markers, was uncovered that was associated with vaccine responsiveness. By contrast, no such transcripts were identified during booster vaccination. Our results document that primary differs from booster vaccination in old age, in regard to antibody responses as well as at the level of gene signatures. www.clinicaltrialsregister.eu, this trial was registered at the EU Clinical Trial Register (EU-CTR) with the EUDRACT-Nr. 2013-002589-38.

Factors influencing and modifying the decision to pursue genetic testing for skin cancer risk.

PubMed

Fogel, Alexander L; Jaju, Prajakta D; Li, Shufeng; Halpern-Felsher, Bonnie; Tang, Jean Y; Sarin, Kavita Y

2017-05-01

Across cancers, the decision to pursue genetic testing is influenced more by subjective than objective factors. However, skin cancer, which is more prevalent, visual, and multifactorial than many other malignancies, may offer different motivations for pursuing such testing. The primary objective was to determine factors influencing the decision to receive genetic testing for skin cancer risk. A secondary objective was to assess the impact of priming with health questions on the decision to receive testing. We distributed anonymous online surveys through ResearchMatch.org to assess participant health, demographics, motivations, and interest in pursuing genetic testing for skin cancer risk. Two surveys with identical questions but different question ordering were used to assess the secondary objective. We received 3783 responses (64% response rate), and 85.8% desired testing. Subjective factors, including curiosity, perceptions of skin cancer, and anxiety, were the most statistically significant determinants of the decision to pursue testing (P < .001), followed by history of sun exposure (odds ratio 1.85, P < .01) and history of skin cancer (odds ratio 0.5, P = .01). Age and family history of skin cancer did not influence this decision. Participants increasingly chose testing if first queried about health behaviors (P < .0001). The decision to pursue hypothetical testing may differ from in-clinic decision-making. Self-selected, online participants may differ from the general population. Surveys may be subject to response bias. The decision to pursue genetic testing for skin cancer is primarily determined by subjective factors, such as anxiety and curiosity. Health factors, including skin cancer history, also influenced decision-making. Priming with consideration of objective health factors can increase the desire to pursue testing. Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Anti-Epidermal Growth Factor Receptor Therapy in Head and Neck Squamous Cell Carcinoma: Focus on Potential Molecular Mechanisms of Drug Resistance

PubMed Central

Baay, Marc; Wouters, An; Specenier, Pol; Vermorken, Jan B.; Peeters, Marc; Lardon, Filip

2013-01-01

Targeted therapy against the epidermal growth factor receptor (EGFR) is one of the most promising molecular therapeutics for head and neck squamous cell carcinoma (HNSCC). EGFR is overexpressed in a wide range of malignancies, including HNSCC, and initiates important signal transduction pathways in HNSCC carcinogenesis. However, primary and acquired resistance are serious problems and are responsible for low single-agent response rate and tumor recurrence. Therefore, an improved understanding of the molecular mechanisms of resistance to EGFR inhibitors may provide valuable indications to identify biomarkers that can be used clinically to predict response to EGFR blockade and to establish new treatment options to overcome resistance. To date, no predictive biomarker for HNSCC is available in the clinic. Therapeutic resistance to anti-EGFR therapy may arise from mechanisms that can compensate for reduced EGFR signaling and/or mechanisms that can modulate EGFR-dependent signaling. In this review, we will summarize some of these molecular mechanisms and describe strategies to overcome that resistance. PMID:23821327

Examing the Validity of the Adapted Alabama Parenting Questionnaire Parent Global Report Version

PubMed Central

Maguin, Eugene; Nochajski, Thomas; Dewit, David; Safyer, Andrew

2015-01-01

The purpose of the present study was to comprehensively examine the validity of an adapted version of the parent global report form of the Alabama Parenting Questionnaire (APQ) with respect to its factor structure, relationships with demographic and response style covariates, and differential item functioning (DIF). The APQ was adapted by omitting the Corporal Punishment and the other discipline items. The sample consisted of 674 Canadian and United States families having a 9–12 year old child and at least one parent-figure who had received treatment within the past five years for alcohol problems or met criteria for alcohol abuse or dependence. The primary parent in each family completed the APQ. The four factor CFA model of the four published scales used and the three factor CFA model of those scales from prior research were rejected. Exploratory structural equation modeling was then used. The final three factor model combined the author-defined Involvement and Positive Parenting scales and retained the original Poor Monitoring/Supervision and Inconsistent Discipline scales. However, there were substantial numbers of moderate magnitude cross-loadings and large magnitude residual covariances. Differential item functioning (DIF) was observed for a number of APQ items. Controlling for DIF, response style and demographic variables were related significantly to the factors. PMID:26348028

Antarctic Space Analog Program

NASA Technical Reports Server (NTRS)

Palinkas, Lawrence A; Gunderson, E. K. Eric; Johnson, Jeffrey C.; Holland, Albert W.

