The role of fluorine-18-fluorodeoxyglucose positron emission tomography in aggressive histological subtypes of thyroid cancer: an overview.

PubMed

Treglia, Giorgio; Annunziata, Salvatore; Muoio, Barbara; Salvatori, Massimo; Ceriani, Luca; Giovanella, Luca

2013-01-01

Aggressive histological subtypes of thyroid cancer are rare and have a poor prognosis. The most important aggressive subtypes of thyroid cancer are Hürthle cell carcinoma (HCTC) and anaplastic and poorly differentiated carcinoma (ATC and PDTC). The American Thyroid Association recently published guidelines for the management of patients with ATC, but no specific guidelines have been done about HCTC. We performed an overview of the literature about the role of Fluorine-18-Fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography (FDG-PET or PET/CT) in aggressive histological subtypes of thyroid cancer. Only few original studies about the role of FDG-PET or PET/CT in HCTC, PDTC, and ATC have been published in the literature. FDG-PET or PET/CT seems to be useful in staging or followup of invasive and metastatic HCTC. FDG-PET or PET/CT should be used in patients with ATC in initial staging and in the followup after surgery to evaluate metastatic disease. Some authors suggest the use of FDG-PET/CT in staging of PDTC, but more studies are needed to define the diagnostic use of FDG-PET/CT in this setting. Limited experience suggests the usefulness of FDG-PET or PET/CT in patients with more aggressive histological subtypes of DTC. However, DTC presenting as radioiodine refractory and FDG-PET positive should be considered aggressive tumours with poor prognosis.

Local and Global Studies of Ion Outflow From the High Latitude Ionosphere

NASA Technical Reports Server (NTRS)

Petersen, W. K.

1997-01-01

Ion outflow from the ionosphere plays a fundamental but poorly defined role in magnetospheric processes. The purpose of the research is to better understand the mass coupling between the Earth's ionosphere and Magnetosphere. The work performed under this grant falls in three areas: (1) event studies using archived data from the DE-1/2 satellites; (2) investigations using Data from the ISTP satellites; and (3) work supporting a Space Physics Educational Outreach (SPEO) grant supplement.

Development of an operational manual for a consultation-liaison psychiatry service.

PubMed

Wand, Anne Pf; Sharma, Swapnil; Carpenter, Lindsay J; Gatsi, Mike

2018-02-01

Consultation-liaison psychiatry (CLP) services sit between mental health and the general hospital, and risk being poorly understood by both systems. The aim of this study was to develop an operational manual for a CLP service, which defined functions and governance. The CLP literature was reviewed with a focus on descriptions of CLP roles, organisational processes, quality measures and service development. The CLP team held service planning meetings and met with members of the mental health and hospital executives. Site visits and collaboration with other CLP services occurred in defining the roles of the CLP service and organisational governance. A CLP operational document was developed, including a description of the service, its functions, staff roles and governance. Procedural information such as the CLP timetable, referral process, triage and assessment, documentation, activity recording, quality assurance and relevant policies were outlined. The development of a dedicated operational manual for CLP clarified the roles, functions and governance of CLP within the general hospital and mental health systems. The development process facilitated the engagement of key clinicians and administrators of these systems, the determination of quality improvement targets and greater transparency and accountability.

Gender Roles and Physical Function in Older Adults: Cross-Sectional Analysis of the International Mobility in Aging Study (IMIAS)

PubMed Central

Ahmed, Tamer; Vafaei, Afshin; Auais, Mohammad; Guralnik, Jack; Zunzunegui, Maria Victoria

2016-01-01

Objectives To examine the relationships between physical function and gender-stereotyped traits and whether these relationships are modified by sex or social context. Methods A total of 1995 community-dwelling older adults from the International Mobility in Aging Study (IMIAS) aged 65 to 74 years were recruited in Natal (Brazil), Manizales (Colombia), Tirana (Albania), Kingston (Ontario, Canada), and Saint-Hyacinthe (Quebec, Canada). We performed a cross-sectional analysis. Study outcomes were mobility disability, defined as having difficulty in walking 400 meters without assistance or climbing a flight of stairs without resting, and low physical performance, defined as a score < 8 on the Short Physical Performance Battery. The 12-item Bem Sex Role Inventory (BSRI) was used to classify participants into four gender roles (Masculine, Feminine, Androgynous, and Undifferentiated) using site-specific medians of femininity and masculinity as cut-off points. Poisson regression models were used to estimate prevalence rate ratios (PRR) of mobility disability and poor physical performance according to gender roles. Results In models adjusted for sex, marital status, education, income, and research site, when comparing to the androgynous role, we found higher prevalence of mobility disability and poor physical performance among participants endorsing the feminine role (PRR = 1.20, 95% confidence interval (CI) 1.03–1.39 and PRR = 1.37, CI 1.01–1.88, respectively) or the undifferentiated role (PRR = 1.23, 95% CI 1.07–1.42 and PRR = 1.58, CI 1.18–2.12, respectively). Participants classified as masculine did not differ from androgynous participants in prevalence rates of mobility disability or low physical performance. None of the multiplicative interactions by sex and research site were significant. Conclusion Feminine and undifferentiated gender roles are independent risk factors for mobility disability and low physical performance in older adults. Longitudinal research is needed to assess the mediation pathways through which gender-stereotyped traits influence functional limitations and to investigate the longitudinal nature of these relationships. PMID:27258050

Study of MET protein levels and MET gene copy number in 72 sinonasal intestinal-type adenocarcinomas.

PubMed

Projetti, Fabrice; Mesturoux, Laura; Coulibaly, Béma; Durand, Karine; Chaunavel, Alain; Léobon, Sophie; Gadeaud, Emilie; Caire, François; Bessède, Jean-Pierre; Labrousse, François

2015-11-01

Sinonasal intestinal-type adenocarcinomas (ITACs) have a poor prognosis, and are defined on the basis of their morphological similarities to colorectal adenocarcinomas. MET signaling pathway is involved in oncogenesis in various cancers. Nothing is currently known about the role of MET in ITACs. In a series of 72 ITACs, we investigated MET protein levels by immunohistochemistry (IHC) and gene copy number by in situ hybridization. These findings were analyzed as a function of clinical data, histological typing, and patient outcome. MET protein was overproduced in 64% of cases and chromosome 7 polysomy was observed in 52% of cases. No tumor displayed MET amplification. The presence of mucinous or solid histological components, T3/T4 tumors, and incomplete resection were associated with a poor outcome. MET is overproduced in about two third of ITACs, suggesting a role for the MET signaling pathway in the oncogenesis of these tumors. © 2014 Wiley Periodicals, Inc.

"Low Income"--Levels in the Jewish Population; The "Jewish Poor" in Los Angeles. A Summary of Findings.

ERIC Educational Resources Information Center

Massarik, Fred

The concept "Jewish Poor" is defined simply as Jewish households (viz. households containing one or more persons defined as Jewish) whose total household cash income (1969, comparable to U.S. Census) was under 4000 dollars. The data were obtained from four sources: (1) analysis of "Jewish Poor" drawn from Los Angeles phase of…

Poverty and transitions in health in later life.

PubMed

Adena, Maja; Myck, Michal

2014-09-01

Using a sample of Europeans aged 50+ from 12 countries in the Survey of Health, Ageing and Retirement in Europe (SHARE), we analyse the role of poor material conditions as a determinant of changes in health over a four- to five-year period. We find that poverty defined with respect to relative income has no effect on changes in health. However, broader measures of poor material conditions, such as subjective poverty or low wealth, significantly increase the probability of transition to poor health among the healthy and reduce the chance of recovery from poor health over the time interval analysed. In addition to this, the subjective measure of poverty has a significant effect on mortality, increasing it by 65% among men and by 68% among those aged 50-64. Material conditions affect health among older people. We suggest that if attempts to reduce poverty in later life and corresponding policy targets are to focus on the relevant measures, they should take into account broader definitions of poverty than those based only on relative incomes. Copyright © 2014 Elsevier Ltd. All rights reserved.

Low junctional adhesion molecule A expression correlates with poor prognosis in gastric cancer.

PubMed

Huang, Jin-Yu; Xu, Ying-Ying; Sun, Zhe; Wang, Zhen-Ning; Zhu, Zhi; Song, Yong-Xi; Luo, Yang; Zhang, Xue; Xu, Hui-Mian

2014-12-01

The aberrant expression of junctional adhesion molecule A (JAM-A), which has a close correlation with the development, progression, metastasis, and prognosis of cancer, has been frequently reported. However, neither JAM-A expression nor its correlation with clinicopathologic variables and patient survival has been defined in gastric cancers. Moreover, little is known about the role of JAM-A in gastric cancer progression. We carried out the present study to investigate the prognostic value of JAM-A expression in gastric cancer patients. Furthermore, the biological roles of JAM-A in gastric cancer progression were also investigated. We determined JAM-A expression in 167 primary gastric cancer tissues and 94 matched adjacent non-tumor tissues by immunohistochemistry. Transwell migration assays and matrigel invasion assays were used to explore the role of JAM-A in gastric cancer cells migration and invasion. CCK-8 assays were used to examine the effect of JAM-A on the proliferation of gastric cancer cells. JAM-A was downregulated in gastric cancer tissues. Low JAM-A expression was significantly associated with tumor size, lymphatic vessel invasion, lymph node metastasis, and TNM stage. Low JAM-A expression was also significantly associated with poor disease-specific survival in gastric cancer patients. Multivariate analysis demonstrated low JAM-A expression as an independent factor predicting poor survival. In addition, JAM-A had the effect on inhibition of gastric cancer cells migration and invasion. However, JAM-A had no significant effects on proliferation of gastric cancer cells. Low JAM-A expression correlates with poor clinical outcome and promotes cell migration and invasion in gastric cancer. Copyright © 2014 Elsevier Inc. All rights reserved.

On being supervised: getting value from a clinical supervisor and making the relationship work when it is not.

PubMed

Parker, Stephen; Suetani, Shuichi; Motamarri, Balaji

2017-12-01

The importance of clinical supervision is emphasised in psychiatric training programs. Despite this, the purpose and processes of supervision are often poorly defined. There is limited guidance available for trainees about their role in making supervision work. This paper considers the nature of supervision in psychiatric training and provides practical advice to help supervisees take active steps to make supervision work. In obtaining value from supervision, the active role of the supervisee in seeking feedback, finding value in criticism and building autonomy is emphasised. Additionally, the importance of exploring what value a supervisor can offer and maintaining realistic expectations is considered. Trainees can benefit from taking an active role in planning and managing their supervision to maximise their learning.

The Role of Fluorine-18-Fluorodeoxyglucose Positron Emission Tomography in Aggressive Histological Subtypes of Thyroid Cancer: An Overview

PubMed Central

Treglia, Giorgio; Annunziata, Salvatore; Muoio, Barbara; Salvatori, Massimo; Ceriani, Luca; Giovanella, Luca

2013-01-01

Aggressive histological subtypes of thyroid cancer are rare and have a poor prognosis. The most important aggressive subtypes of thyroid cancer are Hürthle cell carcinoma (HCTC) and anaplastic and poorly differentiated carcinoma (ATC and PDTC). The American Thyroid Association recently published guidelines for the management of patients with ATC, but no specific guidelines have been done about HCTC. We performed an overview of the literature about the role of Fluorine-18-Fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography (FDG-PET or PET/CT) in aggressive histological subtypes of thyroid cancer. Only few original studies about the role of FDG-PET or PET/CT in HCTC, PDTC, and ATC have been published in the literature. FDG-PET or PET/CT seems to be useful in staging or followup of invasive and metastatic HCTC. FDG-PET or PET/CT should be used in patients with ATC in initial staging and in the followup after surgery to evaluate metastatic disease. Some authors suggest the use of FDG-PET/CT in staging of PDTC, but more studies are needed to define the diagnostic use of FDG-PET/CT in this setting. Limited experience suggests the usefulness of FDG-PET or PET/CT in patients with more aggressive histological subtypes of DTC. However, DTC presenting as radioiodine refractory and FDG-PET positive should be considered aggressive tumours with poor prognosis. PMID:23653645

Structure of the large FK506-binding protein FKBP51, an Hsp90-binding protein and a component of steroid receptor complexes

PubMed Central

Sinars, Cindy R.; Cheung-Flynn, Joyce; Rimerman, Ronald A.; Scammell, Jonathan G.; Smith, David F.; Clardy, Jon

2003-01-01

The ability to bind immunosuppressive drugs such as cyclosporin and FK506 defines the immunophilin family of proteins, and the FK506-binding proteins form the FKBP subfamily of immunophilins. Some FKBPs, notably FKBP12 (the 12-kDa FK506-binding protein), have defined roles in regulating ion channels or cell signaling, and well established structures. Other FKBPs, especially the larger ones, participate in important biological processes, but their exact roles and the structural bases for these roles are poorly defined. FKBP51 (the 51-kDa FKBP) associates with heat shock protein 90 (Hsp90) and appears in functionally mature steroid receptor complexes. In New World monkeys, FKBP51 has been implicated in cortisol resistance. We report here the x-ray structures of human FKBP51, to 2.7 Å, and squirrel monkey FKBP51, to 2.8 Å, by using multiwavelength anomalous dispersion phasing. FKBP51 is composed of three domains: two consecutive FKBP domains and a three-unit repeat of the TPR (tetratricopeptide repeat) domain. This structure of a multi-FKBP domain protein clarifies the arrangement of these domains and their possible interactions with other proteins. The two FKBP domains differ by an insertion in the second that affects the formation of the progesterone receptor complex. PMID:12538866

Neutrophils in Homeostasis, Immunity, and Cancer.

PubMed

Nicolás-Ávila, José Ángel; Adrover, José M; Hidalgo, Andrés

2017-01-17

Neutrophils were among the first leukocytes described and visualized by early immunologists. Prominent effector functions during infection and sterile inflammation classically placed them low in the immune tree as rapid, mindless aggressors with poor regulatory functions. This view is currently under reassessment as we uncover new aspects of their life cycle and identify transcriptional and phenotypic diversity that endows them with regulatory properties that extend beyond their lifetime in the circulation. These properties are revealing unanticipated roles for neutrophils in supporting homeostasis, as well as complex disease states such as cancer. We focus this review on these emerging functions in order to define the true roles of neutrophils in homeostasis, immunity, and disease. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of infant health on family food insecurity: evidence from two U.S. birth cohort studies.

PubMed

Corman, Hope; Noonan, Kelly; Reichman, Nancy E

2014-12-01

Extremely little is known about the effects of health on food insecurity despite strong associations between the two and a theoretical basis for this avenue of inquiry. This study uses data from two national birth cohort studies in the U.S., the Early Childhood Longitudinal Study-Birth Cohort (N = ∼9400) from 2001 to 2003 and the Fragile Families and Child Wellbeing Study (N = 2458) from 1998 to 2003, to estimate the effects of poor infant health on child and household food insecurity and explore the potential buffering effects of public programs that provide food, healthcare, and cash assistance. We address the issue of causality by defining poor infant health as an unexpected shock and conducting relevant specification tests. We find convincing evidence that poor infant health does not affect food insecurity but that it greatly increases reliance on cash assistance for low-income individuals with disabilities, which appears to be playing a buffering role. Copyright © 2014 Elsevier Ltd. All rights reserved.

A new balancing act: The many roles of melatonin and serotonin in plant growth and development

PubMed Central

Erland, Lauren A E; Murch, Susan J; Reiter, Russel J; Saxena, Praveen K

2015-01-01

Melatonin and serotonin are indoleamines first identified as neurotransmitters in vertebrates; they have now been found to be ubiquitously present across all forms of life. Both melatonin and serotonin were discovered in plants several years after their discovery in mammals, but their presence has now been confirmed in almost all plant families. The mechanisms of action of melatonin and serotonin are still poorly defined. Melatonin and serotonin possess important roles in plant growth and development, including functions in chronoregulation and modulation of reproductive development, control of root and shoot organogenesis, maintenance of plant tissues, delay of senescence, and responses to biotic and abiotic stresses. This review focuses on the roles of melatonin and serotonin as a novel class of plant growth regulators. Their roles in reproductive and vegetative plant growth will be examined including an overview of current hypotheses and knowledge regarding their mechanisms of action in specific responses. PMID:26418957

A new balancing act: The many roles of melatonin and serotonin in plant growth and development.

PubMed

Erland, Lauren A E; Murch, Susan J; Reiter, Russel J; Saxena, Praveen K

2015-01-01

Melatonin and serotonin are indoleamines first identified as neurotransmitters in vertebrates; they have now been found to be ubiquitously present across all forms of life. Both melatonin and serotonin were discovered in plants several years after their discovery in mammals, but their presence has now been confirmed in almost all plant families. The mechanisms of action of melatonin and serotonin are still poorly defined. Melatonin and serotonin possess important roles in plant growth and development, including functions in chronoregulation and modulation of reproductive development, control of root and shoot organogenesis, maintenance of plant tissues, delay of senescence, and responses to biotic and abiotic stresses. This review focuses on the roles of melatonin and serotonin as a novel class of plant growth regulators. Their roles in reproductive and vegetative plant growth will be examined including an overview of current hypotheses and knowledge regarding their mechanisms of action in specific responses.

How To Make the Most of Your Human: Design Considerations for Single Pilot Operations

NASA Technical Reports Server (NTRS)

Schutte, Paul C.

2015-01-01

Reconsidering the function allocation between automation and the pilot in the flight deck is the next step in improving aviation safety. The current allocation, based on who does what best, makes poor use of the pilot's resources and abilities. In some cases it may actually handicap pilots from performing their role. Improving pilot performance first lies in defining the role of the pilot - why a human is needed in the first place. The next step is allocating functions based on the needs of that role (rather than fitness), then using automation to target specific human weaknesses in performing that role. Examples are provided (some of which could be implemented in conventional cockpits now). Along the way, the definition of human error and the idea that eliminating/automating the pilot will reduce instances of human error will be challenged.

Immunostimulatory oligonucleotide-induced metaphase cytogenetics detect chromosomal aberrations in 80% of CLL patients: A study of 132 CLL cases with correlation to FISH, IgVH status, and CD38 expression.

PubMed

Dicker, Frank; Schnittger, Susanne; Haferlach, Torsten; Kern, Wolfgang; Schoch, Claudia

2006-11-01

Compared with fluorescence in situ hybridization (FISH), conventional metaphase cytogenetics play only a minor prognostic role in chronic lymphocytic leukemia (CLL) so far, due to technical problems resulting from limited proliferation of CLL cells in vitro. Here, we present a simple method for in vitro stimulation of CLL cells that overcomes this limitation. In our unselected patient population, 125 of 132 cases could be successfully stimulated for metaphase generation by culture with the immunostimulatory CpG-oligonucleotide DSP30 plus interleukin 2. Of 125 cases, 101 showed chromosomal aberrations. The aberration rate is comparable to the rate detected by parallel interphase FISH. In 47 patients, conventional cytogenetics detected additional aberrations not detected by FISH analysis. A complex aberrant karyotype, defined as one having at least 3 aberrations, was detected in 30 of 125 patients, compared with only one such case as defined by FISH. Conventional cytogenetics frequently detected balanced and unbalanced translocations. A significant correlation of the poor-prognosis unmutated IgV(H) status with unbalanced translocations and of the likewise poor-prognosis CD38 expression to balanced translocations and complex aberrant karyotype was found. We demonstrate that FISH analysis underestimates the complexity of chromosomal aberrations in CLL. Therefore, conventional cytogenetics may define subgroups of patients with high risk of progression.

Molecular systematics in the genus Mucor with special regards to species encountered in cheese.

PubMed

Hermet, Antoine; Méheust, Delphine; Mounier, Jérôme; Barbier, Georges; Jany, Jean-Luc

2012-06-01

The genus Mucor, a member of the order Mucorales, comprises different species encountered in cheeses. Although fungi play a fundamental role in cheese manufacturing and ripening, the taxonomy of many fungal species found in cheese is poorly defined; indeed, this is the case for Mucor spp. In the present study, we assessed the phylogenetic relationships among 70 Mucor strains, including 36 cheese isolates, by using a five gene phylogenetic approach combined with morphological analyses. Overall, at least six species of Mucor were identified among the cheese isolates including a possible new taxon. The present study also suggests that the genus Mucor comprises undescribed taxa and needs to be properly defined. Copyright © 2012 The British Mycological Society. Published by Elsevier Ltd. All rights reserved.

Triage of patients with acute gastrointestinal bleeding for intensive care unit admission based on risk factors for poor outcome.

PubMed

Afessa, B

2000-04-01

This study's aim was to determine the prognostic factors and to develop a triage system for intensive care unit (ICU) admission of patients with gastrointestinal bleeding (GIB). This prospective, observational study included 411 adults consecutively hospitalized for GIB. Each patient's selected clinical findings and laboratory values at presentation were obtained. The Acute Physiology and Chronic Health Evaluation (APACHE) II scores were calculated from the initial findings in the emergency department. Poor outcome was defined as recurrent GIB, emergency surgery, or death. The role of hepatic cirrhosis, APACHE II score, active GIB, end-organ dysfunction, and hypotension in predicting outcome was evaluated. Chi-square, Student's t, Mann-Whitney U, and logistic regression analysis tests were used for statistical comparisons. Poor outcome developed in 81 (20%) patients; 39 died, 23 underwent emergency surgery, and 47 rebled. End-organ dysfunction, active bleeding, hepatic cirrhosis, and high APACHE II scores were independent predictors of poor outcome with odds ratios of 3:1, 3:1, 2:3, and 1:1, respectively. The ICU admission rate was 37%. High APACHE II score, active bleeding, end-organ dysfunction, and hepatic cirrhosis are independent predictors of poor outcome in patients with GIB and can be used in the triage of these patients for ICU admission.

Elevated arousal levels enhance contrast perception.

PubMed

Kim, Dongho; Lokey, Savannah; Ling, Sam

2017-02-01

Our state of arousal fluctuates from moment to moment-fluctuations that can have profound impacts on behavior. Arousal has been proposed to play a powerful, widespread role in the brain, influencing processes as far ranging as perception, memory, learning, and decision making. Although arousal clearly plays a critical role in modulating behavior, the mechanisms underlying this modulation remain poorly understood. To address this knowledge gap, we examined the modulatory role of arousal on one of the cornerstones of visual perception: contrast perception. Using a reward-driven paradigm to manipulate arousal state, we discovered that elevated arousal state substantially enhances visual sensitivity, incurring a multiplicative modulation of contrast response. Contrast defines vision, determining whether objects appear visible or invisible to us, and these results indicate that one of the consequences of decreased arousal state is an impaired ability to visually process our environment.

Epidemiology and outcomes of acute encephalitis.

PubMed

Venkatesan, Arun

2015-06-01

This review seeks to describe recent advances in the epidemiology, outcomes, and prognostic factors in acute encephalitis. Infectious causes continue to account for the largest proportion of encephalitis cases in which a cause is identified, although autoimmune causes are increasingly recognized. Type-A gamma-aminobutyric acid (GABAa) receptor antibodies have been recently identified in encephalitis with refractory seizures, whereas the roles of antibodies to the glycine receptor and dipeptidyl peptidase-like protein 6 have been defined in progressive encephalomyelitis with rigidity and myoclonus. Recent findings in the US cases of encephalomyelitis presenting with acute flaccid paralysis raise the possibility that enterovirus D68, a common respiratory pathogen, may cause central nervous system disease. Mortality from acute encephalitis occurs in about 10% of cases, with a large proportion of survivors suffering from cognitive or physical disability. In addition to delay in institution of appropriate antiviral or immune therapy, several potentially reversible factors associated with poor prognosis have been identified, including cerebral edema, status epilepticus, and thrombocytopenia. Encephalitis imposes a significant worldwide health burden and is associated with poor outcomes. Supportive treatment and early institution of therapy may improve outcomes. Careful neurocognitive assessment of survivors of encephalitis is needed to better define long-term outcomes.

Cross-species functional analysis of cancer-associated fibroblasts identifies a critical role for CLCF1 and IL6 in non-small cell lung cancer in vivo

PubMed Central

Vicent, Silvestre; Sayles, Leanne C.; Vaka, Dedeepya; Khatri, Purvesh; Gevaert, Olivier; Chen, Ron; Zheng, Yanyan; Gillespie, Anna K.; Clarke, Nicole; Xu, Yue; Shrager, Joseph; Hoang, Chuong D.; Plevritis, Sylvia; Butte, Atul J.; Sweet-Cordero, E. Alejandro

2013-01-01

Cancer-associated fibroblasts (CAFs) have been reported to support tumor progression by a variety of mechanisms. However, their role in the progression of non-small cell lung cancer (NSCLC) remains poorly defined. In addition, the extent to which specific proteins secreted by CAFs contribute directly to tumor growth is unclear. To study the role of CAFs in NSCLC, a cross-species functional characterization of mouse and human lung CAFs was performed. CAFs supported the growth of lung cancer cells in vivo by secretion of soluble factors that directly stimulate the growth of tumor cells. Gene expression analysis comparing normal mouse lung fibroblasts (NFs) and mouse lung CAFs identified multiple genes that correlate with the CAF phenotype. A gene signature of secreted genes upregulated in CAFs was an independent marker of poor survival in NSCLC patients. This secreted gene signature was upregulated in NFs after long-term exposure to tumor cells, demonstrating that NFs are “educated” by tumor cells to acquire a CAF-like phenotype. Functional studies identified important roles for CLCF1-CNTFR and IL6-IL6R signaling, in promoting growth of NSCLC cells. This study identifies novel soluble factors contributing to the CAF protumorigenic phenotype in NSCLC and suggests new avenues for the development of therapeutic strategies. PMID:22962265

Mitochondrial Hepatopathies: Advances in Genetics and Pathogenesis

PubMed Central

Lee, Way S.; Sokol, Ronald J.

2013-01-01

Hepatic involvement is a common feature in childhood mitochondrial hepatopathies, particularly in the neonatal period. Respiratory chain disorders may present as neonatal acute liver failure, hepatic steatohepatitis, cholestasis, or cirrhosis with chronic liver failure of insidious onset. In recent years, specific molecular defects (mutations in nuclear genes such as SCO1, BCS1L, POLG, DGUOK, and MPV17 and the deletion or rearrangement of mitochondrial DNA) have been identified, with the promise of genetic and prenatal diagnosis. The current treatment of mitochondrial hepatopathies is largely ineffective, and the prognosis is generally poor. The role of liver transplantation in patients with liver failure remains poorly defined because of the systemic nature of the disease, which does not respond to transplantation. Prospective, longitudinal, multicentered studies will be needed to address the gaps in our knowledge in these rare liver diseases. PMID:17538929

Ego depletion interferes with rule-defined category learning but not non-rule-defined category learning.

PubMed

Minda, John P; Rabi, Rahel

2015-01-01

Considerable research on category learning has suggested that many cognitive and environmental factors can have a differential effect on the learning of rule-defined (RD) categories as opposed to the learning of non-rule-defined (NRD) categories. Prior research has also suggested that ego depletion can temporarily reduce the capacity for executive functioning and cognitive flexibility. The present study examined whether temporarily reducing participants' executive functioning via a resource depletion manipulation would differentially impact RD and NRD category learning. Participants were either asked to write a story with no restrictions (the control condition), or without using two common letters (the ego depletion condition). Participants were then asked to learn either a set of RD categories or a set of NRD categories. Resource depleted participants performed more poorly than controls on the RD task, but did not differ from controls on the NRD task, suggesting that self regulatory resources are required for successful RD category learning. These results lend support to multiple systems theories and clarify the role of self-regulatory resources within this theory.

Ego depletion interferes with rule-defined category learning but not non-rule-defined category learning

PubMed Central

Minda, John P.; Rabi, Rahel

2015-01-01

Considerable research on category learning has suggested that many cognitive and environmental factors can have a differential effect on the learning of rule-defined (RD) categories as opposed to the learning of non-rule-defined (NRD) categories. Prior research has also suggested that ego depletion can temporarily reduce the capacity for executive functioning and cognitive flexibility. The present study examined whether temporarily reducing participants’ executive functioning via a resource depletion manipulation would differentially impact RD and NRD category learning. Participants were either asked to write a story with no restrictions (the control condition), or without using two common letters (the ego depletion condition). Participants were then asked to learn either a set of RD categories or a set of NRD categories. Resource depleted participants performed more poorly than controls on the RD task, but did not differ from controls on the NRD task, suggesting that self regulatory resources are required for successful RD category learning. These results lend support to multiple systems theories and clarify the role of self-regulatory resources within this theory. PMID:25688220

ABC Transporters and Their Role in the Neoadjuvant Treatment of Esophageal Cancer

PubMed Central

Vaclavikova, Radka; Neoral, Cestmir; Vrba, Jiri; Aujesky, Rene; Matzenauer, Marcel; Melichar, Bohuslav

2018-01-01

The prognosis of esophageal cancer (EC) is poor, despite considerable effort of both experimental scientists and clinicians. The tri-modality treatment consisting of neoadjuvant chemoradiation followed by surgery has remained the gold standard over decades, unfortunately, without significant progress in recent years. Suitable prognostic factors indicating which patients will benefit from this tri-modality treatment are missing. Some patients rapidly progress on the neoadjuvant chemoradiotherapy, which is thus useless and sometimes even harmful. At the same time, other patients achieve complete remission on neoadjuvant chemoradiotherapy and subsequent surgery may increase their risk of morbidity and mortality. The prognosis of patients ranges from excellent to extremely poor. Considering these differences, the role of drug metabolizing enzymes and transporters, among other factors, in the EC response to chemotherapy may be more important compared, for example, with pancreatic cancer where all patients progress on chemotherapy regardless of the treatment or disease stage. This review surveys published literature describing the potential role of ATP-binding cassette transporters, the genetic polymorphisms, epigenetic regulations, and phenotypic changes in the prognosis and therapy of EC. The review provides knowledge base for further research of potential predictive biomarkers that will allow the stratification of patients into defined groups for optimal therapeutic outcome. PMID:29543757

HENMT1 and piRNA Stability Are Required for Adult Male Germ Cell Transposon Repression and to Define the Spermatogenic Program in the Mouse

PubMed Central

Lim, Shu Ly; Geoghegan, Joel; Hempfling, Anna-Lena; Bergmann, Martin; Goodnow, Christopher C.; Ormandy, Christopher J.; Wong, Lee; Mann, Jeff; Scott, Hamish S.; Jamsai, Duangporn; Adelson, David L.

2015-01-01

piRNAs are critical for transposable element (TE) repression and germ cell survival during the early phases of spermatogenesis, however, their role in adult germ cells and the relative importance of piRNA methylation is poorly defined in mammals. Using a mouse model of HEN methyltransferase 1 (HENMT1) loss-of-function, RNA-Seq and a range of RNA assays we show that HENMT1 is required for the 2’ O-methylation of mammalian piRNAs. HENMT1 loss leads to piRNA instability, reduced piRNA bulk and length, and ultimately male sterility characterized by a germ cell arrest at the elongating germ cell phase of spermatogenesis. HENMT1 loss-of-function, and the concomitant loss of piRNAs, resulted in TE de-repression in adult meiotic and haploid germ cells, and the precocious, and selective, expression of many haploid-transcripts in meiotic cells. Precocious expression was associated with a more active chromatin state in meiotic cells, elevated levels of DNA damage and a catastrophic deregulation of the haploid germ cell gene expression. Collectively these results define a critical role for HENMT1 and piRNAs in the maintenance of TE repression in adult germ cells and setting the spermatogenic program. PMID:26496356

A defined Oct4 level governs cell state transitions of pluripotency entry and differentiation into all embryonic lineages.

PubMed

Radzisheuskaya, Aliaksandra; Chia, Gloryn Le Bin; dos Santos, Rodrigo L; Theunissen, Thorold W; Castro, L Filipe C; Nichols, Jennifer; Silva, José C R

2013-06-01

Oct4 is considered a master transcription factor for pluripotent cell self-renewal, but its biology remains poorly understood. Here, we investigated the role of Oct4 using the process of induced pluripotency. We found that a defined embryonic stem cell (ESC) level of Oct4 is required for pluripotency entry. However, once pluripotency is established, the Oct4 level can be decreased up to sevenfold without loss of self-renewal. Unexpectedly, cells constitutively expressing Oct4 at an ESC level robustly differentiated into all embryonic lineages and germline. In contrast, cells with low Oct4 levels were deficient in differentiation, exhibiting expression of naive pluripotency genes in the absence of pluripotency culture requisites. The restoration of Oct4 expression to an ESC level rescued the ability of these to restrict naive pluripotent gene expression and to differentiate. In conclusion, a defined Oct4 level controls the establishment of naive pluripotency as well as commitment to all embryonic lineages.

The role of selective predation in harmful algal blooms

NASA Astrophysics Data System (ADS)

Solé, Jordi; Garcia-Ladona, Emilio; Estrada, Marta

2006-08-01

A feature of marine plankton communities is the occurrence of rapid population explosions. When the blooming species are directly or indirectly noxious for humans, these proliferations are denoted as harmful algal blooms (HAB). The importance of biological interactions for the appearance of HABs, in particular when the proliferating microalgae produce toxins that affect other organisms in the food web, remains still poorly understood. Here we analyse the role of toxins produced by a microalgal species and affecting its predators, in determining the success of that species as a bloom former. A three-species predator-prey model is used to define a criterion that determines whether a toxic microalga will be able to initiate a bloom in competition against a non-toxic one with higher growth rate. Dominance of the toxic species depends on a critical parameter that defines the degree of feeding selectivity by grazers. The criterion is applied to a particular simplified model and to numerical simulations of a full marine ecosystem model. The results suggest that the release of toxic compounds affecting predators may be a plausible biological factor in allowing the development of HABs.

Economic evaluations of non-communicable disease interventions in developing countries: a critical review of the evidence base

PubMed Central

Mulligan, Jo-Ann; Walker, Damian; Fox-Rushby, Julia

2006-01-01

Background Demographic projections suggest a major increase in non-communicable disease (NCD) mortality over the next two decades in developing countries. In a climate of scarce resources, policy-makers need to know which interventions represent value for money. The prohibitive cost of performing multiple economic evaluations has generated interest in transferring the results of studies from one setting to another. This paper aims to bridge the gap in the current literature by critically evaluating the available published data on economic evaluations of NCD interventions in developing countries. Methods We identified and reviewed the methodological quality of 32 economic evaluations of NCD interventions in developing countries. Developing countries were defined according to the World Bank classification for low- and lower middle-income countries. We defined NCDs as the 12 categories listed in the 1993 World Bank report Investing in Health. English language literature was searched for the period January 1984 and January 2003 inclusive in Medline, Science Citation Index, HealthStar, NHS Economic Evaluation Database and Embase using medical subheading terms and free text searches. We then assessed the quality of studies according to a set of pre-defined technical criteria. Results We found that the quality of studies was poor and resource allocation decisions made by local and global policy-makers on the basis of this evidence could be misleading. Furthermore we have identified some clear gaps in the literature, particularly around injuries and strategies for tackling the consequences of the emerging tobacco epidemic. Conclusion In the face of poor evidence the role of so-called generalised cost-effectiveness analyses has an important role to play in aiding public health decision-making at the global level. Further research is needed to investigates the causes of variation among cost, effects and cost-effectiveness data within and between settings. Such analyses still need to take a broad view, present data in a transparent manner and take account of local constraints. PMID:16584546

Poor Pre-Pregnancy and Antepartum Mental Health Predicts Postpartum Mental Health Problems among US Women: A Nationally Representative Population-Based Study

PubMed Central

Witt, Whitney P.; Wisk, Lauren E.; Cheng, Erika R.; Hampton, John M.; Creswell, Paul; Hagen, Erika W.; Spear, Hilary A.; Maddox, Torsheika; DeLeire, Thomas

2011-01-01

Purpose Mental health problems disproportionately affect women, particularly during childbearing years. However, there is a paucity of research on the determinants of postpartum mental health problems using representative US populations. Taking a life course perspective, we determined the potential risk factors for postpartum mental health problems, with a particular focus on the role of mental health before and during pregnancy. Methods We examined data on 1,863 mothers from eleven panels of the 1996-2006 Medical Expenditure Panel Survey (MEPS). Poor postpartum mental health was defined using self-reports of mental health conditions, symptoms of mental health conditions, or global mental health ratings of “fair” or “poor.” Results 9.5% of women reported experiencing postpartum mental health problems, with over half of these women reporting a history of poor mental health. Poor pre-pregnancy mental health and poor antepartum mental health both independently increased the odds of having postpartum mental health problems. Staged multivariate analyses revealed that poor antepartum mental health attenuated the relationship between pre-pregnancy and postpartum mental health problems. Additionally, significant disparities exist in women's report of postpartum mental health status. Conclusions While poor antepartum mental health is the strongest predictor of postpartum mental health problems, pre-pregnancy mental health is also important. Accordingly, health care providers should identify, treat, and follow women with a history of poor mental health, as they are particularly susceptible to postpartum mental health problems. This will ensure that women and their children are in the best possible health and mental health during the postpartum period and beyond. PMID:21349740

Hox Genes: Choreographers in Neural Development, Architects of Circuit Organization

PubMed Central

Philippidou, Polyxeni; Dasen, Jeremy S.

2013-01-01

Summary The neural circuits governing vital behaviors, such as respiration and locomotion, are comprised of discrete neuronal populations residing within the brainstem and spinal cord. Work over the past decade has provided a fairly comprehensive understanding of the developmental pathways that determine the identity of major neuronal classes within the neural tube. However, the steps through which neurons acquire the subtype diversities necessary for their incorporation into a particular circuit are still poorly defined. Studies on the specification of motor neurons indicate that the large family of Hox transcription factors has a key role in generating the subtypes required for selective muscle innervation. There is also emerging evidence that Hox genes function in multiple neuronal classes to shape synaptic specificity during development, suggesting a broader role in circuit assembly. This review highlights the functions and mechanisms of Hox gene networks, and their multifaceted roles during neuronal specification and connectivity. PMID:24094100

Liver Disease in Mitochondrial Disorders

PubMed Central

Lee, Way S.; Sokol, Ronald J.

2013-01-01

Liver involvement, a common feature in childhood mitochondrial hepatopathies, particularly in the neonatal period, may manifest as neonatal acute liver failure, hepatic steatohepatitis, cholestasis, or cirrhosis with chronic liver failure of insidious onset. There are usually significant neuromuscular symptoms, multisystem involvement, and lactic acidemia. The liver disease is usually progressive and eventually fatal. Current medical therapy of mitochondrial hepatopathies is largely ineffective, and the prognosis is usually poor. The role of liver transplantation in patients with liver failure remains poorly defined because of the systemic nature of the disease that does not respond to transplantation. Several specific molecular defects (mutations in nuclear genes such as SCO1, BCS1L, POLG, DGUOK, and MPV17 and deletion or rearrangement of mitochondrial DNA) have been identified in recent years. Prospective, longitudinal multicenter studies will be needed to address the gaps in our knowledge in these rare liver diseases. PMID:17682973

Lidar monitoring of regions of intense backscatter with poorly defined boundaries

Treesearch

Vladimir A. Kovalev; Alexander Petkov; Cyle Wold; WeiMin Hao

2011-01-01

The upper height of a region of intense backscatter with a poorly defined boundary between this region and a region of clear air above it is found as the maximal height where aerosol heterogeneity is detectable, that is, where it can be discriminated from noise. The theoretical basis behind the retrieval technique and the corresponding lidar-data-processing procedures...

Role of metabolic phenotyping in understanding obesity and related conditions in Gulf Co-operation Council countries.

PubMed

Ahmad, M S; Ashrafian, H; Alsaleh, M; Holmes, E

2015-12-01

Obesity is a major health concern in the Middle East and the incidence is rising in all sections of the population. Efforts to control obesity through diet and lifestyle interventions, and by surgical means, have had limited effect, and the gene-environment interactions underpinning the development of obesity and related pathologies such as metabolic syndrome, cardiovascular disease and certain cancers are poorly defined. Lifestyle, genetics, inflammation and the interaction between the intestinal bacteria and host metabolism have all been implicated in creating an obesogenic environment. We summarize the role of metabolic and microbial phenotyping in understanding the aetiopathogenesis of obesity and in characterizing the metabolic responses to surgical and non-surgical interventions, and explore the potential for clinical translation of this approach. © 2015 World Obesity.

New concept: cellular senescence in pathophysiology of cholangiocarcinoma.

PubMed

Sasaki, Motoko; Nakanuma, Yasuni

2016-01-01

Cholangiocarcinoma, a malignant tumor arising in the hepatobiliary system, presents with poor prognosis because of difficulty in its early detection/diagnosis. Recent progress revealed that cellular senescence may be involved in the pathophysiology of cholangiocarcinoma. Cellular senescence is defined as permanent growth arrest caused by several cellular injuries, such as oncogenic mutations and oxidative stress. "Oncogene-induced" and/or stress-induced senescence may occur in the process of multi-step cholangiocarcinogenesis, and overexpression of a polycomb group protein EZH2 may play a role in the escape from, and/or bypassing of, senescence. Furthermore, senescent cells may play important roles in tumor development and progression via the production of senescence-associated secretory phenotypes. Cellular senescence may be a new target for the prevention, early diagnosis, and therapy of cholangiocarcinoma in the near future.

The nursing contribution to nutritional care in cancer cachexia.

PubMed

Hopkinson, Jane B

2015-11-01

Cancer cachexia is a complex syndrome. Its defining feature is involuntary weight loss, which arises, in part, because of muscle atrophy and is accompanied by functional decline. International expert consensus recommends that nutritional support and counselling is a component of multimodal therapy for cancer cachexia, as poor nutritional intake can contribute to progression of the syndrome. The present paper focuses on what is presently known about the nursing contribution to nutritional care in cancer cachexia. There is potential for nurses to play an important role. However, obstacles to this include lack of a robust evidence base to support their nutritional care practices and unmet need for education about nutrition in cancer. The nursing role's boundaries and the outcomes of nurse-delivered nutritional care in cancer cachexia are both uncertain and should be investigated.

Seborrheic dermatitis: an update.

PubMed

Bukvić Mokos, Zrinka; Kralj, Martina; Basta-Juzbašić, Aleksandra; Lakoš Jukić, Ines

2012-01-01

Seborrheic dermatitis is a chronic relapsing inflammatory skin disorder clinically characterized by scaling and poorly defined erythematous patches. The prevalence of adult seborrheic dermatitis is estimated at 5%. Although the exact cause of seborrheic dermatitis has yet to be understood, Malassezia yeasts, hormones (androgens), sebum levels and immune response are known to play important roles in its development. Additional factors including drugs, winter temperatures and stress may exacerbate seborrheic dermatitis. A variety of treatment modalities are available, including antifungal agents, topical low-potency steroids and calcineurin inhibitors (immunomodulators). This review summarizes current knowledge on the etiopathogenesis and therapy of adult seborrheic dermatitis.

Long-term effects of bullying

PubMed Central

Wolke, Dieter; Lereya, Suzet Tanya

2015-01-01

Bullying is the systematic abuse of power and is defined as aggressive behaviour or intentional harm-doing by peers that is carried out repeatedly and involves an imbalance of power. Being bullied is still often wrongly considered as a ‘normal rite of passage’. This review considers the importance of bullying as a major risk factor for poor physical and mental health and reduced adaptation to adult roles including forming lasting relationships, integrating into work and being economically independent. Bullying by peers has been mostly ignored by health professionals but should be considered as a significant risk factor and safeguarding issue. PMID:25670406

Aerosol Forcing of Climate Change and Anomalous Atmospheric Absorption

NASA Technical Reports Server (NTRS)

Hansen, James E.

2000-01-01

The forcings that drive long-term climate change are not known with an accuracy sufficient to define future climate change, Anthropogenic greenhouse gases (GHGs), which are well-measured, cause a strong positive (warming) forcing. But other, poorly measured, anthropogenic forcings, especially changes of atmospheric aerosols, clouds, and land-use patterns, cause a negative forcing that tends to offset greenhouse warming. We will focus on the role of aerosols as a climate forcing mechanism and the contribution that aerosols might make to the so-called "anomalous" atmospheric absorption that has been inferred from some atmospheric measurements.

Aerosol Forcing of Climate Change and "Anomalous" Atmospheric Absorption

NASA Technical Reports Server (NTRS)

Hansen, James E.

1999-01-01

The forcings that drive long-term climate change are not known with an accuracy sufficient to define future climate change. Anthropogenic greenhouse gases (GHGs), which are well-measured, cause a strong positive (warming) forcing. But other, poorly measured, anthropogenic forcings, especially changes of atmospheric aerosols, clouds, and land-use patterns, cause a negative forcing that tends to offset greenhouse warming. We will focus on the role of aerosols as a climate forcing mechanism and the contribution that aerosols might make to the so- called "anomalous" atmospheric absorption that has been inferred from some atmospheric measurements.

Role of sensory information in the control of postural orientation in Parkinson's disease.

PubMed

Vaugoyeau, Marianne; Azulay, Jean-Philippe

2010-02-15

Clinical findings and experimental studies both in parkinsonian patients and on animal provide evidence that the control of the axial orientation is markedly impaired in Parkinson's disease (stooped posture, Camptocormia, Pisa syndrome). Nevertheless the postural orientation component in Parkinson's disease has been poorly investigated. One study reports that Parkinsonian patients present a major impairment of the postural orientation component in relation with a proprioceptive impairment. On the basis of these results, the visual dependence observed in Parkinsonian patients is re-defined as an adaptive strategy partly compensating for the impaired proprioception.

A novel role for autologous tumour cell vaccination in the immunotherapy of the poorly immunogenic B16-BL6 melanoma.

PubMed

Geiger, J D; Wagner, P D; Shu, S; Chang, A E

1992-06-01

The growth of immunogenic tumours stimulates the generation of tumour-sensitized, but not functional, pre-effector T cells in the draining lymph nodes. These pre-effector cells can mature into effector cells upon in-vitro stimulation with anti-CD3 and IL-2. In the current study, using a defined, poorly immunogenic tumour, B16-BL6 melanoma, the pre-effector cell response was not evident during progressive tumour growth but was elicited by vaccination with irradiated tumour cells admixed with Corynebacterium parvum. After anti-CD3/IL-2 activation, these cells were capable of mediating the regression of established pulmonary metastases. The efficacy of the vaccine depended on the doses of both tumour cells and the adjuvant. While higher numbers of tumour cells were more effective, an optimal dose (12.5 micrograms) of C. parvum was required. The dose of irradiation was not a critical factor. After vaccination, kinetic studies revealed that the pre-effector cell response was evident 4 days later and declined after 14 days. These observations illustrate the potential role of active immunization in the cellular therapy of cancer.

Alteration textures in terrestrial volcanic glass and the associated bacterial community.

PubMed

Cockell, C S; Olsson-Francis, K; Herrera, A; Meunier, A

2009-01-01

Alteration textures were examined in subglacial (hyaloclastite) deposits at Valafell, Southern Iceland. Pitted and 'elongate' alteration features are observed in the glass similar to granular and tubular features reported previously in deep-ocean basaltic glasses, but elongate features generally did not have a length to width ratio greater than five. Elongate features were found in only 7% of surfaces. Crystalline basalt clasts, which are incorporated into the hyaloclastite, did not display elongate structures. Pitted alteration features were poorly defined in crystalline basalt, comprising only 4% of the surface compared to 47% in the case of basaltic glass. Examination of silica-rich glass (obsidian) and rhyolite similarly showed poorly defined pitted textures that comprised less than 15% of the surface and no elongate features were observed. These data highlight the differences in alteration textures between terrestrial basaltic glass and previously studied deep-ocean and subsurface basaltic glass, and the important role of mineralogy in controlling the type and abundance of alteration features. The hyaloclastite contains a diverse and abundant bacterial population, as determined by 16S rDNA analysis, which could be involved in weathering the glass. Despite the presence of phototrophs, we show that they were not involved in the production of most alteration textures in the basaltic glass materials we examined.

Inflammation, Oxidative Stress, and Antioxidants Contribute to Selected Sleep Quality and Cardiometabolic Health Relationships: A Cross-Sectional Study.

PubMed

Kanagasabai, Thirumagal; Ardern, Chris I

2015-01-01

Sleep is vital for cardiometabolic health, but a societal shift toward poor sleep is a prominent feature of many modern cultures. Concurrently, factors such as diet and lifestyle have also changed and may mediate the relationship between sleep quality and cardiometabolic health. Objectives were to explore (1) the interrelationship and (2) mediating effect of inflammation, oxidative stress, and antioxidants on sleep quality and cardiometabolic health. Cross-sectional data from the US National Health and Nutritional Examination Survey 2005-06 (≥20 y; N = 2,072) was used. Cardiometabolic health was defined as per the Joint Interim Statement; overall sleep quality was determined from six sleep habits and categorized as good, fair, poor, and very poor. Fair quality sleepers had optimal inflammation, oxidative stress, and antioxidant levels. Inflammation was above the current clinical reference range across all sleep quality categories, while oxidative stress was only within the clinical reference range for fair sleep quality. Selected sleep quality-cardiometabolic health relationships were mediated by inflammation, oxidative stress, and antioxidants and were moderated by sex. Our results provide initial evidence of a potential role for inflammation, oxidative stress, and antioxidants in the pathway between poor sleep quality-cardiometabolic decline. Further prospective research is needed to confirm our results.

Quality of life from the perspective of the palliative care patient in a resource-poor community in South Africa.

PubMed

Jansen van Rensburg, Jacoba J M; Maree, Johanna E; van Belkum, Corrien

2013-02-01

Quality of life is an ill-defined term, as it means different things to different people. Quality of life has been well researched, especially with respect to people with cancer, but not necessarily from the perspective of the patient, and also, not in Third World, resource-poor countries. The objective of this study was to explore quality of life from the perspective of palliative care patients managed at a palliative care clinic serving a resource-poor community in Tshwane, South Africa. An exploratory, qualitative phenomenological study was conducted. The target population for this study was all patients managed at a palliative care clinic serving a resource-poor community in Tshwane. Self-report data were gathered by means of in-depth interviews. The data were analyzed using a template analysis style as well as content analysis using open coding. Data analysis was done concurrently with data gathering. Data saturation was reached after 10 interviews (n = 10). Three themes arose from the data: factors that had a positive influence on quality of life, factors that had a negative influence on quality of life, and experience of quality of life. Work played the most important role in quality of life whereas only one participant linked symptom control with quality of life. Experiencing symptoms, rejection, and stigmatization had a negative influence on quality of life. Friends and religion played a significant role and added to quality of life. Life was a daily struggle for survival. Poverty was so overwhelming that quality of life was primarily measured in terms of the ability to buy food and other basic commodities.

RON (MST1R) is a novel prognostic marker and therapeutic target for gastroesophageal adenocarcinoma

PubMed Central

Catenacci, Daniel VT; Cervantes, Gustavo; Yala, Soheil; Nelson, Erik A; El-Hashani, Essam; Kanteti, Rajani; El Dinali, Mohamed; Hasina, Rifat; Brägelmann, Johannes; Seiwert, Tanguy; Sanicola, Michele; Henderson, Les; Grushko, Tatyana A; Olopade, Olufunmilayo; Karrison, Theodore; Bang, Yung-Jue; Ho Kim, Woo; Tretiakova, Maria; Vokes, Everett; Frank, David A; Kindler, Hedy L; Huet, Heather

2011-01-01

RON (MST1R) is one of two members of the MET receptor tyrosine kinase family, along with parent receptor MET. RON has a putative role in several cancers, but its expression and function is poorly characterized in gastroesophageal adenocarcinoma. A recognized functional role of MET tyrosine kinase in gastroesophageal cancer has led to early phase clinical trials using MET inhibitors, with unimpressive results. Therefore, the role of RON in gastroesophageal cancer, as well as its role in cooperative signaling with MET and as a mechanism of resistance to MET inhibition, was studied in gastroesophageal tissues and cell lines. By IHC, RON was highly overexpressed in 74% of gastroesophageal samples (n = 94) and overexpression was prognostic of poor survival (p = 0.008); RON and MET co-expression occurred in 43% of samples and was prognostic of worst survival (p = 0.03). High MST1R gene copy number by quantitative polymerase chain reaction and confirmed by fluorescence in situ hybridization and/or array comparative genomic hybridization, was seen in 35.5% (16/45) of cases. High MST1R gene copy number correlated with poor survival (p = 0.01), and was associated with high MET and ERBB2 gene copy number. a novel somatic MST1R juxtamembrane mutation R1018G was found in 11% of samples. RON signaling was functional in cell lines, activating downstream effector STAT3, and resulted in increased viability over controls. RON and MET co-stimulation assays led to enhanced malignant phenotypes over stimulation of either receptor alone. Growth inhibition as evidenced by viability and apoptosis assays was optimal using novel blocking monoclonal antibodies to both ROn and MET, versus either alone. SU11274, a classic MET small molecule tyrosine kinase inhibitor, blocked signaling of both receptors and proved synergistic when combined with STAT3 inhibition (combination index <1). These preclinical studies define RON as an important novel prognostic marker and therapeutic target for gastroesophageal cancer warranting further investigation. PMID:21543897

Altruism in organ donation: an unnecessary requirement?

PubMed Central

Moorlock, Greg; Ives, Jonathan; Draper, Heather

2014-01-01

Altruism has long been taken to be the guiding principle of ethical organ donation in the UK, and has been used as justification for rejecting or allowing certain types of donation. We argue that, despite this prominent role, altruism has been poorly defined in policy and position documents, and used confusingly and inconsistently. Looking at how the term has been used over recent years allows us to define ‘organ donation altruism’, and comparing this with accounts in the philosophical literature highlights its theoretical shortcomings. The recent report from the Nuffield Council on Bioethics reaffirmed the importance of altruism in organ donation, and offered a clearer definition. This definition is, however, more permissive than that of altruism previously seen in UK policy, and as a result allows some donations that previously have been considered unacceptable. We argue that while altruistic motivation may be desirable, it is not necessary. PMID:23538329

A STUDY OF LONGITUDINAL PATTERNS OF FAILURE AMONG HIGH SCHOOL DROP-OUTS AND POORLY PERFORMING GRADUATES.

ERIC Educational Resources Information Center

STOLLER, DAVID S.

THE RELATIONSHIP BETWEEN PATTERNS OF POOR PERFORMANCE AND SIGNIFICANT DISTINGUISHING FACTORS WHICH MIGHT IDENTIFY DROPOUTS IS EXPLORED. DATA WERE OBTAINED ON 270 STUDENTS (FROM A PARENT POPULATION OF 2,500) WHO WERE POOR PERFORMERS (POOR PERFORMANCE BEING DEFINED AS THREE "D'S" OR "F'S" IN HIGH SCHOOL). THE VAST MAJORITY OF…

Interaction of sleep quality and sleep duration on glycemic control in patients with type 2 diabetes mellitus.

PubMed

Tang, Yunzhao; Meng, Lingling; Li, Daiqing; Yang, Min; Zhu, Yanjuan; Li, Chenguang; Jiang, Zhenhuan; Yu, Ping; Li, Zhu; Song, Hongna; Ni, Changlin

2014-01-01

Copious evidence from epidemiological and laboratory studies has revealed that sleep status is associated with glucose intolerance, insulin resistance, thus increasing the risk of developing type 2 diabetes. The aim of this study was to reveal the interaction of sleep quality and sleep quantity on glycemic control in patients with type 2 diabetes mellitus. From May 2013 to May 2014, a total of 551 type 2 diabetes patients in Tianjin Metabolic Diseases Hospital were enrolled. Blood samples were taken to measure glycosylated hemoglobin (HbA1c), and all the patients completed the Chinese version of the Pittsburgh Sleep Quality Index (PSQI) questionnaire to evaluate their sleep status. "Good sleep quality" was defined as PQSI <5, "average sleep quality" was defined as PQSI 6-8, and "poor sleep quality" was defined as PQSI >8. Poor glycemic control was defined as HbA1c ≥7%. Sleep quantity was categorized as <6, 6-8, and >8 hours/night. Short sleep time was defined as sleep duration <6 hours/night. In the poor glycemic control group, the rate of patients who had insufficient sleep was much higher than that in the other group (χ(2) = 11.16, P = 0.037). The rate of poor sleep quality in poor glycemic control group was much greater than that in the average control group (χ(2) = 9.79, P = 0.007). After adjusted by gender, age, body mass index, and disease duration, the adjusted PSQI score's OR was 1.048 (95% CI 1.007-1.092, P = 0.023) for HbA1c level. The sleep duration's OR was 0.464 (95% CI 0.236-0.912, P = 0.026) for HbA1c level. One-way analysis of variance showed that the poor sleep quality group had the highest homeostasis model assessment-insulin resistance (P < 0.01). Inadequate sleep, in both quality and quantity, should be regarded as a plausible risk factor for glycemic control in type 2 diabetes. Poor sleep might bring much more serious insulin resistance and could be the reason for bad glycemic control. A good night's sleep should be seen as a critical health component tool in the prevention and treatment of type 2 diabetes. It is important for clinicians to target the root causes of short sleep duration and/or poor sleep quality.

Global notes: counting the world's poor--how do we define poverty?

PubMed

Vidyasagar, D

2006-06-01

Health professionals are in constant interaction with parents and infants who are victims of poverty and poor socioeconomic status. But an important question remains: do we know how to define poverty? Defining poverty accurately is important as the definition is the basis of policy development. The definition of poverty has changed during the last quarter century. In addition to economic considerations, it is broadened to include other dimensions of life such as literacy, health and longevity. This article attempts to provide national and international definitions of poverty, the magnitude and effects of poverty.

What do peer support workers do? A job description.

PubMed

Jacobson, Nora; Trojanowski, Lucy; Dewa, Carolyn S

2012-07-19

The extant literature suggests that poorly defined job roles make it difficult for peer support workers to be successful, and hinder their integration into multi-disciplinary workplace teams. This article uses data gathered as part of a participatory evaluation of a peer support program at a psychiatric tertiary care facility to specify the work that peers do. Data were gathered through interviews, focus groups, and activity logs and were analyzed using a modified grounded theory approach. Peers engage in direct work with clients and in indirect work that supports their work with clients. The main types of direct work are advocacy, connecting to resources, experiential sharing, building community, relationship building, group facilitation, skill building/mentoring/goal setting, and socialization/self-esteem building. The main types of indirect work are group planning and development, administration, team communication, supervision/training, receiving support, education/awareness building, and information gathering and verification. In addition, peers also do work aimed at building relationships with staff and work aimed at legitimizing the peer role. Experience, approach, presence, role modeling, collaboration, challenge, and compromise can be seen as the tangible enactments of peers' philosophy of work. Candidates for positions as peer support workers require more than experience with mental health and/or addiction problems. The job description provided in this article may not be appropriate for all settings, but it will contribute to a better understanding of the peer support worker position, the skills required, and the types of expectations that could define successful fulfillment of the role.

IRS2 mutations linked to invasion in pleomorphic invasive lobular carcinoma

PubMed Central

Zhu, Sha; Ward, B. Marie; Yu, Jun; Matthew-Onabanjo, Asia N.; Janusis, Jenny; Hsieh, Chung-Cheng; Tomaszewicz, Keith; Hutchinson, Lloyd; Zhu, Lihua Julie; Kandil, Dina; Shaw, Leslie M.

2018-01-01

Pleomorphic invasive lobular carcinoma (PILC) is an aggressive variant of invasive lobular breast cancer that is associated with poor clinical outcomes. Limited molecular data are available to explain the mechanistic basis for PILC behavior. To address this issue, targeted sequencing was performed to identify molecular alterations that define PILC. This sequencing analysis identified genes that distinguish PILC from classic ILC and invasive ductal carcinoma by the incidence of their genomic changes. In particular, insulin receptor substrate 2 (IRS2) is recurrently mutated in PILC, and pathway analysis reveals a role for the insulin receptor (IR)/insulin-like growth factor-1 receptor (IGF1R)/IRS2 signaling pathway in PILC. IRS2 mutations identified in PILC enhance invasion, revealing a role for this signaling adaptor in the aggressive nature of PILC. PMID:29669935

Regulation of metabolism by the Mediator complex.

PubMed

Youn, Dou Yeon; Xiaoli, Alus M; Pessin, Jeffrey E; Yang, Fajun

2016-01-01

The Mediator complex was originally discovered in yeast, but it is conserved in all eukaryotes. Its best-known function is to regulate RNA polymerase II-dependent gene transcription. Although the mechanisms by which the Mediator complex regulates transcription are often complicated by the context-dependent regulation, this transcription cofactor complex plays a pivotal role in numerous biological pathways. Biochemical, molecular, and physiological studies using cancer cell lines or model organisms have established the current paradigm of the Mediator functions. However, the physiological roles of the mammalian Mediator complex remain poorly defined, but have attracted a great interest in recent years. In this short review, we will summarize some of the reported functions of selective Mediator subunits in the regulation of metabolism. These intriguing findings suggest that the Mediator complex may be an important player in nutrient sensing and energy balance in mammals.

Effect of early trauma on the sleep quality of euthymic bipolar patients.

PubMed

Aubert, E; Jaussent, I; Olié, E; Ducasse, D; Azorin, J M; Bellivier, F; Belzeaux, R; Bougerol, T; Etain, B; Gard, S; Henry, C; Kahn, J P; Leboyer, M; Loftus, J; Passerieux, C; Lopez-Castroman, J; Courtet, Ph

2016-12-01

Poor quality of sleep is frequent in euthymic bipolar patients and conveys worse clinical outcomes. We investigated the features of euthymic bipolar patients associated with poor sleep quality, with a focus on the effect of childhood trauma. 493 euthymic patients with DSM-IV-defined bipolar disorders were recruited in FondaMental Advanced Centers of Expertize for Bipolar Disorders (FACE-BD) between 2009 and 2014. Clinical variables were recorded. Subjective sleep quality and history of childhood trauma were respectively measured by the Pittsburgh Sleep Quality Index (PSQI) and the Childhood Trauma Questionnaire (CTQ). Poor sleepers were older, less professionally active, had significantly higher anxiety levels, took more anxiolytic drugs and did endorse more suicide attempts and suicidal ideas than good sleepers after adjusting for anxiety levels and age. Emotional abuse was associated with poor sleep quality after adjustment for BMI, age, professional activity, and bipolar disorders (BD) type (OR=1.83; 95% CI [1.30; 3.10]; p=0.02). However, this association was lost after adjustment for anxiety levels, anxiolytic treatment and suicide ideation/attempts. The main limitation was the type of sleep assessment, which only measured the subjective part of sleep complaints. A history of emotional abuse might underlie sleep problems in many bipolar patients but anxiety seems to act as a confounding factor in this relationship. New studies are needed to elucidate the role of childhood maltreatment on poor sleep among bipolar patients. Copyright © 2016 Elsevier B.V. All rights reserved.

Making parks make a difference: poor alignment of policy, planning and management with protected-area impact, and ways forward

PubMed Central

Pressey, Robert L.; Visconti, Piero; Ferraro, Paul J.

2015-01-01

Policy and practice around protected areas are poorly aligned with the basic purpose of protection, which is to make a difference. The difference made by protected areas is their impact, defined in program evaluation as the outcomes arising from protection relative to the counterfactual of no protection or a different form of protection. Although impact evaluation of programs is well established in fields such as medicine, education and development aid, it is rare in nature conservation. We show that the present weak alignment with impact of policy targets and operational objectives for protected areas involves a great risk: targets and objectives can be achieved while making little difference to the conservation of biodiversity. We also review potential ways of increasing the difference made by protected areas, finding a poor evidence base for the use of planning and management ‘levers’ to better achieve impact. We propose a dual strategy for making protected areas more effective in their basic role of saving nature, outlining ways of developing targets and objectives focused on impact while also improving the evidence for effective planning and management. PMID:26460132

Podiatric involvement in multidisciplinary falls-prevention clinics in Australia.

PubMed

Menz, Hylton B; Hill, Keith D

2007-01-01

Falls in older people are a major public health problem, and there is increasing evidence that foot problems and inappropriate footwear increase the risk of falls. Several multidisciplinary prevention clinics have been established to address the problem of falls; however, the role of podiatry in these clinics has not been clearly defined. The aims of this study were to determine the level of podiatric involvement in multidisciplinary falls clinics in Australia and to describe the assessments undertaken and interventions provided by podiatrists in these settings. A database of falls clinics was developed through consultation with departments of health in each state and territory. Clinic managers were contacted and surveyed as to whether the clinic incorporated podiatry services. If so, the podiatrists were contacted and asked to complete a brief questionnaire regarding their level of involvement and the assessment procedures and interventions offered. Of the 36 clinics contacted, 25 completed the survey. Only four of these clinics reported direct podiatric involvement. Despite the limited involvement of podiatry in these clinics, all of the clinic managers stated that they considered podiatry to have an important role to play in falls prevention. Podiatry service provision in falls clinics varied considerably in relation to eligibility criteria, assessments undertaken, and interventions provided. Despite the recognition that foot problems and inappropriate footwear are risk factors for falls, podiatry currently has a relatively minor and poorly defined role in multidisciplinary falls-prevention clinics in Australia.

Chronic pancreatitis.

PubMed

Majumder, Shounak; Chari, Suresh T

2016-05-07

Chronic pancreatitis describes a wide spectrum of fibro-inflammatory disorders of the exocrine pancreas that includes calcifying, obstructive, and steroid-responsive forms. Use of the term chronic pancreatitis without qualification generally refers to calcifying chronic pancreatitis. Epidemiology is poorly defined, but incidence worldwide seems to be on the rise. Smoking, drinking alcohol, and genetic predisposition are the major risk factors for chronic calcifying pancreatitis. In this Seminar, we discuss the clinical features, diagnosis, and management of chronic calcifying pancreatitis, focusing on pain management, the role of endoscopic and surgical intervention, and the use of pancreatic enzyme-replacement therapy. Management of patients is often challenging and necessitates a multidisciplinary approach. Copyright © 2016 Elsevier Ltd. All rights reserved.

Otosclerosis: Temporal Bone Pathology.

PubMed

Quesnel, Alicia M; Ishai, Reuven; McKenna, Michael J

2018-04-01

Otosclerosis is pathologically characterized by abnormal bony remodeling, which includes bone resorption, new bone deposition, and vascular proliferation in the temporal bone. Sensorineural hearing loss in otosclerosis is associated with extension of otosclerosis to the cochlear endosteum and deposition of collagen throughout the spiral ligament. Persistent or recurrent conductive hearing loss after stapedectomy has been associated with incomplete footplate fenestration, poor incus-prosthesis connection, and incus resorption in temporal bone specimens. Human temporal bone pathology has helped to define the role of computed tomography imaging for otosclerosis, confirming that computed tomography is highly sensitive for diagnosis, yet limited in assessing cochlear endosteal involvement. Copyright © 2017 Elsevier Inc. All rights reserved.

Exploring a regulatory role for mast cells: 'MCregs'?

PubMed

Frossi, Barbara; Gri, Giorgia; Tripodo, Claudio; Pucillo, Carlo

2010-03-01

Regulatory cells can mould the fate of the immune response by direct suppression of specific subsets of effector cells, or by redirecting effectors against invading pathogens and infected or neoplastic cells. These functions have been classically, although not exclusively, ascribed to different subsets of T cells. Recently, mast cells have been shown to regulate physiological and pathological immune responses, and thus to act at the interface between innate and adaptive immunity assuming different functions and behaviors at discrete stages of the immune response. Here, we focus on these poorly defined, and sometimes apparently conflicting, functions of mast cells. Copyright 2010 Elsevier Ltd. All rights reserved.

Echolalia: issues and clinical applications.

PubMed

Schuler, A L

1979-11-01

Echolalic behaviors have been reported within the context of various pathologies but have remained poorly defined. Consequently, it is not easy to determine whether and to what extent normal repetition can be separated from pathological echoing. Hence, it is unclear whether the occurrence of echolalic behavior may be useful for differential diagnostic purposes. Also, much room is left for controversies about the clinical management of echolalic behavior. This article reviews the various conditions associated with echolalia and the role of repetitions in normal language behavior. Suggestions are made in terms of the various dimensions along which echolalic behavior should be assessed, as well as of the desirability of particular intervention techniques.

Radiosurgery for Medial Temporal Lobe Epilepsy Resulting from Mesial Temporal Sclerosis.

PubMed

Gianaris, Thomas; Witt, Thomas; Barbaro, Nicholas M

2016-01-01

Medial temporal lobe epilepsy associated with mesial temporal sclerosis (MTS) is perhaps the most well-defined epilepsy syndrome that is responsive to structural interventions such as surgery. Several minimally invasive techniques have arisen that provide additional options for the treatment of MTS while potentially avoiding many of open surgery's associated risks. By evading these risks, they also open up treatment options to patients who otherwise are poor surgical candidates. Radiosurgery is one of the most intensively studied of these alternatives and has found a growing role in the treatment of medial temporal lobe epilepsy. Copyright © 2016 Elsevier Inc. All rights reserved.

The natural killer cell response to West Nile virus in young and old individuals with or without a prior history of infection.

PubMed

Yao, Yi; Strauss-Albee, Dara M; Zhou, Julian Q; Malawista, Anna; Garcia, Melissa N; Murray, Kristy O; Blish, Catherine A; Montgomery, Ruth R

2017-01-01

West Nile virus (WNV) typically leads to asymptomatic infection but can cause severe neuroinvasive disease or death, particularly in the elderly. Innate NK cells play a critical role in antiviral defenses, yet their role in human WNV infection is poorly defined. Here we demonstrate that NK cells mount a robust, polyfunctional response to WNV characterized by cytolytic activity, cytokine and chemokine secretion. This is associated with downregulation of activating NK cell receptors and upregulation of NK cell activating ligands for NKG2D. The NK cell response did not differ between young and old WNV-naïve subjects, but a history of symptomatic infection is associated with more IFN-γ producing NK cell subsets and a significant decline in a specific NK cell subset. This NK repertoire skewing could either contribute to or follow heightened immune pathogenesis from WNV infection, and suggests that NK cells could play an important role in WNV infection in humans.

[Healthcare: a growing role in international politics].

PubMed

Dixneuf, M; Rey, J L

2004-01-01

Since the end of the cold war the tone of international relations has clearly changed. Whereas relations were once defined strictly in terms of more or less armed confrontation, economic and social issues now play a growing role. Healthcare policies in Africa have long been influenced by the policies of countries sponsoring bilateral and even multilateral foreign aid programs. However the last ten years have witnessed an increasing interaction between international policy and healthcare policy. The two main reasons for this trend involve 1) access to drug treatment and the WTO and 2) the extension and impact of the AIDS epidemic. The problem of access to drug treatment for poor populations (fundamental right) has led to the emergence of an increasingly strong and effective civil society. Because of its social and economic effects as well as its geopolitical and security implications, AIDS has become a major factor in international relations. With regard to both these issues the place and role of the USA is demonstrative of the interaction between healthcare and international relations.

Once a Poor Pitch Singer, Always a Poor Pitch Singer? A Bottom up Study of Factors That May Support Singing Development

ERIC Educational Resources Information Center

Turøy, Anne Kristine Wallace

2018-01-01

Approximately 10% of students have singing difficulties appearing as poor pitch singing. During the period 2012 to 2014, I assessed 2390 recordings from 239 students. 25 students were graded below C, and thus were defined as poor pitch singers (PPS). However, these students showed varying patterns of mastery within their own portfolios of…

Working Poor Families in the Chicago Metropolitan Area. Statistical Profile and Proceedings of the Working Poor Policy Forum (Chicago, Illinois, December 8, 1993).

ERIC Educational Resources Information Center

Latino Inst., Chicago, IL.

A statistical profile of the working poor in Chicago (Illinois) and the proceedings of the Working Poor Policy Forum held to discuss the findings of the profile are presented. In America it is supposed to be impossible to work and remain chronically poor, but in fact this is not the case. There are many ways to define the income working families…

Perspectives on the role of stakeholders in knowledge translation in health policy development in Uganda.

PubMed

Nabyonga Orem, Juliet; Marchal, Bruno; Mafigiri, DavidKaawa; Ssengooba, Freddie; Macq, Jean; Da Silveira, Valeria Campos; Criel, Bart

2013-08-19

Stakeholder roles in the application of evidence are influenced by context, the nature of the evidence, the policy development process, and stakeholder interactions. Past research has highlighted the role of stakeholders in knowledge translation (KT) without paying adequate attention to the peculiarities of low-income countries. Here we identify the roles, relations, and interactions among the key stakeholders involved in KT in Uganda and the challenges that they face. This study employed qualitative approaches to examine the roles of and links among various stakeholders in KT. In-depth interviews were conducted with 21 key informants and focused on the key actors in KT, their perceived roles, and challenges. Major stakeholders included civil society organizations with perceived roles of advocacy, community mobilization, and implementation. These stakeholders may ignore unconvincing evidence. The community's role was perceived as advocacy and participation in setting research priorities. The key role of the media was perceived as knowledge dissemination, but respondents noted that the media may misrepresent evidence if it is received in a poorly packaged form. The perceived roles of policy makers were evidence uptake, establishing platforms for KT and stewardship; negative roles included ignoring or even misrepresenting evidence that is not in their favor. The roles of parliamentarians were perceived as advocacy and community mobilization, but they were noted to pursue objectives that may not be supported by the evidence. The researchers' main role was defined as evidence generation, but focusing disproportionately on academic interests was cited as a concern. The donors' main role was defined as funding research and KT, but respondents were concerned about the local relevance of donor-supported research. Respondents reported that links among stakeholders were weak due to the absence of institutionalized, inclusive platforms. Challenges facing the stakeholders in the process of KT were identified. Our investigation revealed the need to consider the roles that various stakeholders are best placed to play. Links and necessary platforms must be put in place to achieve synergy in KT. Relevant capacities need to be built to overcome the challenges faced by the various stakeholders.

Role of calcium signaling in epithelial bicarbonate secretion.

