Sample records for instruments regulating pathological

  1. Gut microbiota and obesity.

    PubMed

    Scarpellini, Emidio; Campanale, Mariachiara; Leone, Diana; Purchiaroni, Flaminia; Vitale, Giovanna; Lauritano, Ernesto Cristiano; Gasbarrini, Antonio

    2010-10-01

    Intestinal epithelium, mucosal immune system, and bacterial flora represent a morpho-functional system on dynamic balance responsible for the intestinal metabolic and trophic functions, and the regulation of mucosal and systemic host's immunity. Obesity is a pathological condition affecting a growing number of people especially in the Western countries resulting from the failure of the organism's energetic balance based on the perfect equality of income, waste, and storage. Recent evidences explain the mechanisms for the microbial regulation of the host's metabolism both in health and disease. In particular, animal studies have explained how quali-/quantitative changes in microflora composition are able to affect the absorption of the nutrients and the energy distribution. Antibiotics, prebiotics, probiotics, and symbiotics are the instruments utilized in the current clinical practice to modulate the intestinal bacterial flora in man both in health and pathologic conditions with promising preliminary results on prevention and therapy of obesity and related metabolic diseases.

  2. Pathological video-gaming among Singaporean youth.

    PubMed

    Choo, Hyekyung; Gentile, Douglas A; Sim, Timothy; Li, Dongdong; Khoo, Angeline; Liau, Albert K

    2010-11-01

    Increase in internet use and video-gaming contributes to public concern on pathological or obsessive play of video games among children and adolescents worldwide. Nevertheless, little is known about the prevalence of pathological symptoms in video-gaming among Singaporean youth and the psychometric properties of instruments measuring pathological symptoms in video-gaming. A total of 2998 children and adolescents from 6 primary and 6 secondary schools in Singapore responded to a comprehensive survey questionnaire on sociodemographic characteristics, video-gaming habits, school performance, somatic symptoms, various psychological traits, social functioning and pathological symptoms of video-gaming. After weighting, the survey data were analysed to determine the prevalence of pathological video-gaming among Singaporean youth and gender differences in the prevalence. The construct validity of instrument used to measure pathological symptoms of video-gaming was tested. Of all the study participants, 8.7% were classified as pathological players with more boys reporting more pathological symptoms than girls. All variables, including impulse control problem, social competence, hostility, academic performance, and damages to social functioning, tested for construct validity, were significantly associated with pathological status, providing good evidence for the construct validity of the instrument used. The prevalence rate of pathological video-gaming among Singaporean youth is comparable with that from other countries studied thus far, and gender differences are also consistent with the findings of prior research. The positive evidence of construct validity supports the potential use of the instrument for future research and clinical screening on Singapore children and adolescents' pathological video-gaming.

  3. The development of antisocial behavior: what can we learn from functional neuroimaging studies?

    PubMed

    Crowe, S L; Blair, R J R

    2008-01-01

    The recent development of low-risk imaging technologies, such as functional magnetic resonance imaging (fMRI), have had a significant impact on the investigation of psychopathologies in children and adolescents. This review considers what we can infer from fMRI work regarding the development of conduct disorder (CD) and oppositional defiant disorder (ODD). We make two central assumptions that are grounded in the empirical literature. First, the diagnoses of CD and ODD identify individuals with heterogeneous pathologies; that is, different developmental pathologies can receive a CDD or ODD diagnosis. This is indicated by the comorbidities associated with CD/ODD, some of which appear to be mutually exclusive at the biological level (e.g., posttraumatic stress disorder [PTSD] and psychopathic tendencies). Second, two populations of antisocial individuals can be identified: those that show an increased risk for only reactive aggression and those that show an increased risk for both reactive and instrumental aggression. We review the fMRI data indicating that particular comorbidities of CD/ODD (i.e., mood and anxiety conditions such as childhood bipolar disorder and PTSD) are associated with either increased responsiveness of neural regions implicated in the basic response to threat (e.g., the amygdala) or decreased responsiveness in regions of frontal cortex (e.g., ventromedial frontal cortex) that are implicated in the regulation of the basic threat response. We suggest why such pathology would increase the risk for reactive aggression and, in turn, lead to the association with a CD/ODD diagnosis. We also review the literature on psychopathic tendencies, a condition where the individual is at significantly elevated risk for both reactive and instrumental aggression. We show that in individuals with psychopathic tendencies, the functioning of the amygdala in stimulus-reinforcement learning and of the ventromedial frontal cortex in the representation of reinforcement expectancies is impaired. We suggest why such pathology would increase the risk for reactive and instrumental aggression and thus also lead to the association with a CD/ODD diagnosis.

  4. Pathological Gambling and Associated Drug and Alcohol Abuse, Emotion Regulation, and Anxious-Depressive Symptomatology.

    PubMed

    Jauregui, Paula; Estévez, Ana; Urbiola, Irache

    2016-06-01

    Background and aims Pathological gambling is associated with comorbid disorders, such as anxiety, depression, and drug and alcohol abuse. Difficulties of emotion regulation may be one of the factors related to the presence of addictive disorders, along with comorbid symptomatology in pathological gamblers. Therefore, the aim of this study was to evaluate the difficulties of emotion regulation, drug and alcohol abuse, and anxious and depressive symptomatology in pathological gamblers, and the mediating role of difficulties of emotion regulation between anxiety and pathological gambling. Methods The study sample included 167 male pathological gamblers (mean age = 39.29 years) and 107 non-gamblers (mean age = 33.43 years). Pathological gambling (SOGS), difficulties of emotion regulation (DERS), drug and alcohol abuse (MUTICAGE CAD-4), and anxious and depressive symptomatology (SA-45) were measured. Student's t, Pearson's r, stepwise multiple linear regression and multiple mediation analyses were conducted. The study was approved by an Investigational Review Board. Results Relative to non-gamblers, pathological gamblers exhibited greater difficulties of emotion regulation, as well as more anxiety, depression, and drug abuse. Moreover, pathological gambling correlated with emotion regulation difficulties, anxiety, depression, and drug abuse. Besides, emotion regulation difficulties correlated with and predicted pathological gambling, drug and alcohol abuse, and anxious and depressive symptomatology. Finally, emotion regulation difficulties mediated the relationship between anxiety and pathological gambling controlling the effect of age, both when controlling and not controlling for the effect of other abuses. Discussion and conclusions These results suggest that difficulties of emotion regulation may provide new keys to understanding and treating pathological gambling and comorbid disorders.

  5. Pathological Gambling and Associated Drug and Alcohol Abuse, Emotion Regulation, and Anxious-Depressive Symptomatology

    PubMed Central

    Jauregui, Paula; Estévez, Ana; Urbiola, Irache

    2016-01-01

    Background and aims Pathological gambling is associated with comorbid disorders, such as anxiety, depression, and drug and alcohol abuse. Difficulties of emotion regulation may be one of the factors related to the presence of addictive disorders, along with comorbid symptomatology in pathological gamblers. Therefore, the aim of this study was to evaluate the difficulties of emotion regulation, drug and alcohol abuse, and anxious and depressive symptomatology in pathological gamblers, and the mediating role of difficulties of emotion regulation between anxiety and pathological gambling. Methods The study sample included 167 male pathological gamblers (mean age = 39.29 years) and 107 non-gamblers (mean age = 33.43 years). Pathological gambling (SOGS), difficulties of emotion regulation (DERS), drug and alcohol abuse (MUTICAGE CAD-4), and anxious and depressive symptomatology (SA-45) were measured. Student’s t, Pearson’s r, stepwise multiple linear regression and multiple mediation analyses were conducted. The study was approved by an Investigational Review Board. Results Relative to non-gamblers, pathological gamblers exhibited greater difficulties of emotion regulation, as well as more anxiety, depression, and drug abuse. Moreover, pathological gambling correlated with emotion regulation difficulties, anxiety, depression, and drug abuse. Besides, emotion regulation difficulties correlated with and predicted pathological gambling, drug and alcohol abuse, and anxious and depressive symptomatology. Finally, emotion regulation difficulties mediated the relationship between anxiety and pathological gambling controlling the effect of age, both when controlling and not controlling for the effect of other abuses. Discussion and conclusions These results suggest that difficulties of emotion regulation may provide new keys to understanding and treating pathological gambling and comorbid disorders. PMID:27348555

  6. Screening for Generalized Anxiety Disorder in inpatient psychosomatic rehabilitation: pathological worry and the impact of depressive symptoms

    PubMed Central

    Salzer, Simone; Stiller, Christian; Tacke-Pook, Achim; Jacobi, Claus; Leibing, Eric

    2009-01-01

    Objective: Pathological worry is considered to be a defining feature for Generalized Anxiety Disorder (GAD). The Penn State Worry Questionnaire (PSWQ) is an instrument for assessing pathological worry. Two earlier studies demonstrated the suitability of the PSWQ as screening instrument for GAD in outpatient and non-clinical samples. This study examined the suitability of the PSWQ as a screening instrument for GAD in a German inpatient sample (N=237). Furthermore, a comparison of patients with GAD and patients with depression and other anxiety disorders regarding pathological worry and depression was carried out in a sub-sample of N=118 patients. Method: Cut-off scores optimizing sensitivity, optimizing specificity and simultaneously optimizing both sensitivity and specificity were calculated for the PSWQ score by receiver operating characteristic analysis (ROC). Differences regarding pathological worry and depression measured by the PSWQ and the Beck Depression Inventory (BDI) across five diagnostic subgroups were examined by conducting one-way ANOVAs. The influence of depression on pathological worry was controlled by conducting an ANCOVA with BDI score as a covariate. Results: The ROC analysis showed an area under the curve of AUC=.67 (p=0.02) with only 54.4% of the patients correctly classified. Comparison of diagnostic subgroups showed that after controlling the influence of depression, differences referring to pathological worry between diagnostic subgroups no longer existed. Conclusions: Contrary to the earlier results we found that the use of the PSWQ as a screening instrument for GAD at least in a sample of psychotherapy inpatients is not meaningful. Instead of that, the PSWQ can be used to discriminate high from low worriers in clinical samples. Thus, the instrument can be useful in establishing e.g. symptom-oriented group interventions as they are established in behavioural-medicine inpatient settings. Furthermore, our findings stress the influence of (comorbid) depressive symptoms on the process of worrying. PMID:19742048

  7. Screening for Generalized Anxiety Disorder in inpatient psychosomatic rehabilitation: pathological worry and the impact of depressive symptoms.

    PubMed

    Salzer, Simone; Stiller, Christian; Tacke-Pook, Achim; Jacobi, Claus; Leibing, Eric

    2009-07-09

    Pathological worry is considered to be a defining feature for Generalized Anxiety Disorder (GAD). The Penn State Worry Questionnaire (PSWQ) is an instrument for assessing pathological worry. Two earlier studies demonstrated the suitability of the PSWQ as screening instrument for GAD in outpatient and non-clinical samples. This study examined the suitability of the PSWQ as a screening instrument for GAD in a German inpatient sample (N=237). Furthermore, a comparison of patients with GAD and patients with depression and other anxiety disorders regarding pathological worry and depression was carried out in a sub-sample of N=118 patients. Cut-off scores optimizing sensitivity, optimizing specificity and simultaneously optimizing both sensitivity and specificity were calculated for the PSWQ score by receiver operating characteristic analysis (ROC). Differences regarding pathological worry and depression measured by the PSWQ and the Beck Depression Inventory (BDI) across five diagnostic subgroups were examined by conducting one-way ANOVAs. The influence of depression on pathological worry was controlled by conducting an ANCOVA with BDI score as a covariate. The ROC analysis showed an area under the curve of AUC=.67 (p=0.02) with only 54.4% of the patients correctly classified. Comparison of diagnostic subgroups showed that after controlling the influence of depression, differences referring to pathological worry between diagnostic subgroups no longer existed. Contrary to the earlier results we found that the use of the PSWQ as a screening instrument for GAD at least in a sample of psychotherapy inpatients is not meaningful. Instead of that, the PSWQ can be used to discriminate high from low worriers in clinical samples. Thus, the instrument can be useful in establishing e.g. symptom-oriented group interventions as they are established in behavioural-medicine inpatient settings. Furthermore, our findings stress the influence of (comorbid) depressive symptoms on the process of worrying.

  8. Impulsivity, self-regulation,and pathological video gaming among youth: testing a mediation model.

    PubMed

    Liau, Albert K; Neo, Eng Chuan; Gentile, Douglas A; Choo, Hyekyung; Sim, Timothy; Li, Dongdong; Khoo, Angeline

    2015-03-01

    Given the potential negative mental health consequences of pathological video gaming, understanding its etiology may lead to useful treatment developments. The purpose of the study was to examine the influence of impulsive and regulatory processes on pathological video gaming. Study 1 involved 2154 students from 6 primary and 4 secondary schools in Singapore. Study 2 involved 191 students from 2 secondary schools. The results of study 1 and study 2 supported the hypothesis that self-regulation is a mediator between impulsivity and pathological video gaming. Specifically, higher levels of impulsivity was related to lower levels of self-regulation, which in turn was related to higher levels of pathological video gaming. The use of impulsivity and self-regulation in predicting pathological video gaming supports the dual-system model of incorporating both impulsive and reflective systems in the prediction of self-control outcomes. The study highlights the development of self-regulatory resources as a possible avenue for future prevention and treatment research. © 2011 APJPH.

  9. Toward a consensus definition of pathological video-gaming: a systematic review of psychometric assessment tools.

    PubMed

    King, Daniel L; Haagsma, Maria C; Delfabbro, Paul H; Gradisar, Michael; Griffiths, Mark D

    2013-04-01

    Pathological video-gaming, or its proposed DSM-V classification of "Internet Use Disorder", is of increasing interest to scholars and practitioners in allied health disciplines. This systematic review was designed to evaluate the standards in pathological video-gaming instrumentation, according to Cicchetti (1994) and Groth-Marnat's (2009) criteria and guidelines for sound psychometric assessment. A total of 63 quantitative studies, including eighteen instruments and representing 58,415 participants, were evaluated. Results indicated that reviewed instrumentation may be broadly characterized as inconsistent. Strengths of available measures include: (i) short length and ease of scoring, (ii) excellent internal consistency and convergent validity, and (iii) potentially adequate data for development of standardized norms for adolescent populations. However, key limitations included: (a) inconsistent coverage of core addiction indicators, (b) varying cut-off scores to indicate clinical status, (c) a lack of a temporal dimension, (d) untested or inconsistent dimensionality, and (e) inadequate data on predictive validity and inter-rater reliability. An emerging consensus suggests that pathological video-gaming is commonly defined by (1) withdrawal, (2) loss of control, and (3) conflict. It is concluded that a unified approach to assessment of pathological video-gaming is needed. A synthesis of extant research efforts by meta-analysis may be difficult in the context of several divergent approaches to assessment. Copyright © 2013 Elsevier Ltd. All rights reserved.

  10. Medical instrument based on a heat pipe for local cavity hypothermia

    NASA Astrophysics Data System (ADS)

    Vasil'Ev, L. L.; Zhuraviyov, A. S.; Molodkin, F. F.; Khrolenok, V. V.; Zhdanov, V. L.; Vasil'Ev, V. L.; Adamov, S. I.; Tyurin, A. A.

    1996-05-01

    The design and results of tests of an instrument based on a heat pipe for local cavity hypothermia are presented. The instrument is a part of a device for noninvasive nonmedical treatment of inflammatory diseases of the organs of the small pelvis, pathologies of alimentary canal, etc.

  11. Pathology economic model tool: a novel approach to workflow and budget cost analysis in an anatomic pathology laboratory.

    PubMed

    Muirhead, David; Aoun, Patricia; Powell, Michael; Juncker, Flemming; Mollerup, Jens

    2010-08-01

    The need for higher efficiency, maximum quality, and faster turnaround time is a continuous focus for anatomic pathology laboratories and drives changes in work scheduling, instrumentation, and management control systems. To determine the costs of generating routine, special, and immunohistochemical microscopic slides in a large, academic anatomic pathology laboratory using a top-down approach. The Pathology Economic Model Tool was used to analyze workflow processes at The Nebraska Medical Center's anatomic pathology laboratory. Data from the analysis were used to generate complete cost estimates, which included not only materials, consumables, and instrumentation but also specific labor and overhead components for each of the laboratory's subareas. The cost data generated by the Pathology Economic Model Tool were compared with the cost estimates generated using relative value units. Despite the use of automated systems for different processes, the workflow in the laboratory was found to be relatively labor intensive. The effect of labor and overhead on per-slide costs was significantly underestimated by traditional relative-value unit calculations when compared with the Pathology Economic Model Tool. Specific workflow defects with significant contributions to the cost per slide were identified. The cost of providing routine, special, and immunohistochemical slides may be significantly underestimated by traditional methods that rely on relative value units. Furthermore, a comprehensive analysis may identify specific workflow processes requiring improvement.

  12. Transgenic over-expression of YY1 induces pathologic cardiac hypertrophy in a sex-specific manner

    PubMed Central

    Stauffer, Brian L.; Dockstader, Karen; Russell, Gloria; Hijmans, Jamie; Walker, Lisa; Cecil, Mackenzie; Demos-Davies, Kimberly; Medway, Allen; McKinsey, Timothy A.; Sucharov, Carmen C.

    2015-01-01

    YY1 can activate or repress transcription of various genes. In cardiac myocytes in culture YY1 has been shown to regulate expression of several genes involved in myocyte pathology. YY1 can also acutely protect the heart against detrimental changes in gene expression. In this study we show that cardiac over-expression of YY1 induces pathologic cardiac hypertrophy in male mice, measured by changes in gene expression and lower ejection fraction/fractional shortening. In contrast, female animals are protected against pathologic gene expression changes and cardiac dysfunction. Furthermore, we show that YY1 regulates, in a sex-specific manner, the expression of mammalian enable (Mena), a factor that regulates cytoskeletal actin dynamics and whose expression is increased in several models of cardiac pathology, and that Mena expression in humans with heart failure is sex-dependent. Finally, we show that sex differences in YY1 expression are also observed in human heart failure. In summary, this is the first work to show that YY1 has a sex-specific effect in the regulation of cardiac pathology. PMID:25935483

  13. Eating Pathology, Emotion Regulation, and Emotional Overeating in Obese Adults with Binge Eating Disorder

    PubMed Central

    Gianini, Loren M.; White, Marney A.; Masheb, Robin M.

    2013-01-01

    Objective The purpose of the current study was to examine the relationship among emotional regulation, emotional overeating, and general eating pathology in a treatment seeking sample of adults with Binge Eating Disorder (BED). Method The sample was composed of 326 adults (248 women, 78 men) who were obese and met DSM-IV-TR criteria for BED. Prior to treatment, participants completed the Difficulties in Emotion Regulation Scale (DERS), Emotional Overeating Questionnaire (EOQ), Beck Depression Inventory (BDI), and Eating Disorder Examination-Questionnaire (EDE-Q) as part of a larger assessment battery. Results A series of hierarchical regression analyses indicated that difficulties with emotion regulation accounted for unique variance in both emotional overeating and general eating pathology above and beyond sex and negative affect. Discussion Emotion regulation may play a significant role in the maintenance of emotional overeating and eating pathology in obese adults with BED. PMID:23910772

  14. Eating pathology, emotion regulation, and emotional overeating in obese adults with Binge Eating Disorder.

    PubMed

    Gianini, Loren M; White, Marney A; Masheb, Robin M

    2013-08-01

    The purpose of the current study was to examine the relationship among emotional regulation, emotional overeating, and general eating pathology in a treatment seeking sample of adults with Binge Eating Disorder (BED). The sample was composed of 326 adults (248 women, 78 men) who were obese and met DSM-IV-TR criteria for BED. Prior to treatment, participants completed the Difficulties in Emotion Regulation Scale (DERS), Emotional Overeating Questionnaire (EOQ), Beck Depression Inventory (BDI), and Eating Disorder Examination-Questionnaire (EDE-Q) as part of a larger assessment battery. A series of hierarchical regression analyses indicated that difficulties with emotion regulation accounted for unique variance in both emotional overeating and general eating pathology above and beyond sex and negative affect. Emotion regulation may play a significant role in the maintenance of emotional overeating and eating pathology in obese adults with BED. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. Therapists' perspectives on optimal treatment for pathological narcissism.

    PubMed

    Kealy, David; Goodman, Geoff; Rasmussen, Brian; Weideman, Rene; Ogrodniczuk, John S

    2017-01-01

    This study used Q methodology to explore clinicians' perspectives regarding optimal psychotherapy process in the treatment of pathological narcissism, a syndrome of impaired self-regulation. Participants were 34 psychotherapists of various disciplines and theoretical orientations who reviewed 3 clinical vignettes portraying hypothetical cases of grandiose narcissism, vulnerable narcissism, and panic disorder without pathological narcissism. Participants then used the Psychotherapy Process Q set, a 100-item Q-sort instrument, to indicate their views regarding optimal therapy process for each hypothetical case. By-person principal components analysis with varimax rotation was conducted on all 102 Q-sorts, revealing 4 components representing clinicians' perspectives on ideal therapy processes for narcissistic and non-narcissistic patients. These perspectives were then analyzed regarding their relationship to established therapy models. The first component represented an introspective, relationally oriented therapy process and was strongly correlated with established psychodynamic treatments. The second component, most frequently endorsed for the panic disorder vignette, consisted of a cognitive and alliance-building approach that correlated strongly with expert-rated cognitive-behavioral therapy. The third and fourth components involved therapy processes focused on the challenging interpersonal behaviors associated with narcissistic vulnerability and grandiosity, respectively. The perspectives on therapy processes that emerged in this study reflect different points of emphasis in the treatment of pathological narcissism, and may serve as prototypes of therapist-generated approaches to patients suffering from this issue. The findings suggest several areas for further empirical inquiry regarding psychotherapy with this population. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  16. 21 CFR 864.3300 - Cytocentrifuge.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Cytocentrifuge. 864.3300 Section 864.3300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3300 Cytocentrifuge. (a...

  17. 21 CFR 864.3300 - Cytocentrifuge.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Cytocentrifuge. 864.3300 Section 864.3300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3300 Cytocentrifuge. (a...

  18. 21 CFR 864.3300 - Cytocentrifuge.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Cytocentrifuge. 864.3300 Section 864.3300 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3300 Cytocentrifuge. (a...

  19. 21 CFR 864.3010 - Tissue processing equipment.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Tissue processing equipment. 864.3010 Section 864.3010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3010...

  20. 21 CFR 864.3600 - Microscopes and accessories.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Microscopes and accessories. 864.3600 Section 864.3600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3600...

  1. 21 CFR 864.3600 - Microscopes and accessories.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Microscopes and accessories. 864.3600 Section 864.3600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3600...

  2. 21 CFR 864.3400 - Device for sealing microsections.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Device for sealing microsections. 864.3400 Section 864.3400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864...

  3. 21 CFR 864.3800 - Automated slide stainer.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Automated slide stainer. 864.3800 Section 864.3800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3800...

  4. 21 CFR 864.3875 - Automated tissue processor.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Automated tissue processor. 864.3875 Section 864.3875 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3875...

  5. 21 CFR 864.3875 - Automated tissue processor.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Automated tissue processor. 864.3875 Section 864.3875 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3875...

  6. 21 CFR 864.3010 - Tissue processing equipment.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Tissue processing equipment. 864.3010 Section 864.3010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3010...

  7. 21 CFR 864.3400 - Device for sealing microsections.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Device for sealing microsections. 864.3400 Section 864.3400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864...

  8. 21 CFR 864.3010 - Tissue processing equipment.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Tissue processing equipment. 864.3010 Section 864.3010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3010...

  9. 21 CFR 864.3875 - Automated tissue processor.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated tissue processor. 864.3875 Section 864.3875 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3875...

  10. 21 CFR 864.3010 - Tissue processing equipment.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Tissue processing equipment. 864.3010 Section 864.3010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3010...

  11. 21 CFR 864.3600 - Microscopes and accessories.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Microscopes and accessories. 864.3600 Section 864.3600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3600...

  12. 21 CFR 864.3400 - Device for sealing microsections.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Device for sealing microsections. 864.3400 Section 864.3400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864...

  13. 21 CFR 864.3875 - Automated tissue processor.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Automated tissue processor. 864.3875 Section 864.3875 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3875...

  14. 21 CFR 864.3800 - Automated slide stainer.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Automated slide stainer. 864.3800 Section 864.3800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3800...

  15. 21 CFR 864.3400 - Device for sealing microsections.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Device for sealing microsections. 864.3400 Section 864.3400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864...

  16. 21 CFR 864.3600 - Microscopes and accessories.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Microscopes and accessories. 864.3600 Section 864.3600 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3600...

  17. 21 CFR 864.3875 - Automated tissue processor.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Automated tissue processor. 864.3875 Section 864.3875 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3875...

  18. 21 CFR 864.3010 - Tissue processing equipment.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Tissue processing equipment. 864.3010 Section 864.3010 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3010...

  19. 21 CFR 864.3800 - Automated slide stainer.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Automated slide stainer. 864.3800 Section 864.3800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3800...

  20. 21 CFR 864.3400 - Device for sealing microsections.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Device for sealing microsections. 864.3400 Section 864.3400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864...

  1. 21 CFR 864.3800 - Automated slide stainer.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Automated slide stainer. 864.3800 Section 864.3800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3800...

  2. 21 CFR 864.3800 - Automated slide stainer.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Automated slide stainer. 864.3800 Section 864.3800 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864.3800...

  3. Structure-mechanism-based engineering of chemical regulators targeting distinct pathological factors in Alzheimer's disease

    NASA Astrophysics Data System (ADS)

    Beck, Michael W.; Derrick, Jeffrey S.; Kerr, Richard A.; Oh, Shin Bi; Cho, Woo Jong; Lee, Shin Jung C.; Ji, Yonghwan; Han, Jiyeon; Tehrani, Zahra Aliakbar; Suh, Nayoung; Kim, Sujeong; Larsen, Scott D.; Kim, Kwang S.; Lee, Joo-Yong; Ruotolo, Brandon T.; Lim, Mi Hee

    2016-10-01

    The absence of effective therapeutics against Alzheimer's disease (AD) is a result of the limited understanding of its multifaceted aetiology. Because of the lack of chemical tools to identify pathological factors, investigations into AD pathogenesis have also been insubstantial. Here we report chemical regulators that demonstrate distinct specificity towards targets linked to AD pathology, including metals, amyloid-β (Aβ), metal-Aβ, reactive oxygen species, and free organic radicals. We obtained these chemical regulators through a rational structure-mechanism-based design strategy. We performed structural variations of small molecules for fine-tuning their electronic properties, such as ionization potentials and mechanistic pathways for reactivity towards different targets. We established in vitro and/or in vivo efficacies of the regulators for modulating their targets' reactivities, ameliorating toxicity, reducing amyloid pathology, and improving cognitive deficits. Our chemical tools show promise for deciphering AD pathogenesis and discovering effective drugs.

  4. Structure-mechanism-based engineering of chemical regulators targeting distinct pathological factors in Alzheimer's disease.

    PubMed

    Beck, Michael W; Derrick, Jeffrey S; Kerr, Richard A; Oh, Shin Bi; Cho, Woo Jong; Lee, Shin Jung C; Ji, Yonghwan; Han, Jiyeon; Tehrani, Zahra Aliakbar; Suh, Nayoung; Kim, Sujeong; Larsen, Scott D; Kim, Kwang S; Lee, Joo-Yong; Ruotolo, Brandon T; Lim, Mi Hee

    2016-10-13

    The absence of effective therapeutics against Alzheimer's disease (AD) is a result of the limited understanding of its multifaceted aetiology. Because of the lack of chemical tools to identify pathological factors, investigations into AD pathogenesis have also been insubstantial. Here we report chemical regulators that demonstrate distinct specificity towards targets linked to AD pathology, including metals, amyloid-β (Aβ), metal-Aβ, reactive oxygen species, and free organic radicals. We obtained these chemical regulators through a rational structure-mechanism-based design strategy. We performed structural variations of small molecules for fine-tuning their electronic properties, such as ionization potentials and mechanistic pathways for reactivity towards different targets. We established in vitro and/or in vivo efficacies of the regulators for modulating their targets' reactivities, ameliorating toxicity, reducing amyloid pathology, and improving cognitive deficits. Our chemical tools show promise for deciphering AD pathogenesis and discovering effective drugs.

  5. [Development and validation of an inventory of ego functions and self regulation (Hannover Self-Regulation Inventory, HSRI)].

    PubMed

    Jäger, B; Schmid-Ott, G; Ernst, G; Dölle-Lange, E; Sack, M

    2012-06-01

    The aim of this study was to construct and validate a short self-rating questionnaire for the assessment of ego functions and ability of self regulation. An item pool of 120 items covering 6 postulated dimensions was reduced by two steps in independent samples (n = 136 + 470) via factor and item analyses to the final version consisting of 35 items. The 5 resulting questionnaire scales "interpersonal disturbances", "frustration tolerance and impulse control", "identity disturbances", "affect differentiation and affect tolerance" and "self-esteem" were well interpretable and showed in confirmatory factor analysis the best fit to the data (CHI²/df = 3.48; RMSEA = 0.73). Total scores were found to differentiate well between diagnostic groups of patients with more or less ego pathology (FANOVA = 9.8; df = 11; p < 0.001), thus proving good concurrent validity. Reliability was shown by testing internal consistency and test-retest correlations. The "Hannover self-regulation questionnaire" (HSRQ) evidently is an appropriate and reliable screening instrument in order to assess ego functions and capacities of self regulation in an economic and user-friendly means. The scale structure allows differentiated diagnostics of weak vs. stable ego functions and may be used for detailed therapy planning. © Georg Thieme Verlag KG Stuttgart · New York.

  6. 21 CFR 864.3250 - Specimen transport and storage container.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Specimen transport and storage container. 864.3250 Section 864.3250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864...

  7. 21 CFR 864.3250 - Specimen transport and storage container.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Specimen transport and storage container. 864.3250 Section 864.3250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864...

  8. 21 CFR 864.3250 - Specimen transport and storage container.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Specimen transport and storage container. 864.3250 Section 864.3250 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Pathology Instrumentation and Accessories § 864...

  9. 21 CFR 864.5400 - Coagulation instrument.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Coagulation instrument. 864.5400 Section 864.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices § 864...

  10. 21 CFR 864.5400 - Coagulation instrument.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Coagulation instrument. 864.5400 Section 864.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices § 864...

  11. 21 CFR 864.5400 - Coagulation instrument.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Coagulation instrument. 864.5400 Section 864.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices § 864...

  12. 21 CFR 864.5400 - Coagulation instrument.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Coagulation instrument. 864.5400 Section 864.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices § 864...

  13. 21 CFR 864.5400 - Coagulation instrument.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Coagulation instrument. 864.5400 Section 864.5400 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES HEMATOLOGY AND PATHOLOGY DEVICES Automated and Semi-Automated Hematology Devices § 864...

  14. Mechanisms of physiological and pathological cardiac hypertrophy.

    PubMed

    Nakamura, Michinari; Sadoshima, Junichi

    2018-04-19

    Cardiomyocytes exit the cell cycle and become terminally differentiated soon after birth. Therefore, in the adult heart, instead of an increase in cardiomyocyte number, individual cardiomyocytes increase in size, and the heart develops hypertrophy to reduce ventricular wall stress and maintain function and efficiency in response to an increased workload. There are two types of hypertrophy: physiological and pathological. Hypertrophy initially develops as an adaptive response to physiological and pathological stimuli, but pathological hypertrophy generally progresses to heart failure. Each form of hypertrophy is regulated by distinct cellular signalling pathways. In the past decade, a growing number of studies have suggested that previously unrecognized mechanisms, including cellular metabolism, proliferation, non-coding RNAs, immune responses, translational regulation, and epigenetic modifications, positively or negatively regulate cardiac hypertrophy. In this Review, we summarize the underlying molecular mechanisms of physiological and pathological hypertrophy, with a particular emphasis on the role of metabolic remodelling in both forms of cardiac hypertrophy, and we discuss how the current knowledge on cardiac hypertrophy can be applied to develop novel therapeutic strategies to prevent or reverse pathological hypertrophy.

  15. FoxO1 transcriptional activities in VEGF expression and beyond: a key regulator in functional angiogenesis?

    PubMed

    Ren, Bin

    2018-04-24

    FoxO1 has emerged as an important regulator of angiogenesis. Recent work published in this Journal shows that FoxO1 regulates VEGF expression in keratinocytes and is required for angiogenesis in wound healing. Since FoxO1 also regulates CD36 transcription, and endothelial cell differentiation and vascular maturation, this transcription factor may be essential for the formation of functional vascular networks via coupling the regulation of CD36 in vascular endothelial cells under physiological and pathological conditions. Although many outstanding questions remain to be answered, the mechanisms by which FoxO1 regulates VEGF in keratinocytes provide insight into the development of functional angiogenesis and further our understanding of vascular biology. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  16. Disruptive Influences on Research in Academic Pathology Departments: Proposed Changes to the Common Rule Governing Informed Consent for Research Use of Biospecimens and to Rules Governing Return of Research Results.

    PubMed

    Sobel, Mark E; Dreyfus, Jennifer C

    2017-01-01

    Academic pathology departments will be dramatically affected by proposed United States federal government regulatory initiatives. Pathology research will be substantially altered if proposed changes to the Common Rule (Code of Federal Regulations: Protection of Human Subjects title 45 CFR 46) and regulations governing the return of individual research results are approved and finalized, even more so now that the Precision Medicine initiative has been launched. Together, these changes are disruptive influences on academic pathology research as we know it, straining limited resources and compromising advances in diagnostic and academic pathology. Academic research pathologists will be challenged over the coming years and must demonstrate leadership to ensure the continued availability of and the ethical use of research pathology specimens. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  17. 76 FR 39234 - Federal Acquisition Regulation; Unique Procurement Instrument Identifier

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-07-05

    ...-AL70 Federal Acquisition Regulation; Unique Procurement Instrument Identifier AGENCIES: Department of... Acquisition Regulation (FAR) to standardize use of unique Procurement Instrument Identifiers (PIID) throughout... Acquisition Council and the Defense Acquisition Regulations Council (the Councils) reviewed the public...

  18. A Survey of Speech and Language Pathology Services for Down's Syndrome: State of the Art.

    ERIC Educational Resources Information Center

    Kumin, Libby

    1986-01-01

    This article summarizes current trends in speech and language pathology services to individuals with Down's syndrome. Speech and language pathologists (N=112) responded to a survey identifying widely used assessment instruments, therapy materials, sources of information, and needs in relation to services at five age levels. (Author/DB)

  19. Level of Agreement between Self and Spouse in the Assessment of Personality Pathology

    ERIC Educational Resources Information Center

    South, Susan C.; Oltmanns, Thomas F.; Johnson, Jarrod; Turkheimer, Eric

    2011-01-01

    Informant reports can provide important information regarding the presence of pathological personality traits, and they can serve as useful supplements to self-report instruments. Ratings from a spouse may be a particularly valuable source of personality assessment because spouses are very well acquainted with the target person, have typically…

  20. Compact, Automated, Frequency-Agile Microspectrofluorimeter

    NASA Technical Reports Server (NTRS)

    Fernandez, Salvador M.; Guignon, Ernest F.

    1995-01-01

    Compact, reliable, rugged, automated cell-culture and frequency-agile microspectrofluorimetric apparatus developed to perform experiments involving photometric imaging observations of single live cells. In original application, apparatus operates mostly unattended aboard spacecraft; potential terrestrial applications include automated or semiautomated diagnosis of pathological tissues in clinical laboratories, biomedical instrumentation, monitoring of biological process streams, and portable instrumentation for testing biological conditions in various environments. Offers obvious advantages over present laboratory instrumentation.

  1. Endoplasmic Reticulum Stress in Arterial Smooth Muscle Cells: A Novel Regulator of Vascular Disease

    PubMed Central

    Furmanik, Malgorzata; Shanahan, Catherine M.

    2017-01-01

    Cardiovascular disease continues to be the leading cause of death in industrialised societies. The idea that the arterial smooth muscle cell (ASMC) plays a key role in regulating many vascular pathologies has been gaining importance, as has the realisation that not enough is known about the pathological cellular mechanisms regulating ASMC function in vascular remodelling. In the past decade endoplasmic reticulum (ER) stress and the unfolded protein response (UPR) have been recognised as a stress response underlying many physiological and pathological processes in various vascular cell types. Here we summarise what is known about how ER stress signalling regulates phenotypic switching, trans/dedifferentiation and apoptosis of ASMCs and contributes to atherosclerosis, hypertension, aneurysms and vascular calcification.

  2. Posterior Multilevel Instrumentation of the Lower Cervical Spine: Is Bridging the Cervicothoracic Junction Necessary?

    PubMed

    Osterhoff, Georg; Ryang, Yu-Mi; von Oelhafen, Judith; Meyer, Bernhard; Ringel, Florian

    2017-07-01

    Multisegmental cervical instrumentations ending at the cervicothoracic junction may lead to significant adjacent segment degeneration. The purpose of this study was to compare the extent of sequential pathologies in the lower adjacent segment between patient groups with a primarily cervical instrumentation ending at C7 versus an instrumentation including the cervicothoracic junction ending at T1 or T2. A retrospective analysis of 98 consecutive patients with multisegmental posterior cervical fusion surgery ending either at C7 or at T1 or T2 was performed. Radiographic parameters of degeneration at the adjacent segment below the instrumentation were determined postoperatively and at follow-up (FU), and the need for secondary interventions was documented. A total of 74 patients had a FU of at least 6 months (C7: n = 58, age 63 ± 11 years, FU 36 ± 26 months; T1/T2: n = 16, age 65 ± 13 years, FU 37 ± 21 months). There were no significant differences between the C7 and T1/T2 groups with regard to the change in kyphosis angle (P = 0.162), disc height (P = 0.204), or disc degeneration according to the Mimura grading system (P = 0.718). Secondary interventions due to adjacent segmental pathology or implant failure were necessary in 18 of 58 (31%) of the C7 cases and in 1 of 16 (6.3%) of the T1/T2 cases (P = 0.038). Patients with multisegmental posterior cervical fusions ending at C7 showed a greater rate of clinically symptomatic pathologies at the adjacent level below the instrumentation. On the basis of our data and with its limitations in mind, one may consider to bridge the cervicothoracic junction and to end the instrumentation at T1 or T2 in those cases. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Insulin regulates Presenilin 1 localization via PI3K/Akt signaling.

    PubMed

    Maesako, Masato; Uemura, Kengo; Kubota, Masakazu; Ando, Koichi; Kuzuya, Akira; Asada, Megumi; Kihara, Takeshi; Kinoshita, Ayae

    2010-10-15

    Recently, insulin signaling has been highlighted in the pathology of Alzheimer's disease (AD). Although the association between insulin signaling and Tau pathology has been investigated in several studies, the interaction between insulin signaling and Presenilin 1 (PS1), a key molecule of amyloid beta (Abeta) pathology, has not been elucidated so far. In this study, we demonstrated that insulin inhibited PS1 phosphorylation at serine residues (serine 353, 357) via phosphatidylinositol 3-kinase (PI3K)/Akt signal pathway and strengthened the trimeric complex of PS1/N-cadherin/beta-catenin, consequently relocalizing PS1 to the cell surface. Since our recent report suggests that PS1/N-cadherin/beta-catenin complex regulates Abeta production, it is likely that insulin signaling affects Abeta pathology by regulating PS1 localization. 2010 Elsevier Ireland Ltd. All rights reserved.

  4. Integrating gross pathology into teaching of undergraduate medical science students using human cadavers.

    PubMed

    Gopalan, Vinod; Dissabandara, Lakal; Nirthanan, Selvanayagam; Forwood, Mark R; Lam, Alfred King-Yin

    2016-09-01

    Human cadavers offer a great opportunity for histopathology students for the learning and teaching of tissue pathology. In this study, we aimed to implement an integrated learning approach by using cadavers to enhance students' knowledge and to develop their skills in gross tissue identification, handling and dissection techniques. A total of 35 students enrolled in the undergraduate medical science program participated in this study. A 3-hour laboratory session was conducted that included an active exploration of cadaveric specimens to identify normal and pathological tissues as well as tissue dissection. The majority of the students strongly agreed that the integration of normal and morbid anatomy improved their understanding of tissue pathology. All the students either agreed or strongly agreed that this laboratory session was useful to improve their tissue dissection and instrument handling skills. Furthermore, students from both cohorts rated the session as very relevant to their learning and recommended that this approach be added to the existing histopathology curriculum. To conclude, an integrated cadaver-based practical session can be used effectively to enhance the learning experience of histopathology science students, as well as improving their manual skills of tissue treatment, instrument handling and dissection. © 2016 Japanese Society of Pathology and John Wiley & Sons Australia, Ltd.

  5. Speech-Language-Pathology and Audiology Handbook.

    ERIC Educational Resources Information Center

    New York State Education Dept., Albany. Office of the Professions.

    The handbook contains State Education Department rules and regulations that govern speech-language pathology and audiology in New York State. The handbook also describes licensure and first registration as a licensed speech-language pathologist or audiologist. The introduction discusses professional regulation in New York State while the second…

  6. Reliability and Validity of Three Instruments (DSM-IV, CPGI, and PPGM) in the Assessment of Problem Gambling in South Korea.

    PubMed

    Back, Ki-Joon; Williams, Robert J; Lee, Choong-Ki

    2015-09-01

    Most research on the assessment, epidemiology, and treatment of problem gambling has occurred in Western jurisdictions. This potentially limits the cross-cultural validity of problem gambling assessment instruments as well as etiological models of problem gambling. The primary objective of the present research was to investigate the reliability and validity of three problem gambling assessment instruments within a South Korean context. A total of 4,330 South Korean adults participated in a comprehensive assessment of their gambling behavior that included the administration of the DSM-IV criteria for pathological gambling (NODS), the Canadian Problem Gambling Index (CPGI), and the Problem and Pathological Gambling Measure (PPGM). Cronbach alpha showed that all three instruments had good internal consistency. Concurrent validity was established by the significant associations observed between scores on the instruments and measures of gambling involvement (number of gambling formats engaged in; frequency of gambling; and gambling expenditure). Most importantly, kappa statistics showed that all instruments have satisfactory classification accuracy against clinical assessment of problem gambling conducted by South Korean clinicians (NODS κ = .66; PPGM κ = .62; CPGI κ = .51). These results confirm that Western-derived operationalizations of problem gambling have applicability in a South Korean setting.

  7. Insecure Attachment and Eating Pathology in Early Adolescence: Role of Emotion Regulation

    ERIC Educational Resources Information Center

    van Durme, Kim; Braet, Caroline; Goossens, Lien

    2015-01-01

    The present study investigated whether associations exist between attachment dimensions toward mother and different forms of eating pathology (EP) in a group of early adolescent boys and girls, and whether these associations were mediated by maladaptive emotion regulation (ER) strategies. Developmentally appropriate self-report questionnaires were…

  8. Behaviour, physiology and experience of pathological laughing and crying in amyotrophic lateral sclerosis.

    PubMed

    Olney, Nicholas T; Goodkind, Madeleine S; Lomen-Hoerth, Catherine; Whalen, Patrick K; Williamson, Craig A; Holley, Deborah E; Verstaen, Alice; Brown, Laurel M; Miller, Bruce L; Kornak, John; Levenson, Robert W; Rosen, Howard J

    2011-12-01

    Pathological laughing and crying is a disorder of emotional expression seen in a number of neurological diseases. The aetiology is poorly understood, but clinical descriptions suggest a disorder of emotion regulation. The goals of this study were: (i) to characterize the subjective, behavioural and physiological emotional reactions that occur during episodes of pathological laughing and crying; (ii) to compare responses during these episodes to those that occur when emotions are elicited under standard conditions (watching sad and amusing emotional films, being startled); and (iii) to examine the ability of patients with this disorder to regulate their emotions under standardized conditions. Twenty-one patients with pathological laughing and crying due to amyotrophic lateral sclerosis and 14 with amyotrophic lateral sclerosis but no pathological laughing and crying were studied. Emotional measures included self-reported emotional experience, video recordings of facial reactivity and peripheral physiological responses (skin conductance, heart rate and somatic activity). Nineteen of the 21 patients with histories of pathological laughing and crying had at least one episode in the laboratory that they agreed constituted pathological laughing or crying (a total of 56 episodes were documented). Compared with viewing sad and amusing films, the episodes were associated with greater facial and physiological activation. Contrary to many clinical descriptions, episodes were often induced by contextually appropriate stimuli and associated with strong experiences of emotion that were consistent with the display. When instructed to regulate their facial responses to emotion-eliciting films, patients with pathological laughing and crying showed impairments compared with patients who did not have a history of this disorder. These findings support the idea that pathological laughing and crying represents activation of all channels of emotional responding (i.e. behavioural, physiological and subjective). Furthermore, they support previously advanced theories that, rather than being associated with general emotional hyperreactivity, this disorder may be due to dysfunction in frontal neural systems that support voluntary regulation of emotion.

  9. Behaviour, physiology and experience of pathological laughing and crying in amyotrophic lateral sclerosis

    PubMed Central

    Olney, Nicholas T.; Goodkind, Madeleine S.; Lomen-Hoerth, Catherine; Whalen, Patrick K.; Williamson, Craig A.; Holley, Deborah E.; Verstaen, Alice; Brown, Laurel M.; Miller, Bruce L.; Kornak, John; Levenson, Robert W.

    2011-01-01

    Pathological laughing and crying is a disorder of emotional expression seen in a number of neurological diseases. The aetiology is poorly understood, but clinical descriptions suggest a disorder of emotion regulation. The goals of this study were: (i) to characterize the subjective, behavioural and physiological emotional reactions that occur during episodes of pathological laughing and crying; (ii) to compare responses during these episodes to those that occur when emotions are elicited under standard conditions (watching sad and amusing emotional films, being startled); and (iii) to examine the ability of patients with this disorder to regulate their emotions under standardized conditions. Twenty-one patients with pathological laughing and crying due to amyotrophic lateral sclerosis and 14 with amyotrophic lateral sclerosis but no pathological laughing and crying were studied. Emotional measures included self-reported emotional experience, video recordings of facial reactivity and peripheral physiological responses (skin conductance, heart rate and somatic activity). Nineteen of the 21 patients with histories of pathological laughing and crying had at least one episode in the laboratory that they agreed constituted pathological laughing or crying (a total of 56 episodes were documented). Compared with viewing sad and amusing films, the episodes were associated with greater facial and physiological activation. Contrary to many clinical descriptions, episodes were often induced by contextually appropriate stimuli and associated with strong experiences of emotion that were consistent with the display. When instructed to regulate their facial responses to emotion-eliciting films, patients with pathological laughing and crying showed impairments compared with patients who did not have a history of this disorder. These findings support the idea that pathological laughing and crying represents activation of all channels of emotional responding (i.e. behavioural, physiological and subjective). Furthermore, they support previously advanced theories that, rather than being associated with general emotional hyperreactivity, this disorder may be due to dysfunction in frontal neural systems that support voluntary regulation of emotion. PMID:22155983

  10. Lack of shunt response in suspected idiopathic normal pressure hydrocephalus with Alzheimer disease pathology.

    PubMed

    Hamilton, Roy; Patel, Sunil; Lee, Edward B; Jackson, Eric M; Lopinto, Joanna; Arnold, Steven E; Clark, Christopher M; Basil, Anuj; Shaw, Leslie M; Xie, Sharon X; Grady, M Sean; Trojanowski, John Q

    2010-10-01

    To determine the impact of cortical Alzheimer disease pathology on shunt responsiveness in individuals treated for idiopathic normal pressure hydrocephalus (iNPH), 37 patients clinically diagnosed with iNPH participated in a prospective study in which performance on neurologic, psychometric, and gait measures before and 4 months after shunting was correlated with amyloid β plaques, neuritic plaques, and neurofibrillary tangles observed in cortical biopsies obtained during shunt insertion. No complications resulted from biopsy acquisition. Moderate to severe pathology was associated with worse baseline cognitive performance and diminished postoperative improvement on NPH symptom severity scales, gait measures, and cognitive instruments compared to patients lacking pathology.

  11. A novel P53/POMC/Gαs/SASH1 autoregulatory feedback loop activates mutated SASH1 to cause pathologic hyperpigmentation.

    PubMed

    Zhou, Ding'an; Wei, Zhiyun; Kuang, Zhongshu; Luo, Huangchao; Ma, Jiangshu; Zeng, Xing; Wang, Ke; Liu, Beizhong; Gong, Fang; Wang, Jing; Lei, Shanchuan; Wang, Dongsheng; Zeng, Jiawei; Wang, Teng; He, Yong; Yuan, Yongqiang; Dai, Hongying; He, Lin; Xing, Qinghe

    2017-04-01

    p53-Transcriptional-regulated proteins interact with a large number of other signal transduction pathways in the cell, and a number of positive and negative autoregulatory feedback loops act upon the p53 response. P53 directly controls the POMC/α-MSH productions induced by ultraviolet (UV) and is associated with UV-independent pathological pigmentation. When identifying the causative gene of dyschromatosis universalis hereditaria (DUH), we found three mutations encoding amino acid substitutions in the gene SAM and SH3 domain containing 1 (SASH1), and SASH1 was associated with guanine nucleotide-binding protein subunit-alpha isoforms short (Gαs). However, the pathological gene and pathological mechanism of DUH remain unknown for about 90 years. We demonstrate that SASH1 is physiologically induced by p53 upon UV stimulation and SASH and p53 is reciprocally induced at physiological and pathophysiological conditions. SASH1 is regulated by a novel p53/POMC/α-MSH/Gαs/SASH1 cascade to mediate melanogenesis. A novel p53/POMC/Gαs/SASH1 autoregulatory positive feedback loop is regulated by SASH1 mutations to induce pathological hyperpigmentation phenotype. Our study demonstrates that a novel p53/POMC/Gαs/SASH1 autoregulatory positive feedback loop is regulated by SASH1 mutations to induce pathological hyperpigmentation phenotype. © 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.

  12. Recognizing and Reducing Analytical Errors and Sources of Variation in Clinical Pathology Data in Safety Assessment Studies.

    PubMed

    Schultze, A E; Irizarry, A R

    2017-02-01

    Veterinary clinical pathologists are well positioned via education and training to assist in investigations of unexpected results or increased variation in clinical pathology data. Errors in testing and unexpected variability in clinical pathology data are sometimes referred to as "laboratory errors." These alterations may occur in the preanalytical, analytical, or postanalytical phases of studies. Most of the errors or variability in clinical pathology data occur in the preanalytical or postanalytical phases. True analytical errors occur within the laboratory and are usually the result of operator or instrument error. Analytical errors are often ≤10% of all errors in diagnostic testing, and the frequency of these types of errors has decreased in the last decade. Analytical errors and increased data variability may result from instrument malfunctions, inability to follow proper procedures, undetected failures in quality control, sample misidentification, and/or test interference. This article (1) illustrates several different types of analytical errors and situations within laboratories that may result in increased variability in data, (2) provides recommendations regarding prevention of testing errors and techniques to control variation, and (3) provides a list of references that describe and advise how to deal with increased data variability.

  13. Validation of an instrument to measure students' motivation and self-regulation towards technology learning

    NASA Astrophysics Data System (ADS)

    Liou, Pey-Yan; Kuo, Pei-Jung

    2014-05-01

    Background:Few studies have examined students' attitudinal perceptions of technology. There is no appropriate instrument to measure senior high school students' motivation and self-regulation toward technology learning among the current existing instruments in the field of technology education. Purpose:The present study is to validate an instrument for assessing senior high school students' motivation and self-regulation towards technology learning. Sample:A total of 1822 Taiwanese senior high school students (1020 males and 802 females) responded to the newly developed instrument. Design and method:The Motivation and Self-regulation towards Technology Learning (MSRTL) instrument was developed based on the previous instruments measuring students' motivation and self-regulation towards science learning. Exploratory and confirmatory factor analyses were utilized to investigate the structure of the items. Cronbach's alpha was applied for measuring the internal consistency of each scale. Furthermore, multivariate analysis of variance was used to examine gender differences. Results:Seven scales, including 'Technology learning self-efficacy,' 'Technology learning value,' 'Technology active learning strategies,' 'Technology learning environment stimulation,' 'Technology learning goal-orientation,' 'Technology learning self-regulation-triggering,' and 'Technology learning self-regulation-implementing' were confirmed for the MSRTL instrument. Moreover, the results also showed that male and female students did not present the same degree of preference in all of the scales. Conclusions:The MSRTL instrument composed of seven scales corresponding to 39 items was shown to be valid based on validity and reliability analyses. While male students tended to express more positive and active performance in the motivation scales, no gender differences were found in the self-regulation scales.

  14. Gender roles, eating pathology, and body dissatisfaction in men: a meta-analysis.

    PubMed

    Blashill, Aaron J

    2011-01-01

    The current study reviewed relationships between gender roles and (a) eating pathology, (b) body dissatisfaction, and (c) muscle dissatisfaction among men via meta-analysis. Moderators of sexual orientation and type of gender role measure were also investigated. Results revealed the relationship between femininity and eating and body-related variables did not significantly differ from zero. Sexual orientation moderated the relationship between femininity and muscle dissatisfaction (i.e., femininity was negatively related to muscle dissatisfaction for heterosexual but not gay men). Masculinity was negatively associated with eating pathology and body dissatisfaction. Type of masculinity measure moderated the relationship between masculinity and body dissatisfaction (i.e., trait-based measures produced a negative association, multidimensional measures yielded nonsignificant relationships). Type of masculinity measure produced a cross-over interaction when examining muscle dissatisfaction (i.e., trait-based instruments yielded a negative association and multidimensional instruments revealed a positive relationship). Findings highlight the salience of masculinity in men's eating and body concerns. Copyright © 2010 Elsevier Ltd. All rights reserved.

  15. Active vs. Reactive Threat Responding is Associated with Differential c-Fos Expression in Specific Regions of Amygdala and Prefrontal Cortex

    ERIC Educational Resources Information Center

    Martinez, Raquel C. R.; Gupta, Nikita; Lazaro-Munoz, Gabriel; Sears, Robert M.; Kim, Soojeong; Moscarello, Justin M.; LeDoux, Joseph E.; Cain, Christopher K.

    2013-01-01

    Active avoidance (AA) is an important paradigm for studying mechanisms of aversive instrumental learning, pathological anxiety, and active coping. Unfortunately, AA neurocircuits are poorly understood, partly because behavior is highly variable and reflects a competition between Pavlovian reactions and instrumental actions. Here we exploited the…

  16. Lack of Shunt Response in Suspected Idiopathic Normal Pressure Hydrocephalus with Alzheimer Disease Pathology

    PubMed Central

    Hamilton, Roy; Patel, Sunil; Lee, Edward B.; Jackson, Eric M.; Lopinto, Joanna; Arnold, Steven E.; Clark, Christopher M.; Basil, Anuj; Shaw, Leslie M.; Xie, Sharon X.; Grady, M. Sean; Trojanowski, John Q.

    2010-01-01

    To determine the impact of cortical Alzheimer disease pathology on shunt responsiveness in individuals treated for idiopathic normal pressure hydrocephalus (iNPH), 37 patients clinically diagnosed with iNPH participated in a prospective study in which performance on neurologic, psychometric, and gait measures before and 4 months after shunting was correlated with amyloid β plaques, neuritic plaques, and neurofibrillary tangles observed in cortical biopsies obtained during shunt insertion. No complications resulted from biopsy acquisition. Moderate to severe pathology was associated with worse baseline cognitive performance and diminished postoperative improvement on NPH symptom severity scales, gait measures, and cognitive instruments compared to patients lacking pathology. PMID:20687117

  17. A Meta-analysis on the Association Between Emotional Awareness and Borderline Personality Pathology.

    PubMed

    Derks, Youri P M J; Westerhof, Gerben J; Bohlmeijer, Ernst T

    2017-06-01

    Theories on borderline personality pathology (BPP) suggest that characteristic emotional dysregulation is due to low levels of emotional awareness or alexithymia. This study is the first meta-analysis to systematically review and analyze the evidence. A systematic search of the literature was performed using PsycInfo, Web of Science/MEDLINE, and Scopus. The term "borderline personality disorder" was searched for in conjunction with "emotional awareness," "emotional self-awareness," "emotion recognition," "alexithymia," "emotional processing," "emotional granularity," "emotional intelligence," or "emotion regulation." All references in the included studies were reviewed for additional relevant articles. Thirty-nine studies were then evaluated in a random effects meta-analysis to assess the association between BPP and emotional awareness. An overall moderate positive association between BPP and emotional awareness was significant (r = 0.359; 95% CI [0.283, 0.431]; Z = 8.678; p < 0.001) along with high heterogeneity (Q(38) = 456.7; p < .001; I 2 = 91.7%). Studies comparing borderline personality disorder to healthy controls yielded a strong association (r = 0.518; 95% CI [0.411, 0.611]). No significant difference was found between studies using instruments for emotional awareness and those using alexithymia instruments. The strongest associations with regard to aspects of alexithymia were found for difficulties in identifying and describing emotions rather than externally oriented thinking. The results corroborate a moderate relationship between low emotional awareness and BPP. However, the mono-method self-report used in almost all studies is found problematic and precludes drawing definite conclusions. Since leading psychotherapeutic treatments strongly focus on increasing emotional awareness, future research should address this issue and further examine to what extent low levels of emotional awareness, particularly alexithymia, can be treated.