1998-01-01

The primary aim of this project was to examine group dynamics and individual performance in extreme, isolated environments and identify human factors requirements for long-duration space missions using data collected in an analog environment. Specifically, we wished to determine: 1) the characteristics of social relations in small groups of individuals living and working together in extreme, isolated environments, and 2) the environmental, social and psychological determinants of performance effectiveness in such groups. These two issues were examined in six interrelated studies using data collected in small, isolated research stations in Antarctica from 1963 to the present. Results from these six studies indicated that behavior and performance on long-duration space flights is likely to be seasonal or cyclical, situational, social, and salutogenic in nature. The project responded to two NASA program emphases for FY 1997 as described in the NRA: 1) the primary emphasis of the Behavior and Performance Program on determining long-term individual and group performance responses to space, identifying critical factors affecting those responses and understanding underlying mechanisms involved in behavior and performance, and developing and using ground-based models and analogs for studying space-related behavior and performance; and 2) the emphasis of the Data Analysis Program on extended data analysis. Results from the study were used to develop recommendations for the design and development of pre-flight crew training and in-flight psychological countermeasures for long-duration manned space missions.

Compact fluorescent lights and the impact of convenience and knowledge on household recycling rates.

PubMed

Wagner, Travis P

2011-06-01

Increased energy costs, social marketing campaigns, public subsidies, and reduced retail prices have dramatically increased the number of compact fluorescent lights (CFLs) installed worldwide. CFLs provide many benefits, but they contain a very small amount of mercury. Given the billions of CFLs in use worldwide, they represent a significant source of mercury unless CFLs are recycled and the mercury recovered in an environmentally sound manner. In the state of Maine (northeast United States), despite mandated recycling of CFLs and availability of free CFL recycling, the household CFL recycling rate is very low. A study was undertaken to identify the primary factors responsible for low recycling. The first step was to survey householders who use CFLs. The 520 survey responses indicated that insufficient knowledge regarding recycling and inconvenience of the collection system are the two primary factors for the low recycling rate. To validate these findings, the second step was an examination of the current collection system to assess (a) the knowledge requirements necessary for recycling and (b) the convenience of the collection system. The results of this examination validated that knowledge requirements were excessively difficult to fulfill and the collection system is not sufficiently convenient. Based on these results, waste managers should focus on increasing convenience and simplifying access to information when designing or improving household collection and recycling of CFLs. Copyright © 2011 Elsevier Ltd. All rights reserved.

Comparison of interactive voice response, patient mailing, and mailed registry to encourage screening for osteoporosis: a randomized controlled trial.

PubMed

Heyworth, L; Kleinman, K; Oddleifson, S; Bernstein, L; Frampton, J; Lehrer, M; Salvato, K; Weiss, T W; Simon, S R; Connelly, M

2014-05-01

Guidelines recommend screening for osteoporosis with bone mineral density (BMD) testing in menopausal women, particularly those with additional risk factors for fracture. Many eligible women remain unscreened. This randomized study demonstrates that a single outreach interactive voice response phone call improves rates of BMD screening among high-risk women age 50-64. Osteoporotic fractures are a major cause of disability and mortality. Guidelines recommend screening with BMD for menopausal women, particularly those with additional risk factors for fracture. However, many women remain unscreened. We examined whether telephonic interactive voice response (IVR) or patient mailing could increase rates of BMD testing in high risk, menopausal women. We studied 4,685 women age 50-64 years within a not-for-profit health plan in the United States. All women had risk factors for developing osteoporosis and no prior BMD testing or treatment for osteoporosis. Patients were randomly allocated to usual care, usual care plus IVR, or usual care plus mailed educational materials. To avoid contamination, patients within a single primary care physician practice were randomized to receive the same intervention. The primary endpoint was BMD testing at 12 months. Secondary outcomes included BMD testing at 6 months and medication use at 12 months. Mean age was 57 years. Baseline demographic and clinical characteristics were similar across the three study groups. In adjusted analyses, the incidence of BMD screening was 24.6% in the IVR group compared with 18.6% in the usual care group (P < 0.001). There was no difference between the patient mailing group and the usual care group (P = 0.3). In this large community-based randomized trial of high risk, menopausal women age 50-64, IVR, but not patient mailing, improved rates of BMD screening. IVR remains a viable strategy to incorporate in population screening interventions.

Flying qualities and control system characteristics for superaugmented aircraft

NASA Technical Reports Server (NTRS)

Myers, T. T.; Mcruer, D. T.; Johnston, D. E.

1984-01-01

Aircraft-alone dynamics and superaugmented control system fundamental regulatory properties including stability and regulatory responses of the basic closed-loop systems; fundamental high and low frequency margins and governing factors; and sensitivity to aircraft and controller parameters are addressed. Alternative FCS mechanizations, and mechanizational side effects are also discussed. An overview of flying qualities considerations encompasses general pilot operations as a controller in unattended, intermittent and trim, and full-attention regulatory or command control; effective vehicle primary and secondary response properties to pilot inputs and disturbances; pilot control architectural possibilities; and comparison of superaugmented and conventional aircraft path responses for different forms of pilot control. Results of a simple experimental investigation into pilot dynamic behavior in attitude control of superaugmented aircraft configurations with high frequency time laps and time delays are presented.