PubMed

Jung, Jinsei; Lee, Min Goo

2014-06-01

Transepithelial bicarbonate secretion plays a key role in the maintenance of fluid and protein secretion from epithelial cells and the protection of the epithelial cell surface from various pathogens. Epithelial bicarbonate secretion is mainly under the control of cAMP and calcium signaling. While the physiological roles and molecular mechanisms of cAMP-induced bicarbonate secretion are relatively well defined, those induced by calcium signaling remain poorly understood in most epithelia. The present review summarizes the current status of knowledge on the role of calcium signaling in epithelial bicarbonate secretion. Specifically, this review introduces how cytosolic calcium signaling can increase bicarbonate secretion by regulating membrane transport proteins and how it synergizes with cAMP-induced mechanisms in epithelial cells. In addition, tissue-specific variations in the pancreas, salivary glands, intestines, bile ducts, and airways are discussed. We hope that the present report will stimulate further research into this important topic. These studies will provide the basis for future medicines for a wide spectrum of epithelial disorders including cystic fibrosis, Sjögren's syndrome, and chronic pancreatitis. Copyright © 2014 Elsevier Ltd. All rights reserved.

Brain Gut Microbiome Interactions and Functional Bowel Disorders

PubMed Central

Mayer, Emeran A.; Savidge, Tor; Shulman, Robert J.

2014-01-01

Alterations in the bidirectional interactions between the gut and the nervous system play an important role in IBS pathophysiology and symptom generation. A body of largely preclinical evidence suggests that the gut microbiota can modulate these interactions. Characterizations of alterations of gut microbiota in unselected IBS patients, and assessment of changes in subjective symptoms associated with manipulations of the gut microbiota with prebiotics, probiotics and antibiotics support a small, but poorly defined role of dybiosis in overall IBS symptoms. It remains to be determined if the observed abnormalities are a consequence of altered top down signaling from the brain to the gut and microbiota, if they are secondary to a primary perturbation of the microbiota, and if they play a role in the development of altered brain gut interactions early in life. Different mechanisms may play role in subsets of patients. Characterization of gut microbiome alterations in large cohorts of well phenotyped patients as well as evidence correlating gut metabolites with specific abnormalities in the gut brain axis are required to answer these questions. PMID:24583088

Identification and Manipulation of a Novel Signaling Mechanism to Improve Articular Cartilage Restoration After Posttraumatic Joint Injury

DTIC Science & Technology

2014-10-01

collagen II (COL II). As a result, the newly-formed fibrocartilage has poor biomechanical properties and often evidences poor integration with the... fibrocartilage generation at the site of injury defines a new potential avenue of intervention in the field of cartilage restoration. We defined the...lysophosphatidic acid (LPA)-autotaxin (ATX; encoded by the ENPP2 gene) signaling axis as an important mediator of fibrocartilage formation both in vitro and in

Proline-poor hydrophobic domains modulate the assembly and material properties of polymeric elastin.

PubMed

Muiznieks, Lisa D; Reichheld, Sean E; Sitarz, Eva E; Miao, Ming; Keeley, Fred W

2015-10-01

Elastin is a self-assembling extracellular matrix protein that provides elasticity to tissues. For entropic elastomers such as elastin, conformational disorder of the monomer building block, even in the polymeric form, is essential for elastomeric recoil. The highly hydrophobic monomer employs a range of strategies for maintaining disorder and flexibility within hydrophobic domains, particularly involving a minimum compositional threshold of proline and glycine residues. However, the native sequence of hydrophobic elastin domain 30 is uncharacteristically proline-poor and, as an isolated polypeptide, is susceptible to formation of amyloid-like structures comprised of stacked β-sheet. Here we investigated the biophysical and mechanical properties of multiple sets of elastin-like polypeptides designed with different numbers of proline-poor domain 30 from human or rat tropoelastins. We compared the contributions of these proline-poor hydrophobic sequences to self-assembly through characterization of phase separation, and to the tensile properties of cross-linked, polymeric materials. We demonstrate that length of hydrophobic domains and propensity to form β-structure, both affecting polypeptide chain flexibility and cross-link density, play key roles in modulating elastin mechanical properties. This study advances the understanding of elastin sequence-structure-function relationships, and provides new insights that will directly support rational approaches to the design of biomaterials with defined suites of mechanical properties. © 2015 Wiley Periodicals, Inc.

New-onset refractory status epilepticus

PubMed Central

Foreman, Brandon P.; Alvarez, Vincent; Cabrera Kang, Christian; Probasco, John C.; Jongeling, Amy C.; Meyers, Emma; Espinera, Alyssa; Haas, Kevin F.; Schmitt, Sarah E.; Gerard, Elizabeth E.; Gofton, Teneille; Kaplan, Peter W.; Lee, Jong W.; Legros, Benjamin; Szaflarski, Jerzy P.; Westover, Brandon M.; LaRoche, Suzette M.; Hirsch, Lawrence J.

2015-01-01

Objectives: The aims of this study were to determine the etiology, clinical features, and predictors of outcome of new-onset refractory status epilepticus. Methods: Retrospective review of patients with refractory status epilepticus without etiology identified within 48 hours of admission between January 1, 2008, and December 31, 2013, in 13 academic medical centers. The primary outcome measure was poor functional outcome at discharge (defined as a score >3 on the modified Rankin Scale). Results: Of 130 cases, 67 (52%) remained cryptogenic. The most common identified etiologies were autoimmune (19%) and paraneoplastic (18%) encephalitis. Full data were available in 125 cases (62 cryptogenic). Poor outcome occurred in 77 of 125 cases (62%), and 28 (22%) died. Predictors of poor outcome included duration of status epilepticus, use of anesthetics, and medical complications. Among the 63 patients with available follow-up data (median 9 months), functional status improved in 36 (57%); 79% had good or fair outcome at last follow-up, but epilepsy developed in 37% with most survivors (92%) remaining on antiseizure medications. Immune therapies were used less frequently in cryptogenic cases, despite a comparable prevalence of inflammatory CSF changes. Conclusions: Autoimmune encephalitis is the most commonly identified cause of new-onset refractory status epilepticus, but half remain cryptogenic. Outcome at discharge is poor but improves during follow-up. Epilepsy develops in most cases. The role of anesthetics and immune therapies warrants further investigation. PMID:26296517

Autologous hematopoietic stem cell transplantation in peripheral T-cell lymphoma using a uniform high-dose regimen.

PubMed

Smith, S D; Bolwell, B J; Rybicki, L A; Brown, S; Dean, R; Kalaycio, M; Sobecks, R; Andresen, S; Hsi, E D; Pohlman, B; Sweetenham, J W

2007-08-01

The role of high-dose therapy and autologous stem cell transplantation (ASCT) for patients with peripheral T-cell lymphoma (PTCL) is poorly defined. Comparisons of outcomes between PTCL and B-cell non-Hodgkin's lymphoma (NHL) have yielded conflicting results, in part due to the rarity and heterogeneity of PTCL. Some retrospective studies have found comparable survival rates for patients with T- and B-cell NHL. In this study, we report our single-center experience of ASCT over one decade using a uniform chemotherapy-only high-dose regimen. Thirty-two patients with PTCL-unspecified (PTCL-u; 11 patients) and anaplastic large-cell lymphoma (21 patients) underwent autologous stem cell transplant, mostly for relapsed or refractory disease. The preparative regimen consisted of busulfan, etoposide and cyclophosphamide. Kaplan-Meier 5-year overall survival (OS) and relapse-free survival (RFS) are 34 and 18%, respectively. These results suggest a poor outcome for patients with PTCL after ASCT, and new therapies for T-cell lymphoma are needed.

Microbial host interactions and impaired wound healing in mice and humans: defining a role for BD14 and NOD2.

PubMed

Williams, Helen; Campbell, Laura; Crompton, Rachel A; Singh, Gurdeep; McHugh, Brian J; Davidson, Donald J; McBain, Andrew J; Cruickshank, Sheena M; Hardman, Matthew J

2018-04-30

Chronic wounds cause significant patient morbidity and mortality. A key factor in their etiology is microbial infection, yet skin host-microbiota interactions during wound repair remain poorly understood. Microbiome profiles of non-infected human chronic wounds are associated with subsequent healing outcome. Furthermore, poor clinical healing outcome was associated with increased local expression of the pattern recognition receptor NOD2. To investigate NOD2 function in the context of cutaneous healing, we treated mice with the NOD2 ligand muramyl dipeptide (MDP) and analyzed wound repair parameters and expression of anti-microbial peptides. MDP treatment of littermate controls significantly delayed wound repair associated with reduced re-epithelialization, heightened inflammation and upregulation of murine β-Defensins (mBD) 1, 3 and particularly 14. We postulated that although BD14 might impact on local skin microbial communities it may further impact other healing parameters. Indeed, exogenously administered mBD14 directly delayed mouse primary keratinocyte scratch wound closure in vitro. To further explore the role of mBD14 in wound repair, we employed Defb14 -/- mice, and showed they had a global delay in healing in vivo, associated with alterations in wound microbiota. Taken together these studies suggest a key role for NOD2-mediated regulation of local skin microbiota which in turn impacts on chronic wound etiology. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

Biophysical characterization of α-synuclein and its controversial structure

PubMed Central

Alderson, T Reid; Markley, John L

2013-01-01

α-synuclein, a presynaptic protein of poorly defined function, constitutes the main component of Parkinson disease-associated Lewy bodies. Extensive biophysical investigations have provided evidence that isolated α-synuclein is an intrinsically disordered protein (IDP) in vitro. Subsequently serving as a model IDP in numerous studies, α-synuclein has aided in the development of many technologies used to characterize IDPs and arguably represents the most thoroughly analyzed IDP to date. Recent reports, however, have challenged the disordered nature of α-synuclein inside cells and have instead proposed a physiologically relevant helical tetramer. Despite α-synuclein’s rich biophysical history, a single coherent picture has not yet emerged concerning its in vivo structure, dynamics, and physiological role(s). We present herein a review of the biophysical discoveries, developments, and models pertinent to the characterization of α-synuclein’s structure and analysis of the native tetramer controversy. PMID:24634806

Environmental Enteric Dysfunction: Pathogenesis, Diagnosis, and Clinical Consequences

PubMed Central

Keusch, Gerald T.; Denno, Donna M.; Black, Robert E.; Duggan, Christopher; Guerrant, Richard L.; Lavery, James V.; Nataro, James P.; Rosenberg, Irwin H.; Ryan, Edward T.; Tarr, Phillip I.; Ward, Honorine; Bhutta, Zulfiqar A.; Coovadia, Hoosen; Lima, Aldo; Ramakrishna, Balakrishnan; Zaidi, Anita K. M.; Hay Burgess, Deborah C.; Brewer, Thomas

2014-01-01

Stunting is common in young children in developing countries, and is associated with increased morbidity, developmental delays, and mortality. Its complex pathogenesis likely involves poor intrauterine and postnatal nutrition, exposure to microbes, and the metabolic consequences of repeated infections. Acquired enteropathy affecting both gut structure and function likely plays a significant role in this outcome, especially in the first few months of life, and serve as a precursor to later interactions of infection and malnutrition. However, the lack of validated clinical diagnostic criteria has limited the ability to study its role, identify causative factors, and determine cost-effective interventions. This review addresses these issues through a historical approach, and provides recommendations to define and validate a working clinical diagnosis and to guide critical research in this area to effectively proceed. Prevention of early gut functional changes and inflammation may preclude or mitigate the later adverse vicious cycle of malnutrition and infection. PMID:25305288

Regulatory functional territory of PLK-1 and their substrates beyond mitosis.

PubMed

Kumar, Shiv; Sharma, Garima; Chakraborty, Chiranjib; Sharma, Ashish Ranjan; Kim, Jaebong

2017-06-06

Polo-like kinase 1 (PLK-1) is a well-known (Ser/Thr) mitotic protein kinase and is considered as a proto-oncogene. As hyper-activation of PLK-1 is broadly associated with poor prognosis and cancer progression, it is one of the most extensively studied mitotic kinases. During mitosis, PLK-1 regulates various cell cycle events, such as spindle pole maturation, chromosome segregation and cytokinesis. However, studies have demonstrated that the role of PLK-1 is not only restricted to mitosis, but PLK-1 can also regulate other vital events beyond mitosis, including transcription, translation, ciliogenesis, checkpoint adaptation and recovery, apoptosis, chromosomes dynamics etc. Recent reviews have tried to define the regulatory role of PLK-1 during mitosis progression and tumorigenesis, but its' functional role beyond mitosis is still largely unexplored. PLK-1 can regulate the activity of many proteins that work outside of its conventional territory. The dysregulation of these proteins can cause diseases such as Alzheimer's disease, tumorigenesis etc. and may also lead to drug resistance. Thus, in this review, we discussed the versatile role of PLK-1 and tried to collect data to validate its' functional role in cell cycle regulation apart from mitosis.

The role of poor sleep in the relation between workplace bullying/unwanted sexual attention and long-term sickness absence.

PubMed

Nabe-Nielsen, Kirsten; Grynderup, Matias Brødsgaard; Lange, Theis; Andersen, Johan Hviid; Bonde, Jens Peter; Conway, Paul Maurice; Garde, Anne Helene; Høgh, Annie; Kaerlev, Linda; Rugulies, Reiner; Hansen, Åse Marie

2016-08-01

While exposure to bullying and unwanted sexual attention was previously found to increase the risk of sickness absence, the underlying mechanisms are largely unknown. Poor sleep can be a consequence of stressful exposures and a cause of poor health, and poor sleep is also a determinant of insufficient recovery. Therefore, the present study investigated whether poor sleep mediates and/or moderates the association between bullying and unwanted sexual attention, on the one hand, and long-term sickness absence (LTSA), on the other hand. We used questionnaire data from 7650 individuals contributing with 15,040 2-year observation periods. Workplace bullying, unwanted sexual attention, disturbed sleep, and difficulties awakening were measured at three time points, and participants were followed in registers to measure the occurrence of LTSA, defined as ≥30 consecutive days of sickness absence during the subsequent 2 years. The odds of LTSA were significantly increased by workplace bullying (OR 1.77; 95 % CI 1.50-2.12) and unwanted sexual attention (OR 1.55; 95 % CI 1.06-2.29). Together, disturbed sleep and difficulties awakening mediated 12.8 % (95 % CI 8.1-19.8) of the association between bullying and long-term sickness absence, and 8.5 % (95 % CI -0.45 to 37.1) of the association between unwanted sexual attention and long-term sickness absence in the fully adjusted model. Neither disturbed sleep nor difficulties awakening moderated these associations. As expected, bullying and unwanted sexual attention were prospectively associated with long-term sickness absence. Only a small part of this association was mediated by poor sleep.

Defining Social Class Across Time and Between Groups.

PubMed

Cohen, Dov; Shin, Faith; Liu, Xi; Ondish, Peter; Kraus, Michael W

2017-11-01

We examined changes over four decades and between ethnic groups in how people define their social class. Changes included the increasing importance of income, decreasing importance of occupational prestige, and the demise of the "Victorian bargain," in which poor people who subscribed to conservative sexual and religious norms could think of themselves as middle class. The period also saw changes (among Whites) and continuity (among Black Americans) in subjective status perceptions. For Whites (and particularly poor Whites), their perceptions of enhanced social class were greatly reduced. Poor Whites now view their social class as slightly but significantly lower than their poor Black and Latino counterparts. For Black respondents, a caste-like understanding of social class persisted, as they continued to view their class standing as relatively independent of their achieved education, income, and occupation. Such achievement indicators, however, predicted Black respondents' self-esteem more than they predicted self-esteem for any other group.

Defining Hardwood Veneer Log Quality Attributes

Treesearch

Jan Wiedenbeck; Michael Wiemann; Delton Alderman; John Baumgras; William Luppold

2004-01-01

This publication provides a broad spectrum of information on the hardwood veneer industry in North America. Veneer manufacturers and their customers impose guidelines in specifying wood quality attributes that are very discriminating but poorly defined (e.g., exceptional color, texture, and/or figure characteristics). To better understand and begin to define the most...

Cycle cancellation and pregnancy after luteal estradiol priming in women defined as poor responders: a systematic review and meta-analysis

PubMed Central

Reynolds, Kasey A.; Omurtag, Kenan R.; Jimenez, Patricia T.; Rhee, Julie S.; Tuuli, Method G.; Jungheim, Emily S.

2013-01-01

STUDY QUESTION Does a luteal estradiol (LE) stimulation protocol improve outcomes in poor responders to IVF? SUMMARY ANSWER LE priming is associated with decreased cycle cancellation and increased chance of clinical pregnancy in poor responders WHAT IS KNOWN ALREADY Poor responders to IVF are one of the most challenging patient populations to treat. Many standard protocols currently exist for stimulating these patients but all have failed to improve outcomes. STUDY DESIGN, SIZE, DURATION Systematic review and meta-analysis including eight published studies comparing assisted reproduction technology (ART) outcomes in poor responders exposed to controlled ovarian hyperstimulation with and without LE priming. A search of the databases MEDLINE, EMBASE and PUBMED was carried out for studies in the English language published up to January 2012. PARTICIPANTS/MATERIALS, SETTING, METHODS Studies evaluating women defined as poor responders to ART were evaluated. These studies were identified following a systematic review of the literature and data were analyzed using the DerSimonian–Laird random effects model. The main outcomes of interest were cycle cancellation rate and clinical pregnancy. Although the definition of clinical pregnancy varied between studies, the principal definition included fetal cardiac activity as assessed by transvaginal ultrasonography after 5 weeks of gestation. MAIN RESULTS AND THE ROLE OF CHANCE A total of 2249 publications were identified from the initial search, and the bibliographies, abstracts and other sources yielded 11 more. After excluding duplications, 1227 studies remained and 8 ultimately met the inclusion criteria. Compared with women undergoing non-LE primed protocols (n = 621), women exposed to LE priming (n = 468) had a lower risk of cycle cancellation [relative risk (RR): 0.60, 95% confidence interval (CI): 0.45–0.78] and an improved chance of clinical pregnancy (RR: 1.33, 95% CI: 1.02–1.72). There was no significant improvement in the number of mature oocytes obtained or number of zygotes obtained per cycle. LIMITATIONS, REASONS FOR CAUTION These findings are limited by the body of literature currently available. As the poor responder lacks a concrete definition, there is some heterogeneity to these results, which merits caution when applying our findings to individual patients. Furthermore, the increased clinical pregnancy rate demonstrated when using the LE protocol may be principally related to the decreased cycle cancellation rate. WIDER IMPLICATIONS OF THE FINDINGS The LE protocol may be of some utility in the poor responder to IVF and may increase clinical pregnancy rates in this population by improving stimulation and thereby decreasing cycle cancellation. STUDY FUNDING/COMPETING INTERESTS NIH K12 HD063086 (ESJ, MGT), NIH T32 HD0040135-11 (KAR), F32 HD040135-10 NIH (KRO), 5K12HD000849-25 (PTJ). No competing interests. PMID:23887073

Structure and functional dynamics of the mitochondrial Fe/S cluster synthesis complex.

PubMed

Boniecki, Michal T; Freibert, Sven A; Mühlenhoff, Ulrich; Lill, Roland; Cygler, Miroslaw

2017-11-03

Iron-sulfur (Fe/S) clusters are essential protein cofactors crucial for many cellular functions including DNA maintenance, protein translation, and energy conversion. De novo Fe/S cluster synthesis occurs on the mitochondrial scaffold protein ISCU and requires cysteine desulfurase NFS1, ferredoxin, frataxin, and the small factors ISD11 and ACP (acyl carrier protein). Both the mechanism of Fe/S cluster synthesis and function of ISD11-ACP are poorly understood. Here, we present crystal structures of three different NFS1-ISD11-ACP complexes with and without ISCU, and we use SAXS analyses to define the 3D architecture of the complete mitochondrial Fe/S cluster biosynthetic complex. Our structural and biochemical studies provide mechanistic insights into Fe/S cluster synthesis at the catalytic center defined by the active-site Cys of NFS1 and conserved Cys, Asp, and His residues of ISCU. We assign specific regulatory rather than catalytic roles to ISD11-ACP that link Fe/S cluster synthesis with mitochondrial lipid synthesis and cellular energy status.

Plasmacytoid dendritic cells: no longer an enigma and now key to transplant tolerance?

PubMed Central

Rogers, NM; Isenberg, JS; Thomson, AW

2014-01-01

Plasmacytoid (p) dendritic cells (DC) are a specialized subset of DC whose primary role was initially defined by the production of type I interferons in response to viral infection. They are now known to also possess a repertoire of functions capable of determining T cell fate and activation. Under homeostatic conditions, non-lymphoid tissue-resident pDC play a critical role in the regulation of mucosal immunity, as well as the development of central and peripheral tolerance. Although these cells display a number of characteristics that differ from conventional DC, particularly altered costimulatory molecule expression and poor allostimulatory capacity when interacting with T cells, this phenotype favors the generation of alloantigen-specific regulatory CD4+ or CD8+ T cells critical to the development of graft tolerance. In this minireview we discuss pDC ontogeny, functional biology and the emerging data that demonstrate the importance of pDC in the induction of tolerance, as well as recent studies that define mechanisms underlying pDC-mediated tolerance to both solid organ and hematopoietic stem cell transplantats. We also highlight their use in clinical settings and the potential of pDC both as targets and cellular therapeutic agents to improve the outcome of organ transplantation. PMID:23617754

Constitutively active transforming growth factor β receptor 1 in the mouse ovary promotes tumorigenesis

PubMed Central

Gao, Yang; Vincent, David F.; Davis, Anna Jane; Sansom, Owen J.; Bartholin, Laurent; Li, Qinglei

2016-01-01

Despite the well-established tumor suppressive role of TGFβ proteins, depletion of key TGFβ signaling components in the mouse ovary does not induce a growth advantage. To define the role of TGFβ signaling in ovarian tumorigenesis, we created a mouse model expressing a constitutively active TGFβ receptor 1 (TGFBR1) in ovarian somatic cells using conditional gain-of-function approach. Remarkably, these mice developed ovarian sex cord-stromal tumors with complete penetrance, leading to reproductive failure and mortality. The tumors expressed multiple granulosa cell markers and caused elevated serum inhibin and estradiol levels, reminiscent of granulosa cell tumors. Consistent with the tumorigenic effect, overactivation of TGFBR1 altered tumor microenvironment by promoting angiogenesis and enhanced ovarian cell proliferation, accompanied by impaired cell differentiation and dysregulated expression of critical genes in ovarian function. By further exploiting complementary genetic models, we substantiated our finding that constitutively active TGFBR1 is a potent oncogenic switch in mouse granulosa cells. In summary, overactivation of TGFBR1 drives gonadal tumor development. The TGFBR1 constitutively active mouse model phenocopies a number of morphological, hormonal, and molecular features of human granulosa cell tumors and are potentially valuable for preclinical testing of targeted therapies to treat granulosa cell tumors, a class of poorly defined ovarian malignancies. PMID:27344183

Diagnosis and management of heart failure in the fetus

PubMed Central

DAVEY, B.; SZWAST, A.; RYCHIK, J.

2015-01-01

Heart failure can be defined as the inability of the heart to sufficiently support the circulation. In the fetus, heart failure can be caused by a myriad of factors that include fetal shunting abnormalities, genetic cardiomyopathies, extracardiac malformations, arrhythmias and structural congenital heart disease. With advances in ultrasound has come the ability to characterize many complex conditions, previously poorly understood. Fetal echocardiography provides the tools necessary to evaluate and understand the various physiologies that contribute to heart failure in the fetus. In this review, we will explore the different mechanisms of heart failure in this unique patient population and highlight the role of fetal echocardiography in the current management of these conditions PMID:22992530

The photodimerisation of the α- and β-forms of trans-cinnamic acid: a study of single crystals by vibrational microspectroscopy

NASA Astrophysics Data System (ADS)

Atkinson, Samantha D. M.; Almond, Matthew J.; Hollins, Peter; Jenkins, Samantha L.

2003-02-01

Infrared and Raman microspectroscopy have been used to follow the photodimerisation reactions of single crystals, the α- and β-forms of trans-cinnamic acid. This approach allows the starting materials and products—α-truxillic acid that has Ci symmetry and β-truxinic acid, which has Cs symmetry—to be identified. It also allows the topotactic nature of the reaction to be confirmed. Attempts to produce the poorly-defined unreactive γ-form of trans-cinnamic acid resulted only in a mixture of the α- and β-forms. The findings suggest a wide role for these spectroscopic methods in monitoring solid-state organic reactions.

Inferring phylogenetic trees from the knowledge of rare evolutionary events.

PubMed

Hellmuth, Marc; Hernandez-Rosales, Maribel; Long, Yangjing; Stadler, Peter F

2018-06-01

Rare events have played an increasing role in molecular phylogenetics as potentially homoplasy-poor characters. In this contribution we analyze the phylogenetic information content from a combinatorial point of view by considering the binary relation on the set of taxa defined by the existence of a single event separating two taxa. We show that the graph-representation of this relation must be a tree. Moreover, we characterize completely the relationship between the tree of such relations and the underlying phylogenetic tree. With directed operations such as tandem-duplication-random-loss events in mind we demonstrate how non-symmetric information constrains the position of the root in the partially reconstructed phylogeny.

Relevance of Hypersexual Disorder to Family Medicine and Primary Care as a Complex Multidimensional Chronic Disease Construct

PubMed Central

Vrijhoef, Bert; De Maeseneer, Jan; Vansintejan, Johan; Devroey, Dirk

2013-01-01

Hypersexual disorder (HD) is not defined in a uniform way in the psychiatric literature. In the absence of solid evidence on prevalence, causes, empirically validated diagnostic criteria, instruments for diagnosis, consistent guidelines on treatment options, medical and psychosocial consequences, and type of caregivers that need to be involved, HD remains a controversial and relatively poorly understood chronic disease construct. The role of family medicine in the detection, treatment, and followup of HD is not well studied. The purpose of this paper is to describe the complexity of HD as a multidimensional chronic disease construct and its relevance to family medicine and primary care. PMID:24066230

Osteoarthritis of the distal interphalangeal joint.

PubMed

Kaufmann, Robert A; Lögters, Tim T; Verbruggen, Gust; Windolf, Joachim; Goitz, Robert J

2010-12-01

Osteoarthritis occurs with the highest prevalence in the distal interphalangeal joint of the hand and has been divided into an erosive and a nonerosive form. The pathogenesis of the early stages of osteoarthritis is poorly understood, but considerable emphasis has been placed on the role of cartilage and subchondral bone as well as soft tissue structures such as collateral ligaments and tendons. Radiographic evaluation represents the most standardized method to quantify disease progression, with different systems having been developed for defining and grading radiographic features. This current concepts article examines the recent knowledge base regarding the etiology, pathogenesis, and evaluation of osteoarthritis of the distal interphalangeal joint. Copyright © 2010. Published by Elsevier Inc.

Histopathologic diagnosis of eosinophilic conditions in the gastrointestinal tract.

PubMed

Hurrell, Jennifer M; Genta, Robert M; Melton, Shelby D

2011-09-01

Eosinophils, a constitutive component of the columnar-lined gastrointestinal tract, play an essential role in allergic responses and parasitic infections. The tissue density of these cells also increases in a variety of conditions of uncertain etiology. With the exception of the esophageal squamous epithelium, in which no eosinophils are normally present, the population of normal eosinophils in the remainder of the luminal gut is poorly defined. Therefore, histopathologists must rely on their subjective judgment to determine when a diagnosis of eosinophilic gastritis, enteritis, or colitis should be rendered. Eosinophilic esophagitis is currently the best defined and most studied eosinophilic condition of the digestive tract; therefore, the confidence in accurate diagnosis is increasing. In contrast, the characteristic clinicopathologic features of eosinophilic conditions affecting other parts of the digestive tract remain somewhat elusive. This review was designed to present pathologists with simple and practical information for the biopsy-based histopathologic diagnosis of eosinophilic esophagitis, gastritis, enteritis, and colitis. It was prepared by critically reviewing more than 200 articles on the topic, along with incorporating evidence accumulated through our own collective experience. We anticipate that by increasing pathologists' confidence in reporting these abnormal but often nameless eosinophilic infiltrates, we can help better define and characterize their significance.

IVF outcomes in average- and poor-prognosis infertile women according to the number of embryos transferred.

PubMed

Vega, Mario G; Gleicher, Norbert; Darmon, Sarah K; Weghofer, Andrea; Wu, Yan-Guang; Wang, Qi; Zhang, Lin; Albertini, David F; Barad, David H; Kushnir, Vitaly A

2016-09-01

Outcome measures of IVF success, which account for effectiveness of IVF and perinatal outcome risks, have recently been described. The association between number of embryos transferred in average and poor-prognosis IVF patients, and the chances of having good or poor IVF and perinatal outcomes, was investigated. Good IVF and perinatal outcome was defined as the birth of a live, term, normal-weight infant (≥2500 g). Poor IVF and perinatal outcome was defined as no live birth or birth of a very low weight neonate (<1500 g) or severe prematurity (birth at <32 weeks gestation). Each neonate was analysed as a separate outcome. A total of 713 IVF cycles in 504 average and poor-prognosis patients from January 2010 to December 2013 were identified. The odds of having good IVF and perinatal outcomes increased by 28% for each additional embryo transferred. The odds of poor IVF and perinatal outcome decreased by 32% with an additional embryo transferred. The likelihood of live birth with good perinatal outcome in average- and poor-prognosis patients after IVF increases with additional embryos being transferred. These data add to recently reported evidence in favour of multiple embryo transfer in older women and those with average or poor IVF prognosis. Copyright © 2016 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

Victimization of Obese Adolescents

ERIC Educational Resources Information Center

Robinson, Sabrina

2006-01-01

Peer victimization of obese adolescents has been associated with low self-esteem, body dissatisfaction, social isolation, marginalization, poor psychosocial adjustment, depression, eating disorders, and suicidal ideation and attempts, not to mention poor academic performance. Weight-based peer victimization is defined as unsolicited bullying and…

New insights into environmental enteric dysfunction

USDA-ARS?s Scientific Manuscript database

Environmental enteric dysfunction (EED) has been recognised as an important contributing factor to physical and cognitive stunting, poor response to oral vaccines, limited resilience to acute infections and ultimately global childhood mortality. The aetiology of EED remains poorly defined but the ep...

Self-defining memories during exposure to music in Alzheimer's disease.

PubMed

El Haj, Mohamad; Antoine, Pascal; Nandrino, Jean Louis; Gély-Nargeot, Marie-Christine; Raffard, Stéphane

2015-10-01

Research suggests that exposure to music may enhance autobiographical recall in Alzheimer's Disease (AD) patients. This study investigated whether exposure to music could enhance the production of self-defining memories, that is, memories that contribute to self-discovery, self-understanding, and identity in AD patients. Twenty-two mild-stage AD patients and 24 healthy controls were asked to produce autobiographical memories in silence, while listening to researcher-chosen music, and to their own-chosen music. AD patients showed better autobiographical recall when listening to their own-chosen music than to researcher-chosen music or than in silence. More precisely, they produced more self-defining memories during exposure to their own-chosen music than to researcher-chosen music or during silence. Additionally, AD patients produced more self-defining memories than autobiographical episodes or personal-semantics during exposure to their own-chosen music. This pattern contrasted with the poor production of self-defining memories during silence or during exposure to researcher-chosen music. Healthy controls did not seem to enjoy the same autobiographical benefits nor the same self-defining memory enhancement in the self-chosen music condition. Poor production of self-defining memories, as observed in AD, may somehow be alleviated by exposure to self-chosen music.

Low free triiodothyronine predicts poor functional outcome after acute ischemic stroke.

PubMed

Suda, Satoshi; Muraga, Kanako; Kanamaru, Takuya; Okubo, Seiji; Abe, Arata; Aoki, Junya; Suzuki, Kentaro; Sakamoto, Yuki; Shimoyama, Takashi; Nito, Chikako; Kimura, Kazumi

2016-09-15

The aim of this study was to investigate the association of admission serum thyroid hormone concentration with clinical characteristics and functional outcomes in patients after acute ischemic stroke. We retrospectively enrolled 398 consecutive patients admitted to our stroke center between July 2010 and April 2012. Serum thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) were evaluated upon admission. Neurological severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) upon admission and the modified Rankin Scale (mRS) upon discharge. Poor outcome was defined as a mRS score of 3-5 or death (mRS score 6). Separate analyses were conducted according to outcome and quartile serum FT3 concentration. In total, 164 patients (41.2%) demonstrated a poor outcome. Age, male gender, blood glucose level, arterial fibrillation, dyslipidemia, smoking, NIHSS score, cardioembolic stroke type, and periventricular hyperintensities, but not FT4 or TSH, were significantly associated with poor functional outcome. Furthermore, poor functional outcome was independently associated with low FT3 (<2.29pg/mL). In comparisons between FT3 quartiles (Q1 [≤2.11pg/mL], Q2 [2.12-2.45pg/mL], Q3 [2.46-2.77pg/mL], Q4 [≥2.78pg/mL]), patients with poor outcomes were more frequent in Q1 than in Q4 after multivariate adjustment. Death was more frequent in Q1 than in Q4 after adjustment for risk factors and comorbidities, but this difference was non-significant after additional adjustment for age and NIHSS score. Our data suggest that a lower FT3 value upon admission may predict a poor functional outcome in patients with acute ischemic stroke. Further large-scale prospective studies are required to clarify the role of thyroid hormone in the acute phase of ischemic stroke. Copyright © 2016 Elsevier B.V. All rights reserved.

Diagnosis and management of primary central nervous system lymphoma.

PubMed

Han, Catherine H; Batchelor, Tracy T

2017-11-15

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive extranodal non-Hodgkin lymphoma (NHL) that is confined to the brain, eyes, spinal cord, or leptomeninges without systemic involvement. The overall prognosis, diagnosis, and management of PCNSL differ from those for other types of NHL. Prompt diagnosis and initiation of treatment are vital for improving clinical outcomes. PCNSL is responsive to radiation therapy; however, whole-brain radiotherapy (WBRT) inadequately controls the disease when it is used alone, and its delayed neurotoxicity causes neurocognitive impairment, especially in elderly patients. High-dose methotrexate (HD-MTX)-based induction chemotherapy with or without autologous stem cell transplantation (ASCT) or reduced-dose WBRT leads to durable disease control and less neurotoxicity. The optimal treatment has yet to be defined; however, HD-MTX-based induction chemotherapy is considered standard for newly diagnosed PCNSL. Ongoing randomized trials are addressing the roles of rituximab and consolidative treatment with ASCT or reduced-dose WBRT. Despite high tumor response rates with the initial treatment, many patients relapse with a very poor prognosis. The optimal treatment for refractory or relapsed PCNSL is poorly defined. The choice of salvage treatment depends on a patient's age, previous treatment and response, performance status, and comorbidities at the time of relapse. This review provides an overview of the clinical features, diagnosis, pathology, and management of PCNSL in immunocompetent patients, and it focuses on recent advances in treatment. Cancer 2017;123:4314-24. © 2017 American Cancer Society. © 2017 American Cancer Society.

A Study of Poor Black Children Who Are Successful Readers. Reading Education Report No. 33.

ERIC Educational Resources Information Center

Durkin, Dolores

A study was conducted to acquire information about poor black children who were successful readers in order to determine what can be done to increase the number of such children. For purposes of the study, "successful" was defined as scoring at or above grade level on a standardized reading test at the end of fifth grade, while "poor" was defined…

Poor outcome prediction by burst suppression ratio in adults with post-anoxic coma without hypothermia.

PubMed

Yang, Qinglin; Su, Yingying; Hussain, Mohammed; Chen, Weibi; Ye, Hong; Gao, Daiquan; Tian, Fei

2014-05-01

Burst suppression ratio (BSR) is a quantitative electroencephalography (qEEG) parameter. The purpose of our study was to compare the accuracy of BSR when compared to other EEG parameters in predicting poor outcomes in adults who sustained post-anoxic coma while not being subjected to therapeutic hypothermia. EEG was registered and recorded at least once within 7 days of post-anoxic coma onset. Electrodes were placed according to the international 10-20 system, using a 16-channel layout. Each EEG expert scored raw EEG using a grading scale adapted from Young and scored amplitude-integrated electroencephalography tracings, in addition to obtaining qEEG parameters defined as BSR with a defined threshold. Glasgow outcome scales of 1 and 2 at 3 months, determined by two blinded neurologists, were defined as poor outcome. Sixty patients with Glasgow coma scale score of 8 or less after anoxic accident were included. The sensitivity (97.1%), specificity (73.3%), positive predictive value (82.5%), and negative prediction value (95.0%) of BSR in predicting poor outcome were higher than other EEG variables. BSR1 and BSR2 were reliable in predicting death (area under the curve > 0.8, P < 0.05), with the respective cutoff points being 39.8% and 61.6%. BSR1 was reliable in predicting poor outcome (area under the curve  =  0.820, P < 0.05) with a cutoff point of 23.9%. BSR1 was also an independent predictor of increased risk of death (odds ratio  =  1.042, 95% confidence intervals: 1.012-1.073, P  =  0.006). BSR may be a better predictor in prognosticating poor outcomes in patients with post-anoxic coma who do not undergo therapeutic hypothermia when compared to other qEEG parameters.

The Role of Diacylglycerol Acyltransferase (DGAT) 1 and 2 in Cardiac Metabolism and Function.

PubMed

Roe, Nathan D; Handzlik, Michal K; Li, Tao; Tian, Rong

2018-03-21

It is increasingly recognized that synthesis and turnover of cardiac triglyceride (TG) play a pivotal role in the regulation of lipid metabolism and function of the heart. The last step in TG synthesis is catalyzed by diacylglycerol:acyltransferase (DGAT) which esterifies the diacylglycerol with a fatty acid. Mammalian heart has two DGAT isoforms, DGAT1 and DGAT2, yet their roles in cardiac metabolism and function remain poorly defined. Here, we show that inactivation of DGAT1 or DGAT2 in adult mouse heart results in a moderate suppression of TG synthesis and turnover. Partial inhibition of DGAT activity increases cardiac fatty acid oxidation without affecting PPARα signaling, myocardial energetics or contractile function. Moreover, coinhibition of DGAT1/2 in the heart abrogates TG turnover and protects the heart against high fat diet-induced lipid accumulation with no adverse effects on basal or dobutamine-stimulated cardiac function. Thus, the two DGAT isoforms in the heart have partially redundant function, and pharmacological inhibition of one DGAT isoform is well tolerated in adult hearts.

Precise let-7 expression levels balance organ regeneration against tumor suppression

PubMed Central

Wu, Linwei; Nguyen, Liem H; Zhou, Kejin; de Soysa, T Yvanka; Li, Lin; Miller, Jason B; Tian, Jianmin; Locker, Joseph; Zhang, Shuyuan; Shinoda, Gen; Seligson, Marc T; Zeitels, Lauren R; Acharya, Asha; Wang, Sam C; Mendell, Joshua T; He, Xiaoshun; Nishino, Jinsuke; Morrison, Sean J; Siegwart, Daniel J; Daley, George Q; Shyh-Chang, Ng; Zhu, Hao

2015-01-01

The in vivo roles for even the most intensely studied microRNAs remain poorly defined. Here, analysis of mouse models revealed that let-7, a large and ancient microRNA family, performs tumor suppressive roles at the expense of regeneration. Too little or too much let-7 resulted in compromised protection against cancer or tissue damage, respectively. Modest let-7 overexpression abrogated MYC-driven liver cancer by antagonizing multiple let-7 sensitive oncogenes. However, the same level of overexpression blocked liver regeneration, while let-7 deletion enhanced it, demonstrating that distinct let-7 levels can mediate desirable phenotypes. let-7 dependent regeneration phenotypes resulted from influences on the insulin-PI3K-mTOR pathway. We found that chronic high-dose let-7 overexpression caused liver damage and degeneration, paradoxically leading to tumorigenesis. These dose-dependent roles for let-7 in tissue repair and tumorigenesis rationalize the tight regulation of this microRNA in development, and have important implications for let-7 based therapeutics. DOI: http://dx.doi.org/10.7554/eLife.09431.001 PMID:26445246

Protein Kinase Cδ Promotes Transitional B Cell-Negative Selection and Limits Proximal B Cell Receptor Signaling To Enforce Tolerance

PubMed Central

Zikherman, Julie; Lau, Tannia; Leitges, Michael; Weiss, Arthur

2014-01-01

Protein kinase Cδ (PKCδ) deficiency causes autoimmune pathology in humans and mice and is crucial for the maintenance of B cell homeostasis. However, the mechanisms underlying autoimmune disease in PKCδ deficiency remain poorly defined. Here, we address the antigen-dependent and -independent roles of PKCδ in B cell development, repertoire selection, and antigen responsiveness. We demonstrate that PKCδ is rapidly phosphorylated downstream of both the B cell receptor (BCR) and the B cell-activating factor (BAFF) receptor. We found that PKCδ is essential for antigen-dependent negative selection of splenic transitional B cells and is required for activation of the proapoptotic Ca2+-Erk pathway that is selectively activated during B cell-negative selection. Unexpectedly, we also identified a previously unrecognized role for PKCδ as a proximal negative regulator of BCR signaling that substantially impacts survival and proliferation of mature follicular B cells. As a consequence of these distinct roles, PKCδ deficiency leads to the survival and development of a B cell repertoire that is not only aberrantly autoreactive but also hyperresponsive to antigen stimulation. PMID:24515435

Laparoscopic treatment of fulminant ulcerative colitis.

PubMed

Bell, R L; Seymour, N E

2002-12-01

The complexity and risks of the surgical treatment of ulcerative colitis are greater in patients with fulminant disease. Subtotal colectomy is frequently offered to such patients to control acute disease and restore immunological and nutritional status prior to a restorative procedure. The role of laparoscopy in this setting is poorly defined. The records of 18 patients with poorly controlled fulminant colitis on aggressive immunosuppressive therapy who underwent laparoscopic subtotal colectomy were reviewed. Postoperative complications occurred in six patients (33%). Postoperative length of stay was 5.0 +/- 0.3 days vs 8.8 +/- 1.8 days (p<0.05) for a group of six patients who had undergone open subtotal colectomy for the same indications. Systemic steroids were withdrawn in all patients, and 17 patients subsequently underwent proctectomy and pelvic pouch construction. The relatively high morbidity rate in these patients is likely related to their compromised status at the time of surgery. Laparoscopic subtotal colectomy in patients with fulminant ulcerative colitis allows for earlier hospital discharge, facilitates subsequent pelvic pouch, construction, and provides an excellent alternative to conventional two- and three-stage surgical treatment.

Sandstone-filled normal faults: A case study from central California

NASA Astrophysics Data System (ADS)

Palladino, Giuseppe; Alsop, G. Ian; Grippa, Antonio; Zvirtes, Gustavo; Phillip, Ruy Paulo; Hurst, Andrew

2018-05-01

Despite the potential of sandstone-filled normal faults to significantly influence fluid transmissivity within reservoirs and the shallow crust, they have to date been largely overlooked. Fluidized sand, forcefully intruded along normal fault zones, markedly enhances the transmissivity of faults and, in general, the connectivity between otherwise unconnected reservoirs. Here, we provide a detailed outcrop description and interpretation of sandstone-filled normal faults from different stratigraphic units in central California. Such faults commonly show limited fault throw, cm to dm wide apertures, poorly-developed fault zones and full or partial sand infill. Based on these features and inferences regarding their origin, we propose a general classification that defines two main types of sandstone-filled normal faults. Type 1 form as a consequence of the hydraulic failure of the host strata above a poorly-consolidated sandstone following a significant, rapid increase of pore fluid over-pressure. Type 2 sandstone-filled normal faults form as a result of regional tectonic deformation. These structures may play a significant role in the connectivity of siliciclastic reservoirs, and may therefore be crucial not just for investigation of basin evolution but also in hydrocarbon exploration.

Equine uveitis: a UK perspective.

PubMed

Lowe, R C

2010-03-01

Uveitis in the equine population of the UK does not appear to be as prevalent or disastrous as seen across regions of Europe and the USA. Some cases perceived to be recurrent uveitis may be poorly resolved single episodes of uveitis and care should be taken not to make the diagnosis of recurrence without ensuring effective control of the initial episode. Leptospira spp. appear to play only a minor role ERU in the UK which is probably the main reason for the prevalence of the disease being much lower compared to the USA and mainland Europe. Actual data are relatively few on the ground as far as disease surveillance in concerned. This has 2 implications. Firstly unless we are able to effectively monitor the levels of uveitic disease, it will be difficult to pick up early changes in the trend which may allow quicker intervention. Secondly, it is difficult to secure funding for further research if the prevalence of the problem is poorly defined. This may leave the UK equine population at risk should the disease profile suddenly alter for the worse.

Serum tenascin-C predicts severity and outcome of acute intracerebral hemorrhage.

PubMed

Wang, Lin-Guo; Huangfu, Xue-Qin; Tao, Bo; Zhong, Guan-Jin; Le, Zhou-Di

2018-06-01

Tenascin-C is a matricellular protein related to brain injury. We studied serum tenascin-C in acute intracerebral hemorrhage (ICH) and examined the associations with severity and outcome following the acute event. Tenascin-C samples were obtained from 162 patients with acute hemorrhagic stroke and 162 healthy controls. Poor 90-day functional outcome was defined as modified Rankin Scale score > 2. Early neurological deterioration (END) and hematoma growth (HG) were recorded at 24 h. Patients had higher tenascin-C levels than controls. Tenascin-C levels were positively correlated with hematoma volume or National Institutes of Health Stroke Scale score at baseline. Elevated tenascin-C levels were independently associated with END, HG, 90-day mortality and poor functional outcome. Moreover, tenascin-C levels significantly predicted END, HG and 90-day outcomes under receiver operating characteristic curves. An increase in serum tenascin-C level is associated with an adverse outcome in ICH patients, supporting the potential role of serum tenascin-C as a prognostic biomarker for hemorrhagic stroke. Copyright © 2018 Elsevier B.V. All rights reserved.

Therapist strategies early in therapy associated with good or poor outcomes among clients with low proactive agency.

PubMed

von der Lippe, Anna Louise; Oddli, Hanne Weie; Halvorsen, Margrethe Seeger

2017-09-10

Within a mixed methods program of research the present study aimed at expanding knowledge about interactions in the initial therapeutic collaboration by combining focus on client interpersonal style and therapist contribution. The study involves in-depth analyses of therapist-client interactions in the initial two sessions of good and poor outcome therapies. Based on interpersonal theory and previous research, the Inventory of Interpersonal Problems (IIP-64-C) was used to define poor outcome cases, that is, low proactive agency cases. To compare good and poor outcome cases matched on this interpersonal pattern, cases were drawn from two different samples; nine poor outcome cases from a large multi-site outpatient clinic study and nine good outcome cases from a process-outcome study of highly experienced therapists. Qualitative analysis of therapist behaviors resulted in 2 main categories, fostering client's proactive agentic involvement in change work and discouraging client's proactive agentic involvement in change work, 8 categories and 22 sub-categories. The findings revealed distinct and cohesive differences in therapist behaviors between the two outcome groups, and point to the particular therapist role of fostering client agency through engagement in a shared work on change when clients display strong unassertiveness and low readiness for change. Clinical or Methodological Significance Summary: The present analysis combines focus on client interpersonal style, therapist strategies/process and outcome. The categories generated from the present grounded theory analysis may serve as a foundation for identifying interactions that are associated with agentic involvement in future process research and practice, and hence we have formulated principles/strategies that were identified by the analysis.

Molecular Mechanisms of Taste Recognition: Considerations about the Role of Saliva

PubMed Central

Fábián, Tibor Károly; Beck, Anita; Fejérdy, Pál; Hermann, Péter; Fábián, Gábor

2015-01-01

The gustatory system plays a critical role in determining food preferences and food intake, in addition to nutritive, energy and electrolyte balance. Fine tuning of the gustatory system is also crucial in this respect. The exact mechanisms that fine tune taste sensitivity are as of yet poorly defined, but it is clear that various effects of saliva on taste recognition are also involved. Specifically those metabolic polypeptides present in the saliva that were classically considered to be gut and appetite hormones (i.e., leptin, ghrelin, insulin, neuropeptide Y, peptide YY) were considered to play a pivotal role. Besides these, data clearly indicate the major role of several other salivary proteins, such as salivary carbonic anhydrase (gustin), proline-rich proteins, cystatins, alpha-amylases, histatins, salivary albumin and mucins. Other proteins like glucagon-like peptide-1, salivary immunoglobulin-A, zinc-α-2-glycoprotein, salivary lactoperoxidase, salivary prolactin-inducible protein and salivary molecular chaperone HSP70/HSPAs were also expected to play an important role. Furthermore, factors including salivary flow rate, buffer capacity and ionic composition of saliva should also be considered. In this paper, the current state of research related to the above and the overall emerging field of taste-related salivary research alongside basic principles of taste perception is reviewed. PMID:25782158

The role of strigolactones and ethylene in disease caused by Pythium irregulare.

PubMed

Blake, Sara N; Barry, Karen M; Gill, Warwick M; Reid, James B; Foo, Eloise

2016-06-01

Plant hormones play key roles in defence against pathogen attack. Recent work has begun to extend this role to encompass not just the traditional disease/stress hormones, such as ethylene, but also growth-promoting hormones. Strigolactones (SLs) are the most recently defined group of plant hormones with important roles in plant-microbe interactions, as well as aspects of plant growth and development, although the knowledge of their role in plant-pathogen interactions is extremely limited. The oomycete Pythium irregulare is a poorly controlled pathogen of many crops. Previous work has indicated an important role for ethylene in defence against this oomycete. We examined the role of ethylene and SLs in response to this pathogen in pea (Pisum sativum L.) at the molecular and whole-plant levels using a set of well-characterized hormone mutants, including an ethylene-insensitive ein2 mutant and SL-deficient and insensitive mutants. We identified a key role for ethylene signalling in specific cell types that reduces pathogen invasion, extending the work carried out in other species. However, we found no evidence that SL biosynthesis or response influences the interaction of pea with P. irregulare or that synthetic SL influences the growth or hyphal branching of the oomycete in vitro. Future work should seek to extend our understanding of the role of SLs in other plant interactions, including with other fungal, bacterial and viral pathogens, nematodes and insect pests. © 2015 BSPP AND JOHN WILEY & SONS LTD.

Mycotoxins are conventional and novel risk biomarkers for hepatocellular carcinoma

PubMed Central

Matsuda, Yasunobu; Wakai, Toshifumi; Kubota, Masayuki; Osawa, Mami; Sanpei, Ayumi; Fujimaki, Shun

2013-01-01

Hepatocellular carcinoma (HCC) is a common malignant disease with poor prognosis. To improve the clinical outcome, early diagnosis of HCC arising from nonviral agents and hepatitis virus is important. Among several etiological factors, mycotoxins defined as carcinogens by the International Agency for Research in Cancer might be one of the critical risk factors for nonviral HCC. Aflatoxin B1 is the most well-known carcinogenic mycotoxin for HCC, but the role of the other types of mycotoxin remains unclear. Several studies have reported that a chromatographic separation technique based on high-performance liquid chromatography can successfully detect the concentration of mycotoxins in plasma. In this article, we review recent studies of mycotoxin, and discuss its possible significance as a biomarker of HCC. PMID:23674865

[Impairment of attention and executive functions in patients with paranoid schizophrenia].

PubMed

Tsygankov, B D; Khannanova, A N; Nekrasova, S V

2013-01-01

To study changes in attention and executive functions during psychopharmacotherapy in patients with paranoid schizophrenia, we have examined 120 patients with a first episode of paranoid schizophrenia treated with typical and atypical neuroleptics. Clinical and statistical analyses have revealed the heterogeneity within treatment groups that allowed to define two subgroups. These subgroups were characterized by a differed disease course (favorable or poor type). Before remission was achieved, the effect of atypical neuroleptics on cognitive performance was higher compared to typical neuroleptics. After remission, when doses of neuroleptics were decreased, a type of disease course played a main role. At 6 months after remission, attention and executive functions have improved in subgroups with favorable course of disease regardless of treatment.

Burnout in psychiatrists

PubMed Central

KUMAR, SHAILESH

2007-01-01

Psychiatrists as a group are vulnerable to experiencing burnout, more so than other physicians and surgeons. In this paper, various definitions of burnout are reviewed and the tools available for quantifying burnout are compared. The factors that make psychiatry a stressful profession are also examined. These include factors such as patient violence and suicide, limited resources, crowded inpatient wards, changing culture in mental health services, high work demands, poorly defined roles of consultants, responsibility without authority, inability to effect systemic change, conflict between responsibility toward employers vs. toward the patient, and isolation. In order to investigate how exposure to such stressors results in burnout, two theoretical models are examined. Recommendations are also made, on the basis of anecdotal reports, for addressing burnout in psychiatrists. PMID:18188444

Long-term effects of bullying.

PubMed

Wolke, Dieter; Lereya, Suzet Tanya

2015-09-01

Bullying is the systematic abuse of power and is defined as aggressive behaviour or intentional harm-doing by peers that is carried out repeatedly and involves an imbalance of power. Being bullied is still often wrongly considered as a 'normal rite of passage'. This review considers the importance of bullying as a major risk factor for poor physical and mental health and reduced adaptation to adult roles including forming lasting relationships, integrating into work and being economically independent. Bullying by peers has been mostly ignored by health professionals but should be considered as a significant risk factor and safeguarding issue. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

The impact of size on particulate vaccine adjuvants.

PubMed

Shah, Ruchi R; O'Hagan, Derek T; Amiji, Mansoor M; Brito, Luis A

2014-12-01

Particulate adjuvants have been successful at inducing increased immune responses against many poorly immunogenic antigens. However, the mechanism of action of these adjuvants often remains unclear. As more potential vaccine targets are emerging, it is becoming necessary to broaden our knowledge on the factors involved in generating potent immune responses to recombinant antigens with adjuvants. While composition of adjuvants is integral in defining the overall performance of an adjuvant, some physical parameters such as particle size, surface charge and surface modification may also contribute to the potency. In this review, we will try to highlight the role of particle size in controlling the immune responses to adjuvanted vaccines, with a focus on insoluble aluminum salts, oil-in-water emulsions, polymeric particles and liposomes.

Surgical Management of Lung Cancer Involving the Chest Wall.

PubMed

Lanuti, Michael

2017-05-01

The prevalence of chest wall invasion by non-small cell lung cancer is < 10% in published surgical series. The role of radiation or chemotherapy around the complete resection of lung cancer invading the chest wall, excluding the superior sulcus of the chest, is poorly defined. Survival of patients with lung cancer invading the chest wall is dependent on lymph node involvement and completeness of en-bloc resection. In some patients harboring T3N0 disease, 5-year survival in excess of 50% can be achieved. Offering en-bloc resection of lung cancer invading chest wall to patients with T3N1 or T3N2 disease is controversial. Copyright © 2017 Elsevier Inc. All rights reserved.

A parsimonious land data assimilation system for the SMAP/GPM satellite era

USDA-ARS?s Scientific Manuscript database

Land data assimilation systems typically require complex parameterizations in order to: define required observation operators, quantify observing/forecasting errors and calibrate a land surface assimilation model. These parameters are commonly defined in an arbitrary manner and, if poorly specified,...

Plasma Vitamin D Deficiency Is Associated with Poor Sleep Quality and Night-Time Eating at Mid-Pregnancy in Singapore

PubMed Central

Cheng, Tuck Seng; Loy, See Ling; Cheung, Yin Bun; Cai, Shirong; Colega, Marjorelee T.; Godfrey, Keith M.; Chong, Yap-Seng; Tan, Kok Hian; Shek, Lynette Pei-Chi; Lee, Yung Seng; Lek, Ngee; Chan, Jerry Kok Yen; Chong, Mary Foong-Fong; Yap, Fabian

2017-01-01

Plasma 25-hydroxyvitamin D (25OHD) deficiency, poor sleep quality, and night-time eating, have been independently associated with adverse pregnancy outcomes, but their inter-relationships are yet to be evaluated. We aimed to investigate the associations between maternal plasma 25OHD status and sleep quality and circadian eating patterns during pregnancy. Data on pregnant women (n = 890) from a prospective cohort (Growing Up in Singapore Towards healthy Outcomes) were analyzed. Plasma 25OHD concentration was measured, while the Pittsburgh sleep quality index (PSQI) and 24-h dietary recall were administered to women at 26–28 weeks’ gestation. Plasma 25OHD status was defined as sufficient (>75 nmol/L), insufficient (50–75 nmol/L), or deficient (<50 nmol/L). Poor sleep quality was defined by a total global PSQI score >5. Predominantly day-time (pDT) and predominantly night-time (pNT) were defined according to consumption of greater proportion of calories (i.e., >50%) from 07:00–18:59 and from 19:00–06:59, respectively. After adjustment for confounders, women with plasma 25OHD deficiency had higher odds of poor sleep quality (odds ratio (OR) 3.49; 95% confidence interval (CI) 1.84–6.63) and pNT eating (OR: 1.85; 95% CI 1.00–3.41) than those who were 25OHD sufficient. Our findings show the association of maternal plasma 25OHD deficiency with poor sleep quality and pNT eating at mid-pregnancy. PMID:28353643

Public Schools and the Common Good.

ERIC Educational Resources Information Center

Reese, William J.

1988-01-01

Improving public school education, especially for the poor, requires defining and articulating some vision of the common good. This article reviews key positions taken by liberals and conservatives regarding educational reform during the 19th and 20th centuries and critiques these positions with regard to their disservice to the poor. (IAH)

How to diagnose and manage hepatic encephalopathy: a consensus statement on roles and responsibilities beyond the liver specialist

PubMed Central

Dunk, Arthur A.; Jalan, Rajiv; Kircheis, Gerald; de Knegt, Robert J.; Laleman, Wim; Ramage, John K.; Wedemeyer, Heiner; Morgan, Ian E.J.

2016-01-01

Introduction Hepatic encephalopathy is defined as brain dysfunction caused by liver insufficiency and/or portosystemic shunting. Symptoms include nonspecific cognitive impairment, personality changes and changes in consciousness. Overt (symptomatic) hepatic encephalopathy is a common complication of cirrhosis that is associated with a poor prognosis. Patients with hepatic encephalopathy may present to healthcare providers who do not have primary responsibility for management of patients with cirrhosis. Therefore, we developed a series of ‘consensus points’ to provide some guidance on management. Methods Using a modified ‘Delphi’ process, consensus statements were developed that summarize our recommendations for the diagnosis and management of patients with hepatic encephalopathy. Points on which full consensus could not be reached are also discussed. Results Our recommendations emphasize the role of all healthcare providers in the identification of cognitive impairment in patients with cirrhosis and provide guidance on steps that might be considered to make a diagnosis of overt hepatic encephalopathy. In addition, treatment recommendations are summarized. Minimal hepatic encephalopathy can have a significant impact on patients; however, in most circumstances identification and management of minimal hepatic encephalopathy remains the responsibility of specialists in liver diseases. Conclusion Our opinion statements aim to define the roles and responsibilities of all healthcare providers who at times care for patients with cirrhosis and hepatic encephalopathy. We suggest that these recommendations be considered further by colleagues in other disciplines and hope that future guidelines consider the management of patients with cirrhosis and with a ‘suspicion’ of cognitive impairment through to a formal diagnosis of hepatic encephalopathy. PMID:26600154

How to diagnose and manage hepatic encephalopathy: a consensus statement on roles and responsibilities beyond the liver specialist.

PubMed

Shawcross, Debbie L; Dunk, Arthur A; Jalan, Rajiv; Kircheis, Gerald; de Knegt, Robert J; Laleman, Wim; Ramage, John K; Wedemeyer, Heiner; Morgan, Ian E J

2016-02-01

Hepatic encephalopathy is defined as brain dysfunction caused by liver insufficiency and/or portosystemic shunting. Symptoms include nonspecific cognitive impairment, personality changes and changes in consciousness. Overt (symptomatic) hepatic encephalopathy is a common complication of cirrhosis that is associated with a poor prognosis. Patients with hepatic encephalopathy may present to healthcare providers who do not have primary responsibility for management of patients with cirrhosis. Therefore, we developed a series of 'consensus points' to provide some guidance on management. Using a modified 'Delphi' process, consensus statements were developed that summarize our recommendations for the diagnosis and management of patients with hepatic encephalopathy. Points on which full consensus could not be reached are also discussed. Our recommendations emphasize the role of all healthcare providers in the identification of cognitive impairment in patients with cirrhosis and provide guidance on steps that might be considered to make a diagnosis of overt hepatic encephalopathy. In addition, treatment recommendations are summarized. Minimal hepatic encephalopathy can have a significant impact on patients; however, in most circumstances identification and management of minimal hepatic encephalopathy remains the responsibility of specialists in liver diseases. Our opinion statements aim to define the roles and responsibilities of all healthcare providers who at times care for patients with cirrhosis and hepatic encephalopathy. We suggest that these recommendations be considered further by colleagues in other disciplines and hope that future guidelines consider the management of patients with cirrhosis and with a 'suspicion' of cognitive impairment through to a formal diagnosis of hepatic encephalopathy.

The importance of the cortical subarachnoid space in understanding hydrocephalus.

PubMed

Rekate, Harold L; Nadkarni, Trimurti D; Wallace, Donna

2008-07-01

In this paper the authors define the role of the cortical subarachnoid space (CSAS) in poorly understood forms of hydrocephalus to cerebrospinal fluid (CSF) dynamics to improve understanding of the importance of the CSAS and its role in selecting patients for endoscopic third ventriculostomy (ETV). The secondary purpose of this work was to define testable hypotheses to explain enigmatic disorders of CSF dynamics and to suggest how these concepts could be tested. The magnitude of the contribution of the CSAS is explored using the solid geometry of concentric spheres. With this starting point, clinical conditions in which CSF dynamics are not easily understood are explored regarding the potential role of the CSAS. Overall, problems of CSF dynamics are easily understood. Insights may be gained when the results of a pathological process or its treatment vary from what has been expected. Acute changes in ventricular volume at the time that hydrocephalus develops, the failure of shunts, and the changes in ventricular volume with shunt repair may occur very rapidly. Changes in the volume of water in the brain, especially in the brain substance itself, are unlikely to occur at this rapid rate and may be interpreted as a simple redistribution of the CSF between the ventricle and CSAS with no initial change in the actual volume of brain parenchyma. Problems such as pseudotumor cerebri, shunt failure with nonresponsive ventricles, and negative-pressure hydrocephalus can be explained by assessing the ability of ventricular CSF to flow to the CSAS and the ability of this fluid to exit this compartment. Ventricular enlargement at the time of shunt failure implies a failure of flow between the ventricles and CSAS, implying that all patients who show this phenomenon are potential candidates for ETV. The important role of the CSAS in the pathophysiology of various forms of hydrocephalus has been largely ignored. Attention to the dynamics of the CSF in this compartment will improve understanding of enigmatic conditions of hydrocephalus and improve selection criteria for treatment paradigms such as ETV. These concepts lead to clearly defined problems that may be solved by the creation of a central database to address these issues.

The role of trait and ability emotional intelligence in bulimic symptoms.

PubMed

Gardner, Kathryn Jane; Quinton, Stephanie; Qualter, Pamela

2014-04-01

Bulimia is characterized by poor affect regulation, yet the role of emotional intelligence (EI) is little understood. This study examined associations between EI and bulimic symptoms using 235 women from community and student populations. They completed measures of trait and ability EI, and the Eating Disorders Diagnostic Scale. Results showed that deficiencies in different aspects of trait EI and/or ability EI are a function of symptom type: binge eating, compensatory behaviours or weight and shape concerns. Consistent with affect regulation models, self-regulatory aspects of trait EI were related to two bulimic symptoms: binge eating and weight and shape concerns. Ability-based self-emotion management was not important, and explanatory power of lower-level EI facets (traits or abilities) was not superior to more broadly defined EI factors. Results support the conclusion that trait and ability EI may maintain subclinical levels of bulimic symptoms but have different paths. Copyright © 2014 Elsevier Ltd. All rights reserved.

Attributes of γδ intraepithelial lymphocytes as suggested by their transcriptional profile

PubMed Central

Fahrer, Aude M.; Konigshofer, Yves; Kerr, Elizabeth M.; Ghandour, Ghassan; Mack, David H.; Davis, Mark M.; Chien, Yueh-hsiu

2001-01-01

γδ T lymphocytes in the intestinal intraepithelial layer (γδ IELs) are thought to contribute to immune competence, but their actual function remains poorly understood. Here we used DNA microarrays to study the gene expression profile of γδ IELs in a Yersinia infection system to better define their roles. To validate this approach, mesenteric lymph node CD8+ αβ T cells were similarly analyzed. The transcription profiles show that, whereas lymph node CD8+ αβ T cells must be activated to become cytotoxic effectors, γδ IELs are constitutively activated and appear to use different signaling cascades. Our data suggest that γδ IELs may respond efficiently to a broad range of pathological situations irrespective of their diverse T cell antigen receptor repertoire. γδ IELs may modulate local immune responses and participate in intestinal lipid metabolism, cholesterol homeostasis, and physiology. This study provides a strong basis for further investigations of the roles of these cells as well as mucosal immune defense in general. PMID:11526237

Polypyrimidine tract-binding protein influences negative strand RNA synthesis of dengue virus.

PubMed

Jiang, Linbin; Yao, Huiling; Duan, Xiaoqun; Lu, Xi; Liu, Yongming

2009-07-24

Flavivirus non-structural protein 4A (NS4A) induces membrane rearrangements to form viral replication complex and functions as interferon antagonist. However, other non-structural roles of NS4A protein in relation to virus life-cycle are poorly defined. This study elucidated if dengue virus (DENV) NS4A protein interacts with host proteins and contributes to viral pathogenesis by screening human liver cDNA yeast-two-hybrid library. Our study identified polypyrimidine tract-binding protein (PTB) as a novel interacting partner of DENV NS4A protein. We reported for the first time that PTB influenced DENV production. Gene-silencing studies showed that PTB did not have an effect on DENV entry and DENV RNA translation. Further functional studies revealed that PTB influenced DENV production by modulating negative strand RNA synthesis. This is the first study that enlightens the interaction of DENV NS4A protein with PTB, in addition to demonstrating the novel role of PTB in relation to mosquito-borne flavivirus life-cycle.

Developing expertise in surgery.

PubMed

Alderson, David

2010-01-01

The concept of expertise is widely embraced but poorly defined in surgery. Dictionary definitions differentiate between authority and experience, while a third view sees expertise as a mind-set rather than a status. Both absolute and relative models of expertise have been developed, and each allows a richer understanding of the application of these concepts to emerge. Trainees must develop both independent and interdependent expertise, and an appreciation of the essentially constructivist and uncertain nature of medical knowledge. Approach may be more important than innate talent; the concepts of 'flow', sustained 'deliberate practice' and 'adaptive expertise' are examples of expert approaches to learning. Non-analytical reasoning plays a key role in decision making at expert levels of practice. A technically gifted surgeon may be seen as a safety hazard rather than an expert if inter-dependent expertise has not been developed. Key roles of a surgical educator are to facilitate the development of an expert approach to education and to enable entry into and movement towards the centre of an expert community of practice.

Commensal bacteria produce GPCR ligands that mimic human signaling molecules

PubMed Central

Cohen, Louis J.; Esterhazy, Daria; Kim, Seong-Hwan; Lemetre, Christophe; Aguilar, Rhiannon R.; Gordon, Emma A.; Pickard, Amanda J.; Cross, Justin R.; Emiliano, Ana B.; Han, Sun M.; Chu, John; Vila-Farres, Xavier; Kaplitt, Jeremy; Rogoz, Aneta; Calle, Paula Y.; Hunter, Craig; Bitok, J. Kipchirchir; Brady, Sean F.

2017-01-01

Summary Statement Commensal bacteria are believed to play important roles in human health. The mechanisms by which they affect mammalian physiology are poorly understood; however, bacterial metabolites are likely to be key components of host interactions. Here, we use bioinformatics and synthetic biology to mine the human microbiota for N-acyl amides that interact with G-protein-coupled receptors (GPCRs). We found that N-acyl amide synthase genes are enriched in gastrointestinal bacteria and the lipids they encode interact with GPCRs that regulate gastrointestinal tract physiology. Mouse and cell-based models demonstrate that commensal GPR119 agonists regulate metabolic hormones and glucose homeostasis as efficiently as human ligands although future studies are needed to define their potential physiologic role in humans. This work suggests that chemical mimicry of eukaryotic signaling molecules may be common among commensal bacteria and that manipulation of microbiota genes encoding metabolites that elicit host cellular responses represents a new small molecule therapeutic modality (microbiome-biosynthetic-gene-therapy). PMID:28854168

Multiphoton microscopy of ECM proteins in baboon aortic leaflet

NASA Astrophysics Data System (ADS)

Gonzalez, Mariacarla; Saytashev, Ilyas; Luna, Camila; Gonzalez, Brittany; Pinero, Alejandro; Perez, Manuel; Ramaswamy, Sharan; Ramella-Roman, Jessica

2018-02-01

The extracellular matrix (ECM) plays crucial role in defining mechanical properties of a heart valve yet the mechanobiological role of the ECM proteins - collagen and elastin - in living heart valve leaflets is still poorly understood. In this study, non-linear microscopy was used to obtain three dimensional images of collagen and elastin arrangement in aortic leaflets under combined steady flow (850 ml/min) and cyclic flexure (1 Hz) mechanical (dynamic) training. A novel bioreactor capable of mimicking the flow conditions in a living heart was used in this study and was optimized for microscopic imagery. A custom made non-linear microscope was used in this study to provide Second Harmonic Generation (SHG) imaging of collagen arrangement and two-photon imaging of elastin. Two control and three trained leaflet samples from static and dynamic tissue culture were imaged to observe protein changes in the tissue for a period of seven days. Dynamic training led to a decrease in alignment index of the protein fibers compared to the static treatment.

The role of food intolerance in functional gastrointestinal disorders in children.

PubMed

Wilson, Kate; Hill, Rebecca J

2014-10-01

Functional gastrointestinal disorder (FGID) is a common, benign, chronic diagnosis that has a significant negative impact on quality of life. FGIDs that develop in childhood can persist into adulthood. Currently, there is no cure and few treatment options are available. This article provides an outline of current research supporting the role of food intolerance in children with FGIDs. Food intolerances have long been reported by patients with FGIDs; however, randomised controlled trials are lacking in this area. Food intolerances that have been investigated include intolerance to food chemicals, lactose, fructose and, more recently, fer-mentable carbohydrates, termed FODMAPs. The low-FODMAP diet eliminates poorly absorbed short-chain carbohydrates and has a clearly defined mechanism of action. Emerging evidence suggests it alleviates symptoms in adults with irritable bowel syndrome and, potentially, also in children. However, more evidence is required for the efficacy of the diet in children and in oth-er subgroups of FGID. Any dietary restriction in growing children should be undertaken with clinical supervision by a dietitian.

Unrestrained AMPylation targets cytosolic chaperones and activates the heat shock response

PubMed Central

Truttmann, Matthias C.; Zheng, Xu; Hanke, Leo; Damon, Jadyn R.; Grootveld, Monique; Krakowiak, Joanna; Pincus, David; Ploegh, Hidde L.

2017-01-01

Protein AMPylation is a conserved posttranslational modification with emerging roles in endoplasmic reticulum homeostasis. However, the range of substrates and cell biological consequences of AMPylation remain poorly defined. We expressed human and Caenorhabditis elegans AMPylation enzymes—huntingtin yeast-interacting protein E (HYPE) and filamentation-induced by cyclic AMP (FIC)-1, respectively—in Saccharomyces cerevisiae, a eukaryote that lacks endogenous protein AMPylation. Expression of HYPE and FIC-1 in yeast induced a strong cytoplasmic Hsf1-mediated heat shock response, accompanied by attenuation of protein translation, massive protein aggregation, growth arrest, and lethality. Overexpression of Ssa2, a cytosolic heat shock protein (Hsp)70, was sufficient to partially rescue growth. In human cell lines, overexpression of active HYPE similarly induced protein aggregation and the HSF1-dependent heat shock response. Excessive AMPylation also abolished HSP70-dependent influenza virus replication. Our findings suggest a mode of Hsp70 inactivation by AMPylation and point toward a role for protein AMPylation in the regulation of cellular protein homeostasis beyond the endoplasmic reticulum. PMID:28031489

Inflammation-Induced, STING-Dependent Autophagy Restricts Zika Virus Infection in the Drosophila Brain.

PubMed

Liu, Yuan; Gordesky-Gold, Beth; Leney-Greene, Michael; Weinbren, Nathan L; Tudor, Matthew; Cherry, Sara

2018-06-09

The emerging arthropod-borne flavivirus Zika virus (ZIKV) is associated with neurological complications. Innate immunity is essential for the control of virus infection, but the innate immune mechanisms that impact viral infection of neurons remain poorly defined. Using the genetically tractable Drosophila system, we show that ZIKV infection of the adult fly brain leads to NF-kB-dependent inflammatory signaling, which serves to limit infection. ZIKV-dependent NF-kB activation induces the expression of Drosophila stimulator of interferon genes (dSTING) in the brain. dSTING protects against ZIKV by inducing autophagy in the brain. Loss of autophagy leads to increased ZIKV infection of the brain and death of the infected fly, while pharmacological activation of autophagy is protective. These data suggest an essential role for an inflammation-dependent STING pathway in the control of neuronal infection and a conserved role for STING in antimicrobial autophagy, which may represent an ancestral function for this essential innate immune sensor. Copyright © 2018. Published by Elsevier Inc.

The role of basic leucine zipper transcription factor E4BP4 in the immune system and immune-mediated diseases.

PubMed

Yin, Jinghua; Zhang, Jian; Lu, Qianjin

2017-07-01

Basic leucine zipper transcription factor E4BP4 (also known as NFIL3) has been implicated in the molecular and cellular mechanisms of functions and activities in mammals. The interactions between E4BP4 and major regulators of cellular processes have triggered significant interest in the roles of E4BP4 in the pathogenesis of certain chronic diseases. Indeed, novel discoveries have been emerging to illustrate the involvement of E4BP4 in multiple disorders. It is recognized that E4BP4 is extensively involved in some immune-mediated diseases, but the mechanisms of E4BP4 involvement in these complex diseases remain poorly defined. Here we review the regulatory mechanisms of E4BP4 engaging in not only the biological function but also the development of immune-mediated diseases, paving the way for future therapies. Copyright © 2017. Published by Elsevier Inc.