  18. Best practices for veterinary toxicologic clinical pathology, with emphasis on the pharmaceutical and biotechnology industries.

    PubMed

    Tomlinson, Lindsay; Boone, Laura I; Ramaiah, Lila; Penraat, Kelley A; von Beust, Barbara R; Ameri, Mehrdad; Poitout-Belissent, Florence M; Weingand, Kurt; Workman, Heather C; Aulbach, Adam D; Meyer, Dennis J; Brown, Diane E; MacNeill, Amy L; Bolliger, Anne Provencher; Bounous, Denise I

    2013-09-01

    The purpose of this paper by the Regulatory Affairs Committee (RAC) of the American Society for Veterinary Clinical Pathology (ASVCP) is to review the current regulatory guidances (eg, guidelines) and published recommendations for best practices in veterinary toxicologic clinical pathology, particularly in the pharmaceutical and biotechnology industries, and to utilize the combined experience of ASVCP RAC to provide updated recommendations. Discussion points include (1) instrumentation, validation, and sample collection, (2) routine laboratory variables, (3) cytologic laboratory variables, (4) data interpretation and reporting (including peer review, reference intervals and statistics), and (5) roles and responsibilities of clinical pathologists and laboratory personnel. Revision and improvement of current practices should be in alignment with evolving regulatory guidance documents, new technology, and expanding understanding and utility of clinical pathology. These recommendations provide a contemporary guide for the refinement of veterinary toxicologic clinical pathology best practices. © 2013 American Society for Veterinary Clinical Pathology.

  19. Measuring emotion regulation and emotional expression in breast cancer patients: A systematic review.

    PubMed

    Brandão, Tânia; Tavares, Rita; Schulz, Marc S; Matos, Paula Mena

    2016-02-01

    The important role of emotion regulation and expression in adaptation to breast cancer is now widely recognized. Studies have shown that optimal emotion regulation strategies, including less constrained emotional expression, are associated with better adaptation. Our objective was to systematically review measures used to assess the way women with breast cancer regulate their emotions. This systematic review was conducted in accordance with PRISMA guidelines. Nine different databases were searched. Data were independently extracted and assessed by two researchers. English-language articles that used at least one instrument to measure strategies to regulate emotions in women with breast cancer were included. Of 679 abstracts identified 59 studies were deemed eligible for inclusion. Studies were coded regarding their objectives, methods, and results. We identified 16 instruments used to measure strategies of emotion regulation and expression. The most frequently employed instrument was the Courtauld Emotional Control Scale. Few psychometric proprieties other than internal consistency were reported for most instruments. Many studies did not include important information regarding descriptive characteristics and psychometric properties of the instruments used. The instruments used tap different aspects of emotion regulation. Specific instruments should be explored further with regard to content, validity, and reliability in the context of breast cancer. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Diffusion Geometry Based Nonlinear Methods for Hyperspectral Change Detection

    DTIC Science & Technology

    2010-05-12

    for matching biological spectra across a data base of hyperspectral pathology slides acquires with different instruments in different conditions, as...generalizing wavelets and similar scaling mechanisms. Plain Sight Systems, Inc. -7- Proprietary and Confidential To be specific, let the bi-Markov...remarkably well. Conventional nearest neighbor search , compared with a diffusion search. The data is a pathology slide ,each pixel is a digital

  1. GSK-3α is a central regulator of age-related pathologies in mice

    PubMed Central

    Zhou, Jibin; Freeman, Theresa A.; Ahmad, Firdos; Shang, Xiying; Mangano, Emily; Gao, Erhe; Farber, John; Wang, Yajing; Ma, Xin-Liang; Woodgett, James; Vagnozzi, Ronald J.; Lal, Hind; Force, Thomas

    2013-01-01

    Aging is regulated by conserved signaling pathways. The glycogen synthase kinase-3 (GSK-3) family of serine/threonine kinases regulates several of these pathways, but the role of GSK-3 in aging is unknown. Herein, we demonstrate premature death and acceleration of age-related pathologies in the Gsk3a global KO mouse. KO mice developed cardiac hypertrophy and contractile dysfunction as well as sarcomere disruption and striking sarcopenia in cardiac and skeletal muscle, a classical finding in aging. We also observed severe vacuolar degeneration of myofibers and large tubular aggregates in skeletal muscle, consistent with impaired clearance of insoluble cellular debris. Other organ systems, including gut, liver, and the skeletal system, also demonstrated age-related pathologies. Mechanistically, we found marked activation of mTORC1 and associated suppression of autophagy markers in KO mice. Loss of GSK-3α, either by pharmacologic inhibition or Gsk3a gene deletion, suppressed autophagy in fibroblasts. mTOR inhibition rescued this effect and reversed the established pathologies in the striated muscle of the KO mouse. Thus, GSK-3α is a critical regulator of mTORC1, autophagy, and aging. In its absence, aging/senescence is accelerated in multiple tissues. Strategies to maintain GSK-3α activity and/or inhibit mTOR in the elderly could retard the appearance of age-related pathologies. PMID:23549082

  2. RNA-Binding Proteins in Female Reproductive Pathologies.

    PubMed

    Khalaj, Kasra; Miller, Jessica E; Fenn, Christian R; Ahn, SooHyun; Luna, Rayana L; Symons, Lindsey; Monsanto, Stephany P; Koti, Madhuri; Tayade, Chandrakant

    2017-06-01

    RNA-binding proteins are key regulatory molecules involved primarily in post-transcriptional gene regulation of RNAs. Post-transcriptional gene regulation is critical for adequate cellular growth and survival. Recent reports have shown key interactions between these RNA-binding proteins and other regulatory elements, such as miRNAs and long noncoding RNAs, either enhancing or diminishing their response to RNA stabilization. Many RNA-binding proteins have been reported to play a functional role in mediation of cytokines involved in inflammation and immune dysfunction, and some have been classified as global post-transcriptional regulators of inflammation. The ubiquitous expression of RNA-binding proteins in a wide variety of cell types and their unique mechanisms of degradative action provide evidence that they are involved in reproductive tract pathologies. Aberrant inflammation and immune dysfunction are major contributors to the pathogenesis and disease pathophysiology of many reproductive pathologies, including ovarian and endometrial cancers in the female reproductive tract. Herein, we discuss various RNA-binding proteins and their unique contributions to female reproductive pathologies with a focus on those mediated by aberrant inflammation and immune dysfunction. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  3. Emerging Themes in Image Informatics and Molecular Analysis for Digital Pathology.

    PubMed

    Bhargava, Rohit; Madabhushi, Anant

    2016-07-11

    Pathology is essential for research in disease and development, as well as for clinical decision making. For more than 100 years, pathology practice has involved analyzing images of stained, thin tissue sections by a trained human using an optical microscope. Technological advances are now driving major changes in this paradigm toward digital pathology (DP). The digital transformation of pathology goes beyond recording, archiving, and retrieving images, providing new computational tools to inform better decision making for precision medicine. First, we discuss some emerging innovations in both computational image analytics and imaging instrumentation in DP. Second, we discuss molecular contrast in pathology. Molecular DP has traditionally been an extension of pathology with molecularly specific dyes. Label-free, spectroscopic images are rapidly emerging as another important information source, and we describe the benefits and potential of this evolution. Third, we describe multimodal DP, which is enabled by computational algorithms and combines the best characteristics of structural and molecular pathology. Finally, we provide examples of application areas in telepathology, education, and precision medicine. We conclude by discussing challenges and emerging opportunities in this area.

  4. Emerging Themes in Image Informatics and Molecular Analysis for Digital Pathology

    PubMed Central

    Bhargava, Rohit; Madabhushi, Anant

    2017-01-01

    Pathology is essential for research in disease and development, as well as for clinical decision making. For more than 100 years, pathology practice has involved analyzing images of stained, thin tissue sections by a trained human using an optical microscope. Technological advances are now driving major changes in this paradigm toward digital pathology (DP). The digital transformation of pathology goes beyond recording, archiving, and retrieving images, providing new computational tools to inform better decision making for precision medicine. First, we discuss some emerging innovations in both computational image analytics and imaging instrumentation in DP. Second, we discuss molecular contrast in pathology. Molecular DP has traditionally been an extension of pathology with molecularly specific dyes. Label-free, spectroscopic images are rapidly emerging as another important information source, and we describe the benefits and potential of this evolution. Third, we describe multimodal DP, which is enabled by computational algorithms and combines the best characteristics of structural and molecular pathology. Finally, we provide examples of application areas in telepathology, education, and precision medicine. We conclude by discussing challenges and emerging opportunities in this area. PMID:27420575

  5. 15 CFR 301.3 - Application for duty-free entry of scientific instruments.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... scientific instruments. 301.3 Section 301.3 Commerce and Foreign Trade Regulations Relating to Commerce and... REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.3 Application for duty-free entry of scientific instruments. (a) Who may apply. An applicant for duty-free entry of an...

  6. 15 CFR 301.3 - Application for duty-free entry of scientific instruments.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... scientific instruments. 301.3 Section 301.3 Commerce and Foreign Trade Regulations Relating to Commerce and... REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.3 Application for duty-free entry of scientific instruments. (a) Who may apply. An applicant for duty-free entry of an...

  7. 15 CFR 301.3 - Application for duty-free entry of scientific instruments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... scientific instruments. 301.3 Section 301.3 Commerce and Foreign Trade Regulations Relating to Commerce and... REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.3 Application for duty-free entry of scientific instruments. (a) Who may apply. An applicant for duty-free entry of an...

  8. 15 CFR 301.3 - Application for duty-free entry of scientific instruments.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... scientific instruments. 301.3 Section 301.3 Commerce and Foreign Trade Regulations Relating to Commerce and... REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.3 Application for duty-free entry of scientific instruments. (a) Who may apply. An applicant for duty-free entry of an...

  9. 15 CFR 301.3 - Application for duty-free entry of scientific instruments.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... scientific instruments. 301.3 Section 301.3 Commerce and Foreign Trade Regulations Relating to Commerce and... REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.3 Application for duty-free entry of scientific instruments. (a) Who may apply. An applicant for duty-free entry of an...

  10. Cardioprotective Role of Tumor Necrosis Factor Receptor-Associated Factor 2 by Suppressing Apoptosis and Necroptosis.

    PubMed

    Guo, Xiaoyun; Yin, Haifeng; Li, Lei; Chen, Yi; Li, Jing; Doan, Jessica; Steinmetz, Rachel; Liu, Qinghang

    2017-08-22

    Programmed cell death, including apoptosis, mitochondria-mediated necrosis, and necroptosis, is critically involved in ischemic cardiac injury, pathological cardiac remodeling, and heart failure progression. Whereas apoptosis and mitochondria-mediated necrosis signaling is well established, the regulatory mechanisms of necroptosis and its significance in the pathogenesis of heart failure remain elusive. We examined the role of tumor necrosis factor receptor-associated factor 2 (Traf2) in regulating myocardial necroptosis and remodeling using genetic mouse models. We also performed molecular and cellular biology studies to elucidate the mechanisms by which Traf2 regulates necroptosis signaling. We identified a critical role for Traf2 in myocardial survival and homeostasis by suppressing necroptosis. Cardiac-specific deletion of Traf2 in mice triggered necroptotic cardiac cell death, pathological remodeling, and heart failure. Plasma tumor necrosis factor α level was significantly elevated in Traf2 -deficient mice, and genetic ablation of TNFR1 largely abrogated pathological cardiac remodeling and dysfunction associated with Traf2 deletion. Mechanistically, Traf2 critically regulates receptor-interacting proteins 1 and 3 and mixed lineage kinase domain-like protein necroptotic signaling with the adaptor protein tumor necrosis factor receptor-associated protein with death domain as an upstream regulator and transforming growth factor β-activated kinase 1 as a downstream effector. It is important to note that genetic deletion of RIP3 largely rescued the cardiac phenotype triggered by Traf2 deletion, validating a critical role of necroptosis in regulating pathological remodeling and heart failure propensity. These results identify an important Traf2-mediated, NFκB-independent, prosurvival pathway in the heart by suppressing necroptotic signaling, which may serve as a new therapeutic target for pathological remodeling and heart failure. © 2017 American Heart Association, Inc.

  11. The Future of Pathology: A Delphi Study by Pathology Department Chairmen

    ERIC Educational Resources Information Center

    Goodale, Fairfield; Gander, George W.

    1976-01-01

    Over 100 department chairmen in American and Canadian medical schools participated in this questionnaire study. Most are deeply concerned about increasing federal regulation of medicine, expect more emphasis on the basic science aspects of pathology, and foresee a shift of residency training programs away from small hospitals to larger medical…

  12. The efficacy of instrument assisted soft tissue mobilization: a systematic review.

    PubMed

    Cheatham, Scott W; Lee, Matt; Cain, Matt; Baker, Russell

    2016-09-01

    Instrument assisted soft tissue mobilization (IASTM) is a popular treatment for myofascial restriction. IASTM uses specially designed instruments to provide a mobilizing effect to scar tissue and myofascial adhesions. Several IASTM tools and techniques are available such as the Graston® technique. Currently, there are no systematic reviews that have specifically appraised the effects of IASTM as a treatment or to enhance joint range of motion (ROM). The purpose of this study was to systematically appraise the current evidence assessing the effects of IASTM as an intervention to treat a musculoskeletal pathology or to enhance joint ROM. A search of the literature was conducted during the month of December 2015 which included the following databases: PubMed, PEDro, Science Direct, and the EBSCOhost collection. A direct search of known journals was also conducted to identify potential publications. The search terms included individual or a combination of the following: instrument; assisted; augmented; soft-tissue; mobilization; Graston®; and technique. A total of 7 randomized controlled trials were appraised. Five of the studies measured an IASTM intervention versus a control or alternate intervention group for a musculoskeletal pathology. The results of the studies were insignificant (p>.05) with both groups displaying equal outcomes. Two studies measured an IASTM intervention versus a control or alternate intervention group on the effects of joint ROM. The IASTM intervention produced significant (P<.05) short term gains up to 24 hours. The literature measuring the effects of IASTM is still emerging. The current research has indicated insignificant results which challenges the efficacy of IASTM as a treatment for common musculoskeletal pathology, which may be due to the methodological variability among studies. There appears to be some evidence supporting its ability to increase short term joint ROM.

  13. Adenosine Kinase: Exploitation for Therapeutic Gain

    PubMed Central

    2013-01-01

    Adenosine kinase (ADK; EC 2.7.1.20) is an evolutionarily conserved phosphotransferase that converts the purine ribonucleoside adenosine into 5′-adenosine-monophosphate. This enzymatic reaction plays a fundamental role in determining the tone of adenosine, which fulfills essential functions as a homeostatic and metabolic regulator in all living systems. Adenosine not only activates specific signaling pathways by activation of four types of adenosine receptors but it is also a primordial metabolite and regulator of biochemical enzyme reactions that couple to bioenergetic and epigenetic functions. By regulating adenosine, ADK can thus be identified as an upstream regulator of complex homeostatic and metabolic networks. Not surprisingly, ADK dysfunction is involved in several pathologies, including diabetes, epilepsy, and cancer. Consequently, ADK emerges as a rational therapeutic target, and adenosine-regulating drugs have been tested extensively. In recent attempts to improve specificity of treatment, localized therapies have been developed to augment adenosine signaling at sites of injury or pathology; those approaches include transplantation of stem cells with deletions of ADK or the use of gene therapy vectors to downregulate ADK expression. More recently, the first human mutations in ADK have been described, and novel findings suggest an unexpected role of ADK in a wider range of pathologies. ADK-regulating strategies thus represent innovative therapeutic opportunities to reconstruct network homeostasis in a multitude of conditions. This review will provide a comprehensive overview of the genetics, biochemistry, and pharmacology of ADK and will then focus on pathologies and therapeutic interventions. Challenges to translate ADK-based therapies into clinical use will be discussed critically. PMID:23592612

  14. Spanish adaptation of the Gambling Motives Questionnaire (GMQ): Validation in adult pathological gamblers and relationship with anxious-depressive symptomatology and perceived stress.

    PubMed

    Jauregui, Paula; Estevez, Ana; Onaindia, Jaione

    2018-10-01

    Gambling has been found to be related to different motives, such as enhancement, social, and behavioral and emotional coping. The most used instrument in this field is the Gambling Motives Questionnaire (GMQ; Stewart & Zack, 2008), which has not been validated in clinical samples. This study aimed to validate a Spanish version of the GMQ in a sample of adult pathological gamblers and to analyze its relationship with pathological gambling, anxiety, depression, and perceived stress. A sample of 164 gamblers was recruited from centers for the treatment of pathological gambling. The three-factor structure (enhancement, social, and coping motives) of the GMQ was validated through exploratory and confirmatory factorial analyses, and its convergent validity was proven. Gambling motives correlated with pathological gambling, anxiety, depression, and perceived stress. Enhancement motives predicted pathological gambling, while controlling for the effect of anxiety, depression, and perceived stress. These results are relevant for clinical evaluation and intervention with adult pathological gamblers. Copyright © 2018 Elsevier Ltd. All rights reserved.

  15. Morphine via nitric oxide modulates beta-amyloid metabolism: a novel protective mechanism for Alzheimer's disease.

    PubMed

    Pak, Theodore; Cadet, Patrick; Mantione, Kirk J; Stefano, George B

    2005-10-01

    The deposition of intracellular and extracellular beta-amyloid peptide (Abeta) in the brain is a pathologic feature of Alzheimer's disease (AD), a prevalent neurodegenerative disorder. However, the exact role of the Abeta peptide in causing AD's symptoms is unclear. CRL-2266 SH-SY5Y human neuroblastoma cells (ATCC, USA) and HTB-11 human neuroblastoma cells (ATCC, USA) were cultured. Reverse transcription-polymerase chain reaction (RT-PCR) was performed to analyze the effects of beta25-35, morphine, and SNAP treatments upon BACE-1 and BACE-2 mRNA expression semi-quantitative RT-PCR. The production of NO in SH-SY5Y cells was detected using the Apollo 4000 Free Radical Analyzer (World Precision Instruments). Untreated HTB-11 neuroblastoma cells constitutively express BACE-1 and BACE-2 mRNA. Morphine down regulates the expression of BACE-1 and up regulates the expression of BACE-2 in a naloxone antagonizable manner. When HTB-11 cells were treated with L-NAME, a cNOS inhibitor; the effects of morphine were blocked. SNAP (a NO donor) mimicked the effect of morphine. In SH-SY5Y cells, Abeta treated cells show a dose-dependent decrease in NO release, demonstrating that Ab is dose-dependently inhibiting the release of constitutive NO. Ab and morphine/NO each inhibit the production of the other. This suggests that a deficiency of basal NO or endogenous morphine may trigger drastically reduced levels of basal NO. The outcome is chronic vasoconstriction and brain hypoperfusion and eventual neuronal death. This novel theorized mechanism for AD supports an increasingly-accepted vascular pathological hypothesis for the disease.

  16. 78 FR 10002 - Proposed Collection; Comment Request for Regulation Project

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-12

    ...: FI-59-91. Abstract: This regulation relates to the tax treatment of debt instruments that provide for... debt instruments with original issue discount; contingent payments; anti-abuse rule. DATES: Written... Constitution Avenue NW., Washington, DC 20224. SUPPLEMENTARY INFORMATION: Title: Debt Instruments With Original...

  17. Shoulder arthroscopy: the basics.

    PubMed

    Farmer, Kevin W; Wright, Thomas W

    2015-04-01

    Shoulder arthroscopy is a commonly performed and accepted procedure for a wide variety of pathologies. Surgeon experience, patient positioning, knowledge of surgical anatomy, proper portal placement, and proper use of instrumentation can improve technical success and minimize complication risks. This article details the surgical anatomy, indications, patient positioning, portal placement, instrumentation, and complications for basic shoulder arthroscopy. Copyright © 2015 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.

  18. 76 FR 47148 - Application(s) for Duty-Free Entry of Scientific Instruments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-04

    ... work in microbiology and pathology, to study biological materials in order to identify bacterial or viral pathogens with clinical significance in veterinary medicine. Justification for Duty-Free Entry: No...

  19. Instrumental motives in negative emotion regulation in daily life: Frequency, consistency, and predictors.

    PubMed

    Kalokerinos, Elise K; Tamir, Maya; Kuppens, Peter

    2017-06-01

    People regulate their emotions not only for hedonic reasons but also for instrumental reasons, to attain the potential benefits of emotions beyond pleasure and pain. However, such instrumental motives have rarely been examined outside the laboratory as they naturally unfold in daily life. To assess whether and how instrumental motives operate outside the laboratory, it is necessary to examine them in response to real and personally relevant stimuli in ecologically valid contexts. In this research, we assessed the frequency, consistency, and predictors of instrumental motives in negative emotion regulation in daily life. Participants (N = 114) recalled the most negative event of their day each evening for 7 days and reported their instrumental motives and negative emotion goals in that event. Participants endorsed performance motives in approximately 1 in 3 events and social, eudaimonic, and epistemic motives in approximately 1 in 10 events. Instrumental motives had substantially higher within- than between-person variance, indicating that they were context-dependent. Indeed, although we found few associations between instrumental motives and personality traits, relationships between instrumental motives and contextual variables were more extensive. Performance, social, and epistemic motives were each predicted by a unique pattern of contextual appraisals. Our data demonstrate that instrumental motives play a role in daily negative emotion regulation as people encounter situations that pose unique regulatory demands. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

  20. Regulation of Emotions in Socially Challenging Learning Situations: An Instrument to Measure the Adaptive and Social Nature of the Regulation Process

    ERIC Educational Resources Information Center

    Jarvenoja, Hanna; Volet, Simone; Jarvela, Sanna

    2013-01-01

    Self-regulated learning (SRL) research has conventionally relied on measures, which treat SRL as an aptitude. To study self-regulation and motivation in learning contexts as an ongoing adaptive process, situation-specific methods are needed in addition to static measures. This article presents an "Adaptive Instrument for Regulation of Emotions"…

  1. Measuring students' self-regulated learning in professional education: bridging the gap between event and aptitude measurements.

    PubMed

    Endedijk, Maaike D; Brekelmans, Mieke; Sleegers, Peter; Vermunt, Jan D

    Self-regulated learning has benefits for students' academic performance in school, but also for expertise development during their professional career. This study examined the validity of an instrument to measure student teachers' regulation of their learning to teach across multiple and different kinds of learning events in the context of a postgraduate professional teacher education programme. Based on an analysis of the literature, we developed a log with structured questions that could be used as a multiple-event instrument to determine the quality of student teachers' regulation of learning by combining data from multiple learning experiences. The findings showed that this structured version of the instrument measured student teachers' regulation of their learning in a valid and reliable way. Furthermore, with the aid of the Structured Learning Report individual differences in student teachers' regulation of learning could be discerned. Together the findings indicate that a multiple-event instrument can be used to measure regulation of learning in multiple contexts for various learning experiences at the same time, without the necessity of relying on students' ability to rate themselves across all these different experiences. In this way, this instrument can make an important contribution to bridging the gap between two dominant approaches to measure SRL, the traditional aptitude and event measurement approach.

  2. Saliva Proteomics Analysis Offers Insights on Type 1 Diabetes Pathology in a Pediatric Population

    PubMed Central

    Pappa, Eftychia; Vastardis, Heleni; Mermelekas, George; Gerasimidi-Vazeou, Andriani; Zoidakis, Jerome; Vougas, Konstantinos

    2018-01-01

    The composition of the salivary proteome is affected by pathological conditions. We analyzed by high resolution mass spectrometry approaches saliva samples collected from children and adolescents with type 1 diabetes and healthy controls. The list of more than 2000 high confidence protein identifications constitutes a comprehensive characterization of the salivary proteome. Patients with good glycemic regulation and healthy individuals have comparable proteomic profiles. In contrast, a significant number of differentially expressed proteins were identified in the saliva of patients with poor glycemic regulation compared to patients with good glycemic control and healthy children. These proteins are involved in biological processes relevant to diabetic pathology such as endothelial damage and inflammation. Moreover, a putative preventive therapeutic approach was identified based on bioinformatic analysis of the deregulated salivary proteins. Thus, thorough characterization of saliva proteins in diabetic pediatric patients established a connection between molecular changes and disease pathology. This proteomic and bioinformatic approach highlights the potential of salivary diagnostics in diabetes pathology and opens the way for preventive treatment of the disease. PMID:29755368

  3. The effect of environmental regulation on firms' competitive performance: the case of the building & construction sector in some EU regions.

    PubMed

    Testa, Francesco; Iraldo, Fabio; Frey, Marco

    2011-09-01

    There is a considerable debate on the effects of environmental regulation on competitive performance. Based on survey data, this paper analyzes the two main research questions, derived from literature, on the links between environmental regulation and competitiveness, by focusing on firms operating in the building and construction sector, i.e.: 1) whether environmental policy stringency affects the competitive performance of firms in the building and construction sector 2) and how a specific form of environmental regulation (direct regulation, economic instruments and soft instruments) affects this performance? By applying a regression analysis, we find that a more stringent environmental regulation, measured by inspection frequency, provides a positive impulse for increasing investments in advanced technological equipment and innovative products and on business performance. Moreover, a well-designed "direct regulation" appears to be the most effective policy instrument for prompting the positive impact of environmental policies on innovation and intangible performance while economic instruments do negatively affect business performance. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Egr-1 mediated cardiac miR-99 family expression diverges physiological hypertrophy from pathological hypertrophy.

    PubMed

    Ramasamy, Subbiah; Velmurugan, Ganesan; Rekha, Balakrishnan; Anusha, Sivakumar; Shanmugha Rajan, K; Shanmugarajan, Suresh; Ramprasath, Tharmarajan; Gopal, Pandi; Tomar, Dhanendra; Karthik, Karuppusamy V; Verma, Suresh Kumar; Garikipati, Venkata Naga Srikanth; Sudarsan, Rajan

    2018-04-01

    The physiological cardiac hypertrophy is an adaptive condition without myocyte cell death, while pathological hypertrophy is a maladaptive condition associated with myocyte cell death. This study explores the miRNome of α-2M-induced physiologically hypertrophied cardiomyocytes and the role of miRNA-99 family during cardiac hypertrophy. Physiological and pathological cardiac hypertrophy was induced in H9c2 cardiomyoblast cell lines using α-2M and isoproterenol respectively. Total RNA isolation and small RNA sequencing were executed for physiological hypertrophy model. The differentially expressed miRNAs and its target mRNAs were validated in animal models. Transcription factor binding sites were predicted in the promoter of specific miRNAs and validated by ChIP-PCR. Subsequently, the selected miRNA was functionally characterized by overexpression and silencing. The effects of silencing of upstream regulator and downstream target gene were studied. Analysis of small RNA reads revealed the differential expression of a large set of miRNAs during hypertrophy, of which miR-99 family was highly downregulated upon α-2M treatment. However, this miR-99 family expression was upregulated during pathological hypertrophy and confirmed in animal models. ChIP-PCR confirms the binding of Egr-1 transcription factor to the miR-99 promoter. Further, silencing of Egr-1 decreased the expression of miR-99. The overexpression or silencing of miR-99 diverges the physiological hypertrophy to pathological hypertrophy and vice versa by regulating Akt-1 pathway. Silencing of Akt-1 replicates the effect of overexpression of miR-99. The results proved Egr-1 mediated regulation of miR-99 family that plays a key role in determining the fate of cardiac hypertrophy by regulating Akt-1 signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Validation of an Instrument to Measure Students' Motivation and Self-Regulation towards Technology Learning

    ERIC Educational Resources Information Center

    Liou, Pey-Yan; Kuo, Pei-Jung

    2014-01-01

    Background: Few studies have examined students' attitudinal perceptions of technology. There is no appropriate instrument to measure senior high school students' motivation and self-regulation toward technology learning among the current existing instruments in the field of technology education. Purpose: The present study is to validate an…

  6. Methylation and microRNA-mediated epigenetic regulation of SOCS3

    PubMed Central

    Boosani, Chandra S.; Agrawal, Devendra K.

    2017-01-01

    Epigenetic gene silencing of several genes causes different pathological conditions in humans, and DNA methylation has been identified as one of the key mechanisms that underlie this evolutionarily conserved phenomenon associated with developmental and pathological gene regulation. Recent advances in the miRNA technology with high throughput analysis of gene regulation further increased our understanding on the role of miRNAs regulating multiple gene expression. There is increasing evidence supporting that the miRNAs not only regulate gene expression but they also are involved in the hypermethylation of promoter sequences, which cumulatively contributes to the epigenetic gene silencing. Here, we critically evaluated the recent progress on the transcriptional regulation of an important suppressor protein that inhibits cytokine-mediated signaling, SOCS3, whose expression is directly regulated both by promoter methylation and also by microRNAs, affecting its vital cell regulating functions. SOCS3 was identified as a potent inhibitor of Jak/STAT signaling pathway which is frequently upregulated in several pathologies, including cardiovascular disease, cancer, diabetes, viral infections, and the expression of SOCS3 was inhibited or greatly reduced due to hypermethylation of the CpG islands in its promoter region or suppression of its expression by different microRNAs. Additionally, we discuss key intracellular signaling pathways regulated by SOCS3 involving cellular events, including cell proliferation, cell growth, cell migration and apoptosis. Identification of the pathway intermediates as specific targets would not only aid in the development of novel therapeutic drugs, but, would also assist in developing new treatment strategies that could successfully be employed in combination therapy to target multiple signaling pathways. PMID:25682267

  7. [Pathology websites in the World Wide Web. A guide for a specific research of pathology information on the Internet].

    PubMed

    Böhm, J

    2008-05-01

    Being a global information network, the internet has becoming increasingly important for pathologists as a medium for professional communication and information. Although a large number of pathology-specific websites (PSWs) are accessible on the internet, the potentials of PSWs are still barely known. Since there is no global catalog for all the pathology websites, certain PSWs are difficult to find on the internet. PSWs offer lavishly illustrated education material for undergraduates and postgraduates in pathology, but may also be very useful as reference books or as an instrument of continuing medical education (CME) for experienced pathologists. The spectrum of PSW media comprises electronic training manuals, journals, case collections, photo-archives, and even complete section series of virtual microscopy. PSWs are available at any time, can be updated permanently and linked to further online sources of information. We demonstrate how to find PSWs and present an annotated list of some 100 of the best PSWs.

  8. [Apoptosis and pathological process].

    PubMed

    Rami, Mukhammed Salim Iusef

    2007-01-01

    Apoptosis (programmed cell death) occurs normally for maitenance of tissue homeostasis and play an important role in morphogenesis, embriogenesis and tissue growth. On the other hand, apoptosis may be involved in different pathological processes such as malignancy, infectious diseases and autoimmune disorders. Apoptosis is regulated by various mediators. Caspases, death receptors, mitochondria, Bcl-2 protoncogenes and tumor supressor genes are considered to be the most important of them. Advance in apoptosis regulation research suggests enormouse facilities for therapy of wide range of human illnesses.

  9. The Schreber case revisited: schizophrenia as a disorder of self-regulation and of interactional regulation.

    PubMed Central

    Grotstein, J. S.

    1985-01-01

    The Schreber case has been used by generations of psychoanalysts and psychiatrists to exemplify many features of the psychoanalytic conception of psychosis. It has generally been considered the origin of a great debate in psychoanalysis as to whether schizophrenia is a disorder of nature or of nurture. I seek in this contribution to proffer a newer theory of psychopathology, one which is based upon the conception of primary and secondary disorders of attachment (bonding) and which presents itself clinically as disorders of self-regulation and of interactional regulation. I attempt to explicate this theory in the Schreber case by demonstrating that his symptoms revealed: (a) failures of normal mental state regulations, (b) the emergence of symptoms which then secondarily and pathologically restore regulation in a pathological manner, and finally (c) his/her very symptoms seem to regulate a state in the family system and/or in the system of the culture at large. PMID:4049912

  10. Legal issues for pathologists.

    PubMed

    Wood, Jane Pine

    2011-11-01

    For better or for worse, the practice of pathology has evolved rapidly in the last decade, particularly the last several years. The dominance of certain national and regional pathology providers and the in-sourcing of pathology services as a revenue stream by nonpathology specialists have transformed pathology services into a commodity in many market, rather than a professional medical service. Despite significant health care reform and a myriad of compliance laws and regulations, it is unlikely that pathology practice will return to "the good old days." As a result, it is important for pathologists to become familiar with the trends in their specialty and have familiarity with the legal issues presented by these trends.

  11. Pathological narcissism and the obstruction of love.

    PubMed

    Kealy, David; Ogrodniczuk, John S

    2014-03-01

    Pathological narcissism is a form of maladaptive self-regulation that impedes the capacity to love. Although narcissism is often construed as excessive self-love, individuals with pathological narcissism are impaired in being able to love themselves as well as others. With the subject of impaired love in mind, we review selected conceptualizations from an enormous and diverse psychodynamic literature on narcissism. Major theoretical approaches illustrate a number of psychodynamics associated with narcissistic self-regulatory problems. This paper provides a concise overview of major conceptual themes regarding pathological narcissism and impaired capacity to love.

  12. Redox Regulation of Endothelial Cell Fate

    PubMed Central

    Song, Ping; Zou, Ming-Hui

    2014-01-01

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

  13. 78 FR 20614 - Application(s) for Duty-Free Entry of Scientific Instruments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-04-05

    ... will be used to help understand how the human body functions normally, such as in learning, memory or hearing, and to understand the pathologies of human diseases. In order to understand these functions, this...

  14. Level of Agreement between Self and Spouse in the Assessment of Personality Pathology

    PubMed Central

    South, Susan C.; Oltmanns, Thomas F.; Johnson, Jarrod; Turkheimer, Eric

    2011-01-01

    Informant reports can provide important information regarding the presence of pathological personality traits, and they can serve as useful supplements to self-report instruments. Ratings from a spouse may be a particularly valuable source of personality assessment because spouses are very well acquainted with the target person, have typically known the person for a long time, and witness behaviors across a variety of situations. In the current study, self- and spouse report measures based on the DSM-IV personality disorder criteria were collected from a non-clinical sample of 82 couples (N=164). Agreement between self- and spouse report for several pathological personality factors was significant and somewhat higher than has been found for self- and peer agreement. Nevertheless, the magnitude of self-spouse agreement was still moderate in size (Mean r=.36). Findings are discussed with regard to utilizing spouse-report in the assessment of personality pathology. PMID:21220382

  15. [The musician's hand: aspects of music physiology and performing arts medicine].

    PubMed

    Blum, J

    2000-09-01

    Musicians are particularly demanding hand patients. Increased expectancy towards the hand surgeon as well as principle aversion to any kind of operative treatment of the musician's hand impede the relationship between hand surgeon and patient. Knowledge and experience of the specific demands towards the musician's hand--including the background of basics in physiology of music making and instrumental techniques--facilitate history taking, examinations, diagnosing as well as the selection of therapy. Besides tendinitis and tendovaginitis, pathologies of the musician's hand are not more frequent compared to the entire population. Still several pathologies reach a significantly pronounced importance through the specific professional requirements. This is true especially for peripheral nerve compression syndromes, arthritis, ganglia, contractures, joint laxity and focal dystonias. The treatment of these disorders and hand trauma require, besides an utmost of hand surgical care, creativity and the implementation of the professional musical surroundings in therapy and rehabilitation, including also the musical instruments. The indication for surgery might be restrained in certain cases, although there are, without doubt, situations, when a professional musician should be operated on at an early stage. This should enhance a rapid return to play the musical instrument and to exercise delicate and demanding skilled movement patterns of his hand.

  16. 78 FR 666 - Treasury Inflation-Protected Securities Issued at a Premium; Bond Premium Carryforward

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-04

    ... regulations that provide guidance on the tax treatment of a debt instrument with a bond premium carryforward... contains final regulations that provide guidance on the tax treatment of Treasury Inflation-Protected... debt instruments. The text of the temporary regulations in this document also serves as the text of the...

  17. The gut in iron homeostasis: role of HIF-2 under normal and pathological conditions

    PubMed Central

    Mastrogiannaki, Maria; Matak, Pavle

    2013-01-01

    Although earlier, seminal studies demonstrated that the gut per se has the intrinsic ability to regulate the rates of iron absorption, the spotlight in the past decade has been placed on the systemic regulation of iron homeostasis by the hepatic hormone hepcidin and the molecular mechanisms that regulate its expression. Recently, however, attention has returned to the gut based on the finding that hypoxia inducible factor-2 (HIF-2α) regulates the expression of key genes that contribute to iron absorption. Here we review the current understanding of the molecular mechanisms that regulate iron homeostasis in the gut by focusing on the role of HIF-2 under physiological steady-state conditions and in the pathogenesis of iron-related diseases. We also discuss implications for adapting HIF-2–based therapeutic strategies in iron-related pathological conditions. PMID:23678007

  18. Hippo Signaling: Key Emerging Pathway in Cellular and Whole-Body Metabolism.

    PubMed

    Ardestani, Amin; Lupse, Blaz; Maedler, Kathrin

    2018-05-05

    The evolutionarily conserved Hippo pathway is a key regulator of organ size and tissue homeostasis. Its dysregulation is linked to multiple pathological disorders. In addition to regulating development and growth, recent studies show that Hippo pathway components such as MST1/2 and LATS1/2 kinases, as well as YAP/TAZ transcriptional coactivators, are regulated by metabolic pathways and that the Hippo pathway controls metabolic processes at the cellular and organismal levels in physiological and metabolic disease states such as obesity, type 2 diabetes (T2D), nonalcoholic fatty liver disease (NAFLD), cardiovascular disorders, and cancer. In this review we summarize the connection between key Hippo components and metabolism, and how this interplay regulates cellular metabolism and metabolic pathways. The emerging function of Hippo in the regulation of metabolic homeostasis under physiological and pathological conditions is highlighted. Copyright © 2018 Elsevier Ltd. All rights reserved.

  19. Diagnostic change and personality stability following functional restoration treatment in chronic low back pain patients.

    PubMed

    Vittengl, J R; Clark, L A; Owen-Salters, E; Gatchel, R J

    1999-03-01

    This study examined personality pathology in a group of patients with chronic low back pain (CLBP) using both diagnostic interviews and dimensional self-report instruments. A group of CLBP patients (N = 125) was assessed before functional restoration treatment and compared with a matched normal comparison group (N = 75). The CLBP group evidenced broad personality pathology in all assessment modes pretreatment relative to the normal comparison sample. In addition, two subsamples of CLBP patients (n = 49 and n = 56) were assessed after treatment. Reductions in personality pathology between pre- and posttreatment assessments were more pronounced for diagnostic interview than dimensional self-report assessments. These results are discussed in the context of personality assessment and CLBP.

  20. β-Arrestin1 regulates γ-secretase complex assembly and modulates amyloid-β pathology

    PubMed Central

    Liu, Xiaosong; Zhao, Xiaohui; Zeng, Xianglu; Bossers, Koen; Swaab, Dick F; Zhao, Jian; Pei, Gang

    2013-01-01

    Alzheimer's disease (AD) is a progressive and complex neurodegenerative disease in which the γ-secretase-mediated amyloid-β (Aβ) pathology plays an important role. We found that a multifunctional protein, β-arrestin1, facilitated the formation of NCT/APH-1 (anterior pharynx-defective phenotype 1) precomplex and mature γ-secretase complex through its functional interaction with APH-1. Deficiency of β-arrestin1 or inhibition of binding of β-arrestin1 with APH-1 by small peptides reduced Aβ production without affecting Notch processing. Genetic ablation of β-arrestin1 diminished Aβ pathology and behavioral deficits in transgenic AD mice. Moreover, in brains of sporadic AD patients and transgenic AD mice, the expression of β-arrestin1 was upregulated and correlated well with neuropathological severity and senile Aβ plaques. Thus, our study identifies a regulatory mechanism underlying both γ-secretase assembly and AD pathogenesis, and indicates that specific reduction of Aβ pathology can be achieved by regulation of the γ-secretase assembly. PMID:23208420

  1. Streamlined sign-out of capillary protein electrophoresis using middleware and an open-source macro application.

    PubMed

    Mathur, Gagan; Haugen, Thomas H; Davis, Scott L; Krasowski, Matthew D

    2014-01-01

    Interfacing of clinical laboratory instruments with the laboratory information system (LIS) via "middleware" software is increasingly common. Our clinical laboratory implemented capillary electrophoresis using a Sebia(®) Capillarys-2™ (Norcross, GA, USA) instrument for serum and urine protein electrophoresis. Using Data Innovations Instrument Manager, an interface was established with the LIS (Cerner) that allowed for bi-directional transmission of numeric data. However, the text of the interpretive pathology report was not properly transferred. To reduce manual effort and possibility for error in text data transfer, we developed scripts in AutoHotkey, a free, open-source macro-creation and automation software utility. Scripts were written to create macros that automated mouse and key strokes. The scripts retrieve the specimen accession number, capture user input text, and insert the text interpretation in the correct patient record in the desired format. The scripts accurately and precisely transfer narrative interpretation into the LIS. Combined with bar-code reading by the electrophoresis instrument, the scripts transfer data efficiently to the correct patient record. In addition, the AutoHotKey script automated repetitive key strokes required for manual entry into the LIS, making protein electrophoresis sign-out easier to learn and faster to use by the pathology residents. Scripts allow for either preliminary verification by residents or final sign-out by the attending pathologist. Using the open-source AutoHotKey software, we successfully improved the transfer of text data between capillary electrophoresis software and the LIS. The use of open-source software tools should not be overlooked as tools to improve interfacing of laboratory instruments.

  2. Exploring the Neural Basis of Avatar Identification in Pathological Internet Gamers and of Self-Reflection in Pathological Social Network Users

    PubMed Central

    Leménager, Tagrid; Dieter, Julia; Hill, Holger; Hoffmann, Sabine; Reinhard, Iris; Beutel, Martin; Vollstädt-Klein, Sabine; Kiefer, Falk; Mann, Karl

    2016-01-01

    Background and aims Internet gaming addiction appears to be related to self-concept deficits and increased angular gyrus (AG)-related identification with one’s avatar. For increased social network use, a few existing studies suggest striatal-related positive social feedback as an underlying factor. However, whether an impaired self-concept and its reward-based compensation through the online presentation of an idealized version of the self are related to pathological social network use has not been investigated yet. We aimed to compare different stages of pathological Internet game and social network use to explore the neural basis of avatar and self-identification in addictive use. Methods About 19 pathological Internet gamers, 19 pathological social network users, and 19 healthy controls underwent functional magnetic resonance imaging while completing a self-retrieval paradigm, asking participants to rate the degree to which various self-concept-related characteristics described their self, ideal, and avatar. Self-concept-related characteristics were also psychometrically assessed. Results Psychometric testing indicated that pathological Internet gamers exhibited higher self-concept deficits generally, whereas pathological social network users exhibit deficits in emotion regulation only. We observed left AG hyperactivations in Internet gamers during avatar reflection and a correlation with symptom severity. Striatal hypoactivations during self-reflection (vs. ideal reflection) were observed in social network users and were correlated with symptom severity. Discussion and conclusion Internet gaming addiction appears to be linked to increased identification with one’s avatar, evidenced by high left AG activations in pathological Internet gamers. Addiction to social networks seems to be characterized by emotion regulation deficits, reflected by reduced striatal activation during self-reflection compared to during ideal reflection. PMID:27415603

  3. Exploring the Neural Basis of Avatar Identification in Pathological Internet Gamers and of Self-Reflection in Pathological Social Network Users.

    PubMed

    Leménager, Tagrid; Dieter, Julia; Hill, Holger; Hoffmann, Sabine; Reinhard, Iris; Beutel, Martin; Vollstädt-Klein, Sabine; Kiefer, Falk; Mann, Karl

    2016-09-01

    Background and aims Internet gaming addiction appears to be related to self-concept deficits and increased angular gyrus (AG)-related identification with one's avatar. For increased social network use, a few existing studies suggest striatal-related positive social feedback as an underlying factor. However, whether an impaired self-concept and its reward-based compensation through the online presentation of an idealized version of the self are related to pathological social network use has not been investigated yet. We aimed to compare different stages of pathological Internet game and social network use to explore the neural basis of avatar and self-identification in addictive use. Methods About 19 pathological Internet gamers, 19 pathological social network users, and 19 healthy controls underwent functional magnetic resonance imaging while completing a self-retrieval paradigm, asking participants to rate the degree to which various self-concept-related characteristics described their self, ideal, and avatar. Self-concept-related characteristics were also psychometrically assessed. Results Psychometric testing indicated that pathological Internet gamers exhibited higher self-concept deficits generally, whereas pathological social network users exhibit deficits in emotion regulation only. We observed left AG hyperactivations in Internet gamers during avatar reflection and a correlation with symptom severity. Striatal hypoactivations during self-reflection (vs. ideal reflection) were observed in social network users and were correlated with symptom severity. Discussion and conclusion Internet gaming addiction appears to be linked to increased identification with one's avatar, evidenced by high left AG activations in pathological Internet gamers. Addiction to social networks seems to be characterized by emotion regulation deficits, reflected by reduced striatal activation during self-reflection compared to during ideal reflection.

  4. Intracellular Bioinorganic Chemistry and Cross Talk Among Different -Omics.

    PubMed

    Mendola, Diego La; Giacomelli, Chiara; Rizzarelli, Enrico

    2016-01-01

    The description of the cell life needs not only the knowledge of its genome and proteome, but also of the location of the metal ions and their different complex species in the subcellular compartments, that is of metallome. The cross-talk among these players of the omics' world secures the cellular homeostasis by means of a complex network, the alteration of which may give rise to many diseases. Copper and zinc ions levels regulate protein expression and metal-responsive transcription factors and in many pathologies metal dyshomeostasis induces to aberrant expression of different factors. microRNAs, a class of a small non-coding RNA molecules, act as RNA silencing and post-transcriptional regulators of gene expression contributing also to metal regulatory activity. The aim of the present review is to present how metals dyshomeostasis can be cause of diseases, involving different and specific metal chaperones, metal transporters, metalloproteins, small molecules and metal-sensing transcription factors. Two distinct classes of pathologies, cancer and osteoarthritis, are discussed starting from the metallostasis (metal homeostasis) and turning up to miRNAs regulation. The understanding of post-translational regulation, driven by metal ions sensing, may help to identify more specific targets and drugs to pathologies in which metal ions are involved.

  5. Endotoxin-induced basal respiration alterations of renal HK-2 cells: A sign of pathologic metabolism down-regulation

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

    Quoilin, C., E-mail: cquoilin@ulg.ac.be; Mouithys-Mickalad, A.; Duranteau, J.

    Highlights: Black-Right-Pointing-Pointer A HK-2 cells model of inflammation-induced acute kidney injury. Black-Right-Pointing-Pointer Two oximetry methods: high resolution respirometry and ESR spectroscopy. Black-Right-Pointing-Pointer Oxygen consumption rates of renal cells decrease when treated with LPS. Black-Right-Pointing-Pointer Cells do not recover normal respiration when the LPS treatment is removed. Black-Right-Pointing-Pointer This basal respiration alteration is a sign of pathologic metabolism down-regulation. -- Abstract: To study the mechanism of oxygen regulation in inflammation-induced acute kidney injury, we investigate the effects of a bacterial endotoxin (lipopolysaccharide, LPS) on the basal respiration of proximal tubular epithelial cells (HK-2) both by high-resolution respirometry and electron spin resonancemore » spectroscopy. These two complementary methods have shown that HK-2 cells exhibit a decreased oxygen consumption rate when treated with LPS. Surprisingly, this cellular respiration alteration persists even after the stress factor was removed. We suggested that this irreversible decrease in renal oxygen consumption after LPS challenge is related to a pathologic metabolic down-regulation such as a lack of oxygen utilization by cells.« less

  6. Hypoxia and Redox Signaling on Extracellular Matrix Remodeling: From Mechanisms to Pathological Implications.

    PubMed

    Labrousse-Arias, David; Martínez-Ruiz, Antonio; Calzada, María J

    2017-10-20

    The extracellular matrix (ECM) is an essential modulator of cell behavior that influences tissue organization. It has a strong relevance in homeostasis and translational implications for human disease. In addition to ECM structural proteins, matricellular proteins are important regulators of the ECM that are involved in a myriad of different pathologies. Recent Advances: Biochemical studies, animal models, and study of human diseases have contributed to the knowledge of molecular mechanisms involved in remodeling of the ECM, both in homeostasis and disease. Some of them might help in the development of new therapeutic strategies. This review aims to review what is known about some of the most studied matricellular proteins and their regulation by hypoxia and redox signaling, as well as the pathological implications of such regulation. Matricellular proteins have complex regulatory functions and are modulated by hypoxia and redox signaling through diverse mechanisms, in some cases with controversial effects that can be cell or tissue specific and context dependent. Therefore, a better understanding of these regulatory processes would be of great benefit and will open new avenues of considerable therapeutic potential. Characterizing the specific molecular mechanisms that modulate matricellular proteins in pathological processes that involve hypoxia and redox signaling warrants additional consideration to harness the potential therapeutic value of these regulatory proteins. Antioxid. Redox Signal. 27, 802-822.

  7. Florida Journal of Communication Disorders, 1996.

    ERIC Educational Resources Information Center

    Langhans, Joseph J., Ed.

    1996-01-01

    This annual volume is a compilation of professional articles and proceedings from a conference addressing timely issues in speech-language pathology and audiology. Featured articles include: (1) "Glottal Airflow: Instrumentation and Interpretation" (Christine M. Sapienza); (2) "Clinical Implications of Motor Speech Disorders in…

  8. Building blocks of the GIPU, Italian Group of Ultrastructural Pathology.

    PubMed

    Papa, V; Costa, R; Cenacchi, G

    2016-06-01

    The Italian Group of Ultrastructural Pathology, GIPU, is a scientific organization committed to promote the art and science of Electron Microscopy (EM) in the pathology field in Italy, sharing its professional work with a public audience. The history of the GIPU goes back to 1990s when a founder group set up the Italian Group of Ultrastructural Diagnostic (GIDU) in Milan. The central focus of annual meetings was on EM, transmission and scanning one, about interesting cases in which it was instrumental in diagnosis. In the 1990s, ultrastructure was still the gold standard for cell/tissue morphology, biology, biochemistry, diagnostic pathology, and played an important role in tailored medicine. So, especially transmission EM, could play a critical role in the diagnosis of various diseases as in human as in animals. Best topics of the annual scientific meetings of the group were kidney, muscle, heart, and liver pathology, infertility, neuropathology, respiratory diseases, skin diseases, storage diseases, tumor pathology, infectious diseases, parasitology, veterinary pathology and more. Nowadays, EM is a method whose importance for diagnosis and pathology is well established: it is still essential in several pathologies, helpful in others, and welcome implemented in eclectic research pathology. Omission of EM likely makes the studies suboptimal and wasteful. So, from 2007 the name of the group has been changed to the Italian Group of Ultrastructural Pathology (GIPU) to favor broader applications of EM also to pathology research field. During last decades, GIDU/GIPU has interconnected with international (Society for Ultrastructural Pathology) and european (European Society of Pathology and Joint Meeting with the European Electron Microscopy Working Group) scientific society, according its statute. By 1991, GIPU has had 40 members: membership in this Group is still open and welcome to all pathologists, PhD, electron microscopy technologists, pathology trainees, and researchers interested in pathology and electron microscopy. © Copyright Società Italiana di Anatomia Patologica e Citopatologia Diagnostica, Divisione Italiana della International Academy of Pathology.

  9. 42 CFR 485.701 - Basis and scope.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Therapy and Speech-Language Pathology Services § 485.701 Basis and scope. This subpart implements section 1861(p)(4) of the Act, which— (a) Defines outpatient physical therapy and speech pathology services; (b... records; and (c) Authorizes the Secretary to establish by regulation other health and safety requirements...

  10. Predicting Preservice Music Teachers' Performance Success in Instrumental Courses Using Self-Regulated Study Strategies and Predictor Variables

    ERIC Educational Resources Information Center

    Ersozlu, Zehra N.; Nietfeld, John L.; Huseynova, Lale

    2017-01-01

    The purpose of this study was to examine the extent to which self-regulated study strategies and predictor variables predict performance success in instrumental performance college courses. Preservice music teachers (N = 123) from a music education department in two state universities in Turkey completed the Music Self-Regulated Studying…

  11. Self-Regulated Learning in Singaporean Context: A Congeneric Approach of Confirmatory Factor Analysis

    ERIC Educational Resources Information Center

    Ng, Betsy; Wang, C. K. John; Liu, W. C.

    2017-01-01

    The motivated strategies for learning questionnaire (MSLQ) is widely used as a self-report instrument to assess students' motivation and self-regulation. This study utilized the MSLQ Junior High to examine the motivational beliefs and self-regulation of secondary school students (Grades 8 and 9) from Singapore. The instrument was slightly modified…

  12. The validity of the Personality Diagnostic Questionnaire-4 Narcissistic Personality Disorder scale for assessing pathological grandiosity.

    PubMed

    Hopwood, Christopher J; Donnellan, M Brent; Ackerman, Robert A; Thomas, Katherine M; Morey, Leslie C; Skodol, Andrew E

    2013-01-01

    Although controversy surrounds the definition and measurement of narcissism, the claim that pathological grandiosity is central to the construct generates little disagreement. Yet representations of pathological grandiosity vary across measures of narcissism, leading to conceptual confusion in the literature. The validity of a DSM-based measure of pathological narcissism, the Personality Diagnostic Questionnaire-4 Narcissistic Personality Disorder scale (PDQ-4 NPD), was evaluated in 1 clinical and 3 nonclinical samples (total N=2,391) for its ability to measure pathological grandiosity. Findings were generally supportive: average scores were higher in the clinical than nonclinical samples and the PDQ-4 NPD scale correlated most strongly with (a) other measures of NPD; (b) other DSM Cluster B personality disorders; (c) traits involving antagonism, hostility, and assertiveness; and (d) interpersonal distress and disaffiliative dominance. However, the low internal consistency of the PDQ-4 NPD scale and unexpected associations with Cluster A and obsessive-compulsive features point to potential psychometric weaknesses with this instrument. These findings are useful for evaluating the PDQ-4 NPD scale and for informing ongoing debates regarding how to define and assess pathological narcissism.

  13. Long non-coding RNA-CRNDE: a novel regulator of tumor growth and angiogenesis in hepatoblastoma.

    PubMed

    Dong, Rui; Liu, Xiang-Qi; Zhang, Bin-Bin; Liu, Bai-Hui; Zheng, Shan; Dong, Kui-Ran

    2017-06-27

    Long non-coding RNAs (lncRNAs) are involved in many biological processes, such as angiogenesis, invasion, cell proliferation, and apoptosis. They have emerged as key players in the pathology of several tumors, including hepatoblastoma. In this study, we elucidate the biological and clinical significance of CRNDE up-regulation in hepatoblastoma. CRNDE is significantly up-regulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. CRNDE knockdown reduces tumor growth and tumor angiogenesis in vivo, and decreases hepatoblastoma cell viability, proliferation, and angiogenic effect in vitro. Mechanistic studies show that CRNDE knockdown plays its anti-proliferation and anti-angiogenesis role via regulating mammalian target of rapamycin (mTOR) signaling. Taken together, this study reveals a crucial role of CRNDE in the pathology of hepatoblastoma. CRNDE may serve as a promising diagnostic marker and therapeutic target for hepatoblastoma.