TGFβ induces GDNF responsiveness in neurons by recruitment of GFRα1 to the plasma membrane

PubMed Central

Peterziel, H.; Unsicker, K.; Krieglstein, K.

2002-01-01

We have previously shown that the neurotrophic effect of glial cell line–derived neurotrophic factor (GDNF) in vitro and in vivo requires the presence of transforming growth factor (TGF)β. Using primary neurons (chick E8 ciliary) we show that the combination of GDNF plus TGFβ promotes survival, whereas the single factors do not. This cooperative effect is inhibited by blocking the extracellular signal-regulated kinase (ERK)/MAPK pathway, but not by interfering with the PI3 kinase signaling cascade. Although there is no functional GDNF signaling in the absence of TGFβ, pretreatment with TGFβ confers GDNF responsiveness to the cells. This is not due to upregulation of GDNF receptors mRNA and protein, but to TGFβ-induced recruitment of the glycosyl-phosphatidylinositol-anchored GDNF receptor (GFR)α1 to the plasma membrane. This is supported by the fact that GDNF in the presence of a soluble GFRα1 can promote survival in the absence of TGFβ. Our data suggest that TGFβ is involved in GFRα1 membrane translocation, thereby permitting GDNF signaling and neurotrophic effects. PMID:12370242

Variation in Inflammatory/Regulatory Cytokines in Secondary, Tertiary, and Quaternary Challenges with Dengue Virus

PubMed Central

Sierra, Beatriz; Pérez, Ana B.; Alvarez, Mayling; García, Gissel; Vogt, Katrin; Aguirre, Eglys; Schmolke, Kathrin; Volk, Hans-Dieter; Guzmán, María G.

2012-01-01

Secondary heterologous dengue infection is a risk factor for severe disease manifestations because of the immune-enhancement phenomenon. Succeeding clinical infections are seldom reported, and the clinical course of tertiary and quaternary dengue infections is not clear. Cuba represents a unique environment to study tertiary/quaternary dengue infections in a population with known clinical and serologic dengue markers and no dengue endemicity. We took advantage of this exceptional epidemiologic condition to study the effect of primary, secondary, tertiary, and quaternary dengue infection exposure on the expression of pro-inflammatory and regulatory cytokines, critical in dengue infection pathogenesis, by using a dengue infection ex vivo model. Whereas secondary exposure induced a high cytokine response, we found a significantly lower expression of tumor necrosis factor-α, interferon-γ, interleukin-10, and tumor growth factor-β after tertiary and quaternary infectious challenge. Significant differences in expression of the cytokines were seen between the dengue immune profiles, suggesting that the sequence in which the immune system encounters serotypes may be important in determining the nature of the immune response to subsequent infections. PMID:22802438

Developing a response to family violence in primary health care: the New Zealand experience.

PubMed

Gear, Claire; Koziol-McLain, Jane; Wilson, Denise; Clark, Faye

2016-08-20

Despite primary health care being recognised as an ideal setting to effectively respond to those experiencing family violence, responses are not widely integrated as part of routine health care. A lack of evidence testing models and approaches for health sector integration, alongside challenges of transferability and sustainability, means the best approach in responding to family violence is still unknown. The Primary Health Care Family Violence Responsiveness Evaluation Tool was developed as a guide to implement a formal systems-led response to family violence within New Zealand primary health care settings. Given the difficulties integrating effective, sustainable responses to family violence, we share the experience of primary health care sites that embarked on developing a response to family violence, presenting the enablers, barriers and resources required to maintain, progress and sustain family violence response development. In this qualitative descriptive study data were collected from two sources. Firstly semi-structured focus group interviews were conducted during 24-month follow-up evaluation visits of primary health care sites to capture the enablers, barriers and resources required to maintain, progress and sustain a response to family violence. Secondly the outcomes of a group activity to identify response development barriers and implementation strategies were recorded during a network meeting of primary health care professionals interested in family violence prevention and intervention; findings were triangulated across the two data sources. Four sites, representing three PHOs and four general practices participated in the focus group interviews; 35 delegates from across New Zealand attended the network meeting representing a wider perspective on family violence response development within primary health care. Enablers and barriers to developing a family violence response were identified across four themes: 'Getting started', 'Building effective relationships', 'Sourcing funding' and 'Shaping a national approach to family violence'. The strong commitment of key people dedicated to addressing family violence is essential for response sustainability and would be strengthened by prioritising family violence response as a national health target with dedicated resourcing. Further analysis of the health care system as a complex adaptive system may provide insight into effective approaches to response development and health system integration.

Alcohol as a Factor in 911 Calls in Denver.