Prolactin Alters the Mammary Epithelial Hierarchy, Increasing Progenitors and Facilitating Ovarian Steroid Action.

PubMed

O'Leary, Kathleen A; Shea, Michael P; Salituro, Stephanie; Blohm, Courtney E; Schuler, Linda A

2017-10-10

Hormones drive mammary development and function and play critical roles in breast cancer. Epidemiologic studies link prolactin (PRL) to increased risk for aggressive cancers that express estrogen receptor α (ERα). However, in contrast to ovarian steroids, PRL actions on the mammary gland outside of pregnancy are poorly understood. We employed the transgenic NRL-PRL model to examine the effects of PRL alone and with defined estrogen/progesterone exposure on stem/progenitor activity and regulatory networks that drive epithelial differentiation. PRL increased progenitors and modulated transcriptional programs, even without ovarian steroids, and with steroids further raised stem cell activity associated with elevated canonical Wnt signaling. However, despite facilitating some steroid actions, PRL opposed steroid-driven luminal maturation and increased CD61 + luminal cells. Our findings demonstrate that PRL can powerfully influence the epithelial hierarchy alone and temper the actions of ovarian steroids, which may underlie its role in the development of breast cancer. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Sensitivity analysis as an aid in modelling and control of (poorly-defined) ecological systems. [closed ecological systems

NASA Technical Reports Server (NTRS)

Hornberger, G. M.; Rastetter, E. B.

1982-01-01

A literature review of the use of sensitivity analyses in modelling nonlinear, ill-defined systems, such as ecological interactions is presented. Discussions of previous work, and a proposed scheme for generalized sensitivity analysis applicable to ill-defined systems are included. This scheme considers classes of mathematical models, problem-defining behavior, analysis procedures (especially the use of Monte-Carlo methods), sensitivity ranking of parameters, and extension to control system design.

Topological constraints are major determinants of tRNA tertiary structure and dynamics and provide basis for tertiary folding cooperativity

PubMed Central

Mustoe, Anthony M.; Brooks, Charles L.; Al-Hashimi, Hashim M.

2014-01-01

Recent studies have shown that basic steric and connectivity constraints encoded at the secondary structure level are key determinants of 3D structure and dynamics in simple two-way RNA junctions. However, the role of these topological constraints in higher order RNA junctions remains poorly understood. Here, we use a specialized coarse-grained molecular dynamics model to directly probe the thermodynamic contributions of topological constraints in defining the 3D architecture and dynamics of transfer RNA (tRNA). Topological constraints alone restrict tRNA's allowed conformational space by over an order of magnitude and strongly discriminate against formation of non-native tertiary contacts, providing a sequence independent source of folding specificity. Topological constraints also give rise to long-range correlations between the relative orientation of tRNA's helices, which in turn provides a mechanism for encoding thermodynamic cooperativity between distinct tertiary interactions. These aspects of topological constraints make it such that only several tertiary interactions are needed to confine tRNA to its native global structure and specify functionally important 3D dynamics. We further show that topological constraints are conserved across tRNA's different naturally occurring secondary structures. Taken together, our results emphasize the central role of secondary-structure-encoded topological constraints in defining RNA 3D structure, dynamics and folding. PMID:25217593

Biochemical and genetic analysis of the role of the viral polymerase in enterovirus recombination.

PubMed

Woodman, Andrew; Arnold, Jamie J; Cameron, Craig E; Evans, David J

2016-08-19

Genetic recombination in single-strand, positive-sense RNA viruses is a poorly understand mechanism responsible for generating extensive genetic change and novel phenotypes. By moving a critical cis-acting replication element (CRE) from the polyprotein coding region to the 3' non-coding region we have further developed a cell-based assay (the 3'CRE-REP assay) to yield recombinants throughout the non-structural coding region of poliovirus from dually transfected cells. We have additionally developed a defined biochemical assay in which the only protein present is the poliovirus RNA dependent RNA polymerase (RdRp), which recapitulates the strand transfer events of the recombination process. We have used both assays to investigate the role of the polymerase fidelity and nucleotide turnover rates in recombination. Our results, of both poliovirus intertypic and intratypic recombination in the CRE-REP assay and using a range of polymerase variants in the biochemical assay, demonstrate that RdRp fidelity is a fundamental determinant of recombination frequency. High fidelity polymerases exhibit reduced recombination and low fidelity polymerases exhibit increased recombination in both assays. These studies provide the basis for the analysis of poliovirus recombination throughout the non-structural region of the virus genome and provide a defined biochemical assay to further dissect this important evolutionary process. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Promoting leadership and management in Australian general practice nursing: what will it take?

PubMed

Halcomb, Elizabeth J; Davidson, Patricia M; Patterson, Elizabeth

2008-10-01

This paper outlines the current state of Australian practice nursing, describes the context of general practice and establishes the importance of promoting leadership and management in this setting. Australian general practice nurses have emerged as key stakeholders in primary health care. However, their role in leadership and management has been largely invisible. The reasons for this are multifactorial, including the delay to establish a strong professional organization, their negative power relationships with general medical practitioners, limited nursing leadership and poorly defined roles. To date, the impetus for practice nurse growth has been largely external to the nursing profession. Growth has been driven by the increasing burden of chronic disease and workforce shortages. This has further weakened the control of nurse leaders over the development of the specialty. The Australian practice nurse role is at a crossroads. While the practice nurse role is a viable force to improve health outcomes, the growing strength of the practice nurse challenges traditional professional roles and practice patterns. There is an urgent need to develop practice nurse leaders and managers to not only embrace the challenges of Australian general practice from an operational perspective, but also undertake a clinical leadership role. As clinical leaders, these nurses will need to develop a culture that not only optimizes health outcomes but also advances the status of the nursing profession.

Residents of poor nations have a greater sense of meaning in life than residents of wealthy nations.

PubMed

Oishi, Shigehiro; Diener, Ed

2014-02-01

Using Gallup World Poll data, we examined the role of societal wealth for meaning in life across 132 nations. Although life satisfaction was substantially higher in wealthy nations than in poor nations, meaning in life was higher in poor nations than in wealthy nations. In part, meaning in life was higher in poor nations because people in those nations were more religious. The mediating role of religiosity remained significant after we controlled for potential third variables, such as education, fertility rate, and individualism. As Frankl (1963) stated in Man's Search for Meaning, it appears that meaning can be attained even under objectively dire living conditions, and religiosity plays an important role in this search.

The 'patient's physician one-step removed': the evolving roles of medical tourism facilitators.

PubMed

Snyder, Jeremy; Crooks, Valorie A; Adams, Krystyna; Kingsbury, Paul; Johnston, Rory

2011-09-01

Medical tourism involves patients travelling internationally to receive medical services. This practice raises a range of ethical issues, including potential harms to the patient's home and destination country and risks to the patient's own health. Medical tourists often engage the services of a facilitator who may book travel and accommodation and link the patient with a hospital abroad. Facilitators have the potential to exacerbate or mitigate the ethical concerns associated with medical tourism, but their roles are poorly understood. 12 facilitators were interviewed from 10 Canadian medical tourism companies. Three themes were identified: facilitators' roles towards the patient, health system and medical tourism industry. Facilitators' roles towards the patient were typically described in terms of advocacy and the provision of information, but limited by facilitators' legal liability. Facilitators felt they played a positive role in the lives of their patients and the Canadian health system and served as catalysts for reform, although they noted an adversarial relationship with some Canadian physicians. Many facilitators described personally visiting medical tourism sites and forming personal relationships with surgeons abroad, but noted the need for greater regulation of their industry. Facilitators play a substantial and evolving role in the practice of medical tourism and may be entering a period of professionalisation. Because of the key role of facilitators in determining the effects of medical tourism on patients and public health, this paper recommends a planned conversation between medical tourism stakeholders to define and shape facilitators' roles.

The Role of Emotion Regulation in Autism Spectrum Disorder RH: Emotion Regulation in ASD

PubMed Central

Mazefsky, Carla A.; Herrington, John; Siegel, Matthew; Scarpa, Angela; Maddox, Brenna B.; Scahill, Lawrence; White, Susan W.

2013-01-01

Objective Autism spectrum disorder (ASD) is associated with amplified emotional responses and poor emotional control, but little is known about the underlying mechanisms. This paper provides a conceptual and methodological framework for understanding compromised emotion regulation (ER) in ASD. Method After defining ER and related constructs, methods to study ER were reviewed with special consideration on how to apply these approaches to ASD. Against the backdrop of cognitive characteristics in ASD and existing ER theories, available research was examined to identify likely contributors to emotional dysregulation in ASD. Results Little is currently known about ER in youth with ASD. Some mechanisms that contribute to poor ER in ASD may be shared with other clinical populations (e.g., physiological arousal, degree of negative and positive affect, alterations in the amygdala and prefrontal cortex), whereas other mechanisms may be more unique to ASD (e.g., differences in information processing/perception, cognitive factors (e.g., rigidity), less goal-directed behavior and more disorganized emotion in ASD). Conclusions Although assignment of concomitant psychiatric diagnoses is warranted in some cases, poor ER may be inherent in ASD and may provide a more parsimonious conceptualization for the many associated socio-emotional and behavioral problems in this population. Further study of ER in youth with ASD may identify meaningful subgroups of patients and lead to more effective individualized treatments. PMID:23800481

The knowledge, perceptions and practice of pharmacovigilance amongst community pharmacists in Lagos state, south west Nigeria.

PubMed

Oreagba, I A; Ogunleye, O J; Olayemi, S O

2011-01-01

Community Pharmacists both have an important responsibility in monitoring the ongoing safety of medicines and are widely accessible to do it. This study aims to investigate the knowledge, perceptions and practice of Pharmacovigilance amongst community pharmacists in Lagos State, South West Nigeria A cross-sectional observational survey was used in this study. A multistage random sampling technique was employed in the selection of 420 community pharmacies in Lagos. About 55% of respondents have ever heard of the word 'Pharmacovigilance' out of which less than half (representing only 18% of all respondents) could define the term 'Pharmacovigilance'. Forty percent of the respondents stated that patients reported ADRs to them at least once a month, and 20% reported to the relevant authorities. However only 3% of respondents actually reported an ADR to the National Pharmacovigilance Centre. The most important reason for poor reporting was lack of knowledge about how to report ADRs (44.6%).Meanwhile, 90% of respondents believed that the role of the pharmacists in ADR reporting was important. Most community pharmacists were willing to practice pharmacovigilance if they were trained. Community pharmacists in Lagos had poor knowledge about pharmacovigilance. Reporting rate was also poor. There is an urgent need for educational programs to train pharmacists about pharmacovigilance and ADR reporting. Copyright © 2010 John Wiley & Sons, Ltd.

Modeling the geographic distribution of Bacillus anthracis, the causative agent of anthrax disease, for the contiguous United States using predictive ecological [corrected] niche modeling.

PubMed

Blackburn, Jason K; McNyset, Kristina M; Curtis, Andrew; Hugh-Jones, Martin E

2007-12-01

The ecology and distribution of Bacillus anthracis is poorly understood despite continued anthrax outbreaks in wildlife and livestock throughout the United States. Little work is available to define the potential environments that may lead to prolonged spore survival and subsequent outbreaks. This study used the genetic algorithm for rule-set prediction modeling system to model the ecological niche for B. anthracis in the contiguous United States using wildlife and livestock outbreaks and several environmental variables. The modeled niche is defined by a narrow range of normalized difference vegetation index, precipitation, and elevation, with the geographic distribution heavily concentrated in a narrow corridor from southwest Texas northward into the Dakotas and Minnesota. Because disease control programs rely on vaccination and carcass disposal, and vaccination in wildlife remains untenable, understanding the distribution of B. anthracis plays an important role in efforts to prevent/eradicate the disease. Likewise, these results potentially aid in differentiating endemic/natural outbreaks from industrial-contamination related outbreaks or bioterrorist attacks.

The magnitude and origin of groundwater discharge to eastern U.S. and Gulf of Mexico coastal waters

USGS Publications Warehouse

Befus, Kevin; Kroeger, Kevin D.; Smith, Christopher G.; Swarzenski, Peter W.

2017-01-01

Fresh groundwater discharge to coastal environments contributes to the physical and chemical conditions of coastal waters, but the role of coastal groundwater at regional to continental scales remains poorly defined due to diverse hydrologic conditions and the difficulty of tracking coastal groundwater flow paths through heterogeneous subsurface materials. We use three-dimensional groundwater flow models for the first time to calculate the magnitude and source areas of groundwater discharge from unconfined aquifers to coastal waterbodies along the entire eastern U.S. We find that 27.1 km3/yr (22.8–30.5 km3/yr) of groundwater directly enters eastern U.S. and Gulf of Mexico coastal waters. The contributing recharge areas comprised ~175,000 km2 of U.S. land area, extending several kilometers inland. This result provides new information on the land area that can supply natural and anthropogenic constituents to coastal waters via groundwater discharge, thereby defining the subterranean domain potentially affecting coastal chemical budgets and ecosystem processes.

Expression of receptor-type protein tyrosine phosphatase in developing and adult renal vasculature

PubMed Central

Takahashi, Keiko; Kim, Rachel; Lauhan, Colette; Park, Yuna; Nguyen, Nghiep G.; Vestweber, Dietmar; Dominguez, Melissa G.; Valenzuela, David M.; Murphy, Andrew J.; Yancopoulos, George D.; Gale, Nicholas W.; Takahashi, Takamune

2017-01-01

Renal vascular development is a coordinated process that requires ordered endothelial cell proliferation, migration, intercellular adhesion, and morphogenesis. In recent decades, studies have defined the pivotal role of endothelial receptor tyrosine kinases (RPTKs) in the development and maintenance of renal vasculature. However, the expression and the role of receptor tyrosine phosphatases (RPTPs) in renal endothelium are poorly understood, though coupled and counterbalancing roles of RPTKs and RPTPs are well defined in other systems. In this study, we evaluated the promoter activity and immunolocalization of two endothelial RPTPs, VE-PTP and PTPμ, in developing and adult renal vasculature using the heterozygous LacZ knock-in mice and specific antibodies. In adult kidneys, both VE-PTP and PTPμ were expressed in the endothelium of arterial, glomerular, and medullary vessels, while their expression was highly limited in peritubular capillaries and venous endothelium. VE-PTP and PTPμ promoter activity was also observed in medullary tubular segments in adult kidneys. In embryonic (E12.5, E13.5, E15.5, E17.5) and postnatal (P0, P3, P7) kidneys, these RPTPs were expressed in ingrowing renal arteries, developing glomerular microvasculature (as early as the S-shaped stage), and medullary vessels. Their expression became more evident as the vasculatures matured. Peritubular capillary expression of VE-PTP was also noted in embryonic and postnatal kidneys. Compared to VE-PTP, PTPμ immunoreactivity was relatively limited in embryonic and neonatal renal vasculature and evident immunoreactivity was observed from the P3 stage. These findings indicate 1) VE-PTP and PTPμ are expressed in endothelium of arterial, glomerular, and medullary renal vasculature, 2) their expression increases as renal vascular development proceeds, suggesting that these RPTPs play a role in maturation and maintenance of these vasculatures, and 3) peritubular capillary VE-PTP expression is down-regulated in adult kidneys, suggesting a role of VE-PTP in the development of peritubular capillaries. PMID:28542220

Medicaid eligibility policy in the 1980s: medical utilitarianism and the "deserving" poor.

PubMed

Tanenbaum, S J

1995-01-01

Between 1981 and the early 1990s, the Medicaid program grew substantially, in part because, for the first time in the program's history, eligibility for medical assistance was severed from eligibility for income-maintenance payments. Program participation had always been reserved for the "deserving poor," and these were originally defined as persons excluded from market relationships through no fault of their own. The Medicaid expansion of the 1980s, however, created a new constituency of poor, and not-so-poor, persons whose actual or predictable medical problems promised a calculable return on program funds.

How to Classify and Measure Ecosystem Services to Connect to Human Well Being -- Is there an Answer?

EPA Science Inventory

Abstract 2.0: Ecosystem services remain poorly defined despite an extensive and growing literature. While approaches are many and varied, none appear to adequately define a systematic, complete, and non-duplicative solution to the crucial problem of connecting ecosystems to hum...

Netrin-1 guides inflammatory cell migration to control mucosal immune responses during intestinal inflammation

PubMed Central

Aherne, Carol M.; Collins, Colm B.; Eltzschig, Holger K.

2013-01-01

The intestinal epithelium is a dynamic barrier playing an active role in intestinal homeostasis and inflammation. Intestinal barrier function is dysregulated during inflammatory bowel disease (IBD), with epithelial cells playing a significant part in generating an inflammatory milieu through the release of signals that attract leukocytes to the intestinal lamina propria. However, it is increasingly appreciated that the intestinal epithelium mediates a counterbalancing response to drive resolution. Drawing analogies with neuronal development, where the balance of chemoattractive and chemorepellent signals is key to directed neuronal movement it has been postulated that such secreted cues play a role in leukocyte migration. Netrin-1 is one of the best-described neuronal guidance molecules, which has been shown to play a significant role in directed migration of leukocytes. Prior to our study the potential role of netrin-1 in IBD was poorly characterized. We defined netrin-1 as an intestinal epithelial-derived protein capable of limiting neutrophil recruitment to attenuate acute colitis. Our study highlights that the intestinal epithelium releases factors during acute inflammation that are responsible for fine-tuning the immune response. Exploration of these epithelial-mediated protective mechanisms will shed light on the complexity of the intestinal epithelial barrier in health and disease. PMID:24665394

A rho-binding protein kinase C-like activity is required for the function of protein kinase N in Drosophila development.

PubMed

Betson, Martha; Settleman, Jeffrey

2007-08-01

The Rho GTPases interact with multiple downstream effectors to exert their biological functions, which include important roles in tissue morphogenesis during the development of multicellular organisms. Among the Rho effectors are the protein kinase N (PKN) proteins, which are protein kinase C (PKC)-like kinases that bind activated Rho GTPases. The PKN proteins are well conserved evolutionarily, but their biological role in any organism is poorly understood. We previously determined that the single Drosophila ortholog of mammalian PKN proteins, Pkn, is a Rho/Rac-binding kinase essential for Drosophila development. By performing "rescue" studies with various Pkn mutant constructs, we have defined the domains of Pkn required for its role during Drosophila development. These studies suggested that Rho, but not Rac binding is important for Pkn function in development. In addition, we determined that the kinase domain of PKC53E, a PKC family kinase, can functionally substitute for the kinase domain of Pkn during development, thereby exemplifying the evolutionary strategy of "combining" functional domains to produce proteins with distinct biological activities. Interestingly, we also identified a requirement for Pkn in wing morphogenesis, thereby revealing the first postembryonic function for Pkn.

New insights into epididymal biology and function.

PubMed

Cornwall, Gail A

2009-01-01

The epididymis performs an important role in the maturation of spermatozoa including their acquisition of progressive motility and fertilizing ability. However, the molecular mechanisms that govern these maturational events are still poorly defined. This review focuses on recent progress in our understanding of epididymal function including its development, role of the luminal microenvironment in sperm maturation, regulation and novel mechanisms the epididymis utilizes to carry out some of its functions. A systematic search of Pubmed was carried out using the search term 'epididymis'. Articles that were published in the English language until the end of August 2008 and that focused on the specific topics described above were included. Additional papers cited in the primary reference were also included. While the majority of these findings were the result of studies in animal models, recent studies in the human epididymis are also presented including gene profiling studies to examine regionalized expression in normal epididymides as well as in those from vasectomized patients. Significant progress has been made in our understanding of epididymal function providing new insights that ultimately could improve human health. The data also indicate that the human epididymis plays an important role in sperm maturation but has unique properties compared with animal models.

SIRT1 Deficiency in Microglia Contributes to Cognitive Decline in Aging and Neurodegeneration via Epigenetic Regulation of IL-1β

PubMed Central

Cho, Seo-Hyun; Chen, Jason A.; Sayed, Faten; Ward, Michael E.; Gao, Fuying; Nguyen, Thi A.; Krabbe, Grietje; Sohn, Peter Dongmin; Lo, Iris; Minami, Sakura; Devidze, Nino; Zhou, Yungui; Coppola, Giovanni

2015-01-01

Aging is the predominant risk factor for neurodegenerative diseases. One key phenotype as the brain ages is an aberrant innate immune response characterized by proinflammation. However, the molecular mechanisms underlying aging-associated proinflammation are poorly defined. Whether chronic inflammation plays a causal role in cognitive decline in aging and neurodegeneration has not been established. Here we report a mechanistic link between chronic inflammation and aging microglia and a causal role of aging microglia in neurodegenerative cognitive deficits. We showed that SIRT1 is reduced with the aging of microglia and that microglial SIRT1 deficiency has a causative role in aging- or tau-mediated memory deficits via IL-1β upregulation in mice. Interestingly, the selective activation of IL-1β transcription by SIRT1 deficiency is likely mediated through hypomethylating the specific CpG sites on IL-1β proximal promoter. In humans, hypomethylation of IL-1β is strongly associated with chronological age and with elevated IL-1β transcription. Our findings reveal a novel epigenetic mechanism in aging microglia that contributes to cognitive deficits in aging and neurodegenerative diseases. PMID:25589773

[Rethinking the place of primary healthcare in France--role of general practice].

PubMed

Gay, B

2013-06-01

Primary healthcare is poorly structured in France while it is well defined at the international level: it is the point of first medical contact of the population with the healthcare system. General practice is the clinical specialty oriented to primary healthcare. Data in the scientific literature highlight the need of refocusing the health system on primary care known to improve both morbi-mortality and care efficiency. In France, health authorities acknowledge general practitioners as playing a key role in the health care system: its time to move from intention to action. Structural changes are needed to achieve this reinforcement of primary healthcare: to re-orientate medical studies towards primary care; to develop research in primary care; to promote cooperation between care providers; to ease the daily workload of practitioners; to diversify methods of payment; to propose a guide for patient's use of primary care. The transformation of the healthcare system in France requires a real strategy of primary healthcare implementation. Regardless of financial constraints, it is possible to redistribute the resources towards ambulatory care. Strengthening the role of general practice and favoring its societal recognition will be the major stages of this change. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

Probabilities of good, marginal, and poor flying conditions for space shuttle ferry flights

NASA Technical Reports Server (NTRS)

Whiting, D. M.; Guttman, N. B.

1977-01-01

Empirical probabilities are provided for good, marginal, and poor flying weather for ferrying the Space Shuttle Orbiter from Edwards AFB, California, to Kennedy Space Center, Florida, and from Edwards AFB to Marshall Space Flight Center, Alabama. Results are given by month for each overall route plus segments of each route. The criteria for defining a day as good, marginal, or poor and the method of computing the relative frequencies and conditional probabilities for monthly reference periods are described.

More than science: family learning in a Mexican science museum

NASA Astrophysics Data System (ADS)

Briseño-Garzón, Adriana

2013-06-01

Latin American audiences living in their countries of origin are poorly understood as museum learners due to the scarcity of research in this field. Through a case study approach, I investigate and report on the ways of learning of 20 Mexican family groups. In particular, I examine the influence of the Mexican sociocultural context on the participant family members' learning outcomes from a Mexican science museum. Conducted in Universum Museo de las Ciencias, a science museum located in Mexico City, this research study is based on the premise that understanding the role of the sociocultural elements of learning is essential to understanding the nature of learning in museums. The cognitive and social outcomes of the participants are discussed in the light of the sociocultural elements that define Mexicans as museum learners.

Fine needle aspiration cytology of hepatic metastasis from a meningeal hemangiopericytoma. A case report.

PubMed

Ghaffar, Hasan; Parwani, Anil; Rosenthal, Dorothy L

2003-01-01

Hemangiopericytomas (HPCs) are rare spindle cell tumors, constituting 2.5% of soft tissue neoplasms. Few reports have addressed the fine needle aspiration (FNA) cytology of HPC. We describe the FNA biopsy (FNAB) findings in a 44-year-old patient with a previously resected meningeal hemangiopericytoma. The patient underwent ultrasound-guided FNAB of a 16.0-cm, radiographically heterogeneous density in the liver. The FNA smear showed crowded, ovoid to spindle-shaped cells with poorly defined, scant cytoplasm. The neoplastic cells were positive for CD34 and negative for CD31, factor VIII, glial fibrillary acid protein and cytokeratin AE1/AE3, supporting a diagnosis of HPC and compatible with metastasis from the patient's cerebral tumor. This case documents the role of FNA cytology in confirming HPC.

Smoking and diabetes. Epigenetics involvement in osseointegration.

PubMed

Razzouk, Sleiman; Sarkis, Rami

2013-03-01

Bone quality is a poorly defined parameter for successful implant placement, which largely depends upon many environmental and genetic factors unique to every individual. Smoking and diabetes are among the environmental factors that most impact osseointegration. However, there is an inter-individual variability of bone response in smokers and diabetic patients. Recent data on gene-environment interactions highlight the major role of epigenetic changes to induce a specific phenotype. Histone acetylation and DNA methylation are the main events that occur and modulate the gene expression. In this paper, we emphasize the impact of epigenetics on diabetes and smoking and describe their significance in bone healing. Also, we underscore the importance of adopting a new approach in clinical management for implant placement by customizing the treatment according to the patient's specific characteristics.

Obesity: “Priming” the Lung for Injury

PubMed Central

Konter, Jason; Baez, Elizabeth; Summer, Ross S

2012-01-01

Acute lung injury (ALI) is a severe inflammatory condition that develops in response to local and systemic lung challenges. To date, specific risk factors for development of ALI remain poorly defined. Recent epidemiological studies have reported obesity as an important predisposing factor in the development of this condition. Although the pathogenic mechanisms linking obesity and ALI have not been well-elucidated, emerging scientific evidence has described factors secreted by adipose tissue that have important biological activities in lung and has suggested that altered secretion of these factors during obesity contributes to increased ALI susceptibility. The objective of this manuscript is to highlight recent clinical evidence supporting the association between obesity and ALI and to discuss the posited role for adipose tissue-derived factors in the pathogenesis of this condition. PMID:22449512

Impact of mTOR-I on fertility and pregnancy: state of the art and review of the literature.

PubMed

Framarino-dei-Malatesta, Marialuisa; Derme, Martina; Manzia, Tommaso M; Iaria, Giuseppe; De Luca, Linda; Fazzolari, Laura; Napoli, Angela; Berloco, Pasquale; Patel, Timil; Orlando, Giuseppe; Tisone, Giuseppe

2013-08-01

Successful transplantation should lead to improvements in sexual function and sex hormone disturbances in both men and women, but immunosuppressive drugs may interfere with hormone metabolism. In this regard, several studies have showed a potential negative effect of mTOR inhibitors (mTORi) on male gonadal function, while their role in the female patients is not well documented in the literature. Successful pregnancy is possible after solid organ transplantation. The fetal effects of mTORi are still poorly defined but they seem not to represent an absolute contraindication for pregnancy. The aim of our study would be to review the impact of mTORi on fertility and pregnancy in order to have a clearer picture about their possible use after organ transplantation.

Listeria membrane protrusion collapse: Requirement of Cyclophilin A for Listeria cell-to-cell spreading.

PubMed

Dhanda, Aaron S; Lulic, Katarina T; Vogl, A Wayne; Mc Gee, Margaret M; Chiu, Robert H; Guttman, Julian A

2018-05-04

Listeria generate actin-rich tubular protrusions at the plasma membrane that propel the bacteria into neighbouring cells. The precise molecular mechanisms governing the formation of these protrusions remain poorly defined. Here we demonstrate that the PPIase Cyclophilin A (CypA) is hijacked by Listeria at membrane protrusions used for cell-to-cell spreading. CypA localizes within the F-actin of these structures and is crucial for their proper formation, as in cells depleted of CypA, these extended actin-rich structures are mis-shaped and collapsed due to changes within the F-actin network. The lack of structural integrity within the Listeria membrane protrusions hampers the microbes from spreading from CypA null cells. Our results demonstrate a crucial role for CypA during Listeria infections.

Health of the Disadvantaged. Chart Book-II.

ERIC Educational Resources Information Center

Health Resources Administration (DHHS/PHS), Hyattsville, MD.

The tables and charts in this book act as resources for information on the health status of racial and ethnic minorities and the poor. The four minority groups referred to are blacks, Hispanic Americans, Native Americans, and Asian Americans. The poor are defined as those whose income falls below the poverty line specified by the Census Bureau.…

CERT Resiliency Engineering Framework

DTIC Science & Technology

2007-03-01

Heightened threat level and increasing uncertainty Shorter-lived skills 5 Operational risk management problems Poor planning and execution No asset...increasingly effective & efficient Today’s operational environment No operational boundaries Pervasive & rapidly changing technology Dynamic & expanding risks ...management function Seen as a technical function or responsibility Searching for magic bullet: CobiT , ITIL, ISO17799, NFP1600 Poorly defined and measured

Promoting Upward Mobility for the Working Poor.

ERIC Educational Resources Information Center

Rupured, Michael

2000-01-01

The working poor are typically defined by researchers as individuals who work at least part of the year and earn less than a given percentage of the federal poverty level. This definition tends to understate the problem. In 1997, 15.8 million employed parents had incomes below 200 percent of the federal poverty level. The federal Earned Income Tax…

Blood urea nitrogen to serum creatinine ratio is an accurate predictor of outcome in diarrhea-associated hemolytic uremic syndrome, a preliminary study.

PubMed

Keenswijk, Werner; Vanmassenhove, Jill; Raes, Ann; Dhont, Evelyn; Vande Walle, Johan

2017-03-01

Diarrhea-associated hemolytic uremic syndrome (D+HUS) is a common thrombotic microangiopathy during childhood and early identification of parameters predicting poor outcome could enable timely intervention. This study aims to establish the accuracy of BUN-to-serum creatinine ratio at admission, in addition to other parameters in predicting the clinical course and outcome. Records were searched for children between 1 January 2008 and 1 January 2015 admitted with D+HUS. A complicated course was defined as developing one or more of the following: neurological dysfunction, pancreatitis, cardiac or pulmonary involvement, hemodynamic instability, and hematologic complications while poor outcome was defined by death or development of chronic kidney disease. Thirty-four children were included from which 11 with a complicated disease course/poor outcome. Risk of a complicated course/poor outcome was strongly associated with oliguria (p = 0.000006) and hypertension (p = 0.00003) at presentation. In addition, higher serum creatinine (p = 0.000006) and sLDH (p = 0.02) with lower BUN-to-serum creatinine ratio (p = 0.000007) were significantly associated with development of complications. A BUN-to-sCreatinine ratio ≤40 at admission was a sensitive and highly specific predictor of a complicated disease course/poor outcome. A BUN-to-serum Creatinine ratio can accurately identify children with D+HUS at risk for a complicated course and poor outcome. What is Known: • Oliguria is a predictor of poor long-term outcome in D+HUS What is New: • BUN-to-serum Creatinine ratio at admission is an entirely novel and accurate predictor of poor outcome and complicated clinical outcome in D+HUS • Early detection of the high risk group in D+HUS enabling early treatment and adequate monitoring.

A coupled hydrological-hydraulic flood inundation model calibrated using post-event measurements and integrated uncertainty analysis in a poorly gauged Mediterranean basin

NASA Astrophysics Data System (ADS)

Hdeib, Rouya; Abdallah, Chadi; Moussa, Roger; Colin, Francois

2017-04-01

Developing flood inundation maps of defined exceedance probabilities is required to provide information on the flood hazard and the associated risk. A methodology has been developed to model flood inundation in poorly gauged basins, where reliable information on the hydrological characteristics of floods are uncertain and partially captured by the traditional rain-gauge networks. Flood inundation is performed through coupling a hydrological rainfall-runoff (RR) model (HEC-HMS) with a hydraulic model (HEC-RAS). The RR model is calibrated against the January 2013 flood event in the Awali River basin, Lebanon (300 km2), whose flood peak discharge was estimated by post-event measurements. The resulting flows of the RR model are defined as boundary conditions of the hydraulic model, which is run to generate the corresponding water surface profiles and calibrated against 20 post-event surveyed cross sections after the January-2013 flood event. An uncertainty analysis is performed to assess the results of the models. Consequently, the coupled flood inundation model is simulated with design storms and flood inundation maps are generated of defined exceedance probabilities. The peak discharges estimated by the simulated RR model were in close agreement with the results from different empirical and statistical methods. This methodology can be extended to other poorly gauged basins facing common stage-gauge failure or characterized by floods with a stage exceeding the gauge measurement level, or higher than that defined by the rating curve.

A review on quality of life and depression in obsessive-compulsive disorder.

PubMed

Moritz, Steffen

2008-09-01

Quality of life (QoL) is increasingly recognized as a pivotal outcome parameter in research on obsessive-compulsive disorder (OCD). While the concept remains somewhat ill-defined, there is now little dispute that the patients' personal goals deserve foremost consideration during the course of treatment as the primary aim of treatment should be relief from individual despair, which is related but by no means synonymous to symptom reduction. Studies using generic (ie, illness-unspecific) instruments have confirmed poor QoL in OCD patients across a wide range of domains, especially with respect to social, work role functioning, and mental health aspects. Scores are sometimes as low as those obtained by patients with schizophrenia. Depression and obsessions are the symptom clusters that most strongly contribute to low QoL. Findings from a novel survey of 105 OCD participants point to multiple daily life problems, poor work status, and tense social networks in these patients. In order to achieve therapeutic success and improve QoL, functional problems at work and comorbid disorders such as secondary depression and physical impairments should be targeted. While successful treatment sometimes positively impacts well-being, in some studies symptom decline did not translate into improved QoL.

Individual Differences in Anatomy Predict Reading and Oral Language Impairments in Children

ERIC Educational Resources Information Center

Leonard, Christiana; Eckert, Mark; Given, Barbara; Virginia, Berninger; Eden, Guinevere

2006-01-01

Developmental dyslexia (DD) and specific language impairment (SLI) are disorders of language that differ in diagnostic criteria and outcome. DD is defined by isolated reading deficits. SLI is defined by poor receptive and expressive oral language skills. Reading deficits, although prevalent, are not necessary for the diagnosis of SLI. An enduring…

Sampling Methods and the Accredited Population in Athletic Training Education Research

ERIC Educational Resources Information Center

Carr, W. David; Volberding, Jennifer

2009-01-01

Context: We describe methods of sampling the widely-studied, yet poorly defined, population of accredited athletic training education programs (ATEPs). Objective: There are two purposes to this study; first to describe the incidence and types of sampling methods used in athletic training education research, and second to clearly define the…

Prediction and Stability of Reading Problems in Middle Childhood

ERIC Educational Resources Information Center

Ritchey, Kristen D.; Silverman, Rebecca D.; Schatschneider, Christopher; Speece, Deborah L.

2015-01-01

The longitudinal prediction of reading problems from fourth grade to sixth grade was investigated with a sample of 173 students. Reading problems at the end of sixth grade were defined by significantly below average performance (= 15th percentile) on reading factors defining word reading, fluency, and reading comprehension. Sixth grade poor reader…

Wounding induces changes in cytokinin and auxin content in potato tuber, but does not induce formation of gibberellins

USDA-ARS?s Scientific Manuscript database

Cytokinin, auxin and gibberellin content in resting and wound-responding potato tuber are not clearly defined. Consequently, the coordination and possible networking of these classical hormones in the regulation of wound-healing processes are poorly understood. Using a well-defined tuber wound-hea...

Discordance between Psychometric Testing and Questionnaire-Based Definitions of Executive Function Deficits in Individuals with ADHD

ERIC Educational Resources Information Center

Biederman, Joseph; Petty, Carter R.; Fried, Ronna; Black, Sarah; Faneuil, Alicia; Doyle, Alysa E.; Seidman, Larry J.; Faraone, Stephen V.

2008-01-01

Objective: One suspected source of negative outcomes associated with ADHD has been deficits in executive functions. Although both psychometrically defined and self-reported executive function deficits (EFDs) have been shown to be associated with poor academic and occupational outcomes, whether these two approaches define the same individuals…

Defining the Role of Free Flaps in Partial Breast Reconstruction.

PubMed

Smith, Mark L; Molina, Bianca J; Dayan, Erez; Jablonka, Eric M; Okwali, Michelle; Kim, Julie N; Dayan, Joseph H

2018-03-01

 Free flaps have a well-established role in breast reconstruction after mastectomy; however, their role in partial breast reconstruction remains poorly defined. We reviewed our experience with partial breast reconstruction to better understand indications for free tissue transfer.  A retrospective review was performed of all patients undergoing partial breast reconstruction at our center between February 2009 and October 2015. We evaluated the characteristics of patients who underwent volume displacement procedures versus volume replacement procedures and free versus pedicled flap reconstruction.  There were 78 partial breast reconstructions, with 52 reductions/tissue rearrangements (displacement group) and 26 flaps (replacement group). Bra cup size and body mass index (BMI) were significantly smaller in the replacement group. Fifteen pedicled and 11 free flaps were performed. Most pedicled flaps (80.0%) were used for lateral or upper pole defects. Most free flaps (72.7%) were used for medial and inferior defects or when there was inadequate donor tissue for a pedicled flap. Complications included hematoma, cellulitis, and one aborted pedicled flap.  Free and pedicled flaps are useful for partial breast reconstruction, particularly in breast cancer patients with small breasts undergoing breast-conserving treatment (BCT). Flap selection depends on defect size, location, and donor tissue availability. Medial defects are difficult to reconstruct using pedicled flaps due to arc of rotation and intervening breast tissue. Free tissue transfer can overcome these obstacles. Confirming negative margins before flap reconstruction ensures harvest of adequate volume and avoids later re-operation. Judicious use of free flaps for oncoplastic reconstruction expands the possibility for breast conservation. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Sleep-Wake Disturbances in Sedentary Community-Dwelling Elders With Functional Limitations

PubMed Central

Vaz Fragoso, Carlos A.; Miller, Michael E.; Fielding, Roger A.; King, Abby C.; Kritchevsky, Stephen B.; McDermott, Mary M.; Myers, Valerie; Newman, Anne B.; Pahor, Marco; Gill, Thomas M.

2014-01-01

OBJECTIVES To evaluate sleep-wake disturbances in sedentary community-dwelling elders with functional limitations. DESIGN Cross-sectional. SETTING Lifestyle Interventions and Independence in Elder (LIFE) Study. PARTICIPANTS 1635 community-dwelling persons, mean age 78.9, who spent <20 minutes/week in the past month of regular physical activity and <125 minutes/week of moderate physical activity, and had a Short Physical Performance Battery (SPPB) score <10. MEASUREMENTS Mobility was evaluated by the 400-meter walk time (slow gait speed defined as <0.8 m/s) and SPPB score (≤7 defined moderate-to-severe mobility impairment). Physical inactivity was defined by sedentary time, as percent of accelerometry wear time with activity <100 counts/min); top quartile established high sedentary time. Sleep-wake disturbances were evaluated by the Insomnia Severity Index (ISI) (range 0–28; ≥8 defined insomnia), Epworth Sleepiness Scale (ESS) (range 0–24; ≥10 defined daytime drowsiness), Pittsburgh Sleep Quality Index (PSQI) (range 0–21; >5 defined poor sleep quality), and Berlin Questionnaire (high risk of sleep apnea). RESULTS Prevalence rates were 43.5% for slow gait speed and 44.7% for moderate-to-severe mobility impairment, with 77.0% of accelerometry wear time spent as sedentary time. Prevalence rates were 33.0% for insomnia, 18.1% for daytime drowsiness, 47.8% for poor sleep quality, and 32.9% for high risk of sleep apnea. Participants with insomnia, daytime drowsiness, and poor sleep quality had mean values of 12.1 for ISI, 12.5 for ESS, and 9.2 for PSQI, respectively. In adjusted models, measures of mobility and physical inactivity were generally not associated with sleep-wake disturbances, using continuous or categorical variables. CONCLUSION In a large sample of sedentary community-dwelling elders with functional limitations, sleep-wake disturbances were prevalent but only mildly severe, and were generally not associated with mobility impairment or physical inactivity. PMID:24889836

Does social capital protect mental health among migrants in Sweden?

PubMed

Lecerof, Susanne Sundell; Stafström, Martin; Westerling, Ragnar; Östergren, Per-Olof

2016-09-01

Poor mental health is common among migrants. This has been explained by migration-related and socio-economic factors. Weak social capital has also been related to poor mental health. Few studies have explored factors that protect mental health of migrants in the post-migration phase. Such knowledge could be useful for health promotion purposes. Therefore, this study aimed to analyse associations between financial difficulties, housing problems and experience of discrimination and poor mental health; and to detect possible effect modification by social capital, among recently settled Iraqi migrants in Sweden. A postal questionnaire in Arabic was sent to recently settled Iraqi citizens. The response rate was 51% (n = 617). Mental health was measured by the GHQ-12 instrument and social capital was defined as social participation and trust in others. Data were analysed by means of logistic regression. Poor mental health was associated with experience of discrimination (OR 2.88, 95% CI 1.73-4.79), housing problems (OR 2.79, 95% CI 1.84-4.22), and financial difficulties (OR 2.14, 95% CI 1.44-3.19), after adjustments. Trust in others seemed to have a protective effect for mental health when exposed to these factors. Social participation had a protective effect when exposed to experience of discrimination. Social determinants and social capital in the host country play important roles in the mental health of migrants. Social capital modifies the effect of risk factors and might be a fruitful way to promote resilience to factors harmful to mental health among migrants, but must be combined with policy efforts to reduce social inequities. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Variations in Oncologist Recommendations for Chemotherapy for Stage IV Lung Cancer: What Is the Role of Performance Status?

PubMed

Tisnado, Diana; Malin, Jennifer; Kahn, Katherine; Landrum, Mary Beth; Fletcher, Robert; Klabunde, Carrie; Clauser, Steven; Rogers, Selwyn O; Keating, Nancy L

2016-07-01

Chemotherapy prolongs survival in patients with advanced non-small-cell lung cancer. However, few studies have included patients with poor performance status. This study examined rates of oncologists' recommendations for chemotherapy by patient performance status and symptoms and how physician characteristics influence chemotherapy recommendations. We surveyed medical oncologists involved in the care of a population-based cohort of patients with lung cancer from the CanCORS (Cancer Care Outcomes Research and Surveillance) study. Physicians were queried about their likelihood to recommend chemotherapy to patients with stage IV lung cancer with varying performance status (Eastern Cooperative Oncology Group performance status 0 [good] v 3 [poor]) and presence or absence of tumor-related pain. Repeated measures logistic regression was used to estimate the independent associations of patients' performance status and symptoms and physicians' demographic and practice characteristics with chemotherapy recommendations. Nearly all physicians (adjusted rate, 97% to 99%) recommended chemotherapy for patients with good performance status, and approximately half (adjusted rate, 38% to 53%) recommended chemotherapy for patients with poor performance status (P < .001). Compared with patient factors, physician and practice characteristics were less strongly associated with chemotherapy recommendations in adjusted analyses. Strong consensus among oncologists exists for chemotherapy in patients with advanced non-small-cell lung cancer and good performance status. However, the relatively high rate of chemotherapy recommendations for patients with poor performance status despite the unfavorable risk-benefit profile highlights the need for ongoing work to define high-value care in oncology and to implement and evaluate strategies to align incentives for such care. Copyright © 2016 by American Society of Clinical Oncology.

Reaction softening by dissolution–precipitation creep in a retrograde greenschist facies ductile shear zone, New Hampshire, USA

USGS Publications Warehouse

McAleer, Ryan J.; Bish, David L.; Kunk, Michael J.; Sicard, Karri R.; Valley, Peter M.; Walsh, Gregory J.; Wathen, Bryan A.; Wintsch, R.P.

2016-01-01

We describe strain localization by a mixed process of reaction and microstructural softening in a lower greenschist facies ductile fault zone that transposes and replaces middle to upper amphibolite facies fabrics and mineral assemblages in the host schist of the Littleton Formation near Claremont, New Hampshire. Here, Na-poor muscovite and chlorite progressively replace first staurolite, then garnet, and finally biotite porphyroblasts as the core of the fault zone is approached. Across the transect, higher grade fabric-forming Na-rich muscovite is also progressively replaced by fabric-forming Na-poor muscovite. The mineralogy of the new phyllonitic fault-rock produced is dominated by Na-poor muscovite and chlorite together with late albite porphyroblasts. The replacement of the amphibolite facies porphyroblasts by muscovite and chlorite is pseudomorphic in some samples and shows that the chemical metastability of the porphyroblasts is sufficient to drive replacement. In contrast, element mapping shows that fabric-forming Na-rich muscovite is selectively replaced at high-strain microstructural sites, indicating that strain energy played an important role in activating the dissolution of the compositionally metastable muscovite. The replacement of strong, high-grade porphyroblasts by weaker Na-poor muscovite and chlorite constitutes reaction softening. The crystallization of parallel and contiguous mica in the retrograde foliation at the expense of the earlier and locally crenulated Na-rich muscovite-defined foliation destroys not only the metastable high-grade mineralogy, but also its stronger geometry. This process constitutes both reaction and microstructural softening. The deformation mechanism here was thus one of dissolution–precipitation creep, activated at considerably lower stresses than might be predicted in quartzofeldspathic rocks at the same lower greenschist facies conditions.

Clinical markers of vitiligo activity.

PubMed

Benzekri, Laila; Gauthier, Yvon

2017-05-01

Current modalities of understanding disease state (active/stable) are limited when considering treatment of vitiligo. We sought to develop a rapid, accurate, and noninvasive assessment of vitiligo state. In daylight and Wood's light examinations, 2 common clinical types of vitiligo were identified as amelanotic with sharply demarcated borders and hypomelanotic with poorly defined borders. Photographs were taken at the time of examination and a skin biopsy at the edge of a vitiligo lesion was performed. One year after the initial visit, the vitiligo was classified as stable if no new lesions had appeared, and as active if the number, size, or both of existing vitiligo lesions were increased. Skin biopsy specimens from 71 patients were stained and immunostained for melanocytes, CD8 + T lymphocytes, and E-cadherin. The active lesions were associated with hypomelanotic appearance with poorly defined borders (P < .001), and histologically with an infiltration of CD8 + T lymphocytes in the epidermis and dermis (P = .017), with a strong expression of E-cadherin (P = .044). The fact that this was a single-center study and that activity was sometimes site-dependent are limitations. The hypomelanotic with poorly defined borders type could be a good indicator of the actual activity of a vitiligo lesion. Copyright © 2017 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.

Presenting a practical model for governmental political mapping on road traffic injuries in Iran in 2008: a qualitative study.

PubMed

Ainy, E; Soori, Hamid; Mahfozphoor, S; Movahedinejad, Aa

2011-10-01

This study was conducted to assess political mapping in relation to road traffic injuries (RTIs) management and prevention to present a practical model for RTIs. A phenomenological qualitative study was developed to identify stakeholders on RTI in Iran in 2008. The designed questions were discussed by systematic discussion with the relevant specialists. After receiving written consent from the main responsible stakeholders, the questionnaire was filled in by trained experts. Themes were determined and content was analysed in each part. Main responsible stakeholders. By comparing other countries' political mappings which were found in the library and by Internet searching, political mapping of RTI in Iran was suggested. Subjects were 26 experts from governmental and non-governmental organizations. The main proposed leading agencies were traffic police and presidency (13% each). Findings showed that only 31% of our political mapping was formed according to the World Health Organization (WHO). In 94% of cases, the involved organizations had unspecified roles; the reason was poor monitoring for RTI in 39% of organizations. Lack of adequate authority and suitable legislation, appropriate laws and tasks definition were 94% and 18%, respectively. The most essential policy to overcome problems was defined as appropriate legislation (21%), and the most frequent type of support needed was mentioned as adequate budgeting (25%). Traffic police can play the leading agency role by government support, with strong leadership, appropriate legislation, defined tasks and adequate budget.

Factors determining poor prognostic outcomes following diabetic hand infections

PubMed Central

Ince, Bilsev; Dadaci, Mehmet; Arslan, Abdullah; Altuntas, Zeynep; Evrenos, Mustafa Kursat; Fatih Karsli, Mehmet

2015-01-01

Background and Objective: Hand ulcers are seen in a small percentage of patients with diabetes. The predisposing factors of diabetic hand varies between different countries. However, the effects of predisposing factors on prognosis are not clear in diabetic hand infections. In this study, our aim was to determine the effects of predisposing factors on poor prognostic outcomes in patients with diabetes mellitus. Methods: Thirty-four patients with diabetes mellitus who were treated and followed up for a hand infection in between 2008 and 2014 were investigated retrospectively. Patients were evaluated according to predisposing factors defined in the literature that included disease period, age, gender, admission time, presence of neuropathy, smoking habits, HbA1c levels at admission time, peripheral vascular disease, end-stage renal disease (ESRD), and trauma. Death and minor/major amputation cases during treatment were defined as poor prognosis. Results: Patients who had ESRD, peripheral neuropathy, or an HbA1c level greater than 10% had significantly higher amputation rates. Conclusions: Peripheral neuropathy, ESRD, and HbA1c levels greater than 10% at the time of admission were determined as poor prognosis criteria for diabetic hand treatment. PMID:26150838

Effect of regional cerebral oximetry to estimate neurologic prognostic outcomes in patients administered targeted temperature management.

PubMed

Sarıtaş, Aykut; Çinleti, Burcu Acar; Zincircioğlu, Çiler; Uzun, Uğur; Köse, Işıl; Şenoğlu, Nimet

2018-04-09

The aim of our study is to research the role and efficacy of cerebral oximetry in predicting neurologic prognosis when applied during TTM to patients experiencing coma after CA. This study was performed on surviving adult comatose patients after CA treated with TTM. The average scores of rSO 2 was measured at 6h intervals for the first 2days and once a day for the following 3days with a NIRS device during TTM. The CPC scale was used to define the neurologic outcomes of patients. We compared the correlations of rSO 2 values between good (CPC 1-2) and poor (CPC 3-5) neurologic outcomes in CA patients. There was no statistically significant difference identified between the prognosis groups in terms of rSO 2 , CPR durations, hemoglobin values and admission body temperature (p>0.05). When the variation in rSO 2 values over time is investigated, though there was no significant difference between the good and poor prognosis groups, it appeared to fall in the first 6h in both prognosis groups. The median NT-proBNP and lactate values were observed to be higher in the poor prognosis group. There is no significant correlation between rSO 2 values and neurologic outcomes. Multimodal monitoring methods may be useful and further studies with a larger patient population are necessary in this area. Copyright © 2018. Published by Elsevier Inc.

Prevalence of Poor Bone Quality in Women Undergoing Spinal Fusion Using Biomechanical-CT Analysis.

PubMed

Burch, Shane; Feldstein, Michael; Hoffmann, Paul F; Keaveny, Tony M

2016-02-01

Retrospective, cross-sectional analysis of vertebral bone quality in spine-fusion patients at a single medical center. To characterize the prevalence of osteoporosis and fragile bone strength in a spine-fusion population of women with an age range of 50 years to 70 years. Fragile bone strength is defined as the level of vertebral strength below which a patient is at as high a risk of future vertebral fracture as a patient having bone density-defined osteoporosis. Poor bone quality--defined here as the presence of either osteoporosis or fragile bone strength--is a risk factor for spine-fusion patients that often goes undetected but can now be assessed preoperatively by additional postprocessing of computed tomography (CT) scans originally ordered for perioperative clinical assessment. Utilizing such perioperative CT scans for a cohort of 98 women (age range: 51-70 yr) about to undergo spine fusion, we retrospectively used a phantomless calibration technique and biomechanical-CT postprocessing analysis to measure vertebral trabecular bone mineral density (BMD) (in mg/cm³) and by nonlinear finite element analysis, vertebral compressive strength (in Newtons, N) in the L1 or L2 vertebra. Preestablished validated threshold values were used to define the presence of osteoporosis (trabecular BMD of 80 mg/cm³ or lower) and fragile bone strength (vertebral strength of 4500 N or lower). Fourteen percent of the women tested positive for osteoporosis, 27% tested positive for fragile bone strength, and 29% were classified as having poor bone quality (either osteoporosis or fragile bone strength). Over this narrow age range, neither BMD nor vertebral strength were significantly correlated with age, weight, height, or body mass index (P values 0.14-0.97 for BMD; 0.13-0.51 for strength). Poor bone quality appears to be common in women between ages 50 years and 70 years undergoing spinal fusion surgery. 3.

"It's Kind of a Dichotomy": Thoughts Related to Calling and Purpose from Pastors Working and Counseling in Urban Resource-Poor Communities.

PubMed

Payne, Jennifer Shepard

2017-08-01

Pastors serving low-income urban areas are first-responders to emotional issues by default, since fewer mental health resources are available. Thus, it is important to understand how pastors serving urban resource-poor areas reflect on their counseling role. Forty-eight Black, Hispanic, and White pastors with urban congregations in Los Angeles or Chicago reflect on their pastoral calling and its relation to their counseling role. Through phenomenology, the pastors' lived experiences as they counseled in an urban context were explored. Analysis revealed complex feelings about their counseling role in light of their resource-poor environments. Recommendations are provided based on the findings.

Black-white disparity in physical performance among older women with newly diagnosed non-metastatic breast cancer: Exploring the role of inflammation and physical activity.

PubMed

Owusu, Cynthia; Schluchter, Mark; Koroukian, Siran M; Schmitz, Kathryn H; Berger, Nathan A

2018-04-23

To examine racial differences in physical performance among older women with newly diagnosed non-metastatic breast cancer and identify clinical, behavioral and biological factors that might contribute to such disparities. This is a cross-sectional study of women aged ≥65 years with newly diagnosed stage I-III breast cancer recruited from ambulatory oncology clinics at an academic center, between September 2010 and August 2015. Participants completed a Comprehensive Geriatric Assessment and laboratory testing for biomarkers of inflammation [interleukin-6 (IL6)] prior to receiving systemic treatment for cancer. The primary outcome was poor physical performance, defined as scoring ≤7 on the Short Physical Performance Battery, Yes or No. Logistic regression analyses were undertaken. Among 135 women with mean age of 74.8 years (SD = 6.9), 31% were African-American (AA), and 33% had poor physical performance. Controlling for age, education, comorbidities and geriatric syndromes, participants with poor physical performance were more likely to be AA [versus (vs.) Non-Hispanic Whites (NHW)], odds ratio (OR) = 3.10, 95% confidence interval (CI) = 1.18-8.15. Controlling further for physical activity (PA) attenuated the racial disparity in physical performance (OR = 2.50, CI = 0.91-6.84). Lastly, controlling for IL6 further diminished the racial disparity in physical performance (OR = 1.93, CI = 0.67-5.56). In adjusted models, PA and IL6 explained 29% and 38%, respectively, of the racial disparity in poor physical performance. Among older women with newly diagnosed non-metastatic breast cancer, poor physical performance was prevalent and AA were disproportionately affected. Less engagement in physical activity and subclinical inflammation partly contributed to this disparity. Copyright © 2018 Elsevier Inc. All rights reserved.

Diabetes is associated with subclinical functional limitation in nondisabled older individuals: the Health, Aging, and Body Composition study.

PubMed

De Rekeneire, Nathalie; Resnick, Helaine E; Schwartz, Ann V; Shorr, Ronald I; Kuller, Lewis H; Simonsick, Eleanor M; Vellas, Bruno; Harris, Tamara B

2003-12-01

The aim of this study was to examine the role of comorbid conditions and body composition in the association between diabetes and subclinical functional limitation, an indication of early functional decline, in well-functioning older individuals. This was a cross-sectional analysis of 3,075 well-functioning black and white men and women aged 70-79 years, enrolled in the Health, Aging, and Body Composition study. Diabetes was defined by self-report and/or hypoglycemic medication use or fasting glucose >/=126 mg/dl. Subclinical functional limitation was defined using self-report of capacity and objective performance measures. Comorbid conditions were identified by self-reported diagnoses, medication use, and clinical measures. Body composition measures included anthropometry and total fat (dual X-ray absorptiometry). Of 2,926 participants, 1,252 (42.8%) had subclinical functional limitation at baseline. Among 2,370 individuals without diabetes, 40% had subclinical functional limitation, whereas the prevalence was 53% among the 556 diabetic participants with an age/sex/race-adjusted odds ratio (OR) 1.70 (95% CI 1.40-2.06). This association remained significant when adjusted for body composition measures (OR 1.54 [1.26-1.88]), diabetes-related comorbidities, and other potential confounders (OR 1.40 [1.14-1.73]). In the fully adjusted model, consideration of HbA(1c) (< or >/=7%) and diabetes duration showed that poor glycemic control in diabetic individuals explained the association with subclinical functional limitation. In a well-functioning older population, diabetes is associated with early indicators of functional decline, even after accounting for body composition and diabetes-related comorbidities. Poor glycemic control contributes to this relationship. Whether improvement in glycemic control in older people with diabetes would change this association should be tested.

Hyperactivation of HUSH complex function by Charcot-Marie-Tooth disease mutation in MORC2.

PubMed

Tchasovnikarova, Iva A; Timms, Richard T; Douse, Christopher H; Roberts, Rhys C; Dougan, Gordon; Kingston, Robert E; Modis, Yorgo; Lehner, Paul J

2017-07-01

Dominant mutations in the MORC2 gene have recently been shown to cause axonal Charcot-Marie-Tooth (CMT) disease, but the cellular function of MORC2 is poorly understood. Here, through a genome-wide CRISPR-Cas9-mediated forward genetic screen, we identified MORC2 as an essential gene required for epigenetic silencing by the HUSH complex. HUSH recruits MORC2 to target sites in heterochromatin. We exploited a new method, differential viral accessibility (DIVA), to show that loss of MORC2 results in chromatin decompaction at these target loci, which is concomitant with a loss of H3K9me3 deposition and transcriptional derepression. The ATPase activity of MORC2 is critical for HUSH-mediated silencing, and the most common alteration affecting the ATPase domain in CMT patients (p.Arg252Trp) hyperactivates HUSH-mediated repression in neuronal cells. These data define a critical role for MORC2 in epigenetic silencing by the HUSH complex and provide a mechanistic basis underpinning the role of MORC2 mutations in CMT disease.

Hyper-activation of HUSH complex function by Charcot-Marie-Tooth disease mutation in MORC2

PubMed Central

Douse, Christopher H.; Roberts, Rhys C.; Dougan, Gordon; Kingston, Robert E.; Modis, Yorgo; Lehner, Paul J.

2017-01-01

Dominant mutations in the MORC2 gene have recently been shown to cause axonal Charcot-Marie-Tooth (CMT) disease, but the cellular function of MORC2 is poorly understood. Here, through a genome-wide CRISPR/Cas9-mediated forward genetic screen, we identify MORC2 as an essential gene required for epigenetic silencing by the HUSH complex. HUSH recruits MORC2 to target sites in heterochromatin. We exploit a new method – Differential Viral Accessibility (DIVA) – to show that loss of MORC2 results in chromatin decompaction at these target loci, which is concomitant with a loss of H3K9me3 deposition and transcriptional derepression. The ATPase activity of MORC2 is critical for HUSH-mediated silencing, and the most common mutation affecting the ATPase domain found in CMT patients (R252W) hyper-activates HUSH-mediated repression in neuronal cells. These data define a critical role for MORC2 in epigenetic silencing by the HUSH complex and provide a mechanistic basis underpinning the role of MORC2 mutations in CMT disease. PMID:28581500

Receptor-mediated Drp1 oligomerization on endoplasmic reticulum

PubMed Central

Ji, Wei-Ke; Fan, Xintao; Strack, Stefan

2017-01-01

Drp1 is a dynamin guanosine triphosphatase important for mitochondrial and peroxisomal division. Drp1 oligomerization and mitochondrial recruitment are regulated by multiple factors, including interaction with mitochondrial receptors such as Mff, MiD49, MiD51, and Fis. In addition, both endoplasmic reticulum (ER) and actin filaments play positive roles in mitochondrial division, but mechanisms for their roles are poorly defined. Here, we find that a population of Drp1 oligomers is associated with ER in mammalian cells and is distinct from mitochondrial or peroxisomal Drp1 populations. Subpopulations of Mff and Fis1, which are tail-anchored proteins, also localize to ER. Drp1 oligomers assemble on ER, from which they can transfer to mitochondria. Suppression of Mff or inhibition of actin polymerization through the formin INF2 significantly reduces all Drp1 oligomer populations (mitochondrial, peroxisomal, and ER bound) and mitochondrial division, whereas Mff targeting to ER has a stimulatory effect on division. Our results suggest that ER can function as a platform for Drp1 oligomerization, and that ER-associated Drp1 contributes to mitochondrial division. PMID:29158231

Innate NK cells and macrophages recognize and reject allogeneic nonself in vivo via different mechanisms.

PubMed

Liu, Wentao; Xiao, Xiang; Demirci, Gulcin; Madsen, Joren; Li, Xian C

2012-03-15

Both innate and adaptive immune cells are involved in the allograft response. But how the innate immune cells respond to allotransplants remains poorly defined. In the current study, we examined the roles of NK cells and macrophages in recognizing and rejecting allogeneic cells in vivo. We found that in naive mice NK cells are the primary effector cells in the killing of allogeneic cells via "missing self" recognition. However, in alloantigen-presensitized mice, NK cells are dispensable. Instead, macrophages become alloreactive and readily recognize and reject allogeneic nonself. This effect requires help from activated CD4(+) T cells and involves CD40/CD40L engagement, because blocking CD40/CD40L interactions prevents macrophage-mediated rejection of allogeneic cells. Conversely, actively stimulating CD40 triggers macrophage-mediated rejection in the absence of CD4(+) T cells. Importantly, alloantigen-primed and CD4(+) T cell-helped macrophages (licensed macrophages) exhibit potent regulatory function in vivo in an acute graft-versus-host disease model. Together, our data uncover an important role for macrophages in the alloimmune response and may have important clinical implications.

MicroRNA-199 suppresses cell proliferation, migration and invasion by downregulating RGS17 in hepatocellular carcinoma.

PubMed

Zhang, Wei; Qian, Sheng; Yang, Guowei; Zhu, Liang; Zhou, Bo; Wang, Jianhua; Liu, Rong; Yan, Zhiping; Qu, Xudong

2018-06-15

Hepatocellular carcinoma (HCC), the most common primary tumor of the liver, has a poor prognosis and shows rapid progression. MicroRNAs (miRNAs) play important roles in carcinogenesis and tumor progression. Regulators of G-protein signaling (RGS) are critical for defining G-protein-dependent signal fidelity. RGS17 plays an important role in the regulation of cancer cell proliferation, migration and invasion. Here, we showed that miR-199 was downregulated in a hepatocarcinoma cell line. Overexpression of miR-199 significantly suppressed HCC cell proliferation, migration, and invasion in vitro. RGS17 overexpression promoted HCC cell proliferation, migration, and invasion, and reversed the miR-199 mediated inhibition of proliferation, migration, and invasion. Dual-fluorescence reporter experiments confirmed that miR-199 downregulated RGS17 by direct interaction with the 3'-UTR of RGS17 mRNA. In vivo studies showed that miR-199 overexpression significantly inhibited the growth of tumors. Taken together, the results suggested that miR-199 inhibited tumor growth and metastasis by targeting RGS17. Published by Elsevier B.V.

Upregulated miR-29b promotes neuronal cell death by inhibiting Bcl2L2 after ischemic brain injury.

PubMed

Shi, Guodong; Liu, Yang; Liu, Tielong; Yan, Wangjun; Liu, Xiaowei; Wang, Yuan; Shi, Jiangang; Jia, Lianshun

2012-01-01

It is increasingly clear that microRNAs (miRNAs) play an important role in controlling cell survival. However, the functional significance of miRNAs in ischemic brain injury remains poorly understood. In the present study, we assayed the expression levels of miR-29b after ischemic brain injury, and defined the target genes and biological functions of miR-29b. We found that the miR-29b levels were significantly increased in rat brain after transient middle cerebral artery occlusion and neurons after oxygen-glucose deprivation. Moreover, ectopic expression of miR-29b promoted neuronal cell death, whereas its repression decreased cell death. Furthermore, we verified that miR-29b directly targeted and inhibited Bcl2L2 gene expression, and then increased neuronal cell death. Importantly, Bcl2L2 overexpression rescued neuronal cell death induced by miR-29b. These results suggest an important role of miR-29b in regulating neuronal cell death, thus offering a new target for the development of therapeutic agents against ischemic brain injury.

Mammary Tumorigenesis and Metastasis Caused by Overexpression of Insulin Receptor Substrate 1 (IRS-1) or IRS-2▿

PubMed Central

Dearth, Robert K.; Cui, Xiaojiang; Kim, Hyun-Jung; Kuiatse, Isere; Lawrence, Nicole A.; Zhang, Xiaomei; Divisova, Jana; Britton, Ora L.; Mohsin, Syed; Allred, D. Craig; Hadsell, Darryl L.; Lee, Adrian V.

2006-01-01

Insulin receptor substrates (IRSs) are signaling adaptors that play a major role in the metabolic and mitogenic actions of insulin and insulin-like growth factors. Reports have recently noted increased levels, or activity, of IRSs in many human cancers, and some have linked this to poor patient prognosis. We found that overexpressed IRS-1 was constitutively phosphorylated in vitro and in vivo and that transgenic mice overexpressing IRS-1 or IRS-2 in the mammary gland showed progressive mammary hyperplasia, tumorigenesis, and metastasis. Tumors showed extensive squamous differentiation, a phenotype commonly seen with activation of the canonical β-catenin signaling pathway. Consistent with this, IRSs were found to bind β-catenin in vitro and in vivo. IRS-induced tumorigenesis is unique, given that the IRSs are signaling adaptors with no intrinsic kinase activity, and this supports a growing literature indicating a role for IRSs in cancer. This study defines IRSs as oncogene proteins in vivo and provides new models to develop inhibitors against IRSs for anticancer therapy. PMID:17030631

Poor sleep health and its association with mental health, substance use, and condomless anal intercourse among gay, bisexual, and other men who have sex with men

PubMed Central

Duncan, Dustin T.; Goedel, William C.; Mayer, Kenneth H.; Safren, Steven A.; Palamar, Joseph J.; Hagen, Daniel; Jean-Louis, Girardin

2017-01-01

Objectives The purpose of this study was to evaluate the prevalence of poor sleep health (ie, poor sleep quality and short sleep duration) in a sample of men who have sex with men (MSM). In addition, this study examined whether poor sleep health was associated with depressive symptoms, substance use, and sexual risk behaviors in this sample. Design Cross-sectional survey. Participants Broadcast advertisements were placed on a popular smartphone application for MSM in January 2016 to recruit users in the London metropolitan area (n = 202) to complete a Web-based survey, which included validated measures of sleep quality and duration. Measurements Poor sleep quality was defined based on self-report as very or fairly bad. Short sleep duration was defined as less than 7 hours each night. Regression models were used to assess associations between sleep variables and self-reported depressive symptoms, substance use, and sexual risk behaviors. Results About one-third (34.6%) of the respondents reported poor sleep quality and almost half (43.6%) reported sleeping less than 7 hours every night. Several poor sleep health variables were independently associated with depressive symptoms, substance use (eg, use of alcohol or marijuana), and condomless anal intercourse. For example, typical nightly sleep duration of less than 7 hours was associated with condomless receptive anal intercourse with a higher number of sexual partners (incidence rate ratio, 2.65; 95% confidence interval: 1.63–4.30; P < .001). Conclusion Sleep health promotion interventions should be developed for MSM, which may promote positive mental health as well as reduce substance use and sexual risk behaviors in this population. PMID:29073390

Poor sleep health and its association with mental health, substance use, and condomless anal intercourse among gay, bisexual, and other men who have sex with men.

PubMed

Duncan, Dustin T; Goedel, William C; Mayer, Kenneth H; Safren, Steven A; Palamar, Joseph J; Hagen, Daniel; Jean-Louis, Girardin

2016-12-01

The purpose of this study was to evaluate the prevalence of poor sleep health (ie, poor sleep quality and short sleep duration) in a sample of men who have sex with men (MSM). In addition, this study examined whether poor sleep health was associated with depressive symptoms, substance use, and sexual risk behaviors in this sample. Cross-sectional survey. Broadcast advertisements were placed on a popular smartphone application for MSM in January 2016 to recruit users in the London metropolitan area (n=202) to complete a Web-based survey, which included validated measures of sleep quality and duration. Poor sleep quality was defined based on self-report as very or fairly bad. Short sleep duration was defined as less than 7 hours each night. Regression models were used to assess associations between sleep variables and self-reported depressive symptoms, substance use, and sexual risk behaviors. About one-third (34.6%) of the respondents reported poor sleep quality and almost half (43.6%) reported sleeping less than 7 hours every night. Several poor sleep health variables were independently associated with depressive symptoms, substance use (eg, use of alcohol or marijuana), and condomless anal intercourse. For example, typical nightly sleep duration of less than 7 hours was associated with condomless receptive anal intercourse with a higher number of sexual partners (incidence rate ratio, 2.65; 95% confidence interval: 1.63-4.30; P<.001). Sleep health promotion interventions should be developed for MSM, which may promote positive mental health as well as reduce substance use and sexual risk behaviors in this population. Copyright \\© 2016 National Sleep Foundation. Published by Elsevier Inc. All rights reserved.

Genetic Rodent Models of Obesity-Associated Ovarian Dysfunction and Subfertility: Insights into Polycystic Ovary Syndrome

PubMed Central

Huang-Doran, Isabel; Franks, Stephen

2016-01-01

Polycystic ovary syndrome (PCOS) is the most common endocrinopathy affecting women and a leading cause of female infertility worldwide. Defined clinically by the presence of hyperandrogenemia and oligomenorrhoea, PCOS represents a state of hormonal dysregulation, disrupted ovarian follicle dynamics, and subsequent oligo- or anovulation. The syndrome’s prevalence is attributed, at least partly, to a well-established association with obesity and insulin resistance (IR). Indeed, the presence of severe PCOS in human genetic obesity and IR syndromes supports a causal role for IR in the pathogenesis of PCOS. However, the molecular mechanisms underlying this causality, as well as the important role of hyperandrogenemia, remain poorly elucidated. As such, treatment of PCOS is necessarily empirical, focusing on symptom alleviation. The generation of knockout and transgenic rodent models of obesity and IR offers a promising platform in which to address mechanistic questions about reproductive dysfunction in the context of metabolic disease. Similarly, the impact of primary perturbations in rodent gonadotrophin or androgen signaling has been interrogated. However, the insights gained from such models have been limited by the relatively poor fidelity of rodent models to human PCOS. In this mini review, we evaluate the ovarian phenotypes associated with rodent models of obesity and IR, including the extent of endocrine disturbance, ovarian dysmorphology, and subfertility. We compare them to both human PCOS and other animal models of the syndrome (genetic and hormonal), explore reasons for their discordance, and consider the new opportunities that are emerging to better understand and treat this important condition. PMID:27375552

Blood pressure in the initial phase of acute ischaemic stroke: evolution and its role as an independent prognosis factor at discharge and after 3 months of follow-up.

PubMed

Armario, Pedro; Mártin-Baranera, Montserrat; Miguel Ceresuela, Luis; Hernández Del Rey, Raquel; Iribarnegaray, Eduardo; Pintado, Sara; Avila, Asunción; Bello, Juan; Luis Tovar, José; Alvarez-Sabin, José

2008-01-01

A prospective observational study was aimed at assessing the role of blood pressure (BP) during the first 24 h from stroke onset on the outcome of acute ischaemic stroke. Subjects admitted within the first 3 h from stroke onset were included. Stroke severity was evaluated with the Canadian Stroke Scale (CSS). Functional recovery was defined as a modified Rankin Scale score < or =2. One hundred subjects were included. In a logistic regression model, the independent predictors of poor functional recovery at discharge were: age (OR = 1.12; 95% CI 1.04-1.21; p = 0.0033), non-lacunar stroke subtype (OR = 4.31; 95% CI 1.07-17.31; p = 0.0395), diabetes mellitus (OR = 8.38; 95% CI 1.67-41.95; p = 0.0097), a CSS score at admission < or =8 (OR = 28.64; 95% CI 5.59-146.68; p<0.0001), an average systolic BP during the first 6 h > or =180 mmHg (OR = 13.34; 95% CI 1.34-133.10; p = 0.0272) and a lower diastolic BP average from 6 to 24 h (OR for 5 mmHg increase: 0.57; CI 95% 0.36-0.88; p = 0.0115). Similar results were observed after 3 months of follow-up. In ischaemic stroke patients, systolic BP over 180 mmHg in the first 6 h and a decrease of diastolic BP during the 6-24 h from stroke onset were independent predictors of a poor functional recovery.

The Mineralosphere Concept: Mineralogical Control of the Distribution and Function of Mineral-associated Bacterial Communities.

PubMed

Uroz, Stephane; Kelly, Laura Catherine; Turpault, Marie-Pierre; Lepleux, Cendrella; Frey-Klett, Pascale

2015-12-01

Soil is composed of a mosaic of different rocks and minerals, usually considered as an inert substrata for microbial colonization. However, recent findings suggest that minerals, in soils and elsewhere, favour the development of specific microbial communities according to their mineralogy, nutritive content, and weatherability. Based upon recent studies, we highlight how bacterial communities are distributed on the surface of, and in close proximity to, minerals. We also consider the potential role of the mineral-associated bacterial communities in mineral weathering and nutrient cycling in soils, with a specific focus on nutrient-poor and acidic forest ecosystems. We propose to define this microbial habitat as the mineralosphere, where key drivers of the microbial communities are the physicochemical properties of the minerals. Copyright © 2015 Elsevier Ltd. All rights reserved.

Obesity and polycystic ovary syndrome.