  14. Examining the influence of actual-ideal self-discrepancies, depression, and escapism, on pathological gaming among massively multiplayer online adolescent gamers.

    PubMed

    Li, Dongdong; Liau, Albert; Khoo, Angeline

    2011-09-01

    This study examined whether actual-ideal self-discrepancy (AISD) is related to pathological gaming through escapism as a means of reducing depression for adolescent massively multiplayer online gamers. A Discrepancy-reduction Motivation model of pathological video gaming was tested. A survey was conducted on 161 adolescent gamers from secondary schools. Two mediation effects were tested using path analysis: (a) depression would mediate the relationship between AISDs and escapism, and (b) escapism would mediate the relationship between depression and pathological gaming. Results support the hypotheses stated above. The indirect effects of both AISD and depression were significant on pathological gaming. AISD and escapism also had direct effects on pathological gaming. The present study suggests that pathological behaviors may be over-regulated coping strategies of approaching the ideal self and avoiding the actual self.

  15. A comparison of the criterion validity of popular measures of narcissism and narcissistic personality disorder via the use of expert ratings.

    PubMed

    Miller, Joshua D; McCain, Jessica; Lynam, Donald R; Few, Lauren R; Gentile, Brittany; MacKillop, James; Campbell, W Keith

    2014-09-01

    The growing interest in the study of narcissism has resulted in the development of a number of assessment instruments that manifest only modest to moderate convergence. The present studies adjudicate among these measures with regard to criterion validity. In the 1st study, we compared multiple narcissism measures to expert consensus ratings of the personality traits associated with narcissistic personality disorder (NPD; Study 1; N = 98 community participants receiving psychological/psychiatric treatment) according to the Diagnostic and Statistical Manual of Mental Disorders (4th ed., text rev.; DSM-IV-TR; American Psychiatric Association, 2000) using 5-factor model traits as well as the traits associated with the pathological trait model according to the Diagnostic and Statistical Manual of Mental Disorders (5th ed.; American Psychiatric Association, 2013). In Study 2 (N = 274 undergraduates), we tested the criterion validity of an even larger set of narcissism instruments by examining their relations with measures of general and pathological personality, as well as psychopathology, and compared the resultant correlations to the correlations expected by experts for measures of grandiose and vulnerable narcissism. Across studies, the grandiose dimensions from the Five-Factor Narcissism Inventory (FFNI; Glover, Miller, Lynam, Crego, & Widiger, 2012) and the Narcissistic Personality Inventory (Raskin & Terry, 1988) provided the strongest match to expert ratings of DSM-IV-TR NPD and grandiose narcissism, whereas the vulnerable dimensions of the FFNI and the Pathological Narcissism Inventory (Pincus et al., 2009), as well as the Hypersensitive Narcissism Scale (Hendin & Cheek, 1997), provided the best match to expert ratings of vulnerable narcissism. These results should help guide researchers toward the selection of narcissism instruments that are most well suited to capturing different aspects of narcissism. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  16. Comparison of a pocket-size ultrasound device with a premium ultrasound machine: diagnostic value and time required in bedside ultrasound examination.

    PubMed

    Stock, Konrad Friedrich; Klein, Bettina; Steubl, Dominik; Lersch, Christian; Heemann, Uwe; Wagenpfeil, Stefan; Eyer, Florian; Clevert, Dir-Andre

    2015-10-01

    Time savings and clinical accuracy of a new miniature ultrasound device was investigated utilizing comparison with conventional high-end ultrasound instruments. Our objective was to determine appropriate usage and limitations of this diagnostic tool in internal medicine. We investigated 28 patients from the internal-medicine department. Patients were examined with the Acuson P10 portable device and a Sonoline Antares instrument in a cross-over design. All investigations were carried out at the bedside; the results were entered on a standardized report form. The time for the ultrasound examination (transfer time, setting up and disassembly, switching on and off, and complete investigation time) was recorded separately. Mean time for overall examination per patient with the portable ultrasound device was shorter (25.0 ± 4.5 min) than with the high-end machine (29.4 ± 4.4 min; p < 0.001). When measuring the size of liver, spleen, and kidneys, the values obtained differed significantly between portable device and the high-end instrument. In our study, we identified 113 pathological ultrasound findings with the high-end ultrasound machine, while 82 pathological findings (73%) were concordantly detected with the portable ultrasound device. The main diagnostic strengths of the portable device were in the detection of ascites (sensitivity 80%), diagnosis of fatty liver, and identification of severe parenchymal liver damage. The clinical utility of portable ultrasound machines is limited. There will be clinical roles for distinct clinical questions such as detection of ascites or pleural effusion when used by experienced examiners. However, sensitivity in detecting multiple pathologies is not comparable to high-end ultrasound machines.

  17. Analysis of verbal communication during teaching in the operating room and the potentials for surgical training.

    PubMed

    Blom, E M; Verdaasdonk, E G G; Stassen, L P S; Stassen, H G; Wieringa, P A; Dankelman, J

    2007-09-01

    Verbal communication in the operating room during surgical procedures affects team performance, reflects individual skills, and is related to the complexity of the operation process. During the procedural training of surgeons (residents), feedback and guidance is given through verbal communication. A classification method based on structural analysis of the contents was developed to analyze verbal communication. This study aimed to evaluate whether a classification method for the contents of verbal communication in the operating room could provide insight into the teaching processes. Eight laparoscopic cholecystectomies were videotaped. Two entire cholecystectomies and the dissection phase of six additional procedures were analyzed by categorization of the communication in terms of type (4 categories: commanding, explaining, questioning, and miscellaneous) and content (9 categories: operation method, location, direction, instrument handling, visualization, anatomy and pathology, general, private, undefinable). The operation was divided into six phases: start, dissection, clipping, separating, control, closing. Classification of the communication during two entire procedures showed that each phase of the operation was dominated by different kinds of communication. A high percentage of explaining anatomy and pathology was found throughout the whole procedure except for the control and closing phases. In the dissection phases, 60% of verbal communication concerned explaining. These explaining communication events were divided as follows: 27% operation method, 19% anatomy and pathology, 25% location (positioning of the instrument-tissue interaction), 15% direction (direction of tissue manipulation), 11% instrument handling, and 3% other nonclassified instructions. The proposed classification method is feasible for analyzing verbal communication during surgical procedures. Communication content objectively reflects the interaction between surgeon and resident. This information can potentially be used to specify training needs, and may contribute to the evaluation of different training methods.

  18. Photolasertherapy for the treatment of infections in neurosurgery: experimental and clinical study

    NASA Astrophysics Data System (ADS)

    Lombard, Gian F.

    1996-12-01

    At the first time, the CO2 laser was utilised in infective neurosurgical pathology as a surgical cutting instrument to remove inflammatory pseudomembranes in chronic osteomyelitis, and as a vaporising instmment on the dura mater surface. Successively, the instrument, defocused and at a low power, was used for prolonged and diffuse photo coagulation ofthe surgical cavity, particularly, ofthe dural surface and ofthe osteomyelitic bone edges, with the aim to sterilise tissues. So, we saw a shortening of the average time of wound healing and a lack of recurrence of the septic pathology. Then, we have treated, with CO2 laser, intracranial infective pathology: i.e. primary abscesses, capsulated or not, circumscribed purulent encephalitis, secondary abscesses in surgical cavities (patients operated for intracranial hematomas and tumors). In these cases we have obtained a lack of septic recurrences and an improvement ofneurological post-operative course. Thank to these results, we have continued to use laser in infective pathology; for giving an experimental support to these results we have carried on researches in vivo (on the experimental animal) to see the interaction between the laser and inflammatory tissue, and in vitro (on bacterial culture: in solid and liquid media) to see the laser effect on the bacterial cell. The bacterial cell has been also sensibiized to the photo dynamic effect of the laser (Argon, He-Ne), with hematoporphyrin. The goal of these experiments is to understand the role of thermal, photochemical, and mechanic resonance laser effects in the interaction between laser radiation and bacterial cell.

  19. The Pathological Buying Screener: Development and Psychometric Properties of a New Screening Instrument for the Assessment of Pathological Buying Symptoms

    PubMed Central

    Trotzke, Patrick; Mitchell, James E.; de Zwaan, Martina

    2015-01-01

    The study was designed to develop a new screening instrument for pathological buying (PB), and to examine its psychometric properties in a large-scale sample. By using a facet theoretical approach and based on literature as well as on clinical experience, a 20-item Pathological Buying Screener (PBS) was developed and administered to a representative German sample (n = 2,539). Valid data were available from 2,403 participants who were subjects for three subsequent empirical studies. The first study explored the factor structure using exploratory factor analyses in a subsample of 498 participants. Based on factor loadings, a 13-item version with the two factors loss of control / consequences and excessive buying behavior was revealed. This two-factor model was confirmed in study 2 by confirmatory factor analysis performed on another subsample (n = 1,905). Study 3 investigated age and gender effects and convergent validity of the PBS using the Compulsive Buying Scale (CBS) in the full sample (N = 2,403). The total PBS score was adequately correlated with the CBS score. Hierarchical regression analyses with the CBS score as the dependent variable and the two PBS factors as the predictors indicated an own incremental validity of the two factors in participants ≤ 65 years. The reliability of the total score as well as of the two subscales was good to excellent. Overall, the PBS represents a useful measure for PB. Future studies are needed to replicate the two-factor structure in clinical samples and to define a valid cutoff for PB. PMID:26488872

  20. The Pathological Buying Screener: Development and Psychometric Properties of a New Screening Instrument for the Assessment of Pathological Buying Symptoms.

    PubMed

    Müller, Astrid; Trotzke, Patrick; Mitchell, James E; de Zwaan, Martina; Brand, Matthias

    2015-01-01

    The study was designed to develop a new screening instrument for pathological buying (PB), and to examine its psychometric properties in a large-scale sample. By using a facet theoretical approach and based on literature as well as on clinical experience, a 20-item Pathological Buying Screener (PBS) was developed and administered to a representative German sample (n = 2,539). Valid data were available from 2,403 participants who were subjects for three subsequent empirical studies. The first study explored the factor structure using exploratory factor analyses in a subsample of 498 participants. Based on factor loadings, a 13-item version with the two factors loss of control / consequences and excessive buying behavior was revealed. This two-factor model was confirmed in study 2 by confirmatory factor analysis performed on another subsample (n = 1,905). Study 3 investigated age and gender effects and convergent validity of the PBS using the Compulsive Buying Scale (CBS) in the full sample (N = 2,403). The total PBS score was adequately correlated with the CBS score. Hierarchical regression analyses with the CBS score as the dependent variable and the two PBS factors as the predictors indicated an own incremental validity of the two factors in participants ≤ 65 years. The reliability of the total score as well as of the two subscales was good to excellent. Overall, the PBS represents a useful measure for PB. Future studies are needed to replicate the two-factor structure in clinical samples and to define a valid cutoff for PB.

  1. 32 CFR 21.300 - What instruments are subject to the DoD Grant and Agreement Regulations (DoDGARs)?

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 1 2012-07-01 2012-07-01 false What instruments are subject to the DoD Grant and Agreement Regulations (DoDGARs)? 21.300 Section 21.300 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-GENERAL...

  2. 32 CFR 21.300 - What instruments are subject to the DoD Grant and Agreement Regulations (DoDGARs)?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false What instruments are subject to the DoD Grant and Agreement Regulations (DoDGARs)? 21.300 Section 21.300 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-GENERAL...

  3. 32 CFR 21.300 - What instruments are subject to the DoD Grant and Agreement Regulations (DoDGARs)?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 1 2011-07-01 2011-07-01 false What instruments are subject to the DoD Grant and Agreement Regulations (DoDGARs)? 21.300 Section 21.300 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-GENERAL...

  4. 32 CFR 21.300 - What instruments are subject to the DoD Grant and Agreement Regulations (DoDGARs)?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 1 2013-07-01 2013-07-01 false What instruments are subject to the DoD Grant and Agreement Regulations (DoDGARs)? 21.300 Section 21.300 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-GENERAL...

  5. 48 CFR 4.1601 - Policy.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Policy. 4.1601 Section 4... MATTERS Unique Procurement Instrument Identifiers 4.1601 Policy. (a) Procurement Instrument Identifier... regulations, applicable authorities, and agency policies and procedures. (e) Agencies shall not change the...

  6. 48 CFR 4.1601 - Policy.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Policy. 4.1601 Section 4... MATTERS Unique Procurement Instrument Identifiers 4.1601 Policy. (a) Procurement Instrument Identifier... regulations, applicable authorities, and agency policies and procedures. (e) Agencies shall not change the...

  7. C/EBPβ regulates delta-secretase expression and mediates pathogenesis in mouse models of Alzheimer's disease.

    PubMed

    Wang, Zhi-Hao; Gong, Ke; Liu, Xia; Zhang, Zhentao; Sun, Xiaoou; Wei, Zheng Zachory; Yu, Shan Ping; Manfredsson, Fredric P; Sandoval, Ivette M; Johnson, Peter F; Jia, Jianping; Wang, Jian-Zhi; Ye, Keqiang

    2018-05-03

    Delta-secretase cleaves both APP and Tau to mediate the formation of amyloid plaques and neurofibrillary tangle in Alzheimer's disease (AD). However, how aging contributes to an increase in delta-secretase expression and AD pathologies remains unclear. Here we show that a CCAAT-enhancer-binding protein (C/EBPβ), an inflammation-regulated transcription factor, acts as a key age-dependent effector elevating both delta-secretase (AEP) and inflammatory cytokines expression in mediating pathogenesis in AD mouse models. We find that C/EBPβ regulates delta-secretase transcription and protein levels in an age-dependent manner. Overexpression of C/EBPβ in young 3xTg mice increases delta-secretase and accelerates the pathological features including cognitive dysfunctions, which is abolished by inactive AEP C189S. Conversely, depletion of C/EBPβ from old 3xTg or 5XFAD mice diminishes delta-secretase and reduces AD pathologies, leading to amelioration of cognitive impairment in these AD mouse models. Thus, our findings support that C/EBPβ plays a pivotal role in AD pathogenesis via increasing delta-secretase expression.

  8. Roles of leptin, adiponectin and resistin in the transcriptional regulation of steroidogenic genes contributing to decreased Leydig cells function in obesity.

    PubMed

    Roumaud, Pauline; Martin, Luc J

    2015-10-01

    The increase in obesity rate is a major public health issue associated with increased pathological conditions such as type 2 diabetes or cardiovascular diseases. Obesity also contributes to decreased testosterone levels in men. Indeed, the adipose tissue is an endocrine organ which produces hormones such as leptin, adiponectin and resistin. Obesity results in pathological accumulations of leptin and resistin, whereas adiponectin plasma levels are markedly reduced, all having a negative impact on testosterone synthesis. This review focuses on current knowledge related to transcriptional regulation of Leydig cells' steroidogenesis by leptin, adiponectin and resistin. We show that there are crosstalks between the regulatory mechanisms of these hormones and androgen production which may result in a dramatic negative influence on testosterone plasma levels. Indeed leptin, adiponectin and resistin can impact expression of different steroidogenic genes such as Star, Cyp11a1 or Sf1. Further investigations will be required to better define the implications of adipose derived hormones on regulation of steroidogenic genes expression within Leydig cells under physiological as well as pathological conditions.

  9. 78 FR 39712 - University of Illinois, et al.; Notice of Decision on Applications for Duty-Free Entry of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-07-02

    .... Reasons: The instrument will be used to help understand how the human body functions normally, such as in learning, memory or hearing, and to understand the pathologies of human diseases. In order to understand...

  10. Method of Testing Oxygen Regulators

    NASA Technical Reports Server (NTRS)

    Sontag, Harcourt; Borlik, E L

    1935-01-01

    Oxygen regulators are used in aircraft to regulate automatically the flow of oxygen to the pilot from a cylinder at pressures ranging up to 150 atmospheres. The instruments are adjusted to open at an altitude of about 15,000 ft. and thereafter to deliver oxygen at a rate which increases with the altitude. The instruments are tested to determine the rate of flow of oxygen delivered at various altitudes and to detect any mechanical defects which may exist. A method of testing oxygen regulators was desired in which the rate of flow could be determined more accurately than by the test method previously used (reference 1) and by which instruments defective mechanically could be detected. The new method of test fulfills these requirements.

  11. Pavlovian-to-instrumental transfer: A new paradigm to assess pathological mechanisms with regard to the use of Internet applications.

    PubMed

    Vogel, Verena; Kollei, Ines; Duka, Theodora; Snagowski, Jan; Brand, Matthias; Müller, Astrid; Loeber, Sabine

    2018-07-16

    At present, there is a considerable lack of human studies that investigated the impact of conditioned cues on instrumental responding although these processes are considered as core mechanisms contributing to the development and maintenance of addictive behaviours. No studies are available that assessed these processes with regard to Internet gaming or Internet shopping applications. We thus developed a Pavlovian-to-instrumental transfer (PIT)-Paradigm implementing appetitive stimuli related to Internet gaming and Internet shopping applications and investigated whether an outcome-specific PIT-Effect is observed. In addition, we assessed whether the problematic use of gaming or shopping applications, personality traits and stress would affect the acquisition of knowledge of the experimental contingencies during Pavlovian training and the impact of conditioned stimuli on instrumental responding. A PIT-Paradigm, screenings for Internet gaming disorder and Internet shopping disorder (s-IAT), and questionnaires on personality traits (NEO-FFI, BIS-15) and perceived stress (PSQ20) were administered to sixty-six participants. The PIT-Paradigm demonstrated the effects of stimuli conditioned to rewards related to Internet gaming and Internet shopping applications on instrumental responding to obtain such rewards. Findings also indicated that severity of problematic Internet gaming, but not Internet shopping, contributed to the acquisition of knowledge of the experimental contingencies. Stress, extraversion, neuroticism and gender emerged as further predictors. The strength of expectancy of the different reinforcers affected the 'gaming PIT'-Effect; however, none of the variables assessed in the present study showed any effect on the 'shopping PIT'-Effect. Future studies including participants with pathological use patterns that can be classified as internet use disorder are warranted to extend these findings. Copyright © 2018 Elsevier B.V. All rights reserved.

  12. ASVCP guidelines: quality assurance for point-of-care testing in veterinary medicine.

    PubMed

    Flatland, Bente; Freeman, Kathleen P; Vap, Linda M; Harr, Kendal E

    2013-12-01

    Point-of-care testing (POCT) refers to any laboratory testing performed outside the conventional reference laboratory and implies close proximity to patients. Instrumental POCT systems consist of small, handheld or benchtop analyzers. These have potential utility in many veterinary settings, including private clinics, academic veterinary medical centers, the community (eg, remote area veterinary medical teams), and for research applications in academia, government, and industry. Concern about the quality of veterinary in-clinic testing has been expressed in published veterinary literature; however, little guidance focusing on POCT is available. Recognizing this void, the ASVCP formed a subcommittee in 2009 charged with developing quality assurance (QA) guidelines for veterinary POCT. Guidelines were developed through literature review and a consensus process. Major recommendations include (1) taking a formalized approach to POCT within the facility, (2) use of written policies, standard operating procedures, forms, and logs, (3) operator training, including periodic assessment of skills, (4) assessment of instrument analytical performance and use of both statistical quality control and external quality assessment programs, (5) use of properly established or validated reference intervals, (6) and ensuring accurate patient results reporting. Where possible, given instrument analytical performance, use of a validated 13s control rule for interpretation of control data is recommended. These guidelines are aimed at veterinarians and veterinary technicians seeking to improve management of POCT in their clinical or research setting, and address QA of small chemistry and hematology instruments. These guidelines are not intended to be all-inclusive; rather, they provide a minimum standard for maintenance of POCT instruments in the veterinary setting. © 2013 American Society for Veterinary Clinical Pathology and European Society for Veterinary Clinical Pathology.

  13. [Theory of functional systems: postulates and principles of human body construction in health and pathology].

    PubMed

    Sudakov, K V

    2007-01-01

    It is shown that many functional systems with different level of organization harmoniously interact in healthy humans and animals. Early stress discoordinates information links of functional systems which can be easily corrected by nonpharmacological methods. Long-term and intensive stress disturbs mechanisms of self-regulation of the weakest functional systems. This converts a pathological process to a molecular tissue level. Principles of systemic functional human organization in pathology and compensation of impaired functions are considered.

  14. Instruments to assess patients with rotator cuff pathology: a systematic review of measurement properties.

    PubMed

    Longo, Umile Giuseppe; Saris, Daniël; Poolman, Rudolf W; Berton, Alessandra; Denaro, Vincenzo

    2012-10-01

    The aims of this study were to obtain an overview of the methodological quality of studies on the measurement properties of rotator cuff questionnaires and to describe how well various aspects of the design and statistical analyses of studies on measurement properties are performed. A systematic review of published studies on the measurement properties of rotator cuff questionnaires was performed. Two investigators independently rated the quality of the studies using the Consensus-based Standards for the selection of health Measurement Instruments checklist. This checklist was developed in an international Delphi consensus study. Sixteen studies were included, in which two measurement instruments were evaluated, namely the Western Ontario Rotator Cuff Index and the Rotator Cuff Quality-of-Life Measure. The methodological quality of the included studies was adequate on some properties (construct validity, reliability, responsiveness, internal consistency, and translation) but need to be improved on other aspects. The most important methodological aspects that need to be developed are as follows: measurement error, content validity, structural validity, cross-cultural validity, criterion validity, and interpretability. Considering the importance of adequate measurement properties, it is concluded that, in the field of rotator cuff pathology, there is room for improvement in the methodological quality of studies measurement properties. II.

  15. Investigation of human locomotion using Penny & Giles electrogoniometer

    NASA Astrophysics Data System (ADS)

    Jaworek, Krzysztof; Derlatka, Marcin; Dominikowski, Mateusz

    1999-04-01

    This paper deals with the experimental measurements, data filtering and theoretical representation of the angular position of a human led in 3D space during normal and pathological walking. The angular position of a human leg during walking in sagittal plane was measured by a new electrogoniometer made by a UK company named Penny & Giles. This system is a spatial mechanism made of a group of links which are coupled by proper angular sensor. This instrument enables an indirect evaluation of the angular position of a human leg in the 3D space from knowledge of the system geometry and from the angular value readings. This instrument is light, small-sized technologically new and is easy to use. However, its dynamics features have not been analyzed in the literature. Therefore we decided to analyze the instrument in order to built a DWT (Discrete Wavelets Transform) filter for filtering data recorded by a electrogoniometer Penny & Giles. We built filter corresponding to Daubechies wavelets, DAUB #20. The DWT filter is sufficient for filtering high frequency noise which exists during experimental measurement of the angular position of a human leg during normal and pathological gait. Filtering using Daubechies wavelets--DAUB #20 is more efficient than commercial numerical filtering delivered by Penny & Giles company.

  16. Tissue Physiology and Pathology of Aromatase

    PubMed Central

    Stocco, Carlos

    2011-01-01

    Summary Aromatase is expressed in multiple tissues, indicating a crucial role for locally produced oestrogens in the differentiation, regulation and normal function of several organs and processes. This review is an overview of the role of aromatase in different tissues under normal physiological conditions and its contribution to the development of some oestrogen-related pathologies. PMID:22108547

  17. Behaviour, Physiology and Experience of Pathological Laughing and Crying in Amyotrophic Lateral Sclerosis

    ERIC Educational Resources Information Center

    Olney, Nicholas T.; Goodkind, Madeleine S.; Lomen-Hoerth, Catherine; Whalen, Patrick K.; Williamson, Craig A.; Holley, Deborah E.; Verstaen, Alice; Brown, Laurel M.; Miller, Bruce L.; Kornak, John; Levenson, Robert W.; Rosen, Howard J.

    2011-01-01

    Pathological laughing and crying is a disorder of emotional expression seen in a number of neurological diseases. The aetiology is poorly understood, but clinical descriptions suggest a disorder of emotion regulation. The goals of this study were: (i) to characterize the subjective, behavioural and physiological emotional reactions that occur…

  18. The Role of Pre-Service Teachers' Perceived Instrumentality, Goal Commitment, and Motivation in Their Self-Regulation Strategies for Learning in Teacher Education Courses

    ERIC Educational Resources Information Center

    Lee, Jumi; Turner, Jeannine

    2017-01-01

    This study investigated the influence of pre-service teachers' (n = 142) perceived endogenous/exogenous instrumentality, goal commitment, and intrinsic/extrinsic motivation on their use of self-regulation strategies (effort regulation, management of time and study environment) for their teacher-education courses. Data were drawn from a customised…

  19. Long non-coding RNA-CRNDE: a novel regulator of tumor growth and angiogenesis in hepatoblastoma

    PubMed Central

    Dong, Rui; Liu, Xiang-Qi; Zhang, Bin-Bin; Liu, Bai-Hui; Zheng, Shan; Dong, Kui-Ran

    2017-01-01

    Long non-coding RNAs (lncRNAs) are involved in many biological processes, such as angiogenesis, invasion, cell proliferation, and apoptosis. They have emerged as key players in the pathology of several tumors, including hepatoblastoma. In this study, we elucidate the biological and clinical significance of CRNDE up-regulation in hepatoblastoma. CRNDE is significantly up-regulated in human hepatoblastoma specimens and metastatic hepatoblastoma cell lines. CRNDE knockdown reduces tumor growth and tumor angiogenesis in vivo, and decreases hepatoblastoma cell viability, proliferation, and angiogenic effect in vitro. Mechanistic studies show that CRNDE knockdown plays its anti-proliferation and anti-angiogenesis role via regulating mammalian target of rapamycin (mTOR) signaling. Taken together, this study reveals a crucial role of CRNDE in the pathology of hepatoblastoma. CRNDE may serve as a promising diagnostic marker and therapeutic target for hepatoblastoma. PMID:28178668

  20. A-kinase anchoring proteins that regulate cardiac remodeling.

    PubMed

    Carnegie, Graeme K; Burmeister, Brian T

    2011-11-01

    In response to injury or stress, the adult heart undergoes maladaptive changes, collectively defined as pathological cardiac remodeling. Here, we focus on the role of A-kinase anchoring proteins (AKAPs) in 3 main areas associated with cardiac remodeling and the progression of heart failure: excitation-contraction coupling, sarcomeric regulation, and induction of pathological hypertrophy. AKAPs are a diverse family of scaffold proteins that form multiprotein complexes, integrating cAMP signaling with protein kinases, phosphatases, and other effector proteins. Many AKAPs have been characterized in the heart, where they play a critical role in modulating cardiac function.

  1. A-Kinase Anchoring Proteins That Regulate Cardiac Remodeling

    PubMed Central

    Carnegie, Graeme K.; Burmeister, Brian T.

    2012-01-01

    In response to injury or stress, the adult heart undergoes maladaptive changes, collectively defined as pathological cardiac remodeling. Here, we focus on the role of A-kinase anchoring proteins (AKAPs) in 3 main areas associated with cardiac remodeling and the progression of heart failure: excitation–contraction coupling, sarcomeric regulation, and induction of pathological hypertrophy. AKAPs are a diverse family of scaffold proteins that form multi-protein complexes, integrating cAMP signaling with protein kinases, phosphatases, and other effector proteins. Many AKAPs have been characterized in the heart, where they play a critical role in modulating cardiac function. PMID:22075671

  2. The complexity of epigenetic diseases.

    PubMed

    Brazel, Ailbhe Jane; Vernimmen, Douglas

    2016-01-01

    Over the past 30 years, a plethora of pathogenic mutations affecting enhancer regions and epigenetic regulators have been identified. Coupled with more recent genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS) implicating major roles for regulatory mutations in disease, it is clear that epigenetic mechanisms represent important biomarkers for disease development and perhaps even therapeutic targets. Here, we discuss the diversity of disease-causing mutations in enhancers and epigenetic regulators, with a particular focus on cancer. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

  3. Level of agreement between self and spouse in the assessment of personality pathology.

    PubMed

    South, Susan C; Oltmanns, Thomas F; Johnson, Jarrod; Turkheimer, Eric

    2011-06-01

    Informant reports can provide important information regarding the presence of pathological personality traits, and they can serve as useful supplements to self-report instruments. Ratings from a spouse may be a particularly valuable source of personality assessment because spouses are very well acquainted with the target person, have typically known the person for a long time, and witness behaviors across a variety of situations. In the current study, self- and spouse report measures based on the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition (DSM-IV) personality disorder criteria were collected from a nonclinical sample of 82 couples (N = 164). Agreement between self- and spouse report for several pathological personality factors was significant and somewhat higher than has been found for self and peer agreement. Nevertheless, the magnitude of self-spouse agreement was still moderate in size (mean r = .36). Findings are discussed with regard to using spouse report in the assessment of personality pathology.

  4. A Family Study of the DSM-5 Section III Personality Pathology Model Using the Personality Inventory for the DSM-5 (PID-5).

    PubMed

    Katz, Andrea C; Hee, Danelle; Hooker, Christine I; Shankman, Stewart A

    2017-10-03

    In Section III of the DSM-5, the American Psychiatric Association (APA) proposes a pathological personality trait model of personality disorders. The recommended assessment instrument is the Personality Inventory for the DSM-5 (PID-5), an empirically derived scale that assesses personality pathology along five domains and 25 facets. Although the PID-5 demonstrates strong convergent validity with other personality measures, no study has examined whether it identifies traits that run in families, another important step toward validating the DSM-5's dimensional model. Using a family study method, we investigated familial associations of PID-5 domain and facet scores in 195 families, examining associations between parents and offspring and across siblings. The Psychoticism, Antagonism, and Detachment domains showed significant familial aggregation, as did facets of Negative Affect and Disinhibition. Results are discussed in the context of personality pathology and family study methodology. The results also help validate the PID-5, given the familial nature of personality traits.

  5. 31 CFR 800.206 - Convertible voting instrument.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Convertible voting instrument. 800.206 Section 800.206 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF INVESTMENT SECURITY, DEPARTMENT OF THE TREASURY REGULATIONS PERTAINING TO MERGERS, ACQUISITIONS...

  6. Comparative Analysis of Various Aspects of Plateletpheresis on the Fenwal Amicus and Fresenius COM.TEC Cell Separator Instruments.

    PubMed

    Philip, Joseph; Biswas, Amit Kumar; Chatterjee, Tathagata; Mallhi, Rajiv Singh

    2014-01-01

    To compare the Fenwal Amicus and the Fresenius COM.TEC apheresis instruments regarding donor peripheral blood parameters, operational variables of the instruments, and quality control parameters of the product obtained. We performed 100 platelet collections from 100 voluntary donors using the 2 studied devices. We measured platelet count using an automated analyzer and analyzed the activation statuses using a flow cytometer. The median time needed to perform the procedures was significantly longer with the COM.TEC. However, the product we obtained using the Amicus instrument showed higher degrees of platelet-activation. All products we obtained with both instruments had white blood cell counts of less than 5 × 10(6) per bag. We observed no statistical difference regarding collection efficiency and collection rates between the devices. Both instruments collected platelets efficiently, with minimal donor discomfort. Compared with the COM.TEC instrument, the Amicus reached the platelet target yield more quickly; however, it displayed an increase in platelet activation. Copyright© by the American Society for Clinical Pathology (ASCP).

  7. RNA splicing and splicing regulator changes in prostate cancer pathology.

    PubMed

    Munkley, Jennifer; Livermore, Karen; Rajan, Prabhakar; Elliott, David J

    2017-09-01

    Changes in mRNA splice patterns have been associated with key pathological mechanisms in prostate cancer progression. The androgen receptor (abbreviated AR) transcription factor is a major driver of prostate cancer pathology and activated by androgen steroid hormones. Selection of alternative promoters by the activated AR can critically alter gene function by switching mRNA isoform production, including creating a pro-oncogenic isoform of the normally tumour suppressor gene TSC2. A number of androgen-regulated genes generate alternatively spliced mRNA isoforms, including a prostate-specific splice isoform of ST6GALNAC1 mRNA. ST6GALNAC1 encodes a sialyltransferase that catalyses the synthesis of the cancer-associated sTn antigen important for cell mobility. Genetic rearrangements occurring early in prostate cancer development place ERG oncogene expression under the control of the androgen-regulated TMPRSS2 promoter to hijack cell behaviour. This TMPRSS2-ERG fusion gene shows different patterns of alternative splicing in invasive versus localised prostate cancer. Alternative AR mRNA isoforms play a key role in the generation of prostate cancer drug resistance, by providing a mechanism through which prostate cancer cells can grow in limited serum androgen concentrations. A number of splicing regulator proteins change expression patterns in prostate cancer and may help drive key stages of disease progression. Up-regulation of SRRM4 establishes neuronal splicing patterns in neuroendocrine prostate cancer. The splicing regulators Sam68 and Tra2β increase expression in prostate cancer. The SR protein kinase SRPK1 that modulates the activity of SR proteins is up-regulated in prostate cancer and has already given encouraging results as a potential therapeutic target in mouse models.

  8. 78 FR 687 - Bond Premium Carryforward

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-04

    ... regulations provide guidance on the tax treatment of a taxable debt instrument with a bond premium... issue of the Federal Register, the IRS is issuing temporary regulations that provide guidance on the tax treatment of a debt instrument with a bond premium carryforward in the holder's final accrual period...

  9. Maternal 27-hydroxycholesterol concentrations during the course of pregnancy and in pregnancy pathologies.

    PubMed

    Winkler, Brigitte Sophia; Pecks, Ulrich; Najjari, Laila; Kleine-Eggebrecht, Nicola; Maass, Nicolai; Mohaupt, Markus; Escher, Geneviève

    2017-04-04

    The oxysterol 27-hydroxycholesterol (27-OHC) plays an important role in the regulation of cholesterol homeostasis. Pregnancy pathologies like preeclampsia (PE), HELLP-syndrome (HELLP), intrauterine growth restriction (IUGR) and intrahepatic cholestasis in pregnancy (ICP) are linked to disturbances in lipid metabolism. In the present study, we hypothesized a specific gestational regulation of 27-OHC and compromised 27-OHC levels due to placental and hepatic diseases in pregnancy resulting in a dysregulation of lipid metabolism. The 27-OHC was measured by gas-chromatography-mass spectrometry (GC-MS) and related to cholesterol concentrations. In the longitudinal cohort, a complete set of samples of healthy patients (n = 33) obtained at three different time points throughout gestation and once post-partum was analyzed. In the cross sectional cohort, patients with pregnancy pathologies (IUGR n = 14, PE n = 14, HELLP n = 7, ICP n = 7) were matched to a control group (CTRL) of equal gestational ages. The 27-OHC levels already increased in the first trimester despite lower TC concentrations (p < 0.05). During the course of pregnancy, a subtle rise in 27-OHC concentrations results in an overall decrease of 27-OHC/TC ratio in between the first (p < 0.05) and second trimester. The ratio remains stable thereafter including the post-partum period. No significant differences have been observed in pregnancy pathologies as compared to the CTRL group. In conclusion, 27-OHC may have a compensatory role in cholesterol metabolism early in pregnancy. The conserved 27-OHC/TC ratio in pregnancy pathologies suggest that neither the placenta nor the liver is majorly involved in the regulation of 27-OHC metabolism.

  10. A Preliminary Examination of the Role of Emotion Differentiation in the Relationship between Borderline Personality and Urges for Maladaptive Behaviors

    PubMed Central

    Dixon-Gordon, Katherine L.; Chapman, Alexander L.; Weiss, Nicole H.; Rosenthal, M. Zachary

    2015-01-01

    Background and Objectives Impulsive, maladaptive, and potentially self-damaging behaviors are a hallmark feature of borderline personality (BP) pathology. Difficulties with emotion regulation have been implicated in both BP pathology and maladaptive behaviors. One facet of emotion regulation that may be particularly important in the relation between BP pathology and urges for maladaptive behaviors is emotion differentiation. Methods Over one day, 84 participants high (n = 34) and low (n = 50) in BP pathology responded to questions regarding state emotions and urges to engage in maladaptive behaviors using handheld computers, in addition to a measure of emotion-related difficulties controlling impulsive behaviors. Results Results revealed that individuals high in BP pathology reported greater emotion-related impulsivity as well as daily urges to engage in maladaptive behaviors. However, the association between BP group and both baseline emotion-related impulsivity and daily urges for maladaptive behaviors was strongest among individuals who had low levels of positive emotion differentiation. Conversely, negative emotion differentiation did not significantly moderate the relationships between BP group and either emotion-related difficulties controlling impulsive behaviors or state urges for maladaptive behaviors. Limitations Limitations to the present study include the reliance upon an analogue sample and the relatively brief monitoring period. Conclusions Despite limitations, these results suggest that, among individuals with high BP pathology, the ability to differentiate between positive emotions may be a particularly important target in the reduction of maladaptive behaviors. PMID:25750478

  11. Differential and Conditional Activation of PKC-Isoforms Dictates Cardiac Adaptation during Physiological to Pathological Hypertrophy

    PubMed Central

    Naskar, Shaon; Datta, Kaberi; Mitra, Arkadeep; Pathak, Kanchan; Datta, Ritwik; Bansal, Trisha; Sarkar, Sagartirtha

    2014-01-01

    A cardiac hypertrophy is defined as an increase in heart mass which may either be beneficial (physiological hypertrophy) or detrimental (pathological hypertrophy). This study was undertaken to establish the role of different protein kinase-C (PKC) isoforms in the regulation of cardiac adaptation during two types of cardiac hypertrophy. Phosphorylation of specific PKC-isoforms and expression of their downstream proteins were studied during physiological and pathological hypertrophy in 24 week male Balb/c mice (Mus musculus) models, by reverse transcriptase-PCR, western blot analysis and M-mode echocardiography for cardiac function analysis. PKC-δ was significantly induced during pathological hypertrophy while PKC-α was exclusively activated during physiological hypertrophy in our study. PKC-δ activation during pathological hypertrophy resulted in cardiomyocyte apoptosis leading to compromised cardiac function and on the other hand, activation of PKC-α during physiological hypertrophy promoted cardiomyocyte growth but down regulated cellular apoptotic load resulting in improved cardiac function. Reversal in PKC-isoform with induced activation of PKC-δ and simultaneous inhibition of phospho-PKC-α resulted in an efficient myocardium to deteriorate considerably resulting in compromised cardiac function during physiological hypertrophy via augmentation of apoptotic and fibrotic load. This is the first report where PKC-α and -δ have been shown to play crucial role in cardiac adaptation during physiological and pathological hypertrophy respectively thereby rendering compromised cardiac function to an otherwise efficient heart by conditional reversal of their activation. PMID:25116170

  12. Interferon Regulatory Factor 7 Functions as a Novel Negative Regulator of Pathological Cardiac Hypertrophy

    PubMed Central

    Jiang, Ding-Sheng; Liu, Yu; Zhou, Heng; Zhang, Yan; Zhang, Xiao-Dong; Zhang, Xiao-Fei; Chen, Ke; Gao, Lu; Peng, Juan; Gong, Hui; Chen, Yingjie; Yang, Qinglin; Liu, Peter P.; Fan, Guo-Chang; Zou, Yunzeng; Li, Hongliang

    2017-01-01

    Cardiac hypertrophy is a complex pathological process that involves multiple factors including inflammation and apoptosis. Interferon regulatory factor 7 (IRF7) is a multifunctional regulator that participates in immune regulation, cell differentiation, apoptosis, and oncogenesis. However, the role of IRF7 in cardiac hypertrophy remains unclear. We performed aortic banding in cardiac-specific IRF7 transgenic mice, IRF7 knockout mice, and the wild-type littermates of these mice. Our results demonstrated that IRF7 was downregulated in aortic banding–induced animal hearts and cardiomyocytes that had been treated with angiotensin II or phenylephrine for 48 hours. Accordingly, heart-specific overexpression of IRF7 significantly attenuated pressure overload–induced cardiac hypertrophy, fibrosis, and dysfunction, whereas loss of IRF7 led to opposite effects. Moreover, IRF7 protected against angiotensin II–induced cardiomyocyte hypertrophy in vitro. Mechanistically, we identified that IRF7-dependent cardioprotection was mediated through IRF7 binding to inhibitor of κB kinase-β, and subsequent nuclear factor-κB inactivation. In fact, blocking nuclear factor-κB signaling with cardiac-specific inhibitors of κBαS32A/S36A super-repressor transgene counteracted the adverse effect of IRF7 deficiency. Conversely, activation of nuclear factor-κB signaling via a cardiac-specific conditional inhibitor of κB kinase-βS177E/S181E (constitutively active) transgene negated the antihypertrophic effect of IRF7 overexpression. Our data demonstrate that IRF7 acts as a novel negative regulator of pathological cardiac hypertrophy by inhibiting nuclear factor-κB signaling and may constitute a potential therapeutic target for pathological cardiac hypertrophy. PMID:24396025

  13. Content of mitochondrial calcium uniporter (MCU) in cardiomyocytes is regulated by microRNA-1 in physiologic and pathologic hypertrophy

    PubMed Central

    Zaglia, Tania; Ceriotti, Paola; Campo, Antonio; Borile, Giulia; Armani, Andrea; Carullo, Pierluigi; Prando, Valentina; Coppini, Raffaele; Vida, Vladimiro; Stølen, Tomas O.; Ulrik, Wisløff; Cerbai, Elisabetta; Stellin, Giovanni; Faggian, Giuseppe; De Stefani, Diego; Sandri, Marco; Rizzuto, Rosario; Di Lisa, Fabio; Pozzan, Tullio; Catalucci, Daniele; Mongillo, Marco

    2017-01-01

    The mitochondrial Ca2+ uniporter complex (MCUC) is a multimeric ion channel which, by tuning Ca2+ influx into the mitochondrial matrix, finely regulates metabolic energy production. In the heart, this dynamic control of mitochondrial Ca2+ uptake is fundamental for cardiomyocytes to adapt to either physiologic or pathologic stresses. Mitochondrial calcium uniporter (MCU), which is the core channel subunit of MCUC, has been shown to play a critical role in the response to β-adrenoreceptor stimulation occurring during acute exercise. The molecular mechanisms underlying the regulation of MCU, in conditions requiring chronic increase in energy production, such as physiologic or pathologic cardiac growth, remain elusive. Here, we show that microRNA-1 (miR-1), a member of the muscle-specific microRNA (myomiR) family, is responsible for direct and selective targeting of MCU and inhibition of its translation, thereby affecting the capacity of the mitochondrial Ca2+ uptake machinery. Consistent with the role of miR-1 in heart development and cardiomyocyte hypertrophic remodeling, we additionally found that MCU levels are inversely related with the myomiR content, in murine and, remarkably, human hearts from both physiologic (i.e., postnatal development and exercise) and pathologic (i.e., pressure overload) myocardial hypertrophy. Interestingly, the persistent activation of β-adrenoreceptors is likely one of the upstream repressors of miR-1 as treatment with β-blockers in pressure-overloaded mouse hearts prevented its down-regulation and the consequent increase in MCU content. Altogether, these findings identify the miR-1/MCU axis as a factor in the dynamic adaptation of cardiac cells to hypertrophy. PMID:29073097

  14. Involvement of microRNA-Mediated Gene Expression Regulation in the Pathological Development of Stem Canker Disease in Populus trichocarpa

    PubMed Central

    Zhao, Jia-Ping; Jiang, Xiao-Ling; Zhang, Bing-Yu; Su, Xiao-Hua

    2012-01-01

    MicroRNAs (miRNAs), a type of short (21–23 nucleotides), non-coding RNA molecule, mediate repressive gene regulation through RNA silencing at the post-transcriptional level, and play an important role in defense and response to abiotic and biotic stresses. In the present study, Affymetrix® miRNA Array, real-time quantitative PCR (qPCR) for miRNAs and their targets, and miRNA promoter analysis were used to validate the gene expression patterns of miRNAs in Populus trichocarpa plantlets induced with the poplar stem canker pathogen, Botryosphaeria dothidea. Twelve miRNAs (miR156, miR159, miR160, miR164, miR166, miR168, miR172, miR319, miR398, miR408, miR1448, and miR1450) were upregulated in the stem bark of P. trichocarpa, but no downregulated miRNAs were found. Based on analysis of the miRNAs and their targets, a potential co-regulatory network was developed to describe post-transcriptional regulation in the pathological development of poplar stem canker. There was highly complex cross-talk between diverse miRNA pathway responses to biotic and abiotic stresses. The results suggest that miR156 is probably an integral component of the miRNA response to all environmental stresses in plants. Cis-regulatory elements were binding sites for the transcription factors (TFs) on DNA. Promoter analysis revealed that TC-rich repeats and a W1-box motif were both tightly related disease response motifs in Populus. Promoter analysis and target analysis of miRNAs also revealed that some TFs regulate their activation/repression. Furthermore, a feedback regulatory network in the pathological development of poplar stem canker is provided. The results confirm that miRNA pathways regulate gene expression during the pathological development of plant disease, and provide new insights into understanding the onset and development of poplar stem canker. PMID:23028709

  15. Strip mosaicing confocal microscopy for rapid imaging over large areas of excised tissue

    NASA Astrophysics Data System (ADS)

    Abeytunge, Sanjee; Li, Yongbiao; Larson, Bjorg; Peterson, Gary; Toledo-Crow, Ricardo; Rajadhyaksha, Milind

    2012-03-01

    Confocal mosaicing microscopy is a developing technology platform for imaging tumor margins directly in fresh tissue, without the processing that is required for conventional pathology. Previously, basal cell carcinoma margins were detected by mosaicing of confocal images of 12 x 12 mm2 of excised tissue from Mohs surgery. This mosaicing took 9 minutes. Recently we reported the initial feasibility of a faster approach called "strip mosaicing" on 10 x 10 mm2 of tissue that was demonstrated in 3 minutes. In this paper we report further advances in instrumentation and software. Rapid mosaicing of confocal images on large areas of fresh tissue potentially offers a means to perform pathology at the bedside. Thus, strip mosaicing confocal microscopy may serve as an adjunct to pathology for imaging tumor margins to guide surgery.

  16. Behavioral and Emotional Rating Scale: Two Studies of Convergent Validity

    ERIC Educational Resources Information Center

    Trout, Alexandra L.; Ryan, Joseph B.; La Vigne, Steven P.; Epstein, Michael H.

    2003-01-01

    As the field of mental health services shifts its focus to early intervention, the need to develop valid and reliable measures of young children's behavioral functioning is clear. Traditional assessment instruments have focused on deficits, problems, and pathologies to the exclusion of strengths and competencies. However, assessing child strengths…

  17. An Analysis of Thinking Preferences across Three Health Care Disciplines

    ERIC Educational Resources Information Center

    Wium, A. M.; Pitout, H.; Human, A.; du Toit, P. H.

    2017-01-01

    Three lecturers respectively in Speech-Language Pathology and Audiology, Occupational Therapy and Physiotherapy (SLPA, OT and PT) at a public Higher Education Institution in South Africa collaborated to determine thinking preferences. The Herrmann Brain Dominance Instrument (HBDI®) was used to collect data from three lecturers while an adapted…

  18. Evaluation of the Nova StatSensor® XpressTM Creatinine Point-Of-Care Handheld Analyzer

    PubMed Central

    Kosack, Cara Simone; de Kieviet, Wim; Bayrak, Kubra; Milovic, Anastacija; Page, Anne Laure

    2015-01-01

    Creatinine is a parameter that is required to monitor renal function and is important to follow in patients under treatment with potentially toxic renal drugs, such as the anti-HIV drug Tenofovir. A point of care instrument to measure creatinine would be useful for patients monitoring in resource-limited settings, where more instruments that are sophisticated are not available. The StatSensor Xpress Creatinine (Nova Biomedical Cooperation, Waltham, MA, USA) point of care analyzer was evaluated for its diagnostic performance in indicating drug therapy change. Creatinine was measured in parallel using the Nova StatSensor Xpress Creatinine analyzer and the Vitros 5,1FS (Ortho Clinical Diagnostics, Inc, Rochester, USA), which served as reference standard. The precision (i.e., repeatability and reproducibility) and accuracy of the StatSensor Xpress Creatinine analyzer were calculated using a panel of specimens with normal, low pathological and high pathological values. Two different Nova StatSensor Xpress Creatinine analyzers were used for the assessment of accuracy using repeated measurements. The coefficient of variation of the StatSensor Xpress Creatinine analyzers ranged from 2.3 to 5.9% for repeatability and from 4.2 to 9.0% for between-run reproducibility. The concordance correlation agreement was good except for high values (>600 µmol/L). The Bland-Altman analysis in high pathological specimens suggests that the Nova StatSensor Xpress Creatinine test tends to underestimate high creatinine values (i.e., >600 µmol/L). The Nova StatSensor Xpress Creatinine analyzers showed acceptable to good results in terms of repeatability, inter-device reproducibility and between-run reproducibility over time using quality control reagents. The analyzer was found sufficiently accurate for detecting pathological values in patients (age >10 year) and can be used with a moderate risk of misclassification. PMID:25886375

  19. Evaluation of the Nova StatSensor® Xpress(TM) Creatinine point-of-care handheld analyzer.

    PubMed

    Kosack, Cara Simone; de Kieviet, Wim; Bayrak, Kubra; Milovic, Anastacija; Page, Anne Laure

    2015-01-01

    Creatinine is a parameter that is required to monitor renal function and is important to follow in patients under treatment with potentially toxic renal drugs, such as the anti-HIV drug Tenofovir. A point of care instrument to measure creatinine would be useful for patients monitoring in resource-limited settings, where more instruments that are sophisticated are not available. The StatSensor Xpress Creatinine (Nova Biomedical Cooperation, Waltham, MA, USA) point of care analyzer was evaluated for its diagnostic performance in indicating drug therapy change. Creatinine was measured in parallel using the Nova StatSensor Xpress Creatinine analyzer and the Vitros 5,1FS (Ortho Clinical Diagnostics, Inc, Rochester, USA), which served as reference standard. The precision (i.e., repeatability and reproducibility) and accuracy of the StatSensor Xpress Creatinine analyzer were calculated using a panel of specimens with normal, low pathological and high pathological values. Two different Nova StatSensor Xpress Creatinine analyzers were used for the assessment of accuracy using repeated measurements. The coefficient of variation of the StatSensor Xpress Creatinine analyzers ranged from 2.3 to 5.9% for repeatability and from 4.2 to 9.0% for between-run reproducibility. The concordance correlation agreement was good except for high values (>600 µmol/L). The Bland-Altman analysis in high pathological specimens suggests that the Nova StatSensor Xpress Creatinine test tends to underestimate high creatinine values (i.e., >600 µmol/L). The Nova StatSensor Xpress Creatinine analyzers showed acceptable to good results in terms of repeatability, inter-device reproducibility and between-run reproducibility over time using quality control reagents. The analyzer was found sufficiently accurate for detecting pathological values in patients (age >10 year) and can be used with a moderate risk of misclassification.

  20. Regulation of ion transport by microRNAs.

    PubMed

    Elvira-Matelot, Emilie; Jeunemaitre, Xavier; Hadchouel, Juliette

    2011-09-01

    This review aims to describe the recent findings obtained on the regulation of ion transport by microRNAs in physiological and pathological situations in different organs and organisms. The number of ion channels or transporters can be regulated by increasing or decreasing the transcription and/or translation of the corresponding genes. In this context, a new class of regulators of gene expression has emerged as an important modulator of ion transport. microRNAs are short noncoding RNAs which inhibit gene expression by enhancing the degradation or inhibiting the translation of their targets. Most of the studies published so far describe their roles during embryonic development and tumorigenesis. However, recent studies have started to unravel how microRNA-mediated modulation of ion transport could contribute not only to the development of pathological states, such as heart disease, but also to the osmotic regulation of various organisms. The contribution of microRNAs to the regulation of ion transport has only begun to be unraveled, mostly in cardiomyocytes. Only a few studies have focused on the kidney but they strongly suggest that microRNAs could play an important role in the regulation of renal ion transport in response to variation in daily food intake.

  1. Considerations for standardizing predictive molecular pathology for cancer prognosis.

    PubMed

    Fiorentino, Michelangelo; Scarpelli, Marina; Lopez-Beltran, Antonio; Cheng, Liang; Montironi, Rodolfo

    2017-01-01

    Molecular tests that were once ancillary to the core business of cyto-histopathology are becoming the most relevant workload in pathology departments after histopathology/cytopathology and before autopsies. This has resulted from innovations in molecular biology techniques, which have developed at an incredibly fast pace. Areas covered: Most of the current widely used techniques in molecular pathology such as FISH, direct sequencing, pyrosequencing, and allele-specific PCR will be replaced by massive parallel sequencing that will not be considered next generation, but rather, will be considered to be current generation sequencing. The pre-analytical steps of molecular techniques such as DNA extraction or sample preparation will be largely automated. Moreover, all the molecular pathology instruments will be part of an integrated workflow that traces the sample from extraction to the analytical steps until the results are reported; these steps will be guided by expert laboratory information systems. In situ hybridization and immunohistochemistry for quantification will be largely digitalized as much as histology will be mostly digitalized rather than viewed using microscopy. Expert commentary: This review summarizes the technical and regulatory issues concerning the standardization of molecular tests in pathology. A vision of the future perspectives of technological changes is also provided.

  2. An integrative approach to the assessment of narcissism.

    PubMed

    Roche, Michael J; Pincus, Aaron L; Lukowitsky, Mark R; Ménard, Kim S; Conroy, David E

    2013-01-01

    Narcissism research is poorly calibrated across fields of study in part due to confusion over how to integrate normal and pathological descriptions of narcissism. We argue that pathological and normal narcissism can be integrated in a single model that organizes around self-regulation mechanisms. We present theoretical and empirical support for this interpretation, and demonstrate that modeling pathological and normal narcissism as 2 dimensions underlying the narcissistic character can help to resolve some of the inconsistencies in the field regarding how to best assess adaptive and maladaptive expressions of narcissism.

  3. Crossing boundaries: a comprehensive survey of medical licensing laws and guidelines regulating the interstate practice of pathology.

    PubMed

    Hiemenz, Matthew C; Leung, Stanley T; Park, Jason Y

    2014-03-01

    In the United States, recent judicial interpretation of interstate licensure laws has found pathologists guilty of malpractice and, more importantly, the criminal practice of medicine without a license. These judgments against pathologists highlight the need for a timely and comprehensive survey of licensure requirements and laws regulating the interstate practice of pathology. For all 50 states, each state medical practice act and state medical board website was reviewed. In addition, each medical board was directly contacted by electronic mail, telephone, or US registered mail for information regarding specific legislation or guidelines related to the interstate practice of pathology. On the basis of this information, states were grouped according to similarities in legislation and medical board regulations. This comprehensive survey has determined that states define the practice of pathology on the basis of the geographic location of the patient at the time of surgery or phlebotomy. The majority of states (n=32) and the District of Columbia allow for a physician with an out-of-state license to perform limited consultation to a physician with the specific state license. Several states (n=5) prohibit physicians from consultation without a license for the specific state. Overall, these results reveal the heterogeneity of licensure requirements between states. Pathologists who either practice in multiple states, send cases to out-of-state consultants, or serve as consultants themselves should familiarize themselves with the medical licensure laws of the states from which they receive or send cases.

  4. Muscle biopsies from human muscle diseases with myopathic pathology reveal common alterations in mitochondrial function.