PubMed

Joseph, Daniel; Vogel, Jody A; Smith, C Sam; Barrett, Whitney; Bryskiewicz, Gary; Eberhardt, Aaron; Edwards, David; Rappaport, Lara; Colwell, Christopher B; McVaney, Kevin E

2018-02-08

Excessive alcohol consumption is associated with a substantial number of emergency department visits annually and is responsible for a significant number of lives lost each year in the United States. However, a minimal amount is known about the impact of alcohol on the EMS system. The primary objective was to determine the proportion of 9-1-1 calls in Denver, Colorado in which (1) alcohol was a contributing factor or (2) the individual receiving EMS services had recently ingested alcohol. The secondary objectives were to compare the characteristics of EMS calls and to estimate the associated costs. This was a prospective observational cohort study of EMS calls for adults from July 1, 2012, to June 30, 2014. Primary outcomes for the study were alcohol as a contributing factor to the EMS call and recent alcohol consumption by the patient receiving EMS services. Logistic regression was utilized to determine the associations between EMS call characteristics and the outcomes. Cost was estimated using historic data. During the study period, 169,642 EMS calls were completed by the Denver Health Paramedic Division. Of these 71% were medical and 29% were trauma-related. The median age was 45 (interquartile range [IQR] 29-59) years, and 55% were male. 50,383 calls (30%) had alcohol consumption, and 49,165 (29%) had alcohol as a contributing factor. Alcohol related calls were associated with male sex, traumatic injuries including head trauma, emergent response, use of airway adjuncts, cardiac monitoring, glucose measurement, use of restraints, use of spinal precautions, and administration of medications for sedation. Estimated costs to the EMS system due to alcohol intoxication exceeded $14 million dollars over the study period and required in excess of 37 thousand hours of paramedic time. Compared to 9-1-1 calls that do not involve alcohol, alcohol-related calls are more likely to involve male patients, emergent response, traumatic injuries, advanced monitoring, airway adjuncts, and medications for sedation. This represents a significant burden on the emergency system and society. Further studies are needed to evaluate whether additional interventions such as social services could be used to lessen this burden.

Meeting highlights--International Consensus Panel on the treatment of primary breast cancer.

PubMed

Taguchi, Tetsuo

2002-03-01

The 7th International Conference on Adjuvant Therapy of Primary Breast Cancer, with several thousand delegates from 70 countries, was held in February 2001 in St. Gallen, Switzerland. Its consensus recommendations were summarized in the Sept. 15 issue of the Journal of Clinical Oncology (Vol. 19, No. 18, 2001: pp 3817-3827). The panel conference developed guidelines advising that all patients with endocrine-responsive tumors receive anti-hormonal therapy, including those at minimal risk of recurrence (defined as a 10% risk at 10 years). The panel further lowered the threshold defining endocrine-responsive disease to tumors containing as few as 1% of cells that stain positive for steroid hormone receptors. Treatment of primary breast cancer should depend on the hormonal status of tumors. The last set of guidelines, issued in 1998, supported a more limited use of endocrine-based therapy, but recent research has convinced the oncology community otherwise. Postmenopausal women have the greatest prevalence of hormone-positive tumors, and more than one-third of breast cancers in women of child-bearing age are estrogen dependent. The panel also highlighted several other important advances, including: the importance of factoring patient preferences into treatment decisions; the value of sentinel lymph node biopsy in avoiding extensive surgery; and incorporation of new agents and improved outcome in the treatment of breast cancer.

Early Growth Response 1 (Egr-1) Regulates N-Methyl-d-aspartate Receptor (NMDAR)-dependent Transcription of PSD-95 and α-Amino-3-hydroxy-5-methyl-4-isoxazole Propionic Acid Receptor (AMPAR) Trafficking in Hippocampal Primary Neurons*

PubMed Central

Qin, Xike; Jiang, Yongjun; Tse, Yiu Chung; Wang, Yunling; Wong, Tak Pan; Paudel, Hemant K.

2015-01-01

The N-methyl-d-aspartate receptor (NMDAR) controls synaptic plasticity and memory function and is one of the major inducers of transcription factor Egr-1 in the hippocampus. However, how Egr-1 mediates the NMDAR signal in neurons has remained unclear. Here, we show that the hippocampus of mice lacking Egr-1 displays electrophysiology properties and ultrastructure that are similar to mice overexpressing PSD-95, a major scaffolding protein of postsynaptic density involved in synapse formation, synaptic plasticity, and synaptic targeting of AMPA receptors (AMPARs), which mediate the vast majority of excitatory transmission in the CNS. We demonstrate that Egr-1 is a transcription repressor of the PSD-95 gene and is recruited to the PSD-95 promoter in response to NMDAR activation. Knockdown of Egr-1 in rat hippocampal primary neurons blocks NMDAR-induced PSD-95 down-regulation and AMPAR endocytosis. Likewise, overexpression of Egr-1 in rat hippocampal primary neurons causes reduction in PSD-95 protein level and promotes AMPAR endocytosis. Our data indicate that Egr-1 is involved in NMDAR-mediated PSD-95 down-regulation and AMPAR endocytosis, a process important in the expression of long term depression. PMID:26475861

Functional characterisation of bovine TLR5 indicates species-specific recognition of flagellin☆