PubMed

Naderpoor, N; Shorakae, S; Joham, A; Boyle, J; De Courten, B; Teede, H J

2015-03-01

Obesity is now a major international health concern. It is increasingly common in young women with reproductive, metabolic and psychological health impacts. Reproductive health impacts are often poorly appreciated and include polycystic ovary syndrome (PCOS), infertility and pregnancy complications. PCOS is the most common endocrine condition in women and is underpinned by hormonal disturbances including insulin resistance and hyperandrogenism. Obesity exacerbates hormonal and clinical features of PCOS and women with PCOS appear at higher risk of obesity, with multiple underlying mechanisms linking the conditions. Lifestyle intervention is first line in management of PCOS to both prevent weight gain and induce weight loss; however improved engagement and sustainability remain challenges with the need for more research. Medications like metformin, orlistat, GLP1 agonists and bariatric surgery have been used with the need for large scale randomised clinical trials to define their roles.

Supportive Care: Integration of Patient-Centered Kidney Care to Manage Symptoms and Geriatric Syndromes

PubMed Central

Jassal, Sarbjit Vanita

2016-01-01

Dialysis care is often associated with poor outcomes including low quality of life (QOL). To improve patient-reported outcomes, incorporation of the patient’s needs and perspective into the medical care they receive is essential. This article provides a framework to help clinicians integrate symptom assessment and other measures such as QOL and frailty scores into a clinical approach to the contemporary supportive care of patients with advanced CKD. This approach involves (1) defining our understanding of kidney supportive care, patient-centered dialysis, and palliative dialysis; (2) understanding and recognizing common symptoms associated with advanced CKD; (3) discussing the concepts of physical function, frailty, and QOL and their role in CKD; and (4) identifying the structural and process barriers that may arise when patient-centered dialysis is being introduced into clinical practice. PMID:27510454

GABAergic interneurons: The orchestra or the conductor in fear learning and memory?

PubMed

Lucas, Elizabeth K; Clem, Roger L

2017-12-02

Fear conditioning is a form of associative learning that is fundamental to survival and involves potentiation of activity in excitatory projection neurons (PNs). Current models stipulate that the mechanisms underlying this process involve plasticity of PN synapses, which exhibit strengthening in response to fear conditioning. However, excitatory PNs are extensively modulated by a diverse array of GABAergic interneurons whose contributions to acquisition, storage, and expression of fear memory remain poorly understood. Here we review emerging evidence that genetically-defined interneurons play important subtype-specific roles in processing of fear-related stimuli and that these dynamics shape PN firing through both inhibition and disinhibition. Furthermore, interneurons exhibit structural, molecular, and electrophysiological evidence of fear learning-induced synaptic plasticity. These studies warrant discarding the notion of interneurons as passive bystanders in long-term memory. Copyright © 2017. Published by Elsevier Inc.

The StarD4 subfamily of steroidogenic acute regulatory-related lipid transfer (START) domain proteins: new players in cholesterol metabolism

PubMed Central

Calderon-Dominguez, Maria; Gil, Gregorio; Medina, Miguel Angel; Pandak, William M.; Rodríguez-Agudo, Daniel

2014-01-01

Cholesterol levels in the body are maintained through the coordinated regulation of its uptake, synthesis, distribution, storage and efflux. However, the way cholesterol is sorted within cells remains poorly defined. The discovery of the newly described StarD4 subfamily, part of the steroidogenic acute regulatory lipid transfer (START) domain family of proteins, affords an opportunity for the study of intracellular cholesterol movement, metabolism and its disorders. The three members of this intracelular subfamily of proteins (StarD4, StarD5 and StarD6) have a similar lipid binding pocket specific for sterols (cholesterol in particular), but differing regulation and localization. The ability to bind and transport cholesterol through a non-vesicular mean suggests that they play a previously unappreciated role in cholesterol homeostasis. PMID:24440759

Climate forcings in the industrial era.

PubMed

Hansen, J E; Sato, M; Lacis, A; Ruedy, R; Tegen, I; Matthews, E

1998-10-27

The forcings that drive long-term climate change are not known with an accuracy sufficient to define future climate change. Anthropogenic greenhouse gases (GHGs), which are well measured, cause a strong positive (warming) forcing. But other, poorly measured, anthropogenic forcings, especially changes of atmospheric aerosols, clouds, and land-use patterns, cause a negative forcing that tends to offset greenhouse warming. One consequence of this partial balance is that the natural forcing due to solar irradiance changes may play a larger role in long-term climate change than inferred from comparison with GHGs alone. Current trends in GHG climate forcings are smaller than in popular "business as usual" or 1% per year CO2 growth scenarios. The summary implication is a paradigm change for long-term climate projections: uncertainties in climate forcings have supplanted global climate sensitivity as the predominant issue.

Climate Forcings in the Industrial Era

NASA Technical Reports Server (NTRS)

Hansen, James E.; Sato, Makiko; Lacis, Andrew; Ruedy, Reto; Tegen, Ina; Matthews, Elaine

1998-01-01

The forcings that drive long-term climate change are not known with an accuracy sufficient to define future climate change. Anthropogenic greenhouse gases (GHGs), which are well measured, cause a strong positive (warming) forcing. But other, poorly measured, anthropogenic forcings, especially changes of atmospheric aerosols, clouds, and land-use patterns, cause a negative forcing that tends to offset greenhouse warming. One consequence of this partial balance is-that the natural forcing due to solar irradiance changes may play a larger role in long-term climate change than inferred from comparison with GHGs alone. Current trends in GHG climate forcings are smaller than in popular "business as usual" or 1% per year CO2 growth scenarios. The summary implication is a paradigm change for long-term climate projections: uncertainties in climate forcings have supplanted global climate sensitivity as the predominant issue.

Climate forcings in the Industrial era

PubMed Central

Hansen, James E.; Sato, Makiko; Lacis, Andrew; Ruedy, Reto; Tegen, Ina; Matthews, Elaine

1998-01-01

The forcings that drive long-term climate change are not known with an accuracy sufficient to define future climate change. Anthropogenic greenhouse gases (GHGs), which are well measured, cause a strong positive (warming) forcing. But other, poorly measured, anthropogenic forcings, especially changes of atmospheric aerosols, clouds, and land-use patterns, cause a negative forcing that tends to offset greenhouse warming. One consequence of this partial balance is that the natural forcing due to solar irradiance changes may play a larger role in long-term climate change than inferred from comparison with GHGs alone. Current trends in GHG climate forcings are smaller than in popular “business as usual” or 1% per year CO2 growth scenarios. The summary implication is a paradigm change for long-term climate projections: uncertainties in climate forcings have supplanted global climate sensitivity as the predominant issue. PMID:9788985

Climate Simulations of Past, Present and Future

NASA Technical Reports Server (NTRS)

Hansen, James E.

1999-01-01

The forcings that drive long-term climate change are not known with an accuracy sufficient to define future climate change. Anthropogenic greenhouse gases (GHGs), which are well measured, cause a strong positive (warming) forcing. But other, poorly measured, anthropogenic forcings, especially changes of atmospheric aerosols, clouds, and land-use patterns, cause a negative forcing that tends to offset greenhouse warming. One consequence of this partial balance is that the natural forcing due to solar irradiance changes may play a larger role in long-term climate change than inferred from comparison with GHGs alone. Current trends in GHG climate forcings are smaller than in popular "business as usual" or 1% per year CO2 growth scenarios. The summary implication is a paradigm change for long-term climate projections: uncertainties in climate forcings have supplanted global climate sensitivity as the predominant issue.

Climate Forcing in the Industrial Era

NASA Technical Reports Server (NTRS)

Hansen, James E.

1998-01-01

The forcings that drive long-term climate change are not known with an accuracy sufficient to define future climate change. Anthropogenic greenhouse gases (GHGs), which are well measured, cause a strong positive (warming) forcing. But other, poorly measured, anthropogenic forcings, especially changes of atmospheric aerosols, clouds, and land-use patterns, cause a negative forcing that tends to offset greenhouse warming. One consequence of this partial balance is that the natural forcing due to solar irradiance changes may play a larger role in long-term climate change than inferred from comparison with GHGs alone. Current trends in GHG climate forcings are smaller than in popular "business as usual" or 1% per year CO2 growth scenarios. The summary implication is a paradigm change for long-term climate projections: uncertainties in climate forcings have supplanted global climate sensitivity as the predominant issue.

Perspective: Climate Forcings in the Industrial Era

NASA Technical Reports Server (NTRS)

Hansen, James E.; Sato, Makiko; Lacis, Andrew; Ruedy, Reto; Tegen, Ina; Matthews, Elaine

1998-01-01

The forcings that drive long-term climate change are not known with an accuracy sufficient to define future climate change. Anthropogenic greenhouse gases (GHGs), which are well measured, cause a strong positive (warming) forcing. But other, poorly measured, anthropogenic forcings, especially changes of atmospheric aerosols, clouds, and land-use patterns, cause a negative forcing that tends to offset greenhouse warming. One consequence of this partial balance is that the natural forcing due to solar irradiance changes may play a larger role in long-term climate change than inferred from comparison with GHGs alone. Current trends in GHG climate forcings are smaller than in popular "business as usual" or 1% per year CO growth scenarios. The summary implication is a paradigm change for long-term climate projections: uncertainties in climate forcings have supplanted global climate sensitivity as the predominant issue.

Standard & Poor's "Return on Resources" Measure of School Performance. Issue Brief. Volume 1, Issue 1

ERIC Educational Resources Information Center

Reeder, Brian

2004-01-01

Standard & Poors (S&P) uses a measure they call a Performance Cost Index (PCI) as their measure of a school or district?s ?Return on Resources?. The Performance Cost Index is defined as the average cost per measured ?unit? of student performance. In its simplest form, the Performance Cost Index is calculated as per student expenditures divided by…

Management of elderly patients with glioblastoma-multiforme-a systematic review.

PubMed

Almadani, Asmaa; Sanjay, Dixit; Chris, Rowland-Hill; Shailendra, Achawal; Chitoor, Rajaraman; Gerry, O'Reilly; Robin, Highley; Masood, Hussain; Louise, Baker; Lynne, Gill; Holly, Morris; Mohan, Hingorani

2018-03-09

The management of elderly patients with glioblastoma-multiforme (GBM) remains poorly defined with many experts in the past advocating best supportive care, in view of limited evidence on efficacy of more aggressive treatment protocols. There is randomised evidence (NORDIC and NA-O8 studies) to support the use of surgery followed by adjuvant monotherapy with either radiotherapy (RT) using hypofractionated regimes (e.g. 36 Gy in 6 fractions OR 40 Gy in 15 fractions) or chemotherapy with temozolomide (TMZ) in patients expressing methylation of promoter for O 6 -methylguanine-DNA methyltransferase enzyme. However, the role of combined-modality therapy involving the use of combined RT and TMZ protocols has remained controversial with data from the EORTC (European Organisation for Research and Treatment of Cancer)-NCIC (National Cancer Institute of Canada) studies indicating that patients more than 65 years of age may not benefit significantly from combining standard RT fractionation using 60 Gy in 30 fractions with concurrent and adjuvant TMZ. More recently, randomised data has emerged on combining hypofractionated RT with concurrent and adjuvant TMZ. We provide a comprehensive review of literature with the aim of defining an evidence-based algorithm for management of elderly glioblastoma-multiforme population.

Minireview: Toward the Establishment of a Link between Melatonin and Glucose Homeostasis: Association of Melatonin MT2 Receptor Variants with Type 2 Diabetes

PubMed Central

Karamitri, Angeliki; Renault, Nicolas; Clement, Nathalie; Guillaume, Jean-Luc

2013-01-01

The existence of interindividual variations in G protein-coupled receptor sequences has been recognized early on. Recent advances in large-scale exon sequencing techniques are expected to dramatically increase the number of variants identified in G protein-coupled receptors, giving rise to new challenges regarding their functional characterization. The current minireview will illustrate these challenges based on the MTNR1B gene, which encodes the melatonin MT2 receptor, for which exon sequencing revealed 40 rare nonsynonymous variants in the general population and in type 2 diabetes (T2D) cohorts. Functional characterization of these MT2 mutants revealed 14 mutants with loss of Gi protein activation that associate with increased risk of T2D development. This repertoire of disease-associated mutants is a rich source for structure-activity studies and will help to define the still poorly understood role of melatonin in glucose homeostasis and T2D development in humans. Defining the functional defects in carriers of rare MT2 mutations will help to provide personalized therapies to these patients in the future. PMID:23798576

The Protein Interactome of Streptococcus pneumoniae and Bacterial Meta-interactomes Improve Function Predictions.

PubMed

Wuchty, S; Rajagopala, S V; Blazie, S M; Parrish, J R; Khuri, S; Finley, R L; Uetz, P

2017-01-01

The functions of roughly a third of all proteins in Streptococcus pneumoniae , a significant human-pathogenic bacterium, are unknown. Using a yeast two-hybrid approach, we have determined more than 2,000 novel protein interactions in this organism. We augmented this network with meta-interactome data that we defined as the pool of all interactions between evolutionarily conserved proteins in other bacteria. We found that such interactions significantly improved our ability to predict a protein's function, allowing us to provide functional predictions for 299 S. pneumoniae proteins with previously unknown functions. IMPORTANCE Identification of protein interactions in bacterial species can help define the individual roles that proteins play in cellular pathways and pathogenesis. Very few protein interactions have been identified for the important human pathogen S. pneumoniae . We used an experimental approach to identify over 2,000 new protein interactions for S. pneumoniae , the most extensive interactome data for this bacterium to date. To predict protein function, we used our interactome data augmented with interactions from other closely related bacteria. The combination of the experimental data and meta-interactome data significantly improved the prediction results, allowing us to assign possible functions to a large number of poorly characterized proteins.

Early Disparities in Mathematics Gains among Poor and Non-Poor Children: Examining the Role of Behavioral Engagement in Learning

ERIC Educational Resources Information Center

Robinson, Keith

2013-01-01

Multilevel modeling was used to investigate the relationship between poverty status, mathematics achievement gains, and behavioral engagement in learning over kindergarten. Data included information on 11,680 poor, low-income, and non-poor kindergartners from the Early Childhood Longitudinal Study-Kindergarten Cohort of 1998-1999 (ECLS-K). Results…

The clinical nurse specialist in New Zealand: how is the role defined?

PubMed

Roberts, Jennifer; Floyd, Sue; Thompson, Shona

2011-07-01

New Zealand, like many countries, is developing new advanced nursing practice roles to meet emerging needs. While much has been written about the Nurse Practitioner (NP), the role of Clinical Nurse Specialist (CNS) remains relatively unexplored and lacks national definition. This paper reports the findings from research designed to investigate the role of the CNS and how it is defined by New Zealand District Health Boards (DHBs). The study sought to identify the current requirements and expectations for the CNS role and how it is defined in practice. In 2008, 15 CNS job descriptions were collected from eight DHBs throughout the country generating data that were treated both quantitatively and qualitatively. Overall, few areas of consensus were found regarding the essential requirements for the CNS role and there were inconsistencies in how the roles were defined, most notably concerning requirements for postgraduate qualifications and Professional Development Recognition Programmes. Thematic analysis of the documents generated four key areas relevant to the CNS role. These described the CNS as a leader, a clinical expert, a co-ordinator and an educator. The findings indicate that the CNS role is inconsistently defined in New Zealand, particularly with respect to the postgraduate qualifications required and what is meant by 'expertise'.

A Role for USP7 in DNA Replication

PubMed Central

Jagannathan, Madhav; Nguyen, Tin; Gallo, David; Luthra, Niharika; Brown, Grant W.; Saridakis, Vivian

2014-01-01

The minichromosome maintenance (MCM) complex, which plays multiple important roles in DNA replication, is loaded onto chromatin following mitosis, remains on chromatin until the completion of DNA synthesis, and then is unloaded by a poorly defined mechanism that involves the MCM binding protein (MCM-BP). Here we show that MCM-BP directly interacts with the ubiquitin-specific protease USP7, that this interaction occurs predominantly on chromatin, and that MCM-BP can tether USP7 to MCM proteins. Detailed biochemical and structure analyses of the USP7–MCM-BP interaction showed that the 155PSTS158 MCM-BP sequence mediates critical interactions with the TRAF domain binding pocket of USP7. Analysis of the effects of USP7 knockout on DNA replication revealed that lack of USP7 results in slowed progression through late S phase without globally affecting the fork rate or origin usage. Lack of USP7 also resulted in increased levels of MCM proteins on chromatin, and investigation of the cause of this increase revealed a defect in the dissociation of MCM proteins from chromatin in mid- to late S phase. This role of USP7 mirrors the previously described role for MCM-BP in MCM complex unloading and suggests that USP7 works with MCM-BP to unload MCM complexes from chromatin at the end of S phase. PMID:24190967

Children's Sleep and Academic Achievement: The Moderating Role of Effortful Control

ERIC Educational Resources Information Center

Diaz, Anjolii; Berger, Rebecca; Valiente, Carlos; Eisenberg, Nancy; VanSchyndel, Sarah K.; Tao, Chun; Spinrad, Tracy; Doane, Leah D.; Thompson, Marilyn S.; Silva, Kassondra M.; Southworth, Jody

2017-01-01

Poor sleep is thought to interfere with children's learning and academic achievement (AA). However, existing research and theory indicate there are factors that may mitigate the academic risk associated with poor sleep. The purpose of this study was to examine the moderating role of children's effortful control (EC) on the relation between sleep…

40 CFR Appendix D to Part 132 - Great Lakes Water Quality Initiative Methodology for the Development of Wildlife Criteria

Code of Federal Regulations, 2014 CFR

2014-07-01

...-conducted study of 90 days or greater designed to observe subchronic or chronic effects as defined in this document. 2. The avian data must come from at least one well-conducted study of 70 days or greater designed... poorly defined comparative toxicokinetic and toxicodynamic parameters between mammals and birds. However...

40 CFR Appendix D to Part 132 - Great Lakes Water Quality Initiative Methodology for the Development of Wildlife Criteria

Code of Federal Regulations, 2011 CFR

2011-07-01

...-conducted study of 90 days or greater designed to observe subchronic or chronic effects as defined in this document. 2. The avian data must come from at least one well-conducted study of 70 days or greater designed... poorly defined comparative toxicokinetic and toxicodynamic parameters between mammals and birds. However...

40 CFR Appendix D to Part 132 - Great Lakes Water Quality Initiative Methodology for the Development of Wildlife Criteria

Code of Federal Regulations, 2012 CFR

2012-07-01

...-conducted study of 90 days or greater designed to observe subchronic or chronic effects as defined in this document. 2. The avian data must come from at least one well-conducted study of 70 days or greater designed... poorly defined comparative toxicokinetic and toxicodynamic parameters between mammals and birds. However...

40 CFR Appendix D to Part 132 - Great Lakes Water Quality Initiative Methodology for the Development of Wildlife Criteria

Code of Federal Regulations, 2013 CFR

2013-07-01

...-conducted study of 90 days or greater designed to observe subchronic or chronic effects as defined in this document. 2. The avian data must come from at least one well-conducted study of 70 days or greater designed... poorly defined comparative toxicokinetic and toxicodynamic parameters between mammals and birds. However...

40 CFR Appendix D to Part 132 - Great Lakes Water Quality Initiative Methodology for the Development of Wildlife Criteria

Code of Federal Regulations, 2010 CFR

2010-07-01

...-conducted study of 90 days or greater designed to observe subchronic or chronic effects as defined in this document. 2. The avian data must come from at least one well-conducted study of 70 days or greater designed... poorly defined comparative toxicokinetic and toxicodynamic parameters between mammals and birds. However...

Geologic framework of the Alaska Peninsula, southwest Alaska, and the Alaska Peninsula terrane

USGS Publications Warehouse

Wilson, Frederic H.; Detterman, Robert L.; DuBois, Gregory D.

2015-01-01

The boundaries separating the Alaska Peninsula terrane from other terranes are commonly indistinct or poorly defined. A few boundaries have been defined at major faults, although the extensions of these faults are speculative through some areas. The west side of the Alaska Peninsula terrane is overlapped by Tertiary sedimentary and volcanic rocks and Quaternary deposits.

Risk factors for psychosis: impaired social and role functioning.

PubMed

Cornblatt, Barbara A; Carrión, Ricardo E; Addington, Jean; Seidman, Larry; Walker, Elaine F; Cannon, Tyronne D; Cadenhead, Kristin S; McGlashan, Thomas H; Perkins, Diana O; Tsuang, Ming T; Woods, Scott W; Heinssen, Robert; Lencz, Todd

2012-11-01

Risk for psychosis is currently defined primarily on the basis of attenuated positive symptoms (APS), with no inclusion of the functional deficits characteristic of schizophrenia. Impaired social and role functioning have been of interest for reflecting poor outcome but far less is known about the developmental impact of these deficits as vulnerability or risk factors. Age-appropriate social and role functioning were prospectively assessed in 100 individuals at clinical high risk (CHR) for psychosis included in the 8-site North American Prodromal Longitudinal Study database. A nested case-control design was used to compare changes in social and role functioning in 26 individuals converting to psychosis shortly after baseline assessment and 24 converting over a year later. Individuals in each converter subgroup were directly matched to a non-converter at the same site, controlling for time to conversion, age, gender, and severity of baseline symptoms. At baseline, CHR subjects who later became psychotic were significantly more likely to be impaired socially than matched non-converters. Onset of psychosis did not further disrupt social difficulties. Role functioning showed some of the same trends, but the overall pattern was not as consistent as for the social domain. Controlling for neurocognition did not change the pattern of group differences. Early impaired social functioning appears to be a risk factor for psychosis and, added to APS, could potentially contribute to accurate identification of CHR individuals and provide a new direction for early intervention to reduce long-term disability.

Motor testing at 1 year improves the prediction of motor and mental outcome at 2 years after perinatal hypoxic-ischaemic encephalopathy.

PubMed

van Schie, Petra E M; Becher, Jules G; Dallmeijer, Annet J; Barkhof, Frederik; Van Weissenbruch, Mirjam M; Vermeulen, R Jeroen

2010-01-01

To investigate the predictive value of motor testing at 1 year for motor and mental outcome at 2 years after perinatal hypoxic-ischaemic encephalopathy (HIE) in term neonates. Motor and mental outcome at 2 years was assessed with the Bayley Scales of Infant Development, 2nd edition (BSID-II) in 32 surviving children (20 males, 12 females; mean gestational age 40.2 wk, SD 1.4; mean birthweight 3217g, SD 435) participating in a prospective cohort study of HIE. The predictive value of three motor tests (Alberta Infant Motor Scale [AIMS], BSID-II, and the Neurological Optimality Score [NOS]) at 1 year was analysed, in addition to predictions based on neonatal Sarnat staging and magnetic resonance imaging (MRI). Poor motor test results were defined as an AIMS z-score of <-2, a psychomotor developmental index of the BSID-II of <70, or a NOS of <26. Poor motor and poor mental outcome at 2 years was defined as a psychomotor developmental index or mental developmental index of the BSID-II of <70. Twelve children, all with Sarnat grade II, had a poor motor outcome and 12 children, of whom one had Sarnat grade I, had a poor mental outcome at 2 years. Nine children had cerebral palsy, of whom five had quadriplegia, three had dyskinesia, and one had hemiplegia. Poor motor tests at 1 year increased the probability of a poor motor outcome from 71% (range 92 to 100%), and a poor mental outcome from 59% (range 77 to 100%) in children with Sarnat grade II and abnormal MRI, assessed with the AIMS and BSID-II or NOS respectively. Additional motor testing at 1 year improves the prediction of motor and mental outcome at 2 years in children with Sarnat grade II and abnormal MRI.

Inactivation of thiol-dependent enzymes by hypothiocyanous acid: role of sulfenyl thiocyanate and sulfenic acid intermediates

PubMed Central

Barrett, Tessa J.; Pattison, David I.; Leonard, Stephen E.; Carroll, Kate S.; Davies, Michael J.; Hawkins, Clare L.

2012-01-01

Myeloperoxidase (MPO) forms reactive oxidants including hypochlorous and hypothiocyanous acids (HOCl and HOSCN) under inflammatory conditions. HOCl causes extensive tissue damage and plays a role in the progression of many inflammatory-based diseases. Although HOSCN is a major MPO oxidant, particularly in smokers, who have elevated plasma thiocyanate, the role of this oxidant in disease is poorly characterized. HOSCN induces cellular damage by targeting thiols. However, the specific targets and mechanisms involved in this process are not well defined. We show that exposure of macrophages to HOSCN results in the inactivation of intracellular enzymes, including creatine kinase (CK) and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). In each case, the active-site thiol residue is particularly sensitive to oxidation, with evidence for reversible inactivation and the formation of sulfenyl thiocyanate and sulfenic acid intermediates, on treatment with HOSCN (less than fivefold molar excess). Experiments with DAz-2, a cell-permeable chemical trap for sulfenic acids, demonstrate that these intermediates are formed on many cellular proteins, including GAPDH and CK, in macrophages exposed to HOSCN. This is the first direct evidence for the formation of protein sulfenic acids in HOSCN-treated cells and highlights the potential of this oxidant to perturb redox signaling processes. PMID:22248862

An access control model with high security for distributed workflow and real-time application

NASA Astrophysics Data System (ADS)

Han, Ruo-Fei; Wang, Hou-Xiang

2007-11-01

The traditional mandatory access control policy (MAC) is regarded as a policy with strict regulation and poor flexibility. The security policy of MAC is so compelling that few information systems would adopt it at the cost of facility, except some particular cases with high security requirement as military or government application. However, with the increasing requirement for flexibility, even some access control systems in military application have switched to role-based access control (RBAC) which is well known as flexible. Though RBAC can meet the demands for flexibility but it is weak in dynamic authorization and consequently can not fit well in the workflow management systems. The task-role-based access control (T-RBAC) is then introduced to solve the problem. It combines both the advantages of RBAC and task-based access control (TBAC) which uses task to manage permissions dynamically. To satisfy the requirement of system which is distributed, well defined with workflow process and critically for time accuracy, this paper will analyze the spirit of MAC, introduce it into the improved T&RBAC model which is based on T-RBAC. At last, a conceptual task-role-based access control model with high security for distributed workflow and real-time application (A_T&RBAC) is built, and its performance is simply analyzed.

Suppressive role of OGT-mediated O-GlcNAcylation of BAP1 in retinoic acid signaling.

PubMed

Moon, Seungtae; Lee, Yong-Kyu; Lee, Sang-Wang; Um, Soo-Jong

2017-10-07

BRCA1-associated protein 1 (BAP1) has been implicated in diverse biological functions, including tumor suppression. However, its regulation via glycosylation and its role in embryonic stem (ES) cells are poorly defined. BAP1 was recently reported to interact with O-linked N-acetylglucosamine (O-GlcNAc) transferase (OGT). Here, we confirmed the physical interaction and investigated its functional significance. The O-GlcNAcylation of BAP1, which requires OGT, was examined in vivo and in vitro, and was proven using alloxan, an OGT inhibitor. OGT promoted the BAP1-induced repression of retinoic acid (RA)-induced RA receptor (RAR) activation. The repressive activity of BAP1 was relieved by alloxan but exacerbated by PUGNAc, an O-GlcNAcase (OGA) inhibitor. Finally, we addressed the role of O-GlcNAcylation in the RA-induced differentiation of murine ES cells. Alkaline phosphatase staining revealed the cooperation of RA and alloxan for impairing the pluripotency of ES cells. This cooperation was also observed by measuring the size of embryonic bodies and the expression of Sox2, a pluripotency marker. Overall, our data suggest that OGT-mediated O-GlcNAcylation of BAP1 prefers the maintenance of pluripotency, whereas its inhibition facilitates RA-induced differentiation in ES cells. Copyright © 2017 Elsevier Inc. All rights reserved.

Phagocytosis depends on TRPV2-mediated calcium influx and requires TRPV2 in lipids rafts: alteration in macrophages from patients with cystic fibrosis.

PubMed

Lévêque, Manuella; Penna, Aubin; Le Trionnaire, Sophie; Belleguic, Chantal; Desrues, Benoît; Brinchault, Graziella; Jouneau, Stéphane; Lagadic-Gossmann, Dominique; Martin-Chouly, Corinne

2018-03-09

Whereas many phagocytosis steps involve ionic fluxes, the underlying ion channels remain poorly defined. As reported in mice, the calcium conducting TRPV2 channel impacts the phagocytic process. Macrophage phagocytosis is critical for defense against pathogens. In cystic fibrosis (CF), macrophages have lost their capacity to act as suppressor cells and thus play a significant role in the initiating stages leading to chronic inflammation/infection. In a previous study, we demonstrated that impaired function of CF macrophages is due to a deficient phagocytosis. The aim of the present study was to investigate TRPV2 role in the phagocytosis capacity of healthy primary human macrophage by studying its activity, its membrane localization and its recruitment in lipid rafts. In primary human macrophages, we showed that P. aeruginosa recruits TRPV2 channels at the cell surface and induced a calcium influx required for bacterial phagocytosis. We presently demonstrate that to be functional and play a role in phagocytosis, TRPV2 might require a preferential localization in lipid rafts. Furthermore, CF macrophage displays a perturbed calcium homeostasis due to a defect in TRPV2. In this context, deregulated TRPV2-signaling in CF macrophages could explain their defective phagocytosis capacity that contribute to the maintenance of chronic infection.

Dimensions of lay health worker programmes: results of a scoping study and production of a descriptive framework.

PubMed

South, Jane; Meah, Angela; Bagnall, Anne-Marie; Jones, Rebecca

2013-03-01

Approaches that engage and support lay health workers in the delivery of health improvement activities have been widely applied across different health issues and populations. The lack of a common terminology, inconsistency in the use of role descriptors and poor indexing of lay health worker roles are all barriers to the development of a shared evidence base for lay health worker interventions. The aim of the paper is to report results from a scoping study of approaches to involve lay people in public health roles and to present a framework for categorisation of the different dimensions of lay health worker programmes. Our scoping study comprised a systematic scoping review to map the literature on lay health worker interventions and to identify role dimensions and common models. The review, which was limited to interventions relevant to UK public health priorities, covered a total of 224 publications. The scoping study also drew on experiential evidence from UK practice. Research-based and practice-based evidence confirmed the variety of role descriptors in use and the complexity of role dimensions. Five common models that define the primary role of the lay health worker were identified from the literature. A framework was later developed that grouped features of lay health worker programmes into four dimensions: intervention, role, professional support/service and the community. More account needs to be taken of the variations that occur between lay health worker programmes. This framework, with the mapping of key categories of difference, may enable better description of lay health worker programmes, which will in turn assist in building a shared evidence base. More research is needed to examine the transferability of the framework within different contexts.

When Care is a "Systematic Route of Torture": Conceptualizing the Violence of Medical Negligence in Resource-Poor Settings.

PubMed

Heckert, Carina

2016-12-01

Descriptions of patient mistreatment fill ethnographic accounts of healthcare in resource-poor settings. Often, anthropologists point to structural factors and the ways that the global political economy produces substandard care. This approach makes it difficult to hold parties accountable when there is blatant disregard for human life on the part of individuals providing care. In this article, I draw on the illness narrative of Magaly Chacón, the first HIV positive individual in Bolivia to file charges of medical negligence after failing to receive care to prevent mother-to-child transmission. Magaly's narrative demonstrates how structural conditions are often used to explain away poor patient outcomes, shifting attention away from and normalizing the symbolic violence that also perpetuates substandard care of marginalized patients. I use Magaly's accusations to interrogate how defining acts of mistreatment as medical negligence can be a productive exercise, even when it is difficult to disentangle structural constraints from blatant acts of negligence. Defining who is negligent in resource-poor settings is not easy, as Magaly's case demonstrates. However, Magaly's case also demonstrates that accusations of negligence themselves can demand accountability and force changes within the local structures that contribute to the systematic mistreatment of marginalized patients.

Improvements of the offshore earthquake locations in the Earthquake Early Warning System

NASA Astrophysics Data System (ADS)

Chen, Ta-Yi; Hsu, Hsin-Chih

2017-04-01

Since 2014 the Earthworm Based Earthquake Alarm Reporting (eBEAR) system has been operated and been used to issue warnings to schools. In 2015 the system started to provide warnings to the public in Taiwan via television and the cell phone. Online performance of the eBEAR system indicated that the average reporting times afforded by the system are approximately 15 and 28 s for inland and offshore earthquakes, respectively. The eBEAR system in average can provide more warning time than the current EEW system (3.2 s and 5.5 s for inland and offshore earthquakes, respectively). However, offshore earthquakes were usually located poorly because only P-wave arrivals were used in the eBEAR system. Additionally, in the early stage of the earthquake early warning system, only fewer stations are available. The poor station coverage may be a reason to answer why offshore earthquakes are difficult to locate accurately. In the Geiger's inversion procedure of earthquake location, we need to put an initial hypocenter and origin time into the location program. For the initial hypocenter, we defined some test locations on the offshore area instead of using the average of locations from triggered stations. We performed 20 programs concurrently running the Geiger's method with different pre-defined initial position to locate earthquakes. We assume that if the program with the pre-defined initial position is close to the true earthquake location, during the iteration procedure of the Geiger's method the processing time of this program should be less than others. The results show that using pre-defined locations for trial-hypocenter in the inversion procedure is able to improve the accurate of offshore earthquakes. Especially for EEW system, in the initial stage of the EEW system, only use 3 or 5 stations to locate earthquakes may lead to bad results because of poor station coverage. In this study, the pre-defined trial-locations provide a feasible way to improve the estimations of earthquake locations in EEW system.

Indicators of Youth Social Capital: The Case for Not Using Adult Indicators in the Measurement of Youth Social Capital

ERIC Educational Resources Information Center

Billett, Paulina

2012-01-01

Social capital is a difficult concept to define, and the task of defining the social capital of youth is even more complicated. The concept has not only been poorly researched but is also imperfectly understood. This article examines the problems faced in the use of adult indicators in youth social capital research and explores current…

Applying Q-methodology to select and define attributes for non-market valuation: A case study from Northwest Wyoming, United States

Treesearch

Christopher A. Armatas; Tyron J. Venn; Alan E. Watson

2014-01-01

The underlying validity of stated preference non-market valuation methods relies on the analyst's ability to identify, select, define, and articulate the goods being valued in a way that is relevant and understandable to the respondent, which requires detailed understanding of the respondents' experiences and points of view. Poor articulation of the good...

Optimizing the ‘demographic dividend’ in young developing countries: The role of contractual savings and insurance for financing education

PubMed Central

Ssewamala, Fred M.

2014-01-01

Many developing regions are facing a youth bulge, meaning that young people comprise the highest proportion of the population. These regions are at risk of losing what could be a tremendous opportunity for economic growth and development if they do not capitalize on this young and economically productive population - also referred to as the “demographic dividend,” defined as the increase in economic growth that tends to follow increases in the ratio of the working-age population - essentially the labor force - to dependents. Nations undergoing this population transition have the opportunity to capitalize on the demographic dividend if the right social, economic, and human capital policies are in place. In particular, sub-Saharan Africa, the Middle East, and North Africa are at risk of losing the demographic dividend. These regions face high youth unemployment, low primary school completion, and low secondary school enrollment. This results in an undereducated and unskilled segment of the population. The prohibitive costs of education prevent young people from finishing school, thereby entering the labor market unprepared. This article presents a case for youth-focused financial inclusion programs as one of the antidotes to the masses of poor, undereducated, and low-skilled young people swelling the labor markets of poor developing countries. PMID:26273211

Glioma IL13Rα2 Is Associated with Mesenchymal Signature Gene Expression and Poor Patient Prognosis

PubMed Central

Starr, Renate; Deng, Xutao; Badie, Behnam; Yuan, Yate-Ching; Forman, Stephen J.; Barish, Michael E.

2013-01-01

A major challenge for successful immunotherapy against glioma is the identification and characterization of validated targets. We have taken a bioinformatics approach towards understanding the biological context of IL-13 receptor α2 (IL13Rα2) expression in brain tumors, and its functional significance for patient survival. Querying multiple gene expression databases, we show that IL13Rα2 expression increases with glioma malignancy grade, and expression for high-grade tumors is bimodal, with approximately 58% of WHO grade IV gliomas over-expressing this receptor. By several measures, IL13Rα2 expression in patient samples and low-passage primary glioma lines most consistently correlates with the expression of signature genes defining mesenchymal subclass tumors and negatively correlates with proneural signature genes as defined by two studies. Positive associations were also noted with proliferative signature genes, whereas no consistent associations were found with either classical or neural signature genes. Probing the potential functional consequences of this mesenchymal association through IPA analysis suggests that IL13Rα2 expression is associated with activation of proinflammatory and immune pathways characteristic of mesenchymal subclass tumors. In addition, survival analyses indicate that IL13Rα2 over-expression is associated with poor patient prognosis, a single gene correlation ranking IL13Rα2 in the top ~1% of total gene expression probes with regard to survival association with WHO IV gliomas. This study better defines the functional consequences of IL13Rα2 expression by demonstrating association with mesenchymal signature gene expression and poor patient prognosis. It thus highlights the utility of IL13Rα2 as a therapeutic target, and helps define patient populations most likely to respond to immunotherapy in present and future clinical trials. PMID:24204956

Glioma IL13Rα2 is associated with mesenchymal signature gene expression and poor patient prognosis.

PubMed

Brown, Christine E; Warden, Charles D; Starr, Renate; Deng, Xutao; Badie, Behnam; Yuan, Yate-Ching; Forman, Stephen J; Barish, Michael E

2013-01-01

A major challenge for successful immunotherapy against glioma is the identification and characterization of validated targets. We have taken a bioinformatics approach towards understanding the biological context of IL-13 receptor α2 (IL13Rα2) expression in brain tumors, and its functional significance for patient survival. Querying multiple gene expression databases, we show that IL13Rα2 expression increases with glioma malignancy grade, and expression for high-grade tumors is bimodal, with approximately 58% of WHO grade IV gliomas over-expressing this receptor. By several measures, IL13Rα2 expression in patient samples and low-passage primary glioma lines most consistently correlates with the expression of signature genes defining mesenchymal subclass tumors and negatively correlates with proneural signature genes as defined by two studies. Positive associations were also noted with proliferative signature genes, whereas no consistent associations were found with either classical or neural signature genes. Probing the potential functional consequences of this mesenchymal association through IPA analysis suggests that IL13Rα2 expression is associated with activation of proinflammatory and immune pathways characteristic of mesenchymal subclass tumors. In addition, survival analyses indicate that IL13Rα2 over-expression is associated with poor patient prognosis, a single gene correlation ranking IL13Rα2 in the top ~1% of total gene expression probes with regard to survival association with WHO IV gliomas. This study better defines the functional consequences of IL13Rα2 expression by demonstrating association with mesenchymal signature gene expression and poor patient prognosis. It thus highlights the utility of IL13Rα2 as a therapeutic target, and helps define patient populations most likely to respond to immunotherapy in present and future clinical trials.

The Inverse Relation Between Risks and Benefits: The Role of Affect and Expertise.

PubMed

Sokolowska, Joanna; Sleboda, Patrycja

2015-07-01

Although risk and benefits of risky activities are positively correlated in the real world, empirical results indicate that people perceive them as negatively correlated. The common explanation is that confounding benefits and losses stems from affect. In this article, we address the issue that has not been clearly established in studies on the affect heuristic: to what extent boundary conditions, such as judgments' generality and expertise, influence the presence of the inverse relation in judgments of hazards. These conditions were examined in four studies in which respondents evaluated general or specific benefits and risks of "affect-rich" and "affect-poor" hazards (ranging from investments to applications of stem cell research). In line with previous research, affect is defined as good or bad feelings integral to a stimulus. In contrast to previous research, affect is considered as related both to personal feelings and to social controversies associated with a hazard. Expertise is related to personal knowledge (laypersons vs. experts) as well as to objective knowledge (targets well vs. poorly known to science). The direct comparison of the input from personal and objective ignorance into the inverse relation has not been investigated previously. It was found that affect invoked by a hazard guides general but not specific judgments of its benefits and risks. Technical expertise helps to avoid simplified evaluations of consequences as long as they are well known to science. For new, poorly understood hazards (e.g., stem cell research), expertise does not protect from the perception of the inverse relation between benefits and risks. © 2015 Society for Risk Analysis.

Na, K-ATPase subunits as markers for epithelial-mesenchymal transition in cancer and fibrosis

PubMed Central

Rajasekaran, Sigrid A.; Huynh, Thu P.; Wolle, Daniel G.; Espineda, Cromwell E.; Inge, Landon J.; Skay, Anna; Lassman, Charles; Nicholas, Susanne B.; Harper, Jeffrey F.; Reeves, Anna E.; Ahmed, Mansoor M.; Leatherman, James M; Mullin, James M.; Rajasekaran, Ayyappan K.

2010-01-01

Epithelial-to-mesenchymal transition (EMT) is an important developmental process, participates in tissue repair and occurs during pathological processes of tumor invasiveness, metastasis and tissue fibrosis. The molecular mechanisms leading to EMT are poorly understood. While it is well documented that transforming growth factor (TGF)-β plays a central role in the induction of EMT, the targets of TGF-β signaling are poorly defined. We have shown earlier that Na,K-ATPase β1-subunit levels are highly reduced in poorly differentiated kidney carcinoma cells in culture and in patients’ tumor samples. In this study, we provide evidence that Na,K-ATPase is a new target of TGF-β1-mediated EMT in renal epithelial cells, a model system used in studies of both cancer progression and fibrosis. We show that following treatment with TGF-β1 the surface expression of the β1-subunit of Na,K-ATPase is reduced, prior to well-characterized EMT markers and is associated with the acquisition of a mesenchymal phenotype. RNAi mediated knockdown confirmed the specific involvement of the Na,K-ATPase β1-subunit in the loss of the epithelial phenotype and exogenous over-expression of the Na,K-ATPase β1-subunit attenuated TGF-β1-mediated EMT. We further show that both Na,K-ATPase α- and β-subunit levels are highly reduced in renal fibrotic tissues. These findings for the first time reveal that Na,K-ATPase is a target of TGF-β1-mediated EMT and is associated with the progression of EMT in both cancer and fibrosis. PMID:20501797

The Difference Between the Healing and the Nonhealing Diabetic Foot Ulcer: A Review of the Role of the Microcirculation.

PubMed

Lowry, Danielle; Saeed, Mujahid; Narendran, Parth; Tiwari, Alok

2017-09-01

Diabetic foot disease carries a high morbidity and is a leading cause of lower limb amputation. This may in part be due to the effect diabetes mellitus (DM) has on the microcirculation including in the skin. We conducted a review of studies that have examined the relationship between microcirculatory function and wound healing in patients with DM. A search of the Medline, Embase, and Web of Science databases was performed coupled with a review of references for the period 1946 to March 2015. Nineteen studies of diverse methodology and cohort selection were identified. Poor function of the microcirculation was related to poor outcome. Transcutaneous oxygen pressure (TcPO 2 ) was the most commonly used method to measure the microcirculation and thresholds for poor outcome proposed ranged from 10 mmHg to <34 mmHg. Two studies reexamined microcirculatory function following revascularization. Both found an increase in TcPO 2 , however only 1 reached statistical significance. No significant difference in the results of microcirculation tests was found between diabetic and nondiabetic patients. While it is not possible to draw firm conclusions from the evidence currently available there are clear areas that warrant research. Good microcirculation unsurprisingly appears to associate with better wound healing. The influence of DM is not clear, and neither is the degree of improvement required to achieve healing. Studies that examine a clearly defined cohort both with and without DM are urgently required. Accurate quantitative assessment of microcirculation will aid prediction of wound healing identifying those at greatest risk of amputation.

Latent class analysis of lifestyle characteristics and health risk behaviors among college youth.

PubMed

Laska, Melissa Nelson; Pasch, Keryn E; Lust, Katherine; Story, Mary; Ehlinger, Ed

2009-12-01

Few studies have examined the context of a wide range of risk behaviors among emerging adults (ages 18-25 years), approximately half of whom in the USA enroll in post-secondary educational institutions. The objective of this research was to examine behavioral patterning in weight behaviors (diet and physical activity), substance use, sexual behavior, stress, and sleep among undergraduate students. Health survey data were collected among undergraduates attending a large, public US university (n = 2,026). Latent class analysis was used to identify homogeneous, mutually exclusive "classes" (patterns) of ten leading risk behaviors. Resulting classes differed for males and females. Female classes were defined as: (1) poor lifestyle (diet, physical activity, sleep), yet low-risk behaviors (e.g., smoking, binge drinking, sexual risk, drunk driving; 40.0% of females), (2) high risk (high substance use, intoxicated sex, drunk driving, poor diet, inadequate sleep) (24.3%), (3) moderate lifestyle, few risk behaviors (20.4%), (4) "health conscious" (favorable diet/physical activity with some unhealthy weight control; 15.4%). Male classes were: (1) poor lifestyle, low risk (with notably high stress, insufficient sleep, 9.2% of males), (2) high risk (33.6% of males, similar to class 2 in females), (3) moderate lifestyle, low risk (51.0%), and (4) "classic jocks" (high physical activity, binge drinking, 6.2%). To our knowledge, this is among the first research to examine complex lifestyle patterning among college youth, particularly with emphasis on the role of weight-related behaviors. These findings have important implications for targeting much needed health promotion strategies among emerging adults and college youth.

Non-convulsive seizures and electroencephalography findings as predictors of clinical outcomes at a tertiary intensive care unit in Saudi Arabia.

PubMed

Al-Said, Youssef A; Baeesa, Saleh S; Shivji, Zaitoon; Kayyali, Husam; Alqadi, Khalid; Kadi, Ghada; Cupler, Edward J; Abuzinadah, Ahmad R

2018-06-05

Electroencephalography (EEG) in the intensive care unit (ICU) is often done to detect non-convulsive seizures (NCS). The outcome of ICU patients with NCS strongly depends on the underlying etiology. The implication of NCS and other EEG findings on clinical outcome independent from their etiology is not well understood and our aim to investigate it. We retrospectively identified all adult patients in the ICU who underwent EEG monitoring between January 2008 and December 2011. The main goals were to define the rate of NCS or non-convulsive status epilepticus (NCSE) occurrence in our center among patients who underwent EEG monitoring and to examine if NCS/NCSE are associated with poor outcome [defined as death or dependence] with and without adjustment for underlying etiology. The rate of poor outcome among different EEG categories were also investigated. During the study period, 177 patients underwent EEG monitoring in our ICU. The overall outcome was poor in 62.7% of those undergoing EEG. The rate of occurrence of NCS/NCSE was 8.5% and was associated with poor outcome in 86.7% with an odds ratio (OR) of 5.1 (95% confidence interval [CI] 1.09-23.8). This association was maintained after adjusting for underlying etiologies with OR 5.6 (95% CI 1.05-29.6). The rate of poor outcome was high in the presence of periodic discharges and sharp and slow waves of 75% and 61.5%, respectively. Our cohort of ICU patients undergoing EEGs had a poor outcome. Those who developed NCS/NCSE experienced an even worse outcome regardless of the underlying etiology. Copyright © 2018 Elsevier B.V. All rights reserved.

Reverse shoulder arthroplasty for massive rotator cuff tear: risk factors for poor functional improvement.

PubMed

Hartzler, Robert U; Steen, Brandon M; Hussey, Michael M; Cusick, Michael C; Cottrell, Benjamin J; Clark, Rachel E; Frankle, Mark A

2015-11-01

Some patients unexpectedly have poor functional improvement after reverse shoulder arthroplasty (RSA) for massive rotator cuff tear without glenohumeral arthritis. Our aim was to identify risk factors for this outcome. We also assessed the value of RSA for cases with poor functional improvement vs. The study was a retrospective case-control analysis for primary RSA performed for massive rotator cuff tear without glenohumeral arthritis with minimum 2-year follow-up. Cases were defined as Simple Shoulder Test (SST) score improvement of ≤1, whereas controls improved SST score ≥2. Risk factors were chosen on the basis of previous association with poor outcomes after shoulder arthroplasty. Latissimus dorsi tendon transfer results were analyzed as a subgroup. Value was defined as improvement in American Shoulder and Elbow Surgeons (ASES) score per $10,000 hospital cost. In a multivariate binomial logistic regression analysis, neurologic dysfunction (P = .006), age <60 years (P = .02), and high preoperative SST score (P = .03) were independently associated with poor functional improvement. Latissimus dorsi tendon transfer patients significantly improved in active external rotation (-0.3° to 38.7°; P < .01). The value of RSA (ΔASES/$10,000 cost) for cases was 0.8 compared with 17.5 for controls (P < .0001). Young age, high preoperative function, and neurologic dysfunction were associated with poor functional improvement. Surgeons should consider these associations in counseling and selection of patients. Concurrent latissimus dorsi transfer was successful in restoring active external rotation in a subgroup of patients. The critical economic importance of improved patient selection is emphasized by the very low value of the procedure in the case group. Copyright © 2015 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Genome-scale analysis of the high-efficient protein secretion system of Aspergillus oryzae

PubMed Central

2014-01-01

Background The koji mold, Aspergillus oryzae is widely used for the production of industrial enzymes due to its particularly high protein secretion capacity and ability to perform post-translational modifications. However, systemic analysis of its secretion system is lacking, generally due to the poorly annotated proteome. Results Here we defined a functional protein secretory component list of A. oryzae using a previously reported secretory model of S. cerevisiae as scaffold. Additional secretory components were obtained by blast search with the functional components reported in other closely related fungal species such as Aspergillus nidulans and Aspergillus niger. To evaluate the defined component list, we performed transcriptome analysis on three α-amylase over-producing strains with varying levels of secretion capacities. Specifically, secretory components involved in the ER-associated processes (including components involved in the regulation of transport between ER and Golgi) were significantly up-regulated, with many of them never been identified for A. oryzae before. Furthermore, we defined a complete list of the putative A. oryzae secretome and monitored how it was affected by overproducing amylase. Conclusion In combination with the transcriptome data, the most complete secretory component list and the putative secretome, we improved the systemic understanding of the secretory machinery of A. oryzae in response to high levels of protein secretion. The roles of many newly predicted secretory components were experimentally validated and the enriched component list provides a better platform for driving more mechanistic studies of the protein secretory pathway in this industrially important fungus. PMID:24961398

Genome-scale analysis of the high-efficient protein secretion system of Aspergillus oryzae.

PubMed

Liu, Lifang; Feizi, Amir; Österlund, Tobias; Hjort, Carsten; Nielsen, Jens

2014-06-24

The koji mold, Aspergillus oryzae is widely used for the production of industrial enzymes due to its particularly high protein secretion capacity and ability to perform post-translational modifications. However, systemic analysis of its secretion system is lacking, generally due to the poorly annotated proteome. Here we defined a functional protein secretory component list of A. oryzae using a previously reported secretory model of S. cerevisiae as scaffold. Additional secretory components were obtained by blast search with the functional components reported in other closely related fungal species such as Aspergillus nidulans and Aspergillus niger. To evaluate the defined component list, we performed transcriptome analysis on three α-amylase over-producing strains with varying levels of secretion capacities. Specifically, secretory components involved in the ER-associated processes (including components involved in the regulation of transport between ER and Golgi) were significantly up-regulated, with many of them never been identified for A. oryzae before. Furthermore, we defined a complete list of the putative A. oryzae secretome and monitored how it was affected by overproducing amylase. In combination with the transcriptome data, the most complete secretory component list and the putative secretome, we improved the systemic understanding of the secretory machinery of A. oryzae in response to high levels of protein secretion. The roles of many newly predicted secretory components were experimentally validated and the enriched component list provides a better platform for driving more mechanistic studies of the protein secretory pathway in this industrially important fungus.

Integrative analysis identifies targetable CREB1/FoxA1 transcriptional co-regulation as a predictor of prostate cancer recurrence.

PubMed

Sunkel, Benjamin; Wu, Dayong; Chen, Zhong; Wang, Chiou-Miin; Liu, Xiangtao; Ye, Zhenqing; Horning, Aaron M; Liu, Joseph; Mahalingam, Devalingam; Lopez-Nicora, Horacio; Lin, Chun-Lin; Goodfellow, Paul J; Clinton, Steven K; Jin, Victor X; Chen, Chun-Liang; Huang, Tim H-M; Wang, Qianben

2016-05-19

Identifying prostate cancer-driving transcription factors (TFs) in addition to the androgen receptor promises to improve our ability to effectively diagnose and treat this disease. We employed an integrative genomics analysis of master TFs CREB1 and FoxA1 in androgen-dependent prostate cancer (ADPC) and castration-resistant prostate cancer (CRPC) cell lines, primary prostate cancer tissues and circulating tumor cells (CTCs) to investigate their role in defining prostate cancer gene expression profiles. Combining genome-wide binding site and gene expression profiles we define CREB1 as a critical driver of pro-survival, cell cycle and metabolic transcription programs. We show that CREB1 and FoxA1 co-localize and mutually influence each other's binding to define disease-driving transcription profiles associated with advanced prostate cancer. Gene expression analysis in human prostate cancer samples found that CREB1/FoxA1 target gene panels predict prostate cancer recurrence. Finally, we showed that this signaling pathway is sensitive to compounds that inhibit the transcription co-regulatory factor MED1. These findings not only reveal a novel, global transcriptional co-regulatory function of CREB1 and FoxA1, but also suggest CREB1/FoxA1 signaling is a targetable driver of prostate cancer progression and serves as a biomarker of poor clinical outcomes. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

Dealing with teen-age pregnancy.

PubMed

Dempsey, P L

1991-01-01

The author finds that teenage pregnancy is more complicated than access to contraception or abortion. At risk teenagers are not identifiable, only at risk factors such as isolation, lack of perception of future opportunities, lack of self esteem, lack of self worth, poor performance in school, poor role models or lack of role models at home or in the community. There is indictment of parents who are just as much in need. The focus on teen pregnancy as one dimensional belies the reality that health, family, work, social and cultural experience affect people's decisions and sexual behavior. The recommendation is for a holistic approach, regardless of race, ethnicity, or socioeconomic background. Adolescents need education and jobs as well as preventive health, body image, and nutrition in conjunction with contraceptives. Where success is defined by motherhood or fatherhood, birth control pills sit in drawers at home. Teenagers need to be convinced that there is some benefit in being connected to mainstream society. Support services need to help teenagers answer the question of what's in it for me? Why? Teenagers need assistance in attaining educational success, job success, the ability to handle anger, and leadership opportunities. A holistic approach is not only realistic but also is the most practical with the longest term benefit. With resources for teen pregnancy superseded by the problems of AIDs and crack gangs, there is a constantly changing political agenda for resource allocation. In fact, teenage pregnancy is reflective of social ills in an urban society simultaneous with drug abuse, school dropouts, juvenile crime and gang activity. The common denominator is that teens all need good educational opportunities, good health, and good housing. Parent involvement is needed, and it is presumptuous to believe that a couple of hours of contact a week can change lives. Parents need respect and understanding for their important role; they need information and a role also in order to keep these teenagers moving forward. What others are doing in the community must be taken into consideration. Providing real options and hope involves a personal internal process where growth is essential and evident. Target populations may be the same, and brokering to share services is necessary. Know who the social services agencies are.

Circular RNA ZNF609 functions as a competitive endogenous RNA to regulate AKT3 expression by sponging miR-150-5p in Hirschsprung's disease.

PubMed

Peng, Lei; Chen, Guanglin; Zhu, Zhongxian; Shen, Ziyang; Du, Chunxia; Zang, Rujin; Su, Yang; Xie, Hua; Li, Hongxing; Xu, Xiaoqun; Xia, Yankai; Tang, Weibing

2017-01-03

Research over the past decade suggested critical roles for circular RNAs in the natural growth and disease progression. However, it remains poorly defined whether the circular RNAs participate in Hirschsprung disease (HSCR). Here, we reported that the cir-ZNF609 was down-regulated in HSCR compared with normal bowel tissues. Furthermore, suppression of cir-ZNF609 inhibited the proliferation and migration of cells. We screened out several putative cir-ZNF609 ceRNAs of which the AKT3 transcript was selected. Finally, RNA immunoprecipitation and luciferase reporter assays demonstrated that cir-ZNF609 may act as a sponge for miR-150-5p to modulate the expression of AKT3. In conclusion, these findings illustrated that cir-ZNF609 took part in the onset of HSCR through the crosstalk with AKT3 by competing for shared miR-150-5p.

Portfolio careers for medical graduates: implications for postgraduate training and workforce planning.

PubMed

Eyre, Harris A; Mitchell, Rob D; Milford, Will; Vaswani, Nitin; Moylan, Steven

2014-06-01

Portfolio careers in medicine can be defined as significant involvement in one or more portfolios of activity beyond a practitioner's primary clinical role, either concurrently or in sequence. Portfolio occupations may include medical education, research, administration, legal medicine, the arts, engineering, business and consulting, leadership, politics and entrepreneurship. Despite significant interest among junior doctors, portfolios are poorly integrated with prevocational and speciality training programs in Australia. The present paper seeks to explore this issue. More formal systems for portfolio careers in Australia have the potential to increase job satisfaction, flexibility and retention, as well as diversify trainee skill sets. Although there are numerous benefits from involvement in portfolio careers, there are also risks to the trainee, employing health service and workforce modelling. Formalising pathways to portfolio careers relies on assessing stakeholder interest, enhancing flexibility in training programs, developing support programs, mentorship and coaching schemes and improving support structures in health services.

Improvement of force health protection through preventive medicine oversight of contractor support.

PubMed

Mower, Scott A

2009-01-01

Unprecedented numbers of contractors are used throughout the Iraq theater of operations to alleviate military manpower shortages. At virtually every major forward operating base, US-based contractors perform the preponderance of essential life support services. At more remote sites, local national contractors are increasingly relied upon to maintain chemical latrines, remove trash, deliver bulk water, and execute other janitorial functions. Vigorous oversight of contractor performance is essential to ensure services are delivered according to specified standards. Poor oversight can increase the risk of criminal activities, permit substandard performance, elevate disease and nonbattle injury rates, degrade morale, and diminish Soldier readiness. As the principal force health protection proponents in the Department of Defense, preventive medicine units must be tightly integrated into the oversight processes. This article defines the force health protection implications associated with service contracts and provide recommendations for strengthening preventive medicine's oversight role.

Strength of the repulsive part of the interatomic potential determines fragility in metallic liquids

NASA Astrophysics Data System (ADS)

Pueblo, Christopher E.; Sun, Minhua; Kelton, K. F.

2017-08-01

The dynamical behaviour of liquids is frequently characterized by the fragility, which can be defined from the temperature dependence of the shear viscosity, η (ref. ). For a strong liquid, the activation energy for η changes little with cooling towards the glass transition temperature, Tg. The change is much greater in fragile liquids, with the activation energy becoming very large near Tg. While fragility is widely recognized as an important concept--believed, for example, to play an important role in glass formation--the microscopic origin of fragility is poorly understood. Here, we present new experimental evidence showing that fragility reflects the strength of the repulsive part of the interatomic potential, which can be determined from the steepness of the pair distribution function near the hard-sphere cutoff. On the basis of an analysis of scattering data from ten different metallic alloy liquids, we show that stronger liquids have steeper repulsive potentials.

Functional and topological characteristics of mammalian regulatory domains

PubMed Central

Symmons, Orsolya; Uslu, Veli Vural; Tsujimura, Taro; Ruf, Sandra; Nassari, Sonya; Schwarzer, Wibke; Ettwiller, Laurence; Spitz, François

2014-01-01

Long-range regulatory interactions play an important role in shaping gene-expression programs. However, the genomic features that organize these activities are still poorly characterized. We conducted a large operational analysis to chart the distribution of gene regulatory activities along the mouse genome, using hundreds of insertions of a regulatory sensor. We found that enhancers distribute their activities along broad regions and not in a gene-centric manner, defining large regulatory domains. Remarkably, these domains correlate strongly with the recently described TADs, which partition the genome into distinct self-interacting blocks. Different features, including specific repeats and CTCF-binding sites, correlate with the transition zones separating regulatory domains, and may help to further organize promiscuously distributed regulatory influences within large domains. These findings support a model of genomic organization where TADs confine regulatory activities to specific but large regulatory domains, contributing to the establishment of specific gene expression profiles. PMID:24398455

Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation

PubMed Central

Jeon, Jessie S.; Bersini, Simone; Gilardi, Mara; Dubini, Gabriele; Charest, Joseph L.; Moretti, Matteo; Kamm, Roger D.

2015-01-01

A key aspect of cancer metastases is the tendency for specific cancer cells to home to defined subsets of secondary organs. Despite these known tendencies, the underlying mechanisms remain poorly understood. Here we develop a microfluidic 3D in vitro model to analyze organ-specific human breast cancer cell extravasation into bone- and muscle-mimicking microenvironments through a microvascular network concentrically wrapped with mural cells. Extravasation rates and microvasculature permeabilities were significantly different in the bone-mimicking microenvironment compared with unconditioned or myoblast containing matrices. Blocking breast cancer cell A3 adenosine receptors resulted in higher extravasation rates of cancer cells into the myoblast-containing matrices compared with untreated cells, suggesting a role for adenosine in reducing extravasation. These results demonstrate the efficacy of our model as a drug screening platform and a promising tool to investigate specific molecular pathways involved in cancer biology, with potential applications to personalized medicine. PMID:25524628

The role of self-management in designing care for people with osteoarthritis of the hip and knee.

PubMed

Brand, Caroline A

2008-11-17

Osteoarthritis of the hip and knee is an increasingly common condition that is managed principally with lifestyle behaviour changes. Osteoarthritis management can be complex, as it typically affects older patients with multiple comorbidities. There is evidence that opportunities exist to improve uptake of evidence-based recommendations for care, especially for non-pharmacological interventions. The National Chronic Disease Strategy (NCDS) defines key components of programs designed to meet the needs of people with chronic conditions; one component is patient self-management. NCDS principles have been effectively integrated into chronic disease management programs for other conditions, but there is limited evidence of effectiveness for osteoarthritis programs. A comprehensive osteoarthritis management model that reflects NCDS policy is needed. Barriers to implementing such a model include poor integration of decision support, a lack of national infrastructure, workforce constraints and limited funding.

Drosophila arginine methyltransferase 1 (DART1) is an ecdysone receptor co-repressor

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

Kimura, Shuhei; Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574; Sawatsubashi, Shun

2008-07-11

Histone arginine methylation is an epigenetic marker that regulates gene expression by defining the chromatin state. Arginine methyltransferases, therefore, serve as transcriptional co-regulators. However, unlike other transcriptional co-regulators, the physiological roles of arginine methyltransferases are poorly understood. Drosophila arginine methyltransferase 1 (DART1), the mammalian PRMT1 homologue, methylates the arginine residue of histone H4 (H4R3me2). Disruption of DART1 in Drosophila by imprecise P-element excision resulted in low viability during metamorphosis in the pupal stages. In the pupal stage, an ecdysone hormone signal is critical for developmental progression. DART1 interacted with the nuclear ecdysone receptor (EcR) in a ligand-dependent manner, and co-repressedmore » EcR in intact flies. These findings suggest that DART1, a histone arginine methyltransferase, is a co-repressor of EcR that is indispensable for normal pupal development in the intact fly.« less

Strategies for enhancing perioperative safety: promoting joy and meaning in the workforce.

PubMed

Morath, Julianne; Filipp, Rhonda; Cull, Michael

2014-10-01

Workforce safety is a precondition of patient safety, and safety from both physical and psychological harm in the workplace is the foundation for an environment in which joy and meaning can exist. Achieving joy and meaning in the workplace allows health care workers to continuously improve the care they provide. This requires an environment in which disrespectful and harmful behaviors are not tolerated or ignored. Health care leaders have an obligation to create workplace cultures that are characterized by respect, transparency, accountability, learning, and quality care. Evidence suggests, however, that health care settings are rife with disrespectful behavior, poor teamwork, and unsafe working conditions. Solutions for addressing workplace safety problems include defining core values, tasking leaders to act as role models, and committing to becoming a high-reliability organization. Copyright © 2014 AORN, Inc. Published by Elsevier Inc. All rights reserved.

Human 3D vascularized organotypic microfluidic assays to study breast cancer cell extravasation.

PubMed

Jeon, Jessie S; Bersini, Simone; Gilardi, Mara; Dubini, Gabriele; Charest, Joseph L; Moretti, Matteo; Kamm, Roger D

2015-01-06

A key aspect of cancer metastases is the tendency for specific cancer cells to home to defined subsets of secondary organs. Despite these known tendencies, the underlying mechanisms remain poorly understood. Here we develop a microfluidic 3D in vitro model to analyze organ-specific human breast cancer cell extravasation into bone- and muscle-mimicking microenvironments through a microvascular network concentrically wrapped with mural cells. Extravasation rates and microvasculature permeabilities were significantly different in the bone-mimicking microenvironment compared with unconditioned or myoblast containing matrices. Blocking breast cancer cell A3 adenosine receptors resulted in higher extravasation rates of cancer cells into the myoblast-containing matrices compared with untreated cells, suggesting a role for adenosine in reducing extravasation. These results demonstrate the efficacy of our model as a drug screening platform and a promising tool to investigate specific molecular pathways involved in cancer biology, with potential applications to personalized medicine.

Neutrophils suppress intraluminal NK-mediated tumor cell clearance and enhance extravasation of disseminated carcinoma cells

PubMed Central

Spiegel, Asaf; Brooks, Mary W.; Houshyar, Samin; Reinhardt, Ferenc; Ardolino, Michele; Fessler, Evelyn; Chen, Michelle B.; Krall, Jordan A.; DeCock, Jasmine; Zervantonakis, Ioannis K.; Iannello, Alexandre; Iwamoto, Yoshiko; Cortez-Retamozo, Virna; Kamm, Roger D.; Pittet, Mikael J.; Raulet, David H.; Weinberg, Robert A.

2016-01-01

Immune cells promote the initial metastatic dissemination of carcinoma cells from primary tumors. In contrast to their well-studied functions in the initial stages of metastasis, the specific roles of immunocytes in facilitating progression through the critical later steps of the invasion-metastasis cascade remain poorly understood. Here we define novel functions of neutrophils in promoting intraluminal survival and extravasation at sites of metastatic dissemination. We show that CD11b+/Ly6G+ neutrophils enhance metastasis formation via two distinct mechanisms. First, neutrophils inhibit natural killer cell function, which leads to a significant increase in the intraluminal survival time of tumor cells. Thereafter, neutrophils operate to facilitate extravasation of tumor cells through the secretion of IL-1β and matrix metalloproteinases. These results identify neutrophils as key regulators of intraluminal survival and extravasation through their crosstalk with host cells and disseminating carcinoma cells. PMID:27072748

Dorsal hippocampus contributes to model-based planning.

PubMed

Miller, Kevin J; Botvinick, Matthew M; Brody, Carlos D

2017-09-01

Planning can be defined as action selection that leverages an internal model of the outcomes likely to follow each possible action. Its neural mechanisms remain poorly understood. Here we adapt recent advances from human research for rats, presenting for the first time an animal task that produces many trials of planned behavior per session, making multitrial rodent experimental tools available to study planning. We use part of this toolkit to address a perennially controversial issue in planning: the role of the dorsal hippocampus. Although prospective hippocampal representations have been proposed to support planning, intact planning in animals with damaged hippocampi has been repeatedly observed. Combining formal algorithmic behavioral analysis with muscimol inactivation, we provide causal evidence directly linking dorsal hippocampus with planning behavior. Our results and methods open the door to new and more detailed investigations of the neural mechanisms of planning in the hippocampus and throughout the brain.

Low-Dose Intestinal Trichuris muris Infection Alters the Lung Immune Microenvironment and Can Suppress Allergic Airway Inflammation.

PubMed

Chenery, Alistair L; Antignano, Frann; Burrows, Kyle; Scheer, Sebastian; Perona-Wright, Georgia; Zaph, Colby

2016-02-01

Immunological cross talk between mucosal tissues such as the intestine and the lung is poorly defined during homeostasis and disease. Here, we show that a low-dose infection with the intestinally restricted helminth parasite Trichuris muris results in the production of Th1 cell-dependent gamma interferon (IFN-γ) and myeloid cell-derived interleukin-10 (IL-10) in the lung without causing overt airway pathology. This cross-mucosal immune response in the lung inhibits the development of papain-induced allergic airway inflammation, an innate cell-mediated type 2 airway inflammatory disease. Thus, we identify convergent and nonredundant roles of adaptive and innate immunity in mediating cross-mucosal suppression of type 2 airway inflammation during low-dose helminth-induced intestinal inflammation. These results provide further insight in identifying novel intersecting immune pathways elicited by gut-to-lung mucosal cross talk. Copyright © 2016 Chenery et al.

Social-ecological resilience and social conflict: institutions and strategic adaptation in Swedish water management.

PubMed

Galaz, Victor

2005-11-01

Dealing with uncertainty and complexity in social-ecological systems is profoundly dependent on the ability of natural resource users to learn and adapt from ecological surprises and crises. This paper analyzes why and how learning processes are affected by strategic behavior among natural resource users and how social conflict is affected by social and ecological uncertainty. The claim is that social conflict among natural resource users seriously inhibits the possibilities of learning and adaptation in social-ecological systems. This is done combining insights from political science, experimental economics, and social-psychology and an analytical case study elaborating social conflict and institutional change in Swedish water management institutions. This paper also discusses the crucial role the institutional context plays in defining the outcome of learning processes in Swedish water management institutions and hence highlights previously poorly elaborated political aspects of learning processes and institutional change in social-ecological systems.

The United Nations and Climate Change: Legal and Policy Developments

NASA Astrophysics Data System (ADS)

Bunn, Isabella D.

2009-07-01

The Secretary-General of the United Nations, Ban Ki-moon, has declared that climate change is "the defining challenge of our times." Climate change trends indicate increasingly severe negative impacts on the majority of countries, with disproportionate effects on poor and vulnerable populations. The scientific reports of the Intergovernmental Panel on Climate Change (IPCC), as well as the negotiations under the UN Framework Convention on Climate Change (UNFCCC), have placed the issue on the forefront of the international agenda. This article examines how climate change is shaping legal and policy developments in five key areas of UN responsibility: international law, humanitarian affairs, human rights, development, and peace and security. It concludes with some observations about high-level efforts to coordinate the response of multilateral institutions, the changing stance of the US government, and the role of environmental protection in addressing the current global economic crisis.

A novel perivascular cell population in the zebrafish brain.

PubMed

Venero Galanternik, Marina; Castranova, Daniel; Gore, Aniket V; Blewett, Nathan H; Jung, Hyun Min; Stratman, Amber N; Kirby, Martha R; Iben, James; Miller, Mayumi F; Kawakami, Koichi; Maraia, Richard J; Weinstein, Brant M

2017-04-11

The blood-brain barrier is essential for the proper homeostasis and function of the CNS, but its mechanism of function is poorly understood. Perivascular cells surrounding brain blood vessels are thought to be important for blood-brain barrier establishment, but their roles are not well defined. Here, we describe a novel perivascular cell population closely associated with blood vessels on the zebrafish brain. Based on similarities in their morphology, location, and scavenger behavior, these cells appear to be the zebrafish equivalent of cells variably characterized as Fluorescent Granular Perithelial cells (FGPs), perivascular macrophages, or 'Mato Cells' in mammals. Despite their macrophage-like morphology and perivascular location, zebrafish FGPs appear molecularly most similar to lymphatic endothelium, and our imaging studies suggest that these cells emerge by differentiation from endothelium of the optic choroidal vascular plexus. Our findings provide the first report of a perivascular cell population in the brain derived from vascular endothelium.

Genes Important for Schizosaccharomyces pombe Meiosis Identified Through a Functional Genomics Screen

PubMed Central

Blyth, Julie; Makrantoni, Vasso; Barton, Rachael E.; Spanos, Christos; Rappsilber, Juri; Marston, Adele L.

2018-01-01

Meiosis is a specialized cell division that generates gametes, such as eggs and sperm. Errors in meiosis result in miscarriages and are the leading cause of birth defects; however, the molecular origins of these defects remain unknown. Studies in model organisms are beginning to identify the genes and pathways important for meiosis, but the parts list is still poorly defined. Here we present a comprehensive catalog of genes important for meiosis in the fission yeast, Schizosaccharomyces pombe. Our genome-wide functional screen surveyed all nonessential genes for roles in chromosome segregation and spore formation. Novel genes important at distinct stages of the meiotic chromosome segregation and differentiation program were identified. Preliminary characterization implicated three of these genes in centrosome/spindle pole body, centromere, and cohesion function. Our findings represent a near-complete parts list of genes important for meiosis in fission yeast, providing a valuable resource to advance our molecular understanding of meiosis. PMID:29259000

[Challenges and inputs of the gender perspective to the study of vector borne diseases].

PubMed

Arenas-Monreal, Luz; Piña-Pozas, Maricela; Gómez-Dantés, Héctor

2015-01-01

The analysis of social determinants and gender within the health-disease-care process is an imperative to understand the variables that define the vulnerability of populations, their exposure risks, the determinants of their care, and the organization and participation in prevention and control programs. Ecohealth incorporates the study of the social determinants and gender perspectives because the emergency of dengue, malaria and Chagas disease are bound to unplanned urbanization, deficient sanitary infrastructure, and poor housing conditions. Gender emerges as an explanatory element of the roles played by men and women in the different scenarios (domestic, communitarian and social) that shape exposure risks to vectors and offer a better perspective of success for the prevention, control and care strategies. The objective is to contribute to the understanding on the gender perspective in the analysis of health risks through a conceptual framework.

Deadly Flies, Poor Profits, and Veterinary Pharmaceuticals: Sustaining the Control of Sleeping Sickness in Uganda.

PubMed

Bardosh, Kevin Louis

2016-01-01

Efforts to control neglected tropical diseases have increasingly focused on questions of implementation. But how should we conceptualize the implementation process? Drawing on ethnographic fieldwork between 2010 and 2012, in this article I explore efforts by a small-scale public-private partnership to use private veterinarians to sustainably control zoonotic sleeping sickness in Uganda. With a fundamental tension between business incentives and vector control, I show how divergences in knowledge, power, values, and social norms shaped project implementation and community responses. Reflecting more widely on the relationships between project plans and local realities, I argue that these encounters reveal the heuristic value in approaching global health interventions as evolving 'social experiments.' This metaphor reveals the uncertainty inherent to dominant narratives and models, the role of available expertise in defining the limits of action, and the need for continuous adaption to synchronize with emergent social and institutional topographies.