    PubMed

    Sunitha, Balaraju; Gayathri, Narayanappa; Kumar, Manish; Keshava Prasad, Thottethodi Subrahmanya; Nalini, Atchayaram; Padmanabhan, Balasundaram; Srinivas Bharath, Muchukunte Mukunda

    2016-07-01

    Muscle diseases are clinically and genetically heterogeneous and manifest as dystrophic, inflammatory and myopathic pathologies, among others. Our previous study on the cardiotoxin mouse model of myodegeneration and inflammation linked muscle pathology with mitochondrial damage and oxidative stress. In this study, we investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from muscle disease patients, represented by dysferlinopathy (dysfy) (dystrophic pathology; n = 43), polymyositis (PM) (inflammatory pathology; n = 24), and distal myopathy with rimmed vacuoles (DMRV) (distal myopathy; n = 31) were analyzed. Mitochondrial damage (ragged blue and COX-deficient fibers) was revealed in dysfy, PM, and DMRV cases by enzyme histochemistry (SDH and COX-SDH), electron microscopy (vacuolation and altered cristae) and biochemical assays (significantly increased ADP/ATP ratio). Proteomic analysis of muscle mitochondria from all three muscle diseases by isobaric tag for relative and absolute quantitation labeling and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysis demonstrated down-regulation of electron transport chain (ETC) complex subunits, assembly factors and Krebs cycle enzymes. Interestingly, 80 of the under-expressed proteins were common among the three pathologies. Assay of ETC and Krebs cycle enzyme activities validated the MS data. Mitochondrial proteins from muscle pathologies also displayed higher tryptophan (Trp) oxidation and the same was corroborated in the cardiotoxin model. Molecular modeling predicted Trp oxidation to alter the local structure of mitochondrial proteins. Our data highlight mitochondrial alterations in muscle pathologies, represented by morphological changes, altered mitochondrial proteome and protein oxidation, thereby establishing the role of mitochondrial damage in human muscle diseases. We investigated whether human muscle diseases display mitochondrial changes. Muscle biopsies from dysferlinopathy (Dysfy), polymyositis (PM), and distal myopathy with rimmed vacuoles (DMRV) displayed morphological and biochemical evidences of mitochondrial dysfunction. Proteomic analysis revealed down-regulation of electron transport chain (ETC) subunits, assembly factors, and tricarboxylic acid (TCA) cycle enzymes, with 80 proteins common among the three pathologies. Mitochondrial proteins from muscle pathologies also displayed higher Trp oxidation that could alter the local structure. Cover image for this issue: doi: 10.1111/jnc.13324. © 2016 International Society for Neurochemistry.

  5. MicroRNAs as Potential Regulators of Glutathione Peroxidases Expression and Their Role in Obesity and Related Pathologies.

    PubMed

    Matoušková, Petra; Hanousková, Barbora; Skálová, Lenka

    2018-04-14

    Glutathione peroxidases (GPxs) belong to the eight-member family of phylogenetically related enzymes with different cellular localization, but distinct antioxidant function. Several GPxs are important selenoproteins. Dysregulated GPx expression is connected with severe pathologies, including obesity and diabetes. We performed a comprehensive bioinformatic analysis using the programs miRDB, miRanda, TargetScan, and Diana in the search for hypothetical microRNAs targeting 3'untranslated regions (3´UTR) of GPxs. We cross-referenced the literature for possible intersections between our results and available reports on identified microRNAs, with a special focus on the microRNAs related to oxidative stress, obesity, and related pathologies. We identified many microRNAs with an association with oxidative stress and obesity as putative regulators of GPxs. In particular, miR-185-5p was predicted by a larger number of programs to target six GPxs and thus could play the role as their master regulator. This microRNA was altered by selenium deficiency and can play a role as a feedback control of selenoproteins' expression. Through the bioinformatics analysis we revealed the potential connection of microRNAs, GPxs, obesity, and other redox imbalance related diseases.

  6. Dl-3-n-Butylphthalide Inhibits NLRP3 Inflammasome and Mitigates Alzheimer's-Like Pathology via Nrf2-TXNIP-TrX Axis.

    PubMed

    Wang, Chun-Yan; Xu, Ye; Wang, Xu; Guo, Chuang; Wang, Tao; Wang, Zhan-You

    2018-04-25

    Oxidative stress and neuroinflammation play important roles in the pathology of Alzheimer's disease (AD). Thioredoxin-interacting protein (TXNIP), an endogenous inhibitor of antioxidant thioredoxin, is suspected to be an important modulator of oxidative stress and inflammation. However, the underlying mechanism involved in the abnormal homeostasis of TXNIP-thioredoxin (TrX) in AD pathogenesis remains unclear. Using the Swedish mutant form of APP (APPswe)/PSEN1dE9 transgenic mouse (APP/PS1) and human-derived neuronal cells as model systems, we disclosed the impairment of the nuclear factor erythroid 2-related factor 2 (Nrf2)-TXNIP-TrX signaling in Alzheimer's-like pathology. We observed that the immune staining of TXNIP was increased in postmortem AD brain. The chronic accumulation of inflammatory mediator in neuronal cells facilitates interactions of TXNIP-nucleotide binding oligomerization domain-like receptor family, pyrin domain containing 3 (NLRP3) and NLRP3-ASC, which increases β-amyloid (Aβ) secretion. The antioxidant Dl-3-n-butylphthalide (Dl-NBP) is commonly used for cerebral ischemia treatment. In our study, we elucidated for new mechanisms by which Dl-NBP enhanced TrX activity, suppressed TXNIP, and ameliorated neuronal apoptosis in the APP/PS1 mouse brains. In human glioblastoma A172 cells and neuroblastoma SH-SY5Y cells, we delineated the Dl-NBP-mediated signaling pathways by which Dl-NBP-dependent upregulation of Nrf2 mediated the reciprocal regulation of reducing proinflammatory cytokine and inhibiting Aβ production in the glial and neuronal cells overexpressing APPswe. Our data provide a novel insight into the molecular mechanism that impairments of Nrf2-TXNIP-TrX system may be involved in the imbalance of cellular redox homeostasis and inflammatory damage in the AD brain. Dl-NBP treatment could suppress TXNIP-NLRP3 interaction and inhibit NLRP3 inflammasome activation via upregulating Nrf2. These findings may provide an instrumental therapeutic approach for AD. Antioxid. Redox Signal. 00, 000-000.

  7. Diagnostic instruments for behavioural addiction: an overview

    PubMed Central

    Albrecht, Ulrike; Kirschner, Nina Ellen; Grüsser, Sabine M.

    2007-01-01

    In non-substance-related addiction, the so-called behavioural addiction, no external psychotropic substances are consumed. The psychotropic effect consists of the body’s own biochemical processes induced only by excessive activities. Until recently, knowledge was limited with respect to clinically relevant excessive reward-seeking behaviour, such as pathological gambling, excessive shopping and working which meet diagnostic criteria of dependent behaviour. To date, there is no consistent concept for diagnosis and treatment of excessive reward-seeking behaviour, and its classification is uncertain. Therefore, a clear conceptualization of the so-called behavioural addictions is of great importance. The use of adequate diagnostic instruments is necessary for successful therapeutical implications. This article provides an overview of the current popular diagnostic instruments assessing the different forms of behavioural addiction. Especially in certain areas there are only few valid and reliable instruments available to assess excessive rewarding behaviours that fulfill the criteria of addiction. PMID:19742294

  8. Governance and Institutional Autonomy: Governing and Governance in Portuguese Higher Education

    ERIC Educational Resources Information Center

    Magalhaes, Antonio; Veiga, Amelia; Ribeiro, Filipa; Amaral, Alberto

    2013-01-01

    This paper aims at looking at governance instruments beyond managerial technicality. It intends to do so by analysing the impact of governance reforms on the universities autonomy assumed as a regulation instrument to politically steer systems and institutions. The regulation efforts undertaken at the European and national levels reflect a trend…

  9. [The peculiarities of calcium metabolism regulation in different periods of growth and development].

    PubMed

    Moĭsa, S S; Nozdrachev, A D

    2014-01-01

    The review contains literature data about calcium metabolism regulation in different periods of growth and development. The analyses of retrospective and current sources of information about the regulation of calcium homeostasis under the theory of functional systems, the regulation of calcium metabolism in prenatal and postnatal periods of the development, the significance of calcium metabolism disturbances in the development of pathological conditions were showed.

  10. Enhanced upper genital tract pathologies by blocking Tim-3 and PD-L1 signaling pathways in mice intravaginally infected with Chlamydia muridarum.

    PubMed

    Peng, Bo; Lu, Chunxue; Tang, Lingli; Yeh, I-Tien; He, Zhimin; Wu, Yimou; Zhong, Guangming

    2011-12-14

    Although Tim-3 & PD-L1 signaling pathways play important roles in negatively regulating immune responses, their roles in chlamydial infection have not been evaluated. Neutralization antibodies targeting Tim-3 and PD-L1 were used to treat mice. Following an intravaginal infection with C. muridarum organisms, mice with or without the dual antibody treatment were compared for live chlamydial organism shedding from the lower genital tract and inflammatory pathology in the upper genital tract. Mice treated with anti-Tim-3 and anti-PD-L1 antibodies displayed a time course of live organism shedding similar to that of mice treated with equivalent amounts of isotype-matched IgG molecules. The combined antibody blocking failed to alter either the lower genital tract cytokine or systemic humoral and cellular adaptive responses to C. muridarum infection. However, the antibody blocking significantly enhanced C. muridarum-induced pathologies in the upper genital tract, including more significant hydrosalpinx and inflammatory infiltration in uterine horn and oviduct tissues. The Tim-3 and PD-L1-mediated signaling can significantly reduce pathologies in the upper genital tract without suppressing immunity against chlamydial infection, suggesting that Tim-3 and PD-L1-mediated negative regulation may be manipulated to attenuate tubal pathologies in women persistently infected with C. trachomatis organisms.

  11. TRPC6 fulfills a calcineurin signaling circuit during pathologic cardiac remodeling

    PubMed Central

    Kuwahara, Koichiro; Wang, Yanggan; McAnally, John; Richardson, James A.; Bassel-Duby, Rhonda; Hill, Joseph A.; Olson, Eric N.

    2006-01-01

    The heart responds to injury and chronic pressure overload by pathologic growth and remodeling, which frequently result in heart failure and sudden death. Calcium-dependent signaling pathways promote cardiac growth and associated changes in gene expression in response to stress. The calcium/calmodulin-dependent phosphatase calcineurin, which signals to nuclear factor of activated T cells (NFAT) transcription factors, serves as a transducer of calcium signals and is sufficient and necessary for pathologic cardiac hypertrophy and remodeling. Transient receptor potential (TRP) proteins regulate cation entry into cells in response to a variety of signals, and in skeletal muscle, expression of TRP cation channel, subfamily C, member 3 (TRPC3) is increased in response to neurostimulation and calcineurin signaling. Here we show that TRPC6 was upregulated in mouse hearts in response to activated calcineurin and pressure overload, as well as in failing human hearts. Two conserved NFAT consensus sites in the promoter of the TRPC6 gene conferred responsiveness to cardiac stress. Cardiac-specific overexpression of TRPC6 in transgenic mice resulted in heightened sensitivity to stress, a propensity for lethal cardiac growth and heart failure, and an increase in NFAT-dependent expression of β–myosin heavy chain, a sensitive marker for pathologic hypertrophy. These findings implicate TRPC6 as a positive regulator of calcineurin-NFAT signaling and a key component of a calcium-dependent regulatory loop that drives pathologic cardiac remodeling. PMID:17099778

  12. Emotion regulation as a transdiagnostic treatment construct across anxiety, depression, substance, eating and borderline personality disorders: A systematic review.

    PubMed

    Sloan, Elise; Hall, Kate; Moulding, Richard; Bryce, Shayden; Mildred, Helen; Staiger, Petra K

    2017-11-01

    A large body of research has implicated difficulties in emotion regulation as central to the development and maintenance of psychopathology. Emotion regulation has therefore been proposed as a transdiagnostic construct or an underlying mechanism in psychopathology. The transdiagnostic role of emotion regulation has yet to be systematically examined within the psychological treatment outcome literature. It can be proposed that if emotion regulation is indeed a transdiagnostic construct central to the maintenance of psychopathology, then changes in emotion regulation difficulties will occur after effective treatment and this will occur for different disorders. We conducted a systematic review, identifying 67 studies that measured changes in both emotion regulation and symptoms of psychopathology following a psychological intervention for anxiety, depression, substance use, eating pathology or borderline personality disorder. Results demonstrated that regardless of the intervention or disorder, both maladaptive emotion regulation strategy use and overall emotion dysregulation were found to significantly decrease following treatment in all but two studies. Parallel decreases were also found in symptoms of anxiety, depression, substance use, eating pathology and borderline personality disorder. These results contribute to the growing body of evidence supporting the conceptualization of emotion regulation as a transdiagnostic construct. The present study discusses the important implications of these findings for the development of unified treatments that target emotion regulation for individuals who present with multiple disorders. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Complications of Anterior and Posterior Cervical Spine Surgery

    PubMed Central

    Cheung, Jason Pui Yin

    2016-01-01

    Cervical spine surgery performed for the correct indications yields good results. However, surgeons need to be mindful of the many possible pitfalls. Complications may occur starting from the anaesthestic procedure and patient positioning to dura exposure and instrumentation. This review examines specific complications related to anterior and posterior cervical spine surgery, discusses their causes and considers methods to prevent or treat them. In general, avoiding complications is best achieved with meticulous preoperative analysis of the pathology, good patient selection for a specific procedure and careful execution of the surgery. Cervical spine surgery is usually effective in treating most pathologies and only a reasonable complication rate exists. PMID:27114784

  14. Anatomic pathology laboratory information systems: a review.

    PubMed

    Park, Seung Lyung; Pantanowitz, Liron; Sharma, Gaurav; Parwani, Anil Vasdev

    2012-03-01

    The modern anatomic pathology laboratory depends on a reliable information infrastructure to register specimens, record gross and microscopic findings, regulate laboratory workflow, formulate and sign out report(s), disseminate them to the intended recipients across the whole health system, and support quality assurance measures. This infrastructure is provided by the Anatomical Pathology Laboratory Information Systems (APLIS), which have evolved over decades and now are beginning to support evolving technologies like asset tracking and digital imaging. As digital pathology transitions from "the way of the future" to "the way of the present," the APLIS continues to be one of the key effective enablers of the scope and practice of pathology. In this review, we discuss the evolution, necessary components, architecture and functionality of the APLIS that are crucial to today's practicing pathologist and address the demands of emerging trends on the future APLIS.

  15. Effective learning among elite football players: the development of a football-specific self-regulated learning questionnaire.

    PubMed

    Toering, Tynke; Jordet, Geir; Ripegutu, Anders

    2013-01-01

    The present study aimed to develop a football-specific self-report instrument measuring self-regulated learning in the context of daily practice, which can be used to monitor the extent to which players take responsibility for their own learning. Development of the instrument involved six steps: 1. Literature review based on Zimmerman's (2006) theory of self-regulated learning, 2. Item generation, 3. Item validation, 4. Pilot studies, 5. Exploratory factor analysis (EFA), and 6. Confirmatory factor analysis (CFA). The instrument was tested for reliability and validity among 204 elite youth football players aged 13-16 years (Mage = 14.6; s = 0.60; 123 boys, 81 girls). The EFA indicated that a five-factor model fitted the observed data best (reflection, evaluation, planning, speaking up, and coaching). However, the CFA showed that a three-factor structure including 22 items produced a satisfactory model fit (reflection, evaluation, and planning; non-normed fit index [NNFI] = 0.96, comparative fit index [CFI] = 0.95, root mean square error of approximation [RMSEA] = 0.067). While the self-regulation processes of reflection, evaluation, and planning are strongly related and fit well into one model, other self-regulated learning processes seem to be more individually determined. In conclusion, the questionnaire developed in this study is considered a reliable and valid instrument to measure self-regulated learning among elite football players.

  16. 15 CFR 301.8 - Instructions for entering instruments through Customs and Border Protection under subheading 9810...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.8 Instructions for entering instruments through Customs and Border Protection... 15 Commerce and Foreign Trade 2 2014-01-01 2014-01-01 false Instructions for entering instruments...

  17. 15 CFR 301.8 - Instructions for entering instruments through Customs and Border Protection under subheading 9810...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.8 Instructions for entering instruments through Customs and Border Protection... 15 Commerce and Foreign Trade 2 2013-01-01 2013-01-01 false Instructions for entering instruments...

  18. 15 CFR 301.8 - Instructions for entering instruments through Customs and Border Protection under subheading 9810...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.8 Instructions for entering instruments through Customs and Border Protection... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Instructions for entering instruments...

  19. 15 CFR 301.8 - Instructions for entering instruments through Customs and Border Protection under subheading 9810...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.8 Instructions for entering instruments through Customs and Border Protection... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Instructions for entering instruments...

  20. 15 CFR 301.8 - Instructions for entering instruments through Customs and Border Protection under subheading 9810...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.8 Instructions for entering instruments through Customs and Border Protection... 15 Commerce and Foreign Trade 2 2012-01-01 2012-01-01 false Instructions for entering instruments...

  1. 32 CFR 37.110 - What type of instruments are technology investment agreements (TIAs)?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 1 2011-07-01 2011-07-01 false What type of instruments are technology... SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS General § 37.110 What type of instruments are technology investment agreements (TIAs)? TIAs are assistance instruments...

  2. 31 CFR 103.58 - Forfeiture of currency or monetary instruments.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... instruments. 103.58 Section 103.58 Money and Finance: Treasury Regulations Relating to Money and Finance FINANCIAL RECORDKEEPING AND REPORTING OF CURRENCY AND FOREIGN TRANSACTIONS General Provisions § 103.58 Forfeiture of currency or monetary instruments. Any currency or other monetary instruments which are in the...

  3. Ultrasound applicability in Speech Language Pathology and Audiology.

    PubMed

    Barberena, Luciana da Silva; Brasil, Brunah de Castro; Melo, Roberta Michelon; Mezzomo, Carolina Lisbôa; Mota, Helena Bolli; Keske-Soares, Márcia

    2014-01-01

    To present recent studies that used the ultrasound in the fields of Speech Language Pathology and Audiology, which evidence possibilities of the applicability of this technique in different subareas. A bibliographic research was carried out in the PubMed database, using the keywords "ultrasonic," "speech," "phonetics," "Speech, Language and Hearing Sciences," "voice," "deglutition," and "myofunctional therapy," comprising some areas of Speech Language Pathology and Audiology Sciences. The keywords "ultrasound," "ultrasonography," "swallow," "orofacial myofunctional therapy," and "orofacial myology" were also used in the search. Studies in humans from the past 5 years were selected. In the preselection, duplicated studies, articles not fully available, and those that did not present direct relation between ultrasound and Speech Language Pathology and Audiology Sciences were discarded. The data were analyzed descriptively and classified subareas of Speech Language Pathology and Audiology Sciences. The following items were considered: purposes, participants, procedures, and results. We selected 12 articles for ultrasound versus speech/phonetics subarea, 5 for ultrasound versus voice, 1 for ultrasound versus muscles of mastication, and 10 for ultrasound versus swallow. Studies relating "ultrasound" and "Speech Language Pathology and Audiology Sciences" in the past 5 years were not found. Different studies on the use of ultrasound in Speech Language Pathology and Audiology Sciences were found. Each of them, according to its purpose, confirms new possibilities of the use of this instrument in the several subareas, aiming at a more accurate diagnosis and new evaluative and therapeutic possibilities.

  4. Cost-effective design of economic instruments in nutrition policy.

    PubMed

    Jensen, Jørgen D; Smed, Sinne

    2007-04-04

    This paper addresses the potential for using economic regulation, e.g. taxes or subsidies, as instruments to combat the increasing problems of inappropriate diets, leading to health problems such as obesity, diabetes 2, cardiovascular diseases etc. in most countries. Such policy measures may be considered as alternatives or supplements to other regulation instruments, including information campaigns, bans or enhancement of technological solutions to the problems of obesity or related diseases. 7 different food tax and subsidy instruments or combinations of instruments are analysed quantitatively. The analyses demonstrate that the average cost-effectiveness with regard to changing the intake of selected nutritional variables can be improved by 10-30 per cent if taxes/subsidies are targeted against these nutrients, compared with targeting selected food categories. Finally, the paper raises a range of issues, which need to be investigated further, before firm conclusions about the suitability of economic instruments in nutrition policy can be drawn.

  5. Cost-effective design of economic instruments in nutrition policy

    PubMed Central

    Jensen, Jørgen D; Smed, Sinne

    2007-01-01

    This paper addresses the potential for using economic regulation, e.g. taxes or subsidies, as instruments to combat the increasing problems of inappropriate diets, leading to health problems such as obesity, diabetes 2, cardiovascular diseases etc. in most countries. Such policy measures may be considered as alternatives or supplements to other regulation instruments, including information campaigns, bans or enhancement of technological solutions to the problems of obesity or related diseases. 7 different food tax and subsidy instruments or combinations of instruments are analysed quantitatively. The analyses demonstrate that the average cost-effectiveness with regard to changing the intake of selected nutritional variables can be improved by 10–30 per cent if taxes/subsidies are targeted against these nutrients, compared with targeting selected food categories. Finally, the paper raises a range of issues, which need to be investigated further, before firm conclusions about the suitability of economic instruments in nutrition policy can be drawn. PMID:17408494

  6. Item Specification in the Development of a Diagnostic Gambling Instrument: A Focus Group Approach

    ERIC Educational Resources Information Center

    Cunningham-Williams, Renee M.; Zayas, Luis E.; Books, Samantha J.; Cottler, Linda B.

    2008-01-01

    Pathological Gambling Disorder (PGD) is internationally prevalent and contributes to significant disruption and impairment in a gambler's life. For accurate diagnosis and treatment planning, clinicians require standardized criteria as in commonly used DSM and ICD-10 taxonomies, which are conceptually clear, valid, and culturally appropriate. We…

  7. DSM-5 pathological personality traits and the personality assessment inventory.

    PubMed

    Hopwood, Christopher J; Wright, Aidan G C; Krueger, Robert F; Schade, Nick; Markon, Kristian E; Morey, Leslie C

    2013-06-01

    Section 3 of the DSM-5 will include a pathological personality trait system rooted in the quantitative epistemology of personality and clinical psychology. This system has the potential to enhance the clinical utility of the diagnostic nosology by providing a means for the dimensional assessment of individuals with psychopathology. However, there is limited research on the associations of DSM-5 traits with common mental disorders and related clinical phenomena as measured by currently popular assessment instruments. The purpose of this article was to evaluate the convergence of the DSM-5 trait system with a well-validated broadband clinical instrument, the Personality Assessment Inventory (PAI). Bivariate correlations were examined and factor analytic methods were used to examine the degree to which the DSM-5 traits and PAI capture common variance in personality and mental health. In a student sample (N = 1,001), we found broad convergence between the DSM-5 traits and PAI, which could be organized effectively using five factors. The implications of these findings for using traits to address issues related to diagnostic co-occurrence and heterogeneity in routine clinical assessment are discussed.

  8. Religion, Spirituality and Speech-Language Pathology: A Viewpoint for Ensuring Patient-Centred Holistic Care.

    PubMed

    Mathisen, Bernice; Carey, Lindsay B; Carey-Sargeant, Christa L; Webb, Gwendalyn; Millar, CaraJane; Krikheli, Lilli

    2015-12-01

    This paper presents a viewpoint concerning the largely neglected clinical relevance of spirituality and religious belief in speech-language pathology (SLP) assessments, interventions and outcomes across the lifespan. An overview of the refereed SLP literature is presented with regard to religion and spirituality. It was found that while there is increasing research with regard to spirituality, health and well-being, there is very little specific to SLP. What is available and clinically relevant, generally relates to holistic care and/or cultural and linguistic diversity. Amidst the health care literature, however, there is a growing number of recommended instruments (for religious/spiritual screening) sensitive to intercultural and interfaith issues that are currently available to medical, nursing, allied health and chaplaincy practitioners. These instruments can also be of value to SLPs to ensure holistic assessments and interventions. It would seem timely for SLPs (and other allied health practitioners) to consider including spiritual screenings/assessments as part of their clinical practice so as to ensure appropriate holistic care. This would also mean undertaking research and including relevant education within tertiary institutions and professional development programs.

  9. The relationship between parental bonding, social problem solving and eating pathology in an anorexic inpatient sample.

    PubMed

    Swanson, Helen; Power, Kevin; Collin, Paula; Deas, Suzanne; Paterson, Gillian; Grierson, David; Yellowlees, Alex; Park, Katy; Taylor, Louise

    2010-01-01

    Parental relationships and maladaptive problem solving have been associated with anorexic symptomatology. This study investigates the relationship between perceived parental bonding, social problem solving and eating psychopathology. Forty three female inpatients with anorexia nervosa and 76 student controls were assessed using the Parental Bonding Instrument, the Social Problem Solving Inventory and the Eating Disorders Examination or the Eating Disorders Examination-Questionnaire. The anorexic group reported significantly lower levels of parental care than the student control group and used more negative and avoidance style coping. In the anorexic group, disordered eating was significantly correlated with low maternal care and high control. Maternal bonding was found to mediate the relationship between avoidance style coping and eating pathology. Findings suggest a relationship between maternal bonding, the use of maladaptive problem solving techniques and eating disorder pathology in inpatients with anorexia nervosa.

  10. Unresolved mourning, supernatural beliefs and dissociation: a mediation analysis.

    PubMed

    Thomson, Paula; Jaque, S Victoria

    2014-01-01

    Unresolved mourning is marked by disorganized behavior and states of mind. In this study, we speculated that pathological dissociation would mediate the effects of unresolved mourning on supernatural beliefs. This hypothesis was determined based on findings that indicate an association between higher levels of dissociation, stronger beliefs in the supernatural and unresolved mourning. We examined two groups of participants, one classified as non-unresolved (non-U) (n = 56) and the other as unresolved (n = 26) (U) with respect to past loss/trauma as measured by the Adult Attachment Interview (AAI). Two self-report instruments were administered to measure supernatural beliefs and dissociation. As hypothesized, the multivariate analysis of variance indicated mean differences between the two groups. The unresolved group had greater belief in the supernatural and more pathological dissociative processes. The mediation analysis demonstrated that pathological dissociation fully mediated the effects of unresolved mourning on supernatural beliefs.

  11. Short Segment Spinal Instrumentation With Index Vertebra Pedicle Screw Placement for Pathologies Involving the Anterior and Middle Vertebral Column Is as Effective as Long Segment Stabilization With Cage Reconstruction: A Biomechanical Study.

    PubMed

    Bartanusz, Viktor; Harris, Jonathan; Moldavsky, Mark; Cai, Yiwei; Bucklen, Brandon

    2015-11-01

    An in vitro, cadaveric biomechanical study. The aim of the present study was to compare single-segment posterior instrumentation and fracture-level screws with single/multilevel posterior fixation and corpectomy in a simulated, unstable burst fracture model. The optimal extent of instrumentation for surgical cases of non-neoplastic vertebral body pathologies remains uncertain. Although several clinical studies demonstrate advantages of short segment instrumentation with index-level screws over more extensive corpectomy and anterior-posterior techniques, a comprehensive biomechanical comparison of these techniques is currently lacking. Six bovine spines (T11-L5) were tested in flexion, extension, lateral bending (LB), and axial rotation (AR) following simulated burst fracture at L2. Posterior instrumentation included 1 level above/below (1LF) and 2 levels above/below fracture level (2LF), intermediate or index screws at fracture level (FF), and cross-connectors above/below fracture level (CC). Anterior corpectomy devices included expandable corpectomy spacers with/without integrated screws, ACDi and ACD, respectively FORTIFY-Integrated/FORTIFY; Globus Medical, Inc., PA. Constructs were tested in the following order: (1) Intact; (2) 1LF; (3) 1LF and CC; (4) 1LF and FF; (5) 1LF, CC, and FF; (6) 2LF; (7) 2LF and CC; (8) 2LF and FF; (9) 2LF, CC, and FF; (10) 2LF and ACD; (11) 2LF, ACD, and CC; (12) 1LF and ACDi; (13) 1LF, ACDi, and CC. During flexion, all constructs except 1LF reduced motion relative to intact (P ≤ 0.05). Anterior support was most stable, but no differences were found between constructs (P ≥ 0.05). Every construct reduced motion in extension, though no differences were found between constructs and intact (P ≥ 0.05). During LB, all constructs reduced motion relative to intact (P ≤ 0.05); 2LF constructs further reduced motion (P ≤ 0.05). No construct returned AR motion to intact, with significant increases in 1LF and ACDi, 2LF and ACD, and 2LF, ACD, and CC (P ≤ 0.05). Cross-connectors and fracture screws reinforced each other in posterior-only constructs, providing maximum stability (P ≥ 0.05). This biomechanical comparison study found no significant superiority of combined anterior-posterior constructs over short segment fracture screw fixation, only multilevel posterior instrumentation with and without anterior support, providing increased stability in LB. Biomechanical equivalency suggests that short segment fracture screw intervention may provide appropriate stabilization for non-neoplastic pathologies involving the anterior and middle vertebral columns. 2.

  12. Pathological Buying Online as a Specific Form of Internet Addiction: A Model-Based Experimental Investigation

    PubMed Central

    Trotzke, Patrick; Starcke, Katrin; Müller, Astrid; Brand, Matthias

    2015-01-01

    The study aimed to investigate different factors of vulnerability for pathological buying in the online context and to determine whether online pathological buying has parallels to a specific Internet addiction. According to a model of specific Internet addiction by Brand and colleagues, potential vulnerability factors may consist of a predisposing excitability from shopping and as mediating variable, specific Internet use expectancies. Additionally, in line with models on addiction behavior, cue-induced craving should also constitute an important factor for online pathological buying. The theoretical model was tested in this study by investigating 240 female participants with a cue-reactivity paradigm, which was composed of online shopping pictures, to assess excitability from shopping. Craving (before and after the cue-reactivity paradigm) and online shopping expectancies were measured. The tendency for pathological buying and online pathological buying were screened with the Compulsive Buying Scale (CBS) and the Short Internet Addiction Test modified for shopping (s-IATshopping). The results demonstrated that the relationship between individual’s excitability from shopping and online pathological buying tendency was partially mediated by specific Internet use expectancies for online shopping (model’s R² = .742, p < .001). Furthermore, craving and online pathological buying tendencies were correlated (r = .556, p < .001), and an increase in craving after the cue presentation was observed solely in individuals scoring high for online pathological buying (t(28) = 2.98, p < .01, d = 0.44). Both screening instruments were correlated (r = .517, p < .001), and diagnostic concordances as well as divergences were indicated by applying the proposed cut-off criteria. In line with the model for specific Internet addiction, the study identified potential vulnerability factors for online pathological buying and suggests potential parallels. The presence of craving in individuals with a propensity for online pathological buying emphasizes that this behavior merits potential consideration within the non-substance/behavioral addictions. PMID:26465593

  13. Pathological Buying Online as a Specific Form of Internet Addiction: A Model-Based Experimental Investigation.

    PubMed

    Trotzke, Patrick; Starcke, Katrin; Müller, Astrid; Brand, Matthias

    2015-01-01

    The study aimed to investigate different factors of vulnerability for pathological buying in the online context and to determine whether online pathological buying has parallels to a specific Internet addiction. According to a model of specific Internet addiction by Brand and colleagues, potential vulnerability factors may consist of a predisposing excitability from shopping and as mediating variable, specific Internet use expectancies. Additionally, in line with models on addiction behavior, cue-induced craving should also constitute an important factor for online pathological buying. The theoretical model was tested in this study by investigating 240 female participants with a cue-reactivity paradigm, which was composed of online shopping pictures, to assess excitability from shopping. Craving (before and after the cue-reactivity paradigm) and online shopping expectancies were measured. The tendency for pathological buying and online pathological buying were screened with the Compulsive Buying Scale (CBS) and the Short Internet Addiction Test modified for shopping (s-IATshopping). The results demonstrated that the relationship between individual's excitability from shopping and online pathological buying tendency was partially mediated by specific Internet use expectancies for online shopping (model's R² = .742, p < .001). Furthermore, craving and online pathological buying tendencies were correlated (r = .556, p < .001), and an increase in craving after the cue presentation was observed solely in individuals scoring high for online pathological buying (t(28) = 2.98, p < .01, d = 0.44). Both screening instruments were correlated (r = .517, p < .001), and diagnostic concordances as well as divergences were indicated by applying the proposed cut-off criteria. In line with the model for specific Internet addiction, the study identified potential vulnerability factors for online pathological buying and suggests potential parallels. The presence of craving in individuals with a propensity for online pathological buying emphasizes that this behavior merits potential consideration within the non-substance/behavioral addictions.

  14. Nucleus Accumbens Adenosine A2A Receptors Regulate Exertion of Effort by Acting on the Ventral Striatopallidal Pathway

    PubMed Central

    Mingote, Susana; Font, Laura; Farrar, Andrew M.; Vontell, Regina; Worden, Lila T.; Stopper, Colin M.; Port, Russell G.; Sink, Kelly S.; Bunce, Jamie G.; Chrobak, James J.; Salamone, John D.

    2009-01-01

    Goal-directed actions are sensitive to work-related response costs, and dopamine in nucleus accumbens is thought to modulate the exertion of effort in motivated behavior. Dopamine-rich striatal areas such as nucleus accumbens also contain high numbers of adenosine A2A receptors, and, for that reason, the behavioral and neurochemical effects of the adenosine A2A receptor agonist CGS 21680 [2-p-(2-carboxyethyl) phenethylamino-5′-N-ethylcarboxamidoadenosine] were investigated. Stimulation of accumbens adenosine A2A receptors disrupted performance of an instrumental task with high work demands (i.e., an interval lever-pressing schedule with a ratio requirement attached) but had little effect on a task with a lower work requirement. Immunohistochemical studies revealed that accumbens neurons that project to the ventral pallidum showed adenosine A2A receptors immunoreactivity. Moreover, activation of accumbens A2A receptors by local injections of CGS 21680 increased extracellular GABA levels in the ventral pallidum. Combined contralateral injections of CGS 21680 into the accumbens and the GABAA agonist muscimol into ventral pallidum (i.e., “disconnection” methods) also impaired response output, indicating that these structures are part of a common neural circuitry regulating the exertion of effort. Thus, accumbens adenosine A2A receptors appear to regulate behavioral activation and effort-related processes by modulating the activity of the ventral striatopallidal pathway. Research on the effort-related functions of these forebrain systems may lead to a greater understanding of pathological features of motivation, such as psychomotor slowing, anergia, and fatigue in depression. PMID:18768698

  15. Privacy and security of patient data in the pathology laboratory.

    PubMed

    Cucoranu, Ioan C; Parwani, Anil V; West, Andrew J; Romero-Lauro, Gonzalo; Nauman, Kevin; Carter, Alexis B; Balis, Ulysses J; Tuthill, Mark J; Pantanowitz, Liron

    2013-01-01

    Data protection and security are critical components of routine pathology practice because laboratories are legally required to securely store and transmit electronic patient data. With increasing connectivity of information systems, laboratory work-stations, and instruments themselves to the Internet, the demand to continuously protect and secure laboratory information can become a daunting task. This review addresses informatics security issues in the pathology laboratory related to passwords, biometric devices, data encryption, internet security, virtual private networks, firewalls, anti-viral software, and emergency security situations, as well as the potential impact that newer technologies such as mobile devices have on the privacy and security of electronic protected health information (ePHI). In the United States, the Health Insurance Portability and Accountability Act (HIPAA) govern the privacy and protection of medical information and health records. The HIPAA security standards final rule mandate administrative, physical, and technical safeguards to ensure the confidentiality, integrity, and security of ePHI. Importantly, security failures often lead to privacy breaches, invoking the HIPAA privacy rule as well. Therefore, this review also highlights key aspects of HIPAA and its impact on the pathology laboratory in the United States.

  16. A Developmental Neuroscience of Borderline Pathology: Emotion Dysregulation and Social Baseline Theory

    ERIC Educational Resources Information Center

    Hughes, Amy E.; Crowell, Sheila E.; Uyeji, Lauren; Coan, James A.

    2012-01-01

    Theoretical and empirical research has linked poor emotion regulation abilities with dysfunctional frontolimbic circuitry. Consistent with this, research on borderline personality disorder (BPD) finds that frontolimbic dysfunction is a predominant neural substrate underlying the disorder. Emotion regulation is profoundly compromised in BPD.…

  17. 15 CFR 301.9 - Uses and disposition of instruments entered under subheading 9810.00.60, HTSUS.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.9 Uses and disposition of instruments entered under subheading 9810.00.60, HTSUS. (a) An... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Uses and disposition of instruments...

  18. 15 CFR 301.9 - Uses and disposition of instruments entered under subheading 9810.00.60, HTSUS.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.9 Uses and disposition of instruments entered under subheading 9810.00.60, HTSUS. (a) An... 15 Commerce and Foreign Trade 2 2012-01-01 2012-01-01 false Uses and disposition of instruments...

  19. 15 CFR 301.9 - Uses and disposition of instruments entered under subheading 9810.00.60, HTSUS.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.9 Uses and disposition of instruments entered under subheading 9810.00.60, HTSUS. (a) An... 15 Commerce and Foreign Trade 2 2014-01-01 2014-01-01 false Uses and disposition of instruments...

  20. 15 CFR 301.9 - Uses and disposition of instruments entered under subheading 9810.00.60, HTSUS.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.9 Uses and disposition of instruments entered under subheading 9810.00.60, HTSUS. (a) An... 15 Commerce and Foreign Trade 2 2013-01-01 2013-01-01 false Uses and disposition of instruments...

  1. 15 CFR 301.9 - Uses and disposition of instruments entered under subheading 9810.00.60, HTSUS.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.9 Uses and disposition of instruments entered under subheading 9810.00.60, HTSUS. (a) An... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Uses and disposition of instruments...

  2. 31 CFR 103.60 - Enforcement authority with respect to transportation of currency or monetary instruments.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... transportation of currency or monetary instruments. 103.60 Section 103.60 Money and Finance: Treasury Regulations Relating to Money and Finance FINANCIAL RECORDKEEPING AND REPORTING OF CURRENCY AND FOREIGN TRANSACTIONS... instruments. (a) If a customs officer has reasonable cause to believe that there is a monetary instrument...

  3. Loss of Bin1 Promotes the Propagation of Tau Pathology.

    PubMed

    Calafate, Sara; Flavin, William; Verstreken, Patrik; Moechars, Diederik

    2016-10-18

    Tau pathology propagates within synaptically connected neuronal circuits, but the underlying mechanisms are unclear. BIN1-amphiphysin2 is the second most prevalent genetic risk factor for late-onset Alzheimer's disease. In diseased brains, the BIN1-amphiphysin2 neuronal isoform is downregulated. Here, we show that lowering BIN1-amphiphysin2 levels in neurons promotes Tau pathology propagation whereas overexpression of neuronal BIN1-amphiphysin2 inhibits the process in two in vitro models. Increased Tau propagation is caused by increased endocytosis, given our finding that BIN1-amphiphysin2 negatively regulates endocytic flux. Furthermore, blocking endocytosis by inhibiting dynamin also reduces Tau pathology propagation. Using a galectin-3-binding assay, we show that internalized Tau aggregates damage the endosomal membrane, allowing internalized aggregates to leak into the cytoplasm to propagate pathology. Our work indicates that lower BIN1 levels promote the propagation of Tau pathology by efficiently increasing aggregate internalization by endocytosis and endosomal trafficking. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  4. Explaining intermediate filament accumulation in giant axonal neuropathy

    PubMed Central

    Opal, Puneet; Goldman, Robert D.

    2013-01-01

    Giant axonal neuropathy (GAN)1 is a rare autosomal recessive neurological disorder caused by mutations in the GAN gene that encodes gigaxonin, a member of the BTB/Kelch family of E3 ligase adaptor proteins.1 This disease is characterized by the aggregation of Intermediate Filaments (IF)—cytoskeletal elements that play important roles in cell physiology including the regulation of cell shape, motility, mechanics and intra-cellular signaling. Although a range of cell types are affected in GAN, neurons display the most severe pathology, with neuronal intermediate filament accumulation and aggregation; this in turn causes axonal swellings or “giant axons.” A mechanistic understanding of GAN IF pathology has eluded researchers for many years. In a recent study1 we demonstrate that the normal function of gigaxonin is to regulate the degradation of IF proteins via the proteasome. Our findings present the first direct link between GAN mutations and IF pathology; moreover, given the importance of IF aggregations in a wide range of disease conditions, our findings could have wider ramifications. PMID:25003002

  5. Redox Signaling in Diabetic Wound Healing Regulates Extracellular Matrix Deposition.

    PubMed

    Kunkemoeller, Britta; Kyriakides, Themis R

    2017-10-20

    Impaired wound healing is a major complication of diabetes, and can lead to development of chronic foot ulcers in a significant number of patients. Despite the danger posed by poor healing, very few specific therapies exist, leaving patients at risk of hospitalization, amputation, and further decline in overall health. Recent Advances: Redox signaling is a key regulator of wound healing, especially through its influence on the extracellular matrix (ECM). Normal redox signaling is disrupted in diabetes leading to several pathological mechanisms that alter the balance between reactive oxygen species (ROS) generation and scavenging. Importantly, pathological oxidative stress can alter ECM structure and function. There is limited understanding of the specific role of altered redox signaling in the diabetic wound, although there is evidence that ROS are involved in the underlying pathology. Preclinical studies of antioxidant-based therapies for diabetic wound healing have yielded promising results. Redox-based therapeutics constitute a novel approach for the treatment of wounds in diabetes patients that deserve further investigation. Antioxid. Redox Signal. 27, 823-838.

  6. Hybridization-Induced Aggregation Technology for Practical Clinical Testing: KRAS Mutation Detection in Lung and Colorectal Tumors.

    PubMed

    Sloane, Hillary S; Landers, James P; Kelly, Kimberly A

    2016-07-01

    KRAS mutations have emerged as powerful predictors of response to targeted therapies in the treatment of lung and colorectal cancers; thus, prospective KRAS genotyping is essential for appropriate treatment stratification. Conventional mutation testing technologies are not ideal for routine clinical screening, as they often involve complex, time-consuming processes and/or costly instrumentation. In response, we recently introduced a unique analytical strategy for revealing KRAS mutations, based on the allele-specific hybridization-induced aggregation (HIA) of oligonucleotide probe-conjugated microbeads. Using simple, inexpensive instrumentation, this approach allows for the detection of any common KRAS mutation in <10 minutes after PCR. Here, we evaluate the clinical utility of the HIA method for mutation detection (HIAMD). In the analysis of 20 lung and colon tumor pathology specimens, we observed a 100% correlation between the KRAS mutation statuses determined by HIAMD and sequencing. In addition, we were able to detect KRAS mutations in a background of 75% wild-type DNA-a finding consistent with that reported for sequencing. With this, we show that HIAMD allows for the rapid and cost-effective detection of KRAS mutations, without compromising analytical performance. These results indicate the validity of HIAMD as a mutation-testing technology suitable for practical clinical testing. Further expansion of this platform may involve the detection of mutations in other key oncogenic pathways. Copyright © 2016 American Society for Investigative Pathology and the Association for Molecular Pathology. Published by Elsevier Inc. All rights reserved.

  7. Gene regulation by noncoding RNAs

    PubMed Central

    Patil, Veena S.; Zhou, Rui; Rana, Tariq M.

    2015-01-01

    The past two decades have seen an explosion in research on noncoding RNAs and their physiological and pathological functions. Several classes of small (20–30 nucleotides) and long (>200 nucleotides) noncoding RNAs have been firmly established as key regulators of gene expression in myriad processes ranging from embryonic development to innate immunity. In this review, we focus on our current understanding of the molecular mechanisms underlying the biogenesis and function of small interfering RNAs (siRNAs), microRNAs (miRNAs), and Piwi-interacting RNAs (piRNAs). In addition, we briefly review the relevance of small and long noncoding RNAs to human physiology and pathology and their potential to be exploited as therapeutic agents. PMID:24164576

  8. Colon dysregulation in methamphetamine self-administering HIV-1 transgenic rats

    PubMed Central

    Bradaric, Brinda D.; Dodiya, Hemraj B.; Ohene-Nyako, Michael; Forsyth, Christopher B.; Keshavarzian, Ali; Shaikh, Maliha; Napier, T. Celeste

    2018-01-01

    The integrity and function of the gut is impaired in HIV-infected individuals, and gut pathogenesis may play a role in several HIV-associated disorders. Methamphetamine is a popular illicit drug abused by HIV-infected individuals. However, the effect of methamphetamine on the gut and its potential to exacerbate HIV-associated gut pathology is not known. To shed light on this scenario, we evaluated colon barrier pathology in a rat model of the human comorbid condition. Intestinal barrier integrity and permeability were assessed in drug-naïve Fischer 344 HIV-1 transgenic (Tg) and non-Tg rats, and in Tg and non-Tg rats instrumented with jugular cannulae trained to self-administer methamphetamine or serving as saline-yoked controls. Intestinal permeability was determined by measuring the urine content of orally gavaged sugars. Intestinal barrier integrity was evaluated by immunoblotting or immunofluorescence of colon claudin-1 and zonula occludens-1 (ZO-1), two major tight junction proteins that regulate gut epithelial paracellular permeability. Both non-Tg and Tg rats self-administered moderate amounts of methamphetamine. These amounts were sufficient to increase colon permeability, reduce protein level of claudin-1, and reduce claudin-1 and ZO-1 immunofluorescence in Tg rats relative to non-Tg rats. Methamphetamine decreased tight junction immunofluorescence in non-Tg rats, with a similar, but non-significant trend observed in Tg rats. However, the effect of methamphetamine on tight junction proteins was subthreshold to gut leakiness. These findings reveal that both HIV-1 proteins and methamphetamine alter colon barrier integrity, and indicate that the gut may be a pathogenic site for these insults. PMID:29293553

  9. Colon dysregulation in methamphetamine self-administering HIV-1 transgenic rats.

    PubMed

    Persons, Amanda L; Bradaric, Brinda D; Dodiya, Hemraj B; Ohene-Nyako, Michael; Forsyth, Christopher B; Keshavarzian, Ali; Shaikh, Maliha; Napier, T Celeste

    2018-01-01

    The integrity and function of the gut is impaired in HIV-infected individuals, and gut pathogenesis may play a role in several HIV-associated disorders. Methamphetamine is a popular illicit drug abused by HIV-infected individuals. However, the effect of methamphetamine on the gut and its potential to exacerbate HIV-associated gut pathology is not known. To shed light on this scenario, we evaluated colon barrier pathology in a rat model of the human comorbid condition. Intestinal barrier integrity and permeability were assessed in drug-naïve Fischer 344 HIV-1 transgenic (Tg) and non-Tg rats, and in Tg and non-Tg rats instrumented with jugular cannulae trained to self-administer methamphetamine or serving as saline-yoked controls. Intestinal permeability was determined by measuring the urine content of orally gavaged sugars. Intestinal barrier integrity was evaluated by immunoblotting or immunofluorescence of colon claudin-1 and zonula occludens-1 (ZO-1), two major tight junction proteins that regulate gut epithelial paracellular permeability. Both non-Tg and Tg rats self-administered moderate amounts of methamphetamine. These amounts were sufficient to increase colon permeability, reduce protein level of claudin-1, and reduce claudin-1 and ZO-1 immunofluorescence in Tg rats relative to non-Tg rats. Methamphetamine decreased tight junction immunofluorescence in non-Tg rats, with a similar, but non-significant trend observed in Tg rats. However, the effect of methamphetamine on tight junction proteins was subthreshold to gut leakiness. These findings reveal that both HIV-1 proteins and methamphetamine alter colon barrier integrity, and indicate that the gut may be a pathogenic site for these insults.

  10. Better by design: business preferences for environmental regulatory reform.

    PubMed

    Taylor, Christopher M; Pollard, Simon J T; Rocks, Sophie A; Angus, Andrew J

    2015-04-15

    We present the preferences for environmental regulatory reform expressed by 30 UK businesses and industry bodies from 5 sectors. While five strongly preferred voluntary regulation, seven expressed doubts about its effectiveness, and 18 expressed no general preference between instrument types. Voluntary approaches were valued for flexibility and lower burdens, but direct regulation offered stability and a level playing field. Respondents sought regulatory frameworks that: are coherent; balance clarity, prescription and flexibility; are enabled by positive regulatory relationships; administratively efficient; targeted according to risk magnitude and character; evidence-based and that deliver long-term market stability for regulatees. Anticipated differences in performance between types of instrument can be undermined by poor implementation. Results underline the need for policy makers and regulators to tailor an effective mix of instruments for a given sector, and to overcome analytical, institutional and political barriers to greater coherence, to better coordinate existing instruments and tackle new environmental challenges as they emerge. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. T cell-derived IL-10 and its impact on the regulation of host responses during malaria.

    PubMed

    Freitas do Rosario, Ana Paula; Langhorne, Jean

    2012-05-15

    Despite intense research, malaria still is the one of the most devastating diseases killing more people than any other parasitic infection. In an attempt to control the infection, the host immune system produces a potent pro-inflammatory response. However, this response is also associated with complications, such as severe anaemia, hypoglycaemia and cerebral malaria. This pronounced production of pro-inflammatory cytokines response is a common feature of malaria caused by parasites infecting humans as well as rodents and primates. A balance between pro- and anti-inflammatory responses may be fundamental to the elimination of the parasite without inducing excessive host pathology. IL-10 is a key cytokine that has been shown to have an important regulatory function in establishing this balance in malaria. Here we discuss which cells can produce IL-10 during infection, and present an overview of the evidence showing that T-cell derived IL-10 plays an important role in regulating malaria pathology. Many different subsets of T cells can produce IL-10, however, evidence is accumulating that it is effector Th1 CD4(+) T cells which provide the crucial source that down-regulates inflammatory pathology during blood-stage malaria infections. Copyright © 2012 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  12. Cyclic AMP Response Element Binding Protein Mediates Pathological Retinal Neovascularization via Modulating DLL4-NOTCH1 Signaling

    PubMed Central

    Singh, Nikhlesh K.; Kotla, Sivareddy; Kumar, Raj; Rao, Gadiparthi N.

    2015-01-01

    Retinal neovascularization is the most common cause of moderate to severe vision loss in all age groups. Despite the use of anti-VEGFA therapies, this complication continues to cause blindness, suggesting a role for additional molecules in retinal neovascularization. Besides VEGFA and VEGFB, hypoxia induced VEGFC expression robustly. Based on this finding, we tested the role of VEGFC in pathological retinal angiogenesis. VEGFC induced proliferation, migration, sprouting and tube formation of human retinal microvascular endothelial cells (HRMVECs) and these responses require CREB-mediated DLL4 expression and NOTCH1 activation. Furthermore, down regulation of VEGFC levels substantially reduced tip cell formation and retinal neovascularization in vivo. In addition, we observed that CREB via modulating the DLL4-NOTCH1 signaling mediates VEGFC-induced tip cell formation and retinal neovascularization. In regard to upstream mechanism, we found that down regulation of p38β levels inhibited hypoxia-induced CREB-DLL4-NOTCH1 activation, tip cell formation, sprouting and retinal neovascularization. Based on these findings, it may be suggested that VEGFC besides its role in the regulation of lymphangiogenesis also plays a role in pathological retinal angiogenesis and this effect depends on p38β and CREB-mediated activation of DLL4-NOTCH1 signaling. PMID:26870802

  13. Validation of Patient-Reported Outcomes Measurement Information System Computerized Adaptive Tests Against the Foot and Ankle Outcome Score for 6 Common Foot and Ankle Pathologies.

    PubMed

    Koltsov, Jayme C B; Greenfield, Stephen T; Soukup, Dylan; Do, Huong T; Ellis, Scott J

    2017-08-01

    The field of foot and ankle surgery lacks a widely accepted gold-standard patient-reported outcome instrument. With the changing infrastructure of the medical profession, more efficient patient-reported outcome tools are needed to reduce respondent burden and increase participation while providing consistent and reliable measurement across multiple pathologies and disciplines. The primary purpose of the present study was to validate 3 Patient-Reported Outcomes Measurement Information System computer adaptive tests (CATs) most relevant to the foot and ankle discipline against the Foot and Ankle Outcome Score (FAOS) and the Short Form 12 general health status survey in patients with 6 common foot and ankle pathologies. Patients (n = 240) indicated for operative treatment for 1 of 6 common foot and ankle pathologies completed the CATs, FAOS, and Short Form 12 at their preoperative surgical visits, 1 week subsequently (before surgery), and at 6 months postoperatively. The psychometric properties of the instruments were assessed and compared. The Patient-Reported Outcomes Measurement Information System CATs each took less than 1 minute to complete, whereas the FAOS took 6.5 minutes, and the Short Form 12 took 3 minutes. CAT scores were more normally distributed and had fewer floor and ceiling effects than those on the FAOS, which reached as high as 24%. The CATs were more precise than the FAOS and had similar responsiveness and test-retest reliability. The physical function and mobility CATs correlated strongly with the activities subscale of the FAOS, and the pain interference CAT correlated strongly with the pain subscale of the FAOS. The CATs and FAOS were responsive to changes with operative treatment for 6 common foot and ankle pathologies. The CATs performed as well as or better than the FAOS in all aspects of psychometric validity. The Patient-Reported Outcomes Measurement Information System CATs show tremendous potential for improving the study of patient outcomes in foot and ankle research through improved precision and reduced respondent burden. Level II, prospective comparative study.

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

    Vasuri, Francesco; Capizzi, Elisa; Bellavista, Elena

    Despite the central role of proteasomes in relevant physiological pathways and pathological processes, this topic is unexpectedly largely unexplored in human liver. Here we present data on the presence of proteasome and immunoproteasome in human livers from normal adults, fetuses and patients affected by major hepatic diseases such as cirrhosis and chronic active hepatitis. Immunohistochemistry for constitutive ({alpha}4 and {beta}1) and inducible (LMP2 and LMP7) proteasome subunits, and for the PA28{alpha}{beta} regulator, was performed in liver samples from 38 normal subjects, 6 fetuses, 2 pediatric cases, and 19 pathological cases (10 chronic active hepatitis and 9 cirrhosis). The immunohistochemical datamore » have been validated and quantified by Western blotting analysis. The most striking result we found was the concomitant presence in hepatocyte cytoplasm of all healthy subjects, including the pediatric cases, of constitutive proteasome and immunoproteasome subunits, as well as PA28{alpha}{beta}. At variance, immunoproteasome was not present in hepatocytes from fetuses, while a strong cytoplasmic and nuclear positivity for LMP2 and LMP7 was found in pathological samples, directly correlated to the histopathological grade of inflammation. At variance from other organs such as the brain, immunoproteasome is present in livers from normal adult and pediatric cases, in apparent absence of pathological processes, suggesting the presence of a peculiar regulation of the proteasome/immunoproteasome system, likely related to the physiological stimuli derived from the gut microbiota after birth. Other inflammatory stimuli contribute in inducing high levels of immunoproteasome in pathological conditions, where its role deserve further attention.« less

  15. Redox regulation of neuronal voltage-gated calcium channels.

    PubMed

    Todorovic, Slobodan M; Jevtovic-Todorovic, Vesna

    2014-08-20

    Voltage-gated calcium channels are ubiquitously expressed in neurons and are key regulators of cellular excitability and synaptic transmitter release. There is accumulating evidence that multiple subtypes of voltage-gated calcium channels may be regulated by oxidation and reduction. However, the redox mechanisms involved in the regulation of channel function are not well understood. Several studies have established that both T-type and high-voltage-activated subtypes of voltage-gated calcium channel can be redox-regulated. This article reviews different mechanisms that can be involved in redox regulation of calcium channel function and their implication in neuronal function, particularly in pain pathways and thalamic oscillation. A current critical issue in the field is to decipher precise mechanisms of calcium channel modulation via redox reactions. In this review we discuss covalent post-translational modification via oxidation of cysteine molecules and chelation of trace metals, and reactions involving nitric oxide-related molecules and free radicals. Improved understanding of the roles of redox-based reactions in regulation of voltage-gated calcium channels may lead to improved understanding of novel redox mechanisms in physiological and pathological processes. Identification of redox mechanisms and sites on voltage-gated calcium channel may allow development of novel and specific ion channel therapies for unmet medical needs. Thus, it may be possible to regulate the redox state of these channels in treatment of pathological process such as epilepsy and neuropathic pain.

  16. The Utrecht Ophthalmic Hospital and the development of the ophthalmoscope.

    PubMed

    Den Tonkelaar, I; Henkes, H E; van Leersum, G K

    1988-01-01

    The first useful table model ophthalmoscope was designed by Donders and the instrumentmaker Epkens. With the use of this instrument Donders' pupil Van Trigt made the first drawings of the normal and pathological fundus of the eye. His contribution was of great importance for the early diffusion of knowledge of the fundus of the eye.

  17. Modulation of neuroinflammation and pathology in the 5XFAD mouse model of Alzheimer's disease using a biased and selective beta-1 adrenergic receptor partial agonist.