PubMed Central

Metcalfe, Hannah J.; La Ragione, Roberto M.; Smith, David G.E.; Werling, Dirk

2014-01-01

Mammalian toll-like receptor 5 (TLR5) senses flagellin of several bacterial species and has been described to activate the innate immune system. To assess the role of bovine TLR5 (boTLR5) in the cattle system, we cloned and successfully expressed boTLR5 in human embryonic kidney (HEK) 293 cells, as indicated by quantitative PCR and confocal microscopy. However, in contrast to huTLR5-transfected cells, exposure of boTLR5-transfected cells to flagellin neither activated nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) nor CXCL8 production. Subsequent comparison of the flagellin response induced in human and bovine primary macrophages revealed that flagellin did not lead to phosphorylation of major signalling molecules. Furthermore, the CXCL8 and TNFα response of primary bovine macrophages stimulated with flagellin was very low compared to that observed in human primary macrophages. Our results indicate that cattle express a functional TLR5 albeit with different flagellin sensing qualities compared to human TLR5. However, boTLR5 seemed to play a different role in the bovine system compared to the human system in recognizing flagellin, and other potentially intracellular expressed receptors may play a more important role in the bovine system to detect flagellin. PMID:24461722

Activated dendritic cells delivered in tissue compatible biomatrices induce in-situ anti-tumor CTL responses leading to tumor regression

PubMed Central

Verma, Vivek; Kim, Young; Lee, Min-Cheol; Lee, Jae-Tae; Cho, Sunghoon; Park, In-Kyu; Min, Jung Joon; Lee, Je Jung; Lee, Shee Eun; Rhee, Joon Haeng

2016-01-01

Dendritic cell (DC) based anti-cancer immunotherapy is well tolerated in patients with advanced cancers. However, the clinical responses seen after adoptive DC therapy have been suboptimal. Several factors including scarce DC numbers in tumors and immunosuppressive tumor microenvironments contribute to the inefficacy of DCs as cellular vaccines. Hence DC based vaccines can benefit from novel methods of cell delivery that would prevent the direct exposure of immune cells to suppressive tumor microenvironments. Here we evaluated the ability of DCs harbored in biocompatible scaffolds (referred to as biomatrix entrapped DCs; beDCs) in activating specific anti-tumor immune responses against primary and post-surgery secondary tumors. Using a preclinical cervical cancer and a melanoma model in mice, we show that single treatment of primary and post-surgery secondary tumors using beDCs resulted in significant tumor growth retardation while multiple inoculations were required to achieve a significant anti-tumor effect when DCs were given in free form. Additionally, we found that, compared to the tumor specific E6/E7 peptide vaccine, total tumor lysate induced higher expression of CD80 and CD40 on DCs that induced increased levels of IFNγ production upon interaction with host lymphocytes. Remarkably, a strong immunocyte infiltration into the host-implanted DC-scaffold was observed. Importantly, the host-implanted beDCs induced the anti-tumor immune responses in the absence of any stromal cell support, and the biomatrix structure was eventually absorbed into the surrounding host tissue. Collectively, these data indicate that the scaffold-based DC delivery may provide an efficient and safe way of delivering cell-based vaccines for treatment of primary and post-surgery secondary tumors. PMID:27223090

Factors that influence career choice in primary care among medical students starting social service in Honduras.

PubMed

Puertas, E Benjamín; Rivera, Tamara Y

2016-11-01

To 1) describe patterns of specialty choice; 2) investigate relationships between career selection and selected demographic indicators; and 3) identify salary perception, factors that influence career choice in primary care, and factors that influence desired location of future medical practice. The study used a mixed-methods approach that included a cross-sectional questionnaire survey applied to 234 last-year medical students in Honduras (September 2014), and semi-structured interviews with eight key informants (October 2014). Statistical analysis included chi-square and factor analysis. An alpha level of 0.05 was used to determine significance. In the qualitative analysis, several codes were associated with each other, and five major themes emerged. Primary care careers were the preferred choice for 8.1% of students, who preferred urban settings for future practice location. The perceived salary of specialties other than primary care was significantly higher than those of general practitioners, family practitioners, and pediatricians (P < 0.001). Participants considered "making a difference," income, teaching, prestige, and challenging work the most important factors influencing career choice. Practice in ambulatory settings was significantly associated with a preference for primary care specialties (P = < 0.05). Logistic regression analysis found that factors related to patient-based care were statistically significant for selecting primary care (P = 0.006). The qualitative analysis further endorsed the survey findings, identifying additional factors that influence career choice (future work option; availability of residency positions; and social factors, including violence). Rationales behind preference of a specialty appeared to be based on a combination of ambition and prestige, and on personal and altruistic considerations. Most factors that influence primary care career choice are similar to those found in the literature. There are several factors distinctive to medical students in Honduras-most of them barriers to primary care career choice.

Multiple brief interventions in police custody: The MuBIC randomized controlled study for primary prevention in police custody. Protocol and preliminary results of a feasibility study in the Paris metropolitan area, France.