Akt-mTORC1 signaling regulates Acly to integrate metabolic input to control of macrophage activation

PubMed Central

Covarrubias, Anthony J; Aksoylar, Halil Ibrahim; Yu, Jiujiu; Snyder, Nathaniel W; Worth, Andrew J; Iyer, Shankar S; Wang, Jiawei; Ben-Sahra, Issam; Byles, Vanessa; Polynne-Stapornkul, Tiffany; Espinosa, Erika C; Lamming, Dudley; Manning, Brendan D; Zhang, Yijing; Blair, Ian A; Horng, Tiffany

2016-01-01

Macrophage activation/polarization to distinct functional states is critically supported by metabolic shifts. How polarizing signals coordinate metabolic and functional reprogramming, and the potential implications for control of macrophage activation, remains poorly understood. Here we show that IL-4 signaling co-opts the Akt-mTORC1 pathway to regulate Acly, a key enzyme in Ac-CoA synthesis, leading to increased histone acetylation and M2 gene induction. Only a subset of M2 genes is controlled in this way, including those regulating cellular proliferation and chemokine production. Moreover, metabolic signals impinge on the Akt-mTORC1 axis for such control of M2 activation. We propose that Akt-mTORC1 signaling calibrates metabolic state to energetically demanding aspects of M2 activation, which may define a new role for metabolism in supporting macrophage activation. DOI: http://dx.doi.org/10.7554/eLife.11612.001 PMID:26894960

Welfare status, illness and subjective health definition.

PubMed Central

Prince, E O

1978-01-01

The self-defined health status of welfare recipients hospitalized for illness during the preceding year was compared to that of persons not on welfare but hospitalized for illness during the same period. Data were derived from a systematic probability sample of household residents of the Harlem Hospital inpatient district population surveyed July 1967-June 1970. Welfare recipient respondents were more likely to perceive their health as fair/poor than were persons not on welfare. This difference persisted when the data were analyzed by sex, age, reported levels and type of illness, hospital days and number of stays, and current usual activity; usual activity was a major explanatory variable but only partially accounted for the relationship. It has been hypothesized that in achievement-oriented societies, illness may be used as justification for a culturally-induced sense of personal failure to fulfill socially prescribed role obligations. The data are consistent with this hypothesis. PMID:686211

Computational consciousness: building a self-preserving organism.

PubMed

Barros, Allan Kardec

2010-01-01

Consciousness has been a subject of crescent interest among the neuroscience community. However, building machine models of it is quite challenging, as it involves many characteristics and properties of the human brain which are poorly defined or are very abstract. Here I propose to use information theory (IT) to give a mathematical framework to understand consciousness. For this reason, I used the term "computational". This work is grounded on some recent results on the use of IT to understand how the cortex codes information, where redundancy reduction plays a fundamental role. Basically, I propose a system, here called "organism", whose strategy is to extract the maximal amount of information from the environment in order to survive. To highlight the proposed framework, I show a simple organism composed of a single neuron which adapts itself to the outside dynamics by taking into account its internal state, whose perception is understood here to be related to "feelings".

The value of Autoimmune Syndrome Induced by Adjuvant (ASIA) - Shedding light on orphan diseases in autoimmunity.

PubMed

Segal, Yahel; Dahan, Shani; Sharif, Kassem; Bragazzi, Nicola Luigi; Watad, Abdulla; Amital, Howard

2018-05-01

Autoimmune Syndrome Induced by Adjuvant (ASIA) is a definition aimed to describe the common etiological process at the root of five clinical entities sharing similar symptomatology: macrophagic myofasciitis syndrome (MMF), Gulf War Syndrome (GWS), sick building syndrome (SBS), siliconosis, and post vaccination autoimmune phenomena. ASIA illustrates the role of environmental immune stimulating agents, or adjuvants, in the instigation of complex autoimmune reactions among individuals bearing a genetic preponderance for autoimmunity. The value of ASIA lies first in the acknowledgment it provides for patients suffering from these as yet ill-defined medical conditions. Equally important is the spotlight it sheds for further research of these poorly understood conditions sharing a common pathogenesis. In this article we elaborate on the significance of ASIA, review the current evidence in support of the syndrome, and address recent reservations raised regarding its validity. Copyright © 2018 Elsevier B.V. All rights reserved.

Conformational changes of the N-terminal part of Mason-Pfizer monkey virus p12 protein during multimerization

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

Knejzlik, Zdenek; Ulbrich, Pavel; Strohalm, Martin

2009-10-10

The Mason-Pfizer monkey virus is a prototype Betaretrovirus with the defining characteristic that it assembles spherical immature particles from Gag-related polyprotein precursors within the cytoplasm of the infected cell. It was shown previously that the N-terminal part of the Gag p12 domain (wt-Np12) is required for efficient assembly. However, the precise role for p12 in mediating Gag-Gag interaction is still poorly understood. In this study we employed detailed circular dichroism spectroscopy, electron microscopy and ultracentrifugation analyses of recombinant wt-Np12 prepared by in vitro transcription and translation. The wt-Np12 domain fragment forms fibrillar structures in a concentration-dependent manner. Assembly into fibersmore » is linked to a conformational transition from unfolded or another non-periodical state to alpha-helix during multimerization.« less

Hierarchy of stability factors in reverse shoulder arthroplasty.

PubMed

Gutiérrez, Sergio; Keller, Tony S; Levy, Jonathan C; Lee, William E; Luo, Zong-Ping

2008-03-01

Reverse shoulder arthroplasty is being used more frequently to treat irreparable rotator cuff tears in the presence of glenohumeral arthritis and instability. To date, however, design features and functions of reverse shoulder arthroplasty, which may be associated with subluxation and dislocation of these implants, have been poorly understood. We asked: (1) what is the hierarchy of importance of joint compressive force, prosthetic socket depth, and glenosphere size in relation to stability, and (2) is this hierarchy defined by underlying and theoretically predictable joint contact characteristics? We examined the intrinsic stability in terms of the force required to dislocate the humerosocket from the glenosphere of eight commercially available reverse shoulder arthroplasty devices. The hierarchy of factors was led by compressive force followed by socket depth; glenosphere size played a much lesser role in stability of the reverse shoulder arthroplasty device. Similar results were predicted by a mathematical model, suggesting the stability was determined primarily by compressive forces generated by muscles.

[Catastrophe hygiene, its contents and place in the federal surveillance service system in the protection of consumers' rights and human well-being].

PubMed

Shaposhnikov, A A; Lukicheva, T A

2005-01-01

In the past two decades, there has been an increase in the number of earthquakes, tidal waves, accidents at chemically dangerous enterprises, and other types of catastrophes, which have posed an emergency survival problem for society. The scientific development of this problem has given rise to a new area of preventive medicine--catastrophe hygiene that is designed to eliminate (reduce) the poor influence of emergency factors and to offer the suffered population safe conditions of accommodation and/or life, water supply, nutrition, and other elements of survival under these conditions. The paper defines the subject and objects of studies in catastrophe hygiene. It characterizes the value and role of this science in the organization and implementation of preventive measures to liquidate the medicosanitary consequences of emergencies, as well as the place of hygienic facilities and research institutes within the framework of the Russian emergency service.

Evidence synthesis and its role in evidence-based health care.

PubMed

Pearson, Alan

2014-12-01

The central role of evidence synthesis (or the systematic review of evidence) in evidence-based health care is often poorly understood. There are numerous examples in the literature of poorly conceived and/or executed systematic reviews and of a lack of awareness of the international standards developed by the international leaders in systematic reviews. The Cochrane Collaboration has played a critical global role in developing and refining systematic review methods in relation to evidence of effects and of diagnostic accuracy. Copyright © 2014 Elsevier Inc. All rights reserved.

Subjective but Not Actigraphy-Defined Sleep Predicts Next-Day Fatigue in Chronic Fatigue Syndrome: A Prospective Daily Diary Study

PubMed Central

Russell, Charlotte; Wearden, Alison J.; Fairclough, Gillian; Emsley, Richard A.; Kyle, Simon D.

2016-01-01

Study Objectives: This study aimed to (1) examine the relationship between subjective and actigraphy-defined sleep, and next-day fatigue in chronic fatigue syndrome (CFS); and (2) investigate the potential mediating role of negative mood on this relationship. We also sought to examine the effect of presleep arousal on perceptions of sleep. Methods: Twenty-seven adults meeting the Oxford criteria for CFS and self-identifying as experiencing sleep difficulties were recruited to take part in a prospective daily diary study, enabling symptom capture in real time over a 6-day period. A paper diary was used to record nightly subjective sleep and presleep arousal. Mood and fatigue symptoms were rated four times each day. Actigraphy was employed to provide objective estimations of sleep duration and continuity. Results: Multilevel modelling revealed that subjective sleep variables, namely sleep quality, efficiency, and perceiving sleep to be unrefreshing, predicted following-day fatigue levels, with poorer subjective sleep related to increased fatigue. Lower subjective sleep efficiency and perceiving sleep as unrefreshing predicted reduced variance in fatigue across the following day. Negative mood on waking partially mediated these relationships. Increased presleep cognitive and somatic arousal predicted self-reported poor sleep. Actigraphy-defined sleep, however, was not found to predict following-day fatigue. Conclusions: For the first time we show that nightly subjective sleep predicts next-day fatigue in CFS and identify important factors driving this relationship. Our data suggest that sleep specific interventions, targeting presleep arousal, perceptions of sleep and negative mood on waking, may improve fatigue in CFS. Citation: Russell C, Wearden AJ, Fairclough G, Emsley RA, Kyle SD. Subjective but not actigraphy-defined sleep predicts next-day fatigue in chronic fatigue syndrome: a prospective daily diary study. SLEEP 2016;39(4):937–944. PMID:26715232

Principal Leadership and Reading Specialist Role Understanding in the Era of Test-Based Accountability Policies

ERIC Educational Resources Information Center

Prezyna, Dolores Marie; Garrison, Mark J.; Lockte, Hilary A.; Gold, Carol P.

2017-01-01

This study investigates how the role of the reading specialist (RS) is defined and communicated by principals, and examines to what degree a common understanding of this role exists among teachers, building administrators and reading specialists. The principal's responsibility in defining and communicating role, and the effect these efforts have…

Region-specific role of water in collagen unwinding and assembly.

PubMed

Ravikumar, Krishnakumar M; Hwang, Wonmuk

2008-09-01

Conformational stability of the collagen triple helix affects its turnover and determines tissue homeostasis. Although it is known that the presence of imino acids (prolines or hydroxyprolines) confer stability to the molecule, little is known regarding the stability of the imino-poor region lacking imino acids, which plays a key role in collagen cleavage. In particular, there have been continuing debates about the role of water in collagen stability. We addressed these issues using molecular dynamics simulations on 30-residue long collagen triple helices, including a structure that has a biologically relevant 9-residue imino-poor region from type III collagen (PDB ID: 1BKV). A torsional map approach was used to characterize the conformational motion of the molecule that differ between imino-rich and imino-poor regions. At temperatures 300 K and above, unwinding initiates at a common cleavage site, the glycine-isoleucine bond in the imino-poor region. This provides a linkage between previous observations that unwinding of the imino-poor region is a requirement for collagenase cleavage, and that isolated collagen molecules are unstable at body temperature. We found that unwinding of the imino-poor region is controlled by dynamic water bridges between backbone atoms with average lifetimes on the order of a few picoseconds, as the degree of unwinding strongly correlated with the loss of water bridges, and unwinding could be either prevented or enhanced, respectively by enforcing or forbidding water bridge formation. While individual water bridges were short-lived in the imino-poor region, the hydration shell surrounding the entire molecule was stable even at 330 K. The diameter of the hydrated collagen including the first hydration shell was about 14 A, in good agreement with the experimentally measured inter-collagen distances. These results elucidate the general role of water in collagen turnover: water not only affects collagen cleavage by controlling its torsional motion, but it also forms a larger-scale lubrication layer mediating collagen self-assembly. 2008 Wiley-Liss, Inc.

The Specific Role of Inhibition in Reading Comprehension in Good and Poor Comprehenders

ERIC Educational Resources Information Center

Borella, Erika; Carretti, Barbara; Pelegrina, Santiago

2010-01-01

Difficulties in inhibitory processes have been shown to characterize the performance of poor comprehenders. However, the inhibitory inefficiency of poor comprehenders is most often assessed by their resistance to proactive interference, that is, the ability to suppress off-goal task information from working memory (WM). In two studies tasks…

The Affordable Housing Crisis: Residential Mobility of Poor Families and School Mobility of Poor Children.

ERIC Educational Resources Information Center

Crowley, Sheila

2003-01-01

Helping poor families increase their residential stability can have direct bearing on school stability and student academic achievement. Discusses the role of housing in child and family wellbeing; residential mobility and school performance; residential mobility and housing problems; housing affordability; (federal housing policy); homeownership;…

Hsp90 is an essential regulator of EphA2 receptor stability and signaling: Implications for cancer cell migration and metastasis

PubMed Central

Annamalai, Balasubramaniam; Liu, Xueguang; Gopal, Udhayakumar; Isaacs, Jennifer

2011-01-01

A subset of Eph receptors and their corresponding ligands are commonly expressed in tumor cells, where they mediate biological processes such as cell migration and adhesion, while their expression in endothelial cells promotes angiogenesis. In particular, the tumor-specific upregulation of EphA2 confers properties of increased cellular motility, invasiveness, tumor angiogenesis, and tumor progression, and its overexpression correlates with poor prognosis in several cancer types. The cellular chaperone Hsp90 also plays a significant role in regulating cell migration and angiogenesis, although the full repertoire of motility driving proteins dependent upon Hsp90 function remain poorly defined. We explored the hypothesis that Hsp90 may regulate the activity of EphA2 and examined the potential relationship between EphA2 receptor signaling and chaperone function. We demonstrate that geldanamycin (GA), an Hsp90 antagonist, dramatically destabilizes newly synthesized EphA2 protein and diminishes receptor levels in a proteasome-dependent pathway. In addition, GA treatment impairs EphA2 signaling, as evidenced by a decrease in ligand-dependent receptor phosphorylation and subsequent cell rounding. Therefore, Hsp90 exerts a dual role in regulating the stability of nascent EphA2 protein, and maintaining the signaling capacity of the mature receptor. Our findings also suggest that the GA-dependent mitigation of EphA2 signaling in receptor-overexpressing cancer cells may be sufficient to recapitulate the anti-motility effects of this drug. Finally, the identification of a pharmacologic approach to suppress EphA2 expression and signaling highlights the attractive possibility that Hsp90 inhibitors may have clinical utility in antagonizing EphA2-dependent tumorigenic progression. PMID:19567782

Neural networks underlying language and social cognition during self-other processing in Autism spectrum disorders.

PubMed

Kana, Rajesh K; Sartin, Emma B; Stevens, Carl; Deshpande, Hrishikesh D; Klein, Christopher; Klinger, Mark R; Klinger, Laura Grofer

2017-07-28

The social communication impairments defining autism spectrum disorders (ASD) may be built upon core deficits in perspective-taking, language processing, and self-other representation. Self-referential processing entails the ability to incorporate self-awareness, self-judgment, and self-memory in information processing. Very few studies have examined the neural bases of integrating self-other representation and semantic processing in individuals with ASD. The main objective of this functional MRI study is to examine the role of language and social brain networks in self-other processing in young adults with ASD. Nineteen high-functioning male adults with ASD and 19 age-sex-and-IQ-matched typically developing (TD) control participants made "yes" or "no" judgments of whether an adjective, presented visually, described them (self) or their favorite teacher (other). Both ASD and TD participants showed significantly increased activity in the medial prefrontal cortex (MPFC) during self and other processing relative to letter search. Analyses of group differences revealed significantly reduced activity in left inferior frontal gyrus (LIFG), and left inferior parietal lobule (LIPL) in ASD participants, relative to TD controls. ASD participants also showed significantly weaker functional connectivity of the anterior cingulate cortex (ACC) with several brain areas while processing self-related words. The LIFG and IPL are important regions functionally at the intersection of language and social roles; reduced recruitment of these regions in ASD participants may suggest poor level of semantic and social processing. In addition, poor connectivity of the ACC may suggest the difficulty in meeting the linguistic and social demands of this task in ASD. Overall, this study provides new evidence of the altered recruitment of the neural networks underlying language and social cognition in ASD. Published by Elsevier Ltd.

Right ventricular involution: What can we learn from nature's model of compensated hypertrophy?

PubMed

Bowen, Megan E; Liu, Xiaoqing; Sundwall, Peter M; Drakos, Stavros G; Li, Dean Y; Selzman, Craig H; McKellar, Stephen H

2018-05-01

Right ventricular (RV) failure (RVF) is a vexing problem facing patients with various disease processes and carries a high mortality. RVF is a poorly understood phenomenon with limited treatment options. In mammalian fetal circulation, the right ventricle is the systemic ventricle. In neonates, however, the left ventricle assumes that role and gradually thickens compared with the right ventricle. This process, known as right ventricular involution (RVI), is poorly understood. We sought to define the time course and identify mechanisms involved in RVI. Wild-type mice were bred and sacrificed on day of life (DOL) 1, 4, 8, 16, and 30 to evaluate left ventricular (LV) and RV wall thickness and apoptosis. A terminal deoxynucleotidyl transferase nick-end labeling assay and RNA sequencing were performed to measure changes during RVI. Morphometric analysis demonstrated the changes in RV and LV wall thickness occurring between DOL 1 and DOL 16 (RV:LV, 0.53:0.44; P = .03). In addition, apoptosis was most active early, with the highest percentage of apoptotic cells on DOL 1 (1.0%) and a significant decrease by DOL 30 (0.23%) (P = .02). Similarly, expression of the proapoptotic genes BCL2l11 and Pawr were increased at DOL 1, and the antiapoptotic genes Nol3 and Naip2 were significantly increased at DOL 30. RVI is a misnomer, but significant changes occur early (by DOL 16) in neonatal mouse hearts. Apoptosis plays a role in RVI, but whether manipulation of apoptotic pathways can prevent or reverse RVI is unknown and warrants further investigation. Copyright © 2017 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

Sonographic findings of hepatobiliary fascioliasis accompanied by extrahepatic expansion and ectopic lesions.

PubMed

Teke, Memik; Önder, Hakan; Çiçek, Mutalip; Hamidi, Cihad; Göya, Cemil; Çetinçakmak, Mehmet Güli; Hattapoğlu, Salih; Ülger, Burak Veli

2014-12-01

The aim of the study was to describe the sonographic findings of hepatobiliary fascioliasis with extrahepatic expansion and ectopic lesions. The study included 45 patients with fascioliasis. All diagnoses were confirmed via serologic enzyme-linked immunosorbent assays. Sonographic findings in the hepatobiliary system, extrahepatic expansion, and ectopic lesions were defined. The most common hepatic lesions were subcapsular localized, small, confluent, multiple hypoechoic nodules with poorly defined borders. We also detected ectopic lesion in 5 patients (11.1%) and live parasites in the gallbladder and bile duct in 11 (24.4%). The large spectrum of entities in the differential diagnosis of hepatobiliary fascioliasis may lead to misdiagnosis and incorrect treatment. However, the diagnosis can be made when the characteristic sonographic features are seen, such as heterogeneity of the liver with multiple poorly defined hypoechoic-isoechoic lesions and multiple echogenic nonshadowing particles in the gallbladder or common bile ducts. Nonetheless, the differential diagnosis of fascioliasis versus other hepatic lesions may still be difficult. In these situations, pathologic confirmation should be performed to exclude the possibility of malignancy. © 2013 by the American Institute of Ultrasound in Medicine.

European Measures of Poverty and "Social Exclusion": Material Deprivation, Consumption, and Life Satisfaction

ERIC Educational Resources Information Center

Gilbert, Neil

2009-01-01

The conventional view of poverty in the European Union countries is based on a relative measure, which defines all those with incomes below 60 percent of the median as poor. In the U.S., poverty is defined according to an absolute measure--the federal poverty line computed by the Census Bureau--which was $21,200 for a family of four in 2008…

An examination of how women and underrepresented racial/ethnic minorities experience barriers in biomedical research and medical programs

NASA Astrophysics Data System (ADS)

Chakraverty, Devasmita

Women in medicine and biomedical research often face challenges to their retention, promotion, and advancement to leadership positions (McPhillips et al., 2007); they take longer to advance their careers, tend to serve at less research-intensive institutions and have shorter tenures compared to their male colleagues (White, McDade, Yamagata, & Morahan, 2012). Additionally, Blacks and Hispanics are the two largest minority groups that are vastly underrepresented in medicine and biomedical research in the United States (AAMC, 2012; NSF, 2011). The purpose of this study is to examine specific barriers reported by students and post-degree professionals in the field through the following questions: 1. How do women who are either currently enrolled or graduated from biomedical research or medical programs define and make meaning of gender-roles as academic barriers? 2. How do underrepresented groups in medical schools and biomedical research institutions define and make meaning of the academic barriers they face and the challenges these barriers pose to their success as individuals in the program? These questions were qualitatively analyzed using 146 interviews from Project TrEMUR applying grounded theory. Reported gender-role barriers were explained using the "Condition-Process-Outcome" theoretical framework. About one-third of the females (across all three programs; majority White or Black between 25-35 years of age) reported gender-role barriers, mostly due to poor mentoring, time constraints, set expectations and institutional barriers. Certain barriers act as conditions, causing gender-role issues, and gender-role issues influence certain barriers that act as outcomes. Strategies to overcome barriers included interventions mostly at the institutional level (mentor support, proper specialty selection, selecting academia over medicine). Barrier analysis for the two largest URM groups indicated that, while Blacks most frequently reported racism, gender barriers, mentoring, and personal barriers, Hispanics most frequently reported economic barriers, language barriers, institutional and workplace environment barriers, and gender-role barriers. Examining barriers using the "Individual-Institutional" theoretical framework indicated that barriers do not occur in isolation, but due to an interaction between the individual and its institution. Additionally, the barriers of the two groups are qualitatively different and the "one size fits all" approach may not be suitable for interventions. Implications and recommendations were stated.

Targeting the Poor: Evidence from a Field Experiment in Indonesia

PubMed Central

Alatas, Vivi; Banerjee, Abhijit; Hanna, Rema; Olken, Benjamin A.; Tobias, Julia

2014-01-01

This paper reports an experiment in 640 Indonesian villages on three approaches to target the poor: proxy-means tests (PMT), where assets are used to predict consumption; community targeting, where villagers rank everyone from richest to poorest; and a hybrid. Defining poverty based on PPP$2 per-capita consumption, community targeting and the hybrid perform somewhat worse in identifying the poor than PMT, though not by enough to significantly affect poverty outcomes for a typical program. Elite capture does not explain these results. Instead, communities appear to apply a different concept of poverty. Consistent with this finding, community targeting results in higher satisfaction. PMID:25197099

Extending the time window for endovascular procedures according to collateral pial circulation.

PubMed

Ribo, Marc; Flores, Alan; Rubiera, Marta; Pagola, Jorge; Sargento-Freitas, Joao; Rodriguez-Luna, David; Coscojuela, Pilar; Maisterra, Olga; Piñeiro, Socorro; Romero, Francisco J; Alvarez-Sabin, Jose; Molina, Carlos A

2011-12-01

Good collateral pial circulation (CPC) predicts a favorable outcome in patients undergoing intra-arterial procedures. We aimed to determine if CPC status may be used to decide about pursuing recanalization efforts. Pial collateral score (0-5) was determined on initial angiogram. We considered good CPC when pial collateral score<3, defined total time of ischemia (TTI) as onset-to-recanalization time, and clinical improvement>4-point decline in admission-discharge National Institutes of Health Stroke Scale. We studied CPC in 61 patients (31 middle cerebral artery, 30 internal carotid artery). Good CPC patients (n=21 [34%]) had lower discharge National Institutes of Health Stroke Scale score (7 versus 21; P=0.02) and smaller infarcts (56 mL versus 238 mL; P<0.001). In poor CPC patients, a receiver operating characteristic curve defined a TTI cutoff point<300 minutes (sensitivity 67%, specificity 75%) that better predicted clinical improvement (TTI<300: 66.7% versus TTI>300: 25%; P=0.05). For good CPC patients, no temporal cutoff point could be defined. Although clinical improvement was similar for patients recanalizing within 300 minutes (poor CPC: 60% versus good CPC: 85.7%; P=0.35), the likelihood of clinical improvement was 3-fold higher after 300 minutes only in good CPC patients (23.1% versus 90.1%; P=0.01). Similarly, infarct volume was reduced 7-fold in good as compared with poor CPC patients only when TTI>300 minutes (TTI<300: poor CPC: 145 mL versus good CPC: 93 mL; P=0.56 and TTI>300: poor CPC: 217 mL versus good CPC: 33 mL; P<0.01). After adjusting for age and baseline National Institutes of Health Stroke Scale score, TTI<300 emerged as an independent predictor of clinical improvement in poor CPC patients (OR, 6.6; 95% CI, 1.01-44.3; P=0.05) but not in good CPC patients. In a logistic regression, good CPC independently predicted clinical improvement after adjusting for TTI, admission National Institutes of Health Stroke Scale score, and age (OR, 12.5; 95% CI, 1.6-74.8; P=0.016). Good CPC predicts better clinical response to intra-arterial treatment beyond 5 hours from onset. In patients with stroke receiving endovascular treatment, identification of good CPC may help physicians when considering pursuing recanalization efforts in late time windows.

Rating the methodological quality in systematic reviews of studies on measurement properties: a scoring system for the COSMIN checklist.

PubMed

Terwee, Caroline B; Mokkink, Lidwine B; Knol, Dirk L; Ostelo, Raymond W J G; Bouter, Lex M; de Vet, Henrica C W

2012-05-01

The COSMIN checklist is a standardized tool for assessing the methodological quality of studies on measurement properties. It contains 9 boxes, each dealing with one measurement property, with 5-18 items per box about design aspects and statistical methods. Our aim was to develop a scoring system for the COSMIN checklist to calculate quality scores per measurement property when using the checklist in systematic reviews of measurement properties. The scoring system was developed based on discussions among experts and testing of the scoring system on 46 articles from a systematic review. Four response options were defined for each COSMIN item (excellent, good, fair, and poor). A quality score per measurement property is obtained by taking the lowest rating of any item in a box ("worst score counts"). Specific criteria for excellent, good, fair, and poor quality for each COSMIN item are described. In defining the criteria, the "worst score counts" algorithm was taken into consideration. This means that only fatal flaws were defined as poor quality. The scores of the 46 articles show how the scoring system can be used to provide an overview of the methodological quality of studies included in a systematic review of measurement properties. Based on experience in testing this scoring system on 46 articles, the COSMIN checklist with the proposed scoring system seems to be a useful tool for assessing the methodological quality of studies included in systematic reviews of measurement properties.

Using the ovarian sensitivity index to define poor, normal, and high response after controlled ovarian hyperstimulation in the long gonadotropin-releasing hormone-agonist protocol: suggestions for a new principle to solve an old problem.

PubMed

Huber, Malin; Hadziosmanovic, Nermin; Berglund, Lars; Holte, Jan

2013-11-01

To explore the utility of using the ratio between oocyte yield and total dose of FSH, i.e., the ovarian sensitivity index (OSI), to define ovarian response patterns. Retrospective cross-sectional study. University-affiliated private center. The entire unselected cohort of 7,520 IVF/intracytoplasmic sperm injection treatments (oocyte pick-ups [OPUs]) during an 8-year period (long GnRH agonist-recombinant FSH protocol). None. The distribution of the OSI (oocytes recovered × 1,000/total dose of FSH), the cutoff levels for poor and high response, set at ±1 SD, and the relationship between OSI and treatment outcome. OSI showed a log-normal distribution with cutoff levels for poor and high response at 1.697/IU and 10.07/IU, respectively. A nomogram is presented. Live-birth rates per OPU were 10.5 ± 0.1%, 26.9 ± 0.6%, and 36.0 ± 1.4% for poor, normal, and high response treatments, respectively. The predictive power (C-statistic) for OSI to predict live birth was superior to that of oocyte yield. The OSI improves the definition of ovarian response patterns because it takes into account the degree of stimulation. The nomogram presents evidence-based cutoff levels for poor, normal, and high response and could be used for unifying study designs involving ovarian response patterns. Copyright © 2013 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Evidence for an Overlapping Role of CLOCK and NPAS2 Transcription Factors in Liver Circadian Oscillators▿

PubMed Central

Bertolucci, Cristiano; Cavallari, Nicola; Colognesi, Ilaria; Aguzzi, Jacopo; Chen, Zheng; Caruso, Pierpaolo; Foá, Augusto; Tosini, Gianluca; Bernardi, Francesco; Pinotti, Mirko

2008-01-01

The mechanisms underlying the circadian control of gene expression in peripheral tissues and influencing many biological pathways are poorly defined. Factor VII (FVII), the protease triggering blood coagulation, represents a valuable model to address this issue in liver since its plasma levels oscillate in a circadian manner and its promoter contains E-boxes, which are putative DNA-binding sites for CLOCK-BMAL1 and NPAS2-BMAL1 heterodimers and hallmarks of circadian regulation. The peaks of FVII mRNA levels in livers of wild-type mice preceded those in plasma, indicating a transcriptional regulation, and were abolished in Clock−/−; Npas2−/− mice, thus demonstrating a role for CLOCK and NPAS2 circadian transcription factors. The investigation of Npas2−/− and ClockΔ19/Δ19 mice, which express functionally defective heterodimers, revealed robust rhythms of FVII expression in both animal models, suggesting a redundant role for NPAS2 and CLOCK. The molecular bases of these observations were established through reporter gene assays. FVII transactivation activities of the NPAS2-BMAL1 and CLOCK-BMAL1 heterodimers were (i) comparable (a fourfold increase), (ii) dampened by the negative circadian regulators PER2 and CRY1, and (iii) abolished upon E-box mutagenesis. Our data provide the first evidence in peripheral oscillators for an overlapping role of CLOCK and NPAS2 in the regulation of circadianly controlled genes. PMID:18316400

Knocking-out matrix metalloproteinase-13 exacerbates rotator cuff muscle fatty infiltration.

PubMed

Liu, Xuhui; Ravishankar, Bharat; Ning, Anne; Liu, Mengyao; Kim, Hubert T; Feeley, Brian T

2017-01-01

Rotator cuff (RC) tears are common tendon injuries. Clinically, both muscle atrophy and fatty infiltration have generally been attributed to poor functional outcomes. Matrix metalloproteinase-13 plays a crucial role in extracellular matrix remodeling in many physiological and pathological processes. Nevertheless, its role in rotator cuff muscle atrophy and fatty infiltration remains unknown. The purpose of this study is to define the functional role of MMP-13 in rotator cuff muscle atrophy and fatty infiltration using a mouse RC tears model. Unilateral complete supraspinatus and infraspinatus tendon transection and suprascapular nerve transection was performed on nine of MMP-13 (-/-) knockout and nine of MMP-13 (+/+) wildtype mice at 3 months old. Mice were sacrificed 6 weeks after surgery. Supraspinatus (SS) and infraspinatus (IS) muscles were harvested for histology and gene expression analysis with RT-PCR. Six weeks after RC surgery, no significant difference in muscle atrophy and fibrosis between MMP-13 knockout and wild type mice was observed. However, there was a significant increase in the amount of fatty infiltration in MMP-13 knockout mice compared to the wild types. Muscles from MMP-13 knockout mice have significantly higher expression of fatty infiltration related genes. Results from this study suggest that MMP-13 plays a crucial role in rotator cuff muscle fatty degeneration. This novel finding suggests a new molecular mechanism that governs RC muscle FI and MMP-13 may serve as a target for therapeutics to treat muscle FI after RC tears.

Pathogenesis and pathophysiology of yellow fever.

PubMed

Monath, Thomas P; Barrett, Alan D

2003-01-01

It will be apparent to the reader that there is much to learn about the pathogenesis of YF. The role of specific genes and molecular determinants of neurotropism and viscerotropism has been defined only partially. The availability of infectious clones and a small animal (hamster) model should allow dissection of virulence factors, which can then be tested in the more difficult monkey model. The marked differences between wild-type YF strains should be evaluated by evaluating the relationships between virulence and genome sequence. The role of cytokine dysregulation and endothelial injury in YF will be elucidated as access to patients and of patients to more sophisticated medical care improves. The number of cases of YF in unvaccinated travelers hospitalized after return from the tropics has unfortunately increased, but such cases afford unique opportunities to study the pathogenesis of renal failure, coagulopathy, vascular instability, and shock, as well as new treatment modalities. At the cellular level, there are also important opportunities for research on YF virus-cell receptor interactions, the control of apoptotic cell death, and the predilection for cells of the midzone of the liver lobule. The role of dendritic cells in the early stage of YF infection is deserving of study. Finally, the role of the immune response to infection, particularly cellular immunity, is poorly characterized, and the suggestion that immune clearance may aggravate the condition of the host during the period of intoxication should be evaluated in appropriate animal models.

Conditional knockdown of BCL2A1 reveals rate-limiting roles in BCR-dependent B-cell survival

PubMed Central

Sochalska, M; Ottina, E; Tuzlak, S; Herzog, S; Herold, M; Villunger, A

2016-01-01

Bcl2 family proteins control mitochondrial apoptosis and its members exert critical cell type and differentiation stage-specific functions, acting as barriers against autoimmunity or transformation. Anti-apoptotic Bcl2a1/Bfl1/A1 is frequently deregulated in different types of blood cancers in humans but its physiological role is poorly understood as quadruplication of the Bcl2a1 gene locus in mice hampers conventional gene targeting strategies. Transgenic overexpression of A1, deletion of the A1-a paralogue or constitutive knockdown in the hematopoietic compartment of mice by RNAi suggested rate-limiting roles in lymphocyte development, granulopoiesis and mast cell activation. Here we report on the consequences of conditional knockdown of A1 protein expression using a reverse transactivator (rtTA)-driven approach that highlights a critical role for this Bcl2 family member in the maintenance of mature B-cell homeostasis. Furthermore, we define the A1/Bim (Bcl-2 interacting mediator of cell death) axis as a target of key kinases mediating B-cell receptor (BCR)-dependent survival signals, such as, spleen tyrosine kinase (Syk) and Brutons tyrosine kinase (Btk). As such, A1 represents a putative target for the treatment of B-cell-related pathologies depending on hyperactivation of BCR-emanating survival signals and loss of A1 expression accounts, in part, for the pro-apoptotic effects of Syk- or Btk inhibitors that rely on the ‘BH3-only' protein Bim for cell killing. PMID:26450454

Factors associated with persistent poorly controlled diabetes mellitus: clues to improving management in patients with resistant poor control.

PubMed

Crowley, Matthew J; Holleman, Rob; Klamerus, Mandi L; Bosworth, Hayden B; Edelman, David; Heisler, Michele

2014-12-01

Patients with persistent poorly controlled diabetes mellitus (PPDM), defined as an uninterrupted hemoglobin A1c >8.0% for ≥1 year despite standard care, are at high risk for complications. Additional research to define patient factors associated with PPDM could suggest barriers to improvement in this group and inform the development of targeted strategies to address these patients' resistant diabetes. We analyzed patients with type 2 diabetes from a multi-site randomized trial. We characterized patients with PPDM relative to other patients using detailed survey data and multivariable modeling. Of 963 patients, 118 (12%) had PPDM, 265 (28%) were intermittently poorly controlled, and 580 (60%) were well-controlled. Patients with PPDM had younger age, earlier diabetes diagnosis, insulin use, higher antihypertensive burden, higher low-density lipoprotein cholesterol, and lower statin use relative to well-controlled patients. Among patients with objective adherence data (Veterans Affairs patients), a larger oral diabetes medication refill gap was associated with PPDM. Strategies are needed to target-specific barriers to improvement among patients whose diabetes is resistant to standard diabetes care. Our data suggest that strategies for targeting PPDM should accommodate younger patients' lifestyles, include medication management for insulin titration and comorbid disease conditions, and address barriers to self-management adherence. © The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Serotonin 6 receptor controls Alzheimer's disease and depression.

PubMed

Yun, Hyung-Mun; Park, Kyung-Ran; Kim, Eun-Cheol; Kim, Sanghyeon; Hong, Jin Tae

2015-09-29

Alzheimer's disease (AD) and depression in late life are one of the most severe health problems in the world disorders. Serotonin 6 receptor (5-HT6R) has caused much interest for potential roles in AD and depression. However, a causative role of perturbed 5-HT6R function between two diseases was poorly defined. In the present study, we found that a 5-HT6R antagonist, SB271036 rescued memory impairment by attenuating the generation of Aβ via the inhibition of γ-secretase activity and the inactivation of astrocytes and microglia in the AD mouse model. It was found that the reduction of serotonin level was significantly recovered by SB271036, which was mediated by an indirect regulation of serotonergic neurons via GABA. Selective serotonin reuptake inhibitor (SSRI), fluoxetine significantly improved cognitive impairment and behavioral changes. In human brain of depression patients, we then identified the potential genes, amyloid beta (A4) precursor protein-binding, family A, member 2 (APBA2), well known AD modulators by integrating datasets from neuropathology, microarray, and RNA seq. studies with correlation analysis tools. And also, it was demonstrated in mouse models and patients of AD. These data indicate functional network of 5-HT6R between AD and depression.

Lamins in the nuclear interior - life outside the lamina.

PubMed

Naetar, Nana; Ferraioli, Simona; Foisner, Roland

2017-07-01

Nuclear lamins are components of the peripheral lamina that define the mechanical properties of nuclei and tether heterochromatin to the periphery. A-type lamins localize also to the nuclear interior, but the regulation and specific functions of this nucleoplasmic lamin pool are poorly understood. In this Commentary, we summarize known pathways that are potentially involved in the localization and dynamic behavior of intranuclear lamins, including their post-translational modifications and interactions with nucleoplasmic proteins, such as lamina-associated polypeptide 2α (LAP2α; encoded by TMPO ). In addition, new data suggest that lamins in the nuclear interior have an important role in chromatin regulation and gene expression through dynamic binding to both hetero- and euchromatic genomic regions and promoter subdomains, thereby affecting epigenetic pathways and chromatin accessibility. Nucleoplasmic lamins also have a role in spatial chromatin organization and may be involved in mechanosignaling. In view of this newly emerging concept, we propose that the previously reported cellular phenotypes in lamin-linked diseases are, at least in part, rooted in an impaired regulation and/or function of the nucleoplasmic lamin A/C pool. © 2017. Published by The Company of Biologists Ltd.

An oxygen-insensitive Hif-3α isoform inhibits Wnt signaling by destabilizing the nuclear β-catenin complex.

PubMed

Zhang, Peng; Bai, Yan; Lu, Ling; Li, Yun; Duan, Cunming

2016-01-14

Hypoxia-inducible factors (HIFs), while best known for their roles in the hypoxic response, have oxygen-independent roles in early development with poorly defined mechanisms. Here, we report a novel Hif-3α variant, Hif-3α2, in zebrafish. Hif-3α2 lacks the bHLH, PAS, PAC, and ODD domains, and is expressed in embryonic and adult tissues independently of oxygen availability. Hif-3α2 is a nuclear protein with significant hypoxia response element (HRE)-dependent transcriptional activity. Hif-3α2 overexpression not only decreases embryonic growth and developmental timing but also causes left-right asymmetry defects. Genetic deletion of Hif-3α2 by CRISPR/Cas9 genome editing increases, while Hif-3α2 overexpression decreases, Wnt/β-catenin signaling. This action is independent of its HRE-dependent transcriptional activity. Mechanistically, Hif-3α2 binds to β-catenin and destabilizes the nuclear β-catenin complex. This mechanism is distinct from GSK3β-mediated β-catenin degradation and is conserved in humans. These findings provide new insights into the oxygen-independent actions of HIFs and uncover a novel mechanism regulating Wnt/β-catenin signaling.

Ask not what your technician can do for you-ask what you can do for your technician.

PubMed

Ganderton, L

2018-04-27

Historically, the vital roles played by technicians in Higher Education have had little recognition. Job opportunities are often overlooked by those who have no working knowledge of such organisations and poorly defined career pathways mean that it may not be a first choice for well-qualified, ambitious individuals. With just over a third of all Higher Education technicians in the UK now due to retire in the next 10 to 15 years, fundamental changes are needed, both to attract large numbers of people into vacant roles and to retain current technical staff.National initiatives, founded and driven by charitable and professional bodies, are currently working to address the issues of technicians within Higher Education. Organisations have been urged to take action or face potential recruitment difficulties and skills gaps over the coming years. In light of these national campaigns, institutions across the UK are beginning to develop proper structured career pathways, provide professional development and improve recognition for the work of their technical workforce. Whilst these are encouraging signs, only time will tell if enough has been done to raise both the profile and appeal of a technical career in Higher Education.

Sports physicians, ethics and antidoping governance: between assistance and negligence.

PubMed

Dikic, Nenad; McNamee, Michael; Günter, Heinz; Markovic, Snezana Samardzic; Vajgic, Bojan

2013-07-01

Recent positive doping cases and a series of mistakes of medical doctors of the International Federation of Basketball have reopened the debate about the role of medical doctor in elite sport. This study shows that some sports physicians involved in recent positive doping cases are insufficiently aware of the nuances of doping regulations and, most importantly, of the list of prohibited substances. Moreover, several team doctors are shown to have exercised poor judgement in relation to these matters with the consequence that athletes are punished for doping offences on the basis of doctors' negligence. In such circumstances, athletes' rights are jeopardised by a failure of the duty of care that (sports) physicians owe their athlete patients. We argue that, with respect to the World Anti Doping Code, antidoping governance fails to define, with sufficient clarity, the role of medical doctors. There is a need for a new approach emphasising urgent educational and training of medical doctors in this domain, which should be considered prior to the revision of the next World Anti Doping Code in 2013 in order to better regulate doctor's conduct especially in relation to professional errors, whether negligent or intentional.

Silencing microRNA-143 protects the integrity of the blood-brain barrier: implications for methamphetamine abuse

PubMed Central

Bai, Ying; Zhang, Yuan; Hua, Jun; Yang, Xiangyu; Zhang, Xiaotian; Duan, Ming; Zhu, Xinjian; Huang, Wenhui; Chao, Jie; Zhou, Rongbin; Hu, Gang; Yao, Honghong

2016-01-01

MicroRNA-143 (miR-143) plays a critical role in various cellular processes; however, the role of miR-143 in the maintenance of blood-brain barrier (BBB) integrity remains poorly defined. Silencing miR-143 in a genetic animal model or via an anti-miR-143 lentivirus prevented the BBB damage induced by methamphetamine. miR-143, which targets p53 unregulated modulator of apoptosis (PUMA), increased the permeability of human brain endothelial cells and concomitantly decreased the expression of tight junction proteins (TJPs). Silencing miR-143 increased the expression of TJPs and protected the BBB integrity against the effects of methamphetamine treatment. PUMA overexpression increased the TJP expression through a mechanism that involved the NF-κB and p53 transcription factor pathways. Mechanistically, methamphetamine mediated up-regulation of miR-143 via sigma-1 receptor with sequential activation of the mitogen-activated protein kinase (MAPK) and phosphatidylinositol-3′ kinase (PI3K)/Akt and STAT3 pathways. These results indicated that silencing miR-143 could provide a novel therapeutic strategy for BBB damage-related vascular dysfunction. PMID:27767041

The Clinical Features and Surgical Outcomes of Spinal Cord Tanycytic Ependymomas: A Report of 40 Cases.

PubMed

Tao, Xiaogang; Hou, Zonggang; Hao, Shuyu; Zhang, Qi; Wu, Zhen; Zhang, Junting; Liu, Baiyun

2017-10-01

Spinal cord tanycytic ependymomas (TEs) rarely are reported because of extremely low incidence. Understanding of this disease is therefore poor. The aim of this study was to analyze the incidence and clinical, radiologic, pathologic, and prognostic features of spinal cord TEs. Approximately 4000 spinal cord tumors were resected surgically in Beijing Tiantan Hospital between April 2009 and May 2016. We identified all cases of pathologically proved TEs among these patients. TEs accounted for approximately 1% of spinal cord tumors (40 of an estimated 4000). Patients with TE were a mean age of 40.0 years and had no significant sex preference (21 male and 19 female). The median diameter of the maximal tumor was 54.2 mm (range, 16-153 mm). The mean preoperative Japanese Orthopedic Association (JOA) score was 13.0. Radiologically, 47.5% (19/40) cases showed poorly defined tumor border, and 40% (16/40) of them showed preoperative syringomyelia. Gross total resection was achieved in 30 cases, subtotal resection in 8, and partial resection in 2. At the time of discharge, JOA score and neurologic function showed improvement in 26 cases (65%), no change in 12 cases (30%), and worsening in 2 cases (5%). At a median follow-up of 43 months (range, 7-101 months), 1- and 5-year progression-free survival rates were 100.0% and 97.5%, respectively. Only one patient had tumor recurrence which was found 30 months after surgery. No patient died of tumor recurrence. At the latest follow-up, JOA score showed improvement in 30 cases (75%), no change in 8 cases (20%), and worsening in 2 cases (5%). Univariate analysis revealed that tumor size and preoperative JOA score were significantly associated with the short-term outcomes. Meanwhile, age ≥40 years, tumor size ≥50 mm, non-gross total resection, and preoperative JOA score <14 were significantly associated with an increased risk of worsened long-term outcomes. Poorly defined tumor border and preoperative JOA score <14 significantly limited the extent of tumor resection. Spinal cord TE is a rare subtype of ependymomas with low recurrence. Long-term survival can be expected, although poorly defined tumor border is an independent predictor of long-term outcomes. Microsurgical treatment of spinal cord TEs remains a formidable challenge due to the poorly defined border and critical neurovascular structures encasement. It is unnecessary for radical tumor resection at the cost of severe neurologic deficits. Copyright © 2017 Elsevier Inc. All rights reserved.

Re-defining the Unique Roles for Eosinophils in Allergic Respiratory Inflammation

PubMed Central

Jacobsen, Elizabeth A.; Lee, Nancy A.; Lee, James J.

2014-01-01

Summary The role of eosinophils in the progression and resolution of allergic respiratory inflammation is poorly defined despite the commonality of their presence and in some cases their use as a biomarker for disease severity and/or symptom control. However, this ambiguity belies the wealth of insights that have recently been gained through the use of eosinophil-deficient/attenuated strains of mice that have demonstrated novel immunoregulatory and remodeling/repair functions for these cells in the lung following allergen provocation. Specifically, studies of eosinophil-deficient mice suggest that eosinophils contribute to events occurring in the lungs following allergen provocation at several key moments: (i) The initiating phase of events leading to Th2-polarized pulmonary inflammation, (ii) The suppression Th1/Th17 pathways in lung draining lymph nodes, (iii) The recruitment of effector Th2 T cells to the lung, and finally (iv) Mechanisms of inflammatory resolution that re-establish pulmonary homeostasis. These suggested functions have recently been confirmed and expanded upon using allergen provocation of an inducible eosinophil-deficient strain of mice (iPHIL) that demonstrated an eosinophil-dependent mechanism(s) leading to Th2 dominated immune responses in the presence of eosinophils in contrast to neutrophilic as well as mixed Th1/Th17/Th2 variant phenotypes in the absence of eosinophils. These findings highlighted that eosinophils are not exclusively downstream mediators controlled by T cells, dendritic cells (DC), and/or innate lymphocytic cells (ILC2). Instead, eosinophils appear to be more aptly described as significant contributors in complex interrelated pathways that lead to pulmonary inflammation and subsequently promote resolution and the re-establishment of homeostatic baseline. In this review we summarize and put into the context the evolving hypotheses that are now expanding our understanding of the roles eosinophils likely have in the lung following allergen provocation. PMID:24961290

Multi-institutional evaluation of the prognostic significance of EZH2 expression in high-grade upper tract urothelial carcinoma.

PubMed

Singla, Nirmish; Krabbe, Laura-Maria; Aydin, Ahmet M; Panwar, Vandana; Woldu, Solomon L; Freifeld, Yuval; Wood, Christopher G; Karam, Jose A; Weizer, Alon Z; Raman, Jay D; Remzi, Mesut; Rioux-Leclercq, Nathalie; Haitel, Andrea; Roscigno, Marco; Bolenz, Christian; Bensalah, Karim; Sagalowsky, Arthur I; Shariat, Shahrokh F; Lotan, Yair; Bagrodia, Aditya; Kapur, Payal; Margulis, Vitaly

2018-07-01

Enhancer of zeste homolog 2 is a methyltransferase encoded by the EZH2 gene, whose role in upper tract urothelial carcinoma (UTUC) is poorly understood. We sought to evaluate the prognostic value of EZH2 expression in UTUC. We reviewed a multi-institutional cohort of patients who underwent radical nephroureterectomy for high-grade UTUC from 1990 to 2008. Immunohistochemistry for EZH2 was performed on tissue microarrays. Percentage of staining was evaluated, and the discriminative value of EZH2 was tested, with EZH2 positivity defined as>20% staining present. Clinicopathologic characteristics and oncologic outcomes (recurrence-free (RFS), cancer-specific (CSS), and overall survival (OS)) were compared, stratified by EZH2 positivity. The prognostic role of EZH2 was assessed using Kaplan-Meier, univariate (UVA), and multivariate (MVA) Cox regression analyses. Significance was defined for P<0.05. A total of 376 patients were included for analysis, with median follow-up 36.0 months. Overall, 78 (20.7%) were EZH2-positive. EZH2 expression was more often associated with ureteral location, lymphovascular invasion, sessile architecture, necrosis, and concomitant carcinoma in situ. On UVA, increased EZH2 expression was a significant predictor for inferior RFS (HR 1.63, P = 0.033), CSS (HR 2.03, P = 0.003), and OS (HR 2.11, P<0.001). On MVA EZH2 remained a significant predictor of worse CSS (HR 1.99 [95% CI: 1.21-3.27], P = 0.007) and OS (HR 1.54 [95% CI: 1.06-2.24], P = 0.024), while significance was lost for RFS. Increased EZH2 expression is associated with adverse pathologic features and inferior oncologic outcomes in patients with high-grade UTUC. The role of EZH2 biology in UTUC pathogenesis remains to be further elucidated. Copyright © 2018 Elsevier Inc. All rights reserved.

Hepatitis C Virus Proteins Interact with the Endosomal Sorting Complex Required for Transport (ESCRT) Machinery via Ubiquitination To Facilitate Viral Envelopment.

PubMed

Barouch-Bentov, Rina; Neveu, Gregory; Xiao, Fei; Beer, Melanie; Bekerman, Elena; Schor, Stanford; Campbell, Joseph; Boonyaratanakornkit, Jim; Lindenbach, Brett; Lu, Albert; Jacob, Yves; Einav, Shirit

2016-11-01

Enveloped viruses commonly utilize late-domain motifs, sometimes cooperatively with ubiquitin, to hijack the endosomal sorting complex required for transport (ESCRT) machinery for budding at the plasma membrane. However, the mechanisms underlying budding of viruses lacking defined late-domain motifs and budding into intracellular compartments are poorly characterized. Here, we map a network of hepatitis C virus (HCV) protein interactions with the ESCRT machinery using a mammalian-cell-based protein interaction screen and reveal nine novel interactions. We identify HRS (hepatocyte growth factor-regulated tyrosine kinase substrate), an ESCRT-0 complex component, as an important entry point for HCV into the ESCRT pathway and validate its interactions with the HCV nonstructural (NS) proteins NS2 and NS5A in HCV-infected cells. Infectivity assays indicate that HRS is an important factor for efficient HCV assembly. Specifically, by integrating capsid oligomerization assays, biophysical analysis of intracellular viral particles by continuous gradient centrifugations, proteolytic digestion protection, and RNase digestion protection assays, we show that HCV co-opts HRS to mediate a late assembly step, namely, envelopment. In the absence of defined late-domain motifs, K63-linked polyubiquitinated lysine residues in the HCV NS2 protein bind the HRS ubiquitin-interacting motif to facilitate assembly. Finally, ESCRT-III and VPS/VTA1 components are also recruited by HCV proteins to mediate assembly. These data uncover involvement of ESCRT proteins in intracellular budding of a virus lacking defined late-domain motifs and a novel mechanism by which HCV gains entry into the ESCRT network, with potential implications for other viruses. Viruses commonly bud at the plasma membrane by recruiting the host ESCRT machinery via conserved motifs termed late domains. The mechanism by which some viruses, such as HCV, bud intracellularly is, however, poorly characterized. Moreover, whether envelopment of HCV and other viruses lacking defined late domains is ESCRT mediated and, if so, what the entry points into the ESCRT pathway are remain unknown. Here, we report the interaction network of HCV with the ESCRT machinery and a critical role for HRS, an ESCRT-0 complex component, in HCV envelopment. Viral protein ubiquitination was discovered to be a signal for HRS binding and HCV assembly, thereby functionally compensating for the absence of late domains. These findings characterize how a virus lacking defined late domains co-opts ESCRT to bud intracellularly. Since the ESCRT machinery is essential for the life cycle of multiple viruses, better understanding of this virus-host interplay may yield targets for broad-spectrum antiviral therapies. Copyright © 2016 Barouch-Bentov et al.

Solar origins of coronal mass ejections

NASA Technical Reports Server (NTRS)

Kahler, Stephen

1987-01-01

The large scale properties of coronal mass ejections (CMEs), such as morphology, leading edge speed, and angular width and position, have been cataloged for many events observed with coronagraphs on the Skylab, P-78, and SMM spacecraft. While considerable study has been devoted to the characteristics of the SMEs, their solar origins are still only poorly understood. Recent observational work has involved statistical associations of CMEs with flares and filament eruptions, and some evidence exists that the flare and eruptive-filament associated CMEs define two classes of events, with the former being generally more energetic. Nevertheless, it is found that eruptive-filament CMEs can at times be very energetic, giving rise to interplanetary shocks and energetic particle events. The size of the impulsive phase in a flare-associated CME seems to play no significant role in the size or speed of the CME, but the angular sizes of CMEs may correlate with the scale sizes of the 1-8 angstrom x-ray flares. At the present time, He 10830 angstrom observations should be useful in studying the late development of double-ribbon flares and transient coronal holes to yield insights into the CME aftermath. The recently available white-light synoptic maps may also prove fruitful in defining the coronal conditions giving rise to CMEs.

Defining consensus: a systematic review recommends methodologic criteria for reporting of Delphi studies.

PubMed

Diamond, Ivan R; Grant, Robert C; Feldman, Brian M; Pencharz, Paul B; Ling, Simon C; Moore, Aideen M; Wales, Paul W

2014-04-01

To investigate how consensus is operationalized in Delphi studies and to explore the role of consensus in determining the results of these studies. Systematic review of a random sample of 100 English language Delphi studies, from two large multidisciplinary databases [ISI Web of Science (Thompson Reuters, New York, NY) and Scopus (Elsevier, Amsterdam, NL)], published between 2000 and 2009. About 98 of the Delphi studies purported to assess consensus, although a definition for consensus was only provided in 72 of the studies (64 a priori). The most common definition for consensus was percent agreement (25 studies), with 75% being the median threshold to define consensus. Although the authors concluded in 86 of the studies that consensus was achieved, consensus was only specified a priori (with a threshold value) in 42 of these studies. Achievement of consensus was related to the decision to stop the Delphi study in only 23 studies, with 70 studies terminating after a specified number of rounds. Although consensus generally is felt to be of primary importance to the Delphi process, definitions of consensus vary widely and are poorly reported. Improved criteria for reporting of methods of Delphi studies are required. Copyright © 2014 Elsevier Inc. All rights reserved.

The Protein Interactome of Streptococcus pneumoniae and Bacterial Meta-interactomes Improve Function Predictions

PubMed Central

Rajagopala, S. V.; Blazie, S. M.; Parrish, J. R.; Khuri, S.; Finley, R. L.

2017-01-01

ABSTRACT The functions of roughly a third of all proteins in Streptococcus pneumoniae, a significant human-pathogenic bacterium, are unknown. Using a yeast two-hybrid approach, we have determined more than 2,000 novel protein interactions in this organism. We augmented this network with meta-interactome data that we defined as the pool of all interactions between evolutionarily conserved proteins in other bacteria. We found that such interactions significantly improved our ability to predict a protein’s function, allowing us to provide functional predictions for 299 S. pneumoniae proteins with previously unknown functions. IMPORTANCE Identification of protein interactions in bacterial species can help define the individual roles that proteins play in cellular pathways and pathogenesis. Very few protein interactions have been identified for the important human pathogen S. pneumoniae. We used an experimental approach to identify over 2,000 new protein interactions for S. pneumoniae, the most extensive interactome data for this bacterium to date. To predict protein function, we used our interactome data augmented with interactions from other closely related bacteria. The combination of the experimental data and meta-interactome data significantly improved the prediction results, allowing us to assign possible functions to a large number of poorly characterized proteins. PMID:28744484

Evidence from dynamic integrated proctography to redefine anismus.

PubMed

Roberts, J P; Womack, N R; Hallan, R I; Thorpe, A C; Williams, N S

1992-11-01

The role of anismus in the aetiology of defective rectal evacuation was investigated by dynamic integrated proctography in 20 controls and 71 constipated patients. Normal parameters were defined and compared between 21 constipated patients with poor evacuation during proctography (< 40 per cent of contrast evacuated; group 1) and 50 who evacuated fully (> 90 per cent of contrast evacuated; group 2). Nine patients in group 1 failed to evacuate. Radiological abnormalities of the rectum were recorded in all groups but obstructed evacuation was not observed. Anismus (defined as a recruitment of puborectalis electromyogram (EMG) activity of > 50 per cent) was significantly more common in group 1 than group 2 patients (14 of 21 versus 12 of 50, P < 0.01) and present in seven of those unable to evacuate. Eight patients in group 1 failed to raise intrarectal pressure > 50 cmH2O compared with two in group 2 (P < 0.001). Six patients in group 1 demonstrated both anismus and inability to raise intrarectal pressure, which may combine to cause defective evacuation. EMG recruitment alone is insufficient to diagnose anismus. Definition should be based on three criteria: demonstration of puborectalis EMG recruitment of > 50 per cent; evidence of an adequate level of intrarectal pressure (> 50 cmH2O) on straining; and presence of defective evacuation.

What is the veterinary professional identity? Preliminary findings from web-based continuing professional development in veterinary professionalism.

PubMed

Armitage-Chan, E; Maddison, J; May, S A

2016-03-26

Professionalism and professional skills are increasingly being incorporated into veterinary curricula; however, lack of clarity in defining veterinary professionalism presents a potential challenge for directing course outcomes that are of benefit to the veterinary professional. An online continuing education course in veterinary professionalism was designed to address a deficit in postgraduate support in this area; as part of this course, delegates of varying practice backgrounds participated in online discussions reflecting on the implications of professional skills for their clinical practice. The discussions surrounding the role of the veterinary professional and reflecting on strengths and weaknesses in professional skills were analysed using narrative methodology, which provided an understanding of the defining skills and attributes of the veterinary professional, from the perspectives of those involved (i.e. how vets understood their own career identity). The veterinary surgeon was understood to be an interprofessional team member, who makes clinical decisions in the face of competing stakeholder needs and works in a complex environment comprising multiple and diverse challenges (stress, high emotions, financial issues, work-life balance). It was identified that strategies for accepting fallibility, and those necessary for establishing reasonable expectations of professional behaviour and clinical ability, are poorly developed. British Veterinary Association.

Changes in the proportion of facility-based deliveries and related maternal health services among the poor in rural Jhang, Pakistan: results from a demand-side financing intervention.

PubMed

Agha, Sohail

2011-11-30

Demand-side financing projects are now being implemented in many developing countries, yet evidence showing that they reach the poor is scanty. A maternal health voucher scheme provided voucher-paid services in Jhang, a predominantly rural district of Pakistan, during 2010. A pre-test/post-test quasi-experimental design was used to assess the changes in the proportion of facility-based deliveries and related maternal health services among the poor. Household interviews were conducted with randomly selected women in the intervention and control union councils, before and after the intervention.A strong outreach model was used. Voucher promoters were given basic training in identification of poor women using the Poverty Scorecard for Pakistan, in the types of problems women could face during delivery, and in the promotion of antenatal care (ANC), institutional delivery and postnatal care (PNC). Voucher booklets valued at Rs. 4,000 ($48), including three ANC visits, a PNC visit, an institutional delivery, and a postnatal family planning visit, were sold for Rs. 100 ($1.2) to low-income women targeted by project outreach workers. Women suffering from complications were referred to emergency obstetric care services.Analysis was conducted at the bivariate and the multivariate levels. At the multivariate level, logistic regression analysis was conducted to determine whether the increase in institutional delivery was greater among poor women (defined for this study as women in the fourth or fifth quintiles) relative to non-poor women (defined for this study as women in the first quintile) in the intervention union councils compared to the control union councils. Bivariate analysis showed significant increases in the institutional delivery rate among women in the fourth or fifth wealth quintiles in the intervention union councils but no significant changes in this indicator among women in the same wealth quintiles in the control union councils. Multivariate analysis showed that the increase in institutional delivery among poor women relative to non-poor women was significantly greater in the intervention compared to the control union councils. Demand-side financing projects using vouchers can be an effective way of reducing inequities in institutional delivery.

Comparison of Satisfaction, Self-Confidence, and Engagement of Baccalaureate Nursing Students Using Defined Observational Roles and Expectations versus Traditional Role Assignments in High Fidelity Simulation and Debriefing

ERIC Educational Resources Information Center

Howard, Sheri

2017-01-01

The purpose of this study is to compare satisfaction, self-confidence, and engagement of baccalaureate nursing students using defined observational roles and expectations versus traditional observer role assignments in high fidelity simulation and debriefing and to evaluate student perceptions of these constructs. The NLN/Jeffries Simulation…

Sex-Role Stereotyping and Male-Female Character Distribution in Popular, Prestigious, and Sex-Role Defining Children's Literature from 1959 to 1972.

ERIC Educational Resources Information Center

Fraad, Harriet

This dissertation explored the extent and kind of sex-role stereotyping in popular, prestigious, and sex-role defining children's picture books printed between 1959 and 1972. The sample consisted of two categories of popular children's picture books, best-selling golden books and "New York Times" children's best-sellers, one category of Caldecott…

The role of indigenous health workers in promoting oral health during pregnancy: a scoping review.

PubMed

Villarosa, Ariana C; Villarosa, Amy R; Salamonson, Yenna; Ramjan, Lucie M; Sousa, Mariana S; Srinivas, Ravi; Jones, Nathan; George, Ajesh

2018-03-20

Early childhood caries is the most common chronic childhood disease worldwide. Australian Aboriginal and Torres Strait Islander children are twice more likely to develop dental decay, and contributing factors include poor maternal oral health and underutilisation of dental services. Globally, Indigenous health workers are in a unique position to deliver culturally competent oral healthcare because they have a contextual understanding of the needs of the community. This scoping review aimed to identify the role of Indigenous health workers in promoting maternal oral health globally. A systematic search was undertaken of six electronic databases for relevant published literature and grey literature, and expanded to include non-dental health professionals and other Indigenous populations across the lifespan when limited studies were identified. Twenty-two papers met the inclusion criteria, focussing on the role of Indigenous health workers in maternal oral healthcare, types of oral health training programs and screening tools to evaluate program effectiveness. There was a paucity of peer-reviewed evidence on the role of Indigenous health workers in promoting maternal oral health, with most studies focusing on other non-dental health professionals. Nevertheless, there were reports of Indigenous health workers supporting oral health in early childhood. Although some oral health screening tools and training programs were identified for non-dental health professionals during the antenatal period, no specific screening tool has been developed for use by Indigenous health workers. While the role of health workers from Indigenous communities in promoting maternal oral health is yet to be clearly defined, they have the potential to play a crucial role in 'driving' screening and education of maternal oral health especially when there is adequate organisational support, warranting further research.

A cohort study on self-reported role stressors at work and poor sleep: does sense of coherence moderate or mediate the associations?

PubMed

Hansen, Åse Marie; Grynderup, Matias Brødsgaard; Rugulies, Reiner; Conway, Paul Maurice; Garde, Anne Helene; Török, Eszter; Mikkelsen, Eva Gemzøe; Persson, Roger; Hogh, Annie

2018-05-01

The aim of the present study was to examine the bidirectional associations between subjective role ambiguity and role conflicts at work, respectively, and self-reported sleep 2 years later. In addition, we also examine whether sense of coherence (SOC) moderate or mediate the association between role stressors and poor sleep and between poor sleep and role stressors. We used questionnaire data collected in 2006 and 2008 from the Workplace Bullying and Harassment cohort. In 2006, 3363 responded to the questionnaire and in 2008 1671 responded. In total, 1569 participants responded in both 2006 and 2008 to the questions on role stressors (in terms of role ambiguity and role conflicts at work) and sleep problems in both 2006 and 2008. Sleep problems were assessed with the awakening index (AWI) and the disturbed sleep index (DSI). Moderation and mediation analyses of the association were estimated using structural equation modelling. We found a prospective association between role stressors and sleep problems [beta values were 0.07 (95% CI 0.03-0.11) and 0.05 (CI 0.01-0.10) for DSI and AWI, respectively] when adjusting for sleep problems at baseline, age, sex, and life style factors (i.e. alcohol, smoking, and leisure time physical activity). SOC moderated the association showing that participants with lower SOC scores who reported higher role ambiguity reported sleep problems to a higher extent than participants with high SOC scores. SOC also mediated the association between role stressors and sleep problems. We also found support for sleep problems at baseline and role stressors 2 years later [DSI 0.04 (CI 0.00-0.08) and 0.15 (CI 0.09-0.21)] for role ambiguity and role conflicts, respectively. Similar results were observed for AWI. Subjective role stressors were prospectively associated with sleep problems. Yet, sleep problems could also prospectively predict subjective role stressors (i.e. reverse causation). The analyses also showed that SOC may be regarded as both a mediating and a moderating factor of the association between subjective role conflicts and poor sleep. We found that SOC moderated the prospective association so participants with low SOC report more sleep problems with subjective role conflicts compared to participants with high SOC. Finally, we also found SOC mediated the prospective association between subjective role stressors and sleep problems and the reverse association.

Creatine Revealed Anticonvulsant Properties on Chemically and Electrically Induced Seizures in Mice.

PubMed

Shafaroodi, Hamed; Shahbek, Farnaz; Faizi, Mehrdad; Ebrahimi, Farzad; Moezi, Leila

2016-01-01

Creatine exerts beneficial effects on a variety of pathologies in which energy metabolism and oxidative stress play an etiological role. Creatine supplements have shown beneficial effects on neurological disorders including Parkinson׳s disease, Huntington›s disease, amyotrophic lateral sclerosis, as well as Alzheimer›s disease and stroke. However, the potential benefits of creatine for patients with convulsive disorders remain poorly defined. While some authors did not suggest any anti- or pro-convulsant roles for creatine treatment, others suggest that creatine may be an anticonvulsant agent. In this study, we investigated the effects of creatine on seizures in mice. Three models were used to explore the role of creatine on seizures in mice including intravenous pentylenetetrazole (PTZ), intraperitoneal PTZ, and electroshock models. Acute creatine treatment (10, 20, 40 and 80 mg/Kg) significantly increased the clonic seizure threshold in the intravenous PTZ model. Sub-chronic administration of creatine (10 and 20 mg/Kg) revealed a significant anticonvulsant effect in intravenous PTZ model. Acute creatine administration (10, 20 and 40 mg/Kg) significantly decreased the frequency of clonic seizures in the intraperitoneal PTZ model. Besides, acute creatine (40 and 80 mg/Kg) decreased the incidence of tonic seizures after electroshock. In conclusion, creatine exerts anticonvulsant effects in three seizure models; therefore, it may act as a potential drug to help patients with convulsions. However, further investigations should be done to clarify these results more.

Creatine Revealed Anticonvulsant Properties on Chemically and Electrically Induced Seizures in Mice

PubMed Central

Shafaroodi, Hamed; Shahbek, Farnaz; Faizi, Mehrdad; Ebrahimi, Farzad; Moezi, Leila

2016-01-01

Creatine exerts beneficial effects on a variety of pathologies in which energy metabolism and oxidative stress play an etiological role. Creatine supplements have shown beneficial effects on neurological disorders including Parkinson׳s disease, Huntington›s disease, amyotrophic lateral sclerosis, as well as Alzheimer›s disease and stroke. However, the potential benefits of creatine for patients with convulsive disorders remain poorly defined. While some authors did not suggest any anti- or pro-convulsant roles for creatine treatment, others suggest that creatine may be an anticonvulsant agent. In this study, we investigated the effects of creatine on seizures in mice. Three models were used to explore the role of creatine on seizures in mice including intravenous pentylenetetrazole (PTZ), intraperitoneal PTZ, and electroshock models. Acute creatine treatment (10, 20, 40 and 80 mg/Kg) significantly increased the clonic seizure threshold in the intravenous PTZ model. Sub-chronic administration of creatine (10 and 20 mg/Kg) revealed a significant anticonvulsant effect in intravenous PTZ model. Acute creatine administration (10, 20 and 40 mg/Kg) significantly decreased the frequency of clonic seizures in the intraperitoneal PTZ model. Besides, acute creatine (40 and 80 mg/Kg) decreased the incidence of tonic seizures after electroshock. In conclusion, creatine exerts anticonvulsant effects in three seizure models; therefore, it may act as a potential drug to help patients with convulsions. However, further investigations should be done to clarify these results more. PMID:28243281

Comparative functional characterization of the CSR-1 22G-RNA pathway in Caenorhabditis nematodes

PubMed Central

Tu, Shikui; Wu, Monica Z.; Wang, Jie; Cutter, Asher D.; Weng, Zhiping; Claycomb, Julie M.

2015-01-01

As a champion of small RNA research for two decades, Caenorhabditis elegans has revealed the essential Argonaute CSR-1 to play key nuclear roles in modulating chromatin, chromosome segregation and germline gene expression via 22G-small RNAs. Despite CSR-1 being preserved among diverse nematodes, the conservation and divergence in function of the targets of small RNA pathways remains poorly resolved. Here we apply comparative functional genomic analysis between C. elegans and Caenorhabditis briggsae to characterize the CSR-1 pathway, its targets and their evolution. C. briggsae CSR-1-associated small RNAs that we identified by immunoprecipitation-small RNA sequencing overlap with 22G-RNAs depleted in cbr-csr-1 RNAi-treated worms. By comparing 22G-RNAs and target genes between species, we defined a set of CSR-1 target genes with conserved germline expression, enrichment in operons and more slowly evolving coding sequences than other genes, along with a small group of evolutionarily labile targets. We demonstrate that the association of CSR-1 with chromatin is preserved, and show that depletion of cbr-csr-1 leads to chromosome segregation defects and embryonic lethality. This first comparative characterization of a small RNA pathway in Caenorhabditis establishes a conserved nuclear role for CSR-1 and highlights its key role in germline gene regulation across multiple animal species. PMID:25510497

Interleukin-17-induced protein lipocalin 2 is dispensable for immunity to oral candidiasis.

PubMed

Ferreira, Maria Carolina; Whibley, Natasha; Mamo, Anna J; Siebenlist, Ulrich; Chan, Yvonne R; Gaffen, Sarah L

2014-03-01

Oropharyngeal candidiasis (OPC; thrush) is an opportunistic fungal infection caused by the commensal microbe Candida albicans. Immunity to OPC is strongly dependent on CD4+ T cells, particularly those of the Th17 subset. Interleukin-17 (IL-17) deficiency in mice or humans leads to chronic mucocutaneous candidiasis, but the specific downstream mechanisms of IL-17-mediated host defense remain unclear. Lipocalin 2 (Lcn2; 24p3; neutrophil gelatinase-associated lipocalin [NGAL]) is an antimicrobial host defense factor produced in response to inflammatory cytokines, particularly IL-17. Lcn2 plays a key role in preventing iron acquisition by bacteria that use catecholate-type siderophores, and lipocalin 2(-/-) mice are highly susceptible to infection by Escherichia coli and Klebsiella pneumoniae. The role of Lcn2 in mediating immunity to fungi is poorly defined. Accordingly, in this study, we evaluated the role of Lcn2 in immunity to oral infection with C. albicans. Lcn2 is strongly upregulated following oral infection with C. albicans, and its expression is almost entirely abrogated in mice with defective IL-17 signaling (IL-17RA(-/-) or Act1(-/-) mice). However, Lcn2(-/-) mice were completely resistant to OPC, comparably to wild-type (WT) mice. Moreover, Lcn2 deficiency mediated protection from OPC induced by steroid immunosuppression. Therefore, despite its potent regulation during C. albicans infection, Lcn2 is not required for immunity to mucosal candidiasis.

The role of the dynein light intermediate chain in retrograde IFT and flagellar function in Chlamydomonas

PubMed Central

Reck, Jaimee; Schauer, Alexandria M.; VanderWaal Mills, Kristyn; Bower, Raqual; Tritschler, Douglas; Perrone, Catherine A.; Porter, Mary E.

2016-01-01

The assembly of cilia and flagella depends on the activity of two microtubule motor complexes, kinesin-2 and dynein-2/1b, but the specific functions of the different subunits are poorly defined. Here we analyze Chlamydomonas strains expressing different amounts of the dynein 1b light intermediate chain (D1bLIC). Disruption of D1bLIC alters the stability of the dynein 1b complex and reduces both the frequency and velocity of retrograde intraflagellar transport (IFT), but it does not eliminate retrograde IFT. Flagellar assembly, motility, gliding, and mating are altered in a dose-dependent manner. iTRAQ-based proteomics identifies a small subset of proteins that are significantly reduced or elevated in d1blic flagella. Transformation with D1bLIC-GFP rescues the mutant phenotypes, and D1bLIC-GFP assembles into the dynein 1b complex at wild-type levels. D1bLIC-GFP is transported with anterograde IFT particles to the flagellar tip, dissociates into smaller particles, and begins processive retrograde IFT in <2 s. These studies demonstrate the role of D1bLIC in facilitating the recycling of IFT subunits and other proteins, identify new components potentially involved in the regulation of IFT, flagellar assembly, and flagellar signaling, and provide insight into the role of D1bLIC and retrograde IFT in other organisms. PMID:27251063

Perspective: Entering uncharted waters: navigating the transition from trainee to career for the nonphysician clinician-scientist.