    PubMed

    Ardestani, Pooneh Memar; Evans, Andrew K; Yi, Bitna; Nguyen, Tiffany; Coutellier, Laurence; Shamloo, Mehrdad

    2017-04-01

    Degeneration of noradrenergic neurons occurs at an early stage of Alzheimer's Disease (AD). The noradrenergic system regulates arousal and learning and memory, and has been implicated in regulating neuroinflammation. Loss of noradrenergic tone may underlie AD progression at many levels. We have previously shown that acute administration of a partial agonist of the beta-1 adrenergic receptor (ADRB1), xamoterol, restores behavioral deficits in a mouse model of AD. The current studies examined the effects of chronic low dose xamoterol on neuroinflammation, pathology, and behavior in the pathologically aggressive 5XFAD transgenic mouse model of AD. In vitro experiments in cells expressing human beta adrenergic receptors demonstrate that xamoterol is highly selective for ADRB1 and functionally biased for the cAMP over the β-arrestin pathway. Data demonstrate ADRB1-mediated attenuation of TNF-α production with xamoterol in primary rat microglia culture following LPS challenge. Finally, two independent cohorts of 5XFAD and control mice were administered xamoterol from approximately 4.0-6.5 or 7.0-9.5 months, were tested in an array of behavioral tasks, and brains were examined for evidence of neuroinflammation, and amyloid beta and tau pathology. Xamoterol reduced mRNA expression of neuroinflammatory markers (Iba1, CD74, CD14 and TGFβ) and immunohistochemical evidence for microgliosis and astrogliosis. Xamoterol reduced amyloid beta and tau pathology as measured by regional immunohistochemistry. Behavioral deficits were not observed for 5XFAD mice. In conclusion, chronic administration of a selective, functionally biased, partial agonist of ADRB1 is effective in reducing neuroinflammation and amyloid beta and tau pathology in the 5XFAD model of AD. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. [The recent news in endoscopic surgery: a review of the literature and meta-analysis].

    PubMed

    Klimenko, K É

    2012-01-01

    During a few recent years, endonasal surgery has become the principal tool for the operative treatment of many pathologies affecting the base of the skull. The present work was designed to estimate the possibilities of using endoscopic endonasal surgery to treat sinus and skull base lesions and illustrate the recent progress in the development of endoscopic equipment and instrumentation. The meta-analysis of the results of on-going research on the application of the endonasal endoscopic technology is described with the special emphasis on the plastic treatment of liquor fistulas, removal of juvenile nasopharyngeal angiofibromas, treatment of pathological changes in the clivial region and odontoid cervicomedullary junction.

  19. A survey of speech and language pathology services for Down syndrome: state of the art.

    PubMed

    Kumin, L

    1986-01-01

    This article summarizes current trends in speech and language pathology services to individuals with Down syndrome. Data was collected through the use of a questionnaire mailed to speech and language pathologists who regularly serve clients with Down syndrome. Most widely used assessment instruments, therapy materials, sources of information, and need for materials to be developed are presented as they relate to services for birth-3 year olds, 3-5 year olds, school-age-14 year olds, prevocational-18 year olds, and above-age-18 adult services. The discussion addresses specific needs for research and needed direction for evaluation and treatment with the Down syndrome population.

  20. Higs-instrument: design and demonstration of a high performance gas concentration imager

    NASA Astrophysics Data System (ADS)

    Verlaan, A. L.; Klop, W. A.; Visser, H.; van Brug, H.; Human, J.

    2017-09-01

    Climate change and environmental conditions are high on the political agenda of international governments. Laws and regulations are being setup all around the world to improve the air quality and to reduce the impact. The growth of a number of trace gasses, including CO2, Methane and NOx are especially interesting due to their environmental impact. The regulations made are being based on both models and measurements of the trend of those trace gases over the years. Now the regulations are in place also enforcement and therewith measurements become more and more important. Instruments enabling high spectral and spatial resolution as well as high accurate measurements of trace gases are required to deliver the necessary inputs. Nowadays those measurements are usually performed by space based spectrometers. The requirement for high spectral resolution and measurement accuracy significantly increases the size of the instruments. As a result the instrument and satellite becomes very expensive to develop and to launch. Specialized instruments with a small volume and the required performance will offer significant advantages in both cost and performance. Huib's Innovative Gas Sensor (HIGS, named after its inventor Huib Visser), currently being developed at TNO is an instrument that achieves exactly that. Designed to measure only a single gas concentration, opposed to deriving it from a spectrum, it achieves high performance within a small design volume. The instrument enables instantaneous imaging of the gas distribution of the selected gas. An instrument demonstrator has been developed for NO2 detection. Laboratory measurements proved the measurement technique to be successful. An on-sky measurement campaign is in preparation. This paper addresses both the instrument design as well as the demonstrated performances.

  1. 49 CFR 572.77 - Instrumentation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 7 2011-10-01 2011-10-01 false Instrumentation. 572.77 Section 572.77 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY... Instrumentation. (a)(1) Test probe. For the head, thorax, and knee impact test, use a test probe that is rigid, of...

  2. 49 CFR 572.77 - Instrumentation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 7 2013-10-01 2013-10-01 false Instrumentation. 572.77 Section 572.77 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY... Instrumentation. (a)(1) Test probe. For the head, thorax, and knee impact test, use a test probe that is rigid, of...

  3. 49 CFR 572.77 - Instrumentation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 7 2012-10-01 2012-10-01 false Instrumentation. 572.77 Section 572.77 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY... Instrumentation. (a)(1) Test probe. For the head, thorax, and knee impact test, use a test probe that is rigid, of...

  4. 49 CFR 572.77 - Instrumentation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 7 2014-10-01 2014-10-01 false Instrumentation. 572.77 Section 572.77 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY TRAFFIC SAFETY... Instrumentation. (a)(1) Test probe. For the head, thorax, and knee impact test, use a test probe that is rigid, of...

  5. 15 CFR 301.6 - Appeals.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... States an instrument of equivalent scientific value for the purposes for which the instrument to which... ADMINISTRATION, DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.6 Appeals. (a) An appeal from a final decision made by the Director under § 301...

  6. 15 CFR 301.6 - Appeals.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... States an instrument of equivalent scientific value for the purposes for which the instrument to which... ADMINISTRATION, DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.6 Appeals. (a) An appeal from a final decision made by the Director under § 301...

  7. 15 CFR 301.6 - Appeals.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... States an instrument of equivalent scientific value for the purposes for which the instrument to which... ADMINISTRATION, DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.6 Appeals. (a) An appeal from a final decision made by the Director under § 301...

  8. 15 CFR 301.6 - Appeals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... States an instrument of equivalent scientific value for the purposes for which the instrument to which... ADMINISTRATION, DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.6 Appeals. (a) An appeal from a final decision made by the Director under § 301...

  9. 15 CFR 301.6 - Appeals.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... States an instrument of equivalent scientific value for the purposes for which the instrument to which... ADMINISTRATION, DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.6 Appeals. (a) An appeal from a final decision made by the Director under § 301...

  10. The Relationships among Students' Future-Oriented Goals and Subgoals, Perceived Task Instrumentality, and Task-Oriented Self-Regulation Strategies in an Academic Environment

    ERIC Educational Resources Information Center

    Tabachnick, Sharon E.; Miller, Raymond B.; Relyea, George E.

    2008-01-01

    The authors performed path analysis, followed by a bootstrap procedure, to test the predictions of a model explaining the relationships among students' distal future goals (both extrinsic and intrinsic), their adoption of a middle-range subgoal, their perceptions of task instrumentality, and their proximal task-oriented self-regulation strategies.…

  11. The biology of the peroxisome proliferator-activated receptor system in the female reproductive tract.

    PubMed

    Vélez, Leandro Martín; Abruzzese, Giselle Adriana; Motta, Alicia Beatriz

    2013-01-01

    Fuel sensors such as glucose, insulin or leptin, are known to be directly involved in the regulation of fertility at each level of the hypothalamic-pituitary-gonadal axis. The discovery of the peroxisome proliferator-activated receptor (PPAR) family of transcription factors has revealed the link between lipid/glucose availability and long-term metabolic adaptation. By binding to specific regions of DNA in heterodimers with the retinoid X receptors (RXRs), the members of the PPAR family (α, β/δ, γ) are able to regulate the gene expressions of several key regulators of energy homeostasis including several glucose regulators (glucose transporters, insulin receptor, substrate insulin receptor, etc), and also metabolic and endocrine pathways like lipogenesis, steroidogenesis, ovulation, oocyte maturation, maintenance of the corpus luteum, nitric oxide system, several proteases and plasminogen activator among others. All the three PPAR isoforms are expressed in different tissues of the female reproductive tract and regulate gametogenesis, ovulation, corpus luteum regression and the implantation process among others. The present review discusses the mechanisms involved in PPAR activation focusing on endogenous and synthetic ligands of PPAR not only in physiological but also in pathological conditions (such as polycystic ovary syndrome, pathologies of implantation process, chronic anovulation, etc).

  12. 17β-estradiol regulates the RNA-binding protein Nova1, which then regulates the alternative splicing of estrogen receptor β in the aging female rat brain.

    PubMed

    Shults, Cody L; Dingwall, Caitlin B; Kim, Chun K; Pinceti, Elena; Rao, Yathindar S; Pak, Toni R

    2018-01-01

    Alternative RNA splicing results in the translation of diverse protein products arising from a common nucleotide sequence. These alternative protein products are often functional and can have widely divergent actions from the canonical protein. Studies in humans and other vertebrate animals have demonstrated that alternative splicing events increase with advanced age, sometimes resulting in pathological consequences. Menopause represents a critical transition for women, where the beneficial effects of estrogens are no longer evident; therefore, factors underlying increased pathological conditions in women are confounded by the dual factors of aging and declining estrogens. Estrogen receptors (ERs) are subject to alternative splicing, the spliced variants increase following menopause, and they fail to efficiently activate estrogen-dependent signaling pathways. However, the factors that regulate the alternative splicing of ERs remain unknown. We demonstrate novel evidence supporting a potential biological feedback loop where 17β-estradiol regulates the RNA-binding protein Nova1, which, in turn, regulates the alternative splicing of ERβ. These data increase our understanding of ER alternative splicing and could have potential implications for women taking hormone replacement therapy after menopause. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Hormonal Regulation of Extinction: Implications for Gender Differences in the Mechanisms of PTSD

    DTIC Science & Technology

    2010-03-01

    Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT This project investigates the role of gonadal hormones in the regulation of Pavlovian fear conditioning ...and its extinction. Pavlovian fear conditioning and its extinction serve as an animal model for the development of pathological fear in humans that...gonadal hormones in the regulation of Pavlovian fear conditioning and its extinction. Pavlovian fear conditioning and its extinction serve as an animal

  14. Acquiring experience in pathology predominantly from what you see, not from what you read: the HIPON e-learning platform.

    PubMed

    Riccioni, Olga; Vrasidas, Charalambos; Brcic, Luka; Armenski, Goce; Seiwerth, Sven; Smeets, Annemieke; van Krieken, J Han Jm; Lazaris, Andreas C

    2015-01-01

    It is indisputable that nowadays one of the hardest and most important tasks in medicine and especially in medical education, is the conversion of the extensive amount of available data, into medical experience, after a proper analysis. A project under the title "ICT (Information and Communication Technology) eModules on HistoPathology: a useful online tool for students, researchers and professionals - HIPON", co-financed by the Lifelong Learning Program of the Education, Audiovisual and Culture Executive Agency (EACEA), The Commission of the European Union, has been launched at the beginning of 2013. HIPON's purpose is not to provide just another pathology website atlas, but to convey professional experience and thinking in pathology. HIPON has resulted in a well-structured and user-friendly, open resource, multi-language, e-learning platform which, taking advantage of modern image technology, offers medical students, researchers, and professionals a valuable teaching instrument so that they can acquire professional experience in pathology. The mid-term report of HIPON has been favorably evaluated by the EACEA experts who appreciated the potential of our teaching tool in providing the opportunity and the means to acquire medical experience. Through the use of virtual slides, educative videos and microscopic, high resolution, marked images accompanied by relevant questions and answers, HIPON project aims to make end-users able to think as experienced pathologists and become highly efficient in correlating pathologic data with other clinical-laboratory information.

  15. Surgical Management of Spinal Conditions in the Elderly Osteoporotic Spine.

    PubMed

    Goldstein, Christina L; Brodke, Darrel S; Choma, Theodore J

    2015-10-01

    Osteoporosis, the most common form of metabolic bone disease, leads to alterations in bone structure and density that have been shown to compromise the strength of spinal instrumentation. In addition, osteoporosis may contribute to high rates of fracture and instrumentation failure after long posterior spinal fusions, resulting in proximal junctional kyphosis and recurrent spinal deformity. As increasing numbers of elderly patients present for surgical intervention for degenerative and traumatic spinal pathologies, current and future generations of spine surgeons will increasingly be faced with the challenge of obtaining adequate fixation in osteoporotic bone. The purpose of this review is to familiarize the reader with the impact of osteoporosis on spinal instrumentation, the broad variety of techniques that have been developed for addressing these issues, and the biomechanical and clinical evidence in support of the use of these techniques.

  16. Hyperthyroidism Improves the Pathological Condition of Nonalcoholic Steatohepatitis: A Case of Nonalcoholic Steatohepatitis with Graves' Disease.

    PubMed

    Miyake, Teruki; Matsuura, Bunzo; Furukawa, Shinya; Todo, Yasuhiko; Yamamoto, Shin; Yoshida, Osamu; Imai, Yusuke; Watanabe, Takao; Yamamoto, Yasunori; Hirooka, Masashi; Tokumoto, Yoshio; Kumagi, Teru; Abe, Masanori; Seike, Hirotaka; Miyauchi, Shozo; Hiasa, Yoichi

    2016-01-01

    3,5,3'-triiodo-L-thyronine regulates the glucose metabolism, lipid metabolism, and hepatic steatosis. Several groups have shown the relationships between hypothyroidism and nonalcoholic fatty liver and hypothyroidism and nonalcoholic steatohepatitis (NASH). However, the effect of hyperthyroidism on NASH has not yet been investigated. We herein report effects of thyroid hormone on the pathological condition of NASH in a patient with NASH complicated by Graves' disease. In our case, the liver enzyme level improved with the increasing thyroid hormone level; however, the liver enzyme level was aggravated with the improving thyroid hormone level. Therefore, hyperthyroidism may improve the pathological condition of NASH.

  17. Developing brain networks of attention.

    PubMed

    Posner, Michael I; Rothbart, Mary K; Voelker, Pascale

    2016-12-01

    Attention is a primary cognitive function critical for perception, language, and memory. We provide an update on brain networks related to attention, their development, training, and pathologies. An executive attention network, also called the cingulo-opercular network, allows voluntary control of behavior in accordance with goals. Individual differences among children in self-regulation have been measured by a higher order factor called effortful control, which is related to the executive network and to the size of the anterior cingulate cortex. Brain networks of attention arise in infancy and are related to individual differences, including pathology during childhood. Methods of training attention may improve performance and ameliorate pathology.

  18. The role of the postsynaptic density in the pathology of the fragile X syndrome.

    PubMed

    Kindler, Stefan; Kreienkamp, Hans-Jürgen

    2012-01-01

    The protein repertoire of excitatory synapses controls dendritic spine morphology, synaptic plasticity and higher brain functions. In brain neurons, the RNA-associated fragile X mental retardation protein (FMRP) binds in vivo to various transcripts encoding key postsynaptic components and may thereby substantially regulate the molecular composition of dendritic spines. In agreement with this notion functional loss of FMRP in patients affected by the fragile X syndrome (FXS) causes cognitive impairment. Here we address our current understanding of the functional role of individual postsynaptic proteins. We discuss how FMRP controls the abundance of select proteins at postsynaptic sites, which signaling pathways regulate the local activity of FMRP at synapses, and how altered levels of postsynaptic proteins may contribute to FXS pathology.

  19. Action of RORs and Their Ligands in (Patho)physiology

    PubMed Central

    Solt, Laura A.; Burris, Thomas P.

    2012-01-01

    The retinoic-acid-receptor-related orphan receptors (RORs) are members of the nuclear receptor (NR) superfamily whose activity has been implicated in a number of physiological and pathological processes. The RORs, specifically RORα and RORγ, are considered master regulators of TH17 cells, a recently described subset of CD4+ T helper cells that have been demonstrated to have a pathological role in autoimmune disease. As with most members of the NR superfamily, RORs are ligand regulated, suggesting that their activity can be modulated by synthetic ligands. Recent advances in the field have established that selective inhibition of the RORs is a viable therapeutic approach for not only the treatment of autoimmune disorders, but ROR-mediated metabolic disorders as well. PMID:22789990

  20. [Fibroblast growth factors and their effects in pancreas organogenesis].

    PubMed

    Gnatenko, D A; Kopantzev, E P; Sverdlov, E D

    2017-05-01

    Fibroblast growth factors (FGF) - growth factors that regulate many important biological processes, including proliferation and differentiation of embryonic cells during organogenesis. In this review, we will summarize current information about the involvement of FGFs in the pancreas organogenesis. Pancreas organogenesis is a complex process, which involves constant signaling from mesenchymal tissue. This orchestrates the activation of various regulator genes at specific stages, determining the specification of progenitor cells. Alterations in FGF/FGFR signaling pathway during this process lead to incorrect activation of the master genes, which leads to different pathologies during pancreas development. Understanding the full picture about role of FGF factors in pancreas development will make it possible to more accurately understand their role in other pathologies of this organ, including carcinogenesis.

  1. 49 CFR 572.21 - Test conditions and instrumentation.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 49 Transportation 7 2014-10-01 2014-10-01 false Test conditions and instrumentation. 572.21 Section 572.21 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY...-Year-Old Child § 572.21 Test conditions and instrumentation. (a)(1) The test probe used for head and...

  2. 49 CFR 572.21 - Test conditions and instrumentation.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 49 Transportation 7 2013-10-01 2013-10-01 false Test conditions and instrumentation. 572.21 Section 572.21 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY...-Year-Old Child § 572.21 Test conditions and instrumentation. (a)(1) The test probe used for head and...

  3. 49 CFR 572.21 - Test conditions and instrumentation.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 49 Transportation 7 2011-10-01 2011-10-01 false Test conditions and instrumentation. 572.21 Section 572.21 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY...-Year-Old Child § 572.21 Test conditions and instrumentation. (a)(1) The test probe used for head and...

  4. 49 CFR 572.21 - Test conditions and instrumentation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 49 Transportation 7 2012-10-01 2012-10-01 false Test conditions and instrumentation. 572.21 Section 572.21 Transportation Other Regulations Relating to Transportation (Continued) NATIONAL HIGHWAY...-Year-Old Child § 572.21 Test conditions and instrumentation. (a)(1) The test probe used for head and...

  5. 24 CFR 107.25 - Provisions in legal instruments.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 24 Housing and Urban Development 1 2012-04-01 2012-04-01 false Provisions in legal instruments. 107.25 Section 107.25 Housing and Urban Development Regulations Relating to Housing and Urban... Provisions in legal instruments. (a) The following documents shall contain provisions or statements requiring...

  6. 24 CFR 107.25 - Provisions in legal instruments.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 1 2010-04-01 2010-04-01 false Provisions in legal instruments. 107.25 Section 107.25 Housing and Urban Development Regulations Relating to Housing and Urban... Provisions in legal instruments. (a) The following documents shall contain provisions or statements requiring...

  7. The Regulation of Steroid Action by Sulfation and Desulfation

    PubMed Central

    Mueller, Jonathan W.; Gilligan, Lorna C.; Idkowiak, Jan; Arlt, Wiebke

    2015-01-01

    Steroid sulfation and desulfation are fundamental pathways vital for a functional vertebrate endocrine system. After biosynthesis, hydrophobic steroids are sulfated to expedite circulatory transit. Target cells express transmembrane organic anion-transporting polypeptides that facilitate cellular uptake of sulfated steroids. Once intracellular, sulfatases hydrolyze these steroid sulfate esters to their unconjugated, and usually active, forms. Because most steroids can be sulfated, including cholesterol, pregnenolone, dehydroepiandrosterone, and estrone, understanding the function, tissue distribution, and regulation of sulfation and desulfation processes provides significant insights into normal endocrine function. Not surprisingly, dysregulation of these pathways is associated with numerous pathologies, including steroid-dependent cancers, polycystic ovary syndrome, and X-linked ichthyosis. Here we provide a comprehensive examination of our current knowledge of endocrine-related sulfation and desulfation pathways. We describe the interplay between sulfatases and sulfotransferases, showing how their expression and regulation influences steroid action. Furthermore, we address the role that organic anion-transporting polypeptides play in regulating intracellular steroid concentrations and how their expression patterns influence many pathologies, especially cancer. Finally, the recent advances in pharmacologically targeting steroidogenic pathways will be examined. PMID:26213785

  8. Regulated production of free radicals by the mitochondrial electron transport chain: Cardiac ischemic preconditioning.

    PubMed

    Matsuzaki, Satoshi; Szweda, Pamela A; Szweda, Luke I; Humphries, Kenneth M

    2009-11-30

    Excessive production of free radicals by mitochondria is associated with, and likely contributes to, the progression of numerous pathological conditions. Nevertheless, the production of free radicals by the mitochondria may have important biological functions under normal or stressed conditions by activating or modulating redox-sensitive cellular signaling pathways. This raises the intriguing possibility that regulated mitochondrial free radical production occurs via mechanisms that are distinct from pathologies associated with oxidative damage. Indeed, the capacity of mitochondria to produce free radicals in a limited manner may play a role in ischemic preconditioning, the phenomenon whereby short bouts of ischemia protect from subsequent prolonged ischemia and reperfusion. Ischemic preconditioning can thus serve as an important model system for defining regulatory mechanisms that allow for transient, signal-inducing, production of free radicals by mitochondria. Defining how these mechanism(s) occur will provide insight into therapeutic approaches that minimize oxidative damage without altering normal cellular redox biology. The aim of this review is to present and discuss evidence for the regulated production of superoxide by the electron transport chain within the ischemic preconditioning paradigm of redox regulation.

  9. Why Do People Regulate Their Emotions? A Taxonomy of Motives in Emotion Regulation.

    PubMed

    Tamir, Maya

    2016-08-01

    Emotion regulation involves the pursuit of desired emotional states (i.e., emotion goals) in the service of superordinate motives. The nature and consequences of emotion regulation, therefore, are likely to depend on the motives it is intended to serve. Nonetheless, limited attention has been devoted to studying what motivates emotion regulation. By mapping the potential benefits of emotion to key human motives, this review identifies key classes of motives in emotion regulation. The proposed taxonomy distinguishes between hedonic motives that target the immediate phenomenology of emotions, and instrumental motives that target other potential benefits of emotions. Instrumental motives include behavioral, epistemic, social, and eudaimonic motives. The proposed taxonomy offers important implications for understanding the mechanism of emotion regulation, variation across individuals and contexts, and psychological function and dysfunction, and points to novel research directions. © 2015 by the Society for Personality and Social Psychology, Inc.

  10. Targeting GPCR-Gβγ-GRK2 signaling as a novel strategy for treating cardiorenal pathologies.

    PubMed

    Rudomanova, Valeria; Blaxall, Burns C

    2017-08-01

    The pathologic crosstalk between the heart and kidney is known as cardiorenal syndrome (CRS). While the specific mechanisms underlying this crosstalk remain poorly understood, CRS is associated with exacerbated dysfunction of either or both organs and reduced survival. Maladaptive fibrotic remodeling is a key component of both heart and kidney failure pathogenesis and progression. G-protein coupled receptor (GPCR) signaling is a crucial regulator of cardiovascular and renal function. Chronic/pathologic GPCR signaling elicits the interaction of the G-protein Gβγ subunit with GPCR kinase 2 (GRK2), targeting the receptor for internalization, scaffolding to pathologic signals, and receptor degradation. Targeting this pathologic Gβγ-GRK2 interaction has been suggested as a possible strategy for the treatment of HF. In the current review, we discuss recent updates in understanding the role of GPCR-Gβγ-GRK2 signaling as a crucial mediator of maladaptive organ remodeling detected in HF and kidney dysfunction, with specific attention to small molecule-mediated inhibition of pathologic Gβγ-GRK2 interactions. Further, we explore the potential of GPCR-Gβγ-GRK2 signaling as a possible therapeutic target for cardiorenal pathologies. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Distraction systems for ankle arthroscopy.

    PubMed

    Palladino, S J

    1994-07-01

    It is clear that for most of the routine pathology addressed with ankle arthroscopy, including most talar dome transchondral fractures, manual distraction (or none at all) is all that is necessary to successfully complete the procedure. There is little need to add the expense and potential complications associated with some distraction systems. However, some cases involve pathology or surgical techniques that either would be better addressed with distraction or absolutely demand distraction. It is recommended that invasive ankle distraction be reserved for (1) cases in which noninvasive distraction has not yielded adequate field visualization or instrument maneuvering room, (2) cases of preoperatively documented pathology involving the posterior talar dome (including some medial talar dome fractures) or inferior tibial surface, or (3) arthroscopic ankle fusion. Consideration should be given to providing 6 to 12 weeks of protected function of the extremity to avoid delayed fracture presentation. In general, the invasive distraction system should be reserved for those cases that would not ordinarily be managed with aggressive rehabilitation and early return to activities. For those cases where the benefits of distraction are desired (some dome fractures, meniscoid lesions, gutter pathology, and adhesive capsulitis) and aggressive rehabilitation with early return to activities may be planned, noninvasive distraction systems are now available that offer a sustainable joint separation of good magnitude. With the growing availability and effectiveness of the commercial noninvasive ankle distractors, I do not disagree with Stone and Guhl98 when they advocate the use of noninvasive distraction for routine arthroscopic procedures, with conversion to invasive distraction should there be insufficient joint separation. In summary, providing optimal field visualization and maneuvering room for instrumentation is essential for the successful performance of arthroscopic ankle surgery. This article has discussed options available to the arthroscopist that can assist in achieving these objectives. The exact method of distraction selected for a given case may be determined by the arthroscopist by weighing the issues discussed in this article.

  12. Parkin clearance of dysfunctional mitochondria regulates ROS levels and increases survival of human chondrocytes.

    PubMed

    Ansari, M Y; Khan, N M; Ahmad, I; Haqqi, T M

    2017-08-08

    Mitochondrial dysfunction, oxidative stress and chondrocyte death are important contributors to the development and pathogenesis of osteoarthritis (OA). In this study, we determined the expression and role of Parkin in the clearance of damaged/dysfunctional mitochondria, regulation of reactive oxygen species (ROS) levels and chondrocyte survival under pathological conditions. Human chondrocytes were from the unaffected area of knee OA cartilage (n = 12) and were stimulated with IL-1β to mimic pathological conditions. Mitochondrial membrane depolarization and ROS levels were determined using specific dyes and flow cytometry. Autophagy was determined by Western blotting for ATG5, Beclin1, immunofluorescence staining and confocal microscopy. Gene expression was determined by RT-qPCR. siRNA, wild-type and mutant Parkin plasmids were transfected using Amaxa system. Apoptosis was determined by PI staining of chondrocytes and TUNEL assay. IL-1β-stimulated OA chondrocytes showed high levels of ROS generation, mitochondrial membrane damage, accumulation of damaged mitochondria and higher incidence of apoptosis. IL-1β stimulation of chondrocytes with depleted Parkin expression resulted in sustained high levels of ROS, accumulation of damaged/dysfunctional mitochondria and enhanced apoptosis. Parkin translocation to depolarized/damaged mitochondria and recruitment of p62/SQSTM1 was required for the elimination of damaged/dysfunctional mitochondria in IL-1β-stimulated OA chondrocytes. Importantly we demonstrate that Parkin elimination of depolarized/damaged mitochondria required the Parkin ubiquitin ligase activity and resulted in reduced ROS levels and inhibition of apoptosis in OA chondrocytes under pathological conditions. Our data demonstrates that Parkin functions to eliminate depolarized/damaged mitochondria in chondrocytes which is necessary for mitochondrial quality control, regulation of ROS levels and chondrocyte survival under pathological conditions. Copyright © 2017 Osteoarthritis Research Society International. Published by Elsevier Ltd. All rights reserved.

  13. Novel Genetic Models to Study the Role of Inflammation in Brain Injury-Induced Alzheimer’s Pathology

    DTIC Science & Technology

    2014-12-01

    AD_________________ Award Number: W81XWH-12-1-0629 TITLE: Novel Genetic Models to Study the Role...CONTRACT NUMBER Novel Genetic Models to Study the Role of Inflammation in Brain Injury-Induced Alzheimer’s Pathology 5b. GRANT NUMBER W81XWH-12-1...However, our laboratories have recently performed pioneering studies using genetic labels regulated by these chemokine-receptor promoters to show

  14. Laser versus cold instruments for microlaryngoscopic surgery.

    PubMed

    Zeitels, S M

    1996-05-01

    Controversy has arisen concerning the merits of the CO2 laser in microlaryngoscopic surgery because of the potentially harmful effects that the injudicious application of the laser could have on voice production. In an effort to develop a logical approach to instrument selection, the author examined the use of both cold instruments and the CO2 laser in the treatment of various benign and malignant lesions. A retrospective review of 307 microlaryngeal procedures performed over a 3-year period revealed that 263 (86%) were glottal and 44 (14%) were supraglottal. Of the 263 glottal procedures, 203 (77%) employed cold instruments alone and 60 (23%) used both cold instruments and the CO2 laser. The laser was used to assist in all 44 supraglottal procedures. Therefore, 203 (66%) of 307 procedures were done with cold instruments alone, and 104 (34%) of 307 procedures were performed using the CO2 laser with cold instruments. Lesions were stratified on the basis of pathology and size, as well as surgical approach. A primary phonomicrosurgical principle in glottal surgery is to maximally preserve the vocal fold's layered microstructure (laminae propria and epithelium). Precise tangential dissection was necessary for achieving this goal. For limited lesions, this dissection was best accomplished with cold instruments alone. The CO2 laser facilitated hemostatic surgical dissection for all supraglottal lesions and for selected larger glottal lesions in which bleeding would obscure visualization of the microanatomy of the musculomembranous vocal fold.

  15. Near-infrared light-controlled regulation of intracellular calcium to modulate macrophage polarization.

    PubMed

    Kang, Heemin; Zhang, Kunyu; Wong, Dexter Siu Hong; Han, Fengxuan; Li, Bin; Bian, Liming

    2018-04-21

    Macrophages are multifunctional immune cells with diverse physiological functions such as fighting against infection, influencing progression of pathologies, maintaining homeostasis, and regenerating tissues. Macrophages can be induced to adopt distinct polarized phenotypes, such as classically activated pro-inflammatory (M1) phenotypes or alternatively activated anti-inflammatory and pro-healing (M2), to execute diverse and dynamic immune functions. However, unbalanced polarizations of macrophage can lead to various pathologies, such as atherosclerosis, obesity, tumor, and asthma. Thus, the capability to remotely control macrophage phenotypes is important to the success of treating many pathological conditions involving macrophages. In this study, we developed an upconversion nanoparticle (UCNP)-based photoresponsive nanocarrier for near-infrared (NIR) light-mediated control of intracellular calcium levels to regulate macrophage polarization. UCNP was coated with mesoporous silica (UCNP@mSiO 2 ), into which loaded calcium regulators that can either supply or deplete calcium ions. UCNP@mSiO 2 was chemically modified through serial coupling of photocleavable linker and Arg-Gly-Asp (RGD) peptide-bearing molecular cap via cyclodextrin-adamantine host-guest complexation. The RGD-bearing cap functioned as the photolabile gating structure to control the release of calcium regulators and facilitated the cellular uptake of UCNP@mSiO 2 nanocarrier. The upconverted UV light emission from the UCNP@mSiO 2 under NIR light excitation triggered the cleavage of cap and intracellular release of calcium regulators, thereby allowing temporal regulation on the intracellular calcium levels. Application of NIR light through skin tissue promoted M1 or M2 polarization of macrophages, by elevating or depleting intracellular calcium levels, respectively. To the best of our knowledge, this is the first demonstration of NIR light-mediated remote control on macrophage polarization. This photoresponsive nanocarrier offers the potential to remotely manipulate in vivo immune functions, such as inflammation or tissue regeneration, via NIR light-controlled macrophage polarization. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Transfer Technique Is Associated With Shoulder Pain and Pathology in People With Spinal Cord Injury: A Cross-Sectional Investigation.

    PubMed

    Hogaboom, Nathan S; Worobey, Lynn A; Boninger, Michael L

    2016-10-01

    To evaluate how transfer technique and subject characteristics relate to ultrasound measures of shoulder soft tissue pathology and self-reported shoulder pain during transfers in a sample of wheelchair users with spinal cord injury (SCI). Cross-sectional observational study. Research laboratory, national and local veterans' wheelchair sporting events. A convenience sample of wheelchair users (N=76) with nonprogressive SCI. Participants were aged >18 years, >1 year postinjury, and could complete repeated independent wheelchair transfers without the use of their leg muscles. Not applicable. Transfer pain items from the Wheelchair User's Shoulder Pain Index; transfer technique assessed using the Transfer Assessment Instrument (TAI); and shoulder pathology markers examined using the Ultrasound Shoulder Pathology Rating Scale (USPRS). Better transfer technique (higher TAI) correlated with less injury (lower USPRS) (partial η(2)=.062, P<.05) and less pain during transfers (partial η(2)=.049, P<.10). Greater age was the strongest predictor of greater pathology (USPRS total: partial η(2)=.225, supraspinatus grade: partial η(2)=.174, P<.01). An interaction between technique and weight was found (P<.10): participants with lower body weights showed a decrease in pathology markers with better transfer technique (low weight: R(2)=.422, P<.05; middle weight: R(2)=.200, P<.01), while those with higher weight showed little change with technique (R(2)=.018, P>.05). Participants with better transfer technique exhibited less shoulder pathology and reported less pain during transfers. The relationship between technique and pathology was strongest in lower-weight participants. While causation cannot be proven because of study design, it is possible that using a better transfer technique and optimizing body weight could reduce the incidence of shoulder pathology and pain. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  17. Spectral optical coherence tomography: a novel technique for cornea imaging.

    PubMed

    Kaluzny, Bartłomiej J; Kaluzy, Bartłomiej J; Kałuzny, Jakub J; Szkulmowska, Anna; Gorczyńska, Iwona; Szkulmowski, Maciej; Bajraszewski, Tomasz; Wojtkowski, Maciej; Targowski, Piotr

    2006-09-01

    Spectral optical coherence tomography (SOCT) is a new, noninvasive, noncontact, high-resolution technique that provides cross-sectional images of the objects that weakly absorb and scatter light. SOCT, because of very short acquisition time and high sensitivity, is capable of providing tomograms of substantially better quality than the conventional OCT. The aim of this paper is to show the application of the SOCT to cross-sectional imaging of the cornea and its pathologies. Eleven eyes with different corneal pathologies were examined with a slit lamp and the use of a prototype SOCT instrument constructed in the Institute of Physics, Nicolaus Copernicus University, Toruń, Poland. Our SOCT system provides high-resolution (4 microm axial, 10 microm transversal) tomograms composed of 3000-5000 A-scans with an acquisition time of 120-200 ms. The quality of the images is adequate for detailed cross-sectional evaluation of various corneal pathologies. Objective assessment of the localization, size, shape, and light-scattering properties of the changed tissue is possible. Corneal and epithelial thickness and the depth and width of lesions can be estimated. SOCT technique allows acquiring clinically valuable cross-sectional optical biopsy of the cornea and its pathologies.

  18. Privacy and security of patient data in the pathology laboratory

    PubMed Central

    Cucoranu, Ioan C.; Parwani, Anil V.; West, Andrew J.; Romero-Lauro, Gonzalo; Nauman, Kevin; Carter, Alexis B.; Balis, Ulysses J.; Tuthill, Mark J.; Pantanowitz, Liron

    2013-01-01

    Data protection and security are critical components of routine pathology practice because laboratories are legally required to securely store and transmit electronic patient data. With increasing connectivity of information systems, laboratory work-stations, and instruments themselves to the Internet, the demand to continuously protect and secure laboratory information can become a daunting task. This review addresses informatics security issues in the pathology laboratory related to passwords, biometric devices, data encryption, internet security, virtual private networks, firewalls, anti-viral software, and emergency security situations, as well as the potential impact that newer technologies such as mobile devices have on the privacy and security of electronic protected health information (ePHI). In the United States, the Health Insurance Portability and Accountability Act (HIPAA) govern the privacy and protection of medical information and health records. The HIPAA security standards final rule mandate administrative, physical, and technical safeguards to ensure the confidentiality, integrity, and security of ePHI. Importantly, security failures often lead to privacy breaches, invoking the HIPAA privacy rule as well. Therefore, this review also highlights key aspects of HIPAA and its impact on the pathology laboratory in the United States. PMID:23599904

  19. 32 CFR 21.665 - Nonprocurement instrument.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 1 2011-07-01 2011-07-01 false Nonprocurement instrument. 21.665 Section 21.665 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-GENERAL MATTERS Definitions § 21.665 Nonprocurement instrument. A legal...

  20. 32 CFR 21.665 - Nonprocurement instrument.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 1 2012-07-01 2012-07-01 false Nonprocurement instrument. 21.665 Section 21.665 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-GENERAL MATTERS Definitions § 21.665 Nonprocurement instrument. A legal...

  1. 32 CFR 21.665 - Nonprocurement instrument.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 1 2013-07-01 2013-07-01 false Nonprocurement instrument. 21.665 Section 21.665 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-GENERAL MATTERS Definitions § 21.665 Nonprocurement instrument. A legal...

  2. 32 CFR 21.665 - Nonprocurement instrument.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Nonprocurement instrument. 21.665 Section 21.665 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-GENERAL MATTERS Definitions § 21.665 Nonprocurement instrument. A legal...

  3. 32 CFR 21.665 - Nonprocurement instrument.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 1 2014-07-01 2014-07-01 false Nonprocurement instrument. 21.665 Section 21.665 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DoD GRANT AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-GENERAL MATTERS Definitions § 21.665 Nonprocurement instrument. A legal...

  4. Flight Test Guide (Part 61 Revised): Instrument Pilot: Helicopter.

    ERIC Educational Resources Information Center

    Federal Aviation Administration (DOT), Washington, DC. Flight Standards Service.

    The guide provides an outline of the skills required to pass the flight test for an Instrument Pilot Helicopter Rating under Part 61 (revised) of Federal Aviation Regulations. General procedures for flight tests are described and the following pilot operations outlined: maneuvering by reference to instruments, IFR navigation, instrument…

  5. 32 CFR 21.400 - To what instruments does this subpart apply?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false To what instruments does this subpart apply? 21... AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-GENERAL MATTERS Authorities and Responsibilities for Making and Administering Assistance Awards § 21.400 To what instruments does this subpart apply...

  6. 32 CFR 21.400 - To what instruments does this subpart apply?

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 1 2011-07-01 2011-07-01 false To what instruments does this subpart apply? 21... AND AGREEMENT REGULATIONS DoD GRANTS AND AGREEMENTS-GENERAL MATTERS Authorities and Responsibilities for Making and Administering Assistance Awards § 21.400 To what instruments does this subpart apply...

  7. 75 FR 4255 - Reporting of Fraudulent Financial Instruments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-01-27

    ... other words, if a decision to purchase or sell would have been different had the regulated entity... FHFA upon discovery that it has purchased or sold a fraudulent loan or financial instrument, or suspects a possible fraud relating to the purchase or sale of any loan or financial instrument. The final...

  8. Jean-Martin Charcot Pathologist, Neurologist, Psychiatrist and Physician

    PubMed Central

    Pandey, Sanjay

    2012-01-01

    Jean-Martin Charcot is known as father of modern neurology. Before him, neurology was only limited to select disorders like chorea. His contributions were not limited to neurology only, as he was instrumental in many new developments in the field of pathology, psychiatry, and internal medicine. Even after 100 years, Charcot`s clinical methods remain the pillar of modern neurology. PMID:23349597

  9. Stakeholders' perspectives on the regulation and integration of complementary and alternative medicine products in Lebanon: a qualitative study

    PubMed Central

    2011-01-01

    Background The regulation of the markets for Complementary and Alternative Medicine (CAM) products presents a global challenge. There is a dearth of studies that have examined or evaluated the regulatory policies of CAM products in the Eastern Mediterranean Region (EMR). We investigate the regulatory frameworks and the barriers for the proper regulation and integration of CAM products in Lebanon, as an example of an EMR country with a weak public infrastructure. Methods We utilized a qualitative study design involving a series of semi-structured interviews with stakeholders of the CAM market in Lebanon. Snowball sampling was used to identify interviewees; interviews continued until the "saturation" point was reached. A total of 16 interviews were carried out with decision makers, representatives of professional associations, academic researchers, CAM product importers, policy makers and a media representative. Interviews were transcribed and thematic analysis of scripts was carried out. Results There was a consensus among all stakeholders that the regulation of the market for CAM products in Lebanon needs to be strengthened. Thematic analysis identified a number of impediments jeopardizing the safety of public consumption and hindering the integration of CAM therapies into mainstream medicine; including: weak infrastructure, poor regulation, ineffective policies and politics, weak CAM awareness and sub-optimal coordination and cooperation among stakeholders. With respect to policy instruments, voluntary instruments (self regulation) were deemed ineffective by stakeholders due to poor awareness of both users and providers on safe use of CAM products. Stakeholders' rather recommended the adoption of a combination of mixed (enhancing public awareness and integration of CAM into medical and nursing curricula) and compulsory (stricter governmental regulation) policy instruments for the regulation of the market for CAM products. Conclusions The current status quo with respect to the regulation of CAM products in Lebanon is not conducive to public safety, nor does it support the integration of CAM products into the healthcare system. The Ministry of Health indeed plays a dominant role in the regulation of these products through a combination of mixed and compulsory policy instruments. Yet, the proper implementation of these regulations requires political resolve coupled with the cooperation of all CAM stakeholders. PMID:21871124

  10. The role of instrumental emotion regulation in the emotions-creativity link: how worries render individuals with high neuroticism more creative.

    PubMed

    Leung, Angela K-Y; Liou, Shyhnan; Qiu, Lin; Kwan, Letty Y-Y; Chiu, Chi-Yue; Yong, Jose C

    2014-10-01

    Based on the instrumental account of emotion regulation (Tamir, 2005), the current research seeks to offer a novel perspective to the emotions-creativity debate by investigating the instrumental value of trait-consistent emotions in creativity. We hypothesize that emotions such as worry (vs. happy) are trait-consistent experiences for individuals higher on trait neuroticism and experiencing these emotions can facilitate performance in a creativity task. In 3 studies, we found support for our hypothesis. First, individuals higher in neuroticism had a greater preference for recalling worrisome (vs. happy) events in anticipation of performing a creativity task (Study 1). Moreover, when induced to recall a worrisome (vs. happy) event, individuals higher in neuroticism came up with more creative design (Study 2) and more flexible uses of a brick (Study 3) when the task was a cognitively demanding one. Further, Study 3 offers preliminary support that increased intrinsic task enjoyment and motivation mediates the relationship between trait-consistent emotion regulation and creative performance. These findings offer a new perspective to the controversy concerning the emotions-creativity relationship and further demonstrate the role of instrumental emotion regulation in the domain of creative performance. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  11. Prevalence of orthorexia nervosa is less than 1 %: data from a US sample.

    PubMed

    Dunn, Thomas M; Gibbs, Josh; Whitney, Noelle; Starosta, Amy

    2017-03-01

    Orthorexia nervosa, or pathological dieting based on being "healthy," has been of growing interest. Clinical data are limited to less than a half-dozen case studies reporting instances of medical problems due to healthful eating. However, more than a dozen studies using a measure to identify orthorexia, the ORTO-15, report very high prevalence rates in non-clinical samples. Point prevalence rates are reported from 6 % to nearly 90 %. Such variability could be due to cultural issues or psychometric problems with the instrument. This study examines prevalence rate of orthorexia in a US sample. The ORTO-15 was administered to 275 US college students along with other questions regarding diet, exercise, and health. While the ORTO-15 indicated a prevalence rate of 71 %, only 20 % of the sample endorsed a dietary practice of removing a particular food type (e.g. meat) from their diet. Those who endorsed following a vegan diet had the highest (less pathological) mean ORTO-15 score. Further, when classifying participants based on their seriousness about healthy eating and whether their diet had led to impairment in everyday activities and medical problems, less than 1 % of the sample fell into such a category. As in other countries, a large proportion of a non-clinical US sample scored in the orthorexia range on the ORTO-15. However, this instrument is likely unable to distinguish between healthy eating and pathologically healthful eating. Our estimate is that orthorexia nervosa like anorexia nervosa and bulimia nervosa, is not a common condition.

  12. Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation

    PubMed Central

    Pagliaccio, David; Luby, Joan L.; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S.; Belden, Andrew C.; Botteron, Kelly N.; Harms, Michael P.; Barch, Deanna M.

    2015-01-01

    Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within four hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9–14 year olds; N=120). Whole-brain regression analyses indicated that increasing genetic ‘risk’ predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic ‘risk’ and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. PMID:26595470

  13. Amygdala functional connectivity, HPA axis genetic variation, and life stress in children and relations to anxiety and emotion regulation.

    PubMed

    Pagliaccio, David; Luby, Joan L; Bogdan, Ryan; Agrawal, Arpana; Gaffrey, Michael S; Belden, Andrew C; Botteron, Kelly N; Harms, Michael P; Barch, Deanna M

    2015-11-01

    Internalizing pathology is related to alterations in amygdala resting state functional connectivity, potentially implicating altered emotional reactivity and/or emotion regulation in the etiological pathway. Importantly, there is accumulating evidence that stress exposure and genetic vulnerability impact amygdala structure/function and risk for internalizing pathology. The present study examined whether early life stress and genetic profile scores (10 single nucleotide polymorphisms within 4 hypothalamic-pituitary-adrenal axis genes: CRHR1, NR3C2, NR3C1, and FKBP5) predicted individual differences in amygdala functional connectivity in school-age children (9- to 14-year-olds; N = 120). Whole-brain regression analyses indicated that increasing genetic "risk" predicted alterations in amygdala connectivity to the caudate and postcentral gyrus. Experience of more stressful and traumatic life events predicted weakened amygdala-anterior cingulate cortex connectivity. Genetic "risk" and stress exposure interacted to predict weakened connectivity between the amygdala and the inferior and middle frontal gyri, caudate, and parahippocampal gyrus in those children with the greatest genetic and environmental risk load. Furthermore, amygdala connectivity longitudinally predicted anxiety symptoms and emotion regulation skills at a later follow-up. Amygdala connectivity mediated effects of life stress on anxiety and of genetic variants on emotion regulation. The current results suggest that considering the unique and interacting effects of biological vulnerability and environmental risk factors may be key to understanding the development of altered amygdala functional connectivity, a potential factor in the risk trajectory for internalizing pathology. (c) 2015 APA, all rights reserved).

  14. Problem and pathological gambling among college athletes.

    PubMed

    Kerber, Cynthia Sullivan

    2005-01-01

    Problematic gambling is common in college students, and in particular, athletes. The frequency of problem and pathological gambling was determined among 636 college athletes at three Midwest universities using the South Oaks Gambling Screen (SOGS). The Gambling Attitude Scale (GAS) was used to assess college athletes' attitudes toward gambling in general and toward four modes of gambling (casinos, betting on horse races, lottery and the Internet). A profile of college athletes' gambling attitudes and behavior was developed through the data obtained from each of these instruments. Nearly 15% of respondents had a SOGS score >or=3, indicating problem or pathological gambling. Those at risk for a gambling problem gambled frequently, had family and/or friends with perceived gambling problems, were nonwhite, older, started gambling at a younger age, preferred games of skill, and held positive attitudes toward gambling in general and Internet gambling, in particular. Gambling problems are widespread among college athletes who constitute a vulnerable group. Specific interventions are needed to target this group.

  15. Agri-Environmental Policy Measures in Israel: The Potential of Using Market-Oriented Instruments

    NASA Astrophysics Data System (ADS)

    Amdur, Liron; Bertke, Elke; Freese, Jan; Marggraf, Rainer

    2011-05-01

    This paper examines the possibilities of developing agri-environmental policy measures in Israel, focusing on market-oriented instruments. A conceptual framework for developing agri-environmental policy measures is presented, first in very broad lines (mandatory regulations, economic instruments and advisory measures) and subsequently focusing on economic instruments, and specifically, on market-oriented ones. Two criteria of choice between the measures are suggested: their contribution to improving the effectiveness of the policy; and the feasibility of their implementation. This is the framework used for analyzing agri-environmental measures in Israel. Israel currently implements a mix of mandatory regulations, economic instruments and advisory measures to promote the agri-environment. The use of additional economic instruments may improve the effectiveness of the policy. When comparing the effectiveness of various economic measures, we found that the feasibility of implementation of market-oriented instruments is greater, due to the Israeli public's preference for strengthening market orientation in the agricultural sector. Four market-oriented instruments were practiced in a pilot project conducted in an Israeli rural area. We found that in this case study, the institutional feasibility and acceptance by stakeholders were the major parameters influencing the implementation of the market-oriented instruments, whereas the instruments' contribution to enhancing the ecological or economic effectiveness were hardly considered by the stakeholders as arguments in favor of their use.

  16. Agri-environmental policy measures in Israel: the potential of using market-oriented instruments.

    PubMed

    Amdur, Liron; Bertke, Elke; Freese, Jan; Marggraf, Rainer

    2011-05-01

    This paper examines the possibilities of developing agri-environmental policy measures in Israel, focusing on market-oriented instruments. A conceptual framework for developing agri-environmental policy measures is presented, first in very broad lines (mandatory regulations, economic instruments and advisory measures) and subsequently focusing on economic instruments, and specifically, on market-oriented ones. Two criteria of choice between the measures are suggested: their contribution to improving the effectiveness of the policy; and the feasibility of their implementation. This is the framework used for analyzing agri-environmental measures in Israel. Israel currently implements a mix of mandatory regulations, economic instruments and advisory measures to promote the agri-environment. The use of additional economic instruments may improve the effectiveness of the policy. When comparing the effectiveness of various economic measures, we found that the feasibility of implementation of market-oriented instruments is greater, due to the Israeli public's preference for strengthening market orientation in the agricultural sector. Four market-oriented instruments were practiced in a pilot project conducted in an Israeli rural area. We found that in this case study, the institutional feasibility and acceptance by stakeholders were the major parameters influencing the implementation of the market-oriented instruments, whereas the instruments' contribution to enhancing the ecological or economic effectiveness were hardly considered by the stakeholders as arguments in favor of their use.

  17. Platelet-derived growth factor-DD targeting arrests pathological angiogenesis by modulating glycogen synthase kinase-3beta phosphorylation.

    PubMed

    Kumar, Anil; Hou, Xu; Lee, Chunsik; Li, Yang; Maminishkis, Arvydas; Tang, Zhongshu; Zhang, Fan; Langer, Harald F; Arjunan, Pachiappan; Dong, Lijin; Wu, Zhijian; Zhu, Linda Y; Wang, Lianchun; Min, Wang; Colosi, Peter; Chavakis, Triantafyllos; Li, Xuri

    2010-05-14

    Platelet-derived growth factor-DD (PDGF-DD) is a recently discovered member of the PDGF family. The role of PDGF-DD in pathological angiogenesis and the underlying cellular and molecular mechanisms remain largely unexplored. In this study, using different animal models, we showed that PDGF-DD expression was up-regulated during pathological angiogenesis, and inhibition of PDGF-DD suppressed both choroidal and retinal neovascularization. We also demonstrated a novel mechanism mediating the function of PDGF-DD. PDGF-DD induced glycogen synthase kinase-3beta (GSK3beta) Ser(9) phosphorylation and Tyr(216) dephosphorylation in vitro and in vivo, leading to increased cell survival. Consistently, GSK3beta activity was required for the antiangiogenic effect of PDGF-DD targeting. Moreover, PDGF-DD regulated the expression of GSK3beta and many other genes important for angiogenesis and apoptosis. Thus, we identified PDGF-DD as an important target gene for antiangiogenic therapy due to its pleiotropic effects on vascular and non-vascular cells. PDGF-DD inhibition may offer new therapeutic options to treat neovascular diseases.

  18. Deletion of Galgt2 (B4Galnt2) Reduces Muscle Growth in Response to Acute Injury and Increases Muscle Inflammation and Pathology in Dystrophin-Deficient Mice

    PubMed Central

    Xu, Rui; Singhal, Neha; Serinagaoglu, Yelda; Chandrasekharan, Kumaran; Joshi, Mandar; Bauer, John A.; Janssen, Paulus M.L.; Martin, Paul T.

    2016-01-01

    Transgenic overexpression of Galgt2 (official name B4Galnt2) in skeletal muscle stimulates the glycosylation of α dystroglycan (αDG) and the up-regulation of laminin α2 and dystrophin surrogates known to inhibit muscle pathology in mouse models of congenital muscular dystrophy 1A and Duchenne muscular dystrophy. Skeletal muscle Galgt2 gene expression is also normally increased in the mdx mouse model of Duchenne muscular dystrophy compared with the wild-type mice. To assess whether this increased endogenous Galgt2 expression could affect disease, we quantified muscular dystrophy measures in mdx mice deleted for Galgt2 (Galgt2−/−mdx). Galgt2−/− mdx mice had increased heart and skeletal muscle pathology and inflammation, and also worsened cardiac function, relative to age-matched mdx mice. Deletion of Galgt2 in wild-type mice also slowed skeletal muscle growth in response to acute muscle injury. In each instance where Galgt2 expression was elevated (developing muscle, regenerating muscle, and dystrophic muscle), Galgt2-dependent glycosylation of αDG was also increased. Overexpression of Galgt2 failed to inhibit skeletal muscle pathology in dystroglycan-deficient muscles, in contrast to previous studies in dystrophin-deficient mdx muscles. This study demonstrates that Galgt2 gene expression and glycosylation of αDG are dynamically regulated in muscle and that endogenous Galgt2 gene expression can ameliorate the extent of muscle pathology, inflammation, and dysfunction in mdx mice. PMID:26435413

  19. Redox Regulation of Neuronal Voltage-Gated Calcium Channels

    PubMed Central

    Jevtovic-Todorovic, Vesna

    2014-01-01

    Abstract Significance: Voltage-gated calcium channels are ubiquitously expressed in neurons and are key regulators of cellular excitability and synaptic transmitter release. There is accumulating evidence that multiple subtypes of voltage-gated calcium channels may be regulated by oxidation and reduction. However, the redox mechanisms involved in the regulation of channel function are not well understood. Recent Advances: Several studies have established that both T-type and high-voltage-activated subtypes of voltage-gated calcium channel can be redox-regulated. This article reviews different mechanisms that can be involved in redox regulation of calcium channel function and their implication in neuronal function, particularly in pain pathways and thalamic oscillation. Critical Issues: A current critical issue in the field is to decipher precise mechanisms of calcium channel modulation via redox reactions. In this review we discuss covalent post-translational modification via oxidation of cysteine molecules and chelation of trace metals, and reactions involving nitric oxide-related molecules and free radicals. Improved understanding of the roles of redox-based reactions in regulation of voltage-gated calcium channels may lead to improved understanding of novel redox mechanisms in physiological and pathological processes. Future Directions: Identification of redox mechanisms and sites on voltage-gated calcium channel may allow development of novel and specific ion channel therapies for unmet medical needs. Thus, it may be possible to regulate the redox state of these channels in treatment of pathological process such as epilepsy and neuropathic pain. Antioxid. Redox Signal. 21, 880–891. PMID:24161125

  20. Instrumentation for Non-Invasive Assessment of Cardiovascular Regulation

    NASA Technical Reports Server (NTRS)

    Cohen, Richard J.