PubMed

Lefèvre, Thomas; Denis, Céline; Marchand, Claire; Vidal, Camille; Gagnayre, Rémi; Chariot, Patrick

2018-07-01

The 15- to 35-year-old population has little contact with the health care system and is exposed to risk factors. Several studies demonstrated the feasibility of brief interventions (BIs) in different settings, e.g., in addiction medicine during police custody, where arrestees are entitled to a medical examination. Approximately 700,000 individuals are detained in police custody in France annually, and custody is an opportunity for young people to be medically examined. The characteristics of the detainees and previous experience with BIs suggest that custody is an opportunity to contribute to primary prevention. We propose to investigate the feasibility of such a contribution. The aim of this article is to present a study protocol and some preliminary results. The primary research objective is to assess the feasibility of performing brief interventions without a specific topic in police custody settings in arrestees aged 15-35 years. The secondary research objectives include i) testing four strategies for engaging in BIs that maximize the chances of success of the BI; ii) identifying the determinants that can orient the practitioner's choice to use a specific strategy over another one; and iii) analysing the differences between individuals who engage in BIs and those who do not and, in those who do engage, the determinants of success of the intervention. A two-step randomized and prospective study: i) randomization of eligible patients into 4 groups of 500 patients each; analysis of the response rates for each strategy; performance of the BI; and analyses of the associated factors and ii) a real-life, full-scale phase study evaluating the effectiveness of BIs performance of the BI; and analyses of the interventions. Analyses of the determinants of a positive response to BI, of success and of the topic of intervention will be conducted. The rates of BI performed, rates of success, and characteristics associated with response and with success are the main expected results. Additionally, the development and assessment of filter questions and an improved BI dedicated to primary prevention for police custody settings will be attained. Copyright © 2016 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.

Determining the effectiveness of a video-based contact intervention in improving attitudes of Penang primary care nurses towards people with mental illness

PubMed Central

Rashid, Abdul; O’Brien, Finian

2017-01-01

Background Mental illness-related stigma is common, and is associated with poorer outcomes in people with mental illness. This study evaluated the attitudes of primary care nurses towards people with mental illness and its associated factors; and the effectiveness of a short video-based contact intervention (VBCI) in improving these attitudes using a Malay version of the 15-item Opening Minds Stigma Scale for Healthcare Providers (OMS-HC-15-M). Methods A 5-minute VBCI was developed comprising elements of psychoeducation and interviews of people with mental illness and the people they interact with, relating to experience of mental illness and recovery. A pre-post cross-sectional study was conducted on 206 randomly selected primary care nurses in Penang, Malaysia. The OMS-HC-15-M questionnaire was administered before and immediately after participants viewed the VBCI. The difference in mean pre-post VBCI scores using paired t-tests, effect size and standardised response mean (SRM) were obtained. Factors correlating to attitudes were obtained using univariate and multivariate regression analyses. Results Differences in pre-post VBCI score were statistically significant (p<0.001) with a 14% score reduction, a moderate effect size and SRM at 0.97 (0.85–0.11) and 1.1 (0.97–1.2) respectively. By factoring in the Minimal Detectable Change statistic of 7.76, the VBCI produced a significant improvement of attitudes in 30% of the participants. Factors associated with less stigmatising attitudes at baseline were previous psychiatry-related training, desiring psychiatric training, and positive contact with people with mental illness. Conclusions This is the first study in Malaysia to show that a brief VBCI is effective in improving attitudes of primary care nurses towards people with mental illness in the immediate term. Further studies are needed to determine if these results can be sustained in the longer term and generalizable to other health care professionals. Qualitative studies are warranted to provide insight to the factors correlating to these attitudes. (300 words) PMID:29131841

Microbial diversity and community structure across environmental gradients in an seawater intruded shallow confined aquifer

NASA Astrophysics Data System (ADS)

Zhang, X.; Hu, B.

2017-12-01

Seawater intrusion has been an important topic in coastal hydrogeology and making previously freshwater ecosystems saline. Plant and animal responses to variation in the freshwater-saline interface have been well studied in the coastal zone. However, little is known about the biogeography or stability of microbial community response to seawater intrusion. The objective of this study is to characterize and compare bacterial and archaea community diversity and composition in 15 groundwater samples with varied salinity using high-throughput-sequencing of 16S ribosomal RNA genes. The dominant taxonomic group identified in all samples are proteobacteria for bacteria and crenarchaeota for archaea. The other main bacterial groups are varied in samples with different salinities including bacteroidetes, firmicutes and several unidentified taxonomys. A combination of environmental factors seems to influence the microbial community composition where organic carbon is a primary factor shaping microbial communities. Correlation analysis between the relative abundance of bacterial taxa and geochemical parameters uggested that rare taxa may contribute to biogeochemical processes taking place at the mixing zone of freshewater and saltwater. Our results help to understand how the physical and chemical factors shape the microbial community composition and set a baseline for upcoming studies to evaluate the response of this ecosystem to future changes and the efficacy of new remediation efforts.

Historical emissions of black and organic carbon aerosol from energy-related combustion, 1850-2000

NASA Astrophysics Data System (ADS)

Bond, Tami C.; Bhardwaj, Ekta; Dong, Rong; Jogani, Rahil; Jung, Soonkyu; Roden, Christoph; Streets, David G.; Trautmann, Nina M.