PubMed

MacDonald, Shannon E; Sharpe, Heather M; Shikako-Thomas, Keiko; Larsen, Bodil; MacKay, Lyndsay

2013-01-01

The transition from trainee to career clinician-scientist can be a stressful and challenging time, particularly for those entering the less established role of nonphysician clinician-scientist. These individuals are typically PhD-prepared clinicians in the allied health professions, who have either a formal or informal joint appointment between a clinical institution and an academic or research institution. The often poorly defined boundaries and expectations of these developing roles can pose additional challenges for the trainee-to-career transition.It is important for these trainees to consider what they want and need in a position in order to be successful, productive, and fulfilled in both their professional and personal lives. It is also critical for potential employers, whether academic or clinical (or a combination of both), to be fully aware of the supports and tools necessary to recruit and retain new nonphysician clinician-scientists. Issues of relevance to the trainee and the employer include finding and negotiating a position; the importance of mentorship; the value of effective time management, particularly managing clinical and academic time commitments; and achieving work-life balance. Attention to these issues, by both the trainee and those in a position to hire them, will facilitate a smooth transition to the nonphysician clinician-scientist role and ultimately contribute to individual and organizational success.

The global land rush and climate change

NASA Astrophysics Data System (ADS)

Davis, Kyle Frankel; Rulli, Maria Cristina; D'Odorico, Paolo

2015-08-01

Climate change poses a serious global challenge in the face of rapidly increasing human demand for energy and food. A recent phenomenon in which climate change may play an important role is the acquisition of large tracts of land in the developing world by governments and corporations. In the target countries, where land is relatively inexpensive, the potential to increase crop yields is generally high and property rights are often poorly defined. By acquiring land, investors can realize large profits and countries can substantially alter the land and water resources under their control, thereby changing their outlook for meeting future demand. While the drivers, actors, and impacts involved with land deals have received substantial attention in the literature, we propose that climate change plays an important yet underappreciated role, both through its direct effects on agricultural production and through its influence on mitigative or adaptive policy decisions. Drawing from various literature sources as well as a new global database on reported land deals, we trace the evolution of the global land rush and highlight prominent examples in which the role of climate change is evident. We find that climate change—both historical and anticipated—interacts substantially with drivers of land acquisitions, having important implications for the resilience of communities in targeted areas. As a result of this synthesis, we ultimately contend that considerations of climate change should be integrated into future policy decisions relating to the large-scale land acquisitions.

Comparative Proteomic Analysis of Supportive and Unsupportive Extracellular Matrix Substrates for Human Embryonic Stem Cell Maintenance*

PubMed Central

Soteriou, Despina; Iskender, Banu; Byron, Adam; Humphries, Jonathan D.; Borg-Bartolo, Simon; Haddock, Marie-Claire; Baxter, Melissa A.; Knight, David; Humphries, Martin J.; Kimber, Susan J.

2013-01-01

Human embryonic stem cells (hESCs) are pluripotent cells that have indefinite replicative potential and the ability to differentiate into derivatives of all three germ layers. hESCs are conventionally grown on mitotically inactivated mouse embryonic fibroblasts (MEFs) or feeder cells of human origin. In addition, feeder-free culture systems can be used to support hESCs, in which the adhesive substrate plays a key role in the regulation of stem cell self-renewal or differentiation. Extracellular matrix (ECM) components define the microenvironment of the niche for many types of stem cells, but their role in the maintenance of hESCs remains poorly understood. We used a proteomic approach to characterize in detail the composition and interaction networks of ECMs that support the growth of self-renewing hESCs. Whereas many ECM components were produced by supportive and unsupportive MEF and human placental stromal fibroblast feeder cells, some proteins were only expressed in supportive ECM, suggestive of a role in the maintenance of pluripotency. We show that identified candidate molecules can support attachment and self-renewal of hESCs alone (fibrillin-1) or in combination with fibronectin (perlecan, fibulin-2), in the absence of feeder cells. Together, these data highlight the importance of specific ECM interactions in the regulation of hESC phenotype and provide a resource for future studies of hESC self-renewal. PMID:23658023

Brain Activation during Sentence Comprehension among Good and Poor Readers

PubMed Central

Keller, Timothy A.; Cherkassky, Vladimir L.; Lee, Donghoon; Hoeft, Fumiko; Whitfield-Gabrieli, Susan; Gabrieli, John D. E.; Just, Marcel Adam

2008-01-01

This study sought to increase current understanding of the neuro-psychological basis of poor reading ability by using fMRI to examine brain activation during a visual sentence comprehension task among good and poor readers in the third (n = 32) and fifth (n = 35) grades. Reading ability, age, and the combination of both factors made unique contributions to cortical activation. The main finding was of parietotemporal underactivation (less activation than controls) among poor readers at the 2 grade levels. A positive linear relationship (spanning both the poor and good readers) was found between reading ability and activation in the left posterior middle temporal and postcentral gyri and in the right inferior parietal lobule such that activation increased with reading ability. Different developmental trajectories characterized good and poor readers in the left angular gyrus: activation increased with age among good readers, a change that failed to occur among poor readers. The parietotemporal cortex is discussed in terms of its role in reading acquisition, with the left angular gyrus playing a key role. It is proposed that the functioning of the cortical network underlying reading is dependent on a combination of interacting factors, including physiological maturation, neural integrity, skill level, and the nature of the task. PMID:17317678

Physiotherapy beyond Our Borders: Investigating Ideal Competencies for Canadian Physiotherapists Working in Resource-Poor Countries

PubMed Central

Cassady, Christina; Meru, Rehana; Chan, Nga Man Carmen; Engelhardt, Julie; Fraser, Michelle

2014-01-01

ABSTRACT Purpose: To explore the perspectives of Canadian physiotherapists with global health experience on the ideal competencies for Canadian physiotherapists working in resource-poor countries. Method: A qualitative interpretive methodology was used, and the Essential Competency Profile for Physiotherapists in Canada, 2009 (ECP), was employed as a starting point for investigation and analysis. Semi-structured one-on-one interviews (60–90 minutes) were conducted with 17 Canadian physiotherapists who have worked in resource-poor countries. Descriptive and thematic analyses were conducted collaboratively. Results: The seven ECP roles—Expert, Communicator, Collaborator, Manager, Advocate, Scholarly Practitioner, and Professional—were all viewed as important for Canadian physiotherapists working in resource-poor countries. Two roles, Communicator and Manager, have additional competencies that participants felt were important. Three novel roles—Global Health Learner, Critical Thinker, and Respectful Guest—were created to describe other competencies related to global health deemed crucial by participants. Conclusions: This is the first study to examine competencies required by Canadian physiotherapists working in resource-poor countries. In addition to the ECP roles, supplementary competencies are recommended for engagement in resource-poor countries. These findings align with ideas in current global health and international development literature. Future research should examine the relevance of these findings to resource-poor settings within Canada. PMID:24719503

[Thyroid carcinoma--differentiated, poorly differentiated and anaplastic carcinoma].

PubMed

Kakudo, Kennichi; Bai, Yanhua; Li, Yaqiong; Wakasa, Tomoko; Mori, Ichiro

2007-11-01

The poorly differentiated carcinoma was first added as a new member in the lists of classification of thyroid carcinomas in the WHO 2004 edition. However its histological criteria include necrosis and increased mitoses in addition to the original definition by Sakamoto's proposal, solid, trabecular and schirrhous growth. This modification creates a significant change in the incidence and prognosis of this carcinoma. This carcinoma, defined by the new WHO classification, is about 1-5% of all thyroid malignancy and has more aggressive outcome than the previous definition.

A Validation of the Proposed Royal Australian Navy Standard Work Week and Naval Management Diary Using a Simulated Crew of an Armidale Class Patrol Boat

DTIC Science & Technology

2015-12-01

Reduced mental capacity, poor decision making, emotional outbursts or withdrawals, and reduced alertness are among the side effects that have been...Guide.” The guide defined fatigue as “the product of intense and prolonged emotional strain, poor and inadequate diet, strenuous physical exertion...scheduling bodily functions and periods of sleepiness and wakefulness. Circadian rhythms control numerous factors in the human body including body

Multiple scene attitude estimator performance for LANDSAT-1

NASA Technical Reports Server (NTRS)

Rifman, S. S.; Monuki, A. T.; Shortwell, C. P.

1979-01-01

Initial results are presented to demonstrate the performance of a linear sequential estimator (Kalman Filter) used to estimate a LANDSAT 1 spacecraft attitude time series defined for four scenes. With the revised estimator a GCP poor scene - a scene with no usable geodetic control points (GCPs) - can be rectified to higher accuracies than otherwise based on the use of GCPs in adjacent scenes. Attitude estimation errors was determined by the use of GCPs located in the GCP-poor test scene, but which are not used to update the Kalman filter. Initial results achieved indicate that errors of 500m (rms) can be attained for the GCP-poor scenes. Operational factors are related to various scenarios.

Poor Comprehenders in the Classroom: Teacher Ratings of Behavior in Children with Poor Reading Comprehension and Its Relationship with Individual Differences in Working Memory

ERIC Educational Resources Information Center

Pimperton, Hannah; Nation, Kate

2014-01-01

Differing etiological explanations have been proposed to account for poor comprehenders' difficulties with reading comprehension, with some researchers emphasizing working memory deficits and others arguing for oral language weaknesses playing a key causal role. The authors contrasted these two theoretical accounts using data obtained from direct…

The Role of Training in Reducing Poverty: The Case of the Ultra-Poor in Bangladesh

ERIC Educational Resources Information Center

Khan, Mohammad Aktaruzzaman; Ali, Anees Janee

2014-01-01

Although microcredit is considered the main vehicle for increasing the income of the poor and alleviating poverty in Bangladesh, it is now well recognised that more than this is needed to reach the ultra poor in rural areas. Consequently, almost half of the Bangladesh population is in some way linked to non-governmental organizations' development…

The Effect of Social Programs and Exposure to Professionals on the Educational Aspirations of the Poor

ERIC Educational Resources Information Center

Chiapa, Carlos; Garrido, Jose Luis; Prina, Silvia

2012-01-01

Investment in human capital is an important tool for reducing poverty. However, the poor may lack the capacity to aspire, which often results in underinvestment in their children's education. This paper studies the effect of a social program on the educational aspirations poor parents have for their children, and explores the role of exposure to…

ADEQUACY OF DISINFECTION FOR CONTROL OF NEWLY RECOGNIZED WATERBORNE PATHOGENS

EPA Science Inventory

Agents recently recognized as causes or potential causes of waterborne outbreaks include pathogenic bacteria (Campylobacter jejuni, Yersinia enterocoliticia), viruses (rotavirus, Norwalk virus and other poorly defined viral agents) and Giardia lamblia, a protozoan agent. Although...

SOCIODEMOGRAPHIC DOMAINS OF DEPRIVATION AND PRETERM BIRTH

EPA Science Inventory

Area-level deprivation is consistently associated with poor health outcomes. Using US census data (2000) and principal components analysis, a priori defined socio-demographic indices of poverty, housing, residential stability, occupation, employment and education were created fo...

EFFECT OF STRUCTURED PHYSICAL ACTIVITY ON SLEEP-WAKE BEHAVIORS IN SEDENTARY ELDERS WITH MOBILITY LIMITATIONS

PubMed Central

Vaz Fragoso, Carlos A.; Miller, Michael E.; King, Abby C.; Kritchevsky, Stephen B.; Liu, Christine K.; Myers, Valerie H.; Nadkarni, Neelesh K.; Pahor, Marco; Spring, Bonnie J.; Gill, Thomas M.

2016-01-01

OBJECTIVE To evaluate the effect of structured physical activity on sleep-wake behaviors in sedentary community-dwelling elders with mobility limitations. DESIGN Multicenter, randomized trial of moderate-intensity physical activity versus health education, with sleep-wake behaviors pre-specified as a tertiary outcome over a planned intervention period ranging between 24 and 30 months. SETTING Lifestyle Interventions and Independence in Elder (LIFE) Study. PARTICIPANTS 1635 community-dwelling persons, aged 70–89 years, who were initially sedentary with a Short Physical Performance Battery score <10. MEASUREMENTS Sleep-wake behaviors were evaluated by the Insomnia Severity Index (ISI) (≥8 defined insomnia), Epworth Sleepiness Scale (ESS) (≥10 defined daytime drowsiness), and Pittsburgh Sleep Quality Index (PSQI) (> 5 defined poor sleep quality) — administered at baseline and subsequently at 6, 18, and 30 months. RESULTS The randomized groups were similar on baseline demographic variables, including mean age (79 years) and sex (67% female). Relative to health education, structured physical activity significantly reduced the likelihood of having poor sleep quality (adjusted odds ratios [adjOR] for PSQI >5 of 0.80 [0.68, 0.94]), including a reduction in new cases (adjOR for PSQI >5 of 0.70 [0.54, 0.89]) but not in resolution of prevalent cases (adjOR for PSQI ≤5 of 1.13 [0.90, 1.43]). No significant intervention effects were observed for ISI or ESS. CONCLUSION Structured physical activity reduced the likelihood of developing poor sleep quality (PSQI >5) over the intervention period, when compared with health education, but had no effect on prevalent cases of poor sleep quality, or on sleep-wake behaviors evaluated by the ISI or ESS. These results suggest that the benefit of physical activity in this sample was preventive and limited to sleep-wake behaviors evaluated by the PSQI. PMID:26115386

Effect of Structured Physical Activity on Sleep-Wake Behaviors in Sedentary Elderly Adults with Mobility Limitations.

PubMed

Vaz Fragoso, Carlos A; Miller, Michael E; King, Abby C; Kritchevsky, Stephen B; Liu, Christine K; Myers, Valerie H; Nadkarni, Neelesh K; Pahor, Marco; Spring, Bonnie J; Gill, Thomas M

2015-07-01

To evaluate the effect of structured physical activity on sleep-wake behaviors in sedentary community-dwelling elderly adults with mobility limitations. Multicenter, randomized trial of moderate-intensity physical activity versus health education, with sleep-wake behaviors prespecified as a tertiary outcome over a planned intervention period ranging from 24 to 30 months. Lifestyle Interventions and Independence for Elders Study. Community-dwelling persons aged 70 to 89 who were initially sedentary and had a Short Physical Performance Battery score less than 10 (N = 1,635). Sleep-wake behaviors were evaluated using the Insomnia Severity Index (ISI) (≥8 defined insomnia), Epworth Sleepiness Scale (ESS) (≥10 defined daytime drowsiness), and Pittsburgh Sleep Quality Index (PSQI) (>5 defined poor sleep quality) administered at baseline and 6, 18, and 30 months. The randomized groups were similar in terms of baseline demographic variables, including mean age (79) and sex (67% female). Structured physical activity resulted in a significantly lower likelihood of having poor sleep quality (adjusted odds ratios (aOR) for PSQI >5 = 0.80, 95% confidence interval (CI) = 0.68-0.94), including fewer new cases (aOR for PSQI >5 = 0.70, 95% CI = 0.54-0.89), than health education but not in resolution of prevalent cases (aOR for PSQI ≤5 = 1.13, 95% CI = 0.90-1.43). No significant intervention effects were observed for the ISI or ESS. Structured physical activity resulted in a lower likelihood of developing poor sleep quality (PSQI >5) over the intervention period than health education but had no effect on prevalent cases of poor sleep quality or on sleep-wake behaviors evaluated using the ISI or ESS. These results suggest that the benefit of physical activity in this sample was preventive and limited to sleep-wake behaviors evaluated using the PSQI. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

A relationship between eye movement patterns and performance in a precognitive tracking task

NASA Technical Reports Server (NTRS)

Repperger, D. W.; Hartzell, E. J.

1977-01-01

Eye movements made by various subjects in the performance of a precognitive tracking task are studied. The tracking task persented by an antiaircraft artillery (AAA) simulator has an input forcing function represented by a deterministic aircraft fly-by. The performance of subjects is ranked by two metrics. Good, mediocre, and poor trackers are selected for analysis based on performance during the difficult segment of the tracking task and over replications. Using phase planes to characterize both the eye movement patterns and the displayed error signal, a simple metric is developed to study these patterns. Two characterizations of eye movement strategies are defined and quantified. Using these two types of eye strategies, two conclusions are obtained about good, mediocre, and poor trackers. First, the eye tracker who used a fixed strategy will consistently perform better. Secondly, the best fixed strategy is defined as a Crosshair Fixator.

The paradox of transient worsening renal function in patients with acute heart failure: the role of B-type natriuretic peptide and diuretic response.

PubMed

Ruocco, Gaetano; Nuti, Ranuccio; Giambelluca, Amalia; Evangelista, Isabella; De Vivo, Oreste; Daniello, Cosimo; Palazzuoli, Alberto

2017-11-01

Worsening renal function (WRF) occurs in one-third of patients hospitalized for acute decompensated heart failure. Recently, WRF was categorized in two subtypes: persistent and transient WRF. Thus, we sought to investigate the different prognostic impact of persistent vs. transient WRF; we also evaluate the relation of two WRF phenotypes with congestion, B-type natriuretic peptide (BNP) changes, and diuretic response at discharge. The prospective was a single centre study including patients screened for interventional Diur-heart failure Trial (NCT01441245). Patients were eligible if they were admitted with a primary diagnosis of acute heart failure with evidence of volume overload. Persistent WRF was defined as a sustained creatinine increase by at least 0.3 mg/dl throughout the hospitalisation; transient WRF was defined as creatinine increase by at least 0.3 mg/dl within 72 h and a return to baseline levels at discharge. Patients were followed for 6 months after discharge. Our population included 192 acute decompensated heart failure patients. In total, 61 patients developed persistent WRF and 29 developed transient WRF. Patients with persistent WRF showed a lower mean urine output with respect to the transient WRF group and patients with preserved renal function (1618 ± 374 vs. 2132 ± 392 vs. 2075 ± 442 ml; P < 0.001). Similarly, patients with transient WRF demonstrated a higher rate of BNP decrease more than 30% than seen in patients with stable creatinine levels and in the persistent WRF group (95 vs. 76 vs. 54%; P = 0.001). Univariate Cox regression analysis demonstrated that BNP decrease less than 30% [HR 2.15 (1.40-3.40); P < 0.001] and persistent WRF [HR 1.70 (1.11-2.61); P = 0.01] were related to poor outcome; conversely, transient WRF should be considered as a protective factor [HR 0.42 (0.19-0.93); P = 0.03]. In the multivariable model, only persistent WRF appeared to be related to poor prognosis [HR 1.61 (1.02-2.57); P = 0.04]. WRF occurring during hospitalization has a different significance: transient deterioration appears to be associated with a favourable clinical course; conversely, persistent WRF is related to poor outcome.

Bone morphogenetic protein and Notch signalling crosstalk in poor-prognosis, mesenchymal-subtype colorectal cancer.

PubMed

Irshad, Shazia; Bansal, Mukesh; Guarnieri, Paolo; Davis, Hayley; Al Haj Zen, Ayman; Baran, Brygida; Pinna, Claudia Maria Assunta; Rahman, Haseeb; Biswas, Sujata; Bardella, Chiara; Jeffery, Rosemary; Wang, Lai Mun; East, James Edward; Tomlinson, Ian; Lewis, Annabelle; Leedham, Simon John

2017-06-01

The functional role of bone morphogenetic protein (BMP) signalling in colorectal cancer (CRC) is poorly defined, with contradictory results in cancer cell line models reflecting the inherent difficulties of assessing a signalling pathway that is context-dependent and subject to genetic constraints. By assessing the transcriptional response of a diploid human colonic epithelial cell line to BMP ligand stimulation, we generated a prognostic BMP signalling signature, which was applied to multiple CRC datasets to investigate BMP heterogeneity across CRC molecular subtypes. We linked BMP and Notch signalling pathway activity and function in human colonic epithelial cells, and normal and neoplastic tissue. BMP induced Notch through a γ-secretase-independent interaction, regulated by the SMAD proteins. In homeostasis, BMP/Notch co-localization was restricted to cells at the top of the intestinal crypt, with more widespread interaction in some human CRC samples. BMP signalling was downregulated in the majority of CRCs, but was conserved specifically in mesenchymal-subtype tumours, where it interacts with Notch to induce an epithelial-mesenchymal transition (EMT) phenotype. In intestinal homeostasis, BMP-Notch pathway crosstalk is restricted to differentiating cells through stringent pathway segregation. Conserved BMP activity and loss of signalling stringency in mesenchymal-subtype tumours promotes a synergistic BMP-Notch interaction, and this correlates with poor patient prognosis. BMP signalling heterogeneity across CRC subtypes and cell lines can account for previous experimental contradictions. Crosstalk between the BMP and Notch pathways will render mesenchymal-subtype CRC insensitive to γ-secretase inhibition unless BMP activation is concomitantly addressed. © 2017 The Authors. Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2017 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

A semi-quantitative World Health Organization grading scheme evaluating worst tumor differentiation predicts disease-free survival in oral squamous carcinoma patients.

PubMed

Jain, Dhruv; Tikku, Gargi; Bhadana, Pallavi; Dravid, Chandrashekhar; Grover, Rajesh Kumar

2017-08-01

We investigated World Health Organization (WHO) grading and pattern of invasion based histological schemes as independent predictors of disease-free survival, in oral squamous carcinoma patients. Tumor resection slides of eighty-seven oral squamous carcinoma patients [pTNM: I&II/III&IV-32/55] were evaluated. Besides examining various patterns of invasion, invasive front grade, predominant and worst (highest) WHO grade were recorded. For worst WHO grading, poor-undifferentiated component was estimated semi-quantitatively at advancing tumor edge (invasive growth front) in histology sections. Tumor recurrence was observed in 31 (35.6%) cases. The 2-year disease-free survival was 47% [Median: 656; follow-up: 14-1450] days. Using receiver operating characteristic curves, we defined poor-undifferentiated component exceeding 5% of tumor as the cutoff to assign an oral squamous carcinoma as grade-3, when following worst WHO grading. Kaplan-Meier curves for disease-free survival revealed prognostic association with nodal involvement, tumor size, worst WHO grading; most common pattern of invasion and invasive pattern grading score (sum of two most predominant patterns of invasion). In further multivariate analysis, tumor size (>2.5cm) and worst WHO grading (grade-3 tumors) independently predicted reduced disease-free survival [HR, 2.85; P=0.028 and HR, 3.37; P=0.031 respectively]. The inter-observer agreement was moderate for observers who semi-quantitatively estimated percentage of poor-undifferentiated morphology in oral squamous carcinomas. Our results support the value of semi-quantitative method to assign tumors as grade-3 with worst WHO grading for predicting reduced disease-free survival. Despite limitations, of the various histological tumor stratification schemes, WHO grading holds adjunctive value for its prognostic role, ease and universal familiarity. Copyright © 2017 Elsevier Inc. All rights reserved.

Germline BRCA mutations are associated with higher risk of nodal involvement, distant metastasis, and poor survival outcomes in prostate cancer.

PubMed

Castro, Elena; Goh, Chee; Olmos, David; Saunders, Ed; Leongamornlert, Daniel; Tymrakiewicz, Malgorzata; Mahmud, Nadiya; Dadaev, Tokhir; Govindasami, Koveela; Guy, Michelle; Sawyer, Emma; Wilkinson, Rosemary; Ardern-Jones, Audrey; Ellis, Steve; Frost, Debra; Peock, Susan; Evans, D Gareth; Tischkowitz, Marc; Cole, Trevor; Davidson, Rosemarie; Eccles, Diana; Brewer, Carole; Douglas, Fiona; Porteous, Mary E; Donaldson, Alan; Dorkins, Huw; Izatt, Louise; Cook, Jackie; Hodgson, Shirley; Kennedy, M John; Side, Lucy E; Eason, Jacqueline; Murray, Alex; Antoniou, Antonis C; Easton, Douglas F; Kote-Jarai, Zsofia; Eeles, Rosalind

2013-05-10

To analyze the baseline clinicopathologic characteristics of prostate tumors with germline BRCA1 and BRCA2 (BRCA1/2) mutations and the prognostic value of those mutations on prostate cancer (PCa) outcomes. This study analyzed the tumor features and outcomes of 2,019 patients with PCa (18 BRCA1 carriers, 61 BRCA2 carriers, and 1,940 noncarriers). The Kaplan-Meier method and Cox regression analysis were used to evaluate the associations between BRCA1/2 status and other PCa prognostic factors with overall survival (OS), cause-specific OS (CSS), CSS in localized PCa (CSS_M0), metastasis-free survival (MFS), and CSS from metastasis (CSS_M1). PCa with germline BRCA1/2 mutations were more frequently associated with Gleason ≥ 8 (P = .00003), T3/T4 stage (P = .003), nodal involvement (P = .00005), and metastases at diagnosis (P = .005) than PCa in noncarriers. CSS was significantly longer in noncarriers than in carriers (15.7 v 8.6 years, multivariable analyses [MVA] P = .015; hazard ratio [HR] = 1.8). For localized PCa, 5-year CSS and MFS were significantly higher in noncarriers (96% v 82%; MVA P = .01; HR = 2.6%; and 93% v 77%; MVA P = .009; HR = 2.7, respectively). Subgroup analyses confirmed the poor outcomes in BRCA2 patients, whereas the role of BRCA1 was not well defined due to the limited size and follow-up in this subgroup. Our results confirm that BRCA1/2 mutations confer a more aggressive PCa phenotype with a higher probability of nodal involvement and distant metastasis. BRCA mutations are associated with poor survival outcomes and this should be considered for tailoring clinical management of these patients.

Endovascular therapy versus thrombolysis in patients with large vessel occlusions within the anterior circulation aged ≥80 years.

PubMed

Kastrup, Andreas; Brunner, Freimuth; Hildebrandt, Helmut; Roth, Christian; Winterhalter, Michael; Papanagiotou, Panagiotis

2018-03-16

In patients with large vessel occlusions, endovascular treatment (ET) has been shown to be superior to intravenous thrombolysis (IVT) in recent trials. However, the effectiveness of ET in elderly patients is uncertain. Using our stroke database, we compared the rates of good outcome (modified Rankin scale (mRS) ≤2), excellent outcome (mRS 0-1), poor outcome (mRS 5-6) at discharge, in-hospital death, infarct size, and symptomatic intracranial hemorrhage (SICH) in patients aged ≥80 years with distal intracranial carotid artery, M1 and M2 occlusions during two time periods. From January 2008 to October 2012, 217 patients were treated with IVT and, from November 2012 to October 2017, 209 patients received ET with stent retrievers (with or without IVT). Significantly more patients in the ET group than in the IVT group had a good outcome (25% vs 16%, P<0.05), as well as an excellent outcome (12% vs 4%, P<0.01). Significantly fewer patients in the ET group than in the IVT group died (14% vs 22%, P<0.05) or had a poor outcome (35% vs 52%, P<001). The SICH rates were lower after ET than after IVT (1% vs 6%, P<0.01), and the infarct sizes were smaller after ET than after IVT. Compared with IVT, the routine use of ET significantly improved the early clinical and radiological outcome in patients with anterior circulation large vessel occlusions aged ≥80 years. Nevertheless, poor outcome rates were high so the role of ET needs to be defined further in this population. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Correlation of pathologic features with CpG island methylator phenotype (CIMP) by quantitative DNA methylation analysis in colorectal carcinoma.

PubMed

Ogino, Shuji; Odze, Robert D; Kawasaki, Takako; Brahmandam, Mohan; Kirkner, Gregory J; Laird, Peter W; Loda, Massimo; Fuchs, Charles S

2006-09-01

Extensive gene promoter methylation in colorectal carcinoma has been termed the CpG island methylator phenotype (CIMP). Previous studies on CIMP used primarily methylation-specific polymerase chain reaction (PCR), which, unfortunately, may detect low levels of methylation that has little or no biological significance. Utilizing quantitative real-time PCR (MethyLight), we measured DNA methylation in a panel of 5 CIMP-specific gene promoters (CACNA1G, CDKN2A (p16), CRABP1, MLH1, and NEUROG1) in 459 colorectal carcinomas obtained from 2 large prospective cohort studies. CIMP was defined as tumors that showed methylation in >or=4/5 promoters. CIMP was significantly associated with the presence of mucinous or signet ring cell morphology, marked Crohn's-like lymphoid reaction, tumor infiltrating lymphocytes, marked peritumoral lymphocytic reaction, tumor necrosis, tumor cell sheeting, and poor differentiation. All these features have previously been associated with microsatellite instability (MSI). Therefore, we divided the 459 colorectal carcinomas into 6 subtypes, namely, MSI-high (MSI-H)/CIMP, MSI-H/non-CIMP, MSI-low (MSI-L)/CIMP, MSI-L/non-CIMP, microsatellite stable/CIMP, and micro satellite sstable/non-CIMP. Compared with MSI-H/non-CIMP, MSI-H/CIMP was associated with marked tumor infiltrating lymphocytes, tumor necrosis, sheeting, and poor differentiation (all P

Germline BRCA Mutations Are Associated With Higher Risk of Nodal Involvement, Distant Metastasis, and Poor Survival Outcomes in Prostate Cancer

PubMed Central

Castro, Elena; Goh, Chee; Olmos, David; Saunders, Ed; Leongamornlert, Daniel; Tymrakiewicz, Malgorzata; Mahmud, Nadiya; Dadaev, Tokhir; Govindasami, Koveela; Guy, Michelle; Sawyer, Emma; Wilkinson, Rosemary; Ardern-Jones, Audrey; Ellis, Steve; Frost, Debra; Peock, Susan; Evans, D. Gareth; Tischkowitz, Marc; Cole, Trevor; Davidson, Rosemarie; Eccles, Diana; Brewer, Carole; Douglas, Fiona; Porteous, Mary E.; Donaldson, Alan; Dorkins, Huw; Izatt, Louise; Cook, Jackie; Hodgson, Shirley; Kennedy, M. John; Side, Lucy E.; Eason, Jacqueline; Murray, Alex; Antoniou, Antonis C.; Easton, Douglas F.; Kote-Jarai, Zsofia; Eeles, Rosalind

2013-01-01

Purpose To analyze the baseline clinicopathologic characteristics of prostate tumors with germline BRCA1 and BRCA2 (BRCA1/2) mutations and the prognostic value of those mutations on prostate cancer (PCa) outcomes. Patients and Methods This study analyzed the tumor features and outcomes of 2,019 patients with PCa (18 BRCA1 carriers, 61 BRCA2 carriers, and 1,940 noncarriers). The Kaplan-Meier method and Cox regression analysis were used to evaluate the associations between BRCA1/2 status and other PCa prognostic factors with overall survival (OS), cause-specific OS (CSS), CSS in localized PCa (CSS_M0), metastasis-free survival (MFS), and CSS from metastasis (CSS_M1). Results PCa with germline BRCA1/2 mutations were more frequently associated with Gleason ≥ 8 (P = .00003), T3/T4 stage (P = .003), nodal involvement (P = .00005), and metastases at diagnosis (P = .005) than PCa in noncarriers. CSS was significantly longer in noncarriers than in carriers (15.7 v 8.6 years, multivariable analyses [MVA] P = .015; hazard ratio [HR] = 1.8). For localized PCa, 5-year CSS and MFS were significantly higher in noncarriers (96% v 82%; MVA P = .01; HR = 2.6%; and 93% v 77%; MVA P = .009; HR = 2.7, respectively). Subgroup analyses confirmed the poor outcomes in BRCA2 patients, whereas the role of BRCA1 was not well defined due to the limited size and follow-up in this subgroup. Conclusion Our results confirm that BRCA1/2 mutations confer a more aggressive PCa phenotype with a higher probability of nodal involvement and distant metastasis. BRCA mutations are associated with poor survival outcomes and this should be considered for tailoring clinical management of these patients. PMID:23569316

Latent Class Analysis of Lifestyle Characteristics and Health Risk Behaviors among College Youth

PubMed Central

Pasch, Keryn E.; Lust, Katherine; Story, Mary; Ehlinger, Ed

2010-01-01

Few studies have examined the context of a wide range of risk behaviors among emerging adults (ages 18–25 years), approximately half of whom in the USA enroll in post-secondary educational institutions. The objective of this research was to examine behavioral patterning in weight behaviors (diet and physical activity), substance use, sexual behavior, stress, and sleep among undergraduate students. Health survey data were collected among undergraduates attending a large, public US university (n=2,026). Latent class analysis was used to identify homogeneous, mutually exclusive “classes” (patterns) of ten leading risk behaviors. Resulting classes differed for males and females. Female classes were defined as: (1) poor lifestyle (diet, physical activity, sleep), yet low-risk behaviors (e.g., smoking, binge drinking, sexual risk, drunk driving; 40.0% of females), (2) high risk (high substance use, intoxicated sex, drunk driving, poor diet, inadequate sleep) (24.3%), (3) moderate lifestyle, few risk behaviors (20.4%), (4) “health conscious” (favorable diet/physical activity with some unhealthy weight control; 15.4%). Male classes were: (1) poor lifestyle, low risk (with notably high stress, insufficient sleep, 9.2% of males), (2) high risk (33.6% of males, similar to class 2 in females), (3) moderate lifestyle, low risk (51.0%), and (4) “classic jocks” (high physical activity, binge drinking, 6.2%). To our knowledge, this is among the first research to examine complex lifestyle patterning among college youth, particularly with emphasis on the role of weight-related behaviors. These findings have important implications for targeting much needed health promotion strategies among emerging adults and college youth. PMID:19499339

Association of food-hygiene practices and diarrhea prevalence among Indonesian young children from low socioeconomic urban areas.

PubMed

Agustina, Rina; Sari, Tirta P; Satroamidjojo, Soemilah; Bovee-Oudenhoven, Ingeborg M J; Feskens, Edith J M; Kok, Frans J

2013-10-19

Information on the part that poor food-hygiene practices play a role in the development of diarrhea in low socioeconomic urban communities is lacking. This study was therefore aimed at assessing the contribution of food-hygiene practice to the prevalence of diarrhea among Indonesian children. A cross-sectional study was conducted among 274 randomly selected children aged 12-59 months in selected low socioeconomic urban areas of East Jakarta. The prevalence of diarrhea was assessed from 7-day records on frequency and consistency of the child's defecation pattern. Food-hygiene practices including mother's and child's hand washing, food preparation, cleanliness of utensils, water source and safe drinking water, habits of buying cooked food, child's bottle feeding hygiene, and housing and environmental condition were collected through home visit interviews and observations by fieldworkers. Thirty-six practices were scored and classified into poor (median and below) and better (above median) food-hygiene practices. Nutritional status of children, defined anthropometrically, was measured through height and weight. Among the individual food-hygiene practices, children living in a house with less dirty sewage had a significantly lower diarrhea prevalence compared to those who did not [adjusted odds ratio (OR) 0.16, 95% confidence interval (CI) = 0.03-0.73]. The overall food-hygiene practice score was not significantly associated with diarrhea in the total group, but it was in children aged < 2 years (adjusted OR 4.55, 95% CI = 1.08-19.1). Overall poor mother's food-hygiene practices did not contribute to the occurrence of diarrhea in Indonesian children. However, among children < 2 years from low socioeconomic urban areas they were associated with more diarrhea.

Association of food-hygiene practices and diarrhea prevalence among Indonesian young children from low socioeconomic urban areas

PubMed Central

2013-01-01

Background Information on the part that poor food-hygiene practices play a role in the development of diarrhea in low socioeconomic urban communities is lacking. This study was therefore aimed at assessing the contribution of food-hygiene practice to the prevalence of diarrhea among Indonesian children. Methods A cross-sectional study was conducted among 274 randomly selected children aged 12–59 months in selected low socioeconomic urban areas of East Jakarta. The prevalence of diarrhea was assessed from 7-day records on frequency and consistency of the child’s defecation pattern. Food-hygiene practices including mother’s and child’s hand washing, food preparation, cleanliness of utensils, water source and safe drinking water, habits of buying cooked food, child’s bottle feeding hygiene, and housing and environmental condition were collected through home visit interviews and observations by fieldworkers. Thirty-six practices were scored and classified into poor (median and below) and better (above median) food-hygiene practices. Nutritional status of children, defined anthropometrically, was measured through height and weight. Results Among the individual food-hygiene practices, children living in a house with less dirty sewage had a significantly lower diarrhea prevalence compared to those who did not [adjusted odds ratio (OR) 0.16, 95% confidence interval (CI) = 0.03-0.73]. The overall food-hygiene practice score was not significantly associated with diarrhea in the total group, but it was in children aged < 2 years (adjusted OR 4.55, 95% CI = 1.08-19.1). Conclusions Overall poor mother’s food-hygiene practices did not contribute to the occurrence of diarrhea in Indonesian children. However, among children < 2 years from low socioeconomic urban areas they were associated with more diarrhea. PMID:24138899

Association between PTGS1 polymorphisms and functional outcomes in Chinese patients with stroke during aspirin therapy: Interaction with smoking.

PubMed

Cai, Huan; Cai, Biyang; Sun, Lingli; Zhang, Hao; Zhou, Shuyu; Cao, Liping; Guo, Hongquan; Sun, Wen; Yan, Bernard; Davis, Stephen M; Zhang, Zhizhong; Liu, Xinfeng

2017-05-15

Prostaglandin-Endoperoxide Synthase 1 (PTGS1) and smoking may play important roles in aspirin nonresponsiveness, but the effect of their interaction on stroke outcomes remains largely unknown. We examined the effects of PTGS1 polymorphisms, smoking status, and their interaction on functional outcomes in a cohort of Chinese Han patients with stroke during aspirin therapy. A total of 617 ischemic stroke patients taking aspirin were enrolled. Three single nucleotide polymorphisms (SNPs) rs1330344, rs3842788, and rs5788 in PTGS1 were determined for genotyping. Poor functional outcomes were defined as a modified Rankin Scale (mRS) of 3-6 at 90-day follow-up. The influence of PTGS1 gene-smoking interaction on functional outcomes was examined. Poor functional outcomes occurred in 145 (23.5%) patients. When adjusting multiple factors by logistic regression, CC genotype of rs1330344 was associated with poor functional outcomes (risk ratio [RR]=1.73; 95% confidence interval [CI]: 1.17-2.37). A similar connection was found in the CGC haplotype (RR=1.40; 95% CI: 1.08-1.77). Furthermore, we found a significant interaction between rs1330344 and smoking status (P interaction =0.018); the interaction effect between the PTGS1 haplotype and smoking also showed statistical significance (P interaction =0.040). In Chinese Han stroke patients with aspirin therapy, the adverse effect of PTGS1 polymorphisms on functional outcomes may be modulated by the smoking status. PTGS1 gene-smoking interaction might in part reflect the heterogeneity in the prognosis of patients treated with aspirin. Copyright © 2017 Elsevier B.V. All rights reserved.

Health and environmental policy issues in Canada: the role of watershed management in sustaining clean drinking water quality at surface sources.

PubMed

Davies, John-Mark; Mazumder, Asit

2003-07-01

Sustaining clean and safe drinking water sources is increasingly becoming a priority because of global pollution. The means of attaining and maintaining clean drinking water sources requires effective policies that identify, document, and reduce watershed risks. These risks are defined by their potential impact to human health. Health and risk are, therefore, indelibly linked because they are in part defined by each other. Understanding pathogen ecology and identifying watershed sources remains a priority because of the associated acute risks. Surface water quality changes resulting from inputs of human waste, nutrients and chemicals are associated with higher drinking water risks. Nutrient input can increase primary production and the resulting increase of organic matter results in greater disinfection by-product formation or requires greater treatment intensity. Many drinking water disease outbreaks have resulted from breaches in treatment facilities, therefore, even with greater treatment intensity poor source water quality intrinsically has greater associated health risks. Government and international agencies play a critical role in developing policy. The goal of maintaining water supplies whose availability is maximized and risks are minimized (i.e. sustainable) should be a vital part of such policy. Health risks are discussed in the context of a multi-barrier perspective and it is concluded that both passive (protection) and active (prescriptive management) management is necessary for sustainability. Canadian aboriginal water systems, British Columbian water policy and US EPA policies are given as examples. The basis for developing effective policies includes a strong reliance on sound science and effective instrumentation with careful consideration of stakeholders' interests. Only with such directed policies can the future availability of clean drinking water sources be ensured.

Biglycan, a danger signal that activates the NLRP3 inflammasome via toll-like and P2X receptors.

PubMed

Babelova, Andrea; Moreth, Kristin; Tsalastra-Greul, Wasiliki; Zeng-Brouwers, Jinyang; Eickelberg, Oliver; Young, Marian F; Bruckner, Peter; Pfeilschifter, Josef; Schaefer, Roland M; Gröne, Hermann-Josef; Schaefer, Liliana

2009-09-04

The role of endogenous inducers of inflammation is poorly understood. To produce the proinflammatory master cytokine interleukin (IL)-1beta, macrophages need double stimulation with ligands to both Toll-like receptors (TLRs) for IL-1beta gene transcription and nucleotide-binding oligomerization domain-like receptors for activation of the inflammasome. It is particularly intriguing to define how this complex regulation is mediated in the absence of an infectious trigger. Biglycan, a ubiquitous leucine-rich repeat proteoglycan of the extracellular matrix, interacts with TLR2/4 on macrophages. The objective of this study was to define the role of biglycan in the synthesis and activation of IL-1beta. Here we show that in macrophages, soluble biglycan induces the NLRP3/ASC inflammasome, activating caspase-1 and releasing mature IL-1beta without the need for additional costimulatory factors. This is brought about by the interaction of biglycan with TLR2/4 and purinergic P2X(4)/P2X(7) receptors, which induces receptor cooperativity. Furthermore, reactive oxygen species formation is involved in biglycan-mediated activation of the inflammasome. By signaling through TLR2/4, biglycan stimulates the expression of NLRP3 and pro-IL-1beta mRNA. Both in a model of non-infectious inflammatory renal injury (unilateral ureteral obstruction) and in lipopolysaccharide-induced sepsis, biglycan-deficient mice displayed lower levels of active caspase-1 and mature IL-1beta in the kidney, lung, and circulation. Our results provide evidence for direct activation of the NLRP3 inflammasome by biglycan and describe a fundamental paradigm of how tissue stress or injury is monitored by innate immune receptors detecting the release of the extracellular matrix components and turning such a signal into a robust inflammatory response.

Matrix metalloproteinase-10/TIMP-2 structure and analyses define conserved core interactions and diverse exosite interactions in MMP/TIMP complexes.

PubMed

Batra, Jyotica; Soares, Alexei S; Mehner, Christine; Radisky, Evette S

2013-01-01

Matrix metalloproteinases (MMPs) play central roles in vertebrate tissue development, remodeling, and repair. The endogenous tissue inhibitors of metalloproteinases (TIMPs) regulate proteolytic activity by binding tightly to the MMP active site. While each of the four TIMPs can inhibit most MMPs, binding data reveal tremendous heterogeneity in affinities of different TIMP/MMP pairs, and the structural features that differentiate stronger from weaker complexes are poorly understood. Here we report the crystal structure of the comparatively weakly bound human MMP-10/TIMP-2 complex at 2.1 Å resolution. Comparison with previously reported structures of MMP-3/TIMP-1, MT1-MMP/TIMP-2, MMP-13/TIMP-2, and MMP-10/TIMP-1 complexes offers insights into the structural basis of binding selectivity. Our analyses identify a group of highly conserved contacts at the heart of MMP/TIMP complexes that define the conserved mechanism of inhibition, as well as a second category of diverse adventitious contacts at the periphery of the interfaces. The AB loop of the TIMP N-terminal domain and the contact loops of the TIMP C-terminal domain form highly variable peripheral contacts that can be considered as separate exosite interactions. In some complexes these exosite contacts are extensive, while in other complexes the AB loop or C-terminal domain contacts are greatly reduced and appear to contribute little to complex stability. Our data suggest that exosite interactions can enhance MMP/TIMP binding, although in the relatively weakly bound MMP-10/TIMP-2 complex they are not well optimized to do so. Formation of highly variable exosite interactions may provide a general mechanism by which TIMPs are fine-tuned for distinct regulatory roles in biology.

Imaging Findings Associated with Space-Occupying Edema in Patients with Large Middle Cerebral Artery Infarcts.

PubMed

Horsch, A D; Dankbaar, J W; Stemerdink, T A; Bennink, E; van Seeters, T; Kappelle, L J; Hofmeijer, J; de Jong, H W; van der Graaf, Y; Velthuis, B K

2016-05-01

Prominent space-occupying cerebral edema is a devastating complication occurring in some but not all patients with large MCA infarcts. It is unclear why differences in the extent of edema exist. Better knowledge of factors related to prominent edema formation could aid treatment strategies. This study aimed to identify variables associated with the development of prominent edema in patients with large MCA infarcts. From the Dutch Acute Stroke Study (DUST), 137 patients were selected with large MCA infarcts on follow-up NCCT (3 ± 2 days after stroke onset), defined as ASPECTS ≤4. Prominent edema was defined as a midline shift of ≥5 mm on follow-up. Admission patient and treatment characteristics were collected. Admission CT parameters used were ASPECTS on NCCT and CBV and MTT maps, and occlusion site, clot burden, and collaterals on CTA. Permeability on admission CTP, and day 3 recanalization and reperfusion statuses were obtained if available. Unadjusted and adjusted (age and NIHSS) odds ratios were calculated for all variables in relation to prominent edema. Prominent edema developed in 51 patients (37%). Adjusted odds ratios for prominent edema were higher with lower ASPECTS on NCCT (adjusted odds ratio, 1.32; 95% CI, 1.13-1.55) and CBV (adjusted odds ratio, 1.26; 95% CI, 1.07-1.49), higher permeability (adjusted odds ratio, 2.35; 95% CI, 1.30-4.24), more proximal thrombus location (adjusted odds ratio, 3.40; 95% CI, 1.57-7.37), higher clot burden (adjusted odds ratio, 2.88; 95% CI, 1.11-7.45), and poor collaterals (adjusted odds ratio, 3.93; 95% CI, 1.78-8.69). Extensive proximal occlusion, poor collaterals, and larger ischemic deficits with higher permeability play a role in the development of prominent edema in large MCA infarcts. © 2016 by American Journal of Neuroradiology.

Subjective but Not Actigraphy-Defined Sleep Predicts Next-Day Fatigue in Chronic Fatigue Syndrome: A Prospective Daily Diary Study.

PubMed

Russell, Charlotte; Wearden, Alison J; Fairclough, Gillian; Emsley, Richard A; Kyle, Simon D

2016-04-01

This study aimed to (1) examine the relationship between subjective and actigraphy-defined sleep, and next-day fatigue in chronic fatigue syndrome (CFS); and (2) investigate the potential mediating role of negative mood on this relationship. We also sought to examine the effect of presleep arousal on perceptions of sleep. Twenty-seven adults meeting the Oxford criteria for CFS and self-identifying as experiencing sleep difficulties were recruited to take part in a prospective daily diary study, enabling symptom capture in real time over a 6-day period. A paper diary was used to record nightly subjective sleep and presleep arousal. Mood and fatigue symptoms were rated four times each day. Actigraphy was employed to provide objective estimations of sleep duration and continuity. Multilevel modelling revealed that subjective sleep variables, namely sleep quality, efficiency, and perceiving sleep to be unrefreshing, predicted following-day fatigue levels, with poorer subjective sleep related to increased fatigue. Lower subjective sleep efficiency and perceiving sleep as unrefreshing predicted reduced variance in fatigue across the following day. Negative mood on waking partially mediated these relationships. Increased presleep cognitive and somatic arousal predicted self-reported poor sleep. Actigraphy-defined sleep, however, was not found to predict following-day fatigue. For the first time we show that nightly subjective sleep predicts next-day fatigue in CFS and identify important factors driving this relationship. Our data suggest that sleep specific interventions, targeting presleep arousal, perceptions of sleep and negative mood on waking, may improve fatigue in CFS. © 2016 Associated Professional Sleep Societies, LLC.

The problem of institutional fit in integrated water resources management: A case of Zimbabwe’s Mazowe catchment

NASA Astrophysics Data System (ADS)

Chereni, A.

Integrated Water Resources Management (IWRM) concepts have now been accepted in various contexts and efforts are now being made to implement these concepts. Zimbabwe adopted and indigenized IWRM within the 1990s Water Reforms and stakeholder institutions designed to engender cross-sectoral efforts are now in place. Using evidence from Mazowe Catchment, this paper observes that far from fostering integration, institutions involved in water resources management are multiple, disparate and discordant. In practice, associational relationships - specifications of mandate based roles, lines and direction of accountability and evaluation criteria - of institutions intended to foster sectoral integration in natural resources management are not defined. These poorly defined associational relationships coupled with a dearth of a catchment management and development outline plan have translated into a lack of compulsion of duty among institutions. The study derives its evidence from a blend of qualitative unstructured interviews, participant observation and secondary sources. Although the weaknesses of IWRM are more contextual, it is argued, there are certain weaknesses that are also conceptual. IWRM, it is argued, has to contend with a growing plethora of methodological and motivational questions. Whilst it is agreeable within IWRM discourse that institutions need to be integrated, in practice, the approach falls short of a methodological approach that addresses ways in which the various aspects of these disparate institutions could be harmonized. The paper suggests that associational relationships or modes of interaction among institutions need to be defined. This definition should be based on a catchment development master plan.

Synthesis and Characterization of the Actinium Aquo Ion

PubMed Central

2017-01-01

Metal aquo ions occupy central roles in all equilibria that define metal complexation in natural environments. These complexes are used to establish thermodynamic metrics (i.e., stability constants) for predicting metal binding, which are essential for defining critical parameters associated with aqueous speciation, metal chelation, in vivo transport, and so on. As such, establishing the fundamental chemistry of the actinium(III) aquo ion (Ac-aquo ion, Ac(H2O)x3+) is critical for current efforts to develop 225Ac [t1/2 = 10.0(1) d] as a targeted anticancer therapeutic agent. However, given the limited amount of actinium available for study and its high radioactivity, many aspects of actinium chemistry remain poorly defined. We overcame these challenges using the longer-lived 227Ac [t1/2 = 21.772(3) y] isotope and report the first characterization of this fundamentally important Ac-aquo coordination complex. Our X-ray absorption fine structure study revealed 10.9 ± 0.5 water molecules directly coordinated to the AcIII cation with an Ac–OH2O distance of 2.63(1) Å. This experimentally determined distance was consistent with molecular dynamics density functional theory results that showed (over the course of 8 ps) that AcIII was coordinated by 9 water molecules with Ac–OH2O distances ranging from 2.61 to 2.76 Å. The data is presented in the context of other actinide(III) and lanthanide(III) aquo ions characterized by XAFS and highlights the uniqueness of the large AcIII coordination numbers and long Ac–OH2O bond distances. PMID:28386595

Rural Poor Economies and Foreign Investors: An Opportunity or a Risk?

PubMed Central

Antoci, Angelo; Russu, Paolo; Ticci, Elisa

2014-01-01

In the current age of commercial and financial openness, remote and poor local economies are becoming increasingly exposed to inflows of external capital. The new investors - enjoying lower credit constraints than local dwellers - might play a propulsive role in local development. At the same time, inflows of external capital can have negative impacts on local natural resource-dependent activities. We analyze a two-sector model where both sectors damage the environment, but only that of domestic producers relies on natural resources. We assess under which conditions the coexistence of the two sectors is compatible with sustainability, defined as convergence to a stationary state characterized by a positive stock of the natural resource. Moreover, we find that capital inflows can be stimulated by an increase in the pollution intensity of incoming activities, but also in the pollution intensity of the domestic sector; in both cases, capital inflows generate environmental degradation and a decrease in welfare for the local population. Finally, we show that a reduction in the cost of capital for external investors and the consequent capital inflows have the effect to increase wages, local investments and welfare of the local populations only if the environmental impact of the external sector is relatively low with respect to that of local activities. Otherwise, an unexpected scenario characterized by a reduction in domestic capital accumulation and the impoverishment of local agents can occur. PMID:25506694

Solid dispersions, part I: recent evolutions and future opportunities in manufacturing methods for dissolution rate enhancement of poorly water-soluble drugs.

PubMed

Bikiaris, Dimitrios N

2011-11-01

In recent years, the number of active pharmaceutical ingredients with high therapeutic impact, but very low water solubility, has increased significantly. Thus, a great challenge for pharmaceutical technology is to create new formulations and efficient drug-delivery systems to overcome these dissolution problems. Drug formulation in solid dispersions (SDs) is one of the most commonly used techniques for the dissolution rate enhancement of poorly water-soluble drugs. Generally, SDs can be defined as a dispersion of active ingredients in molecular, amorphous and/or microcrystalline forms into an inert carrier. This review covers literature which states that the dissolution enhancement of SDs is based on the fact that drugs in the nanoscale range, or in amorphous phase, dissolve faster and to a greater extent than micronized drug particles. This is in accordance to the Noyes-Whitney equation, while the wetting properties of the used polymer may also play an important role. The main factors why SD-based pharmaceutical products on the market are steadily increasing over the last few years are: the recent progress in various methods used for the preparation of SDs, the effect of evolved interactions in physical state of the drug and formulation stability during storage, the characterization of the physical state of the drug and the mechanism of dissolution rate enhancement.

Rural poor economies and foreign investors: an opportunity or a risk?

PubMed

Antoci, Angelo; Russu, Paolo; Ticci, Elisa

2014-01-01

In the current age of commercial and financial openness, remote and poor local economies are becoming increasingly exposed to inflows of external capital. The new investors - enjoying lower credit constraints than local dwellers - might play a propulsive role in local development. At the same time, inflows of external capital can have negative impacts on local natural resource-dependent activities. We analyze a two-sector model where both sectors damage the environment, but only that of domestic producers relies on natural resources. We assess under which conditions the coexistence of the two sectors is compatible with sustainability, defined as convergence to a stationary state characterized by a positive stock of the natural resource. Moreover, we find that capital inflows can be stimulated by an increase in the pollution intensity of incoming activities, but also in the pollution intensity of the domestic sector; in both cases, capital inflows generate environmental degradation and a decrease in welfare for the local population. Finally, we show that a reduction in the cost of capital for external investors and the consequent capital inflows have the effect to increase wages, local investments and welfare of the local populations only if the environmental impact of the external sector is relatively low with respect to that of local activities. Otherwise, an unexpected scenario characterized by a reduction in domestic capital accumulation and the impoverishment of local agents can occur.

Comorbid renal tubular damage and hypoalbuminemia exacerbate cardiac prognosis in patients with chronic heart failure.

PubMed

Otaki, Yoichiro; Watanabe, Tetsu; Takahashi, Hiroki; Funayama, Akira; Kinoshita, Daisuke; Yokoyama, Miyuki; Takahashi, Tetsuya; Nishiyama, Satoshi; Arimoto, Takanori; Shishido, Tetsuro; Miyamoto, Takuya; Konta, Tsuneo; Kubota, Isao

2016-02-01

Renal tubular damage (RTD) and hypoalbuminemia are risks for poor prognosis in patients with chronic heart failure (CHF). Renal tubules play a pivotal role in amino acid and albumin reabsorption, which maintain serum albumin levels. The aims of the present study were to (1) examine the association of RTD with hypoalbuminemia, and (2) assess the prognostic importance of comorbid RTD and hypoalbuminemia in patients with CHF. We measured N-acetyl-β-D-glucosamidase (NAG) levels and the urinary β2-microglobulin to creatinine ratio (UBCR) in 456 patients with CHF. RTD was defined as UBCR ≥ 300 μg/g or NAG ≥ 14.2 U/g. There were moderate correlations between RTD markers and serum albumin (NAG, r = -0.428, P < 0.0001; UBCR, r = -0.399, P < 0.0001). Multivariate logistic analysis showed that RTD was significantly related to hypoalbuminemia in patients with CHF. There were 134 cardiac events during a median period of 808 days. The comorbidity of RTD and hypoalbuminemia was increased with advancing New York Heart Association functional class. Multivariate Cox proportional hazard regression analysis showed that the presence of RTD and hypoalbuminemia was associated with cardiac events. The net reclassification index was significantly improved by adding RTD and hypoalbuminemia to the basic risk factors. Comorbid RTD and hypoalbuminemia are frequently observed and increase the risk for extremely poor outcome in patients with CHF.

Induction of Inhibitory Receptors on T Cells During Plasmodium vivax Malaria Impairs Cytokine Production

PubMed Central

Costa, Pedro A. C.; Leoratti, Fabiana M. S.; Figueiredo, Maria M.; Tada, Mauro S.; Pereira, Dhelio B.; Junqueira, Caroline; Soares, Irene S.; Barber, Daniel L.; Gazzinelli, Ricardo T.; Antonelli, Lis R. V.

2015-01-01

The function and regulation of the immune response triggered during malaria is complex and poorly understood, and there is a particular paucity of studies conducted in humans infected with Plasmodium vivax. While it has been proposed that T-cell-effector responses are crucial for protection against blood-stage malaria in mice, the mechanisms behind this in humans remain poorly understood. Experimental models of malaria have shown that the regulatory molecules, cytotoxic T-lymphocyte attenuator-4 (CTLA-4), lymphocyte activation gene-3 (LAG-3), and programmed death-1 (PD-1) are involved in the functional impairment of T cells during infection. Our goal was to define the role of these molecules during P. vivax malaria. We demonstrate that infection triggers the expression of regulatory molecules on T cells. The pattern of expression differs in CD4+ and CD8+ T cells. Higher frequencies of CD4+ express more than 1 regulatory molecule compared to CD8+ T cells. Moreover, lower proportions of CD4+ T cells coexpress regulatory molecules, but are still able to proliferate. Importantly, simultaneously blockade of the CLTA-4, PD-1, and T-cell immunoglobulin and mucin–3 signaling restores the cytokine production by antigen-specific cells. These data support the hypothesis that upregulation of inhibitory receptors on T cells during P. vivax malaria impairs parasite-specific T-cell effector function. PMID:26019284

Rhythm production at school entry as a predictor of poor reading and spelling at the end of first grade.

PubMed

Lundetræ, Kjersti; Thomson, Jenny M

2018-01-01

Rhythm plays an organisational role in the prosody and phonology of language, and children with literacy difficulties have been found to demonstrate poor rhythmic perception. This study explored whether students' performance on a simple rhythm task at school entry could serve as a predictor of whether they would face difficulties in word reading and spelling at the end of grade 1. The participants were 479 Norwegian 6-year-old first graders randomized as controls in the longitudinal RCT on track (n = 1171). Rhythmic timing and pre-reading skills were tested individually at school entry on a digital tablet. On the rhythm task, the students were told to tap a drum appearing on the screen to two different rhythms (2 Hz paced and 1.5 Hz paced). Children's responses were recorded as they tapped on the screen with their index finger. Significant group differences were found in rhythm tapping ability measured at school entry, when groups were defined upon whether children went on to score above or below the 20th percentile reading and spelling thresholds in national assessment tests at the end of grade one. Inclusion of the school-entry rhythmic tapping measure into a model of classification accuracy for above or below threshold reading and spelling improved accuracy of classification by 6.2 and 9.2% respectively.

The Gradual Shift of Overweight, Obesity, and Abdominal Obesity Towards the Poor in a Multi-ethnic Developing Country: Findings From the Malaysian National Health and Morbidity Surveys

PubMed Central

Mariapun, Jeevitha; Ng, Chiu-Wan; Hairi, Noran N.

2018-01-01

Background Economic development is known to shift the distribution of obesity from the socioeconomically more advantaged to the less advantaged. We assessed the socioeconomic trends in overweight, obesity, and abdominal obesity across a period of significant economic growth. Methods We used the Malaysian National Health and Morbidity Survey data sets for the years 1996, 2006, and 2011 to analyze the trends among adults aged 30 years and above. The World Health Organization’s Asian body mass index cut-off points of ≥23.0 kg/m2 and ≥27.5 kg/m2 were used to define overweight and obesity, respectively. Abdominal obesity was defined as having a waist circumference of ≥90 cm for men and ≥80 cm for women. Household per-capita income was used as a measure of socioeconomic position. As a summary measure of inequality, we computed the concentration index. Results Women in Peninsular Malaysia demonstrated patterns that were similar to that of developed countries in which the distributions for overweight, obesity, and abdominal obesity became concentrated among the poor. For women in East Malaysia, distributions became neither concentrated among the rich nor poor, while distributions for men were still concentrated among the rich. Chinese women, particularly from the richest quintile, had the lowest rates and lowest increase in overweight and obesity. All distributions of Chinese women were concentrated among the poor. The distributions of Malay men were still concentrated among the rich, while distributions for Chinese and Indian men and Malay and Indian women were neither concentrated among the rich nor poor. Conclusion As the country continues to progress, increasing risks of overweight and obesity among the socioeconomically less advantaged is expected. PMID:29657257

The Gradual Shift of Overweight, Obesity, and Abdominal Obesity Towards the Poor in a Multi-ethnic Developing Country: Findings From the Malaysian National Health and Morbidity Surveys.

PubMed

Mariapun, Jeevitha; Ng, Chiu-Wan; Hairi, Noran N

2018-06-05

Economic development is known to shift the distribution of obesity from the socioeconomically more advantaged to the less advantaged. We assessed the socioeconomic trends in overweight, obesity, and abdominal obesity across a period of significant economic growth. We used the Malaysian National Health and Morbidity Survey data sets for the years 1996, 2006, and 2011 to analyze the trends among adults aged 30 years and above. The World Health Organization's Asian body mass index cut-off points of ≥23.0 kg/m 2 and ≥27.5 kg/m 2 were used to define overweight and obesity, respectively. Abdominal obesity was defined as having a waist circumference of ≥90 cm for men and ≥80 cm for women. Household per-capita income was used as a measure of socioeconomic position. As a summary measure of inequality, we computed the concentration index. Women in Peninsular Malaysia demonstrated patterns that were similar to that of developed countries in which the distributions for overweight, obesity, and abdominal obesity became concentrated among the poor. For women in East Malaysia, distributions became neither concentrated among the rich nor poor, while distributions for men were still concentrated among the rich. Chinese women, particularly from the richest quintile, had the lowest rates and lowest increase in overweight and obesity. All distributions of Chinese women were concentrated among the poor. The distributions of Malay men were still concentrated among the rich, while distributions for Chinese and Indian men and Malay and Indian women were neither concentrated among the rich nor poor. As the country continues to progress, increasing risks of overweight and obesity among the socioeconomically less advantaged is expected.

High urinary albumin/creatinine ratio at admission predicts poor functional outcome in patients with acute ischaemic stroke.

PubMed

Watanabe, Yoko; Suda, Satoshi; Kanamaru, Takuya; Katsumata, Toshiya; Okubo, Seiji; Kaneko, Tomohiro; Mii, Akiko; Sakai, Yukinao; Katayama, Yasuo; Kimura, Kazumi; Tsuruoka, Shuichi

2017-03-01

Albuminuria and a low estimated glomerular filtration rate (eGFR) are widely recognized indices of kidney dysfunction and have been linked to cardiovascular events, including stroke. We evaluated albuminuria, measured using the urinary albumin/creatinine ratio (UACR), and the eGFR in the acute phase of ischaemic stroke, and investigated the clinical characteristics of ischaemic stroke patients with and those without kidney dysfunction. The study included 422 consecutive patients admitted between June 2010 and May 2012. General blood and urine examinations were performed at admission. Kidney dysfunction was defined as a low eGFR (<60 mL/min per 1.73 m 2 ), high albuminuria (≥30 mg/g creatinine), or both. Neurological severity was evaluated using the National Institutes of Health Stroke Scale (NIHSS) at admission and the modified Rankin scale (mRS) at discharge. A poor outcome was defined as a mRS score of 3-5 or death. The impacts of the eGFR and UACR on outcomes at discharge were evaluated using multiple logistic regression analysis. Kidney dysfunction was diagnosed in 278 of the 422 patients (65.9%). The eGFR was significantly lower and UACR was significantly higher in patients with a poor outcome than in those with a good outcome. In multivariate analyses performed after adjusting for confounding factors, UACR >31.2 mg/g creatinine (OR, 2.58; 95% CI, 1.52-4.43; P = 0.0005) was independently associated with a poor outcome, while a low eGFR was not associated. A high UACR at admission may predict a poor outcome at discharge in patients with acute ischaemic stroke. © 2016 Asian Pacific Society of Nephrology.

Sleep and Depression in Postpartum Women: A Population-Based Study

PubMed Central

Dørheim, Signe Karen; Bondevik, Gunnar Tschudi; Eberhard-Gran, Malin; Bjorvatn, Bjørn

2009-01-01

Study Objectives: (1) To describe the prevalence of and risk factors for postpartum maternal sleep problems and depressive symptoms simultaneously, (2) identify factors independently associated with either condition, and (3) explore associations between specific postpartum sleep components and depression. Design: Cross-sectional. Setting: Population-based. Participants: All women (n = 4191) who had delivered at Stavanger University Hospital from October 2005 to September 2006 were mailed a questionnaire seven weeks postpartum. The response rate was 68% (n = 2830). Interventions: None. Measurements and results: Sleep was measured using the Pittsburgh Sleep Quality Index (PSQI), and depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS). The prevalence of sleep problems, defined as PSQI > 5, was 57.7%, and the prevalence of depression, defined as EPDS ≥ 10, was 16.5%. The mean self-reported nightly sleep duration was 6.5 hours and sleep efficiency 73%. Depression, previous sleep problems, being primiparous, not exclusively breastfeeding, or having a younger or male infant were factors associated with poor postpartum sleep quality. Poor sleep was also associated with depression when adjusted for other significant risk factors for depression, such as poor partner relationship, previous depression, depression during pregnancy and stressful life events. Sleep disturbances and subjective sleep quality were the aspects of sleep most strongly associated with depression. Conclusions: Poor sleep was associated with depression independently of other risk factors. Poor sleep may increase the risk of depression in some women, but as previously known risk factors were also associated, mothers diagnosed with postpartum depression are not merely reporting symptoms of chronic sleep deprivation. Citation: Dørheim SK; Bondevik GT; Eberhard-Gran M; Bjorvatn B. Sleep and depression in postpartum women: a population-based study. SLEEP 2009;32(7):847-855. PMID:19639747

Language Impairment From 4 to 12 Years: Prediction and Etiology

PubMed Central

Hayiou-Thomas, Marianna E.; Dale, Philip S.; Plomin, Robert

2014-01-01

Purpose The authors of this article examined the etiology of developmental language impairment (LI) at 4 and 12 years of age, as well as the relationship between the 2. Method Phenotypic and quantitative genetic analyses using longitudinal data from the Twins Early Development Study (Oliver & Plomin, 2007) were conducted. A total of 2,923 pairs of twins (1,075 monozygotic [MZ]; 975 dizygotic same sex [DZss]; and 873 dizygotic opposite sex [DZos]) provided data at 4 and 12 years. At 4 years, (a) psychometric LI was defined on the basis of a low parent-reported expressive vocabulary score (−1.25 SDs; 226 MZ and 115 DZss probands for genetic analysis); and (b) parent referral was defined as having seen a medical professional or speech-language pathologist following parental concern (112 MZ and 104 DZss probands). The 12-year language measure was a composite of 4 web-administered receptive language tests. Results (a) Psychometric LI at 4 years is more predictive than parent referral of poor language performance at age 12 years, and (b) parent referral is substantially and significantly more heritable than psychometric LI. Conclusions Parents’ concern about their child’s language development seems to be the marker of a more heritable disorder than poor expressive language skills alone. However, the language difficulties that arouse parental concern in preschool children, although more heritable, are not predictive of language difficulties in early adolescence. Rather, poor expressive language skills at age 4 years, psychometrically defined, are a better predictor than parent referral of continuing language difficulties at age 12 years. PMID:24167234

Evidence for Broadening Criteria for Atypical Depression Which May Define a Reactive Depressive Disorder.

PubMed

Silverstein, Brett; Angst, Jules

2015-01-01

Objective. Arguing that additional symptoms should be added to the criteria for atypical depression. Method. Published research articles on atypical depression are reviewed. Results. (1) The original studies upon which the criteria for atypical depression were based cited fatigue, insomnia, pain, and loss of weight as characteristic symptoms. (2) Several studies of DSM depressive criteria found patients with atypical depression to exhibit high levels of insomnia, fatigue, and loss of appetite/weight. (3) Several studies have found atypical depression to be comorbid with headaches, bulimia, and body image issues. (4) Most probands who report atypical depression meet criteria for "somatic depression," defined as depression associated with several of disordered eating, poor body image, headaches, fatigue, and insomnia. The gender difference in prevalence of atypical depression results from its overlap with somatic depression. Somatic depression is associated with psychosocial measures related to gender, linking it with the descriptions of atypical depression as "reactive" appearing in the studies upon which the original criteria for atypical depression were based. Conclusion. Insomnia, disordered eating, poor body image, and aches/pains should be added as criteria for atypical depression matching criteria for somatic depression defining a reactive depressive disorder possibly distinct from endogenous melancholic depression.

Unilateral congenital corneal keloid with anterior segment mesenchymal dysgenesis and subluxated lens: case report and review of literature.

PubMed

Vanathi, M; Sen, Seema; Panda, Anita; Dada, Tanuj; Behera, Geeta; Khokhar, Sudharshan

2007-01-01

To report the unusual association of unilateral congenital corneal keloid with anterior-segment mesenchymal dysgenesis and bilateral subluxated lens. A 20-year old man presented with a mass lesion involving the left cornea. The corneal lesion had been present since birth. On biomicroscopic examination, a well-defined vascularized, grayish-white mass occupying the whole of the left cornea was seen. The right eye showed multiple peripheral corneal opacities with iridocorneal adhesions, a poorly defined supranasal limbus, and a subluxated lens. Excision biopsy of the mass was done for histopathologic examination. Histopathologic examination of the excised corneal mass showed features consistent with that of a corneal keloid: thickened keratinized epithelium, absent Bowman membrane layer, and fibrovascular hyperplasia composed of hyalinized collagen fibers with irregular orientation of the collagen lamellae. During penetrating keratoplasty of the left eye, an anomalous iris pattern with poorly defined angle and a supranasal subluxated lens was also observed. Extraction of the subluxated lens was also done. The graft failed subsequent to a nonhealing persistent epithelial defect. Our case report highlights the rare association of a unilateral congenital corneal keloid with anterior-segment mesenchymal dysgenesis and bilateral subluxated lens.

Planning the Breast Boost: Comparison of Three Techniques and Evolution of Tumor Bed During Treatment

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

Hepel, Jaroslaw T.; Department of Radiation Oncology, Brown University, Rhode Island Hospital, Providence, RI; Evans, Suzanne B.

2009-06-01

Purpose: To evaluate the accuracy of two clinical techniques for electron boost planning compared with computed tomography (CT)-based planning. Additionally, we evaluated the tumor bed characteristics at whole breast planning and boost planning. Methods and Materials: A total of 30 women underwent tumor bed boost planning within 2 weeks of completing whole breast radiotherapy using three planning techniques: scar-based planning, palpation/clinical-based planning, and CT-based planning. The plans were analyzed for dosimetric coverage of the CT-delineated tumor bed. The cavity visualization score was used to define the CT-delineated tumor bed as well or poorly defined. Results: Scar-based planning resulted in inferiormore » tumor bed coverage compared with CT-based planning, with the minimal dose received by 90% of the target volume >90% in 53% and a geographic miss in 53%. The results of palpation/clinical-based planning were significantly better: 87% and 10% for the minimal dose received by 90% of the target volume >90% and geographic miss, respectively. Of the 30 tumor beds, 16 were poorly defined by the cavity visualization score. Of these 16, 8 were well demarcated by the surgical clips. The evaluation of the 22 well-defined tumor beds revealed similar results. A comparison of the tumor bed volume from the initial planning CT scan to the boost planning CT scan revealed a decrease in size in 77% of cases. The mean decrease in volume was 52%. Conclusion: The results of our study have shown that CT-based planning allows for optimal tumor bed coverage compared with clinical and scar-based approaches. However, in the setting of a poorly visualized cavity on CT without surgical clips, palpation/clinical-based planning can help delineate the appropriate target volumes and is superior to scar-based planning. CT simulation at boost planning could allow for a reduction in the boost volumes.« less

A tissue-engineered subcutaneous pancreatic cancer model for antitumor drug evaluation.

PubMed

He, Qingyi; Wang, Xiaohui; Zhang, Xing; Han, Huifang; Han, Baosan; Xu, Jianzhong; Tang, Kanglai; Fu, Zhiren; Yin, Hao

2013-01-01

The traditional xenograft subcutaneous pancreatic cancer model is notorious for its low incidence of tumor formation, inconsistent results for the chemotherapeutic effects of drug molecules of interest, and a poor predictive capability for the clinical efficacy of novel drugs. These drawbacks are attributed to a variety of factors, including inoculation of heterogeneous tumor cells from patients with different pathological histories, and use of poorly defined Matrigel(®). In this study, we aimed to tissue-engineer a pancreatic cancer model that could readily cultivate a pancreatic tumor derived from highly homogenous CD24(+)CD44(+) pancreatic cancer stem cells delivered by a well defined electrospun scaffold of poly(glycolide-co-trimethylene carbonate) and gelatin. The scaffold supported in vitro tumorigenesis from CD24(+)CD44(+) cancer stem cells for up to 7 days without inducing apoptosis. Moreover, CD24(+)CD44(+) cancer stem cells delivered by the scaffold grew into a native-like mature pancreatic tumor within 8 weeks in vivo and exhibited accelerated tumorigenesis as well as a higher incidence of tumor formation than the traditional model. In the scaffold model, we discovered that oxaliplatin-gemcitabine (OXA-GEM), a chemotherapeutic regimen, induced tumor regression whereas gemcitabine alone only capped tumor growth. The mechanistic study attributed the superior antitumorigenic performance of OXA-GEM to its ability to induce apoptosis of CD24(+)CD44(+) cancer stem cells. Compared with the traditional model, the scaffold model demonstrated a higher incidence of tumor formation and accelerated tumor growth. Use of a tiny population of highly homogenous CD24(+)CD44(+) cancer stem cells delivered by a well defined scaffold greatly reduces the variability associated with the traditional model, which uses a heterogeneous tumor cell population and poorly defined Matrigel. The scaffold model is a robust platform for investigating the antitumorigenesis mechanism of novel chemotherapeutic drugs with a special focus on cancer stem cells.