    1999-01-01

    It is critically important to be able to assess alterations in cardiovascular regulation during and after space flight. We propose to develop an instrument for the non-invasive assessment of such alterations that can be used on the ground and potentially during space flight. This instrumentation would be used by the Cardiovascular Alterations Team at multiple sites for the study of the effects of space flight on the cardiovascular system and the evaluation of countermeasures. In particular, the Cardiovascular Alterations Team will use this instrumentation in conjunction with ground-based human bed-rest studies and during application of acute stresses e.g., tilt, lower body negative pressure, and exercise. In future studies, the Cardiovascular Alterations Team anticipates using this instrumentation to study astronauts before and after space flight and ultimately, during space flight. The instrumentation may also be used by the Bone Demineralization/Calcium Metabolism Team, the Neurovestibular Team and the Human Performance Factors, Sleep and Chronobiology Team to measure changes in autonomic nervous function. The instrumentation will be based on a powerful new technology - cardiovascular system identification (CSI) - which has been developed in our laboratory. CSI provides a non-invasive approach for the study of alterations in cardiovascular regulation. This approach involves the analysis of second-to-second fluctuations in physiologic signals such as heart rate and non-invasively measured arterial blood pressure in order to characterize quantitatively the physiologic mechanisms responsible for the couplings between these signals. Through the characterization of multiple physiologic mechanisms, CSI provides a closed-loop model of the cardiovascular regulatory state in an individual subject.

  1. Control of Endothelin-A Receptor Expression by Progesterone Is Enhanced by Synergy With Gata2

    PubMed Central

    Zhang, Yanping; Knutsen, Gregory R.; Brown, Matthew D.

    2013-01-01

    The endothelin-A receptor (Ednra) is involved in several physiological, pathological, and developmental pathways. Known for its function in vasoconstriction after being activated by endothelin-1, Ednra also controls cephalic neural crest cell development and appears to play a role in several pathologies, including cancer and periodontitis. However, the mechanisms regulating Ednra expression have not been identified despite its important functions. In this study, we investigated the role progesterone plays in Ednra gene expression in vivo and in vitro. In mice, pregnancy promotes Ednra expression in the heart, kidney, lung, uterus, and placenta, and the up-regulation is mediated by progesterone. We determined that the conserved region between −5.7 and −4.2 kb upstream of the mouse Ednra gene is necessary for the progesterone response. We also found that progesterone mediates Ednra activation through progesterone receptor B activation by its recruitment to PRE6, one of the 6 progesterone response elements found in that locus. However, gene activation by means of a GATA2 site was also necessary for the progesterone response. The Gata2 transcription factor enhances the progesterone response mediated by the progesterone receptor B. Together these results indicate that progesterone regulates Ednra expression by synergizing with Gata2 activity, a previously unknown mechanism. This mechanism may have an impact on pathologies involving the endothelin signaling. PMID:23592430

  2. Alterations of overused supraspinatus tendon: a possible role of glycosaminoglycans and HARP/pleiotrophin in early tendon pathology.

    PubMed

    Attia, Mohamed; Scott, Alexander; Duchesnay, Arlette; Carpentier, Gilles; Soslowsky, Louis J; Huynh, Minh Bao; Van Kuppevelt, Toin H; Gossard, Camille; Courty, José; Tassoni, Marie-Claude; Martelly, Isabelle

    2012-01-01

    Supraspinatus tendon overuse injuries lead to significant pain and disability in athletes and workers. Despite the prevalence and high social cost of these injuries, the early pathological events are not well known. We analyzed the potential relation between glycosaminoglycan (GAG) composition and phenotypic cellular alteration using a rat model of rotator cuff overuse. Total sulfated GAGs increased after 4 weeks of overuse and remained elevated up to 16 weeks. GAG accumulation was preceded by up-regulation of decorin, versican, and aggrecan proteoglycans (PGs) mRNAs and proteins and biglycan PG mRNA after 2 weeks. At 2 weeks, collagen 1 transcript decreased whereas mRNAs for collagen 2, collagen 3, collagen 6, and the transcription factor Sox9 were increased. Protein levels of heparin affine regulatory peptide (HARP)/pleiotrophin, a cytokine known to regulate developmental chondrocyte formation, were enhanced especially at 4 weeks, without up-regulation of HARP/pleiotrophin mRNA. Further results suggest that the increased GAGs present in early lesions may sequester HARP/pleiotrophin, which could contribute to a loss of tenocyte's phenotype. All these modifications are characteristic of a shift towards the chondrocyte phenotype. Identification of these early changes in the extra-cellular matrix may help to prevent the progression of the pathology to more disabling, degenerative alterations. Copyright © 2011 Orthopaedic Research Society.

  3. Monoacylglycerol signalling and ABHD6 in health and disease.

    PubMed

    Poursharifi, Pegah; Madiraju, Sri Ramachandra Murthy; Prentki, Marc

    2017-09-01

    Lipid metabolism dysregulation underlies chronic pathologies such as obesity, diabetes and cancer. Besides their role in structure and energy storage, lipids are also important signalling molecules regulating multiple biological functions. Thus, understanding the precise lipid metabolism enzymatic steps that are altered in some pathological conditions is helpful for designing better treatment strategies. Several monoacylglycerol (MAG) species are only recently being recognized as signalling lipid molecules in different tissues. Recent studies indicated the importance of the ubiquitously expressed serine hydrolase α/β-hydrolase domain 6 (ABHD6), which is a MAG hydrolase, in regulating signalling competent MAG in both central and peripheral tissues. The central and peripheral function of the endocannabinoid 2-arachidonoylglycerol, which is a 2-MAG, and its breakdown by both ABHD6 and classical MAG lipase has been well documented. ABHD6 and its substrate MAG appear to be involved in the regulation of various physiological and pathological processes including insulin secretion, adipose browning, food intake, neurotransmission, autoimmune disorders, neurological and metabolic diseases as well as cancer. Diverse cellular targets such as mammalian unc13-1 (Munc13-1), PPARs, GPR119 and CB1/2 receptors, for MAG-mediated signalling processes have been proposed in different cell types. The purpose of this review is to provide a comprehensive summary of the current state of knowledge regarding ABHD6/MAG signalling and its possible therapeutic implications. © 2017 John Wiley & Sons Ltd.

  4. 40 CFR 204.56 - Testing by the Administrator.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... which case instrumentation and equipment of the type required by these regulations shall be made... equipment, which shall be equal to or exceed the performance specifications of the instrumentation or...

  5. Development and Validation of an Instrument to Measure Students' Motivation and Self-Regulation in Science Learning

    NASA Astrophysics Data System (ADS)

    Velayutham, Sunitadevi; Aldridge, Jill; Fraser, Barry

    2011-10-01

    Students' motivational beliefs and self-regulatory practices have been identified as instrumental in influencing the engagement of students in the learning process. An important aim of science education is to empower students by nurturing the belief that they can succeed in science learning and to cultivate the adaptive learning strategies required to help to bring about that success. This article reports the development and validation of an instrument to measure salient factors related to the motivation and self-regulation of students in lower secondary science classrooms. The development of the instrument involved identifying key determinants of students' motivation and self-regulation in science learning based on theoretical and research underpinnings. Once the instrument was developed, a pilot study involving 52 students from two Grade 8 science classes was undertaken. Quantitative data were collected from 1,360 students in 78 classes across Grades 8, 9, and 10, in addition to in-depth qualitative information gathered from 10 experienced science teachers and 12 Grade 8 students. Analyses of the data suggest that the survey has strong construct validity when used with lower secondary students. This survey could be practically valuable as a tool for gathering information that may guide classroom teachers in refocusing their teaching practices and help to evaluate the effectiveness of intervention programmes.

  6. Professor Samuel David Gross (1805-1884) and His Innovations in Surgery and Medicine.

    PubMed

    Laios, Konstantinos

    2018-06-01

    Professor Samuel David Gross (1805-1884) is considered as one of the founders of American surgery. He was a skillful surgeon who could excellently perform a lithotomy, an amputation, and a cataract surgery. He introduced many new surgical techniques and designed new surgical and medical instruments. He expertise was not limited to surgery alone; he also published studies concerning internal medicine, pathology, experimental physiology, and pharmacology. His most important treatise was his 2-volume work, A System of Surgery, Pathological, Diagnostic, Therapeutic and Operative (1861), which was a standard reference book in surgery in the United States during the second half of 19th century. Gross received many honors during his life. He was active in the operating room until his death.

  7. Ex Vivo (Fluorescence) Confocal Microscopy in Surgical Pathology: State of the Art.

    PubMed

    Ragazzi, Moira; Longo, Caterina; Piana, Simonetta

    2016-05-01

    First developed in 1957, confocal microscopy is a powerful imaging tool that can be used to obtain near real-time reflected light images of untreated human tissue with nearly histologic resolution. Besides its research applications, in the last decades, confocal microscopy technology has been proposed as a useful device to improve clinical diagnosis, especially in ophthalmology, dermatology, and endomicroscopy settings, thanks to advances in instrument development. Compared with the wider use of the in vivo tissue assessment, ex vivo applications of confocal microscopy are not fully explored. A comprehensive review of the current literature was performed here, focusing on the reliable applications of ex vivo confocal microscopy in surgical pathology and on some potential evolutions of this new technique from pathologists' viewpoint.

  8. Mapping of thermal injury in biologic tissues using quantitative pathologic techniques

    NASA Astrophysics Data System (ADS)

    Thomsen, Sharon L.

    1999-05-01

    Qualitative and quantitative pathologic techniques can be used for (1) mapping of thermal injury, (2) comparisons lesion sizes and configurations for different instruments or heating sources and (3) comparisons of treatment effects. Concentric zones of thermal damage form around a single volume heat source. The boundaries between some of these zones are distinct and measurable. Depending on the energy deposition, heating times and tissue type, the zones can include the following beginning at the hotter center and progressing to the cooler periphery: (1) tissue ablation, (2) carbonization, (3) tissue water vaporization, (4) structural protein denaturation (thermal coagulation), (5) vital enzyme protein denaturation, (6) cell membrane disruption, (7) hemorrhage, hemostasis and hyperhemia, (8) tissue necrosis and (9) wound organization and healing.

  9. Impaired JIP3-dependent axonal lysosome transport promotes amyloid plaque pathology

    PubMed Central

    Gowrishankar, Swetha; Wu, Yumei

    2017-01-01

    Lysosomes robustly accumulate within axonal swellings at Alzheimer’s disease (AD) amyloid plaques. However, the underlying mechanisms and disease relevance of such lysosome accumulations are not well understood. Motivated by these problems, we identified JNK-interacting protein 3 (JIP3) as an important regulator of axonal lysosome transport and maturation. JIP3 knockout mouse neuron primary cultures accumulate lysosomes within focal axonal swellings that resemble the dystrophic axons at amyloid plaques. These swellings contain high levels of amyloid precursor protein processing enzymes (BACE1 and presenilin 2) and are accompanied by elevated Aβ peptide levels. The in vivo importance of the JIP3-dependent regulation of axonal lysosomes was revealed by the worsening of the amyloid plaque pathology arising from JIP3 haploinsufficiency in a mouse model of AD. These results establish the critical role of JIP3-dependent axonal lysosome transport in regulating amyloidogenic amyloid precursor protein processing and support a model wherein Aβ production is amplified by plaque-induced axonal lysosome transport defects. PMID:28784610

  10. Targeting G protein-coupled receptor kinases (GRKs) in Heart Failure

    PubMed Central

    Brinks, Henriette; Koch, Walter J

    2010-01-01

    In the human body, over 1000 different G protein-coupled receptors (GPCRs) mediate a broad spectrum of extracellular signals at the plasma membrane, transmitting vital physiological features such as pain, sight, smell, inflammation, heart rate and contractility of muscle cells. Signaling through these receptors is primarily controlled and regulated by a group of kinases, the GPCR kinases (GRKs), of which only seven are known and thus, interference with these common downstream GPCR regulators suggests a powerful therapeutic strategy. Molecular modulation of the kinases that are ubiquitously expressed in the heart has proven GRK2, and also GRK5, to be promising targets for prevention and reversal of one of the most severe pathologies in man, chronic heart failure (HF). In this article we will focus on the structural aspects of these GRKs important for their physiological and pathological regulation as well as well known and novel therapeutic approaches that target these GRKs in order to overcome the development of cardiac injury and progression of HF. PMID:21218155

  11. Genome-wide analysis of the genetic regulation of gene expression in human neutrophils

    PubMed Central

    Andiappan, Anand Kumar; Melchiotti, Rossella; Poh, Tuang Yeow; Nah, Michelle; Puan, Kia Joo; Vigano, Elena; Haase, Doreen; Yusof, Nurhashikin; San Luis, Boris; Lum, Josephine; Kumar, Dilip; Foo, Shihui; Zhuang, Li; Vasudev, Anusha; Irwanto, Astrid; Lee, Bernett; Nardin, Alessandra; Liu, Hong; Zhang, Furen; Connolly, John; Liu, Jianjun; Mortellaro, Alessandra; Wang, De Yun; Poidinger, Michael; Larbi, Anis; Zolezzi, Francesca; Rotzschke, Olaf

    2015-01-01

    Neutrophils are an abundant immune cell type involved in both antimicrobial defence and autoimmunity. The regulation of their gene expression, however, is still largely unknown. Here we report an eQTL study on isolated neutrophils from 114 healthy individuals of Chinese ethnicity, identifying 21,210 eQTLs on 832 unique genes. Unsupervised clustering analysis of these eQTLs confirms their role in inflammatory responses and immunological diseases but also indicates strong involvement in dermatological pathologies. One of the strongest eQTL identified (rs2058660) is also the tagSNP of a linkage block reported to affect leprosy and Crohn's disease in opposite directions. In a functional study, we can link the C allele with low expression of the β-chain of IL18-receptor (IL18RAP). In neutrophils, this results in a reduced responsiveness to IL-18, detected both on the RNA and protein level. Thus, the polymorphic regulation of human neutrophils can impact beneficial as well as pathological inflammatory responses. PMID:26259071

  12. Functional TASK-3-Like Channels in Mitochondria of Aldosterone-Producing Zona Glomerulosa Cells.

    PubMed

    Yao, Junlan; McHedlishvili, David; McIntire, William E; Guagliardo, Nick A; Erisir, Alev; Coburn, Craig A; Santarelli, Vincent P; Bayliss, Douglas A; Barrett, Paula Q

    2017-08-01

    Ca 2+ drives aldosterone synthesis in the cytosolic and mitochondrial compartments of the adrenal zona glomerulosa cell. Membrane potential across each of these compartments regulates the amplitude of the Ca 2+ signal; yet, only plasma membrane ion channels and their role in regulating cell membrane potential have garnered investigative attention as pathological causes of human hyperaldosteronism. Previously, we reported that genetic deletion of TASK-3 channels (tandem pore domain acid-sensitive K + channels) from mice produces aldosterone excess in the absence of a change in the cell membrane potential of zona glomerulosa cells. Here, we report using yeast 2-hybrid, immunoprecipitation, and electron microscopic analyses that TASK-3 channels are resident in mitochondria, where they regulate mitochondrial morphology, mitochondrial membrane potential, and aldosterone production. This study provides proof of principle that mitochondrial K + channels, by modulating inner mitochondrial membrane morphology and mitochondrial membrane potential, have the ability to play a pathological role in aldosterone dysregulation in steroidogenic cells. © 2017 American Heart Association, Inc.

  13. MYOCARDIAL AKT: THE OMNIPRESENT NEXUS

    PubMed Central

    Sussman, Mark A.; Völkers, Mirko; Fischer, Kimberlee; Bailey, Brandi; Cottage, Christopher T.; Din, Shabana; Gude, Natalie; Avitabile, Daniele; Alvarez, Roberto; Sundararaman, Balaji; Quijada, Pearl; Mason, Matt; Konstandin, Mathias H.; Malhowski, Amy; Cheng, Zhaokang; Khan, Mohsin; McGregor, Michael

    2013-01-01

    One of the greatest examples of integrated signal transduction is revealed by examination of effects mediated by AKT kinase in myocardial biology. Positioned at the intersection of multiple afferent and efferent signals, AKT exemplifies a molecular sensing node that coordinates dynamic responses of the cell in literally every aspect of biological responses. The balanced and nuanced nature of homeostatic signaling is particularly essential within the myocardial context, where regulation of survival, energy production, contractility, and response to pathological stress all flow through the nexus of AKT activation or repression. Equally important, the loss of regulated AKT activity is primarily the cause or consequence of pathological conditions leading to remodeling of the heart and eventual decompensation. This review presents an overview compendium of the complex world of myocardial AKT biology gleaned from more than a decade of research. Summarization of the widespread influence that AKT exerts upon myocardial responses leaves no doubt that the participation of AKT in molecular signaling will need to be reckoned with as a seemingly omnipresent regulator of myocardial molecular biological responses. PMID:21742795

  14. 15 CFR 301.4 - Processing of applications by the Department of the Treasury (Customs and Border Protection).

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC... educational purposes and therefore authorized to import instruments into the U.S. under subheading 9810.00.60... eligibility under this paragraph; (2) Whether the instrument or apparatus falls within the classes of...

  15. 15 CFR 301.4 - Processing of applications by the Department of the Treasury (Customs and Border Protection).

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC... educational purposes and therefore authorized to import instruments into the U.S. under subheading 9810.00.60... eligibility under this paragraph; (2) Whether the instrument or apparatus falls within the classes of...

  16. 15 CFR 301.4 - Processing of applications by the Department of the Treasury (Customs and Border Protection).

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC... educational purposes and therefore authorized to import instruments into the U.S. under subheading 9810.00.60... eligibility under this paragraph; (2) Whether the instrument or apparatus falls within the classes of...

  17. 15 CFR 301.4 - Processing of applications by the Department of the Treasury (Customs and Border Protection).

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC... educational purposes and therefore authorized to import instruments into the U.S. under subheading 9810.00.60... eligibility under this paragraph; (2) Whether the instrument or apparatus falls within the classes of...

  18. 10 CFR 603.565 - Use of a hybrid instrument.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 4 2011-01-01 2011-01-01 false Use of a hybrid instrument. 603.565 Section 603.565 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Pre-Award Business Evaluation Fixed-Support Or Expenditure-Based Approach § 603.565 Use of a hybrid instrument. For a RD&D...

  19. 10 CFR 603.565 - Use of a hybrid instrument.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 4 2010-01-01 2010-01-01 false Use of a hybrid instrument. 603.565 Section 603.565 Energy DEPARTMENT OF ENERGY (CONTINUED) ASSISTANCE REGULATIONS TECHNOLOGY INVESTMENT AGREEMENTS Pre-Award Business Evaluation Fixed-Support Or Expenditure-Based Approach § 603.565 Use of a hybrid instrument. For a RD&D...

  20. 32 CFR 552.98 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... REGULATIONS AFFECTING MILITARY RESERVATIONS Firearms and Weapons § 552.98 Purpose. This regulation establishes... dangerous weapons and instruments on Fort Stewart/Hunter Army Airfield (AAF) installations. ...

  1. 32 CFR 552.98 - Purpose.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... REGULATIONS AFFECTING MILITARY RESERVATIONS Firearms and Weapons § 552.98 Purpose. This regulation establishes... dangerous weapons and instruments on Fort Stewart/Hunter Army Airfield (AAF) installations. ...

  2. An overview of lymphatic vessels and their emerging role in cardiovascular disease

    PubMed Central

    Jones, Dennis; Min, Wang

    2011-01-01

    Over the past decade, molecular details of lymphatic vessels (lymphatics) have been rapidly acquired due to the identification of lymphatic endothelial-specific markers. Separate from the cardiovascular system, the lymphatic system is also an elaborate network of vessels that are important in normal physiology. Lymphatic vessels have the unique task to regulate fluid homeostasis, assist in immune surveillance, and transport dietary lipids. However, dysfunctional lymphatic vessels can cause pathology, while normal lymphatics can exacerbate pathology. This review summarizes the development and growth of lymphatic vessels in addition to highlighting their critical roles in physiology and pathology. Also, we discuss recent work that suggests a connection between lymphatic dysfunction and cardiovascular disease. PMID:22022141

  3. [Individual typological peculiarities of system blood flow, physical capacity for work and cardiac activity regulation in patients with different resistance to periodontal diseases].

    PubMed

    Bragin, A V

    2008-01-01

    From position of typological variability of physiological individuality concept-functional constitution types - the principle of organism integrity was substantiated for stomatological pathology. There were isolated typical and specific reactions of cardiac-vessel system in patients with different resistance to periodontal diseases. Each functional type - patients with different levels of usual motion activity - had their own physiological peculiarities of parameters of system blood flow, physical capacity for work and cardiac activity regulation, that determined individual typological organism reaction in cases of maxillo-facial system pathology. The received data gives the objective base for physiological approach to single out the extreme variants of norm for forming risk contingent and groups of resistant people to periodontal diseases.

  4. Roles and regulation of the matrix metalloproteinase system in parturition.

    PubMed

    Geng, Junnan; Huang, Cong; Jiang, Siwen

    2016-04-01

    Significant tissue destruction, repair, and remodeling are involved in parturition, which involves fetal membrane rupture, cervical ripening, and uterine contraction and its subsequent involution. Extracellular matrix degradation and remodeling by proteolytic enzymes, such as matrix metalloproteinases (MMPs), are required for the final steps of parturition. MMPs participate in physiological degradation and remodeling through their proteolytic activities on specific substrates, and are balanced by the action of their inhibitors. Disruption to this balance can result in pathological stress that ends with preterm or post-term birth or pre-eclampsia. In this review, we examine the roles and regulation of the MMP system in physiological and pathological labor, and propose a model that illustrates the mechanisms by which the MMP system contributes to these processes. © 2016 Wiley Periodicals, Inc.

  5. A new method for the measurement of tremor at rest.

    PubMed

    Comby, B; Chevalier, G; Bouchoucha, M

    1992-01-01

    This paper establishes a standard method for measuring human tremor. The electronic instrument described is an application of this method. It solves the need for an effective and simple tremor-measuring instrument fit for wide distribution. This instrument consists of a piezoelectric accelerometer connected to an electronic circuit and to an LCD display. The signal is also analysed by a computer after accelerometer analogic/digital conversion in order to test the method. The tremor of 1079 healthy subjects was studied. Spectral analysis showed frequency peaks between 5.85 and 8.80 Hz. Chronic cigarette-smoking and coffee drinking did not modify the tremor as compared with controls. Relaxation session decreased tremor significantly in healthy subjects (P less than 0.01). This new tremor-measuring method opens new horizons in the understanding of physiological and pathological tremor, stress, anxiety and in the means to avoid or compensate them.

  6. 78 FR 77591 - Drawbridge Operation Regulation; Shark River, NJ

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-24

    ..., NJ. The deviation is necessary to facilitate the replacement of motor seals and instrumentation on... motor seals and instrumentation on the bridge. The Route 71 Bridge across Shark River (South Channel...

  7. Specific features of cytological and colposcopical pattern in pregnant women with benign cervix uteri pathology in anamnesis.

    PubMed

    Bysaha, Nataliya Yu

    2016-01-01

    a tendency of increasing incidence of the cervix uteri precancer and cancer in women of reproductive age is noticed recently being related to the growth of number of the sexually-transmitted infections. The cervix uteri pathology incidence in women of fertile age is 20-25%. to study the specific features of the cytological and colposcopical pattern in pregnant patients with benign cervix uteri pathology in the anamnesis and the character of its change post partum. we have examined 195 women during their pregnancy and 3-5 months post partum. All pregnant women, alongside with generally accepted clinical and laboratory examinations, were subjected to the simple and extended colposcopy, cytology of the targeted smears and, according to indications, the histological studies of bioptate. according to the results of the colcoscopical studies and the signs of the cervix uteri pathology found, the patients were divided into several groups. A control group included 49 pregnant women. The clinical and instrumental examination of 146 women with cervix uteri pathology has been carried out both during pregnancy and post partum. the structure of the clinical forms of benign and premalignant changes in the cervix uteri epithelium in pregnant patients has been found. Specific features of the cytological and colposcopical pattern in pregnant patients with benign cervix uteri pathology in anamnesis have been studied. The relationship between the parity of pregnancy, delivery, route of delivery and regress of both benign and premalignant changes in the cervix uteri epithelium 3-5 months post partum has been determined.

  8. Policy instruments for pollution control in developing countries.

    PubMed

    Eskeland, G S; Jimenez, E

    1992-07-01

    Economic development in developing countries must be accomplished in a manner that does not harm the environment with pollution. Pollution harms human health and productivity. Thus appropriate strategies must be developed that promote growth, reduce poverty, and protect the environment. A review of the current literature is performed with attention paid to cost-effective interventions i.e., comparisons of regulatory and fiscal instruments that can reduce pollution. Both direct instruments (like effluent charges, tradable permits, deposit refund systems, emission regulations and regulatory agency funding for purification, cleanup, waste disposal, and enforcement) and indirect instruments (like input/output taxes and subsidies, substitution subsidies, abatement inputs, regulation of equipment and processes, and development of clean technologies) are examined. Examples are used to show how indirect instruments can be successful when monitoring and enforcement is too costly. A careful examination of distributive concerns illustrate how the effect on the poor may need particular consideration and how groups with vested interests can help evaluate the probable success of such interventions.

  9. Metabolic Regulation of Caspase 2 in Breast Cancer

    DTIC Science & Technology

    2011-04-01

    S. The apoptosome: physiological, developmental, and pathological modes of regulation. Dev Cell 10, 549-61 ( 2006 ). 3. Baliga, B.C., Read, S.H...Mol Biol Cell 17, 2150-7 ( 2006 ). 9. Bergeron, L. et al. Defects in regulation of apoptosis in caspase-2-deficient mice. Genes Dev 12, 1304-14 (1998...Warburg, O. On the origin of cancer cells. Science 123, 309-14 (1956). 17. Lassus, P., Opitz- Araya , X. & Lazebnik, Y. Requirement for caspase-2 in

  10. Complement activation in the tubulointerstitium: AKI, CKD, and in between.

    PubMed

    Brar, Jyoti E; Quigg, Richard J

    2014-10-01

    Complement activation is actively regulated to prevent injudicious activation, such as on peritubular endothelia and basolateral aspects of tubules. Miao et al. studied mice in which the key complement regulator, Crry, was deleted from tubular cells. This lacked functional consequence in unmanipulated animals. Yet, following ischemia-reperfusion, there was greater injury due to alternative pathway activation of C5. When the balance between complement activation and regulation is tipped towards the former, pathologic complement activation can ensue.

  11. Regression of Pathological Cardiac Hypertrophy: Signaling Pathways and Therapeutic Targets

    PubMed Central

    Hou, Jianglong; Kang, Y. James

    2012-01-01

    Pathological cardiac hypertrophy is a key risk factor for heart failure. It is associated with increased interstitial fibrosis, cell death and cardiac dysfunction. The progression of pathological cardiac hypertrophy has long been considered as irreversible. However, recent clinical observations and experimental studies have produced evidence showing the reversal of pathological cardiac hypertrophy. Left ventricle assist devices used in heart failure patients for bridging to transplantation not only improve peripheral circulation but also often cause reverse remodeling of the geometry and recovery of the function of the heart. Dietary supplementation with physiologically relevant levels of copper can reverse pathological cardiac hypertrophy in mice. Angiogenesis is essential and vascular endothelial growth factor (VEGF) is a constitutive factor for the regression. The action of VEGF is mediated by VEGF receptor-1, whose activation is linked to cyclic GMP-dependent protein kinase-1 (PKG-1) signaling pathways, and inhibition of cyclic GMP degradation leads to regression of pathological cardiac hypertrophy. Most of these pathways are regulated by hypoxia-inducible factor. Potential therapeutic targets for promoting the regression include: promotion of angiogenesis, selective enhancement of VEGF receptor-1 signaling pathways, stimulation of PKG-1 pathways, and sustention of hypoxia-inducible factor transcriptional activity. More exciting insights into the regression of pathological cardiac hypertrophy are emerging. The time of translating the concept of regression of pathological cardiac hypertrophy to clinical practice is coming. PMID:22750195

  12. Distinct chronology of neuronal cell cycle re-entry and tau pathology in the 3xTg-AD mouse model and Alzheimer's disease patients.

    PubMed

    Hradek, Alex C; Lee, Hyun-Pil; Siedlak, Sandra L; Torres, Sandy L; Jung, Wooyoung; Han, Ashley H; Lee, Hyoung-gon

    2015-01-01

    Cell cycle re-entry in Alzheimer's disease (AD) has emerged as an important pathological mechanism in the progression of the disease. This appearance of cell cycle related proteins has been linked to tau pathology in AD, but the causal and temporal relationship between the two is not completely clear. In this study, we found that hyperphosphorylated retinoblastoma protein (ppRb), a key regulator for G1/S transition, is correlated with a late marker for hyperphosphorylation of tau but not with other early markers for tau alteration in the 3xTg-AD mouse model. However, in AD brains, ppRb can colocalize with both early and later markers for tau alterations, and can often be found singly in many degenerating neurons, indicating the distinct development of pathology between the 3xTg-AD mouse model and human AD patients. The conclusions of this study are two-fold. First, our findings clearly demonstrate the pathological link between the aberrant cell cycle re-entry and tau pathology. Second, the chronological pattern of cell cycle re-entry with tau pathology in the 3xTg-AD mouse is different compared to AD patients suggesting the distinct pathogenic mechanism between the animal AD model and human AD patients.

  13. Infection with spinal instrumentation: Review of pathogenesis, diagnosis, prevention, and management

    PubMed Central

    Kasliwal, Manish K.; Tan, Lee A.; Traynelis, Vincent C.

    2013-01-01

    Background: Instrumentation has become an integral component in the management of various spinal pathologies. The rate of infection varies from 2% to 20% of all instrumented spinal procedures. Every occurrence produces patient morbidity, which may adversely affect long-term outcome and increases health care costs. Methods: A comprehensive review of the literature from 1990 to 2012 was performed utilizing PubMed and several key words: Infection, spine, instrumentation, implant, management, and biofilms. Articles that provided a current review of the pathogenesis, diagnosis, prevention, and management of instrumented spinal infections over the years were reviewed. Results: There are multiple risk factors for postoperative spinal infections. Infections in the setting of instrumentation are more difficult to diagnose and treat due to biofilm. Infections may be early or delayed. C Reactive Protein (CRP) and Magnetic Resonance Imaging (MRI) are important diagnostic tools. Optimal results are obtained with surgical debridement followed by parenteral antibiotics. Removal or replacement of hardware should be considered in delayed infections. Conclusions: An improved understanding of the role of biofilm and the development of newer spinal implants has provided insight in the pathogenesis and management of infected spinal implants. This literature review highlights the mechanism, pathogenesis, prevention, and management of infection after spinal instrumentation. It is important to accurately identify and treat postoperative spinal infections. The treatment is often multimodal and prolonged. PMID:24340238

  14. A practical approach to instrument selection, evaluation, basic financial management and implementation in pathology and research.

    PubMed

    Mina, Ashraf; Favaloro, Emmanuel J; Koutts, Jerry

    2008-01-01

    In response to increasingly complex demands in terms of productivity and budgets, there is a critical need to avoid mistakes during instrument selection that will be financially costly, and adversely affect customers, staff, productivity and test turnaround time. As there is no "one size fits all", guidelines must be appropriate to permit informed decision making. A Medline search was conducted to assess background knowledge in this area, using the terms "laboratory instrument selection" and "laboratory instrument evaluation". Searches returned over 800 articles, of which only seven were directly related to the topic of the search, with most outdated, and suggesting a paucity of appropriate information. Additional resources used included the American Association of Clinical Chemistry (AACC) website and the Internet. Appropriate criteria for instrument selection were established in the current report based on subjective and objective (technical) evaluations. Additionally, a sound and simple financial approach is also suggested to help in making informed decisions and avoid costly mistakes. We propose that such a process as outlined in our report will protect laboratories from making costly and avoidable mistakes in the acquisition of major equipment.

  15. 78 FR 33993 - Defense Federal Acquisition Regulation Supplement; Clarification of “F” Orders in the Procurement...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-06-06

    ... DEPARTMENT OF DEFENSE Defense Acquisition Regulations System 48 CFR Part 204 RIN 0750-AH80 Defense Federal Acquisition Regulation Supplement; Clarification of ``F'' Orders in the Procurement Instrument Identification Number Structure (DFARS Case 2012-D040); Correction AGENCY: Defense Acquisition Regulations System...

  16. Emotion regulation strategy selection in daily life: The role of social context and goals.

    PubMed

    English, Tammy; Lee, Ihno A; John, Oliver P; Gross, James J

    2017-04-01

    Recent studies have begun to document the diversity of ways people regulate their emotions. However, one unanswered question is why people regulate their emotions as they do in everyday life. In the present research, we examined how social context and goals influence strategy selection in daily high points and low points. As expected, suppression was particularly tied to social features of context: it was used more when others were present, especially non-close partners, and when people had instrumental goals, especially more interpersonal ones (e.g., avoid conflict). Distraction and reappraisal were used more when regulating for hedonic reasons (e.g., to feel better), but these strategies were also linked to certain instrumental goals (e.g., getting work done). When contra-hedonic regulation occurred, it primarily took the form of dampening positive emotion during high points. Suppression was more likely to be used for contra-hedonic regulation, whereas reappraisal and distraction were used more for pro-hedonic regulation. Overall, these findings highlight the social nature of emotion regulation and underscore the importance of examining regulation in both positive and negative contexts.

  17. Emotion regulation strategy selection in daily life: The role of social context and goals

    PubMed Central

    Lee, Ihno A.; John, Oliver P.; Gross, James J.

    2016-01-01

    Recent studies have begun to document the diversity of ways people regulate their emotions. However, one unanswered question is why people regulate their emotions as they do in everyday life. In the present research, we examined how social context and goals influence strategy selection in daily high points and low points. As expected, suppression was particularly tied to social features of context: it was used more when others were present, especially non-close partners, and when people had instrumental goals, especially more interpersonal ones (e.g., avoid conflict). Distraction and reappraisal were used more when regulating for hedonic reasons (e.g., to feel better), but these strategies were also linked to certain instrumental goals (e.g., getting work done). When contra-hedonic regulation occurred, it primarily took the form of dampening positive emotion during high points. Suppression was more likely to be used for contra-hedonic regulation, whereas reappraisal and distraction were used more for pro-hedonic regulation. Overall, these findings highlight the social nature of emotion regulation and underscore the importance of examining regulation in both positive and negative contexts. PMID:28652647

  18. Automation in clinical biochemistry: core, peripheral, STAT, and specialist laboratories in Australia.

    PubMed

    Streitberg, George S; Angel, Lyndall; Sikaris, Kenneth A; Bwititi, Phillip T

    2012-10-01

    Pathology has developed substantially since the 1990s with the introduction of total laboratory automation (TLA), in response to workloads and the need to improve quality. TLA has enhanced core laboratories, which evolved from discipline-based laboratories. Work practices have changed, with central reception now loading samples onto the Inlet module of the TLA. It is important to continually appraise technology. This study looked at the impact of technology using a self-administered survey to seniors in clinical biochemistry in NATA GX/GY-classified laboratories in Australia. The responses were yes, no, or not applicable and are expressed as percentages of responses. Some of the questions sourced for descriptive answers. Eighty-one laboratories responded, and the locations were 63%, 33%, and 4% in capital cities, regional cities, and country towns, respectively. Forty-two percent were public and 58% private. Clinical biochemistry was in all core laboratories of various sizes, and most performed up to 20 tests per sample. Thirty percent of the 121 surveyed laboratories had plans to install an automated line. Fifty-eight percent had hematology and biochemistry instrumentations in their peripheral laboratory, and 16% had a STAT laboratory on the same site as the core laboratory. There were varied instruments in specialist laboratories, and analyzers with embedded computers were in all laboratories. Medium and large laboratories had workstations with integrated instruments, and some large laboratories had TLA. Technology evolution and rising demand for pathology services make it imperative for laboratories to embrace such changes and reorganize the laboratories to take into account point-of-care testing and the efficiencies of core laboratories and TLA.

  19. [Mediating role of emotional regulation between impulsive behavior in gambling, Internet and videogame abuse, and dysfunctional symptomatology in young adults and adolescents].

    PubMed

    Estévez Gutiérrez, Ana; Herrero Fernández, David; Sarabia Gonzalvo, Izaskun; Jáuregui Bilbao, Paula

    2014-01-01

    The way emotions are regulated might affect the engagement on risk behaviors in adolescents and young adults. Therefore, studying the relationship between these variables could be of great importance. Some of the less studied risky behaviors are pathological gambling, and Internet and videogame abuse. This research aims to analyze the existing relationship between such risky behaviors, emotion regulation, and dysfunctional psychological symptomatology (depression, anxiety, phobic anxiety, somatization, obsessive-–compulsive behavior, interpersonal sensitivity, hostility, paranoid ideation, and psychoticism). In addition, it also looks to assess whether emotional regulation plays a mediating role between pathological gambling, and Internet and videogame abuse, and psychological symptomatology. The sample was composed of 1312 young adults and adolescents, aged between 12 and 30, recruited from scholar centers, universities and free time groups, and from associations and centers associated with FEJAR (Spanish Federation of Rehabilitated Gamblers). Participants completed measurements of impulsive behavior, emotion regulation, and dysfunctional symptomatology. Results showed that there is generally a positive and significant relation between these variables. Moreover, it has been pointed out that emotion regulation mediates the association between impulsive behavior and dysfunctional symptomatology among those young adults and adolescents who engage in these impulsive behaviors, except for the relation between videogame abuse and depressive symptomatology. Training in emotional regulation skills could be useful in dealing with and treating this type of behaviors in adolescents and young adults.

  20. Gene Expression Profile Change and Associated Physiological and Pathological Effects in Mouse Liver Induced by Fasting and Refeeding

    PubMed Central

    Zhang, Fang; Xu, Xiang; Zhou, Ben; He, Zhishui; Zhai, Qiwei

    2011-01-01

    Food availability regulates basal metabolism and progression of many diseases, and liver plays an important role in these processes. The effects of food availability on digital gene expression profile, physiological and pathological functions in liver are yet to be further elucidated. In this study, we applied high-throughput sequencing technology to detect digital gene expression profile of mouse liver in fed, fasted and refed states. Totally 12162 genes were detected, and 2305 genes were significantly regulated by food availability. Biological process and pathway analysis showed that fasting mainly affected lipid and carboxylic acid metabolic processes in liver. Moreover, the genes regulated by fasting and refeeding in liver were mainly enriched in lipid metabolic process or fatty acid metabolism. Network analysis demonstrated that fasting mainly regulated Drug Metabolism, Small Molecule Biochemistry and Endocrine System Development and Function, and the networks including Lipid Metabolism, Small Molecule Biochemistry and Gene Expression were affected by refeeding. In addition, FunDo analysis showed that liver cancer and diabetes mellitus were most likely to be affected by food availability. This study provides the digital gene expression profile of mouse liver regulated by food availability, and demonstrates the main biological processes, pathways, gene networks and potential hepatic diseases regulated by fasting and refeeding. These results show that food availability mainly regulates hepatic lipid metabolism and is highly correlated with liver-related diseases including liver cancer and diabetes. PMID:22096593

  1. Gene expression profile change and associated physiological and pathological effects in mouse liver induced by fasting and refeeding.

    PubMed

    Zhang, Fang; Xu, Xiang; Zhou, Ben; He, Zhishui; Zhai, Qiwei

    2011-01-01

    Food availability regulates basal metabolism and progression of many diseases, and liver plays an important role in these processes. The effects of food availability on digital gene expression profile, physiological and pathological functions in liver are yet to be further elucidated. In this study, we applied high-throughput sequencing technology to detect digital gene expression profile of mouse liver in fed, fasted and refed states. Totally 12162 genes were detected, and 2305 genes were significantly regulated by food availability. Biological process and pathway analysis showed that fasting mainly affected lipid and carboxylic acid metabolic processes in liver. Moreover, the genes regulated by fasting and refeeding in liver were mainly enriched in lipid metabolic process or fatty acid metabolism. Network analysis demonstrated that fasting mainly regulated Drug Metabolism, Small Molecule Biochemistry and Endocrine System Development and Function, and the networks including Lipid Metabolism, Small Molecule Biochemistry and Gene Expression were affected by refeeding. In addition, FunDo analysis showed that liver cancer and diabetes mellitus were most likely to be affected by food availability. This study provides the digital gene expression profile of mouse liver regulated by food availability, and demonstrates the main biological processes, pathways, gene networks and potential hepatic diseases regulated by fasting and refeeding. These results show that food availability mainly regulates hepatic lipid metabolism and is highly correlated with liver-related diseases including liver cancer and diabetes.

  2. Spleen transcriptome response to infection with avian pathogenic Escherichia coli in broiler chickens

    PubMed Central

    2011-01-01

    Background Avian pathogenic Escherichia coli (APEC) is detrimental to poultry health and its zoonotic potential is a food safety concern. Regulation of antimicrobials in food-production animals has put greater focus on enhancing host resistance to bacterial infections through genetics. To better define effective mechanism of host resistance, global gene expression in the spleen of chickens, harvested at two times post-infection (PI) with APEC, was measured using microarray technology, in a design that will enable investigation of effects of vaccination, challenge, and pathology level. Results There were 1,101 genes significantly differentially expressed between severely infected and non-infected groups on day 1 PI and 1,723 on day 5 PI. Very little difference was seen between mildly infected and non-infected groups on either time point. Between birds exhibiting mild and severe pathology, there were 2 significantly differentially expressed genes on day 1 PI and 799 on day 5 PI. Groups with greater pathology had more genes with increased expression than decreased expression levels. Several predominate immune pathways, Toll-like receptor, Jak-STAT, and cytokine signaling, were represented between challenged and non-challenged groups. Vaccination had, surprisingly, no detectible effect on gene expression, although it significantly protected the birds from observable gross lesions. Functional characterization of significantly expressed genes revealed unique gene ontology classifications during each time point, with many unique to a particular treatment or class contrast. Conclusions More severe pathology caused by APEC infection was associated with a high level of gene expression differences and increase in gene expression levels. Many of the significantly differentially expressed genes were unique to a particular treatment, pathology level or time point. The present study not only investigates the transcriptomic regulations of APEC infection, but also the degree of pathology associated with that infection. This study will allow for greater discovery into host mechanisms for disease resistance, providing targets for marker assisted selection and advanced drug development. PMID:21951686

  3. Spleen transcriptome response to infection with avian pathogenic Escherichia coli in broiler chickens.

    PubMed

    Sandford, Erin E; Orr, Megan; Balfanz, Emma; Bowerman, Nate; Li, Xianyao; Zhou, Huaijun; Johnson, Timothy J; Kariyawasam, Subhashinie; Liu, Peng; Nolan, Lisa K; Lamont, Susan J

    2011-09-27

    Avian pathogenic Escherichia coli (APEC) is detrimental to poultry health and its zoonotic potential is a food safety concern. Regulation of antimicrobials in food-production animals has put greater focus on enhancing host resistance to bacterial infections through genetics. To better define effective mechanism of host resistance, global gene expression in the spleen of chickens, harvested at two times post-infection (PI) with APEC, was measured using microarray technology, in a design that will enable investigation of effects of vaccination, challenge, and pathology level. There were 1,101 genes significantly differentially expressed between severely infected and non-infected groups on day 1 PI and 1,723 on day 5 PI. Very little difference was seen between mildly infected and non-infected groups on either time point. Between birds exhibiting mild and severe pathology, there were 2 significantly differentially expressed genes on day 1 PI and 799 on day 5 PI. Groups with greater pathology had more genes with increased expression than decreased expression levels. Several predominate immune pathways, Toll-like receptor, Jak-STAT, and cytokine signaling, were represented between challenged and non-challenged groups. Vaccination had, surprisingly, no detectible effect on gene expression, although it significantly protected the birds from observable gross lesions. Functional characterization of significantly expressed genes revealed unique gene ontology classifications during each time point, with many unique to a particular treatment or class contrast. More severe pathology caused by APEC infection was associated with a high level of gene expression differences and increase in gene expression levels. Many of the significantly differentially expressed genes were unique to a particular treatment, pathology level or time point. The present study not only investigates the transcriptomic regulations of APEC infection, but also the degree of pathology associated with that infection. This study will allow for greater discovery into host mechanisms for disease resistance, providing targets for marker assisted selection and advanced drug development.

  4. 2 CFR 1.205 - Applicability to grants and other funding instruments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 2 Grants and Agreements 1 2010-01-01 2010-01-01 false Applicability to grants and other funding instruments. 1.205 Section 1.205 Grants and Agreements ABOUT TITLE 2 OF THE CODE OF FEDERAL REGULATIONS AND SUBTITLE A Introduction toSubtitle A § 1.205 Applicability to grants and other funding instruments. The...

  5. 15 CFR 301.10 - Importation of repair components and maintenance tools under HTSUS subheadings 9810.00.65 and...

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC... maintenance tools under HTSUS subheadings 9810.00.65 and 9810.00.67 for instruments previously the subject of... and 9810.00.67 for instruments previously the subject of an entry liquidated under subheading 9810.00...

  6. 15 CFR 301.10 - Importation of repair components and maintenance tools under HTSUS subheadings 9810.00.65 and...

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC... maintenance tools under HTSUS subheadings 9810.00.65 and 9810.00.67 for instruments previously the subject of... and 9810.00.67 for instruments previously the subject of an entry liquidated under subheading 9810.00...

  7. 15 CFR 301.10 - Importation of repair components and maintenance tools under HTSUS subheadings 9810.00.65 and...

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC... maintenance tools under HTSUS subheadings 9810.00.65 and 9810.00.67 for instruments previously the subject of... and 9810.00.67 for instruments previously the subject of an entry liquidated under subheading 9810.00...

  8. 15 CFR 301.10 - Importation of repair components and maintenance tools under HTSUS subheadings 9810.00.65 and...

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC... maintenance tools under HTSUS subheadings 9810.00.65 and 9810.00.67 for instruments previously the subject of... and 9810.00.67 for instruments previously the subject of an entry liquidated under subheading 9810.00...

  9. Instrument Pilot: Airplane. Flight Test Guide, Part 61 Revised 1973, AC 61-56.

    ERIC Educational Resources Information Center

    Federal Aviation Administration (DOT), Washington, DC. Flight Standards Service.

    This flight test guide is designed to assist the applicant and his instructor in preparing for the flight test for Instrument Pilot Airplane Rating under Part 61 (revised) of Federal Aviation Regulations. It contains information concerning pilot operations, procedures, and maneuvers relevant to the flight test required for the Instrument Rating.…

  10. 75 FR 42377 - Application(s) for Duty-Free Entry of Scientific Instruments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-07-21

    ... States. Comments must comply with 15 CFR 301.5(a)(3) and (4) of the regulations and be postmarked on or... Microscope. Manufacturer: FEI Company, Czech Republic. Intended Use: The instrument will be used to provide 3... the cells, proteins of the tissues and metallic nanostructures will be analyzed with the instrument...

  11. Just a Spoonful of Sugar, HTLV-1 Style.

    PubMed

    Taylor, Naomi

    2017-11-16

    Host cell metabolism regulates viral infection. In this issue of Cell Chemical Biology, Kulkarni et al. (2017) reveal the importance of oxygen concentrations and glycolysis in the reactivation of human T cell leukemia virus (HTLV-1). Identifying the host metabolic networks that regulate infection will foster our understanding of HTLV-1-associated pathologies. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. [Proteolysis in digestive system regulation].

    PubMed

    Korot'ko, G F

    2013-01-01

    Signal enzymes with direct and indirect hormone releasing action are formed by means of proteolysis from exogenic and endogenic proteins. The proteolysis is the basis of hormone processing. The limited proteolysis forms hormones from pro-hormones, ligand proteolysis excludes or reduces their stimulated or inhibited effects. The existence of polipotent proteinaso-activated receptors with regulative and modulated role in norm and pathology was proved.

  13. Modulation of cardiac fibrosis by Krüppel-like factor 6 through transcriptional control of thrombospondin 4 in cardiomyocytes

    PubMed Central

    Sawaki, Daigo; Hou, Lianguo; Tomida, Shota; Sun, Junqing; Zhan, Hong; Aizawa, Kenichi; Son, Bo-Kyung; Kariya, Taro; Takimoto, Eiki; Otsu, Kinya; Conway, Simon J.; Manabe, Ichiro; Komuro, Issei; Friedman, Scott L.; Nagai, Ryozo; Suzuki, Toru

    2015-01-01

    Aims Krüppel-like factors (KLFs) are a family of transcription factors which play important roles in the heart under pathological and developmental conditions. We previously identified and cloned Klf6 whose homozygous mutation in mice results in embryonic lethality suggesting a role in cardiovascular development. Effects of KLF6 on pathological regulation of the heart were investigated in the present study. Methods and results Mice heterozygous for Klf6 resulted in significantly diminished levels of cardiac fibrosis in response to angiotensin II infusion. Intriguingly, a similar phenotype was seen in cardiomyocyte-specific Klf6 knockout mice, but not in cardiac fibroblast-specific knockout mice. Microarray analysis revealed increased levels of the extracellular matrix factor, thrombospondin 4 (TSP4), in the Klf6-ablated heart. Mechanistically, KLF6 directly suppressed Tsp4 expression levels, and cardiac TSP4 regulated the activation of cardiac fibroblasts to regulate cardiac fibrosis. Conclusion Our present studies on the cardiac function of KLF6 show a new mechanism whereby cardiomyocytes regulate cardiac fibrosis through transcriptional control of the extracellular matrix factor, TSP4, which, in turn, modulates activation of cardiac fibroblasts. PMID:25987545

  14. Dexmedetomidine attenuates pancreatic injury and inflammatory response in mice with pancreatitis by possible reduction of NLRP3 activation and up-regulation of NET expression.

    PubMed

    Li, Yong; Pan, Yiyuan; Gao, Lin; Lu, Guotao; Zhang, Jingzhu; Xie, Xiaochun; Tong, Zhihui; Li, Baiqiang; Li, Gang; Li, Weiqin

    2018-01-22

    Previous studies have shown that acute inflammation is associated with increased sympathetic activity, which in turn increases the inflammatory response and leads to organ damage. The present study aimed to investigate whether dexmedetomidine administration during acute pancreatitis (AP) lessens pancreatic pathological and functional injury and the inflammatory response, and to explore the underlying mechanisms. Mild pancreatitis was induced in mice with caerulein, and severe pancreatitis was induced with caerulein plus lipopolysaccharide (LPS). After pancreatitis induction, dexmedetomidine at 10 or 20 μg/kg was injected via the tail vein. Pancreatic pathological and functional injury was assessed by histology and serum levels of amylase and lipase, respectively. The inflammatory response was evaluated by determining serum levels of inflammatory factors. The expression of myeloperoxidase (MPO) was examined by immunohistochemistry. The expression of norepinephrine transporter (NET), NLRP3, pro-IL-1β, and interleukin (IL)-1β in pancreatic tissue was detected by Western blot and real-time PCR. Dexmedetomidine at 20 μg/kg significantly attenuated pancreatic pathological injury, reduced serum levels of amylase, lipase, IL-1β, IL-6, and tumor necrosis factor (TNF)-α, and decreased the expression of MPO in pancreatic tissue in both mouse models of pancreatitis. In addition, dexmedetomidine at 20 μg/kg significantly down-regulated the expression of NLRP3, pro-IL-1β, and IL-1β in pancreatic tissue, but up-regulated the expression of NET in both mouse models. Dexmedetomidine attenuates pancreatic injury and inflammatory response in mice with pancreatitis possibly by reducing NLRP3 activation and up-regulating NET expression. Copyright © 2018 Elsevier Inc. All rights reserved.

  15. Redox-Dependent Calcium-Mediated Signaling Networks that Control the Senescence-Associated Secretory Phenotype

    NASA Astrophysics Data System (ADS)

    Chandrasekaran, Akshaya

    Cellular senescence has evolved as a protective mechanism to arrest growth of cells with oncogenic potential. While senescent cells have lost the ability to divide, they remain metabolically active and adapt a deleterious senescence associated secretory phenotype (SASP) central to the progression of several age-associated disease pathologies. The SASP is mechanistically regulated by the pro-inflammatory cytokine interleukin-1 alpha (IL-1alpha) whose expression and activity is responsive to the senescence associated (SA) oxidant production and the accompanying disruption of calcium (Ca2+) homeostasis. Using primary IMR-90 human fetal lung fibroblasts as a model of replicative senescence, we explored the molecular underpinnings driving Ca2+ dysregulation in senescent cells. We establish that the redox-responsive Transient Receptor Potential TRPC6 channel is compromised due to desensitization owing to SA increases in steady state hydrogen peroxide (H2O2) production. SA dysregulation of Ca2+ is also accompanied by loss of response to H2O2-induced Ca2+ influx that can be rescued with catalase pre-treatments. Senescent cells are also insensitive to Ca2+ entry induced by hyperforin, a specific activator of TRPC6, that can be restored by catalase pre-treatments, further suggesting redox regulation of TRPC6 in senescence. Inhibition of TRPC6 channel activity restores the ability of senescent cells to respond to peroxide-induced Ca2+ in addition to suppressing SASP gene expression. Furthermore, mammalian target of rapamycin (mTOR) signaling regulates SASP by means of modulating TRPC6 channel expression. Together, our findings provide compelling evidence that redox and mTOR-mediated regulation of TRPC6 channel modulate SASP gene expression. Further, the gain-of-function mutation of TRPC6 has pathological implications in several chronic pathologies and renders it a viable target in age-associated diseases.

  16. CytometryML and other data formats

    NASA Astrophysics Data System (ADS)

    Leif, Robert C.

    2006-02-01

    Cytology automation and research will be enhanced by the creation of a common data format. This data format would provide the pathology and research communities with a uniform way for annotating and exchanging images, flow cytometry, and associated data. This specification and/or standard will include descriptions of the acquisition device, staining, the binary representations of the image and list-mode data, the measurements derived from the image and/or the list-mode data, and descriptors for clinical/pathology and research. An international, vendor-supported, non-proprietary specification will allow pathologists, researchers, and companies to develop and use image capture/analysis software, as well as list-mode analysis software, without worrying about incompatibilities between proprietary vendor formats. Presently, efforts to create specifications and/or descriptions of these formats include the Laboratory Digital Imaging Project (LDIP) Data Exchange Specification; extensions to the Digital Imaging and Communications in Medicine (DICOM); Open Microscopy Environment (OME); Flowcyt, an extension to the present Flow Cytometry Standard (FCS); and CytometryML. The feasibility of creating a common data specification for digital microscopy and flow cytometry in a manner consistent with its use for medical devices and interoperability with both hospital information and picture archiving systems has been demonstrated by the creation of the CytometryML schemas. The feasibility of creating a software system for digital microscopy has been demonstrated by the OME. CytometryML consists of schemas that describe instruments and their measurements. These instruments include digital microscopes and flow cytometers. Optical components including the instruments' excitation and emission parts are described. The description of the measurements made by these instruments includes the tagged molecule, data acquisition subsystem, and the format of the list-mode and/or image data. Many of the CytometryML data-types are based on the Digital Imaging and Communications in Medicine (DICOM). Binary files for images and list-mode data have been created and read.

  17. Quantitative proteomics identify an association between extracellular matrix degradation and immunopathology of genotype VII Newcastle disease virus in the spleen in chickens.

    PubMed

    Hu, Zenglei; Gu, Han; Hu, Jiao; Hu, Shunlin; Wang, Xiaoquan; Liu, Xiaowen; Jiao, Xinan; Liu, Xiufan

    2018-06-15

    Pathogenesis of genotype VII Newcastle disease virus (NDV) is characterized with remarkable immunopathology in the spleen in chickens. However, the mechanism for this unique pathological phenotype is not fully understood. Previous transcriptomics data showed that genotype VII NDV JS5/05 caused a greater downregulation of extracellular matrix (ECM) genes than genotype IV virus Herts/33 in the spleen. In this study, the role of ECM in pathology of genotype VII NDV was investigated using quantitative proteomics. Pathology studies showed that JS5/05 caused severe immunopathology characterized with remarkable necrosis in the spleen, whereas Herts/33 only induced mild pathological changes. The ECM was firstly enriched from the spleens and ECM proteins of different categories were identified by LC-MS/MS. Quantitative proteomic analysis showed that JS5/05 caused a significant disruption of ECM integrity and molecular composition compared to Herts/33. Particularly, JS5/05 induced a more remarkable collagen breakdown in the spleen compared to Herts/33. Moreover, matrix metalloproteinase (MMP)-13 and -14 were significantly upregulated by JS5/05 infection. KEGG pathway analysis suggested that differential regulation of ECM proteins by JS5/05 and Herts/33 may impact pathology through different pathways. Therefore, our results suggested that MMP upregulation and consequent ECM degradation contribute to immunopathology of genotype VII NDV in the spleen. Pathogenesis of genotype VII NDV is characterized with severe immunopathology in the spleen in chickens. Elucidating the mechanism of this pathology phenotype is critical to understand pathogenesis of genotype VII NDV. Here, we present the proteomic data of an important non-cellular compartment, the extracellular matrix (ECM), in the spleen from chickens infected with genotype VII and IV NDVs. Our results suggest that significant upregulation of matrix metalloproteinases by genotype VII NDV and consequent disruption of ECM integrity and composition may be associated with immunopathology in the spleen. Moreover, ECM degradation, represented by collagen breakdown, is an important pathology event in the process of genotype VII NDV infection. Our study for the first time presents evidence of ECM regulation by NDV and adds ECM remodeling as a new manifestation for NDV pathology. Our findings also deepen the understanding of NDV pathogenesis. Copyright © 2018. Published by Elsevier B.V.