2007-06-01

We present an emission inventory of primary black carbon (BC) and primary organic carbon (OC) aerosols from fossil fuel and biofuel combustion between 1850 and 2000. We reconstruct fossil fuel consumption and represent changes in technology on a national and sectoral basis. Our estimates rely on new estimates of biofuel consumption, and updated emission factors for old technologies. Emissions of black carbon increase almost linearly, totaling about 1000 Gg in 1850, 2200 Gg in 1900, 3000 Gg in 1950, and 4400 Gg in 2000. Primary organic carbon shows a similar pattern, with emissions of 4100 Gg, 5800 Gg, 6700 Gg, and 8700 Gg in 1850, 1900, 1950, and 2000, respectively. Biofuel is responsible for over half of BC emission until about 1890, and dominates energy-related primary OC emission throughout the entire period. Coal contributes the greatest fraction of BC emission between 1880 and 1975, and is overtaken by emissions from biofuel around 1975, and by diesel engines around 1990. Previous work suggests a rapid rise in BC emissions between 1950 and 2000. This work supports a more gradual increase between 1950 and 2000, similar to the increase between 1850 and 1925; implementation of clean technology is a primary reason.

Arctigenin Increases Hemeoxygenase-1 Gene Expression by Modulating PI3K/AKT Signaling Pathway in Rat Primary Astrocytes.

PubMed

Jeong, Yeon-Hui; Park, Jin-Sun; Kim, Dong-Hyun; Kim, Hee-Sun

2014-11-01

In the present study, we found that the natural compound arctigenin inhibited hydrogen peroxide-induced reactive oxygen species (ROS) production in rat primary astrocytes. Since hemeoxygenase-1 (HO-1) plays a critical role as an antioxidant defense factor in the brain, we examined the effect of arctigenin on HO-1 expression in rat primary astrocytes. We found that arctigenin increased HO-1 mRNA and protein levels. Arctigenin also increases the nuclear translocation and DNA binding of Nrf2/c-Jun to the antioxidant response element (ARE) on HO-1 promoter. In addition, arctigenin increased ARE-mediated transcriptional activities in rat primary astrocytes. Further mechanistic studies revealed that arctigenin increased the phosphorylation of AKT, a downstream substrate of phosphatidylinositol 3-kinase (PI3K). Treatment of cells with a PI3K-specific inhibitor, LY294002, suppressed the HO-1 expression, Nrf2 DNA binding and ARE-mediated transcriptional activities in arctigenin-treated astrocyte cells. The results collectively suggest that PI3K/AKT signaling pathway is at least partly involved in HO-1 expression by arctigenin via modulation of Nrf2/ARE axis in rat primary astrocytes.

Arctigenin Increases Hemeoxygenase-1 Gene Expression by Modulating PI3K/AKT Signaling Pathway in Rat Primary Astrocytes

PubMed Central

Jeong, Yeon-Hui; Park, Jin-Sun; Kim, Dong-Hyun; Kim, Hee-Sun

2014-01-01

In the present study, we found that the natural compound arctigenin inhibited hydrogen peroxide-induced reactive oxygen species (ROS) production in rat primary astrocytes. Since hemeoxygenase-1 (HO-1) plays a critical role as an antioxidant defense factor in the brain, we examined the effect of arctigenin on HO-1 expression in rat primary astrocytes. We found that arctigenin increased HO-1 mRNA and protein levels. Arctigenin also increases the nuclear translocation and DNA binding of Nrf2/c-Jun to the antioxidant response element (ARE) on HO-1 promoter. In addition, arctigenin increased ARE-mediated transcriptional activities in rat primary astrocytes. Further mechanistic studies revealed that arctigenin increased the phosphorylation of AKT, a downstream substrate of phosphatidylinositol 3-kinase (PI3K). Treatment of cells with a PI3K-specific inhibitor, LY294002, suppressed the HO-1 expression, Nrf2 DNA binding and ARE-mediated transcriptional activities in arctigenin-treated astrocyte cells. The results collectively suggest that PI3K/AKT signaling pathway is at least partly involved in HO-1 expression by arctigenin via modulation of Nrf2/ARE axis in rat primary astrocytes. PMID:25489416

Modelling multiple hospital outcomes: the impact of small area and primary care practice variation.

PubMed

Congdon, Peter

2006-11-16

Appropriate management of care--for example, avoiding unnecessary attendances at, or admissions to, hospital emergency units when they could be handled in primary care--is an important part of health strategy. However, some variations in these outcomes could be due to genuine variations in health need. This paper proposes a new method of explaining variations in hospital utilisation across small areas and the general practices (GPs) responsible for patient primary care. By controlling for the influence of true need on such variations, one may identify remaining sources of excess emergency attendances and admissions, both at area and practice level, that may be related to the quality, resourcing or organisation of care. The present paper accordingly develops a methodology that recognises the interplay between population mix factors (health need) and primary care factors (e.g. referral thresholds), that allows for unobserved influences on hospitalisation usage, and that also reflects interdependence between hospital outcomes. A case study considers relativities in attendance and admission rates at a North London hospital involving 149 small areas and 53 GP practices. A fixed effects model shows variations in attendances and admissions are significantly related (positively) to area and practice need, and nursing home patients, and related (negatively) to primary care access and distance of patient homes from the hospital. Modelling the impact of known factors alone is not sufficient to produce a satisfactory fit to the observations, and random effects at area and practice level are needed to improve fit and account for overdispersion. The case study finds variation in attendance and admission rates across areas and practices after controlling for need, and remaining differences between practices may be attributable to referral behaviour unrelated to need, or to staffing, resourcing, and access issues. In managerial terms, the analysis points to the utility of formal statistical analysis of hospitalisation rates as a prelude to non-statistical investigation of primary care resourcing and organisation. For example, there may be implications for the location of staff involved in community management of chronic conditions; health managers may also investigate whether some practices have unusual populations (homeless, asylum seekers, students) that explain different hospital use patterns.