THE MULTIDISCIPLINARY INFLUENCE OF COMMON SUSTAINABILITY INDICES

EPA Science Inventory

Sustainability is often poorly defined and difficult to measure. We describe several concepts based in ecology, economics, and physics that have contributed to sustainability indices, and discuss their positive and negative aspects. Indices range from mostly ecological (such as e...

Prognostic factors for return-to-work following surgery for carpal tunnel syndrome: a systematic review.

PubMed

Peters, Susan; Johnston, Venerina; Hines, Sonia; Ross, Mark; Coppieters, Michel

2016-09-01

Carpal tunnel syndrome (CTS) is a common problem, that can be effectively managed by surgery. Screening for prognostic factors is important to identify workers who are at a greater risk of a poor work outcome in order to implement tailored interventions to facilitate their return-to-work. To synthesize the best available evidence on the association of preoperative prognostic factors with work-related outcomes in people who have undergone carpal tunnel surgery. Participants included those who were employed at the time of surgery, underwent carpal tunnel surgery and planned to return-to-work. The primary outcome was return-to-work. Quantitative studies investigating at least one prognostic factor for a work-related outcome in studies of workers who had carpal tunnel surgery were considered. Eleven electronic databases were searched from their respective inception date up to July 2015. A total of 3893 publications were reviewed. The quality of the included studies was assessed by two reviewers using a modified version of an appraisal tool (Joanna Briggs Institute Meta-analysis of Statistical Assessment and Review Instrument [JBI-MAStARI]). The following criteria were evaluated: study population representativeness, clearly defined prognostic factors and outcomes, potential confounding variables and appropriate statistical analysis. Data extraction was performed using a modified version of the standardized extraction tool from JBI-MAStARI. Statistical pooling was not possible. Findings are presented in tables and narrative format. Eleven studies (13 publications) investigating 93 prognostic factors for delayed return-to-work or prolonged work disability outcomes and 27 prognostic factors for work role functioning in 4187 participants were identified.Prognostic factors associated with workers' increased likelihood of an earlier return-to-work in a moderate-to-high-quality study included worker expected or desired fewer days off work, occupation, lower pain anxiety and if CTS had not altered their work role.Prognostic factors for a poorer work-related outcome included older age, lower household income, greater upper extremity functional limitation, greater than two musculoskeletal pain sites, lower recovery expectations, worse mental health status, job accommodation availability, high job strain, high job demands with high job control, poor co-worker relationships, poor baseline work role functioning, less-supportive workplace policies, preoperative work absence due to CTS or work disability of any cause, workers' compensation status, attorney involvement, and post-diagnosis surgical wait time. For workers who have had carpal tunnel surgery, there are a number of factors which may be modified in order to improve return-to-work times.

The relationship between serum asymmetric dimethylarginine levels and subjective sleep quality in normotensive patients with type 2 diabetes mellitus.

PubMed

Aribas, Alpay; Kayrak, Mehmet; Tekinalp, Mehmet; Akilli, Hakan; Alibasic, Hayrudin; Yildirim, Serkan; Gunduz, Mehmet; Taner, Alpaslan; Unlu, Ali

2015-05-01

Poor sleep quality (SQ) is associated with increased cardiovascular mortality and morbidity. Additionally, asymmetric dimethylarginine (ADMA) is an independent predictor of cardiovascular mortality and morbidity. However, no sufficient data regarding the relationship between ADMA levels and SQ have been reported. The goal of the current study was to evaluate the association between SQ and ADMA levels in normotensive patients with type 2 diabetes mellitus. The study participants consisted of 78 normotensive type 2 diabetics. The SQ of all participants was assessed using the Pittsburgh Sleep Quality Index (PSQI). Patients with a global PSQI score > 5 were defined as "poor sleepers." Factors associated with poor SQ were analyzed using a multiple regression model. Serum ADMA levels were measured using high performance liquid chromatography. The median ADMA levels of the poor sleepers were increased compared with patients defined as good sleepers (5.5 [4.2 to 6.6] vs. 4.4 [2.9 to 5.4], p < 0.01, respectively). However, the L-arginine/ADMA ratio was decreased in poor sleepers (p < 0.01). Global PSQI scores were positively correlated with ADMA levels (p < 0.01) and negatively correlated with the L-arginine/ADMA ratio (p = 0.02). ADMA levels were correlated with sleep latency (p < 0.01) and sleep efficiency (p = 0.01). Logistic regression analysis showed that ADMA levels (odds ratio [OR], 1.68; 95% confidence interval [CI], 1.16 to 2.44; p = 0.01) and body mass index (OR, 1.15; 95% CI, 1.01 to 1.31; p = 0.04) were associated with poor SQ independently of glomerular filtration rate, sex, age, duration of diabetes, hemoglobin A1c, total cholesterol, and systolic blood pressure. Self-reported SQ was independently associated with ADMA levels in normotensive patients with diabetes mellitus.

Poor safety climate, long work hours, and musculoskeletal discomfort among Latino horse farm workers.

PubMed

Swanberg, Jennifer; Clouser, Jessica Miller; Gan, Wenqi; Flunker, John C; Westneat, Susan; Browning, Steven R

2017-09-03

This study investigated the prevalence of self-reported musculoskeletal discomfort (MSD) and work-related factors associated with elevated MSD among Latino thoroughbred farm workers. Participants (N = 225) were recruited using a community-based purposive sampling approach to participate in in-person interviews. Of these workers, 85% experienced MSD. MSD was divided into tertiles; the upper tertile was defined as elevated. Multivariable Poisson regression revealed associations between any elevated MSD and longer tenure on horse farms, longer work hours, and poor safety climate. Elevated neck/back MSD was associated with longer tenure, longer work hours, and poor safety climate. Elevated upper extremity MSD was associated with age and poor safety climate. Elevated lower extremity MSD was associated with longer tenure, longer work hours, and being female. Musculoskeletal discomfort is common among these workers. Improving safety climate and minimizing long work hours is recommended.

[Analysis of population survey for determining the factors associated with the control diabetes mellitus in Mexico].

PubMed

Hernández-Romieu, Alfonso Claudio; Elnecavé-Olaiz, Alejandro; Huerta-Uribe, Nidia; Reynoso-Noverón, Nancy

2011-01-01

Determine the influence of nutritional counseling, exercise, access to social healthcare and drugs, and the quality of medical care on the control of diabetics. The information and blood samples were obtained in 2005. Glycemic control was defined as good if HbA1c was ≤7.0%, poor from 7.01%-9.50% and very poor if HbA1c >9.5%. Binary logistic regression models were used to determine the association of these factors with HbA1c>9.5%. Thirty percent of the patients with a medical diagnosis of diabetes had adequate metabolic control. Nutritional guidance was associated with an increase in the degree of control. A majority of diabetics have poor or very poor glycemic control. Strengthening the quality of and access to medical care for these patients is urgently needed.

Job role quality and intention to leave current facility and to leave profession of direct care workers in Japanese residential facilities for elderly.

PubMed

Nakanishi, Miharu; Imai, Hisato

2012-01-01

The aim of the present study is to examine job role quality relating to intention to leave current facility and to leave profession among direct care workers in residential facilities for elderly in Japan. Direct care workers completed a paper questionnaire on October 2009. From 746 facilities in three prefectures (Tokyo, Shizuoka, and Yamagata) 6428 direct care workers with complete data were included in the analyses. The Job Role Quality (JRQ) scale was translated into Japanese language to assess job role quality. Hierarchical multiple regression analysis showed that intention to leave current facility was primarily associated with job role quality: poor skill discretion, high job demand, and poor relationship with supervisor. Intention to leave profession was primarily associated with poor skill discretion. The results of the present study imply the strategies to direct care worker retention for each facility and policy efforts. Each facility can implement specific strategies such as enhanced variety of work and opportunity for use of skills, adequate job allocation, and improvement of supervisor-employee relationship in work place. Policy efforts should enhance broader career opportunities in care working such as advanced specialization and authorized medical practice. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

48 CFR 1509.170-4 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-10-01

... each performance category. Ratings are defined as follows: 0 = unsatisfactory, 1 = poor, 2 = fair, 3... PLANNING CONTRACTOR QUALIFICATIONS Contractor Performance Evaluations 1509.170-4 Definitions. (a) Contractor Performance Report is an evaluation of a contractor's performance for a specified period of time...

Knocking-out matrix metalloproteinase-13 exacerbates rotator cuff muscle fatty infiltration

PubMed Central

Liu, Xuhui; Ravishankar, Bharat; Ning, Anne; Liu, Mengyao; Kim, Hubert T.; Feeley, Brian T.

2017-01-01

Summary Introduction Rotator cuff (RC) tears are common tendon injuries. Clinically, both muscle atrophy and fatty infiltration have generally been attributed to poor functional outcomes. Matrix metalloproteinase-13 plays a crucial role in extracellular matrix remodeling in many physiological and pathological processes. Nevertheless, its role in rotator cuff muscle atrophy and fatty infiltration remains unknown. The purpose of this study is to define the functional role of MMP-13 in rotator cuff muscle atrophy and fatty infiltration using a mouse RC tears model. Materials and methods Unilateral complete supraspinatus and infraspinatus tendon transection and suprascapular nerve transection was performed on nine of MMP-13 (−/−) knockout and nine of MMP-13 (+/+) wildtype mice at 3 months old. Mice were sacrificed 6 weeks after surgery. Supraspinatus (SS) and infraspinatus (IS) muscles were harvested for histology and gene expression analysis with RT-PCR. Results Six weeks after RC surgery, no significant difference in muscle atrophy and fibrosis between MMP-13 knockout and wild type mice was observed. However, there was a significant increase in the amount of fatty infiltration in MMP-13 knockout mice compared to the wild types. Muscles from MMP-13 knockout mice have significantly higher expression of fatty infiltration related genes. Discussion Results from this study suggest that MMP-13 plays a crucial role in rotator cuff muscle fatty degeneration. This novel finding suggests a new molecular mechanism that governs RC muscle FI and MMP-13 may serve as a target for therapeutics to treat muscle FI after RC tears. PMID:29264329

Role of India's wildlife in the emergence and re-emergence of zoonotic pathogens, risk factors and public health implications.

PubMed

Singh, B B; Gajadhar, A A

2014-10-01

Evolving land use practices have led to an increase in interactions at the human/wildlife interface. The presence and poor knowledge of zoonotic pathogens in India's wildlife and the occurrence of enormous human populations interfacing with, and critically linked to, forest ecosystems warrant attention. Factors such as diverse migratory bird populations, climate change, expanding human population and shrinking wildlife habitats play a significant role in the emergence and re-emergence of zoonotic pathogens from India's wildlife. The introduction of a novel Kyasanur forest disease virus (family flaviviridae) into human populations in 1957 and subsequent occurrence of seasonal outbreaks illustrate the key role that India's wild animals play in the emergence and reemergence of zoonotic pathogens. Other high priority zoonotic diseases of wildlife origin which could affect both livestock and humans include influenza, Nipah, Japanese encephalitis, rabies, plague, leptospirosis, anthrax and leishmaniasis. Continuous monitoring of India's extensively diverse and dispersed wildlife is challenging, but their use as indicators should facilitate efficient and rapid disease-outbreak response across the region and occasionally the globe. Defining and prioritizing research on zoonotic pathogens in wildlife are essential, particularly in a multidisciplinary one-world one-health approach which includes human and veterinary medical studies at the wildlife-livestock-human interfaces. This review indicates that wild animals play an important role in the emergence and re-emergence of zoonotic pathogens and provides brief summaries of the zoonotic diseases that have occurred in wild animals in India. Copyright © 2014 Elsevier B.V. All rights reserved.

The underestimated role of temperature-oxygen relationship in large-scale studies on size-to-temperature response.

PubMed

Walczyńska, Aleksandra; Sobczyk, Łukasz

2017-09-01

The observation that ectotherm size decreases with increasing temperature (temperature-size rule; TSR) has been widely supported. This phenomenon intrigues researchers because neither its adaptive role nor the conditions under which it is realized are well defined. In light of recent theoretical and empirical studies, oxygen availability is an important candidate for understanding the adaptive role behind TSR. However, this hypothesis is still undervalued in TSR studies at the geographical level. We reanalyzed previously published data about the TSR pattern in diatoms sampled from Icelandic geothermal streams, which concluded that diatoms were an exception to the TSR. Our goal was to incorporate oxygen as a factor in the analysis and to examine whether this approach would change the results. Specifically, we expected that the strength of size response to cold temperatures would be different than the strength of response to hot temperatures, where the oxygen limitation is strongest. By conducting a regression analysis for size response at the community level, we found that diatoms from cold, well-oxygenated streams showed no size-to-temperature response, those from intermediate temperature and oxygen conditions showed reverse TSR, and diatoms from warm, poorly oxygenated streams showed significant TSR. We also distinguished the roles of oxygen and nutrition in TSR. Oxygen is a driving factor, while nutrition is an important factor that should be controlled for. Our results show that if the geographical or global patterns of TSR are to be understood, oxygen should be included in the studies. This argument is important especially for predicting the size response of ectotherms facing climate warming.

Role of neurotransmitter Substance P in progression of oral squamous cell carcinoma.

PubMed

Mehboob, Riffat; Tanvir, Imrana; Warraich, Riaz Ahmad; Perveen, Shahida; Yasmeen, Sehrish; Ahmad, Fridoon Jawad

2015-03-01

Oral squamous cell carcinoma (OSCC) is the most frequent type of head and neck cancers. In the present study, we evaluated the expression and distribution of Substance P (SP) in different grades of OSCC and role of SP in its proliferation and progression. Forty OSCC biopsies were immunohistochemically analyzed by using SP antibody, including 29 male and 11 female cases. 35% were well differentiated, 35% moderately differentiated and 30% poorly differentiated OSCC. The majority of patients were in the age range of 41-80 years. 62% of the cases were positive for SP. SP positivity was expressed in the cytoplasm of the tumor cells. Most of the positive cases were from the tongue region. 93% of moderately differentiated, 92% of poorly differentiated and 8% of well-differentiated carcinomas were SP-positive, but SP expression intensity was highest in poorly differentiated cases (+3). More positive patients were males (68.96% of all male patients) with moderately and poorly differentiated OSCC. Among all positive cases, 48% were poorly differentiated, 48% moderately differentiated and 4% well differentiated. Strong expression of SP in poorly and moderately differentiated cases suggests a role of SP in the progression and development of tumor. Expression of SP in the current study increased as the proliferation of cells increased. Prevalence of oral cancer in males may be due to the fact that they smoke and use pan, chewing gum, beetle nut etc. in this region. SP antagonists can help in the reduction and inhibition of oral cancer. SP has a diagnostic value with sensitivity of 92.5% and specificity of 93.7%. The positive predictive value is 96.2% and the negative predictive value 88.2%. Copyright © 2014 Elsevier GmbH. All rights reserved.

Genome-wide profiles of CtBP link metabolism with genome stability and epithelial reprogramming in breast cancer.

PubMed

Di, Li-Jun; Byun, Jung S; Wong, Madeline M; Wakano, Clay; Taylor, Tara; Bilke, Sven; Baek, Songjoon; Hunter, Kent; Yang, Howard; Lee, Maxwell; Zvosec, Cecilia; Khramtsova, Galina; Cheng, Fan; Perou, Charles M; Miller, C Ryan; Raab, Rachel; Olopade, Olufunmilayo I; Gardner, Kevin

2013-01-01

The C-terminal binding protein (CtBP) is a NADH-dependent transcriptional repressor that links carbohydrate metabolism to epigenetic regulation by recruiting diverse histone-modifying complexes to chromatin. Here global profiling of CtBP in breast cancer cells reveals that it drives epithelial-to-mesenchymal transition, stem cell pathways and genome instability. CtBP expression induces mesenchymal and stem cell-like features, whereas CtBP depletion or caloric restriction reverses gene repression and increases DNA repair. Multiple members of the CtBP-targeted gene network are selectively downregulated in aggressive breast cancer subtypes. Differential expression of CtBP-targeted genes predicts poor clinical outcome in breast cancer patients, and elevated levels of CtBP in patient tumours predict shorter median survival. Finally, both CtBP promoter targeting and gene repression can be reversed by small molecule inhibition. These findings define broad roles for CtBP in breast cancer biology and suggest novel chromatin-based strategies for pharmacologic and metabolic intervention in cancer.

Establishing good collaborative research practices in the responsible conduct of research in nursing science.

PubMed

Ulrich, Connie M; Wallen, Gwenyth R; Cui, Naixue; Chittams, Jesse; Sweet, Monica; Plemmons, Dena

2015-01-01

Team science is advocated to speed the pace of scientific discovery, yet the goals of collaborative practice in nursing science and the responsibilities of nurse stakeholders are sparse and inconclusive. The purpose of this study was to examine nurse scientists' views on collaborative research as part of a larger study on standards of scientific conduct. Web-based descriptive survey of nurse scientists randomly selected from 50 doctoral graduate programs in the United States. Nearly forty percent of nurse respondents were not able to identify good collaborative practices for the discipline; more than three quarters did not know of any published guidelines available to them. Successful research collaborations were challenged by different expectations of authorship and data ownership, lack of timeliness and communication, poorly defined roles and responsibilities, language barriers, and when they involve junior and senior faculty working together on a project. Individual and organizational standards, practices, and policies for collaborative research needs clarification within the discipline. Copyright © 2015 Elsevier Inc. All rights reserved.

Radiation recall dermatitis, panniculitis, and myositis following cyclophosphamide therapy: histopathologic findings of a patient affected by multiple myeloma.

PubMed

Borroni, Giovanni; Vassallo, Camilla; Brazzelli, Valeria; Martinoli, Sara; Ardigò, Marco; Alessandrino, Paolo Emilio; Borroni, Riccardo Giovanni; Franchini, Pietro

2004-06-01

Radiation recall dermatitis is one of the skin sequelae that may affect oncology patients. It occurs in a previously irradiated field, when subsequent chemotherapy is given. The eruption may be elicited by chemotherapy, even several months after radiotherapy. Its mechanism is poorly understood, and the histopathologic findings have received, to date, only sketchy descriptions. A 55-year-old male affected by multiple myeloma received radiation therapy both on his left coxofemoral area, and lumbar region (D11-L1). After cyclophosphamide administration, he developed 2 well defined square-shaped, infiltrated erythematoviolaceous plaques in the prior irradiated fields. Histopathologic findings revealed a diffusely fibrosclerosing process, involving deep dermis, hypodermis, as well as the underlying muscle, while sparing the epidermis and superficial-mid dermis. Histopathology was indistinguishable from deep radio-dermatitis, panniculitis, and myositis. This is the first case providing clear evidence of the causative role of cyclophosphamide in inducing a cutaneous and subcutaneous radiation recall reaction.

Gut microbiota utilize immunoglobulin A for mucosal colonization.

PubMed

Donaldson, G P; Ladinsky, M S; Yu, K B; Sanders, J G; Yoo, B B; Chou, W-C; Conner, M E; Earl, A M; Knight, R; Bjorkman, P J; Mazmanian, S K

2018-05-18

The immune system responds vigorously to microbial infection while permitting lifelong colonization by the microbiome. Mechanisms that facilitate the establishment and stability of the gut microbiota remain poorly described. We found that a regulatory system in the prominent human commensal Bacteroides fragilis modulates its surface architecture to invite binding of immunoglobulin A (IgA) in mice. Specific immune recognition facilitated bacterial adherence to cultured intestinal epithelial cells and intimate association with the gut mucosal surface in vivo. The IgA response was required for B. fragilis (and other commensal species) to occupy a defined mucosal niche that mediates stable colonization of the gut through exclusion of exogenous competitors. Therefore, in addition to its role in pathogen clearance, we propose that IgA responses can be co-opted by the microbiome to engender robust host-microbial symbiosis. Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

COLD CO GAS IN THE DISK OF THE YOUNG ERUPTIVE STAR EX LUP

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

Kóspál, Á.; Ábrahám, P.; Moór, A.

EX Lupi-type objects (EXors) form a sub-class of T Tauri stars, defined by sudden sporadic flare-ups of 1–5 mag at optical wavelengths. These eruptions are attributed to enhanced mass accretion from the circumstellar disk to the star, and may constitute important events in shaping the structure of the inner disk and the forming planetary system. Although disk properties must play a fundamental role in driving the outbursts, they are surprisingly poorly known. In order to characterize the dust and gas components of EXor disks, here we report on observations of the {sup 12}CO J = 3−2 and 4–3 lines, and themore » {sup 13}CO 3–2 line in EX Lup, the prototype of the EXor class. We reproduce the observed line fluxes and profiles with a line radiative transfer model and compare the obtained parameters with corresponding ones of other T Tauri disks.« less

Exploring the metabolic syndrome: Nonalcoholic fatty pancreas disease

PubMed Central

Catanzaro, Roberto; Cuffari, Biagio; Italia, Angelo; Marotta, Francesco

2016-01-01

After the first description of fatty pancreas in 1933, the effects of pancreatic steatosis have been poorly investigated, compared with that of the liver. However, the interest of research is increasing. Fat accumulation, associated with obesity and the metabolic syndrome (MetS), has been defined as “fatty infiltration” or “nonalcoholic fatty pancreas disease” (NAFPD). The term “fatty replacement” describes a distinct phenomenon characterized by death of acinar cells and replacement by adipose tissue. Risk factors for developing NAFPD include obesity, increasing age, male sex, hypertension, dyslipidemia, alcohol and hyperferritinemia. Increasing evidence support the role of pancreatic fat in the development of type 2 diabetes mellitus, MetS, atherosclerosis, severe acute pancreatitis and even pancreatic cancer. Evidence exists that fatty pancreas could be used as the initial indicator of “ectopic fat deposition”, which is a key element of nonalcoholic fatty liver disease and/or MetS. Moreover, in patients with fatty pancreas, pancreaticoduodenectomy is associated with an increased risk of intraoperative blood loss and post-operative pancreatic fistula. PMID:27678349

ptk7 mutant zebrafish models of congenital and idiopathic scoliosis implicate dysregulated Wnt signalling in disease

PubMed Central

Hayes, Madeline; Gao, Xiaochong; Yu, Lisa X; Paria, Nandina; Henkelman, R. Mark; Wise, Carol A.; Ciruna, Brian

2014-01-01

Scoliosis is a complex genetic disorder of the musculoskeletal system, characterized by three-dimensional rotation of the spine. Curvatures caused by malformed vertebrae (congenital scoliosis (CS)) are apparent at birth. Spinal curvatures with no underlying vertebral abnormality (idiopathic scoliosis (IS)) most commonly manifest during adolescence. The genetic and biological mechanisms responsible for IS remain poorly understood due largely to limited experimental models. Here we describe zygotic ptk7 (Zptk7) mutant zebrafish, deficient in a critical regulator of Wnt signalling, as the first genetically defined developmental model of IS. We identify a novel sequence variant within a single IS patient that disrupts PTK7 function, consistent with a role for dysregulated Wnt activity in disease pathogenesis. Furthermore, we demonstrate that embryonic loss-of-gene function in maternal-zygotic ptk7 mutants (MZptk7) leads to vertebral anomalies associated with CS. Our data suggest novel molecular origins of, and genetic links between, congenital and idiopathic forms of disease. PMID:25182715

The use of thermal capsulorrhaphy in the treatment of multidirectional instability.

PubMed

Fitzgerald, Brian T; Watson, B Thomas; Lapoint, John M

2002-01-01

The purpose of this study is to report on our experience with thermal capsulorrhaphy in the treatment of multidirectional instability of the shoulder. Thirty-three consecutive patients (33 shoulders) with multidirectional instability were treated with arthroscopic thermal capsulorrhaphy. Twelve patients had a history of traumatic dislocation. Three patients had been previously treated with open inferior capsular shift procedures. At a mean follow-up of 36 months (range, 24-40 months), results were available for 30 patients. On the basis of the UCLA rating scale, out of a possible 35 points, the mean preoperative score was 16.7 points and postoperatively it was 30.1 points, with 3 excellent, 20 good, and 7 poor results. Twenty-three patients (76%) were returned to full activity. In our experience the majority of patients with multidirectional instability were able to return to their previous occupations in the armed forces following thermal capsulorrhaphy. More information further defining the biomechanical pathology of capsular laxity and the specific role of electrothermal shrinkage in treating shoulder instability is needed.

Forebrain deletion of the dystonia protein torsinA causes dystonic-like movements and loss of striatal cholinergic neurons

PubMed Central

Pappas, Samuel S; Darr, Katherine; Holley, Sandra M; Cepeda, Carlos; Mabrouk, Omar S; Wong, Jenny-Marie T; LeWitt, Tessa M; Paudel, Reema; Houlden, Henry; Kennedy, Robert T; Levine, Michael S; Dauer, William T

2015-01-01

Striatal dysfunction plays an important role in dystonia, but the striatal cell types that contribute to abnormal movements are poorly defined. We demonstrate that conditional deletion of the DYT1 dystonia protein torsinA in embryonic progenitors of forebrain cholinergic and GABAergic neurons causes dystonic-like twisting movements that emerge during juvenile CNS maturation. The onset of these movements coincides with selective degeneration of dorsal striatal large cholinergic interneurons (LCI), and surviving LCI exhibit morphological, electrophysiological, and connectivity abnormalities. Consistent with the importance of this LCI pathology, murine dystonic-like movements are reduced significantly with an antimuscarinic agent used clinically, and we identify cholinergic abnormalities in postmortem striatal tissue from DYT1 dystonia patients. These findings demonstrate that dorsal LCI have a unique requirement for torsinA function during striatal maturation, and link abnormalities of these cells to dystonic-like movements in an overtly symptomatic animal model. DOI: http://dx.doi.org/10.7554/eLife.08352.001 PMID:26052670

The diagnostic ability of echocardiography for infective endocarditis and its associated complications.

PubMed

Vilacosta, Isidre; Olmos, Carmen; de Agustín, Alberto; López, Javier; Islas, Fabián; Sarriá, Cristina; Ferrera, Carlos; Ortiz-Bautista, Carlos; Sánchez-Enrique, Cristina; Vivas, David; San Román, Alberto

2015-11-01

Echocardiography, transthoracic and transoesophageal, plays a key role in the diagnosis and prognosis assessment of patients with infective endocarditis. It constitutes a major Duke criterion and is pivotal in treatment guiding. Seven echocardiographic findings are major criteria in the diagnosis of infective endocarditis (IE) (vegetation, abscess, pseudoaneurysm, fistulae, new dehiscence of a prosthetic valve, perforation and valve aneurysm). Echocardiography must be performed as soon as endocarditis is suspected. Transoesophageal echocardiography should be done in most cases of left-sided endocarditis to better define the anatomic lesions and to rule out local complications. Transoesophageal echocardiography is not necessary in isolated right-sided native valve IE with good quality transthoracic examination and unequivocal echocardiographic findings. Echocardiography is a very useful tool to assess the prognosis of patients with IE at any time during the course of the disease. Echocardiographic predictors of poor outcome include presence of periannular complications, prosthetic dysfunction, low left ventricular ejection fraction, pulmonary hypertension and very large vegetations.

Bacterial fatty acids enhance recovery from the dauer larva in Caenorhabditis elegans.

PubMed

Kaul, Tiffany K; Reis Rodrigues, Pedro; Ogungbe, Ifedayo V; Kapahi, Pankaj; Gill, Matthew S

2014-01-01

The dauer larva is a specialized dispersal stage in the nematode Caenorhabditis elegans that allows the animal to survive starvation for an extended period of time. The dauer does not feed, but uses chemosensation to identify new food sources and to determine whether to resume reproductive growth. Bacteria produce food signals that promote recovery of the dauer larva, but the chemical identities of these signals remain poorly defined. We find that bacterial fatty acids in the environment augment recovery from the dauer stage under permissive conditions. The effect of increased fatty acids on different dauer constitutive mutants indicates a role for insulin peptide secretion in coordinating recovery from the dauer stage in response to fatty acids. These data suggest that worms can sense the presence of fatty acids in the environment and that elevated levels can promote recovery from dauer arrest. This may be important in the natural environment where the dauer larva needs to determine whether the environment is appropriate to support reproductive growth following dauer exit.

Tetherin Suppresses Type I Interferon Signaling by Targeting MAVS for NDP52-Mediated Selective Autophagic Degradation in Human Cells.

PubMed

Jin, Shouheng; Tian, Shuo; Luo, Man; Xie, Weihong; Liu, Tao; Duan, Tianhao; Wu, Yaoxing; Cui, Jun

2017-10-19

Tetherin (BST2/CD317) is an interferon-inducible antiviral factor known for its ability to block the release of enveloped viruses from infected cells. Yet its role in type I interferon (IFN) signaling remains poorly defined. Here, we demonstrate that Tetherin is a negative regulator of RIG-I like receptor (RLR)-mediated type I IFN signaling by targeting MAVS. The induction of Tetherin by type I IFN accelerates MAVS degradation via ubiquitin-dependent selective autophagy in human cells. Moreover, Tetherin recruits E3 ubiquitin ligase MARCH8 to catalyze K27-linked ubiquitin chains on MAVS at lysine 7, which serves as a recognition signal for NDP52-dependent autophagic degradation. Taken together, our findings reveal a negative feedback loop of RLR signaling generated by Tetherin-MARCH8-MAVS-NDP52 axis and provide insights into a better understanding of the crosstalk between selective autophagy and optimal deactivation of type I IFN signaling. Copyright © 2017 Elsevier Inc. All rights reserved.

Impact of autologous and allogeneic stem cell transplantation in peripheral T-cell lymphomas.

PubMed

Reimer, Peter

2010-01-01

Peripheral T/NK-cell lymphomas (PTCLs) are rare malignancies characterized by poor prognosis. So far, no standard therapy has been established, due to the lack of randomised studies. High-dose therapy and autologous stem cell transplantation (HDT-autoSCT) have shown good feasibility with low toxicity in retrospective studies. In relapsing and refractory PTCL several comparison analyses suggest similar efficacy for PTCL when compared with aggressive B-cell lymphoma. In the upfront setting, prospective data show promising results with a long-lasting overall survival in a relevant subset of patients. Achieving a complete remission at transplantation seems to be the most important prognostic factor. Allogeneic stem cell transplantation (alloSCT) has been investigated only as salvage treatment. Especially when using reduced intensity conditioning regimen, eligible patients seem to benefit from this approach. To define the role for upfront stem cell transplantation a randomised trial by the German High-Grade Non-Hodgkin Lymphoma Study Group comparing HDT-autoSCT and alloSCT will be initiated this year.

Scientific Statement on the Diagnostic Criteria, Epidemiology, Pathophysiology, and Molecular Genetics of Polycystic Ovary Syndrome

PubMed Central

Dumesic, Daniel A.; Oberfield, Sharon E.; Stener-Victorin, Elisabet; Marshall, John C.; Laven, Joop S.

2015-01-01

Polycystic ovary syndrome (PCOS) is a heterogeneous and complex disorder that has both adverse reproductive and metabolic implications for affected women. However, there is generally poor understanding of its etiology. Varying expert-based diagnostic criteria utilize some combination of oligo-ovulation, hyperandrogenism, and the presence of polycystic ovaries. Criteria that require hyperandrogenism tend to identify a more severe reproductive and metabolic phenotype. The phenotype can vary by race and ethnicity, is difficult to define in the perimenarchal and perimenopausal period, and is exacerbated by obesity. The pathophysiology involves abnormal gonadotropin secretion from a reduced hypothalamic feedback response to circulating sex steroids, altered ovarian morphology and functional changes, and disordered insulin action in a variety of target tissues. PCOS clusters in families and both female and male relatives can show stigmata of the syndrome, including metabolic abnormalities. Genome-wide association studies have identified a number of candidate regions, although their role in contributing to PCOS is still largely unknown. PMID:26426951

Coordinated temporal and spatial control of motor neuron and serotonergic neuron generation from a common pool of CNS progenitors.

PubMed

Pattyn, Alexandre; Vallstedt, Anna; Dias, José M; Samad, Omar Abdel; Krumlauf, Robb; Rijli, Filippo M; Brunet, Jean-Francois; Ericson, Johan

2003-03-15

Neural progenitor cells often produce distinct types of neurons in a specific order, but the determinants that control the sequential generation of distinct neuronal subclasses in the vertebrate CNS remain poorly defined. We examined the sequential generation of visceral motor neurons and serotonergic neurons from a common pool of neural progenitors located in the ventral hindbrain. We found that the temporal specification of these neurons varies along the anterior-posterior axis of the hindbrain, and that the timing of their generation critically depends on the integrated activities of Nkx- and Hox-class homeodomain proteins. A primary function of these proteins is to coordinate the spatial and temporal activation of the homeodomain protein Phox2b, which in turn acts as a binary switch in the selection of motor neuron or serotonergic neuronal fate. These findings assign new roles for Nkx, Hox, and Phox2 proteins in the control of temporal neuronal fate determination, and link spatial and temporal patterning of CNS neuronal fates.

Adolescent knowledge, values, and coping strategies: implications for health in sub-Saharan Africa.

PubMed

Balmer, D H; Gikundi, E; Billingsley, M C; Kihuho, F G; Kimani, M; Wang'ondu, J; Njoroge, H

1997-07-01

The purposes of this study were to investigate the experiences and knowledge of adolescents living in an urban center in Kenya and to understand how the decisions they make affect their physical and psychological health. A sample of 216 adolescents was drawn and they met weekly in small groups with trained facilitators for a period of 6 months. A research team monitored the developments of the groups and the topics they discussed. The findings were corroborated by the adolescents. It was found that adolescents were primarily concerned with developing a coherent and consistent set of personal values which would govern their behavior. Unfortunately, they could not always achieve those values and they resorted to dysfunctional coping strategies which were injurious to their health. The role of the adolescent in developing countries is complex and poorly defined. In a period of unprecedented change, an urgent and comprehensive review is necessary by all sections of society if the health of this group is to improve.

The placebo effect.

PubMed

Margo, C E

1999-01-01

Placebos have been traditionally regarded as deceptive therapies and have not been understood in the broader context of social symbols and of interpersonal factors that surround the healing process itself. Although the power of inert substances to heal is well recognized, the placebo effect also influences the outcome of conventional therapies. The role of the placebo in modern medicine is poorly defined because of a lack of a common understanding of what the placebo effect is and because of the negative connotions associated with its use. The response rate to placebo varies by illness. The natural course of disease and patient or physician bias can be misinterpreted as a placebo response. In research, the placebo effect is therapeutic noise to be removed by placebo-controlled trials. Few studies are designed to measure the placebo response rate directly. Placebos are a reminder of how little is known about mind-body interaction. The placebo effect may be one of the most versatile and underused therapeutic tools at the disposal of physicians.

A Myc-driven self-reinforcing regulatory network maintains mouse embryonic stem cell identity

PubMed Central

Fagnocchi, Luca; Cherubini, Alessandro; Hatsuda, Hiroshi; Fasciani, Alessandra; Mazzoleni, Stefania; Poli, Vittoria; Berno, Valeria; Rossi, Riccardo L.; Reinbold, Rolland; Endele, Max; Schroeder, Timm; Rocchigiani, Marina; Szkarłat, Żaneta; Oliviero, Salvatore; Dalton, Stephen; Zippo, Alessio

2016-01-01

Stem cell identity depends on the integration of extrinsic and intrinsic signals, which directly influence the maintenance of their epigenetic state. Although Myc transcription factors play a major role in stem cell self-renewal and pluripotency, their integration with signalling pathways and epigenetic regulators remains poorly defined. We addressed this point by profiling the gene expression and epigenetic pattern in ESCs whose growth depends on conditional Myc activity. Here we show that Myc potentiates the Wnt/β-catenin signalling pathway, which cooperates with the transcriptional regulatory network in sustaining ESC self-renewal. Myc activation results in the transcriptional repression of Wnt antagonists through the direct recruitment of PRC2 on these targets. The consequent potentiation of the autocrine Wnt/β-catenin signalling induces the transcriptional activation of the endogenous Myc family members, which in turn activates a Myc-driven self-reinforcing circuit. Thus, our data unravel a Myc-dependent self-propagating epigenetic memory in the maintenance of ESC self-renewal capacity. PMID:27301576

Staphylococcus aureus leukocidin ED contributes to systemic infection by targeting neutrophils and promoting bacterial growth in vivo

PubMed Central

Alonzo, Francis; Benson, Meredith A.; Chen, John; Novick, Richard P.; Shopsin, Bo; Torres, Victor J.

2011-01-01

SUMMARY Bloodstream infection with Staphylococcus aureus is common and can be fatal. However, virulence factors that contribute to lethality in S. aureus bloodstream infection are poorly defined. We discovered that LukED, a commonly overlooked leukotoxin, is critical for S. aureus bloodstream infection in mice. We also determined that LukED promotes S. aureus replication in vivo by directly killing phagocytes recruited to sites of hematogenously-seeded tissue. Furthermore, we established that murine neutrophils are the primary target of LukED, as the greater virulence of wild type S. aureus compared to a lukED mutant was abrogated by depleting neutrophils. The in vivo toxicity of LukED toward murine phagocytes is unique among S. aureus leukotoxins, implying its crucial role in pathogenesis. Moreover, the tropism of LukED for murine phagocytes highlights the utility of murine models to study LukED pathobiology, including development and testing of strategies to inhibit toxin activity and control bacterial infection. PMID:22142035

Getting the Message? Native Reactive Electrophiles Pass Two Out of Three Thresholds to be Bona Fide Signaling Mediators.

PubMed

Poganik, Jesse R; Long, Marcus J C; Aye, Yimon

2018-05-01

Precision cell signaling activities of reactive electrophilic species (RES) are arguably among the most poorly-understood means to transmit biological messages. Latest research implicates native RES to be a chemically-distinct subset of endogenous redox signals that influence cell decision making through non-enzyme-assisted modifications of specific proteins. Yet, fundamental questions remain regarding the role of RES as bona fide second messengers. Here, we lay out three sets of criteria we feel need to be met for RES to be considered as true cellular signals that directly mediate information transfer by modifying "first-responding" sensor proteins. We critically assess the available evidence and define the extent to which each criterion has been fulfilled. Finally, we offer some ideas on the future trajectories of the electrophile signaling field taking inspiration from work that has been done to understand canonical signaling mediators. Also see the video abstract here: https://youtu.be/rG7o0clVP0c. © 2018 WILEY Periodicals, Inc.

A novel perivascular cell population in the zebrafish brain

PubMed Central

Galanternik, Marina Venero; Castranova, Daniel; Gore, Aniket V; Blewett, Nathan H; Jung, Hyun Min; Stratman, Amber N; Kirby, Martha R; Iben, James; Miller, Mayumi F; Kawakami, Koichi; Maraia, Richard J; Weinstein, Brant M

2017-01-01

The blood-brain barrier is essential for the proper homeostasis and function of the CNS, but its mechanism of function is poorly understood. Perivascular cells surrounding brain blood vessels are thought to be important for blood-brain barrier establishment, but their roles are not well defined. Here, we describe a novel perivascular cell population closely associated with blood vessels on the zebrafish brain. Based on similarities in their morphology, location, and scavenger behavior, these cells appear to be the zebrafish equivalent of cells variably characterized as Fluorescent Granular Perithelial cells (FGPs), perivascular macrophages, or ‘Mato Cells’ in mammals. Despite their macrophage-like morphology and perivascular location, zebrafish FGPs appear molecularly most similar to lymphatic endothelium, and our imaging studies suggest that these cells emerge by differentiation from endothelium of the optic choroidal vascular plexus. Our findings provide the first report of a perivascular cell population in the brain derived from vascular endothelium. DOI: http://dx.doi.org/10.7554/eLife.24369.001 PMID:28395729

Silicon as Versatile Player in Plant and Human Biology: Overlooked and Poorly Understood

PubMed Central

Farooq, Muhammad Ansar; Dietz, Karl-Josef

2015-01-01

Silicon (Si) serves as bioactive beneficial element. Si is highly abundant in soil, and occurs ubiquitously in all organisms including plants and humans. During the last three decades, nutritional significance of Si for plant and human health has received increasing attention. Plant Si plays a pivotal role in growth and development, and this beneficial effect depends usually on accumulation in plant tissues, which are then protected from various forms of biotic and abiotic stresses. Likewise, human exposure to Si imparts health benefits and essentially occurs through plant-derived food products. Si bioavailability in human diet, e.g., strengthens bones and improves immune response, as well as neuronal and connective tissue health. Despite this empiric knowledge, the essentiality of Si still remains enigmatic. Thus the link between Si availability for plant development and its profound implication for human welfare should receive attention. This review aims to provide a broad perspective on Si as important element for plant and human nutrition and to define research fields for interdisciplinary research. PMID:26617630

The role of failure/problems in engineering: A commentary of failures experienced - lessons learned

NASA Technical Reports Server (NTRS)

Ryan, R. S.

1992-01-01

The written version of a series of seminars given to several aerospace companies and three NASA centers are presented. The results are lessons learned through a study of the problems experienced in 35 years of engineering. The basic conclusion is that the primary cause of problems has not been mission technologies, as important as technology is, but the neglect of basic principles. Undergirding this is the lack of a systems focus from determining requirements through design, verification, and operations phases. Many of the concepts discussed are fundamental to total quality management (TQM) and can be used to augment this product enhanced philosophy. Fourteen principles are addressed with problems experienced and are used as examples. Included is a discussion of the implication of constraints, poorly defined requirements, and schedules. Design guidelines, lessons learned, and future tasks are listed. Two additional sections are included that deal with personal lessons learned and thoughts on future thrusts (TQM).

A Myc-driven self-reinforcing regulatory network maintains mouse embryonic stem cell identity.

PubMed

Fagnocchi, Luca; Cherubini, Alessandro; Hatsuda, Hiroshi; Fasciani, Alessandra; Mazzoleni, Stefania; Poli, Vittoria; Berno, Valeria; Rossi, Riccardo L; Reinbold, Rolland; Endele, Max; Schroeder, Timm; Rocchigiani, Marina; Szkarłat, Żaneta; Oliviero, Salvatore; Dalton, Stephen; Zippo, Alessio

2016-06-15

Stem cell identity depends on the integration of extrinsic and intrinsic signals, which directly influence the maintenance of their epigenetic state. Although Myc transcription factors play a major role in stem cell self-renewal and pluripotency, their integration with signalling pathways and epigenetic regulators remains poorly defined. We addressed this point by profiling the gene expression and epigenetic pattern in ESCs whose growth depends on conditional Myc activity. Here we show that Myc potentiates the Wnt/β-catenin signalling pathway, which cooperates with the transcriptional regulatory network in sustaining ESC self-renewal. Myc activation results in the transcriptional repression of Wnt antagonists through the direct recruitment of PRC2 on these targets. The consequent potentiation of the autocrine Wnt/β-catenin signalling induces the transcriptional activation of the endogenous Myc family members, which in turn activates a Myc-driven self-reinforcing circuit. Thus, our data unravel a Myc-dependent self-propagating epigenetic memory in the maintenance of ESC self-renewal capacity.

Influence of fluctuations of historic water bodies on fault stability and earthquake recurrence interval: The Dead Sea Rift as a case study

NASA Astrophysics Data System (ADS)

Belferman, Mariana; Katsman, Regina; Agnon, Amotz; Ben-Avraham, Zvi

2017-04-01

Despite the global, social and scientific impact of earthquakes, their triggering mechanisms remain often poorly defined. We suggest that dynamic changes in the levels of the historic water bodies occupying tectonic depressions at the Dead Sea Rift cause significant variations in the shallow crustal stress field and affect local fault systems in a way that may promote or suppress earthquakes. This mechanism and its spatial and temporal scales differ from those in tectonically-driven deformations. We use analytical and numerical poroelastic models to simulate immediate and delayed seismic responses resulting from the observed historic water level changes. The role of variability in the poroelastic and the elastic properties of the rocks composing the upper crust in inducing or retarding deformations under a strike-slip faulting regime is studied. The solution allows estimating a possible reduction in a seismic recurrence interval. Considering the historic water level fluctuation, our preliminary simulations show a promising agreement with paleo-seismic rates identified in the field.

The epidemiology of bovine respiratory disease: What is the evidence for predisposing factors?

PubMed Central

Taylor, Jared D.; Fulton, Robert W.; Lehenbauer, Terry W.; Step, Douglas L.; Confer, Anthony W.

2010-01-01

Bovine respiratory disease (BRD) is the most costly disease of beef cattle in North America. It is multi-factorial, with a variety of physical and physiological stressors combining to predispose cattle to pneumonia. However, efforts to discern which factors are most important have frequently failed to establish definitive answers. Calves are at highest risk shortly after transport. Risk factors include purchasing from sale barns and commingling. It is unclear whether or not these practices increase susceptibility, increase exposure, or are proxies for poor management. Lighter-weight calves appear to be at greater risk, although this has not been consistent. Persistent infection (PI) with bovine virus diarrhea virus increases BRD occurrence, but it is unclear if PI calves affect other cattle in the feedlot. The complexity of BRD has made it difficult to define involvement of individual factors. Stressors may play a role as “necessary but not sufficient” components, requiring additive effects to cause disease. PMID:21197200

Stochastic Community Assembly: Does It Matter in Microbial Ecology?

PubMed

Zhou, Jizhong; Ning, Daliang

2017-12-01

Understanding the mechanisms controlling community diversity, functions, succession, and biogeography is a central, but poorly understood, topic in ecology, particularly in microbial ecology. Although stochastic processes are believed to play nonnegligible roles in shaping community structure, their importance relative to deterministic processes is hotly debated. The importance of ecological stochasticity in shaping microbial community structure is far less appreciated. Some of the main reasons for such heavy debates are the difficulty in defining stochasticity and the diverse methods used for delineating stochasticity. Here, we provide a critical review and synthesis of data from the most recent studies on stochastic community assembly in microbial ecology. We then describe both stochastic and deterministic components embedded in various ecological processes, including selection, dispersal, diversification, and drift. We also describe different approaches for inferring stochasticity from observational diversity patterns and highlight experimental approaches for delineating ecological stochasticity in microbial communities. In addition, we highlight research challenges, gaps, and future directions for microbial community assembly research. Copyright © 2017 American Society for Microbiology.

Meta-Analysis of DNA Tumor-Viral Integration Site Selection Indicates a Role for Repeats, Gene Expression and Epigenetics

PubMed Central

Doolittle-Hall, Janet M.; Cunningham Glasspoole, Danielle L.; Seaman, William T.; Webster-Cyriaque, Jennifer

2015-01-01

Oncoviruses cause tremendous global cancer burden. For several DNA tumor viruses, human genome integration is consistently associated with cancer development. However, genomic features associated with tumor viral integration are poorly understood. We sought to define genomic determinants for 1897 loci prone to hosting human papillomavirus (HPV), hepatitis B virus (HBV) or Merkel cell polyomavirus (MCPyV). These were compared to HIV, whose enzyme-mediated integration is well understood. A comprehensive catalog of integration sites was constructed from the literature and experimentally-determined HPV integration sites. Features were scored in eight categories (genes, expression, open chromatin, histone modifications, methylation, protein binding, chromatin segmentation and repeats) and compared to random loci. Random forest models determined loci classification and feature selection. HPV and HBV integrants were not fragile site associated. MCPyV preferred integration near sensory perception genes. Unique signatures of integration-associated predictive genomic features were detected. Importantly, repeats, actively-transcribed regions and histone modifications were common tumor viral integration signatures. PMID:26569308

Modeling human endothelial cell transformation in vascular neoplasias

PubMed Central

Wen, Victoria W.; MacKenzie, Karen L.

2013-01-01

Endothelial cell (EC)-derived neoplasias range from benign hemangioma to aggressive metastatic angiosarcoma, which responds poorly to current treatments and has a very high mortality rate. The development of treatments that are more effective for these disorders will be expedited by insight into the processes that promote abnormal proliferation and malignant transformation of human ECs. The study of primary endothelial malignancy has been limited by the rarity of the disease; however, there is potential for carefully characterized EC lines and animal models to play a central role in the discovery, development and testing of molecular targeted therapies for vascular neoplasias. This review describes molecular alterations that have been identified in EC-derived neoplasias, as well as the processes that underpin the immortalization and tumorigenic conversion of ECs. Human EC lines, established through the introduction of defined genetic elements or by culture of primary tumor tissue, are catalogued and discussed in relation to their relevance as models of vascular neoplasia. PMID:24046386

Epidermal Notch1 recruits RORγ(+) group 3 innate lymphoid cells to orchestrate normal skin repair.

PubMed

Li, Zhi; Hodgkinson, Tom; Gothard, Elizabeth J; Boroumand, Soulmaz; Lamb, Rebecca; Cummins, Ian; Narang, Priyanka; Sawtell, Amy; Coles, Jenny; Leonov, German; Reboldi, Andrea; Buckley, Christopher D; Cupedo, Tom; Siebel, Christian; Bayat, Ardeshir; Coles, Mark C; Ambler, Carrie A

2016-04-21

Notch has a well-defined role in controlling cell fate decisions in the embryo and the adult epidermis and immune systems, yet emerging evidence suggests Notch also directs non-cell-autonomous signalling in adult tissues. Here, we show that Notch1 works as a damage response signal. Epidermal Notch induces recruitment of immune cell subsets including RORγ(+) ILC3s into wounded dermis; RORγ(+) ILC3s are potent sources of IL17F in wounds and control immunological and epidermal cell responses. Mice deficient for RORγ(+) ILC3s heal wounds poorly resulting from delayed epidermal proliferation and macrophage recruitment in a CCL3-dependent process. Notch1 upregulates TNFα and the ILC3 recruitment chemokines CCL20 and CXCL13. TNFα, as a Notch1 effector, directs ILC3 localization and rates of wound healing. Altogether these findings suggest that Notch is a key stress/injury signal in skin epithelium driving innate immune cell recruitment and normal skin tissue repair.

Divergent Routing of Positive and Negative Information from the Amygdala during Memory Retrieval.

PubMed

Beyeler, Anna; Namburi, Praneeth; Glober, Gordon F; Simonnet, Clémence; Calhoon, Gwendolyn G; Conyers, Garrett F; Luck, Robert; Wildes, Craig P; Tye, Kay M

2016-04-20

Although the basolateral amygdala (BLA) is known to play a critical role in the formation of memories of both positive and negative valence, the coding and routing of valence-related information is poorly understood. Here, we recorded BLA neurons during the retrieval of associative memories and used optogenetic-mediated phototagging to identify populations of neurons that synapse in the nucleus accumbens (NAc), the central amygdala (CeA), or ventral hippocampus (vHPC). We found that despite heterogeneous neural responses within each population, the proportions of BLA-NAc neurons excited by reward predictive cues and of BLA-CeA neurons excited by aversion predictive cues were higher than within the entire BLA. Although the BLA-vHPC projection is known to drive behaviors of innate negative valence, these neurons did not preferentially code for learned negative valence. Together, these findings suggest that valence encoding in the BLA is at least partially mediated via divergent activity of anatomically defined neural populations. Copyright © 2016 Elsevier Inc. All rights reserved.

The development of organized visual search

PubMed Central

Woods, Adam J.; Goksun, Tilbe; Chatterjee, Anjan; Zelonis, Sarah; Mehta, Anika; Smith, Sabrina E.

2013-01-01

Visual search plays an important role in guiding behavior. Children have more difficulty performing conjunction search tasks than adults. The present research evaluates whether developmental differences in children's ability to organize serial visual search (i.e., search organization skills) contribute to performance limitations in a typical conjunction search task. We evaluated 134 children between the ages of 2 and 17 on separate tasks measuring search for targets defined by a conjunction of features or by distinct features. Our results demonstrated that children organize their visual search better as they get older. As children's skills at organizing visual search improve they become more accurate at locating targets with conjunction of features amongst distractors, but not for targets with distinct features. Developmental limitations in children's abilities to organize their visual search of the environment are an important component of poor conjunction search in young children. In addition, our findings provide preliminary evidence that, like other visuospatial tasks, exposure to reading may influence children's spatial orientation to the visual environment when performing a visual search. PMID:23584560

The intercrater plains of Mercury and the Moon: Their nature, origin and role in terrestrial planet evolution. Cratering histories of the intercrater plains. Ph.D. Thesis

NASA Technical Reports Server (NTRS)

Leake, M. A.

1982-01-01

The intercrater plains of Mercury and the Moon are defined, in part, by their high densities of small craters. The crater size frequency statistics presented in this chapter may help constrain the relative ages and origins of these surfaces. To this end, the effects of common geologic processes on crater frequency statistics are compared with the diameter frequency distributions of the intercrater regions of the Moon and Mercury. Such analyses may determine whether secondary craters dominate the distribution at small diameters, and whether volcanic plains or ballistic deposits form the intercrater surface. Determining the mass frequency distribution and flux of the impacting population is a more difficult problem. The necessary information such as scaling relationships between projectile energy and crater diameter, the relative fluxes of solar system objects, and the absolute ages of surface units is model dependent and poorly constrained, especially for Mercury.

COPI mediates recycling of an exocytic SNARE by recognition of a ubiquitin sorting signal

PubMed Central

Xu, Peng; Hankins, Hannah M; MacDonald, Chris; Erlinger, Samuel J; Frazier, Meredith N; Diab, Nicholas S; Piper, Robert C; Jackson, Lauren P; MacGurn, Jason A

2017-01-01

The COPI coat forms transport vesicles from the Golgi complex and plays a poorly defined role in endocytic trafficking. Here we show that COPI binds K63-linked polyubiquitin and this interaction is crucial for trafficking of a ubiquitinated yeast SNARE (Snc1). Snc1 is a v-SNARE that drives fusion of exocytic vesicles with the plasma membrane, and then recycles through the endocytic pathway to the Golgi for reuse in exocytosis. Removal of ubiquitin from Snc1, or deletion of a β'-COP subunit propeller domain that binds K63-linked polyubiquitin, disrupts Snc1 recycling causing aberrant accumulation in internal compartments. Moreover, replacement of the β'-COP propeller domain with unrelated ubiquitin-binding domains restores Snc1 recycling. These results indicate that ubiquitination, a modification well known to target membrane proteins to the lysosome or vacuole for degradation, can also function as recycling signal to sort a SNARE into COPI vesicles in a non-degradative pathway. PMID:29058666

Perceptual Grouping Affects Pitch Judgments Across Time and Frequency

PubMed Central

Borchert, Elizabeth M. O.; Micheyl, Christophe; Oxenham, Andrew J.

2010-01-01

Pitch, the perceptual correlate of fundamental frequency (F0), plays an important role in speech, music and animal vocalizations. Changes in F0 over time help define musical melodies and speech prosody, while comparisons of simultaneous F0 are important for musical harmony, and for segregating competing sound sources. This study compared listeners’ ability to detect differences in F0 between pairs of sequential or simultaneous tones that were filtered into separate, non-overlapping spectral regions. The timbre differences induced by filtering led to poor F0 discrimination in the sequential, but not the simultaneous, conditions. Temporal overlap of the two tones was not sufficient to produce good performance; instead performance appeared to depend on the two tones being integrated into the same perceptual object. The results confirm the difficulty of comparing the pitches of sequential sounds with different timbres and suggest that, for simultaneous sounds, pitch differences may be detected through a decrease in perceptual fusion rather than an explicit coding and comparison of the underlying F0s. PMID:21077719

Causation in negligence: from anti-jurisprudence to principle--individual responsibility as the cornerstone for the attribution of liability.

PubMed

Bagaric, Mirko; Erbacher, Sharon

2011-06-01

Causation is one of the most esoteric and poorly defined legal principles. The common law standards of the "but for" test and common sense are, in reality, code for unconstrained judicial choice. This leads to a high degree of unpredictability in negligence cases. Changes to the causation standard following the torts reforms have done nothing to inject principle into this area of law: the concept of "appropriateness" is no more illuminating than common sense. Despite this, the trend of recent High Court decisions offers some prospect of clarifying the test for causation. Key themes to emerge are an increased emphasis on individual responsibility and the associated concept of coherency with other legal standards. This article examines the doctrinal reasons underpinning the increasingly important role of these ideals and suggests how they can be accommodated into the test for causation to inject greater coherence and predictability into this area of law.

Interlocked feedforward loops control cell-type-specific Rhodopsin expression in the Drosophila eye.

PubMed

Johnston, Robert J; Otake, Yoshiaki; Sood, Pranidhi; Vogt, Nina; Behnia, Rudy; Vasiliauskas, Daniel; McDonald, Elizabeth; Xie, Baotong; Koenig, Sebastian; Wolf, Reinhard; Cook, Tiffany; Gebelein, Brian; Kussell, Edo; Nakagoshi, Hideki; Desplan, Claude

2011-06-10

How complex networks of activators and repressors lead to exquisitely specific cell-type determination during development is poorly understood. In the Drosophila eye, expression patterns of Rhodopsins define at least eight functionally distinct though related subtypes of photoreceptors. Here, we describe a role for the transcription factor gene defective proventriculus (dve) as a critical node in the network regulating Rhodopsin expression. dve is a shared component of two opposing, interlocked feedforward loops (FFLs). Orthodenticle and Dve interact in an incoherent FFL to repress Rhodopsin expression throughout the eye. In R7 and R8 photoreceptors, a coherent FFL relieves repression by Dve while activating Rhodopsin expression. Therefore, this network uses repression to restrict and combinatorial activation to induce cell-type-specific expression. Furthermore, Dve levels are finely tuned to yield cell-type- and region-specific repression or activation outcomes. This interlocked FFL motif may be a general mechanism to control terminal cell-fate specification. Copyright © 2011 Elsevier Inc. All rights reserved.

Negative regulation of glial engulfment activity by Draper terminates glial responses to axon injury

PubMed Central

Logan, Mary A.; Hackett, Rachel; Doherty, Johnna; Sheehan, Amy; Speese, Sean D.; Freeman, Marc R.

2012-01-01

Neuronal injury elicits potent cellular responses from glia, but molecular pathways modulating glial activation, phagocytic function, and termination of reactive responses remain poorly defined. Here we show that positive or negative regulation of glial reponses to axon injury are molecularly encoded by unique isoforms of the Drosophila engulfment receptor Draper. Draper-I promotes engulfment of axonal debris through an immunoreceptor tyrosine-based activation motif (ITAM). In contrast, Draper-II, an alternative splice variant, potently inhibits glial engulfment function. Draper-II suppresses Draper-I signaling through a novel immunoreceptor tyrosine-based inhibitory motif (ITIM)-like domain and the tyrosine phosphatase Corkscrew (Csw). Intriguingly, loss of Draper-II/Csw signaling prolongs expression of glial engulfment genes after axotomy and reduces the ability of glia to respond to secondary axotomy. Our work highlights a novel role for Draper-II in inhibiting glial responses to neurodegeneration, and indicates a balance of opposing Draper-I/-II signaling events is essential to maintain glial sensitivity to brain injury. PMID:22426252

Seipin is required for converting nascent to mature lipid droplets

PubMed Central

Wang, Huajin; Becuwe, Michel; Housden, Benjamin E; Chitraju, Chandramohan; Porras, Ashley J; Graham, Morven M; Liu, Xinran N; Thiam, Abdou Rachid; Savage, David B; Agarwal, Anil K; Garg, Abhimanyu; Olarte, Maria-Jesus; Lin, Qingqing; Fröhlich, Florian; Hannibal-Bach, Hans Kristian; Upadhyayula, Srigokul; Perrimon, Norbert; Kirchhausen, Tomas; Ejsing, Christer S; Walther, Tobias C; Farese, Robert V

2016-01-01

How proteins control the biogenesis of cellular lipid droplets (LDs) is poorly understood. Using Drosophila and human cells, we show here that seipin, an ER protein implicated in LD biology, mediates a discrete step in LD formation—the conversion of small, nascent LDs to larger, mature LDs. Seipin forms discrete and dynamic foci in the ER that interact with nascent LDs to enable their growth. In the absence of seipin, numerous small, nascent LDs accumulate near the ER and most often fail to grow. Those that do grow prematurely acquire lipid synthesis enzymes and undergo expansion, eventually leading to the giant LDs characteristic of seipin deficiency. Our studies identify a discrete step of LD formation, namely the conversion of nascent LDs to mature LDs, and define a molecular role for seipin in this process, most likely by acting at ER-LD contact sites to enable lipid transfer to nascent LDs. DOI: http://dx.doi.org/10.7554/eLife.16582.001 PMID:27564575

Poorly cited articles in peer-reviewed cardiovascular journals from 1997 to 2007: analysis of 5-year citation rates.

PubMed

Ranasinghe, Isuru; Shojaee, Abbas; Bikdeli, Behnood; Gupta, Aakriti; Chen, Ruijun; Ross, Joseph S; Masoudi, Frederick A; Spertus, John A; Nallamothu, Brahmajee K; Krumholz, Harlan M

2015-05-19

The extent to which articles are cited is a surrogate of the impact and importance of the research conducted; poorly cited articles may identify research of limited use and potential wasted investments. We assessed trends in the rates of poorly cited articles and journals in the cardiovascular literature from 1997 to 2007. We identified original articles published in cardiovascular journals and indexed in the Scopus citation database from 1997 to 2007. We defined poorly cited articles as those with ≤5 citations in the 5 years following publication and poorly cited journals as those with >75% of journal content poorly cited. We identified 164 377 articles in 222 cardiovascular journals from 1997 to 2007. From 1997 to 2007, the number of cardiovascular articles and journals increased by 56.9% and 75.2%, respectively. Of all the articles, 75 550 (46.0%) were poorly cited, of which 25 650 (15.6% overall) had no citations. From 1997 to 2007, the proportion of poorly cited articles declined slightly (52.1%-46.2%, trend P<0.001), although the absolute number of poorly cited articles increased by 2595 (trend P<0.001). At a journal level, 44% of cardiovascular journals had more than three-fourths of the journal's content poorly cited at 5 years. Nearly half of all peer-reviewed articles published in cardiovascular journals are poorly cited 5 years after publication, and many are not cited at all. The cardiovascular literature and the number of poorly cited articles both increased substantially from 1997 to 2007. The high proportion of poorly cited articles and journals suggests inefficiencies in the cardiovascular research enterprise. © 2015 American Heart Association, Inc.

Poorly Cited Articles in Peer-Reviewed Cardiovascular Journals from 1997–2007: Analysis of 5-Year Citation Rates

PubMed Central

Ranasinghe, Isuru; Shojaee, Abbas; Bikdeli, Behnood; Gupta, Aakriti; Chen, Ruijun; Ross, Joseph S.; Masoudi, Frederick; Spertus, John A.; Nallamothu, Brahmajee K.; Krumholz, Harlan M.

2015-01-01

Background The extent to which articles are cited is a surrogate of the impact and importance of the research conducted; poorly cited papers may identify research of limited use and potential wasted investments. We assessed trends in the rates of poorly cited articles and journals in the cardiovascular literature from 1997–2007. Methods and Results We identified original articles published in cardiovascular journals and indexed in the Scopus citation database from 1997–2007. We defined poorly cited articles as those with ≤5 citations in the 5 years following publication and poorly cited journals as those with >75% of journal content poorly cited. We identified 164,377 articles in 222 cardiovascular journals from 1997–2007. From 1997–2007, the number of cardiovascular articles and journals increased by 56.9% and 75.2% respectively. Of all the articles, 75,550 (46.0%) were poorly cited, of which 25,650 (15.6% overall) had no citations. From 1997–2007, the proportion of poorly cited articles declined slightly (52.1% to 46.2%, trend P<0.001), although the absolute number of poorly cited articles increased by 2,595 (trend P<0.001). At a journal level, 44% of cardiovascular journals had more than three quarters of the journal’s content poorly cited at 5 years. Conclusion Nearly half of all peer-reviewed articles published in cardiovascular journals are poorly cited 5 years after publication, and many are not cited at all. The cardiovascular literature, and the number of poorly cited articles, have both increased substantially from 1997–2007. The high proportion of poorly cited articles and journals suggest inefficiencies in the cardiovascular research enterprise. PMID:25812573

Factors associated with poor control of 9/11-related asthma 10–11 years after the 2001 World Trade Center terrorist attacks

PubMed Central

Jordan, Hannah T.; Stellman, Steven D.; Reibman, Joan; Farfel, Mark R.; Brackbill, Robert M.; Friedman, Stephen M.; Li, Jiehui; Cone, James E.

2015-01-01

Abstract Objective: To identify key factors associated with poor asthma control among adults in the World Trade Center (WTC) Health Registry, a longitudinal study of rescue/recovery workers and community members who were directly exposed to the 2001 WTC terrorist attacks and their aftermath. Methods: We studied incident asthma diagnosed by a physician from 12 September 2001 through 31 December 2003 among participants aged ≥18 on 11 September 2001, as reported on an enrollment (2003–2004) or follow-up questionnaire. Based on modified National Asthma Education and Prevention Program criteria, asthma was considered controlled, poorly-controlled, or very poorly-controlled at the time of a 2011–2012 follow-up questionnaire. Probable post-traumatic stress disorder, depression, and generalized anxiety disorder were defined using validated scales. Self-reported gastroesophageal reflux symptoms (GERS) and obstructive sleep apnea (OSA) were obtained from questionnaire responses. Multinomial logistic regression was used to examine factors associated with poor or very poor asthma control. Results: Among 2445 participants, 33.7% had poorly-controlled symptoms and 34.6% had very poorly-controlled symptoms in 2011–2012. Accounting for factors including age, education, body mass index, and smoking, there was a dose–response relationship between the number of mental health conditions and poorer asthma control. Participants with three mental health conditions had five times the odds of poor control and 13 times the odds of very poor control compared to participants without mental health comorbidities. GERS and OSA were significantly associated with poor or very poor control. Conclusions: Rates of poor asthma control were very high in this group with post-9/11 diagnosed asthma. Comprehensive care of 9/11-related asthma should include management of mental and physical health comorbidities. PMID:25539137

Potential role of combined FDG PET/CT & contrast enhancement MRI in a rectal carcinoma model with nodal metastases characterized by a poor FDG-avidity.

PubMed

Farace, Paolo; Conti, Giamaica; Merigo, Flavia; Tambalo, Stefano; Marzola, Pasquina; Sbarbati, Andrea; Quarta, Carmelo; D'Ambrosio, Daniela; Chondrogiannis, Sotirios; Nanni, Cristina; Rubello, Domenico

2012-04-01

To investigate the additional role of MRI contrast enhancement (CE) in the primary tumor and the FDG uptake at PET in the lymph-node metastases. A model of colorectal cancer induced by orthotopic HT-29 cells microinjection, producing pelvic lymph node metastases, was assessed using CE-MRI and FDG-PET. Histology and GLUT-1 immunohistochemistry were performed on primary tumors and iliac lymph nodes. Primary tumors were characterized by low FDG-uptake but high CE-MRI, particularly at tumor periphery. Undetectable FDG-uptake characterized the metastatic lymph-nodes. Histology revealed large stromal bundles at tumor periphery and a dense network of stromal fibers and neoplastic cells in the inner portion of the tumors. Both primary tumors and positive lymph nodes showed poor GLUT-1 staining. Our data support the complementary role of MRI-CE and FDG PET in some types of carcinomas characterized by abundant cancer-associated stroma and poor FDG avidity consequent to poor GLUT-1 transported. In these tumors FDG-PET alone may be not completely adequate to obtain an adequate tumor radiotherapy planning, and a combination with dual CE-MRI is strongly recommended. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Crisis Communication Plans: Poor Predictors of Excellent Crisis Public Relations.

ERIC Educational Resources Information Center

Marra, Francis J.

1998-01-01

Argues that newly developed theory in crisis public relations suggests a shift is necessary in the way practitioners view crises. Notes that the new paradigm defines excellent crisis public relations very differently from the literature of the past 20 years. (RS)

Needs and Wants. The Iconoclast.

ERIC Educational Resources Information Center

McMurtry, John

1997-01-01

Sharply criticizes current free market practices especially in light of the globalization of capitalism. Maintains that a laissez-faire approach to the allocation of resources and consumer choices is no longer relevant in a world defined by an increasing disparity between rich and poor. (MJP)

Identification of Mycobacterium avium subsp. hominissuis Isolated From Drinking Water

EPA Science Inventory

Mycobacterium avium (MA) is divided into four subspecies based primarily on host-range and consists of MA subsp. avium (birds), MA subsp. silvaticum (wood pigeons), MA subsp. paratuberculosis (broad, poorly-defined host range), and the recently described MA subsp. hominissuis (hu...

The role of preoccupation in attributions for poor sleep.

PubMed

Ellis, Jason; Hampson, Sarah E; Cropley, Mark

2007-04-01

Studies examining the impact of daytime preoccupations with sleep are rare. The aim of the present study was to determine whether daytime preoccupations mediate the relationship between anxiety and attributions for poor sleep within older adults. A cross-sectional study examined the mediational role of sleep preoccupations in the link between anxiety and attributions for poor sleep in a sample of late-life insomniacs (n=92). The findings show that a preoccupation with sleep during the day mediates the relationship between anxiety and both sleep effort and sleep pattern problem attributions but does not mediate cognitive arousal attributions for insomnia and only partially mediates the relationship between anxiety and physical tension attributions for insomnia. The results are discussed in terms of the existing models of insomnia and cognitive intervention strategies.

A Salute to a Leader: ARL's Assessment Protocol Initiatives

ERIC Educational Resources Information Center

Heath, Fred

2009-01-01

This brief salute to Duane Webster and his defining role over the past several decades at the Association of Research Libraries (ARL) focuses on his formative role in defining and evolving the assessment protocols employed by both the association and the profession. (Contains 8 notes.)

Upregulation of Soluble HLA-G5 and HLA-G6 Isoforms in the Milder Histopathological Stages of Helicobacter pylori Infection: A Role for Subverting Immune Responses?

PubMed

Souza, D M B Oliveira; Genre, J; Silva, T G Alves; Soares, C P; Rocha, K Borges Ferreira; Oliveira, C Nunes; Jatobá, C A Nunes; Andrade, J Marco de Leon; Moreau, P; Medeiros, A da Cunha; Donadi, E A; Crispim, J C de Oliveira

2016-01-01

The subversion mechanisms employed by Helicobacter pylori (H. pylori) to escape from immune surveillance and to establish persistent infection are poorly understood. Growing evidence indicates that expression of HLA-G, a non-classical major histocompatibility complex molecule, negatively regulates immune responses in pathological conditions, including infectious diseases. In this context, we aimed to evaluate HLA-G expression in the gastric microenvironment of individuals harbouring H. pylori and to correlate it with histological variables. Fifty-four gastric specimens from patients harbouring H. pylori infection were evaluated by immunohistochemistry using anti-HLA-G monoclonal antibody. As a result, HLA-G expression was detected in 43 of 54 specimens harbouring H. pylori. The presence of HLA-G was significantly associated with milder colonization by H. pylori (P < 0.02), milder inflammatory activity (P < 0.02) and bacterium histological location in the gastric antrum. This study is the first to explore HLA-G expression in the context of bacterial infection. Whether the biological role of HLA-G during H. pylori infection is beneficial or hazardous for patients remains to be defined. © 2015 The Authors. Scandinavian Journal of Immunology published by John Wiley & Sons Ltd on behalf of The Foundation for the Scandinavian Journal of Immunology.

POLYGALACTURONASE INVOLVED IN EXPANSION1 functions in cell elongation and flower development in Arabidopsis.

PubMed

Xiao, Chaowen; Somerville, Chris; Anderson, Charles T

2014-03-01

Pectins are acidic carbohydrates that comprise a significant fraction of the primary walls of eudicotyledonous plant cells. They influence wall porosity and extensibility, thus controlling cell and organ growth during plant development. The regulated degradation of pectins is required for many cell separation events in plants, but the role of pectin degradation in cell expansion is poorly defined. Using an activation tag screen designed to isolate genes involved in wall expansion, we identified a gene encoding a putative polygalacturonase that, when overexpressed, resulted in enhanced hypocotyl elongation in etiolated Arabidopsis thaliana seedlings. We named this gene POLYGALACTURONASE INVOLVED IN EXPANSION1 (PGX1). Plants lacking PGX1 display reduced hypocotyl elongation that is complemented by transgenic PGX1 expression. PGX1 is expressed in expanding tissues throughout development, including seedlings, roots, leaves, and flowers. PGX1-GFP (green fluorescent protein) localizes to the apoplast, and heterologously expressed PGX1 displays in vitro polygalacturonase activity, supporting a function for this protein in apoplastic pectin degradation. Plants either overexpressing or lacking PGX1 display alterations in total polygalacturonase activity, pectin molecular mass, and wall composition and also display higher proportions of flowers with extra petals, suggesting PGX1's involvement in floral organ patterning. These results reveal new roles for polygalacturonases in plant development.

Side effects, adherence self-efficacy, and adherence to antiretroviral treatment: a mediation analysis in a Chinese sample.

PubMed

Zhang, Liying; Li, Xiaoming; Lin, Zhenping; Jacques-Tiura, Angela J; Xu, Jinping; Zhou, Yuejiao; Qiao, Shan; Shen, Zhiyong; Stanton, Bonita

2016-07-01

Antiretroviral therapy (ART) is a lifelong treatment. To date, ART adherence is suboptimal for most patients in resource-poor settings. Previous research indicates that medication side effects are perceived to be a significant barrier of high ART adherence. Data regarding the role of adherence self-efficacy in mediating the relationship between side effects from ART and adherence to ART are limited; thus, this study examines this potential mediational role of self-efficacy. A cross-sectional survey of 2987 people living with HIV aged ≥18 years was conducted in 2012-2013 in Guangxi Autonomous Region (Guangxi) which has one of the fastest-growing HIV rates in China. Of the total sample, 2146 (72.1%) participants had initiated ART. Participants reported the number of days of completing the daily dose of ART in the past month; adherence was defined as completing the daily dose at least 28 days in the last month (≥90%). Side effects were significantly negatively related to adherence to ART. Mediation analyses indicated that adherence self-efficacy significantly mediated the side effects-adherence relationship. Future interventions to increase adherence self-efficacy and effective coping with side effects among HIV patients are needed in order to improve their ART adherence.