  18. [Pathological Internet use--epidemiology, diagnostics, co-occurring disorders and treatment].

    PubMed

    Petersen, K U; Weymann, N; Schelb, Y; Thiel, R; Thomasius, R

    2009-05-01

    In 2009, we can look back on a history of 40 years of internet use. While most consumers make use of the internet in a controlled fashion, a progressive loss of the ability to control the frequency and duration of internet activities emerges in some users. As a consequence, the excessive time devoted to internet use and the behavioural narrowing can lead to dramatic psychosocial outcomes. This phenomenon is referred to as "pathological internet use" (PIU). On behalf of the German ministry of health a systematic review of the literature since 1996 has been carried out. The main results will be presented in this review. Prevalence data on pathological internet use are limited by methodological difficulties concerning the diagnosis and the heterogeneity of diagnostical instruments. International prevalence rates range from 1.5 % to 8.2 %. Annual studies on representative samples of the German population describe their internet use and patterns of use, but information on the prevalence of PIU is missing. Diagnostical instruments are needed that show sufficient reliability and validity and allow international comparisons. Research on the Dutch "Compulsive Internet Use Scale" may close this gap. Cross-sectional studies on samples of patients report high comorbidity of PIU with psychiatric disorders, e. g. affective disorder and attention deficit hyperactivity disorder (ADHD). If PIU and these co-occurring disorders could be explained by shared risk factors or better as secondary disorders is largely unknown. The treatment currently is based on therapeutical interventions and strategies successful in the treatment of substance use disorders. Due to the lack of methodological sufficient research it is currently impossible to recommend any evidence-based treatment of PIU.

  19. Effects of using intravenous antibiotic only versus local intrawound vancomycin antibiotic powder application in addition to intravenous antibiotics on postoperative infection in spine surgery in 907 patients.

    PubMed

    Tubaki, Vijay Ramappa; Rajasekaran, S; Shetty, Ajoy Prasad

    2013-12-01

    A prospective randomized controlled trial. To assess the ability of local vancomycin powder in controlling postoperative infection in spine surgery. Despite improvements through the use of prophylactic systemic antibiotics, surgical site infections remain a significant problem in spine surgical procedures. Various retrospective and prospective studies have reported the efficacy of local application of vancomycin powder in reducing the infection in animal and human studies. However, there were no randomized control trials that reported on its efficacy. Prospective randomized controls of 907 patients with various spinal pathologies were treated surgically during a period of 18 months. The control group received standard systemic prophylaxis only, whereas the treatment group received vancomycin powder in the surgical wound in addition to systemic prophylaxis. Patient demographics, comorbidities, level of spinal pathology, estimated blood loss, nutritional status, and hemoglobin were recorded. Incidence of infection was the primary outcome evaluated. There were 8 infections (1.68%) in the control group (6 instrumented and 2 noninstrumented, 6 deep and 2 superficial) with bacteria cultured in 3 (1 Escherichia coli and 2 Staphylococcus aureus). In the treatment group, 7 infections (1.61%) were observed (6 instrumented and 1 noninstrumented surgical procedures, 6 deep and 1 superficial) with bacteria cultured in 3 (1 Staphylococcus aureus and 2 Klebsiella). No adverse effects were observed from the use of vancomycin powder. Statistically no significant difference was seen in infection rate between the treatment group and control group. The local application of vancomycin powder in surgical wounds did not significantly reduce the incidence of infection in patients with surgically treated spinal pathologies. The use of vancomycin powder may not be effective when incidence of infection is low.

  20. Long term outcome of treatment of vertebral body hemangiomas with direct ethanol injection and short segment stabilization.

    PubMed

    Chandra, P Sarat; Singh, Pankaj; K, Rajender; Agarwal, Deepak; Tandon, Vivek; Kale, S S; Sarkar, Chitra

    2018-06-08

    Vertebral body (VH) hemangiomas with myelopathy are difficult to manage. To evaluate the role of intra-operative ethanol embolization, surgical decompression and instrumented short segment fusion in VH with myelopathy and long-term outcome (>24 months). Prospective study: Symptomatic VH with cord compression with myelopathy. Excluded: pathological fractures, and/or deformity or multi-level pathologies. Surgery consisted of intra-operative bilateral pedicular absolute alcohol (<1% hydrated ethyl alcohol) injection, laminectomy and cord decompression at the level of pathology followed by a short segment instrumented fusion using pedicle screws. 33 patients (Mean 26.9 + 13.2, range: 10-68 years, 18 females). myelopathy all (5 paraplegic), sphincter involvement (13), and mid back/ lower pain (7). Pre-operative American Spinal Injury Association (ASIA) scores: A(7), B(11), C(6), D(8) and E(1). Majority had single vertebral involvement (30), 3 multiple level. Six underwent surgery earlier (1 alcohol embolization here). Mean surgical time: 124+39 minutes, average blood: 274+80 cc. Mean amount of absolute alcohol injected: 14.6+5.7 cc. (2 requiring 20 & 25 cc). Immediate embolization achieved in all, allowing laminectomy and soft-tissue hemangioma removal easily. Post-surgery, 1 patient had transient deterioration, rest all patients improved (sphincters improved in 9) at a follow up ranging 28-103 months (mean 47.6+22.3). Follow-up ASIA scores: E(26), D(4), B(2) & C(1). All patients showed evidence of bone sclerosis and relief of cord compression on follow-up imaging. This is largest study in literature showing excellent improvement, low re-operation rates following ethanol embolization and short segment fixation. Copyright © 2018. Published by Elsevier Inc.

  1. The Pathology Laboratory Act 2007 explained.

    PubMed

    Looi, Lai-Meng

    2008-06-01

    The past century has seen tremendous changes in the scope and practice of pathology laboratories in tandem with the development of the medical services in Malaysia. Major progress was made in the areas of training and specialization of pathologists and laboratory technical staff. Today the pathology laboratory services have entered the International arena, and are propelled along the wave of globalization. Many new challenges have emerged as have new players in the field. Landmark developments over the past decade include the establishment of national quality assurance programmes, the mushrooming of private pathology laboratories, the establishment of a National Accreditation Standard for medical testing laboratories based on ISO 15189, and the passing of the Pathology Laboratory Act in Parliament in mid-2007. The Pathology Laboratory Act 2007 seeks to ensure that the pathology laboratory is accountable to the public, meets required standards of practice, participates in Quality Assurance programmes, is run by qualified staff, complies with safety requirements and is subject to continuous audit. The Act is applicable to all private laboratories (stand alone or hospital) and laboratories in statutory bodies (Universities, foundations). It is not applicable to public laboratories (established and operated by the government) and side-room laboratories established in clinics of registered medical or dental practitioners for their own patients (tests as in the First and Second Schedules respectively). Tests of the Third Schedule (home test blood glucose, urine glucose, urine pregnancy test) are also exempted. The Act has 13 Parts and provides for control of the pathology laboratory through approval (to establish and maintain) and licensing (to operate or provide). The approval or license may only be issued to a sole proprietor, partnership or body corporate, and then only if the entity includes a registered medical practitioner. Details of personnel qualifications and laboratory practices are left to be specified by the Director-General of Health, providing for a formal recognition process and room for revision as pathology practices evolve. Encompassed in the responsibilities of the licensee is the requirement that samples are received and results issued through, and management vested in, a registered medical or dental practitioner. This effectively prohibits "walk-ins" to the laboratory and indiscriminate public screening. The requirement for a person-in-charge in accordance with class and speciality of laboratory ensures that the laboratory is under the charge of the pathology profession. Examined carefully, the requirements of the Act are similar to laboratory accreditation, but are backed by legislation. Many of these details will be spelt out in the Regulations, and these in turn are likely to fall back on National professional guidelines, as accreditation does. Although not at first obvious, enforcement of the Act is based on self-regulation by pathology laboratory professionals. Sincere professional input is thus required to embrace its philosophy, ensure rational and transparent enforcement of legislation, and develop National guidelines for good pathology practices upon which enforcement may be based.

  2. Review of the emerging role of optical polarimetry in characterization of pathological myocardium.

    PubMed

    Ahmad, Iftikhar

    2017-10-01

    Myocardial infarction (MI), a cause of significant morbidity and mortality, is typically followed by microstructural alterations where the necrotic myocardium is steadily replaced with a collagen scar. Engineered remodeling of the fibrotic scar via stem cell regeneration has been shown to improve/restore the myocardium function after MI. Nevertheless, the heterogeneous nature of the scar patch may impair the myocardial electrical integrity, leading to the formation of arrhythmogenesis. Radiofrequency ablation (RFA) offers an effective treatment for focal arrhythmias where local heating generated via electric current at specific spots in the myocardium ablate the arrhythmogenic foci. Characterization of these myocardial pathologies (i.e., infarcted, stem cell regenerated, and RFA-ablated myocardial tissues) is of potential clinical importance. Optical polarimetry, the use of light to map and characterize the polarization signatures of a sample, has emerged as a powerful imaging tool for structural characterization of myocardial tissues, exploiting the underlying highly fibrous tissue nature. This study aims to review the recent progress in optical polarimetry pertaining to the characterization of myocardial pathologies while describing the underlying biological rationales that give rise to the optical imaging contrast in various pathologies of the myocardium. Future possibilities of and challenges to optical polarimetry in cardiac imaging clinics are also discussed. (2017) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE).

  3. [Age characteristics of the cardiovascular system, depending on the thyroid function in type 2 diabetes mellitus].

    PubMed

    Ignateva, P A; Ballyuzek, M F; Shpakov, A O

    To study the features of cardiovascular system in patients with diabetes mellitus type 2 considering the thyroid pathology and age, 264 patients were examined. They were divided into three groups: 1st - patients with diffuse-nodular changes in the thyroid gland, 2nd - patients with autoimmune thyroid disease, 3rd - a control group of patients without thyroid disease. The patients of different ages were examined in each of these groups. All patients were in euthyroid state. It was established that identified in diabetes mellitus type 2 thyroid pathology and the thyroid disease contribute special features to the clinical picture for combined diabetic and cardiovascular pathology even in a euthyroid state including the age features. The laboratory and instrumental researches showed that the patients with combined diabetes and thyroid pathology have a higher incidence of atrial fibrillation, ischemic heart disease, and ventricular arrhythmias of high grades. They also were noticed to have a more adverse form of the left ventricle remodeling, also the combination of diastolic and systolic dysfunctions were found to be more frequent. It was concluded about the necessity of early diagnosis and correction of the cardiovascular disorders and thyroid systems in type 2 diabetes mellitus patients, including euthyroid patients.

  4. The combined endonasal and transoral approach for the management of skull base and nasopharyngeal pathology: a case series.

    PubMed

    Sreenath, Satyan B; Rawal, Rounak B; Zanation, Adam M

    2014-01-01

    The posterior skull base and the nasopharynx have historically represented technically difficult regions to approach surgically given their central anatomical locations. Through continued improvements in endoscopic instrumentation and technology, the expanded endonasal approach (EEA) has introduced a new array of surgical options in the management of pathology involving these anatomically complex areas. Similarly, the transoral robotic surgical (TORS) approach was introduced as a minimally invasive surgical option to approach tongue base, nasopharyngeal, parapharyngeal, and laryngeal lesions. Although both the EEA and the TORS approach have been extensively described as viable surgical options in managing nasopharyngeal and centrally located head and neck pathology, both endonasal and transoral techniques have inherent limitations. Given these limitations, several institutions have published feasibility studies with the combined EEA and TORS approaches for a variety of skull base and nasopharyngeal pathologies. In this article, the authors present their clinical experience with the combined endonasal and transoral approach through a case series presentation, and discuss advantages and limitations of this approach for surgical management of the middle and posterior skull base and nasopharynx. In addition, a presentation is included of a unique, simultaneous endonasal and transoral dissection of the nasopharynx through an innovative intraoperative setup.

  5. Pathological motivations for exercise and eating disorder specific health-related quality of life.

    PubMed

    Cook, Brian; Engel, Scott; Crosby, Ross; Hausenblas, Heather; Wonderlich, Stephen; Mitchell, James

    2014-04-01

    To examine associations among pathological motivations for exercise with eating disorder (ED) specific health-related quality of life (HRQOL). Survey data assessing ED severity (i.e., Eating Disorder Diagnostic Survey), ED specific HRQOL (i.e., Eating Disorders Quality of Life Instrument), and pathological motivations for exercise (i.e., Exercise Dependence Scale) were collected from female students (N = 387) at seven universities throughout the United States. Regression analyses were conducted to examine the associations among exercise dependence, ED-specific HRQOL and ED severity, and the interaction of exercise dependence and ED severity on HRQOL scores. The overall model examining the impact of ED severity and exercise dependence (independent variables) on HRQOL (dependent variable) was significant and explained 16.1% of the variance in HRQOL scores. Additionally, the main effects for ED severity and exercise dependence and the interaction among ED severity and exercise dependence were significant, suggesting that the combined effects of ED severity and exercise dependence significantly impacts HRQOL. Our results suggest that pathological motivations for exercise may exacerbate ED's detrimental impact on HRQOL. Our results offer one possible insight into why exercise may be associated with deleterious effects on ED HRQOL. Future research is needed to elucidate the relationship among psychological aspects of exercise, ED, and HRQOL. Copyright © 2013 Wiley Periodicals, Inc.

  6. Lumbar vertebral haemangioma causing pathological fracture, epidural haemorrhage, and cord compression: a case report and review of literature.

    PubMed

    Vinay, S; Khan, S K; Braybrooke, J R

    2011-01-01

    Vertebral haemangiomas are recognized to be one of the commonest benign tumours of the vertebral column, occurring mostly in the thoracic spine. The vast majority of these are asymptomatic. Infrequently, these can turn symptomatic and cause neurological deficit (cord compression) through any of four reported mechanisms: (1) epidural extension; (2) expansion of the involved vertebra(e) causing spinal canal stenosis; (3) spontaneous epidural haemorrhage; (4) pathological burst fracture. Thoracic haemangiomas have been reported to be more likely to produce cord compression than lumbar haemangiomas. A forty-nine year old male with acute onset spinal cord compression from a pathological fracture in a first lumbar vertebral haemangioma. An MRI delineated the haemangioma and extent of bleeding that caused the cord compression. These were confirmed during surgery and the haematoma was evacuated. The spine was instrumented from T12 to L2, and a cement vertebroplasty was performed intra-operatively. Written consent for publication was obtained from the patient. The junctional location of the first lumbar vertebra, and the structural weakness from normal bone being replaced by the haemangioma, probably caused it to fracture under axial loading. This pathological fracture caused bleeding from the vascularized bone, resulting in cord compression.

  7. Lumbar vertebral haemangioma causing pathological fracture, epidural haemorrhage, and cord compression: a case report and review of literature

    PubMed Central

    Vinay, S; Khan, SK; Braybrooke, JR

    2011-01-01

    Context Vertebral haemangiomas are recognized to be one of the commonest benign tumours of the vertebral column, occurring mostly in the thoracic spine. The vast majority of these are asymptomatic. Infrequently, these can turn symptomatic and cause neurological deficit (cord compression) through any of four reported mechanisms: (1) epidural extension; (2) expansion of the involved vertebra(e) causing spinal canal stenosis; (3) spontaneous epidural haemorrhage; (4) pathological burst fracture. Thoracic haemangiomas have been reported to be more likely to produce cord compression than lumbar haemangiomas. Findings A forty-nine year old male with acute onset spinal cord compression from a pathological fracture in a first lumbar vertebral haemangioma. An MRI delineated the haemangioma and extent of bleeding that caused the cord compression. These were confirmed during surgery and the haematoma was evacuated. The spine was instrumented from T12 to L2, and a cement vertebroplasty was performed intra-operatively. Written consent for publication was obtained from the patient. Clinical Relevance The junctional location of the first lumbar vertebra, and the structural weakness from normal bone being replaced by the haemangioma, probably caused it to fracture under axial loading. This pathological fracture caused bleeding from the vascularized bone, resulting in cord compression. PMID:21756575

  8. [First experience in the thyroid and parathyroid surgery using the da Vinci® system].

    PubMed

    Al Kadah, B; Siemer, S; Schick, B

    2014-01-01

    Endoscopic surgery for the treatment of thyroid and parathyroid pathologies is gaining increasing attention. The da Vinci® system has been already widely used in different fields of medicine including recently thyroid and parathyroid surgery. Herein we report our first experiences in endoscopic surgery of thyroid and parathyroid pathologies using the da Vinci® system. 8 patients presenting with struma nodosa in 6 cases and parathyroid adenomas in 2 cases have been treated using the da Vinci® system at the ENT department of Homburg/Saar University. The skin incision to introduce the instruments with the da Vinci® system were axilar or at the lateral segment of the clavicle. The neurovascular structures like inferior laryngeal nerve as well as the pathologies were clearly 3-dimensional visualized in all 8 cases. No paralysis of the vocal cord was observed. All patients had in histological examination a benign pathology. The endoscopic surgery of the thyroid and parathyroid gland can be performed using the da Vinci® system and offers an excellent, intraoperative, 3-dimensional visualization of the neurovascular structures. Additionally the da Vinci® system enables skin incisions within considerable distance from the thyroid and parathyroid gland. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Dentist phobia.

    PubMed

    Schroeder, H E; Schroeder, U; Santibánez-H, G

    1986-01-01

    This study analyzes so-called hopeless gaggers, i.e., patients in whom dental treatment and wearing of a prosthesis produced a retching or vomiting reaction, in order to investigate the sources and properties of this pathologic reaction. In 35 patients, an anamnestic inquiry, a determination of the reflexogenic zone, a recording of the peripheral pattern of the pathologic reflex, and extinction training were performed. A group of six normal persons served as a comparison group. It was shown that patients, in comparison with normals, had an enlarged receptive field, were sensitive to a broader population of stimuli, and showed precursors and aftereffects of the retching-vomiting not found in normals. This pathologic reaction was the symptom of different psychopathologic processes, such as specific fear, repugnance-fear-based disturbances, diffuse anxiety, goal-directed behavior, depressive states and, at least in one case, visceral pathology. The various patients differed with respect to properties of the reaction as well as in the sensitivity to the extinction procedure. It is discussed that different integrative nervous processes play a role in the origin and development of the syndrome: activation of unconditional reflexes, activation of classic and instrumental conditional reflexes, activation of such reflexes by an increase of the reactivity level of specific and unspecific structures of the brain, generalization of stimuli, etc.

  10. The structural and functional connectivity of the amygdala: From normal emotion to pathological anxiety

    PubMed Central

    Kim, M. Justin; Loucks, Rebecca A.; Palmer, Amy L.; Brown, Annemarie C.; Solomon, Kimberly M.; Marchante, Ashley N.; Whalen, Paul J.

    2011-01-01

    The dynamic interactions between the amygdala and the medial prefrontal cortex (mPFC) are usefully conceptualized as a circuit that both allows us to react automatically to biologically relevant predictive stimuli as well as regulate these reactions when the situation calls for it. In this review, we will begin by discussing the role of this amygdala-mPFC circuitry in the conditioning and extinction of aversive learning in animals. We will then relate these data to emotional regulation paradigms in humans. Finally, we will consider how these processes are compromised in normal and pathological anxiety. We conclude that the capacity for efficient crosstalk between the amygdala and the mPFC, which is represented as the strength of the amygdala-mPFC circuitry, is crucial to beneficial outcomes in terms of reported anxiety. PMID:21536077

  11. Immunity by equilibrium.

    PubMed

    Eberl, Gérard

    2016-08-01

    The classical model of immunity posits that the immune system reacts to pathogens and injury and restores homeostasis. Indeed, a century of research has uncovered the means and mechanisms by which the immune system recognizes danger and regulates its own activity. However, this classical model does not fully explain complex phenomena, such as tolerance, allergy, the increased prevalence of inflammatory pathologies in industrialized nations and immunity to multiple infections. In this Essay, I propose a model of immunity that is based on equilibrium, in which the healthy immune system is always active and in a state of dynamic equilibrium between antagonistic types of response. This equilibrium is regulated both by the internal milieu and by the microbial environment. As a result, alteration of the internal milieu or microbial environment leads to immune disequilibrium, which determines tolerance, protective immunity and inflammatory pathology.

  12. MicroRNAs as Regulators of Endothelial Cell Functions in Cardiometabolic Diseases

    PubMed Central

    Araldi, Elisa; Suárez, Yajaira

    2016-01-01

    Endothelial cells (ECs) provide nutrients and oxygen essential for tissue homeostasis. Metabolic imbalances and other environmental stimuli, like cytokines or low shear stress, trigger endothelial inflammation, increase permeability, compromise vascular tone, promote cell proliferation and ultimately cause cell death. These factors contribute to EC dysfunction, which is crucial in the development of cardiometabolic diseases. microRNAs (miRNAs) are small non-coding RNAs that have important functions in the regulation of ECs. In the present review, we discuss the role of miRNAs in various aspects of EC pathology in cardiometabolic diseases like atherosclerosis, type 2 diabetes, obesity, and the metabolic syndrome, and in complication of those pathologies, like ischemia. We also discuss the potential therapeutic applications of miRNAs in promoting angiogenesis and neovascularization in tissues where the endothelium is damaged in different cardiometabolic diseases. PMID:26825686

  13. Bestrophin 1 is indispensable for volume regulation in human retinal pigment epithelium cells.

    PubMed

    Milenkovic, Andrea; Brandl, Caroline; Milenkovic, Vladimir M; Jendryke, Thomas; Sirianant, Lalida; Wanitchakool, Potchanart; Zimmermann, Stephanie; Reiff, Charlotte M; Horling, Franziska; Schrewe, Heinrich; Schreiber, Rainer; Kunzelmann, Karl; Wetzel, Christian H; Weber, Bernhard H F

    2015-05-19

    In response to cell swelling, volume-regulated anion channels (VRACs) participate in a process known as regulatory volume decrease (RVD). Only recently, first insight into the molecular identity of mammalian VRACs was obtained by the discovery of the leucine-rich repeats containing 8A (LRRC8A) gene. Here, we show that bestrophin 1 (BEST1) but not LRRC8A is crucial for volume regulation in human retinal pigment epithelium (RPE) cells. Whole-cell patch-clamp recordings in RPE derived from human-induced pluripotent stem cells (hiPSC) exhibit an outwardly rectifying chloride current with characteristic functional properties of VRACs. This current is severely reduced in hiPSC-RPE cells derived from macular dystrophy patients with pathologic BEST1 mutations. Disruption of the orthologous mouse gene (Best1(-/-)) does not result in obvious retinal pathology but leads to a severe subfertility phenotype in agreement with minor endogenous expression of Best1 in murine RPE but highly abundant expression in mouse testis. Sperm from Best1(-/-) mice showed reduced motility and abnormal sperm morphology, indicating an inability in RVD. Together, our data suggest that the molecular identity of VRACs is more complex--that is, instead of a single ubiquitous channel, VRACs could be formed by cell type- or tissue-specific subunit composition. Our findings provide the basis to further examine VRAC diversity in normal and diseased cell physiology, which is key to exploring novel therapeutic approaches in VRAC-associated pathologies.

  14. ASVCP quality assurance guidelines: control of general analytical factors in veterinary laboratories.

    PubMed

    Flatland, Bente; Freeman, Kathy P; Friedrichs, Kristen R; Vap, Linda M; Getzy, Karen M; Evans, Ellen W; Harr, Kendal E

    2010-09-01

    Owing to lack of governmental regulation of veterinary laboratory performance, veterinarians ideally should demonstrate a commitment to self-monitoring and regulation of laboratory performance from within the profession. In response to member concerns about quality management in veterinary laboratories, the American Society for Veterinary Clinical Pathology (ASVCP) formed a Quality Assurance and Laboratory Standards (QAS) committee in 1996. This committee recently published updated and peer-reviewed Quality Assurance Guidelines on the ASVCP website. The Quality Assurance Guidelines are intended for use by veterinary diagnostic laboratories and veterinary research laboratories that are not covered by the US Food and Drug Administration Good Laboratory Practice standards (Code of Federal Regulations Title 21, Chapter 58). The guidelines have been divided into 3 reports on 1) general analytic factors for veterinary laboratory performance and comparisons, 2) hematology and hemostasis, and 3) clinical chemistry, endocrine assessment, and urinalysis. This report documents recommendations for control of general analytical factors within veterinary clinical laboratories and is based on section 2.1 (Analytical Factors Important In Veterinary Clinical Pathology, General) of the newly revised ASVCP QAS Guidelines. These guidelines are not intended to be all-inclusive; rather, they provide minimum guidelines for quality assurance and quality control for veterinary laboratory testing. It is hoped that these guidelines will provide a basis for laboratories to assess their current practices, determine areas for improvement, and guide continuing professional development and education efforts. ©2010 American Society for Veterinary Clinical Pathology.

  15. MiR-153 Regulates Amelogenesis by Targeting Endocytotic and Endosomal/lysosomal Pathways–Novel Insight into the Origins of Enamel Pathologies

    PubMed Central

    Yin, Kaifeng; Lin, Wenting; Guo, Jing; Sugiyama, Toshihiro; Snead, Malcolm L.; Hacia, Joseph G.; Paine, Michael L.

    2017-01-01

    Amelogenesis imperfecta (AI) is group of inherited disorders resulting in enamel pathologies. The involvement of epigenetic regulation in the pathogenesis of AI is yet to be clarified due to a lack of knowledge about amelogenesis. Our previous genome-wide microRNA and mRNA transcriptome analyses suggest a key role for miR-153 in endosome/lysosome-related pathways during amelogenesis. Here we show that miR-153 is significantly downregulated in maturation ameloblasts compared with secretory ameloblasts. Within ameloblast-like cells, upregulation of miR-153 results in the downregulation of its predicted targets including Cltc, Lamp1, Clcn4 and Slc4a4, and a number of miRNAs implicated in endocytotic pathways. Luciferase reporter assays confirmed the predicted interactions between miR-153 and the 3′-UTRs of Cltc, Lamp1 (in a prior study), Clcn4 and Slc4a4. In an enamel protein intake assay, enamel cells transfected with miR-153 show a decreased ability to endocytose enamel proteins. Finally, microinjection of miR-153 in the region of mouse first mandibular molar at postnatal day 8 (PN8) induced AI-like pathologies when the enamel development reached maturity (PN12). In conclusion, miR-153 regulates maturation-stage amelogenesis by targeting key genes involved in the endocytotic and endosomal/lysosomal pathways, and disruption of miR-153 expression is a potential candidate etiologic factor contributing to the occurrence of AI. PMID:28287144

  16. MiR-153 Regulates Amelogenesis by Targeting Endocytotic and Endosomal/lysosomal Pathways-Novel Insight into the Origins of Enamel Pathologies.

    PubMed

    Yin, Kaifeng; Lin, Wenting; Guo, Jing; Sugiyama, Toshihiro; Snead, Malcolm L; Hacia, Joseph G; Paine, Michael L

    2017-03-13

    Amelogenesis imperfecta (AI) is group of inherited disorders resulting in enamel pathologies. The involvement of epigenetic regulation in the pathogenesis of AI is yet to be clarified due to a lack of knowledge about amelogenesis. Our previous genome-wide microRNA and mRNA transcriptome analyses suggest a key role for miR-153 in endosome/lysosome-related pathways during amelogenesis. Here we show that miR-153 is significantly downregulated in maturation ameloblasts compared with secretory ameloblasts. Within ameloblast-like cells, upregulation of miR-153 results in the downregulation of its predicted targets including Cltc, Lamp1, Clcn4 and Slc4a4, and a number of miRNAs implicated in endocytotic pathways. Luciferase reporter assays confirmed the predicted interactions between miR-153 and the 3'-UTRs of Cltc, Lamp1 (in a prior study), Clcn4 and Slc4a4. In an enamel protein intake assay, enamel cells transfected with miR-153 show a decreased ability to endocytose enamel proteins. Finally, microinjection of miR-153 in the region of mouse first mandibular molar at postnatal day 8 (PN8) induced AI-like pathologies when the enamel development reached maturity (PN12). In conclusion, miR-153 regulates maturation-stage amelogenesis by targeting key genes involved in the endocytotic and endosomal/lysosomal pathways, and disruption of miR-153 expression is a potential candidate etiologic factor contributing to the occurrence of AI.

  17. Roles of PDE1 in Pathological Cardiac Remodeling and Dysfunction.

    PubMed

    Chen, Si; Knight, Walter E; Yan, Chen

    2018-04-23

    Pathological cardiac hypertrophy and dysfunction is a response to various stress stimuli and can result in reduced cardiac output and heart failure. Cyclic nucleotide signaling regulates several cardiac functions including contractility, remodeling, and fibrosis. Cyclic nucleotide phosphodiesterases (PDEs), by catalyzing the hydrolysis of cyclic nucleotides, are critical in the homeostasis of intracellular cyclic nucleotide signaling and hold great therapeutic potential as drug targets. Recent studies have revealed that the inhibition of the PDE family member PDE1 plays a protective role in pathological cardiac remodeling and dysfunction by the modulation of distinct cyclic nucleotide signaling pathways. This review summarizes recent key findings regarding the roles of PDE1 in the cardiac system that can lead to a better understanding of its therapeutic potential.

  18. Rab GTPases and Membrane Trafficking in Neurodegeneration

    PubMed Central

    Kiral, Ferdi Ridvan; Kohrs, Friederike Elisabeth; Jin, Eugene Jennifer; Hiesinger, Peter Robin

    2018-01-01

    Defects in membrane trafficking are hallmarks of neurodegeneration. Rab GTPases are key regulators of membrane trafficking. Alterations of Rab GTPases, or the membrane compartments they regulate, are associated with virtually all neuronal activities in health and disease. The observation that many Rab GTPases are associated with neurodegeneration has proven a challenge in the quest for cause and effect. Neurodegeneration can be a direct consequence of a defect in membrane trafficking. Alternatively, changes in membrane trafficking may be secondary consequences or cellular responses. The secondary consequences and cellular responses, in turn, may protect, represent inconsequential correlates or function as drivers of pathology. Here, we attempt to disentangle the different roles of membrane trafficking in neurodegeneration by focusing on selected associations with Alzheimer’s disease, Parkinson’s disease, Huntington’s disease and selected neuropathies. We provide an overview of current knowledge on Rab GTPase functions in neurons and review the associations of Rab GTPases with neurodegeneration with respect to the following classifications: primary cause, secondary cause driving pathology or secondary correlate. This analysis is devised to aid the interpretation of frequently observed membrane trafficking defects in neurodegeneration and facilitate the identification of true causes of pathology. PMID:29689231

  19. Pericytes in kidney fibrosis.

    PubMed

    Ren, Shuyu; Duffield, Jeremy S

    2013-07-01

    Pericytes and perivascular fibroblasts have emerged as poorly appreciated yet extensive populations of mesenchymal cells in the kidney that play important roles in homeostasis and responses to injury. This review will update readers on the evolving understanding of the biology of these cells. Fate mapping has identified pericytes and perivascular fibroblasts as the major source of pathological fibrillar matrix-forming cells in interstitial kidney disease. In other organs similar cells have been described and independent fate mapping indicates that pericytes or perivascular cells are myofibroblast progenitors in multiple organs. Over the last year, new insights into the function of pericytes in kidney homeostasis has been uncovered and new molecular pathways that regulate detachment and their transdifferentiation into pathological myofibroblasts, including Wingless/Int, ephrin, transforming growth factor β, platelet derived growth factor, and Hedgehog signaling pathways, have been reported. In addition provocative studies indicate that microRNAs, which regulate posttranscriptional gene expression, may also play important roles in their transdifferentiation. Pericytes and perivascular fibroblasts are the major source of pathological collagen fiber-forming cells in interstitial kidney diseases. New avenues of research into their activation and differentiation has identified new drug candidates for the treatment of interstitial kidney disease.

  20. The Alzheimer's Amyloid-Degrading Peptidase, Neprilysin: Can We Control It?

    PubMed Central

    Nalivaeva, N. N.; Belyaev, N. D.; Zhuravin, I. A.; Turner, A. J.

    2012-01-01

    The amyloid cascade hypothesis of Alzheimer's disease (AD) postulates that accumulation in the brain of amyloid β-peptide (Aβ) is the primary trigger for neuronal loss specific to this pathology. In healthy brain, Aβ levels are regulated by a dynamic equilibrium between Aβ release from the amyloid precursor protein (APP) and its removal by perivascular drainage or by amyloid-degrading enzymes (ADEs). During the last decade, the ADE family was fast growing, and currently it embraces more than 20 members. There are solid data supporting involvement of each of them in Aβ clearance but a zinc metallopeptidase neprilysin (NEP) is considered as a major ADE. NEP plays an important role in brain function due to its role in terminating neuropeptide signalling and its decrease during ageing or after such pathologies as hypoxia or ischemia contribute significantly to the development of AD pathology. The recently discovered mechanism of epigenetic regulation of NEP by the APP intracellular domain (AICD) opens new avenues for its therapeutic manipulation and raises hope for developing preventive strategies in AD. However, consideration needs to be given to the diverse physiological roles of NEP. This paper critically evaluates general biochemical and physiological functions of NEP and their therapeutic relevance. PMID:22900228

  1. Alteration of Developmental and Pathological Retinal Angiogenesis in angptl4-deficient Mice*

    PubMed Central

    Perdiguero, Elisa Gomez; Galaup, Ariane; Durand, Mélanie; Teillon, Jérémie; Philippe, Josette; Valenzuela, David M.; Murphy, Andrew J.; Yancopoulos, George D.; Thurston, Gavin; Germain, Stéphane

    2011-01-01

    Proper vessel maturation, remodeling of endothelial junctions, and recruitment of perivascular cells is crucial for establishing and maintaining vessel functions. In proliferative retinopathies, hypoxia-induced angiogenesis is associated with disruption of the vascular barrier, edema, and vision loss. Therefore, identifying factors that regulate vascular maturation is critical to target pathological angiogenesis. Given the conflicting role of angiopoietin-like-4 (ANGPTL4) reported in the current literature using gain of function systems both in vitro and in vivo, the goal of this study was to characterize angiogenesis, focusing on perinatal retinal vascularization and pathological circumstances in angpl4-deficient mice. We report altered organization of endothelial junctions and pericyte coverage, both leading to impaired angiogenesis and increased vascular leakage that were eventually caught up, suggesting a delay in vessel maturation. In a model of oxygen-induced retinopathy, pathological neovascularization, which results from tissue hypoxia, was also strongly inhibited in angptl4-deficient mice. This study therefore shows that ANGPTL4 tunes endothelial cell junction organization and pericyte coverage and controls vascular permeability and angiogenesis, both during development and in pathological conditions. PMID:21832056

  2. The Integrative Role of the Sigh in Psychology, Physiology, Pathology, and Neurobiology

    PubMed Central

    Ramirez, Jan-Marino

    2015-01-01

    “Sighs, tears, grief, distress” expresses Johann Sebastian Bach in a musical example for the relationship between sighs and deep emotions. This review explores the neurobiological basis of the sigh and its relationship with psychology, physiology, and pathology. Sighs monitor changes in brain states, induce arousal, and reset breathing variability. These behavioral roles homeostatically regulate breathing stability under physiological and pathological conditions. Sighs evoked in hypoxia evoke arousal and thereby become critical for survival. Hypoarousal and failure to sigh have been associated with sudden infant death syndrome. Increased breathing irregularity may provoke excessive sighing and hyperarousal, a behavioral sequence that may play a role in panic disorders. Essential for generating sighs and breathing is the pre-Bötzinger complex. Modulatory and synaptic interactions within this local network and between networks located in the brainstem, cerebellum, cortex, hypothalamus, amygdala, and the periaqueductal gray may govern the relationships between physiology, psychology, and pathology. Unraveling these circuits will lead to a better understanding of how we balance emotions and how emotions become pathological. PMID:24746045

  3. A Meta-Analysis Examining the Influence of Pro-Eating Disorder Websites on Body Image and Eating Pathology.

    PubMed

    Rodgers, Rachel F; Lowy, Alice S; Halperin, Daniella M; Franko, Debra L

    2016-01-01

    Previous research has indicated that exposure to pro-eating disorder websites might increase eating pathology; however, the magnitude of this effect is unknown. This study aimed to conduct a systematic review and meta-analysis to examine the effect of exposure to pro-eating disorder websites on body image and eating pathology. Studies examining the relationship between exposure to pro-eating disorder websites and eating pathology-related outcomes were included. The systematic review identified nine studies. Findings revealed significant effect sizes of exposure to pro-eating disorder websites on body image dissatisfaction (five studies), d = .41, p = .003; dieting (six studies), d = .68, p < .001, and negative affect (three studies), d = 1.00, p < .001. No effect emerged for bulimic symptoms (four studies), d = .22, p = .73. Findings confirmed the effect of pro-eating disorder websites on body image and eating pathology, highlighting the need for enforceable regulation of these websites. Copyright © 2015 John Wiley & Sons, Ltd and Eating Disorders Association.

  4. Gender differences in eating behavior and eating pathology: The mediating role of rumination.

    PubMed

    Opwis, Mareile; Schmidt, Jennifer; Martin, Alexandra; Salewski, Christel

    2017-03-01

    Rumination is a maladaptive emotion regulation strategy which contributes to psychopathology and is more frequently used by women than men. It has been found to mediate the relationship between gender and the occurrence of anxiety disorders or depression. Since gender differences also appear in dysfunctional eating, the aim of the study is to test, whether rumination mediates the association between gender and several facets of eating pathology. A total of 295 participants (205 women) completed an online-questionnaire including the assessment of different facets of dysfunctional eating and rumination. Mediation analyses were conducted with PROCESS. Women reported significantly higher levels in both, rumination and eating pathology. Moreover, rumination mediated the relationship between gender and all assessed aspects of dysfunctional eating. The present study extends findings on the mediating role of rumination accounting for gender differences in psychopathology to eating pathology in a community sample. Results suggest that cognitive factors play a substantial role in explaining gender differences in eating pathology which tend to be reduced to biologicals factors and beauty ideals. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Reconciling Pasteur and Darwin to control infectious diseases

    PubMed Central

    Méthot, Pierre-Olivier

    2018-01-01

    The continual emergence of new pathogens and the increased spread of antibiotic resistance in bacterial populations remind us that microbes are living entities that evolve at rates that impact public health interventions. Following the historical thread of the works of Pasteur and Darwin shows how reconciling clinical microbiology, ecology, and evolution can be instrumental to understanding pathology, developing new therapies, and prolonging the efficiency of existing ones. PMID:29346373

  6. Noninvasive Spatially Offset and Transmission Raman Mapping of Breast Tissue: A Multimodal Approach Towards the In Vivo Assessment of Tissue Pathology

    DTIC Science & Technology

    2013-06-01

    spectroscopy on tissue biopsies to correlate spectral bands with healthy and diseased breast tissue. Observed spectral changes are compared to infrared...capabilities and performance. Additionally, we conduct spectroscopy on tissue biopsies to correlate spectral bands with healthy and diseased ... disease states, ie hyperplasia, dysplasia, malignant, benign. The instrumentation has been built and characterized using archived tissue that was

  7. Sexuality as an Independent Variable: The Contribution to (or Protection against) Chronic Disease,

    DTIC Science & Technology

    1978-01-05

    science has come to indict a long list of risk factors in disabling and fatal diseases: dietary intake, physical exercise activities, food chain pollutants...impulses, sensations, behaviors, and physiological happenings coincident with the instrumental acts of sexual stimulation , excitation, and expression...agent. The Freudian theory of psycho- pathology (e.g., Freud, 1935) invokes repressed sexuality as a fore- runner of psychoneurosis. Sexual stimulation

  8. Evaluation of Safety Programs with Respect to the Causes of General Aviation Accidents. Volume I. Technical Report,

    DTIC Science & Technology

    1980-05-01

    65 Physical Impairment 66 Spatial disorientation. 67 Psychological condition. 71 Misused or failed to use flaps. 74 Left aircraft unattended, engine...ARTS III - (Software) (1975) 203 Weather Radar Display System (ASR - 57) 204 ATARS - Automated Terminal Area Radar Service (1974) 205 Instrument Landing...Generated Trauma, Pathological and Psychological Dysfunction accident causes. Collectively, the distribution of safety programs throughout the fault

  9. Cell death cascade and molecular therapy in ADAR2-deficient motor neurons of ALS.

    PubMed

    Yamashita, Takenari; Kwak, Shin

    2018-06-23

    TAR DNA-binding protein (TDP-43) pathology in the motor neurons is the most reliable pathological hallmark of amyotrophic lateral sclerosis (ALS), and motor neurons bearing TDP-43 pathology invariably exhibit failure in RNA editing at the GluA2 glutamine/arginine (Q/R) site due to down-regulation of adenosine deaminase acting on RNA 2 (ADAR2). Conditional ADAR2 knockout (AR2) mice display ALS-like phenotype, including progressive motor dysfunction due to loss of motor neurons. Motor neurons devoid of ADAR2 express Q/R site-unedited GluA2, and AMPA receptors with unedited GluA2 in their subunit assembly are abnormally permeable to Ca 2+ , which results in progressive neuronal death. Moreover, analysis of AR2 mice has demonstrated that exaggerated Ca 2+ influx through the abnormal AMPA receptors overactivates calpain, a Ca 2+ -dependent protease, that cleaves TDP-43 into aggregation-prone fragments, which serve as seeds for TDP-43 pathology. Activated calpain also disrupts nucleo-cytoplasmic transport and gene expression by cleaving molecules involved in nucleocytoplasmic transport, including nucleoporins. These lines of evidence prompted us to develop molecular targeting therapy for ALS by normalization of disrupted intracellular environment due to ADAR2 down-regulation. In this review, we have summarized the work from our group on the cell death cascade in sporadic ALS and discussed a potential therapeutic strategy for ALS. Copyright © 2018 Elsevier Ireland Ltd and the Japan Neuroscience Society. All rights reserved.

  10. Regulation of age-related macular degeneration-like pathology by complement factor H

    PubMed Central

    Toomey, Christopher B.; Kelly, Una; Saban, Daniel R.; Bowes Rickman, Catherine

    2015-01-01

    Complement factor H (CFH) is a major susceptibility gene for age-related macular degeneration (AMD); however, its impact on AMD pathobiology is unresolved. Here, the role of CFH in the development of AMD pathology in vivo was interrogated by analyzing aged Cfh+/− and Cfh−/− mice fed a high-fat, cholesterol-enriched diet. Strikingly, decreased levels of CFH led to increased sub-retinal pigmented epithelium (sub-RPE) deposit formation, specifically basal laminar deposits, following high-fat diet. Mechanistically, our data show that deposits are due to CFH competition for lipoprotein binding sites in Bruch’s membrane. Interestingly and despite sub-RPE deposit formation occurring in both Cfh+/− and Cfh−/− mice, RPE damage accompanied by loss of vision occurred only in old Cfh+/− mice. We demonstrate that such pathology is a function of excess complement activation in Cfh+/− mice versus complement deficiency in Cfh−/− animals. Due to the CFH-dependent increase in sub-RPE deposit height, we interrogated the potential of CFH as a previously unidentified regulator of Bruch’s membrane lipoprotein binding and show, using human Bruch’s membrane explants, that CFH removes endogenous human lipoproteins in aged donors. Thus, advanced age, high-fat diet, and decreased CFH induce sub-RPE deposit formation leading to complement activation, which contributes to RPE damage and visual function impairment. This new understanding of the complicated interactions of CFH in AMD-like pathology provides an improved foundation for the development of targeted therapies for AMD. PMID:25991857

  11. A biphasic endothelial stress-survival mechanism regulates the cellular response to vascular endothelial growth factor A

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

    Latham, Antony M.; Odell, Adam F.; Mughal, Nadeem A.

    2012-11-01

    Vascular endothelial growth factor A (VEGF-A) is an essential cytokine that regulates endothelial function and angiogenesis. VEGF-A binding to endothelial receptor tyrosine kinases such as VEGFR1 and VEGFR2 triggers cellular responses including survival, proliferation and new blood vessel sprouting. Increased levels of a soluble VEGFR1 splice variant (sFlt-1) correlate with endothelial dysfunction in pathologies such as pre-eclampsia; however the cellular mechanism(s) underlying the regulation and function of sFlt-1 are unclear. Here, we demonstrate the existence of a biphasic stress response in endothelial cells, using serum deprivation as a model of endothelial dysfunction. The early phase is characterized by a highmore » VEGFR2:sFlt-1 ratio, which is reversed in the late phase. A functional consequence is a short-term increase in VEGF-A-stimulated intracellular signaling. In the late phase, sFlt-1 is secreted and deposited at the extracellular matrix. We hypothesized that under stress, increased endothelial sFlt-1 levels reduce VEGF-A bioavailability: VEGF-A treatment induces sFlt-1 expression at the cell surface and VEGF-A silencing inhibits sFlt-1 anchorage to the extracellular matrix. Treatment with recombinant sFlt-1 inhibits VEGF-A-stimulated in vitro angiogenesis and sFlt-1 silencing enhances this process. In this response, increased VEGFR2 levels are regulated by the phosphatidylinositol-3-kinase and PKB/Akt signaling pathways and increased sFlt-1 levels by the ERK1/2 signaling pathway. We conclude that during serum withdrawal, cellular sensing of environmental stress modulates sFlt-1 and VEGFR2 levels, regulating VEGF-A bioavailability and ensuring cell survival takes precedence over cell proliferation and migration. These findings may underpin an important mechanism contributing to endothelial dysfunction in pathological states. -- Highlights: Black-Right-Pointing-Pointer Endothelial cells mount a stress response under conditions of low serum. Black-Right-Pointing-Pointer Endothelial VEGFR levels are modulated during this response. Black-Right-Pointing-Pointer The cell regulates VEGF-A bioavailability and cell survival. Black-Right-Pointing-Pointer This may partly underlie endothelial dysfunction seen in many pathologies.« less

  12. The Challenges of Dysphagia Management and Rehabilitation in Two Complex Cases Post Chemical Ingestion Injury.

    PubMed

    Rumbach, Anna F; Cremer, Rebecca; Chatwood, Astra; Fink, Sari; Haider, Sadaf; Yee, Michelle

    2016-11-01

    Dysphagia is common sequelae of chemical ingestion injury, resulting from damage to critical swallowing structures. From a speech-language pathology perspective, this study outlines the physiological deficits in 2 individuals with severe injury (1 woman, acid; 1 man, alkali) and the pattern of dysphagia rehabilitation and recovery. A retrospective chart review of clinical and instrumental assessments was conducted to examine swallow characteristics and speech-language pathology management (compensatory and rehabilitation strategies) at multiple time points. Chemical ingestion injury resulted in severe pharyngeal dysphagia for both participants, warranting speech-language pathology management. Dysphagia was characterized by poor base of tongue mobility and reduced laryngeal excursion. Decreased airway patency and protection, secondary to mucosal sloughing, widespread edema, and structural deficits necessitated tracheostomy. Recovery was complicated by physical alterations of pharyngeal and laryngeal structures (e.g., interarytenoid adhesions) and esophageal strictures. Participant 1 was discharged (Day 135) consuming a texture-modified diet; Participant 2 remained nil by mouth (Day 329). Dysphagia recovery subsequent to chemical ingestion is protracted and complex. Clinical outcomes may be improved through individualized and intensive rehabilitation by speech-language pathologists.

  13. Computed tomography angiography reveals the crime instrument – case report

    PubMed Central

    Banaszek, Anna; Guziński, Maciej; Sąsiadek, Marek

    2010-01-01

    Summary Background: The development of multislice CT technology enabled imaging of post-traumatic brain lesions with isotropic resolution, which led to unexpected results in the presented case Case Report: An unconscious, 49-year-old male with a suspected trauma underwent a routine CT examination of the head, which revealed an unusual intracerebral bleeding and therefore was followed by CT angiography (CTA). The thorough analysis of CTA source scans led to the detection of the bleeding cause. Conclusions: The presented case showed that a careful analysis of a CT scan allows not only to define the extent of pathological lesions in the intracranial space but it also helps to detect the crime instrument, which is of medico-legal significance. PMID:22802784

  14. A novel DYRK1A (dual specificity tyrosine phosphorylation-regulated kinase 1A) inhibitor for the treatment of Alzheimer's disease: effect on Tau and amyloid pathologies in vitro.

    PubMed

    Coutadeur, Séverine; Benyamine, Hélène; Delalonde, Laurence; de Oliveira, Catherine; Leblond, Bertrand; Foucourt, Alicia; Besson, Thierry; Casagrande, Anne-Sophie; Taverne, Thierry; Girard, Angélique; Pando, Matthew P; Désiré, Laurent

    2015-05-01

    The dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) gene is located within the Down Syndrome (DS) critical region on chromosome 21 and is implicated in the generation of Tau and amyloid pathologies that are associated with the early onset Alzheimer's Disease (AD) observed in DS. DYRK1A is also found associated with neurofibrillary tangles in sporadic AD and phosphorylates key AD players (Tau, amyloid precursor, protein, etc). Thus, DYRK1A may be an important therapeutic target to modify the course of Tau and amyloid beta (Aβ) pathologies. Here, we describe EHT 5372 (methyl 9-(2,4-dichlorophenylamino) thiazolo[5,4-f]quinazoline-2-carbimidate), a novel, highly potent (IC50 = 0.22 nM) DYRK1A inhibitor with a high degree of selectivity over 339 kinases. Models in which inhibition of DYRK1A by siRNA reduced and DYRK1A over-expression induced Tau phosphorylation or Aβ production were used. EHT 5372 inhibits DYRK1A-induced Tau phosphorylation at multiple AD-relevant sites in biochemical and cellular assays. EHT 5372 also normalizes both Aβ-induced Tau phosphorylation and DYRK1A-stimulated Aβ production. DYRK1A is thus as a key element of Aβ-mediated Tau hyperphosphorylation, which links Tau and amyloid pathologies. EHT 5372 and other compounds in its class warrant in vivo investigation as a novel, high-potential therapy for AD and other Tau opathies. Inhibition of the dual specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) is a new high-potential therapeutic approach for Alzheimer disease. Here we describe EHT 5372, a novel potent and selective DYRK1A inhibitor. EHT 5372 inhibits DYRK1A-induced Tau phosphorylation, Aβ production and Aβ effects on phospho-Tau, including Tau aggregation. © 2014 International Society for Neurochemistry.

  15. A comprehensive data mining study shows that most nuclear receptors act as newly proposed homeostasis-associated molecular pattern receptors.

    PubMed

    Wang, Luqiao; Nanayakkara, Gayani; Yang, Qian; Tan, Hongmei; Drummer, Charles; Sun, Yu; Shao, Ying; Fu, Hangfei; Cueto, Ramon; Shan, Huimin; Bottiglieri, Teodoro; Li, Ya-Feng; Johnson, Candice; Yang, William Y; Yang, Fan; Xu, Yanjie; Xi, Hang; Liu, Weiqing; Yu, Jun; Choi, Eric T; Cheng, Xiaoshu; Wang, Hong; Yang, Xiaofeng

    2017-10-24

    Nuclear receptors (NRs) can regulate gene expression; therefore, they are classified as transcription factors. Despite the extensive research carried out on NRs, still several issues including (1) the expression profile of NRs in human tissues, (2) how the NR expression is modulated during atherosclerosis and metabolic diseases, and (3) the overview of the role of NRs in inflammatory conditions are not fully understood. To determine whether and how the expression of NRs are regulated in physiological/pathological conditions, we took an experimental database analysis to determine expression of all 48 known NRs in 21 human and 17 murine tissues as well as in pathological conditions. We made the following significant findings: (1) NRs are differentially expressed in tissues, which may be under regulation by oxygen sensors, angiogenesis pathway, stem cell master regulators, inflammasomes, and tissue hypo-/hypermethylation indexes; (2) NR sequence mutations are associated with increased risks for development of cancers and metabolic, cardiovascular, and autoimmune diseases; (3) NRs have less tendency to be upregulated than downregulated in cancers, and autoimmune and metabolic diseases, which may be regulated by inflammation pathways and mitochondrial energy enzymes; and (4) the innate immune sensor inflammasome/caspase-1 pathway regulates the expression of most NRs. Based on our findings, we propose a new paradigm that most nuclear receptors are anti-inflammatory homeostasis-associated molecular pattern receptors (HAMPRs). Our results have provided a novel insight on NRs as therapeutic targets in metabolic diseases, inflammations, and malignancies.

  16. An examination of the relationship between childhood emotional abuse and borderline personality disorder features: the role of difficulties with emotion regulation.

    PubMed

    Kuo, Janice R; Khoury, Jennifer E; Metcalfe, Rebecca; Fitzpatrick, Skye; Goodwill, Alasdair

    2015-01-01

    Childhood abuse has been consistently linked with borderline personality disorder (BPD) and recent studies suggest that some forms of childhood abuse might be uniquely related to both BPD and BPD features. In addition, difficulties with emotion regulation have been found to be associated with childhood abuse, BPD, as well as BPD features. The present study examined (1) whether frequency of childhood emotional abuse is uniquely associated with BPD feature severity when controlling for other forms of childhood abuse and (2) whether difficulties with emotion regulation accounts for the relationship between childhood emotional abuse and BPD feature severity. A sample of undergraduates (n=243) completed the Childhood Trauma Questionnaire - Short Form, Difficulties in Emotion Regulation Scale, and Borderline Symptom List-23. Multiple regression analyses and Structural Equation Modeling were conducted. Results indicated that frequency of childhood emotional abuse (and not sexual or physical abuse) was uniquely associated with BPD feature severity. In addition, while there was no direct path between childhood emotional abuse, childhood physical abuse, or childhood sexual abuse and BPD features, there was an indirect relationship between childhood emotional abuse and BPD features through difficulties with emotion regulation. These findings suggest that, of the different forms of childhood abuse, emotional abuse specifically, may have a developmental role in BPD pathology. Prevention and treatment of BPD pathology might benefit from the provision of emotion regulation strategies. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Bmi-1: At the crossroads of physiological and pathological biology

    PubMed Central

    Bhattacharya, Resham; Mustafi, Soumyajit Banerjee; Street, Mark; Dey, Anindya; Dwivedi, Shailendra Kumar Dhar

    2015-01-01

    Bmi-1 is a member of the Polycomb Repressor Complex1 that mediates gene silencing by regulating chromatin structure and is indispensable for self-renewal of both normal and cancer stem cells. Despite three decades of research that have elucidated the transcriptional regulation, post-translational modifications and functions of Bmi-1 in regulating the DNA damage response, cellular bioenergetics, and pathologies, the entire potential of a protein with such varied function remains to be realized. This review attempts to synthesize the current knowledge on Bmi-1 with an emphasis on its role in both normal physiology and cancer. Additionally, since cancer stem cells are emerging as a new paradigm for therapy resistance, the role of Bmi-1 in this perspective is also highlighted. The wide spectrum of malignancies that implicate Bmi-1 as a signature for stemness and oncogenesis also make it a suitable candidate for therapy. Nonetheless new approaches are vitally needed to further characterize physiological roles of Bmi-1 with the long-term goal of using Bmi-1 as a prognostic marker and a therapeutic target. PMID:26448339

  18. The Mitochondrial Protein NLRX1 Controls the Balance between Extrinsic and Intrinsic Apoptosis*

    PubMed Central

    Soares, Fraser; Tattoli, Ivan; Rahman, Muhammed A.; Robertson, Susan J.; Belcheva, Antoaneta; Liu, Daniel; Streutker, Catherine; Winer, Shawn; Winer, Daniel A.; Martin, Alberto; Philpott, Dana J.; Arnoult, Damien; Girardin, Stephen E.