The Factors and Features of Museum Fatigue in Science Centres Felt by Korean Students

NASA Astrophysics Data System (ADS)

Kim, Minchul; Dillon, Justin; Song, Jinwoong

2018-03-01

One of the objectives of science education in science centres has been the enhancement of interest in science. However, museum fatigue has a negative impact on interest. Museum fatigue has been described as physical tiredness or a decrease in visitors' interest in a museum. The learning experience of students in science centres is also influenced by museum fatigue. The purpose of this study is to identify the phenomena of museum fatigue in science centres and to identity how it is manifested. First, we identified the factors causing museum fatigue in science centres using the data from an open-ended questionnaire which was given to 597 primary, middle and high school students in South Korea. From the responses to the questionnaire, 50 factors causing museum fatigue in science centres were identified. A second Likert-type questionnaire with the 50 factors of museum fatigue in science centres was administered to 610 primary, middle and high school students in South Korea. Using reliability and factor analyses, we developed a framework of the factors causing museum fatigue in science centres, which consists of three contexts, 12 categories and 50 factors. Secondly, through statistical analyses including T test and ANOVA analysis, the features of students' museum fatigue in science centres were analysed and compared regarding student gender, school level, interest in science, grade of school science, the number of visits, and type of visit. The results, which were found to be statistically significant, are reported and discussed. The findings of this study are intended to serve for a deeper understanding and practical improvement of science learning in science centres.

[Evaluation of the quality of medical care in primary care patients with metabolic syndrome].

PubMed

Modrego Navarro, Angel; Ramírez Espinosa, Manuel; Fustero Fernández, Mariví; Tarraga López, Pedro Juan; Bastida Calvo, José Carlos; Torras Tohà, Núria

2009-08-01

As there is a high prevalence of metabolic syndrome (MS) in the overweight population, their cardiovascular risk is also high and the review system in Spain appears to be inadequate. The present study was carried out to evaluate the quality of the medical care of these patients. Epidemiological, cross-sectional and multicenter study. A total of 138 primary care general practitioners from all over Spain included outpatients of both sexes, > 18 years old, with body mass index > or = 25 and with biochemical data from the last 6 months for fasting glucose, triglycerides, HDL-c and blood pressure. Self-evaluation, retrospective, internal and with data processing. Principal determinations: Degree of compliance of 12 evaluation criteria and description of MS factors. A total of 2,280 patients were analysed. MS prevalence was 53.2%. Biochemical data were significantly higher in patients with MS and the most prevalent risk factors were: triglycerides > 150 (49.6%), systolic blood pressure > 140 (40.8%), fasting glucose > or = 126 (38.4%). Poor compliance of a few but relevant criteria was responsible for a high percentage of errors in the medical care quality. Introduction of improvement activities in patients with MS in primary care is essential in the management and prevention of cardiovascular complications.

Response of Free-Living Nitrogen-Fixing Microorganisms to Land Use Change in the Amazon Rainforest

PubMed Central

Mirza, Babur S.; Potisap, Chotima; Nüsslein, Klaus; Bohannan, Brendan J. M.

2014-01-01

The Amazon rainforest, the largest equatorial forest in the world, is being cleared for pasture and agricultural use at alarming rates. Tropical deforestation is known to cause alterations in microbial communities at taxonomic and phylogenetic levels, but it is unclear whether microbial functional groups are altered. We asked whether free-living nitrogen-fixing microorganisms (diazotrophs) respond to deforestation in the Amazon rainforest, using analysis of the marker gene nifH. Clone libraries were generated from soil samples collected from a primary forest, a 5-year-old pasture originally converted from primary forest, and a secondary forest established after pasture abandonment. Although diazotroph richness did not significantly change among the three plots, diazotroph community composition was altered with forest-to-pasture conversion, and phylogenetic similarity was higher among pasture communities than among those in forests. There was also 10-fold increase in nifH gene abundance following conversion from primary forest to pasture. Three environmental factors were associated with the observed changes: soil acidity, total N concentration, and C/N ratio. Our results suggest a partial restoration to initial levels of abundance and community structure of diazotrophs following pasture abandonment, with primary and secondary forests sharing similar communities. We postulate that the response of diazotrophs to land use change is a direct consequence of changes in plant communities, particularly the higher N demand of pasture plant communities for supporting aboveground plant growth. PMID:24162570