Female partners of patients after surgical prostate cancer treatment: interactions with physicians and support needs

PubMed Central

2010-01-01

Background Few studies have explored the women's experiences as a result of a partners' diagnosis of prostate cancer. This study begins to explore women's interactions with physicians (primary care and urologist) and the support needs associated with the diagnosis and treatment of their partners' prostate cancer. Methods Two focus groups (n = 14) of women whose partners were diagnosed with prostate cancer (diagnoses' 1 - 18 months). A trained facilitator used open-ended questions to explore ideas. The framework approach was used to analyze the transcripts. Results Three main themes emerged: 1. More support. Validation and information is needed for women including emotional support and opportunities to share experiences. 2. Role of the physician. The transfer of care once specialized treatment is no longer needed remained poorly defined, which increased confusion and feelings of abandonment related to the role of the primary physician. 3. Partners' relationship changes. Men became more dependent on their partners for support and to act as the primary communicator and caregiver. Conclusions Additional research is needed in this field to confirm the importance of training primary care physicians to consider holistic treatment approaches that recognize the partner and family needs as important in the complete physical and emotional healing of their patients. PMID:20211019

Novel pharmacotherapy for the treatment of hospital-acquired and ventilator-associated pneumonia caused by resistant gram-negative bacteria.

PubMed

Kidd, James M; Kuti, Joseph L; Nicolau, David P

2018-03-01

Hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) are among the most prevalent infections in hospitalized patients, particularly those in the intensive care unit. Importantly, the frequency of multidrug resistant (MDR) Gram-negative (GN) bacteria as the bacteriologic cause of HABP/VABP is increasing. These include MDR Pseudomonas aeruginosa, Acinetobacter baumannii, and carbapenem resistant Enterobacteriaceae (CRE). Few antibiotics are currently available when such MDR Gram-negatives are encountered and older agents such as polymyxin B, colistin (polymyxin E), and tigecycline have typically performed poorly in HABP/VABP. Areas covered: In this review, the authors summarize novel antibiotics which have reached phase 3 clinical trials including patients with HABP/VABP. For each agent, the spectrum of activity, pertinent pharmacological characteristics, clinical trial data, and potential utility in the treatment of MDR-GN HABP/VABP is discussed. Expert opinion: Novel antibiotics currently available, and those soon to be, will expand opportunities to treat HABP/VABP caused by MDR-GN organisms and minimize the use of more toxic, less effective drugs. However, with sparse clinical data available, defining the appropriate role for each of the new agents is challenging. In order to maximize the utility of these antibiotics, combination therapy and the role of therapeutic drug monitoring should be investigated.

miR-150 Regulates Memory CD8 T Cell Differentiation via c-Myb.

PubMed

Chen, Zeyu; Stelekati, Erietta; Kurachi, Makoto; Yu, Sixiang; Cai, Zhangying; Manne, Sasikanth; Khan, Omar; Yang, Xiaolu; Wherry, E John

2017-09-12

MicroRNAs play an important role in T cell responses. However, how microRNAs regulate CD8 T cell memory remains poorly defined. Here, we found that miR-150 negatively regulates CD8 T cell memory in vivo. Genetic deletion of miR-150 disrupted the balance between memory precursor and terminal effector CD8 T cells following acute viral infection. Moreover, miR-150-deficient memory CD8 T cells were more protective upon rechallenge. A key circuit whereby miR-150 repressed memory CD8 T cell development through the transcription factor c-Myb was identified. Without miR-150, c-Myb was upregulated and anti-apoptotic targets of c-Myb, such as Bcl-2 and Bcl-xL, were also increased, suggesting a miR-150-c-Myb survival circuit during memory CD8 T cell development. Indeed, overexpression of non-repressible c-Myb rescued the memory CD8 T cell defects caused by overexpression of miR-150. Overall, these results identify a key role for miR-150 in memory CD8 T cells through a c-Myb-controlled enhanced survival circuit. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Overload-mediated skeletal muscle hypertrophy is not impaired by loss of myofiber STAT3.

PubMed

Pérez-Schindler, Joaquín; Esparza, Mary C; McKendry, James; Breen, Leigh; Philp, Andrew; Schenk, Simon

2017-09-01

Although the signal pathways mediating muscle protein synthesis and degradation are well characterized, the transcriptional processes modulating skeletal muscle mass and adaptive growth are poorly understood. Recently, studies in mouse models of muscle wasting or acutely exercised human muscle have suggested a potential role for the transcription factor signal transducer and activator of transcription 3 (STAT3), in adaptive growth. Hence, in the present study we sought to define the contribution of STAT3 to skeletal muscle adaptive growth. In contrast to previous work, two different resistance exercise protocols did not change STAT3 phosphorylation in human skeletal muscle. To directly address the role of STAT3 in load-induced (i.e., adaptive) growth, we studied the anabolic effects of 14 days of synergist ablation (SA) in skeletal muscle-specific STAT3 knockout (mKO) mice and their floxed, wild-type (WT) littermates. Plantaris muscle weight and fiber area in the nonoperated leg (control; CON) was comparable between genotypes. As expected, SA significantly increased plantaris weight, muscle fiber cross-sectional area, and anabolic signaling in WT mice, although interestingly, this induction was not impaired in STAT3 mKO mice. Collectively, these data demonstrate that STAT3 is not required for overload-mediated hypertrophy in mouse skeletal muscle. Copyright © 2017 the American Physiological Society.

The golgin GMAP-210 is required for efficient membrane trafficking in the early secretory pathway

PubMed Central

Roboti, Peristera; Sato, Keisuke; Lowe, Martin

2015-01-01

Golgins are coiled-coil proteins that participate in membrane-tethering events at the Golgi complex. Golgin-mediated tethering is thought to be important for vesicular trafficking and Golgi organization. However, the degree to which individual golgins contribute to these processes is poorly defined, and it has been proposed that golgins act in a largely redundant manner. Previous studies on the golgin GMAP-210 (also known as TRIP11), which is mutated in the rare skeletal disorder achondrogenesis type 1A, have yielded conflicting results regarding its involvement in trafficking. Here, we re-investigated the trafficking role of GMAP-210, and found that it is indeed required for efficient trafficking in the secretory pathway. GMAP-210 acts at both the endoplasmic reticulum (ER)-to-Golgi intermediate compartment (ERGIC) and Golgi complex during anterograde trafficking, and is also required for retrograde trafficking to the ER. Using co-depletion experiments, we also found that GMAP-210 acts in a partially redundant manner with the golgin GM130 to ensure efficient anterograde cargo delivery to the cis-Golgi. In summary, our results indicate a role for GMAP-210 in several trafficking steps at the ER–Golgi interface, some of which are partially redundant with another golgin, namely GM130 (also known as GOLGA2). PMID:25717001

Cryptococcus neoformans sexual reproduction is controlled by a quorum sensing peptide.

PubMed

Tian, Xiuyun; He, Guang-Jun; Hu, Pengjie; Chen, Lei; Tao, Changyu; Cui, Ying-Lu; Shen, Lan; Ke, Weixin; Xu, Haijiao; Zhao, Youbao; Xu, Qijiang; Bai, Fengyan; Wu, Bian; Yang, Ence; Lin, Xiaorong; Wang, Linqi

2018-06-01

Bacterial quorum sensing is a well-characterized communication system that governs a large variety of collective behaviours. By comparison, quorum sensing regulation in eukaryotic microbes remains poorly understood, especially its functional role in eukaryote-specific behaviours, such as sexual reproduction. Cryptococcus neoformans is a prevalent fungal pathogen that has two defined sexual cycles (bisexual and unisexual) and is a model organism for studying sexual reproduction in fungi. Here, we show that the quorum sensing peptide Qsp1 serves as an important signalling molecule for both forms of sexual reproduction. Qsp1 orchestrates various differentiation and molecular processes, including meiosis, the hallmark of sexual reproduction. It activates bisexual mating, at least in part through the control of pheromone, a signal necessary for bisexual activation. Notably, Qsp1 also plays a major role in the intercellular regulation of unisexual initiation and coordination, in which pheromone is not strictly required. Through a multi-layered genetic screening approach, we identified the atypical zinc finger regulator Cqs2 as an important component of the Qsp1 signalling cascade during both bisexual and unisexual reproduction. The absence of Cqs2 eliminates the Qsp1-stimulated mating response. Together, these findings extend the range of behaviours governed by quorum sensing to sexual development and meiosis.

Pure alexia as a disconnection syndrome: new diffusion imaging evidence for an old concept.

PubMed

Epelbaum, Stéphane; Pinel, Philippe; Gaillard, Raphael; Delmaire, Christine; Perrin, Muriel; Dupont, Sophie; Dehaene, Stanislas; Cohen, Laurent

2008-09-01

Functional neuroimaging and studies of brain-damaged patients made it possible to delineate the main components of the cerebral system for word reading. However, the anatomical connections subtending the flow of information within this network are still poorly defined. Here we study the connectivity of the Visual Word Form Area (VWFA), a pivotal component of the reading network achieving the invariant identification of letter strings, and reproducibly located in the left lateral occipitotemporal sulcus. Diffusion images and functional imaging data were gathered in a patient who developed pure alexia following a small surgical lesion in the vicinity of his VWFA. We had a unique opportunity to compare images obtained before, early after, and late after surgery. Analysis of diffusion images with white matter tractography and voxel-based morphometry showed that the VWFA was mainly linked to the occipital cortex through the inferior longitudinal fasciculus (ILF), and to perisylvian language areas (supramarginal gyrus) through the arcuate fasciculus. After surgery, we observed the progressive and selective degeneration of the ILF, while the VWFA was anatomically intact. This allowed us to establish the critical causal role of this fiber tract in normal reading, and to show that its disruption is one pathophysiological mechanism of pure alexia, thus clarifying a long-standing debate on the role of disconnection in neurocognitive disorders.

Organizational and Teamwork Factors of Tele-Intensive Care Units.

PubMed

Wilkes, Michael S; Marcin, James P; Ritter, Lois A; Pruitt, Sherilyn

2016-09-01

Use of tele-intensive care involves organizational and teamwork factors across geographic locations. This situation adds to the complexity of collaboration in providing quality patient-centered care. To evaluate cross-agency teamwork of health care professionals caring for patients in tele-intensive care units in rural and urban regions. A national qualitative study was conducted in 3 US geographic regions with tele-intensive care programs. Discussions and interviews were held with key participants during site visits at 3 hub sites (specialist services location) and 8 rural spoke sites (patient location). The effects of communication and culture between the hub team and the spoke team on use of the services and effectiveness of care were evaluated. A total of 34 participants were interviewed. Specific organizational and teamwork factors significantly affect the functionality of a tele-intensive care unit. Key operational and cultural barriers that limit the benefits of the units include unrealistic expectations about operational capabilities, lack of trust, poorly defined leadership, and a lack of communication policies. Potential solutions include education on spoke facility resources, clearly defined expectations and role reversal education, team-building activities, and feedback mechanisms to share concerns, successes, and suggestions. Proper administration and attention to important cultural and teamwork factors are essential to making tele-intensive care units effective, practical, and sustainable. ©2016 American Association of Critical-Care Nurses.

Obesity paradox and the heart: which indicator of obesity best describes this complex relationship?

PubMed

De Schutter, Alban; Lavie, Carl J; Patel, Dharmendrakumar A; Milani, Richard V

2013-09-01

Despite the detrimental effects of obesity on coronary heart disease (CHD) and heart failure, obesity is found to be paradoxically associated with improved survival in secondary care of CHD and heart failure. This 'obesity paradox' is an area of active research, and it might be the result of an inaccurate working definition of obesity, which is traditionally defined in terms of BMI. We reviewed the recent literature on the paradox and examined different anthropomorphic measurements and their association with prognosis in cardiovascular diseases. In CHD, obesity is associated with improved prognosis when defined by high BMI and body fat, independent of fat-free mass (FFM). High waist circumference seems to be associated with worse prognosis in some studies, but is associated with protection and an obesity paradox in those with poor cardiorespiratory fitness (CRF). In patients with heart failure, BMI, body fat and waist circumference, and possibly FFM, have been associated with improved survival. Despite these findings, intentional weight loss remains protective. In both CHD and heart failure, CRF seems to significantly impact the relationship between adiposity and subsequent prognosis, and an obesity paradox is only present with low CRF. Body composition, including waist circumference, body fat and FFM have a role in clinical practice. Emphasis should be placed on improving CRF, regardless of weight status. Intentional weight loss, particularly while maintaining FFM, should be encouraged in obese individuals.

Practical aspects of the two FIGO systems for management of abnormal uterine bleeding in the reproductive years.

PubMed

Munro, Malcolm G

2017-04-01

The FIGO systems defining the nomenclature and symptoms of abnormal uterine bleeding (AUB) in the reproductive years (System 1) and the PALM-COEIN classification of causes of AUB (System 2) are designed to facilitate research, education, and the provision of optimum clinical care for affected women. Development of these systems has been the result of a collaborative effort of experts in bench and translational and clinical research from six continents aided by a spectrum of representatives from relevant medical societies, journals, and regulatory bodies. Integral to this development has been a decision to cease the use of poorly defined and inconsistently used terms such as menorrhagia, metrorrhagia, and dysfunctional uterine bleeding, to name a few, and replace them with a set of terms and definitions that are relatively easily understood and translated into the spectrum of languages used by medical providers and patients globally. The utilization of these systems requires a disciplined approach to obtaining a menstrual history, relatively simple laboratory investigations, and the appropriate use of imaging techniques accessible to most clinicians worldwide. This section describes the two systems, their crucial role in guiding investigation, and an approach to implementation, all designed to facilitate the creation of a menu of therapeutic options, considering the identified factors contributing to the problem of nongestational AUB. Copyright © 2016. Published by Elsevier Ltd.

Natural concepts in a juvenile gorilla (gorilla gorilla gorilla) at three levels of abstraction.

PubMed Central

Vonk, Jennifer; MacDonald, Suzanne E

2002-01-01

The extent to which nonhumans are able to form conceptual versus perceptual discriminations remains a matter of debate. Among the great apes, only chimpanzees have been tested for conceptual understanding, defined as the ability to form discriminations not based solely on simple perceptual features of stimuli, and to transfer this learning to novel stimuli. In the present investigation, a young captive female gorilla was trained at three levels of abstraction (concrete, intermediate, and abstract) involving sets of photographs representing natural categories (e.g., orangutans vs. humans, primates vs. nonprimate animals, animals vs. foods). Within each level of abstraction, when the gorilla had learned to discriminate positive from negative exemplars in one set of photographs, a novel set was introduced. Transfer was defined in terms of high accuracy during the first two sessions with the new stimuli. The gorilla acquired discriminations at all three levels of abstraction but showed unambiguous transfer only with the concrete and abstract stimulus sets. Detailed analyses of response patterns revealed little evidence of control by simple stimulus features. Acquisition and transfer involving abstract stimulus sets suggest a conceptual basis for gorilla categorization. The gorilla's relatively poor performance with intermediate-level discriminations parallels findings with pigeons, and suggests a need to reconsider the role of perceptual information in discriminations thought to indicate conceptual behavior in nonhumans. PMID:12507006

Anatomy and Aesthetics of the Labia Minora: The Ideal Vulva?

PubMed

Clerico, C; Lari, A; Mojallal, A; Boucher, F

2017-06-01

Female genital cosmetic surgery is becoming more and more widespread both in the field of plastic and gynaecological surgery. The increased demand for vulvar surgery is spurred by the belief that the vulva is abnormal in appearance. What is normal in terms of labial anatomy? Labia minora enlargement or hypertrophy remains a clinical diagnosis which is poorly defined as it could be considered a variation of the normal anatomy. Enlarged labia minora can cause functional, aesthetic and psychosocial problems. In reality, given the wide variety of vulvar morphology among people, it is a very subjective issue to define the "normal" vulva. The spread of nudity in the general media plays a major role in creating an artificial image and standards with regard to the ideal form. Physicians should be aware that the patient's self-perception of the normal or ideal vulva is highly influenced by the arguably distorted image related to our socio-psychological environment, as presented to us by the general media and internet. As physicians, we have to educate our patients on the variation of vulvar anatomy and the potential risks of these surgeries. Level of Evidence V This journal requires that authors assign a level of evidence to each article. For a full description of these evidence-based medicine ratings, please refer to Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Explaining the Role of Proximate Determinants on Fertility Decline among Poor and Non-Poor in Asian Countries

PubMed Central

Majumder, Nabanita; Ram, Faujdar

2015-01-01

Objectives We examined the overall contributions of the poor and non-poor in fertility decline across the Asian countries. Further, we analyzed the direct and indirect factors that determine the reproductive behaviour of two distinct population sub-groups. Design Data from several new rounds of DHS surveys are available over the past few years. The DHS provides cross-nationally comparable and useful data on fertility, family planning, maternal and child health along with the other information. Six selected Asian countries namely: Bangladesh, India, Indonesia, Nepal, Philippines, and Vietnam are considered for the purpose of the study. Three rounds of DHS surveys for each country (except Vietnam) are considered in the present study. Methods Economic status is measured by computing a “wealth index”, i.e. a composite indicator constructed by aggregating data on asset ownership and housing characteristics using principal components analysis (PCA). Computed household wealth index has been broken into three equal parts (33.3 percent each) and the lowest and the highest 33.3 percent is considered as poor and non-poor respectively. The Bongaarts model was employed to quantify the contribution of each of the proximate determinants of fertility among poor and non-poor women. Results Fertility reduction across all population subgroups is now an established fact despite the diversity in the level of socio-economic development in Asian countries. It is clear from the analysis that fertility has declined irrespective of economic status at varying degrees within and across the countries which can be attributed to the increasing level of contraceptive use especially among poor women. Over the period of time changing marriage pattern and induced abortion are playing an important role in reducing fertility among poor women. Conclusions Fertility decline among majority of the poor women across the Asian countries is accompanied by high prevalence of contraceptive use followed by changing marriage pattern and induced abortion. PMID:25689843

Family-based intervention in adolescent restrictive eating disorders: early treatment response and low weight suppression is associated with favourable one-year outcome.

PubMed

Swenne, Ingemar; Parling, Thomas; Salonen Ros, Helena

2017-09-15

Family-based treatments are first-line treatments for adolescents with restrictive eating disorders (ED) but have to be improved since outcome is poor for some. We have investigated the one-year outcome of a family-based intervention programme with defined and decisive interventions at the start of treatment. Data pertaining 201 adolescents with restrictive ED with features of anorexia nervosa but not fulfilling the weight criterion starting treatment 2010-2015, had a wide range of body mass index (BMI) and of weight loss at presentation, and completed a one-year follow-up was analysed. Recovery from the ED was defined as an Eating Disorder Examination-questionnaire (EDE-Q) score < 2.0 or as not fulfilling criteria for an ED at a clinical interview. By EDE-Q 130 (65%) had recovered at 1 year and by clinical interview 106 (53%). According to the EDE-Q criterion recovery was independently associated with lower EDE-Q score at presentation, higher weight gain after 3 months of treatment and lower weight suppression at follow-up, weight suppression being defined as the difference between premorbid and current BMI. Not fulfilling criteria for an ED was associated with the same factors and also by higher BMI at presentation. The observations that low weight and high ED cognitions confer a poor prognosis but that rapid weight gain at the start of treatment predicts a better prognosis are presently extended to adolescents with restrictive ED with a wide range of BMI at presentation. High weight suppression at follow-up is associated with a poor prognosis and indicates the importance of taking premorbid BMI into account when setting weight targets for treatment.

Minorities, the Poor and School Finance Reform. Vol. 2: The Impact of Texas' 1975 School Finance Reform on Poor and Minority Children.

ERIC Educational Resources Information Center

Brischetto, Robert

As part of a nine-volume, six-state study of the impact of school finance reforms on minorities and the poor, the author examines the history and effects of finance reform in Texas. He presents a political and socioeconomic profile of the state and discusses past Texas school financing, the role of the Rodriguez v. San Antonio Independent School…

A study on the sleep quality of incoming university students.

PubMed

Cheng, Shu Hui; Shih, Chi-Chen; Lee, I Hui; Hou, Yi-Wen; Chen, Kao Chin; Chen, Kow-Tong; Yang, Yen Kuang; Yang, Yi Ching

2012-05-30

This study was designed to examine the prevalence and the risk factors of poor sleep quality in 4318 incoming university students in Taiwan. The test battery comprised a self-administered structured questionnaire, including items related to personal medical history and lifestyle habits, the Measurement of Support Functions (MSF), Pittsburgh Sleep Quality Index (PSQI), Chinese Internet Addiction Scale-Revision (CIAS-R), neuroticism subscale of the Maudsley Personality Inventory (MPI), and the 12-item Chinese Health Questionnaire (CHQ-12). Of the total study population, 2360 students (54.7%) were classified into the poor sleep quality group, as defined by a PSQI score ≥6. Based on the results of multivariate logistic regression analysis, poor sleep quality was significantly associated with undergraduate students, female gender, skipping breakfast, tea drinking, a higher tendency toward internet addition, poor social support, higher neuroticism, and higher CHQ scores. Poor sleep quality is prevalent among incoming university students in Taiwan, and more work is needed on the identification of the factors influencing poor sleep, and in providing systematic education in the importance of sleep and time management skills to university students. Copyright © 2012 Elsevier Ltd. All rights reserved.

Family poverty and trajectories of children's emotional and behavioural problems: the moderating roles of self-regulation and verbal cognitive ability.

PubMed

Flouri, Eirini; Midouhas, Emily; Joshi, Heather

2014-08-01

Socio-economic disadvantage is strongly associated with children's emotional (internalising) and behavioural (externalising) problems. Self-regulation and verbal cognitive ability have been related to children's emotional and behavioural resilience to socio-economic disadvantage. Despite being inter-related, self-regulation and verbal cognitive ability have not been examined jointly as promoting resilience in young children. This study investigated the roles of self-regulation and verbal cognitive ability in children's emotional and behavioural resilience to family socio-economic disadvantage from early to middle childhood (ages 3, 5, and 7 years; N = 16,916; 49 % girls). Using multivariate response growth curve modelling, we found that the relationship between socio-economic disadvantage and internalising problems was stronger for children with lower verbal cognitive ability. Also, poor children with high and low levels of self-regulation showed a widening gap in both emotional and behavioural problems over time. Poor and non-poor children alike benefited from self-regulation, but poor children appeared to be more vulnerable to low self-regulation. Self-regulation and verbal cognitive ability seem to be important protective factors for young children growing up in poor families.

American Society for Enhanced Recovery and Perioperative Quality Initiative Joint Consensus Statement on Nutrition Screening and Therapy Within a Surgical Enhanced Recovery Pathway.

PubMed

Wischmeyer, Paul E; Carli, Franco; Evans, David C; Guilbert, Sarah; Kozar, Rosemary; Pryor, Aurora; Thiele, Robert H; Everett, Sotiria; Grocott, Mike; Gan, Tong J; Shaw, Andrew D; Thacker, Julie K M; Miller, Timothy E; Hedrick, Traci L; McEvoy, Matthew D; Mythen, Michael G; Bergamaschi, Roberto; Gupta, Ruchir; Holubar, Stefan D; Senagore, Anthony J; Abola, Ramon E; Bennett-Guerrero, Elliott; Kent, Michael L; Feldman, Liane S; Fiore, Julio F

2018-06-01

Perioperative malnutrition has proven to be challenging to define, diagnose, and treat. Despite these challenges, it is well known that suboptimal nutritional status is a strong independent predictor of poor postoperative outcomes. Although perioperative caregivers consistently express recognition of the importance of nutrition screening and optimization in the perioperative period, implementation of evidence-based perioperative nutrition guidelines and pathways in the United States has been quite limited and needs to be addressed in surgery-focused recommendations. The second Perioperative Quality Initiative brought together a group of international experts with the objective of providing consensus recommendations on this important topic with the goal of (1) developing guidelines for screening of nutritional status to identify patients at risk for adverse outcomes due to malnutrition; (2) address optimal methods of providing nutritional support and optimizing nutrition status preoperatively; and (3) identifying when and how to optimize nutrition delivery in the postoperative period. Discussion led to strong recommendations for implementation of routine preoperative nutrition screening to identify patients in need of preoperative nutrition optimization. Postoperatively, nutrition delivery should be restarted immediately after surgery. The key role of oral nutrition supplements, enteral nutrition, and parenteral nutrition (implemented in that order) in most perioperative patients was advocated for with protein delivery being more important than total calorie delivery. Finally, the role of often-inadequate nutrition intake in the posthospital setting was discussed, and the role of postdischarge oral nutrition supplements was emphasized.

Interleukin-17-Induced Protein Lipocalin 2 Is Dispensable for Immunity to Oral Candidiasis

PubMed Central

Ferreira, Maria Carolina; Whibley, Natasha; Mamo, Anna J.; Siebenlist, Ulrich; Chan, Yvonne R.

2014-01-01

Oropharyngeal candidiasis (OPC; thrush) is an opportunistic fungal infection caused by the commensal microbe Candida albicans. Immunity to OPC is strongly dependent on CD4+ T cells, particularly those of the Th17 subset. Interleukin-17 (IL-17) deficiency in mice or humans leads to chronic mucocutaneous candidiasis, but the specific downstream mechanisms of IL-17-mediated host defense remain unclear. Lipocalin 2 (Lcn2; 24p3; neutrophil gelatinase-associated lipocalin [NGAL]) is an antimicrobial host defense factor produced in response to inflammatory cytokines, particularly IL-17. Lcn2 plays a key role in preventing iron acquisition by bacteria that use catecholate-type siderophores, and lipocalin 2−/− mice are highly susceptible to infection by Escherichia coli and Klebsiella pneumoniae. The role of Lcn2 in mediating immunity to fungi is poorly defined. Accordingly, in this study, we evaluated the role of Lcn2 in immunity to oral infection with C. albicans. Lcn2 is strongly upregulated following oral infection with C. albicans, and its expression is almost entirely abrogated in mice with defective IL-17 signaling (IL-17RA−/− or Act1−/− mice). However, Lcn2−/− mice were completely resistant to OPC, comparably to wild-type (WT) mice. Moreover, Lcn2 deficiency mediated protection from OPC induced by steroid immunosuppression. Therefore, despite its potent regulation during C. albicans infection, Lcn2 is not required for immunity to mucosal candidiasis. PMID:24343647

Comparative functional characterization of the CSR-1 22G-RNA pathway in Caenorhabditis nematodes.

PubMed

Tu, Shikui; Wu, Monica Z; Wang, Jie; Cutter, Asher D; Weng, Zhiping; Claycomb, Julie M

2015-01-01

As a champion of small RNA research for two decades, Caenorhabditis elegans has revealed the essential Argonaute CSR-1 to play key nuclear roles in modulating chromatin, chromosome segregation and germline gene expression via 22G-small RNAs. Despite CSR-1 being preserved among diverse nematodes, the conservation and divergence in function of the targets of small RNA pathways remains poorly resolved. Here we apply comparative functional genomic analysis between C. elegans and Caenorhabditis briggsae to characterize the CSR-1 pathway, its targets and their evolution. C. briggsae CSR-1-associated small RNAs that we identified by immunoprecipitation-small RNA sequencing overlap with 22G-RNAs depleted in cbr-csr-1 RNAi-treated worms. By comparing 22G-RNAs and target genes between species, we defined a set of CSR-1 target genes with conserved germline expression, enrichment in operons and more slowly evolving coding sequences than other genes, along with a small group of evolutionarily labile targets. We demonstrate that the association of CSR-1 with chromatin is preserved, and show that depletion of cbr-csr-1 leads to chromosome segregation defects and embryonic lethality. This first comparative characterization of a small RNA pathway in Caenorhabditis establishes a conserved nuclear role for CSR-1 and highlights its key role in germline gene regulation across multiple animal species. © The Author(s) 2014. Published by Oxford University Press on behalf of Nucleic Acids Research.

Lipopolysaccharide Clearance, Bacterial Clearance, and Systemic Inflammatory Responses Are Regulated by Cell Type–Specific Functions of TLR4 during Sepsis

PubMed Central

Deng, Meihong; Loughran, Patricia; Gibson, Gregory; Sodhi, Chhinder; Watkins, Simon; Hackam, David

2013-01-01

The morbidity associated with bacterial sepsis is the result of host immune responses to pathogens, which are dependent on pathogen recognition by pattern recognition receptors, such as TLR4. TLR4 is expressed on a range of cell types, yet the mechanisms by which cell-specific functions of TLR4 lead to an integrated sepsis response are poorly understood. To address this, we generated mice in which TLR4 was specifically deleted from myeloid cells (LysMTLR4KO) or hepatocytes (HCTLR4KO) and then determined survival, bacterial counts, host inflammatory responses, and organ injury in a model of cecal ligation and puncture (CLP), with or without antibiotics. LysM-TLR4 was required for phagocytosis and efficient bacterial clearance in the absence of antibiotics. Survival, the magnitude of the systemic and local inflammatory responses, and liver damage were associated with bacterial levels. HCTLR4 was required for efficient LPS clearance from the circulation, and deletion of HCTLR4 was associated with enhanced macrophage phagocytosis, lower bacterial levels, and improved survival in CLP without antibiotics. Antibiotic administration during CLP revealed an important role for hepatocyte LPS clearance in limiting sepsis-induced inflammation and organ injury. Our work defines cell type–selective roles for TLR4 in coordinating complex immune responses to bacterial sepsis and suggests that future strategies for modulating microbial molecule recognition should account for varying roles of pattern recognition receptors in multiple cell populations. PMID:23562812

Antibody Responses to Marburg Virus in Egyptian Rousette Bats and Their Role in Protection against Infection.

PubMed

Storm, Nadia; Jansen Van Vuren, Petrus; Markotter, Wanda; Paweska, Janusz T

2018-02-10

Egyptian rousette bats (ERBs) are reservoir hosts for the Marburg virus (MARV). The immune dynamics and responses to MARV infection in ERBs are poorly understood, and limited information exists on the role of antibodies in protection of ERBs against MARV infection. Here, we determine the duration of maternal immunity to MARV in juvenile ERBs, and evaluate the duration of the antibody response to MARV in bats naturally or experimentally infected with the virus. We further explore whether antibodies in previously naturally exposed bats is fully protective against experimental reinfection with MARV. Maternal immunity was lost in juvenile ERBs by 5 months of age. Antibodies to MARV remained detectable in 67% of experimentally infected bats approximately 4 months post inoculation (p.i.), while antibodies to MARV remained present in 84% of naturally exposed bats at least 11 months after capture. Reinfection of seropositive ERBs with MARV produced an anamnestic response from day 5 p.i. Although PCR-defined viremia was present in 73.3% of reinfected ERBs, replicating virus was recovered from the serum of only one bat on day 3 p.i. The negative PCR results in the salivary glands, intestines, bladders and reproductive tracts of reinfected bats, and the apparent absence of MARV in the majority of swabs collected from these bats suggest that reinfection may only play a minor role in the transmission and maintenance of MARV amongst ERBs in nature.

Emerging roles for IL-11 signaling in cancer development and progression: Focus on breast cancer.

PubMed

Johnstone, Cameron N; Chand, Ashwini; Putoczki, Tracy L; Ernst, Matthias

2015-10-01

Interleukin (IL)-11 is a member of the IL-6 family of cytokines that is defined by the shared use of the GP130 signal transducing receptor subunit. In addition of its long recognized activities as a hemopoietic growth factor, IL-11 has an emerging role in epithelial cancer biology. Through the activation of the GP130-Janus kinase signaling cascade and associated transcription factor STAT3, IL-11 can confer many of the tumor intrinsic 'hallmark' capabilities to neoplastic cells, if they express the ligand-specific IL-11Rα receptor subunit. Accordingly, IL-11 signaling has recently been identified as a rate-limiting step for the growth tumors arising from the mucosa of the gastrointestinal tract. However, there is less appreciation for a potential role of IL-11 to support breast cancer progression, apart from its well documented capacity to facilitate bone metastasis. Here we review evidence that IL-11 expression in breast cancer correlates with poor disease outcome and discuss some of the molecular mechanisms that are likely to underpin these observations. These include the capacity of IL-11 to stimulate survival and proliferation of cancer cells alongside angiogenesis of the primary tumor and of metastatic progenies at distant organs. We review current strategies to interfere with IL-11 signaling and advocate that inhibition of IL-11 signaling may represent an emerging therapeutic opportunity for numerous cancers. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Obesity, metabolic dysfunction and cardiac fibrosis: pathophysiologic pathways, molecular mechanisms and therapeutic opportunities

PubMed Central

Cavalera, Michele; Wang, Junhong; Frangogiannis, Nikolaos G

2014-01-01

Cardiac fibrosis is strongly associated with obesity and metabolic dysfunction and may contribute to the increased incidence of heart failure, atrial arrhythmias and sudden cardiac death in obese subjects. Our review discusses the evidence linking obesity and myocardial fibrosis in animal models and human patients, focusing on the fundamental pathophysiologic alterations that may trigger fibrogenic signaling, the cellular effectors of fibrosis and the molecular signals that may regulate the fibrotic response. Obesity is associated with a wide range of pathophysiologic alterations (such as pressure and volume overload, metabolic dysregulation, neurohumoral activation and systemic inflammation); their relative role in mediating cardiac fibrosis is poorly defined. Activation of fibroblasts likely plays a major role in obesity-associated fibrosis; however, inflammatory cells, cardiomyocytes and vascular cells may also contribute to fibrogenic signaling. Several molecular processes have been implicated in regulation of the fibrotic response in obesity. Activation of the Renin-Angiotensin-Aldosterone System, induction of Transforming Growth Factor-β, oxidative stress, advanced glycation end-products (AGEs), endothelin-1, Rho-kinase signaling, leptin-mediated actions and upregulation of matricellular proteins (such as thrombospondin-1) may play a role in the development of fibrosis in models of obesity and metabolic dysfunction. Moreover, experimental evidence suggests that obesity and insulin resistance profoundly affect the fibrotic and remodeling response following cardiac injury. Understanding the pathways implicated in obesity-associated fibrosis may lead to development of novel therapies to prevent heart failure and to attenuate post-infarction cardiac remodeling in obese patients. PMID:24880146

Methionine Regulates mTORC1 via the T1R1/T1R3-PLCβ-Ca2+-ERK1/2 Signal Transduction Process in C2C12 Cells.

PubMed

Zhou, Yuanfei; Ren, Jiao; Song, Tongxing; Peng, Jian; Wei, Hongkui

2016-10-11

The mammalian target of rapamycin complex 1 (mTORC1) integrates amino acid (AA) availability to support protein synthesis and cell growth. Taste receptor type 1 member (T1R) is a G protein-coupled receptor that functions as a direct sensor of extracellular AA availability to regulate mTORC1 through Ca 2+ stimulation and extracellular signal-regulated kinases 1 and 2 (ERK1/2) activation. However, the roles of specific AAs in T1R1/T1R3-regulated mTORC1 are poorly defined. In this study, T1R1 and T1R3 subunits were expressed in C2C12 myotubes, and l-AA sensing was accomplished by T1R1/T1R3 to activate mTORC1. In response to l-AAs, such as serine (Ser), arginine (Arg), threonine (Thr), alanine (Ala), methionine (Met), glutamine (Gln), and glycine (Gly), Met induced mTORC1 activation and promoted protein synthesis. Met also regulated mTORC1 via T1R1/T1R3-PLCβ-Ca 2+ -ERK1/2 signal transduction. Results revealed a new role for Met-regulated mTORC1 via an AA receptor. Further studies should be performed to determine the role of T1R1/T1R3 in mediating extracellular AA to regulate mTOR signaling and to reveal its mechanism.

The key role of exudative lesions and their encapsulation: lessons learned from the pathology of human pulmonary tuberculosis.

PubMed

Cardona, Pere-Joan

2015-01-01

A review of the pathology of human pulmonary TB cases at different stages of evolution in the pre-antibiotic era suggests that neutrophils play an instrumental role in the progression toward active TB. This progression is determined by the type of lesion generated. Thus, exudative lesions, in which neutrophils are the major cell type, are both triggered by and induce local high bacillary load, and tend to enlarge and progress toward liquefaction and cavitation. In contrast, proliferative lesions are triggered by low bacillary loads, mainly comprise epithelioid cells and fibroblasts and tend to fibrose, encapsulate and calcify, thus controlling the infection. Infection of the upper lobes is key to the progression toward active TB for two main reasons, namely poor breathing amplitude, which allows local bacillary accumulation, and the high mechanical stress to which the interlobular septae (which enclose secondary lobes) are submitted, which hampers their ability to encapsulate lesions. Overall, progressing factors can be defined as internal (exudative lesion, local bronchogenous dissemination, coalescence of lesions), with lympho-hematological dissemination playing a very limited role, or external (exogenous reinfection). Abrogating factors include control of the bacillary load and the local encapsulation process, as directed by interlobular septae. The age and extent of disease depend on the quality and speed with which lesions liquefy and disseminate bronchially, the volume of the slough, and the amount and distribution of the sloughing debris dispersed.

The key role of exudative lesions and their encapsulation: lessons learned from the pathology of human pulmonary tuberculosis

PubMed Central

Cardona, Pere-Joan

2015-01-01

A review of the pathology of human pulmonary TB cases at different stages of evolution in the pre-antibiotic era suggests that neutrophils play an instrumental role in the progression toward active TB. This progression is determined by the type of lesion generated. Thus, exudative lesions, in which neutrophils are the major cell type, are both triggered by and induce local high bacillary load, and tend to enlarge and progress toward liquefaction and cavitation. In contrast, proliferative lesions are triggered by low bacillary loads, mainly comprise epithelioid cells and fibroblasts and tend to fibrose, encapsulate and calcify, thus controlling the infection. Infection of the upper lobes is key to the progression toward active TB for two main reasons, namely poor breathing amplitude, which allows local bacillary accumulation, and the high mechanical stress to which the interlobular septae (which enclose secondary lobes) are submitted, which hampers their ability to encapsulate lesions. Overall, progressing factors can be defined as internal (exudative lesion, local bronchogenous dissemination, coalescence of lesions), with lympho-hematological dissemination playing a very limited role, or external (exogenous reinfection). Abrogating factors include control of the bacillary load and the local encapsulation process, as directed by interlobular septae. The age and extent of disease depend on the quality and speed with which lesions liquefy and disseminate bronchially, the volume of the slough, and the amount and distribution of the sloughing debris dispersed. PMID:26136741

Controlling the burn and fueling the fire: defining the role for the alarmin interleukin-33 in alloimmunity.

PubMed

Liu, Quan; Turnquist, Heth R

2016-02-01

The purpose of this review is to provide a general update on recent developments in the immunobiology of IL-33 and IL-33-targeted immune cells. We also discuss emerging concepts regarding the potential role IL-33 appears to play in altering alloimmune responses mediating host-versus-graft and graft-versus-host alloresponses. Stromal cells and leukocytes display regulated expression of IL-33 and may actively or passively secrete this pleotropic cytokine. Type 2 innate lymphoid cells and a large proportion of tissue resident regulatory T cells (Treg) express membrane-bound suppressor of tumorigenicity 2 (ST2), the IL-33 receptor. Although Treg are appreciated suppressors of the inflammatory function of immune cells, both type 2 innate lymphoid cells and tissue resident Treg could play key roles in tissue repair and homeostasis. The functions of IL-33 in transplantation are poorly understood. However, like other disease models, the functions of IL-33 in alloimmunity appear to be quite pleiotropic. IL-33 is associated with immune regulation and graft protection in cardiac transplant settings. Yet, it is highly proinflammatory and stimulates lethal graft-versus-host disease through its capacity to stimulate type 1 immunity. Intensive studies on IL-33/ST2 signaling pathways and ST2 cell populations in solid organ and cell transplantation are warranted. A better understanding of this important pathway will provide promising therapeutic targets controlling pathogenic alloimmune responses, as well as potentially facilitating the function of regulatory and reparative immune cells posttransplantation.

Temperature variability during targeted temperature management is not associated with neurological outcomes following cardiac arrest.

PubMed

Nayeri, Arash; Bhatia, Nirmanmoh; Holmes, Benjamin; Borges, Nyal; Armstrong, William; Xu, Meng; Farber-Eger, Eric; Wells, Quinn S; McPherson, John A

2017-06-01

Recent studies on comatose survivors of cardiac arrest undergoing targeted temperature management (TTM) have shown similar outcomes at multiple target temperatures. However, details regarding core temperature variability during TTM and its prognostic implications remain largely unknown. We sought to assess the association between core temperature variability and neurological outcomes in patients undergoing TTM following cardiac arrest. We analyzed a prospectively collected cohort of 242 patients treated with TTM following cardiac arrest at a tertiary care hospital between 2007 and 2014. Core temperature variability was defined as the statistical variance (i.e. standard deviation squared) amongst all core temperature recordings during the maintenance phase of TTM. Poor neurological outcome at hospital discharge, defined as a Cerebral Performance Category (CPC) score>2, was the primary outcome. Death prior to hospital discharge was assessed as the secondary outcome. Multivariable logistic regression was used to examine the association between temperature variability and neurological outcome or death at hospital discharge. A poor neurological outcome was observed in 147 (61%) patients and 136 (56%) patients died prior to hospital discharge. In multivariable logistic regression, increased core temperature variability was not associated with increased odds of poor neurological outcomes (OR 0.38, 95% CI 0.11-1.38, p=0.142) or death (OR 0.43, 95% CI 0.12-1.53, p=0.193) at hospital discharge. In this study, individual core temperature variability during TTM was not associated with poor neurological outcomes or death at hospital discharge. Copyright © 2017 Elsevier Inc. All rights reserved.

Defining Metabolically Healthy Obesity: Role of Dietary and Lifestyle Factors

PubMed Central

Phillips, Catherine M.; Dillon, Christina; Harrington, Janas M.; McCarthy, Vera J. C.; Kearney, Patricia M.; Fitzgerald, Anthony P.; Perry, Ivan J.

2013-01-01

Background There is a current lack of consensus on defining metabolically healthy obesity (MHO). Limited data on dietary and lifestyle factors and MHO exist. The aim of this study is to compare the prevalence, dietary factors and lifestyle behaviours of metabolically healthy and unhealthy obese and non-obese subjects according to different metabolic health criteria. Method Cross-sectional sample of 1,008 men and 1,039 women aged 45-74 years participated in the study. Participants were classified as obese (BMI ≥30kg/m2) and non-obese (BMI <30kg/m2). Metabolic health status was defined using five existing MH definitions based on a range of cardiometabolic abnormalities. Dietary composition and quality, food pyramid servings, physical activity, alcohol and smoking behaviours were examined. Results The prevalence of MHO varied considerably between definitions (2.2% to 11.9%), was higher among females and generally increased with age. Agreement between MHO classifications was poor. Among the obese, prevalence of MH was 6.8% to 36.6%. Among the non-obese, prevalence of metabolically unhealthy subjects was 21.8% to 87%. Calorie intake, dietary macronutrient composition, physical activity, alcohol and smoking behaviours were similar between the metabolically healthy and unhealthy regardless of BMI. Greater compliance with food pyramid recommendations and higher dietary quality were positively associated with metabolic health in obese (OR 1.45-1.53 unadjusted model) and non-obese subjects (OR 1.37-1.39 unadjusted model), respectively. Physical activity was associated with MHO defined by insulin resistance (OR 1.87, 95% CI 1.19-2.92, p = 0.006). Conclusion A standard MHO definition is required. Moderate and high levels of physical activity and compliance with food pyramid recommendations increase the likelihood of MHO. Stratification of obese individuals based on their metabolic health phenotype may be important in ascertaining the appropriate therapeutic or intervention strategy. PMID:24146838

Promoting Positive Special Education Practices

ERIC Educational Resources Information Center

Conderman, Greg; Pedersen, Theresa

2005-01-01

Special education is defined as specialized instruction for students with disabilities. Sometimes, however, legal requirements as well as the day-to-day demands of teaching secondary students with disabilities cloud the real intent of special education. This article acknowledges some poor practices occurring in secondary special education and…

The geography of spatial synchrony

Treesearch

Jonathan A. Walter; Lawrence W. Sheppard; Thomas L. Anderson; Jude H. Kastens; Ottar N. Bjørnstad; Andrew M. Liebhold; Daniel C. Reuman; Bernd Blasius

2017-01-01

Spatial synchrony, defined as correlated temporal fluctuations among populations, is a fundamental feature of population dynamics, but many aspects of synchrony remain poorly understood. Few studies have examined detailed geographical patterns of synchrony; instead most focus on how synchrony declines with increasing linear distance between locations, making the...

78 FR 691 - Guarantee Fee Rates for Guaranteed Loans for Fiscal Year 2013; Maximum Portion of Guarantee...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-04

... benefiting financially or must be a high impact business investment as defined in 7 CFR 4279.155(b)(5) and be... persistently poor, are experiencing trauma as a result of natural disaster, or are experiencing fundamental...

Working Memory Compensates for Hearing Related Phonological Processing Deficit

ERIC Educational Resources Information Center

Classon, Elisabet; Rudner, Mary; Ronnberg, Jerker

2013-01-01

Acquired hearing impairment is associated with gradually declining phonological representations. According to the Ease of Language Understanding (ELU) model, poorly defined representations lead to mismatch in phonologically challenging tasks. To resolve the mismatch, reliance on working memory capacity (WMC) increases. This study investigated…

Health Seeking in Men: A Concept Analysis.

PubMed

Hooper, Gwendolyn L; Quallich, Susanne A

2016-01-01

This article describes the analysis of the concept of health seeking in men. Men have shorter life expectancies and utilize health services less often than women, leading to poor health outcomes, but a gendered basis for health seeking remains poorly defined. Walker and Avant’s framework was used to guide this concept analysis. Literature published in English from 1990-2015 was reviewed. Thematic analysis identified attributes, antecedents, and consequences of the concept. Based on the analysis, a contemporary definition for health seeking in men was constructed, rooted in the concept of health. The definition is based on the concept analysis and the defining attributes that were identified. This analysis provides a definition specifically for health seeking in American men, making it more specific and gender-based than the parent concept of “health.” This concept analysis provides conceptual clarity that can guide development of a conceptual framework that may be uniquely relevant to providers in urology. Further exploration will uncover specific cultural, social, sexual, and geographic perspectives.

Prognostic indicators of poor short-term outcome of physiotherapy intervention in women with stress urinary incontinence.

PubMed

Hendriks, Erik J M; Kessels, Alfons G H; de Vet, Henrica C W; Bernards, Arnold T M; de Bie, Rob A

2010-03-01

To identify prognostic indicators independently associated with poor outcome of physiotherapy intervention in women with primary or recurrent stress urinary incontinence (stress UI). A prospective cohort study was performed in physiotherapy practices in primary care to identify prognostic indicators 12 weeks after initiation of physiotherapy intervention. Patients were referred by general practitioners or urogynecologists. Risk factors for stress UI were examined as potential prognostic indicators of poor outcome. The primary outcomes were defined as poor outcome on the binary Leakage Severity scale (LS scale) and the binary global perceived effectiveness (GPE) score. Two hundred sixty-seven women, with a mean age of 47.7 (SD = 8.3), with stress UI for at least 6 months were included. At 12 weeks, 43% and 59% of the women were considered recovered on the binary LS scale and the binary GPE score, respectively. Prognostic indicators associated with poor outcome included 11 indicators based on the binary LS scale and 8 based on the binary GPE score. The prognostic indicators shared by both models show that poor recovery was associated with women with severe stress UI, POP-Q stage > II, poor outcome of physiotherapy intervention for a previous UI episode, prolonged second stage of labor, BMI > 30, high psychological distress, and poor physical health. This study provides robust evidence of clinically meaningful prognostic indicators of poor short-term outcome. These findings need to be confirmed by replication studies. (c) 2009 Wiley-Liss, Inc.

Defining the light emitting area for displays in the unipolar regime of highly efficient light emitting transistors

PubMed Central

Ullah, Mujeeb; Armin, Ardalan; Tandy, Kristen; Yambem, Soniya D.; Burn, Paul L.; Meredith, Paul; Namdas, Ebinazar B.

2015-01-01

Light-emitting field effect transistors (LEFETs) are an emerging class of multifunctional optoelectronic devices. It combines the light emitting function of an OLED with the switching function of a transistor in a single device architecture. The dual functionality of LEFETs has the potential applications in active matrix displays. However, the key problem of existing LEFETs thus far has been their low EQEs at high brightness, poor ON/OFF and poorly defined light emitting area - a thin emissive zone at the edge of the electrodes. Here we report heterostructure LEFETs based on solution processed unipolar charge transport and an emissive polymer that have an EQE of up to 1% at a brightness of 1350 cd/m2, ON/OFF ratio > 104 and a well-defined light emitting zone suitable for display pixel design. We show that a non-planar hole-injecting electrode combined with a semi-transparent electron-injecting electrode enables to achieve high EQE at high brightness and high ON/OFF ratio. Furthermore, we demonstrate that heterostructure LEFETs have a better frequency response (fcut-off = 2.6 kHz) compared to single layer LEFETs. The results presented here therefore are a major step along the pathway towards the realization of LEFETs for display applications. PMID:25743444

Synthesis and Characterization of the Actinium Aquo Ion

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

Ferrier, Maryline G.; Stein, Benjamin W.; Batista, Enrique R.

Metal aquo ions occupy central roles in all equilibria that define metal complexation in natural environments. These complexes are used to establish thermodynamic metrics (i.e., stability constants) for predicting metal binding, which are essential for defining critical parameters associated with aqueous speciation, metal chelation, in vivo transport, and so on. As such, establishing the fundamental chemistry of the actinium(III) aquo ion (Ac-aquo ion, Ac(H 2O) x 3+) is critical for current efforts to develop 225Ac [t 1/2 = 10.0(1) d] as a targeted anticancer therapeutic agent. However, given the limited amount of actinium available for study and its high radioactivity,more » many aspects of actinium chemistry remain poorly defined. We overcame these challenges using the longer-lived 227Ac [t 1/2 = 21.772(3) y] isotope and report the first characterization of this fundamentally important Ac-aquo coordination complex. Our X-ray absorption fine structure study revealed 10.9 ± 0.5 water molecules directly coordinated to the Ac III cation with an Ac–O H2O distance of 2.63(1) Å. This experimentally determined distance was consistent with molecular dynamics density functional theory results that showed (over the course of 8 ps) that Ac III was coordinated by 9 water molecules with Ac–O H2O distances ranging from 2.61 to 2.76 Å. Lastly, the data is presented in the context of other actinide(III) and lanthanide(III) aquo ions characterized by XAFS and highlights the uniqueness of the large Ac III coordination numbers and long Ac–O H2O bond distances.« less

Synthesis and Characterization of the Actinium Aquo Ion

DOE PAGES

Ferrier, Maryline G.; Stein, Benjamin W.; Batista, Enrique R.; ...

2017-02-01

Metal aquo ions occupy central roles in all equilibria that define metal complexation in natural environments. These complexes are used to establish thermodynamic metrics (i.e., stability constants) for predicting metal binding, which are essential for defining critical parameters associated with aqueous speciation, metal chelation, in vivo transport, and so on. As such, establishing the fundamental chemistry of the actinium(III) aquo ion (Ac-aquo ion, Ac(H 2O) x 3+) is critical for current efforts to develop 225Ac [t 1/2 = 10.0(1) d] as a targeted anticancer therapeutic agent. However, given the limited amount of actinium available for study and its high radioactivity,more » many aspects of actinium chemistry remain poorly defined. We overcame these challenges using the longer-lived 227Ac [t 1/2 = 21.772(3) y] isotope and report the first characterization of this fundamentally important Ac-aquo coordination complex. Our X-ray absorption fine structure study revealed 10.9 ± 0.5 water molecules directly coordinated to the Ac III cation with an Ac–O H2O distance of 2.63(1) Å. This experimentally determined distance was consistent with molecular dynamics density functional theory results that showed (over the course of 8 ps) that Ac III was coordinated by 9 water molecules with Ac–O H2O distances ranging from 2.61 to 2.76 Å. Lastly, the data is presented in the context of other actinide(III) and lanthanide(III) aquo ions characterized by XAFS and highlights the uniqueness of the large Ac III coordination numbers and long Ac–O H2O bond distances.« less

Genetic and mechanistic diversity of piRNA 3' end formation

PubMed Central

Handler, Dominik; Mohn, Fabio; Ameres, Stefan L.; Brennecke, Julius

2016-01-01

Small regulatory RNAs guide Argonaute (Ago) proteins in a sequence-specific manner to their targets and thereby play important roles in eukaryotic gene silencing1. Of the three small RNA classes, microRNAs and siRNAs are processed from double-stranded precursors into defined 21- to 23-mers by Dicer, an endoribonuclease with intrinsic ruler function. piRNAs—the 22-30 nt long guides for PIWI-clade Ago proteins that silence transposons in animal gonads—are generated Dicer-independently from single-stranded precursors2,3. piRNA 5' ends are defined either by Zucchini, a mitochondria-anchored endonuclease4,5, or by piRNA-guided target cleavage6,7. Formation of piRNA 3' ends is poorly understood. Here, we find that two genetically and mechanistically distinct pathways generate piRNA 3' ends in Drosophila. The initiating nucleases are either Zucchini or the PIWI-clade proteins Aubergine (Aub)/Ago3. While Zucchini-mediated cleavages directly define mature piRNA 3' ends8,9, Aub/Ago3-mediated cleavages liberate pre-piRNAs that require extensive resection by the 3'-to-5' exoribonuclease Nibbler/Mut-710–13. The relative activity of these two pathways dictates the extent to which piRNAs are fueled into cytoplasmic or nuclear PIWI-clade proteins and thereby sets the balance between post-transcriptional and transcriptional silencing. Strikingly, loss of both Zucchini and Nibbler reveals a minimal, Argonaute-driven small RNA biogenesis pathway where piRNA 5' and 3' ends are directly produced by closely spaced Aub/Ago3-mediated cleavage events. Our data establish a coherent blueprint for piRNA biogenesis, and set the stage for the mechanistic dissection of the processes that govern piRNA 3' end formation. PMID:27851737

Pathways to Occupational Attainment among Poor Youth of Color: The Role of Sociopolitical Development

ERIC Educational Resources Information Center

Diemer, Matthew A.

2009-01-01

The formation of future occupational expectations is a critical career-development task for adolescents that has a significant impact on adult occupational attainment. However, sociopolitical barriers constrain the occupational expectations and attainment of poor youth of color. Extant research has suggested that sociopolitical development, the…

Room To Grow.

ERIC Educational Resources Information Center

Rake, Melissa

1999-01-01

A West Virginia study that found that smaller poor schools did better academically than larger poor schools is being replicated in four states. Discusses the survival and successes of one tiny Ohio school, the role of small schools' social capital in compensating for poverty, a small-school researcher's recommended school sizes, and changing…

[Competencies and Role Experiences of Peer Support - A Participatory Research Report].

PubMed

Heumann, Kolja; Schmid, Christine; Wilfer, Antje; Bolkan, Suzan; Mahlke, Candelaria; von Peter, Sebastian

2018-05-25

This study explores the peer support providers' competencies and role experiences. A multiple coding approach has been used to collaboratively analyze and discuss ethnographic material. Compared to other professionals, peer support provider engage with patients in a more open and less classificatory way. Their role is often unclear and defined by both more flexibility and dependencies. It is important to clearly define the competencies and roles of peer support providers and balance them with the expectations of the other professionals. © Georg Thieme Verlag KG Stuttgart · New York.

The Longitudinal Association Between Poor Sleep Quality and Cyberbullying, Mediated by Anger.

PubMed

Erreygers, Sara; Vandebosch, Heidi; Vranjes, Ivana; Baillien, Elfi; De Witte, Hans

2018-01-09

Adolescents tend to go to bed later and sleep less as they grow older, although their need for sleep stays the same throughout adolescence. Poor sleep has negative consequences on personal and interpersonal functioning, including increased aggressive tendencies. With adolescents' social life increasingly including interactions via digital media, these interactions may also become more aggressive when adolescents' sleep problems increase. One of the ways in which online aggression may be enacted is through cyberbullying. Although previous research has examined the role of sleep disruptions in offline bullying, the role of sleep in cyberbullying has not yet been addressed. Therefore, this study examines the longitudinal effect of poor sleep quality on later cyberbullying behavior. Thirteen- to fourteen-year-old adolescents completed self-report measures on sleep quality, anger, cyberbullying perpetration, and frequency of digital media use. Because one of the pathways through which sleep is proposed to be linked to aggression is an affective pathway, namely via angry affect, a mediation model of poor sleep quality predicting cyberbullying via feelings of anger was tested. Results from structural equation modeling and a bootstrap test indicated that poor sleep quality was indeed indirectly associated with later cyberbullying behavior through heightened feelings of anger, even when taking the effects of the use of digital media and previous cyberbullying behavior into account. This finding provides support for the proposed affective pathway linking sleep problems to aggression. As sleep problems and anger seem to play a predicting role in cyberbullying behavior, suggestions for cyberbullying intervention and prevention strategies are formulated.

Caregiver Strain among Black and White Daughter Caregivers: A Role Theory Perspective.

ERIC Educational Resources Information Center

Mui, Ada C.

1992-01-01

Examined caregiving strain of 117 African-American and 464 white daughter caregivers. African Americans reported less role strain. Conflict between caregiving duties and caregivers' personal/social life was predictor for both groups. Unique predictors were poor perceived health, unavailability of respite support, and lower caregiving role demand…

Sarcopenia Screened by the SARC-F Questionnaire and Physical Performances of Elderly Women: A Cross-Sectional Study.

PubMed

Rolland, Yves; Dupuy, Charlotte; Abellan Van Kan, Gabor; Cesari, Matteo; Vellas, Bruno; Faruch, Marie; Dray, Cedric; de Souto Barreto, Philipe

2017-10-01

Screening for sarcopenia in daily practice can be challenging. Our objective was to explore whether the SARC-F questionnaire is a valid screening tool for sarcopenia (defined by the Foundation for the National Institutes of Health [FNIH] criteria). Moreover, we evaluated the physical performance of older women according to the SARC-F questionnaire. Cross-sectional study. Data from the Toulouse and Lyon EPIDémiologie de l'OStéoporose study (EPIDOS) on 3025 women living in the community (mean age: 80.5 ± 3.9 years), without a previous history of hip fracture, were assessed. The SARC-F self-report questionnaire score ranges from 0 to 10: a score ≥4 defines sarcopenia. The FNIH criteria uses handgrip strength (GS) and appendicular lean mass (ALM; assessed by DXA) divided by body mass index (BMI) to define sarcopenia. Outcome measures were the following performance-based tests: knee-extension strength, 6-m gait speed, and a repeated chair-stand test. The associations of sarcopenia with performance-based tests was examined using bootstrap multiple linear-regression models; adjusted R 2 determined the percentage variation for each outcome explained by the model. Prevalence of sarcopenia was 16.7% (n = 504) according to the SARC-F questionnaire and 1.8% (n = 49) using the FNIH criteria. Sensibility and specificity of the SARC-F to diagnose sarcopenia (defined by FNIH criteria) were 34% and 85%, respectively. Sarcopenic women defined by SARC-F had significantly lower physical performance than nonsarcopenic women. The SARC-F improved the ability to predict poor physical performance. The validity of the SARC-F questionnaire to screen for sarcopenia, when compared with the FNIH criteria, was limited. However, sarcopenia defined by the SARC-F questionnaire substantially improved the predictive value of clinical characteristics of patients to predict poor physical performance. Copyright © 2017 AMDA – The Society for Post-Acute and Long-Term Care Medicine. Published by Elsevier Inc. All rights reserved.

2-Way k-Means as a Model for Microbiome Samples.

PubMed

Jackson, Weston J; Agarwal, Ipsita; Pe'er, Itsik

2017-01-01

Motivation . Microbiome sequencing allows defining clusters of samples with shared composition. However, this paradigm poorly accounts for samples whose composition is a mixture of cluster-characterizing ones and which therefore lie in between them in the cluster space. This paper addresses unsupervised learning of 2-way clusters. It defines a mixture model that allows 2-way cluster assignment and describes a variant of generalized k -means for learning such a model. We demonstrate applicability to microbial 16S rDNA sequencing data from the Human Vaginal Microbiome Project.

2-Way k-Means as a Model for Microbiome Samples

PubMed Central

2017-01-01

Motivation. Microbiome sequencing allows defining clusters of samples with shared composition. However, this paradigm poorly accounts for samples whose composition is a mixture of cluster-characterizing ones and which therefore lie in between them in the cluster space. This paper addresses unsupervised learning of 2-way clusters. It defines a mixture model that allows 2-way cluster assignment and describes a variant of generalized k-means for learning such a model. We demonstrate applicability to microbial 16S rDNA sequencing data from the Human Vaginal Microbiome Project. PMID:29177026

Moving Beyond 2% Uncertainty: A New Framework for Quantifying Lidar Uncertainty

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

Newman, Jennifer F.; Clifton, Andrew

2017-03-08

Remote sensing of wind using lidar is revolutionizing wind energy. However, current generations of wind lidar are ascribed a climatic value of uncertainty, which is based on a poor description of lidar sensitivity to external conditions. In this presentation, we show how it is important to consider the complete lidar measurement process to define the measurement uncertainty, which in turn offers the ability to define a much more granular and dynamic measurement uncertainty. This approach is a progression from the 'white box' lidar uncertainty method.

A potential role for endogenous proteins as sacrificial sunscreens and antioxidants in human tissues.

PubMed

Hibbert, Sarah A; Watson, Rachel E B; Gibbs, Neil K; Costello, Patrick; Baldock, Clair; Weiss, Anthony S; Griffiths, Christopher E M; Sherratt, Michael J

2015-08-01

Excessive ultraviolet radiation (UVR) exposure of the skin is associated with adverse clinical outcomes. Although both exogenous sunscreens and endogenous tissue components (including melanins and tryptophan-derived compounds) reduce UVR penetration, the role of endogenous proteins in absorbing environmental UV wavelengths is poorly defined. Having previously demonstrated that proteins which are rich in UVR-absorbing amino acid residues are readily degraded by broadband UVB-radiation (containing UVA, UVB and UVC wavelengths) here we hypothesised that UV chromophore (Cys, Trp and Tyr) content can predict the susceptibility of structural proteins in skin and the eye to damage by physiologically relevant doses (up to 15.4 J/cm(2)) of solar UVR (95% UVA, 5% UVB). We show that: i) purified suspensions of UV-chromophore-rich fibronectin dimers, fibrillin microfibrils and β- and γ-lens crystallins undergo solar simulated radiation (SSR)-induced aggregation and/or decomposition and ii) exposure to identical doses of SSR has minimal effect on the size or ultrastructure of UV chromophore-poor tropoelastin, collagen I, collagen VI microfibrils and α-crystallin. If UV chromophore content is a factor in determining protein stability in vivo, we would expect that the tissue distribution of Cys, Trp and Tyr-rich proteins would correlate with regional UVR exposure. From bioinformatic analysis of 244 key structural proteins we identified several biochemically distinct, yet UV chromophore-rich, protein families. The majority of these putative UV-absorbing proteins (including the late cornified envelope proteins, keratin associated proteins, elastic fibre-associated components and β- and γ-crystallins) are localised and/or particularly abundant in tissues that are exposed to the highest doses of environmental UVR, specifically the stratum corneum, hair, papillary dermis and lens. We therefore propose that UV chromophore-rich proteins are localised in regions of high UVR exposure as a consequence of an evolutionary pressure to express sacrificial protein sunscreens which reduce UVR penetration and hence mitigate tissue damage. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Constraints faced by urban poor in managing diabetes care: patients' perspectives from South India.

PubMed

Bhojani, Upendra; Mishra, Arima; Amruthavalli, Subramani; Devadasan, Narayanan; Kolsteren, Patrick; De Henauw, Stefaan; Criel, Bart

2013-10-03

Four out of five adults with diabetes live in low- and middle-income countries (LMIC). India has the second highest number of diabetes patients in the world. Despite a huge burden, diabetes care remains suboptimal. While patients (and families) play an important role in managing chronic conditions, there is a dearth of studies in LMIC and virtually none in India capturing perspectives and experiences of patients in regard to diabetes care. The objective of this study was to better understand constraints faced by patients from urban slums in managing care for type 2 diabetes in India. We conducted in-depth interviews, using a phenomenological approach, with 16 type 2- diabetes patients from a poor urban neighbourhood in South India. These patients were selected with the help of four community health workers (CHWs) and were interviewed by two trained researchers exploring patients' experiences of living with and seeking care for diabetes. The sampling followed the principle of saturation. Data were initially coded using the NVivo software. Emerging themes were periodically discussed among the researchers and were refined over time through an iterative process using a mind-mapping tool. Despite an abundance of healthcare facilities in the vicinity, diabetes patients faced several constraints in accessing healthcare such as financial hardship, negative attitudes and inadequate communication by healthcare providers and a fragmented healthcare service system offering inadequate care. Strongly defined gender-based family roles disadvantaged women by restricting their mobility and autonomy to access healthcare. The prevailing nuclear family structure and inter-generational conflicts limited support and care for elderly adults. There is a need to strengthen primary care services with a special focus on improving the availability and integration of health services for diabetes at the community level, enhancing patient centredness and continuity in delivery of care. Our findings also point to the need to provide social services in conjunction with health services aiming at improving status of women and elderly in families and society.

From contact angle titration to chemical force microscopy: a new route to assess the pH-dependent character of the stratum corneum.

PubMed

Wagner, Matthieu; Mavon, Alain; Haidara, Hamidou; Vallat, Marie-France; Duplan, Hélène; Roucoules, Vincent

2012-02-01

Despite of its complex multicomponent organization and its compact architecture, the Stratum corneum (SC) is not completely impermeable to substances directly applied on the skin surface. A huge number of works have been dedicated to the understanding of the mechanisms involved in substance permeation by exploring deeper layers than the SC itself. Surprisingly, there is a poor interest in studies relating to interactions which may occur in the near-surface region (i.e. approximately 1 nm depth) of the SC. In this work, equilibrium proton-transfer reactions have been used as probes to define in a fundamental point of view the nature of the SC interactions with its environment. Such titration curves are investigated on 'in vitro' SC (isolated SC from abdominal skin tissue) and on 'in vivo' volar forearm (a sebum poor area). The results are discussed in term of work of adhesion and surface pKa values. Because SC can 'reconstruct' under heating, influence of the temperature on titration curves is investigated and the role of the different components is discussed. Different sigmoidal transitions were observed. Two common pKa values (pKa(1) = 4 and pKa(2) = 11.5) were clearly identified in both cases and associated to an acid-base character. By playing with the temperature of 'in vitro' SC, the 'accessibility' of polar functions was increased, thus refining the results by revealing an amphoteric character with an acid-to-base transition at pH 3.5 and two acid transitions at pH = 6.5 and pH = 11.5. Adhesion forces between an Atomic Force Microscopy (AFM) tip and a single isolated corneocyte through buffered liquid media were also investigated to better understand the role of the individual corneocytes. © 2011 The Authors. ICS © 2011 Society of Cosmetic Scientists and the Société Française de Cosmétologie.

MyD88 Mutation in Elderly Predicts Poor Prognosis in Primary Central Nervous System Lymphoma: Multi-Institutional Analysis.

PubMed

Takano, Shingo; Hattori, Keiichiro; Ishikawa, Eiichi; Narita, Yoshitaka; Iwadate, Yasuo; Yamaguchi, Fumio; Nagane, Motoo; Akimoto, Jiro; Oka, Hidehiro; Tanaka, Satoshi; Sakata, Mamiko; Matsuda, Masahide; Yamamoto, Tetsuya; Chiba, Shigeru; Matsumura, Akira

2018-04-01

Recent genetic analysis of primary central nervous system lymphoma (PCNSL) showed that the MyD88 L265P mutation, which is related to NF-κB signaling, was a genetic hallmark for PCNSL; thus it could serve as a genetic marker for diagnosis and a potential target for molecular therapy. However, the role of the MyD88 mutation in PCNSL has not been defined. In this study, we investigated the role of the MyD88 mutation and clinical features of PCNSL-treated patients at several institutions to determine its significance as a prognostic factor. Forty-one PCNSL (diffuse large B-cell type) patients from 8 institutions were included in this study. Their median age was 68 years; median follow-up was 26.7 months; median overall survival was 26.7 months; and their 1-year, 3-year, and 5-year survival rates were 75.6%, 58.5%, and 43.9%, respectively. Deoxyribonucleic acid was extracted from frozen tissue, and the MyD88 L265P mutation was evaluated by polymerase chain reaction and direct sequencing. The MyD88 L265P mutation was found in 61.0% (25/41) of cases. Kaplan-Meier analysis revealed that neither MyD88 L265P mutation nor age >65 years alone significantly predicted overall survival relative to MyD88 wild type and age <65. The MyD88 L265P mutation was predominantly present in patients aged >65 years. Among age >65 patients, the MyD88 L265P mutation portended a worse overall survival compared with the MyD88 wild type (11.5 vs. 56.2 months P < 0.04). The MyD88 L265P mutation predicted a poor prognosis in elderly PCNSL patients. A new tailor-made treatment strategy might be needed for these patients. Copyright © 2017. Published by Elsevier Inc.

A potential role for endogenous proteins as sacrificial sunscreens and antioxidants in human tissues

PubMed Central

Hibbert, Sarah A.; Watson, Rachel E.B.; Gibbs, Neil K.; Costello, Patrick; Baldock, Clair; Weiss, Anthony S.; Griffiths, Christopher E.M.; Sherratt, Michael J.

2015-01-01

Excessive ultraviolet radiation (UVR) exposure of the skin is associated with adverse clinical outcomes. Although both exogenous sunscreens and endogenous tissue components (including melanins and tryptophan-derived compounds) reduce UVR penetration, the role of endogenous proteins in absorbing environmental UV wavelengths is poorly defined. Having previously demonstrated that proteins which are rich in UVR-absorbing amino acid residues are readily degraded by broadband UVB-radiation (containing UVA, UVB and UVC wavelengths) here we hypothesised that UV chromophore (Cys, Trp and Tyr) content can predict the susceptibility of structural proteins in skin and the eye to damage by physiologically relevant doses (up to 15.4 J/cm2) of solar UVR (95% UVA, 5% UVB). We show that: i) purified suspensions of UV-chromophore-rich fibronectin dimers, fibrillin microfibrils and β- and γ-lens crystallins undergo solar simulated radiation (SSR)-induced aggregation and/or decomposition and ii) exposure to identical doses of SSR has minimal effect on the size or ultrastructure of UV chromophore-poor tropoelastin, collagen I, collagen VI microfibrils and α-crystallin. If UV chromophore content is a factor in determining protein stability in vivo, we would expect that the tissue distribution of Cys, Trp and Tyr-rich proteins would correlate with regional UVR exposure. From bioinformatic analysis of 244 key structural proteins we identified several biochemically distinct, yet UV chromophore-rich, protein families. The majority of these putative UV-absorbing proteins (including the late cornified envelope proteins, keratin associated proteins, elastic fibre-associated components and β- and γ-crystallins) are localised and/or particularly abundant in tissues that are exposed to the highest doses of environmental UVR, specifically the stratum corneum, hair, papillary dermis and lens. We therefore propose that UV chromophore-rich proteins are localised in regions of high UVR exposure as a consequence of an evolutionary pressure to express sacrificial protein sunscreens which reduce UVR penetration and hence mitigate tissue damage. PMID:25911998

Leading Charters: How Charter School Administrators Define Their Roles and Their Ability to Lead

ERIC Educational Resources Information Center

Carpenter, Dick Michael, II; Peak, Charity

2013-01-01

Charter schools have been studied from numerous perspectives. One topic that remains under-researched, however, is charter school leadership. Therefore, we examine how charter administrators define their leadership roles and their ability to lead. Results indicate that charter principals see three primary functions in their leadership--building…

Torn in Two: An Examiniation of Elementary School Counselors' Perceptions on Self-Efficacy

ERIC Educational Resources Information Center

Sesto, Casper

2013-01-01

The American School Counselor Association (ASCA; The ASCA National Model: A Framework for School Counseling Programs, 2005) developed the ASCA National Model to define the prescribed roles and functions of the professional school counselor. Although the national model initially defines school counselors' roles, counselors find it difficult to…

[Formula: see text]Executive functioning and its relation to ASD and ADHD symptomatology in 22q11.2 deletion syndrome.

PubMed

de Sonneville, Leo M J; Hidding, Elske; van Engeland, Herman; Vorstman, Jacob A S; Sijmens-Morcus, Monique E J; Swaab, Hanna

2018-01-01

Children with 22q11.2 deletion syndrome (22q11DS; velo-cardio-facial-syndrome) are at risk for the developmental disorders, attention deficit hyperactivity disorder (ADHD) and autism spectrum disorder (ASD). In this study, the relation between executive functioning (EF) and the severity of ADHD and ASD symptoms is examined, since EF is known to be important in relation to emotional and behavioral problems. The participants consist of 58 children (38 females) with a mean age of 13.5 years (SD 2.6). Standardized assessment was used to evaluate the severity of ASD and ADHD symptomatology. The major aspects of EF, i.e., cognitive flexibility, inhibition, sustained attention, distractibility, working memory and reaction speed, were evaluated. The profile of EF in 22q11DS was found to be characterized by weaker performance compared to the norms on all subdomains of EF. Poor cognitive flexibility and inhibition, as well as high distractibility, were found to be related to more severe ASD symptoms, while poor quality of sustained attention and high distractibility were found to be related to more severe ADHD symptoms. It is concluded that children with 22q11DS experience impairments in EF, and that the degree of impairment on specific EF subdomains is related to the severity of ASD and/or ADHD symptomatology. These results may help in defining the mediating role of neurocognitive dysfunctions in the development of social and behavioral problems in 22q11DS.