    2014-01-01

    NLRX1 is a mitochondrial Nod-like receptor (NLR) protein whose function remains enigmatic. Here, we observed that NLRX1 expression was glucose-regulated and blunted by SV40 transformation. In transformed but not primary murine embryonic fibroblasts, NLRX1 expression mediated resistance to an extrinsic apoptotic signal, whereas conferring susceptibility to intrinsic apoptotic signals, such as glycolysis inhibition, increased cytosolic calcium and endoplasmic reticulum stress. In a murine model of colorectal cancer induced by azoxymethane, NLRX1−/− mice developed fewer tumors than wild type mice. In contrast, in a colitis-associated cancer model combining azoxymethane and dextran sulfate sodium, NLRX1−/− mice developed a more severe pathology likely due to the increased sensitivity to dextran sulfate sodium colitis. Together, these results identify NLRX1 as a critical mitochondrial protein implicated in the regulation of apoptosis in cancer cells. The unique capacity of NLRX1 to regulate the cellular sensitivity toward intrinsic versus extrinsic apoptotic signals suggests a critical role for this protein in numerous physiological processes and pathological conditions. PMID:24867956

  19. KUS121, an ATP regulator, mitigates chorioretinal pathologies in animal models of age-related macular degeneration.

    PubMed

    Muraoka, Yuki; Iida, Yuto; Ikeda, Hanako O; Iwai, Sachiko; Hata, Masayuki; Iwata, Takeshi; Nakayama, Mao; Shimozawa, Nobuhiro; Katakai, Yuko; Kakizuka, Akira; Yoshimura, Nagahisa; Tsujikawa, Akitaka

    2018-05-01

    Age-related macular degeneration (AMD) is a leading cause of blindness among elderly people. The appearance of drusen is a clinical manifestation and a harbinger of both exudative and atrophic AMD. Recently, antibody-based medicines have been used to treat the exudative type. However, they do not restore good vision in patients. Moreover, no effective treatment is available for atrophic AMD. We have created small chemicals (Kyoto University Substances; KUSs) that act as ATP regulators inside cells. In the present study, we examined the in vivo efficacy of KUS121 in C-C chemokine receptor type 2-deficient mice, a mouse model of AMD. Systemic administration of KUS121 prevented or reduced drusen-like lesions and endoplasmic reticulum stress, and then substantially mitigated chorioretinal pathologies with significant preservation of visual function. Additionally, we confirmed that long-term oral administration of KUS121 caused no systemic complications in drusen-affected monkeys. ATP regulation by KUSs may represent a novel strategy in the treatment of drusen and prevention of disease progression in AMD.

  20. Mouse Tmem135 mutation reveals a mechanism involving mitochondrial dynamics that leads to age-dependent retinal pathologies

    PubMed Central

    Lee, Wei-Hua; Higuchi, Hitoshi; Ikeda, Sakae; Macke, Erica L; Takimoto, Tetsuya; Pattnaik, Bikash R; Liu, Che; Chu, Li-Fang; Siepka, Sandra M; Krentz, Kathleen J; Rubinstein, C Dustin; Kalejta, Robert F; Thomson, James A; Mullins, Robert F; Takahashi, Joseph S; Pinto, Lawrence H; Ikeda, Akihiro

    2016-01-01

    While the aging process is central to the pathogenesis of age-dependent diseases, it is poorly understood at the molecular level. We identified a mouse mutant with accelerated aging in the retina as well as pathologies observed in age-dependent retinal diseases, suggesting that the responsible gene regulates retinal aging, and its impairment results in age-dependent disease. We determined that a mutation in the transmembrane 135 (Tmem135) is responsible for these phenotypes. We observed localization of TMEM135 on mitochondria, and imbalance of mitochondrial fission and fusion in mutant Tmem135 as well as Tmem135 overexpressing cells, indicating that TMEM135 is involved in the regulation of mitochondrial dynamics. Additionally, mutant retina showed higher sensitivity to oxidative stress. These results suggest that the regulation of mitochondrial dynamics through TMEM135 is critical for protection from environmental stress and controlling the progression of retinal aging. Our study identified TMEM135 as a critical link between aging and age-dependent diseases. DOI: http://dx.doi.org/10.7554/eLife.19264.001 PMID:27863209

  1. EMMPRIN, an upstream regulator of MMPs, in CNS biology.

    PubMed

    Kaushik, Deepak Kumar; Hahn, Jennifer Nancy; Yong, V Wee

    2015-01-01

    Matrix metalloproteinases (MMPs) are engaged in pathologies associated with infections, tumors, autoimmune disorders and neurological dysfunctions. With the identification of an upstream regulator of MMPs, EMMPRIN (Extracellular matrix metalloproteinase inducer, CD147), it is relevant to address if EMMPRIN plays a role in the pathology of central nervous system (CNS) diseases. This would enable the possibility of a more upstream and effective therapeutic target. Indeed, conditions including gliomas, Alzheimer's disease (AD), multiple sclerosis (MS), and other insults such as hypoxia/ischemia show elevated levels of EMMPRIN which correlate with MMP production. In contrast, given EMMPRIN's role in CNS homeostasis with respect to regulation of monocarboxylate transporters (MCTs) and interactions with adhesion molecules including integrins, we need to consider that EMMPRIN may also serve important regulatory or protective functions. This review summarizes the current understanding of EMMPRIN's involvement in CNS homeostasis, its possible roles in escalating or reducing neural injury, and the mechanisms of EMMPRIN including and apart from MMP induction. Copyright © 2015 International Society of Matrix Biology. Published by Elsevier B.V. All rights reserved.

  2. 19 CFR 10.114 - General provisions.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. General Provisions Instruments and Apparatus for Educational and Scientific Institutions § 10.114 General provisions. The consolidated regulations of the Commerce and Treasury Departments relating to the entry of instruments and apparatus for...

  3. 19 CFR 10.114 - General provisions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. General Provisions Instruments and Apparatus for Educational and Scientific Institutions § 10.114 General provisions. The consolidated regulations of the Commerce and Treasury Departments relating to the entry of instruments and apparatus for...

  4. 19 CFR 10.114 - General provisions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. General Provisions Instruments and Apparatus for Educational and Scientific Institutions § 10.114 General provisions. The consolidated regulations of the Commerce and Treasury Departments relating to the entry of instruments and apparatus for...

  5. 19 CFR 10.114 - General provisions.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... ARTICLES CONDITIONALLY FREE, SUBJECT TO A REDUCED RATE, ETC. General Provisions Instruments and Apparatus for Educational and Scientific Institutions § 10.114 General provisions. The consolidated regulations of the Commerce and Treasury Departments relating to the entry of instruments and apparatus for...

  6. 7 CFR 4287.124 - Alterations of loan instruments.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 4287.124 Agriculture Regulations of the Department of Agriculture (Continued) RURAL BUSINESS-COOPERATIVE SERVICE AND RURAL UTILITIES SERVICE, DEPARTMENT OF AGRICULTURE SERVICING Servicing Business and... approve any alterations of any loan instrument without the prior written approval of the Agency. ...

  7. 78 FR 32532 - Submission for OMB Review; Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-30

    ... recordkeeping requirements for integrated debt instruments. Affected Public: Private Sector: Businesses or other... qualified health plans available to individuals and employers. Affected Public: Private Sector: Not-for...: The regulations provide definitions, general rules, and reporting requirements for debt instruments...

  8. MicroRNAs in Breast Cancer: One More Turn in Regulation.

    PubMed

    Eroles, Pilar; Asensio, Pilar E; Tormo, Eduardo; Martin, Eduardo T; Pineda, Begoña; Merlo, Begoña P; Espin, Estefanía; Armas, Estefanía E; Lluch, Ana; Hernández, Ana L

    2016-01-01

    MicroRNAs (miRNAs) are small non-coding RNA molecules that critically regulate the expression of genes. MiRNAs are involved in physiological cellular processes; however, their deregulation has been associated with several pathologies, including cancer. In human breast cancer, differently expressed levels of miRNAs have been identified from those in normal breast tissues. Moreover, several miRNAs have been correlated with pathological phenotype, cancer subtype and therapy response in breast cancer. The resistance to therapy is increasingly a problem in patient management, and miRNAs are emerging as novel therapeutic targets and potential predictive biomarkers for treatment. This review provides an overview of the current situation of miRNAs in breast cancer, focusing on their involvement in resistance and the circulating miRNA. The mechanisms of therapeutic resistance regulated by miRNAs, such as the regulation of receptors, the modification of enzymes of drug metabolism, the inhibition of cell cycle control or pro-apoptotic proteins, the alteration of histone activity and the regulation of DNA repair machinery among others, are discussed for breast cancer clinical subtypes. Additionally, in this review, we summarize the recent knowledge that has established miRNA detection in peripheral body fluids as a suitable biomarker. We review the detection of miRNA in liquid biopsies and its implications for the diagnosis and monitoring of breast cancer. This new generation of cancer biomarkers may lead to a significant improvement in patient management.

  9. Implications of Circadian Rhythm in Dopamine and Mood Regulation.

    PubMed

    Kim, Jeongah; Jang, Sangwon; Choe, Han Kyoung; Chung, Sooyoung; Son, Gi Hoon; Kim, Kyungjin

    2017-07-31

    Mammalian physiology and behavior are regulated by an internal time-keeping system, referred to as circadian rhythm. The circadian timing system has a hierarchical organization composed of the master clock in the suprachiasmatic nucleus (SCN) and local clocks in extra-SCN brain regions and peripheral organs. The circadian clock molecular mechanism involves a network of transcription-translation feedback loops. In addition to the clinical association between circadian rhythm disruption and mood disorders, recent studies have suggested a molecular link between mood regulation and circadian rhythm. Specifically, genetic deletion of the circadian nuclear receptor Rev-erbα induces mania-like behavior caused by increased midbrain dopaminergic (DAergic) tone at dusk. The association between circadian rhythm and emotion-related behaviors can be applied to pathological conditions, including neurodegenerative diseases. In Parkinson's disease (PD), DAergic neurons in the substantia nigra pars compacta progressively degenerate leading to motor dysfunction. Patients with PD also exhibit non-motor symptoms, including sleep disorder and neuropsychiatric disorders. Thus, it is important to understand the mechanisms that link the molecular circadian clock and brain machinery in the regulation of emotional behaviors and related midbrain DAergic neuronal circuits in healthy and pathological states. This review summarizes the current literature regarding the association between circadian rhythm and mood regulation from a chronobiological perspective, and may provide insight into therapeutic approaches to target psychiatric symptoms in neurodegenerative diseases involving circadian rhythm dysfunction.

  10. Role of Regulators of G Protein Signaling Proteins in Bone Physiology and Pathophysiology

    PubMed Central

    Jules, Joel; Yang, Shuying; Chen, Wei; Li, Yi-Ping

    2016-01-01

    Regulators of G protein signaling (RGS) proteins enhance the intrinsic GTPase activity of α subunits of the heterotrimeric G protein complex of G protein-coupled receptors (GPCRs) and thereby inactivate signal transduction initiated by GPCRs. The RGS family consists of nearly 37 members with a conserved RGS homology domain which is critical for their GTPase accelerating activity. RGS proteins are expressed in most tissues, including heart, lung, brain, kidney, and bone and play essential roles in many physiological and pathological processes. In skeletal development and bone homeostasis as well as in many bone disorders, RGS proteins control the functions of various GPCRs, including the parathyroid hormone receptor type 1 and calcium-sensing receptor and also regulate various critical signaling pathways, such as Wnt and calcium oscillations. This chapter will discuss the current findings on the roles of RGS proteins in regulating signaling of key GPCRs in skeletal development and bone homeostasis. We also will examine the current updates of RGS proteins’ regulation of calcium oscillations in bone physiology and highlight the roles of RGS proteins in selected bone pathological disorders. Despite the recent advances in bone and mineral research, RGS proteins remain understudied in the skeletal system. Further understanding of the roles of RGS proteins in bone should not only provide great insights into the molecular basis of various bone diseases but also generate great therapeutic drug targets for many bone diseases. PMID:26123302

  11. Maladaptive behavioral consequences of conditioned fear-generalization: a pronounced, yet sparsely studied, feature of anxiety pathology.

    PubMed

    van Meurs, Brian; Wiggert, Nicole; Wicker, Isaac; Lissek, Shmuel

    2014-06-01

    Fear-conditioning experiments in the anxiety disorders focus almost exclusively on passive-emotional, Pavlovian conditioning, rather than active-behavioral, instrumental conditioning. Paradigms eliciting both types of conditioning are needed to study maladaptive, instrumental behaviors resulting from Pavlovian abnormalities found in clinical anxiety. One such Pavlovian abnormality is generalization of fear from a conditioned danger-cue (CS+) to resembling stimuli. Though lab-based findings repeatedly link overgeneralized Pavlovian-fear to clinical anxiety, no study assesses the degree to which Pavlovian overgeneralization corresponds with maladaptive, overgeneralized instrumental-avoidance. The current effort fills this gap by validating a novel fear-potentiated startle paradigm including Pavlovian and instrumental components. The paradigm is embedded in a computer game during which shapes appear on the screen. One shape paired with electric-shock serves as CS+, and other resembling shapes, presented in the absence of shock, serve as generalization stimuli (GSs). During the game, participants choose whether to behaviorally avoid shock at the cost of poorer performance. Avoidance during CS+ is considered adaptive because shock is a real possibility. By contrast, avoidance during GSs is considered maladaptive because shock is not a realistic prospect and thus unnecessarily compromises performance. Results indicate significant Pavlovian-instrumental relations, with greater generalization of Pavlovian fear associated with overgeneralization of maladaptive instrumental-avoidance. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Performance assessment of diffuse optical spectroscopic imaging instruments in a 2-year multicenter breast cancer trial

    NASA Astrophysics Data System (ADS)

    Leproux, Anaïs; O'Sullivan, Thomas D.; Cerussi, Albert; Durkin, Amanda; Hill, Brian; Hylton, Nola; Yodh, Arjun G.; Carp, Stefan A.; Boas, David; Jiang, Shudong; Paulsen, Keith D.; Pogue, Brian; Roblyer, Darren; Yang, Wei; Tromberg, Bruce J.

    2017-12-01

    We present a framework for characterizing the performance of an experimental imaging technology, diffuse optical spectroscopic imaging (DOSI), in a 2-year multicenter American College of Radiology Imaging Network (ACRIN) breast cancer study (ACRIN-6691). DOSI instruments combine broadband frequency-domain photon migration with time-independent near-infrared (650 to 1000 nm) spectroscopy to measure tissue absorption and reduced scattering spectra and tissue hemoglobin, water, and lipid composition. The goal of ACRIN-6691 was to test the effectiveness of optically derived imaging endpoints in predicting the final pathologic response of neoadjuvant chemotherapy (NAC). Sixty patients were enrolled over a 2-year period at participating sites and received multiple DOSI scans prior to and during 3- to 6-month NAC. The impact of three sources of error on accuracy and precision, including different operators, instruments, and calibration standards, was evaluated using a broadband reflectance standard and two different solid tissue-simulating optical phantoms. Instruments showed <0.0010 mm-1 (10.3%) and 0.06 mm-1 (4.7%) deviation in broadband absorption and reduced scattering, respectively, over the 2-year duration of ACRIN-6691. These variations establish a useful performance criterion for assessing instrument stability. The proposed procedures and tests are not limited to DOSI; rather, they are intended to provide methods to characterize performance of any instrument used in translational optical imaging.

  13. 77 FR 59456 - Proposed Collection; Comment Request for Form 8281

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-09-27

    ... 8281, Information Return for Publicity Offered Original Issue Discount Instructions. DATES: Written... Offered Original Issue Discount Instruments. OMB Number: 1545-0887. Form Number: 8281. Abstract: Internal... publicity offered debt instruments having original issue discount. Regulations section 1.1275- 3 prescribes...

  14. Learning Styles and Self-Regulation.

    ERIC Educational Resources Information Center

    Vermunt, Jan D. H. M.

    Data from 211 adult students (ages 20 to 75) at the Open University, The Netherlands, were used to construct and test an instrument to measure learning styles and regulation processes. Test development was guided by a three-tiered model of self-regulation encompassing: (1) cognitive learning processes (deep, surface, elaborative); (2) regulation…

  15. Impact of sleep disordered breathing on behaviour among elementary school-aged children: a cross-sectional analysis of a large community-based sample.

    PubMed

    Smith, Dale L; Gozal, David; Hunter, Scott J; Philby, Mona F; Kaylegian, Jaeson; Kheirandish-Gozal, Leila

    2016-12-01

    Sleep disordered breathing (SDB) in children has been associated with inattention, impulsivity and hyperactivity, but the associations between SDB severity and the type and severity of behavioural disruption are unclear.1022 children aged 5-7 years old prospectively underwent sleep studies and behavioural assessments through completion of standardised instruments. Participants were subdivided into four categorical groups based on the apnoea-hypopnoea index (AHI; measured per hour of total sleep time (hTST)), i.e. Group 1: nonsnoring and AHI <1 hTST -1 ; Group 2: habitual snoring and AHI <1 hTST -1 ; Group 3: habitual snoring and AHI 1-5 hTST -1 ; and Group 4: habitual snoring and AHI >5 hTST -1 , followed by comparisons of behavioural functioning across the groups.All 10 behavioural variables differed significantly between Group 1 and all other groups. Post hoc comparisons indicated that Group 2 was the most impaired for most behavioural measures. Furthermore, differences between Group 2 and more severe sleep pathology conditions were rarely significant.This large community-based paediatric cohort confirms earlier findings highlighting a significant impact of SDB on behavioural regulation, with the greatest impact being already apparent among habitually snoring children. Thus, a likely low asymptote exists regarding SDB behavioural impact, such that further increases in severity do not measurably increase parent-rated difficulties with behavioural regulation relative to controls. Our findings do support the need for considering early intervention, particularly among those children manifesting a behavioural impact of SDB. Copyright ©ERS 2016.

  16. The structural and functional connectivity of the amygdala: from normal emotion to pathological anxiety.

    PubMed

    Kim, M Justin; Loucks, Rebecca A; Palmer, Amy L; Brown, Annemarie C; Solomon, Kimberly M; Marchante, Ashley N; Whalen, Paul J

    2011-10-01

    The dynamic interactions between the amygdala and the medial prefrontal cortex (mPFC) are usefully conceptualized as a circuit that both allows us to react automatically to biologically relevant predictive stimuli as well as regulate these reactions when the situation calls for it. In this review, we will begin by discussing the role of this amygdala-mPFC circuitry in the conditioning and extinction of aversive learning in animals. We will then relate these data to emotional regulation paradigms in humans. Finally, we will consider how these processes are compromised in normal and pathological anxiety. We conclude that the capacity for efficient crosstalk between the amygdala and the mPFC, which is represented as the strength of the amygdala-mPFC circuitry, is crucial to beneficial outcomes in terms of reported anxiety. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. Surfing the Big WAVE: Insights into the Role of WAVE3 as a Driving Force in Cancer Progression and Metastasis

    PubMed Central

    Sossey-Alaoui, Khalid

    2014-01-01

    WAVE3 belongs to the WASP/WAVE family of actin cytoskeleton remodeling proteins. These proteins are known to be involved in several biological functions ranging from controlling cell shape and movement, to being closely associated with pathological conditions such as cancer progression and metastasis. Last decade has seen an explosion in the literature reporting significant scientific advances on the molecular mechanisms whereby the WASP/WAVE proteins are regulated both in normal physiological as well as pathological conditions. The purpose of this review is to present the major findings pertaining to how WAVE3 has become a critical player in the regulation of signaling pathways involved in cancer progression and metastasis. The review will conclude with suggesting options for the potential use of WAVE3 as a therapeutic target to prevent the progression of cancer to the lethal stage that is the metastatic disease. PMID:23116924

  18. FOXO1 regulates VEGFA expression and promotes angiogenesis in healing wounds.

    PubMed

    Jeon, Hyeran Helen; Yu, Quan; Lu, Yongjian; Spencer, Evelyn; Lu, Chanyi; Milovanova, Tatyana; Yang, Yang; Zhang, Chenying; Stepanchenko, Olga; Vafa, Rameen P; Coelho, Paulo G; Graves, Dana T

    2018-03-25

    Angiogenesis is a critical aspect of wound healing. We investigated the role of keratinocytes in promoting angiogenesis in mice with lineage-specific deletion of the transcription factor FOXO1. The results indicate that keratinocyte-specific deletion of Foxo1 reduces VEGFA expression in mucosal and skin wounds and leads to reduced endothelial cell proliferation, reduced angiogenesis, and impaired re-epithelialization and granulation tissue formation. In vitro FOXO1 was needed for VEGFA transcription and expression. In a porcine dermal wound-healing model that closely resembles healing in humans, local application of a FOXO1 inhibitor reduced angiogenesis. This is the first report that FOXO1 directly regulates VEGFA expression and that FOXO1 is needed for normal angiogenesis during wound healing. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

  19. Glycogen Synthase Kinase-3 (GSK3): Inflammation, Diseases, and Therapeutics

    PubMed Central

    Jope, Richard S.; Yuskaitis, Christopher J.; Beurel, Eléonore

    2007-01-01

    Deciphering what governs inflammation and its effects on tissues is vital for understanding many pathologies. The recent discovery that glycogen synthase kinase-3 (GSK3) promotes inflammation reveals a new component of its well-documented actions in several prevalent diseases which involve inflammation, including mood disorders, Alzheimer’s disease, diabetes, and cancer. Involvement in such disparate conditions stems from the widespread influences of GSK3 on many cellular functions, with this review focusing on its regulation of inflammatory processes. GSK3 promotes the production of inflammatory molecules and cell migration, which together make GSK3 a powerful regulator of inflammation, while GSK3 inhibition provides protection from inflammatory conditions in animal models. The involvement of GSK3 and inflammation in these diseases are highlighted. Thus, GSK3 may contribute not only to primary pathologies in these diseases, but also to the associated inflammation, suggesting that GSK3 inhibitors may have multiple effects influencing these conditions. PMID:16944320

  20. Role of Oxidative Stress as Key Regulator of Muscle Wasting during Cachexia.

    PubMed

    Ábrigo, Johanna; Elorza, Alvaro A; Riedel, Claudia A; Vilos, Cristian; Simon, Felipe; Cabrera, Daniel; Estrada, Lisbell; Cabello-Verrugio, Claudio

    2018-01-01

    Skeletal muscle atrophy is a pathological condition mainly characterized by a loss of muscular mass and the contractile capacity of the skeletal muscle as a consequence of muscular weakness and decreased force generation. Cachexia is defined as a pathological condition secondary to illness characterized by the progressive loss of muscle mass with or without loss of fat mass and with concomitant diminution of muscle strength. The molecular mechanisms involved in cachexia include oxidative stress, protein synthesis/degradation imbalance, autophagy deregulation, increased myonuclear apoptosis, and mitochondrial dysfunction. Oxidative stress is one of the most common mechanisms of cachexia caused by different factors. It results in increased ROS levels, increased oxidation-dependent protein modification, and decreased antioxidant system functions. In this review, we will describe the importance of oxidative stress in skeletal muscles, its sources, and how it can regulate protein synthesis/degradation imbalance, autophagy deregulation, increased myonuclear apoptosis, and mitochondrial dysfunction involved in cachexia.

  1. The role of Krüppel-like factor 14 in the pathogenesis of atherosclerosis.

    PubMed

    Xie, Wei; Li, Liang; Zheng, Xi-Long; Yin, Wei-Dong; Tang, Chao-Ke

    2017-08-01

    The Krüppel-like factor (KLF) family, as the SP/XKLF transcription factors, plays important roles in regulating the expression of genes required for the proper execution of important biological and pathological processes. Recent studies have demonstrated that KLF14, a member of the KLF family, participates in the initiation and progression of atherosclerotic cardiovascular disease (CVD). From the molecular function aspect, this review focuses on the impact of KLF14-mediated regulation in major atherosclerosis-related diseases and pathological processes, such as insulin resistance, type 2 diabetes, dyslipidemia, inflammation, obesity, metabolic syndrome, cell proliferation and differentiation. This review was designed to help understand the roles of KLF14 in the pathogenesis of atherosclerosis and define KLF14 as a potential disease biomarker and a novel therapeutic target in CVD. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Developing mechanisms of self-regulation.

    PubMed

    Posne, M I; Rothbart, M K

    2000-01-01

    Child development involves both reactive and self-regulatory mechanisms that children develop in conjunction with social norms. A half-century of research has uncovered aspects of the physical basis of attentional networks that produce regulation, and has given us some knowledge of how the social environment may alter them. In this paper, we discuss six forms of developmental plasticity related to aspects of attention. We then focus on effortful or executive aspects of attention, reviewing research on temperamental individual differences and important pathways to normal and pathological development. Pathologies of development may arise when regulatory and reactive systems fail to reach the balance that allows for both self-expression and socially acceptable behavior. It remains a challenge for our society during the next millennium to obtain the information necessary to design systems that allow a successful balance to be realized by the largest possible number of children.

  3. [Quality management in pathology--an executive function and political implications].

    PubMed

    Turzynski, A

    2013-09-01

    Quality management (QM) is primarily an in-house executive function. It conduces to ensure a high quality service and has the external object to satisfy customer expectations. In Germany the implementation of quality management systems (QMS) is made compulsory for all medical facilities by law. However, details are not regulated and there is no need to certify the in-house QMS. Within the last 10 years many pathology institutions have become certified or accredited and have implemented voluntary measures of external quality assurance, such as quality circles and round robin trials. For non-certified institutions it might be helpful to be guided by established QM standards like the ISO 9001:2008. The fundamental concepts of QM, some pathology-specific aspects and some implications for the professional associations are discussed in this article.

  4. Ventromedial prefrontal cortex activity and pathological worry in generalised anxiety disorder.

    PubMed

    Via, E; Fullana, M A; Goldberg, X; Tinoco-González, D; Martínez-Zalacaín, I; Soriano-Mas, C; Davey, C G; Menchón, J M; Straube, B; Kircher, T; Pujol, J; Cardoner, N; Harrison, B J

    2018-05-09

    Pathological worry is a hallmark feature of generalised anxiety disorder (GAD), associated with dysfunctional emotional processing. The ventromedial prefrontal cortex (vmPFC) is involved in the regulation of such processes, but the link between vmPFC emotional responses and pathological v. adaptive worry has not yet been examined.AimsTo study the association between worry and vmPFC activity evoked by the processing of learned safety and threat signals. In total, 27 unmedicated patients with GAD and 56 healthy controls (HC) underwent a differential fear conditioning paradigm during functional magnetic resonance imaging. Compared to HC, the GAD group demonstrated reduced vmPFC activation to safety signals and no safety-threat processing differentiation. This response was positively correlated with worry severity in GAD, whereas the same variables showed a negative and weak correlation in HC. Poor vmPFC safety-threat differentiation might characterise GAD, and its distinctive association with GAD worries suggests a neural-based qualitative difference between healthy and pathological worries.Declaration of interestNone.

  5. Regulation of immunity and inflammation by hypoxia in immunological niches.

    PubMed

    Taylor, Cormac T; Colgan, Sean P

    2017-12-01

    Immunological niches are focal sites of immune activity that can have varying microenvironmental features. Hypoxia is a feature of physiological and pathological immunological niches. The impact of hypoxia on immunity and inflammation can vary depending on the microenvironment and immune processes occurring in a given niche. In physiological immunological niches, such as the bone marrow, lymphoid tissue, placenta and intestinal mucosa, physiological hypoxia controls innate and adaptive immunity by modulating immune cell proliferation, development and effector function, largely via transcriptional changes driven by hypoxia-inducible factor (HIF). By contrast, in pathological immunological niches, such as tumours and chronically inflamed, infected or ischaemic tissues, pathological hypoxia can drive tissue dysfunction and disease development through immune cell dysregulation. Here, we differentiate between the effects of physiological and pathological hypoxia on immune cells and the consequences for immunity and inflammation in different immunological niches. Furthermore, we discuss the possibility of targeting hypoxia-sensitive pathways in immune cells for the treatment of inflammatory disease.

  6. Dysregulation of prefrontal cortex-mediated slow evolving limbic dynamics drives stress-induced emotional pathology

    PubMed Central

    Hultman, Rainbo; Mague, Stephen D.; Li, Qiang; Katz, Brittany M.; Michel, Nadine; Lin, Lizhen; Wang, Joyce; David, Lisa K.; Blount, Cameron; Chandy, Rithi; Carlson, David; Ulrich, Kyle; Carin, Lawrence; Dunson, David; Kumar, Sunil; Deisseroth, Karl; Moore, Scott D.; Dzirasa, Kafui

    2016-01-01

    Summary Circuits distributed across cortico-limbic brain regions compose the networks that mediate emotional behavior. The prefrontal cortex (PFC) regulates ultraslow (<1Hz) dynamics across these networks, and PFC dysfunction is implicated in stress-related illnesses including major depressive disorder (MDD). To uncover the mechanism whereby stress-induced changes in PFC circuitry alter emotional networks to yield pathology, we used a multi-disciplinary approach including in vivo recordings in mice and chronic social-defeat stress. Our network model, inferred using machine learning, linked stress-induced behavioral pathology to the capacity of PFC to synchronize amygdala and VTA activity. Direct stimulation of PFC-amygdala circuitry with DREADDs normalized PFC-dependent limbic synchrony in stress-susceptible animals and restored normal behavior. In addition to providing insights into MDD mechanisms, our findings demonstrate an interdisciplinary approach that can be used to identify the large-scale network changes that underlie complex emotional pathologies and the specific network nodes that can be used to develop targeted interventions. PMID:27346529

  7. MiR-125a-3p timely inhibits oligodendroglial maturation and is pathologically up-regulated in human multiple sclerosis

    PubMed Central

    Lecca, Davide; Marangon, Davide; Coppolino, Giusy T.; Méndez, Aida Menéndez; Finardi, Annamaria; Costa, Gloria Dalla; Martinelli, Vittorio; Furlan, Roberto; Abbracchio, Maria P.

    2016-01-01

    In the mature central nervous system (CNS), oligodendrocytes provide support and insulation to axons thanks to the production of a myelin sheath. During their maturation to myelinating cells, oligodendroglial precursors (OPCs) follow a very precise differentiation program, which is finely orchestrated by transcription factors, epigenetic factors and microRNAs (miRNAs), a class of small non-coding RNAs involved in post-transcriptional regulation. Any alterations in this program can potentially contribute to dysregulated myelination, impaired remyelination and neurodegenerative conditions, as it happens in multiple sclerosis (MS). Here, we identify miR-125a-3p, a developmentally regulated miRNA, as a new actor of oligodendroglial maturation, that, in the mammalian CNS regulates the expression of myelin genes by simultaneously acting on several of its already validated targets. In cultured OPCs, over-expression of miR-125a-3p by mimic treatment impairs while its inhibition with an antago-miR stimulates oligodendroglial maturation. Moreover, we show that miR-125a-3p levels are abnormally high in the cerebrospinal fluid of MS patients bearing active demyelinating lesions, suggesting that its pathological upregulation may contribute to MS development, at least in part by blockade of OPC differentiation leading to impaired repair of demyelinated lesions. PMID:27698367

  8. The Impact of Environmental Factors in Influencing Epigenetics Related to Oxidative States in the Cardiovascular System.

    PubMed

    Angelini, Francesco; Pagano, Francesca; Bordin, Antonella; Milan, Marika; Chimenti, Isotta; Peruzzi, Mariangela; Valenti, Valentina; Marullo, Antonino; Schirone, Leonardo; Palmerio, Silvia; Sciarretta, Sebastiano; Murdoch, Colin E; Frati, Giacomo; De Falco, Elena

    2017-01-01

    Oxidative states exert a significant influence on a wide range of biological and molecular processes and functions. When their balance is shifted towards enhanced amounts of free radicals, pathological phenomena can occur, as the generation of reactive oxygen species (ROS) in tissue microenvironment or in the systemic circulation can be detrimental. Epidemic chronic diseases of western societies, such as cardiovascular disease, obesity, and diabetes correlate with the imbalance of redox homeostasis. Current advances in our understanding of epigenetics have revealed a parallel scenario showing the influence of oxidative stress as a major regulator of epigenetic gene regulation via modification of DNA methylation, histones, and microRNAs. This has provided both the biological link and a potential molecular explanation between oxidative stress and cardiovascular/metabolic phenomena. Accordingly, in this review, we will provide current insights on the physiological and pathological impact of changes in oxidative states on cardiovascular disorders, by specifically focusing on the influence of epigenetic regulation. A special emphasis will highlight the effect on epigenetic regulation of human's current life habits, external and environmental factors, including food intake, tobacco, air pollution, and antioxidant-based approaches. Additionally, the strategy to quantify oxidative states in humans in order to determine which biological marker could best match a subject's profile will be discussed.

  9. The Impact of Environmental Factors in Influencing Epigenetics Related to Oxidative States in the Cardiovascular System

    PubMed Central

    Angelini, Francesco; Pagano, Francesca; Bordin, Antonella; Milan, Marika; Valenti, Valentina; Marullo, Antonino; Schirone, Leonardo; Palmerio, Silvia; Sciarretta, Sebastiano; Frati, Giacomo

    2017-01-01

    Oxidative states exert a significant influence on a wide range of biological and molecular processes and functions. When their balance is shifted towards enhanced amounts of free radicals, pathological phenomena can occur, as the generation of reactive oxygen species (ROS) in tissue microenvironment or in the systemic circulation can be detrimental. Epidemic chronic diseases of western societies, such as cardiovascular disease, obesity, and diabetes correlate with the imbalance of redox homeostasis. Current advances in our understanding of epigenetics have revealed a parallel scenario showing the influence of oxidative stress as a major regulator of epigenetic gene regulation via modification of DNA methylation, histones, and microRNAs. This has provided both the biological link and a potential molecular explanation between oxidative stress and cardiovascular/metabolic phenomena. Accordingly, in this review, we will provide current insights on the physiological and pathological impact of changes in oxidative states on cardiovascular disorders, by specifically focusing on the influence of epigenetic regulation. A special emphasis will highlight the effect on epigenetic regulation of human's current life habits, external and environmental factors, including food intake, tobacco, air pollution, and antioxidant-based approaches. Additionally, the strategy to quantify oxidative states in humans in order to determine which biological marker could best match a subject's profile will be discussed. PMID:28607629

  10. Reviewing Two Types of Addiction – Pathological Gambling and Substance Use

    PubMed Central

    Jazaeri, Seyed Amir; Habil, Mohammad Hussain Bin

    2012-01-01

    Gambling, including pathological gambling and problem gambling, has received increased attention from clinicians and researchers over the past three decades since gambling opportunities have expanded around the world. Gambling disorders affect 0.2–5.3% of adults worldwide, although measurement and prevalence varies according to the screening instruments and methods used, and availability and accessibility of gambling opportunities. Several distinct treatment approaches have been favorably evaluated, such as cognitive behavioral and brief treatment models and pharmacological interventions. Although promising, family therapy and support from Gamblers Anonymous are less well empirically supported. Gambling disorders are highly comorbid with other mental health and substance use disorders, and a further understanding is needed of both the causes and treatment implications of this disorder. This article reviews definition, causes and associated features with substance abuse, screening and diagnosis, and treatment approaches. PMID:22661800

  11. Endovascular blood flow measurement system

    NASA Astrophysics Data System (ADS)

    Khe, A. K.; Cherevko, A. A.; Chupakhin, A. P.; Krivoshapkin, A. L.; Orlov, K. Yu

    2016-06-01

    In this paper an endovascular measurement system used for intraoperative cerebral blood flow monitoring is described. The system is based on a Volcano ComboMap Pressure and Flow System extended with analogue-to-digital converter and PC laptop. A series of measurements performed in patients with cerebrovascular pathologies allows us to introduce “velocity-pressure” and “flow rate-energy flow rate” diagrams as important characteristics of the blood flow. The measurement system presented here can be used as an additional instrument in neurosurgery for assessment and monitoring of the operation procedure. Clinical data obtained with the system are used for construction of mathematical models and patient-specific simulations. The monitoring of the blood flow parameters during endovascular interventions was approved by the Ethics Committee at the Meshalkin Novosibirsk Research Institute of Circulation Pathology and included in certain surgical protocols for pre-, intra- and postoperative examinations.

  12. Endothelial TWIST1 Promotes Pathological Ocular Angiogenesis

    PubMed Central

    Li, Jie; Liu, Chi-Hsiu; Sun, Ye; Gong, Yan; Fu, Zhongjie; Evans, Lucy P.; Tian, Katherine T.; Juan, Aimee M.; Hurst, Christian G.; Mammoto, Akiko; Chen, Jing

    2014-01-01

    Purpose. Pathological neovessel formation impacts many blinding vascular eye diseases. Identification of molecular signatures distinguishing pathological neovascularization from normal quiescent vessels is critical for developing new interventions. Twist-related protein 1 (TWIST1) is a transcription factor important in tumor and pulmonary angiogenesis. This study investigated the potential role of TWIST1 in modulating pathological ocular angiogenesis in mice. Methods. Twist1 expression and localization were analyzed in a mouse model of oxygen-induced retinopathy (OIR). Pathological ocular angiogenesis in Tie2-driven conditional Twist1 knockout mice were evaluated in both OIR and laser-induced choroidal neovascularization models. In addition, the effects of TWIST1 on angiogenesis and endothelial cell function were analyzed in sprouting assays of aortic rings and choroidal explants isolated from Twist1 knockout mice, and in human retinal microvascular endothelial cells treated with TWIST1 small interfering RNA (siRNA). Results. TWIST1 is highly enriched in pathological neovessels in OIR retinas. Conditional Tie2-driven depletion of Twist1 significantly suppressed pathological neovessels in OIR without impacting developmental retinal angiogenesis. In a laser-induced choroidal neovascularization model, Twist1 deficiency also resulted in significantly smaller lesions with decreased vascular leakage. In addition, loss of Twist1 significantly decreased vascular sprouting in both aortic ring and choroid explants. Knockdown of TWIST1 in endothelial cells led to dampened expression of vascular endothelial growth factor receptor 2 (VEGFR2) and decreased endothelial cell proliferation. Conclusions. Our study suggests that TWIST1 is a novel regulator of pathologic ocular angiogenesis and may represent a new molecular target for developing potential therapeutic treatments to suppress pathological neovascularization in vascular eye diseases. PMID:25414194

  13. Portable fixture facilitates pressure testing of instrumentation fittings

    NASA Technical Reports Server (NTRS)

    Olson, G. A.

    1967-01-01

    Portable fixture facilitates pressure testing to detect possible leaks in instrumentation fittings mounted on tank bulkheads. It uses a vacuum cup which seals a pressure regulator adapter around one side of the fitting to be pressure tested. Leakage is detected with a gas sniffer.

  14. 24 CFR 232.555 - Security instrument and lien.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Security instrument and lien. 232.555 Section 232.555 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR HOUSING-FEDERAL HOUSING COMMISSIONER, DEPARTMENT OF...

  15. 24 CFR 232.570 - Endorsement of credit instrument.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 2 2010-04-01 2010-04-01 false Endorsement of credit instrument. 232.570 Section 232.570 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR HOUSING-FEDERAL HOUSING COMMISSIONER, DEPARTMENT OF...

  16. 5 CFR 2634.407 - Restrictions on fiduciaries and interested parties.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ETHICS EXECUTIVE BRANCH FINANCIAL DISCLOSURE, QUALIFIED TRUSTS, AND CERTIFICATES OF DIVESTITURE Qualified... instrument; (2) Acquire any holding: (i) Directly from an interested party without the prior written approval... of the Act, the implementing regulations, the trust instrument, or with other applicable statutes and...

  17. Analysis of global and absorption, distribution, metabolism, and elimination gene expression in the progressive stages of human nonalcoholic fatty liver disease.

    PubMed

    Lake, April D; Novak, Petr; Fisher, Craig D; Jackson, Jonathan P; Hardwick, Rhiannon N; Billheimer, D Dean; Klimecki, Walter T; Cherrington, Nathan J

    2011-10-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by a series of pathological changes that range from simple fatty liver to nonalcoholic steatohepatitis (NASH). The objective of this study is to describe changes in global gene expression associated with the progression of human NAFLD. This study is focused on the expression levels of genes responsible for the absorption, distribution, metabolism, and elimination (ADME) of drugs. Differential gene expression between three clinically defined pathological groups-normal, steatosis, and NASH-was analyzed. Genome-wide mRNA levels in samples of human liver tissue were assayed with Affymetrix GeneChip Human 1.0ST arrays. A total of 11,633 genes exhibited altered expression out of 33,252 genes at a 5% false discovery rate. Most gene expression changes occurred in the progression from steatosis to NASH. Principal component analysis revealed that hepatic disease status was the major determinant of differential ADME gene expression rather than age or sex of sample donors. Among the 515 drug transporters and 258 drug-metabolizing enzymes (DMEs) examined, uptake transporters but not efflux transporters or DMEs were significantly over-represented in the number of genes down-regulated. These results suggest that uptake transporter genes are coordinately targeted for down-regulation at the global level during the pathological development of NASH and that these patients may have decreased drug uptake capacity. This coordinated regulation of uptake transporter genes is indicative of a hepatoprotective mechanism acting to prevent accumulation of toxic intermediates in disease-compromised hepatocytes.

  18. Tenascin-C and mechanotransduction in the development and diseases of cardiovascular system

    PubMed Central

    Imanaka-Yoshida, Kyoko; Aoki, Hiroki

    2014-01-01

    Living tissue is composed of cells and extracellular matrix (ECM). In the heart and blood vessels, which are constantly subjected to mechanical stress, ECM molecules form well-developed fibrous frameworks to maintain tissue structure. ECM is also important for biological signaling, which influences various cellular functions in embryonic development, and physiological/pathological responses to extrinsic stimuli. Among ECM molecules, increased attention has been focused on matricellular proteins. Matricellular proteins are a growing group of non-structural ECM proteins highly up-regulated at active tissue remodeling, serving as biological mediators. Tenascin-C (TNC) is a typical matricellular protein, which is highly expressed during embryonic development, wound healing, inflammation, and cancer invasion. The expression is tightly regulated, dependent on the microenvironment, including various growth factors, cytokines, and mechanical stress. In the heart, TNC appears in a spatiotemporal-restricted manner during early stages of development, sparsely detected in normal adults, but transiently re-expressed at restricted sites associated with tissue injury and inflammation. Similarly, in the vascular system, TNC is strongly up-regulated during embryonic development and under pathological conditions with an increase in hemodynamic stress. Despite its intriguing expression pattern, cardiovascular system develops normally in TNC knockout mice. However, deletion of TNC causes acute aortic dissection (AAD) under strong mechanical and humoral stress. Accumulating reports suggest that TNC may modulate the inflammatory response and contribute to elasticity of the tissue, so that it may protect cardiovascular tissue from destructive stress responses. TNC may be a key molecule to control cellular activity during development, adaptation, or pathological tissue remodeling. PMID:25120494

  19. Multimodal full-field optical coherence tomography on biological tissue: toward all optical digital pathology

    NASA Astrophysics Data System (ADS)

    Harms, F.; Dalimier, E.; Vermeulen, P.; Fragola, A.; Boccara, A. C.

    2012-03-01

    Optical Coherence Tomography (OCT) is an efficient technique for in-depth optical biopsy of biological tissues, relying on interferometric selection of ballistic photons. Full-Field Optical Coherence Tomography (FF-OCT) is an alternative approach to Fourier-domain OCT (spectral or swept-source), allowing parallel acquisition of en-face optical sections. Using medium numerical aperture objective, it is possible to reach an isotropic resolution of about 1x1x1 ìm. After stitching a grid of acquired images, FF-OCT gives access to the architecture of the tissue, for both macroscopic and microscopic structures, in a non-invasive process, which makes the technique particularly suitable for applications in pathology. Here we report a multimodal approach to FF-OCT, combining two Full-Field techniques for collecting a backscattered endogeneous OCT image and a fluorescence exogeneous image in parallel. Considering pathological diagnosis of cancer, visualization of cell nuclei is of paramount importance. OCT images, even for the highest resolution, usually fail to identify individual nuclei due to the nature of the optical contrast used. We have built a multimodal optical microscope based on the combination of FF-OCT and Structured Illumination Microscopy (SIM). We used x30 immersion objectives, with a numerical aperture of 1.05, allowing for sub-micron transverse resolution. Fluorescent staining of nuclei was obtained using specific fluorescent dyes such as acridine orange. We present multimodal images of healthy and pathological skin tissue at various scales. This instrumental development paves the way for improvements of standard pathology procedures, as a faster, non sacrificial, operator independent digital optical method compared to frozen sections.

  20. The advantages of a swept source optical coherence tomography system in the evaluation of occlusal disorders

    NASA Astrophysics Data System (ADS)

    Marcauteanu, Corina; Bradu, Adrian; Sinescu, Cosmin; Topala, Florin Ionel; Negrutiu, Meda Lavinia; Duma, Virgil Florin; Podoleanu, Adrian Gh.

    2014-01-01

    Occlusal disorders are characterized by multiple dental and periodontal signs. Some of these are reversible (such as excessive tooth mobility, fremitus, tooth pain, migration of teeth in the absence of periodontitis), some are not (pathological occlusal/incisal wear, abfractions, enamel cracks, tooth fractures, gingival recessions). In this paper we prove the advantages of a fast swept source OCT system in the diagnosis of pathological incisal wear, a key sign of the occlusal disorders. On 15 extracted frontal teeth four levels of pathological incisal wear facets were artificially created. After every level of induced defect, OCT scanning was performed. B scans were acquired and 3D reconstructions were generated. A swept source OCT instrument is used in this study. The swept source is has a central wavelength of 1050 nm and a sweeping rate of 100 kHz. A depth resolution determined by the swept source of 12 μm in air was experimentally measured. The pathological incisal wear is qualitatively observed on the B-scans as 2D images and 3D reconstructions (volumes). For quantitative evaluations of volumes, we used the Image J software. Our swept source OCT system has several advantages, including the ability to measure (in air) a minimal volume of 2352 μm3 and to collect high resolution volumetric images in 2.5 s. By calculating the areas of the amount of lost tissue corresponding to each difference of B-scans, the final volumes of incisal wear were obtained. This swept source OCT method is very useful for the dynamic evaluation of pathological incisal wear.

  1. Long Non-Coding RNAs Regulating Immunity in Insects

    PubMed Central

    Satyavathi, Valluri; Ghosh, Rupam; Subramanian, Srividya

    2017-01-01

    Recent advances in modern technology have led to the understanding that not all genetic information is coded into protein and that the genomes of each and every organism including insects produce non-coding RNAs that can control different biological processes. Among RNAs identified in the last decade, long non-coding RNAs (lncRNAs) represent a repertoire of a hidden layer of internal signals that can regulate gene expression in physiological, pathological, and immunological processes. Evidence shows the importance of lncRNAs in the regulation of host–pathogen interactions. In this review, an attempt has been made to view the role of lncRNAs regulating immune responses in insects. PMID:29657286

  2. Disordered gambling in adolescents : epidemiology, diagnosis, and treatment.

    PubMed

    Pietrzak, Robert H; Ladd, George T; Petry, Nancy M

    2003-01-01

    Rapid expansion of legalized gambling has been associated with increased rates of gambling disorders among adults and adolescents worldwide. Epidemiologic studies suggest that, in North America, up to 6% of adults and 20% of adolescents have a gambling problem. Despite increasing prevalence rates of gambling disorders, little research is available on how to treat such disorders in adolescents. Much of what is known about how to treat adolescent problem and pathological gambling comes from research on psychosocial and psychopharmacologic treatments for adult pathological gambling. Risk factors for adolescent gambling disorders include male gender, alcohol and drug use, deviant peers, family history of gambling, and impulsive behavior. While several risk factors characterize disordered gambling among adolescents, the extent to which these characteristics are related remains to be determined. In terms of screening for adolescent problem and pathological gambling, several instruments designed to reflect the Diagnostic and Statistical Manual of Mental Disorders diagnostic criteria for pathological gambling are available. Psychosocial approaches used to treat adult pathological gambling include Gamblers Anonymous, cognitive-behavioral therapy (CBT), and motivational enhancement therapy (MET). Among adolescents, CBT as well as an eclectic therapy have been helpful in reducing problematic gambling behavior. In terms of pharmacotherapy, three classes of psychotropic drugs have been used to treat adult pathological gambling - serotonin reuptake inhibitors, opioid antagonists, and mood stabilizers. While some of these pharmacotherapies have been efficacious in treating adult pathological gambling, additional double-blind, placebo-controlled studies are needed to determine the long-term effectiveness of these treatments. No known study has evaluated the use of psychopharmacologic agents in treating adolescent pathological gambling. Possible reasons for the lack of research on treatment for adolescent gambling disorders include lack of motivation to pursue treatment, feelings of self-control, and negative perception of therapy. Referrals from parents, teachers, and peers of adolescents, as well as community outreach programs, may be useful in successfully deriving a treatment population. Clinicians are advised to be sensitive to behavioral risk factors and to screen for disordered gambling in high risk adolescents. A combination of CBT and MET, as well as medication for any comorbid psychiatric condition, is recommended.

  3. HUMAN--A Comprehensive Physiological Model.

    ERIC Educational Resources Information Center

    Coleman, Thomas G.; Randall, James E.

    1983-01-01

    Describes computer program (HUMAN) used to simulate physiological experiments on patient pathology. Program (available from authors, including versions for microcomputers) consists of dynamic interactions of over 150 physiological variables and integrating approximations of cardiovascular, renal, lung, temperature regulation, and some hormone…

  4. Unicameral bone cyst of a cervical vertebral body and lateral mass with associated pathological fracture in a child. Case report and review of the literature.

    PubMed

    Snell, B E; Adesina, A; Wolfla, C E

    2001-10-01

    The authors present the case of a 10-year-old girl with a history of cervical trauma in whom a cystic lesion was found to involve all three columns of C-7 with evidence of pathological fracture. Computerized tomography scanning revealed a lytic lesion with sclerotic margins involving the left vertebral body, pedicle, lateral mass, and lamina of C-7 with an associated pathological compression fracture. Magnetic resonance imaging demonstrated mixed signal on both T1- and T2-weighted sequences, with cystic and enhancing solid portions. Magnetic resonance angiography demonstrated anterior displacement of the left vertebral artery at C-7. The patient underwent C-7 subtotal corpectomy and posterior resection of the tumor mass; anterior and posterior fusion were performed in which instrumentation was placed. Histological examination disclosed cystic areas lined by fibromembranous tissue with calcification and osteoid deposits consistent with unicameral bone cyst. Of the four previously reported cases of unicameral bone cysts in the cervical spine, none involved all three columns simultaneously or was associated with pathological fracture. The most common differential diagnostic considerations for cystic lesions in the spine are aneurysmal bone cyst, osteoblastoma, or giant cell tumor of bone. Unicameral bone cyst, in this location, although rare, must be considered in the differential diagnosis and may require resection and spinal reconstruction.

  5. Pathology of Podocytopathies Causing Nephrotic Syndrome in Children.

    PubMed

    Ranganathan, Sarangarajan

    2016-01-01

    Nephrotic syndrome (NS) in children includes a diverse group of diseases that range from genetic diseases without any immunological defects to causes that are primarily due to immunological effects. Recent advances in molecular and genomic studies have resulted in a plethora of genetic defects that have been localized to the podocyte, the basic structure that is instrumental in normal filtration process. Although the disease can manifest from birth and into adulthood, the primary focus of this review would be to describe the novel genes and pathology of primary podocyte defects that cause NS in children. This review will restrict itself to the pathology of congenital NS, minimal change disease (MCD), and its variants and focal segmental glomerulosclerosis (FSGS). The two major types of congenital NS are Finnish type characterized by dilated sausage shaped tubules morphologically and diffuse mesangial sclerosis characterized by glomerulosclerosis. MCD has usually normal appearing biopsy features on light microscopy and needs electron microscopy for diagnosis, whereas FSGS in contrast has classic segmental sclerosing lesions identified in different portions of the glomeruli and tubular atrophy. This review summarizes the pathological characteristics of these conditions and also delves into the various genetic defects that have been described as the cause of these primary podocytopathies. Other secondary causes of NS in children, such as membranoproliferative and membranous glomerulonephritis, will not be covered in this review.

  6. High wall shear stress and spatial gradients in vascular pathology: a review.

    PubMed

    Dolan, Jennifer M; Kolega, John; Meng, Hui

    2013-07-01

    Cardiovascular pathologies such as intracranial aneurysms (IAs) and atherosclerosis preferentially localize to bifurcations and curvatures where hemodynamics are complex. While extensive knowledge about low wall shear stress (WSS) has been generated in the past, due to its strong relevance to atherogenesis, high WSS (typically >3 Pa) has emerged as a key regulator of vascular biology and pathology as well, receiving renewed interests. As reviewed here, chronic high WSS not only stimulates adaptive outward remodeling, but also contributes to saccular IA formation (at bifurcation apices or outer curves) and atherosclerotic plaque destabilization (in stenosed vessels). Recent advances in understanding IA pathogenesis have shed new light on the role of high WSS in pathological vascular remodeling. In complex geometries, high WSS can couple with significant spatial WSS gradient (WSSG). A combination of high WSS and positive WSSG has been shown to trigger aneurysm initiation. Since endothelial cells (ECs) are sensors of WSS, we have begun to elucidate EC responses to high WSS alone and in combination with WSSG. Understanding such responses will provide insight into not only aneurysm formation, but also plaque destabilization and other vascular pathologies and potentially lead to improved strategies for disease management and novel targets for pharmacological intervention.

  7. [Quality Management System in Pathological Laboratory].

    PubMed

    Koyatsu, Junichi; Ueda, Yoshihiko

    2015-07-01

    Even compared to other clinical laboratories, the pathological laboratory conducts troublesome work, and many of the work processes are also manual. Therefore, the introduction of the systematic management of administration is necessary. It will be a shortcut to use existing standards such as ISO 15189 for this purpose. There is no standard specialized for the pathological laboratory, but it is considered to be important to a pathological laboratory in particular. 1. Safety nianagement of the personnel and environmental conditions. Comply with laws and regulations concerning the handling of hazardous materials. 2. Pre-examination processes. The laboratory shall have documented procedures for the proper collection and handling of primary samples. Developed and documented criteria for acceptance or rejection of samples are applied. 3. Examination processes. Selection, verification, and validation of the examination procedures. Devise a system that can constantly monitor the traceability of the sample. 4. Post-examination processes. Storage, retention, and disposal of clinical samples. 5. Release of results. When examination results fall within established alert or critical intervals, immediately notify the physicians. The important point is to recognize the needs of the client and be aware that pathological diagnoses are always "the final diagnoses".

  8. Connecting Eating Pathology with Risk for Engaging in Suicidal Behavior: The Mediating Role of Experiential Avoidance.

    PubMed

    Skinner, Kayla D; Rojas, Sasha M; Veilleux, Jennifer C

    2017-02-01

    Individuals with eating pathology, particularly those with diagnosed eating disorders, are at high risk for suicide. It is less clear whether undiagnosed eating pathology and subsyndromal eating disorders carry the same risk and, if so, what mechanisms may explain why higher levels of eating pathology yield greater risk for engaging in suicidal behaviors. The indirect relationship between disordered eating and risk for suicidal behaviors via facets of experiential avoidance was tested using a multiple-mediator model. The model was tested using bootstrapping estimates of indirect effects in a sample of 218 noncollege student adults (Mage = 32.33, 66.1% women) with a history of suicidal attempt and/or history of nonsuicidal self-injury (NSSI). Results revealed that disordered eating indirectly predicted risk for suicidal behaviors, distress aversion (i.e., negative attitudes or dislike of distress), and procrastination (i.e., delaying engagement with distressing activities). Results suggest that targeting experiential avoidance and helping those who have a history of engaging in suicidal behaviors and/or NSSI develop regulation strategies to use during times of distress may be of utmost importance for treatment and prevention of eating pathology. © 2016 The American Association of Suicidology.

  9. IL-10 restrains IL-17 to limit lung pathology characteristics following pulmonary infection with Francisella tularensis live vaccine strain.

    PubMed

    Slight, Samantha R; Monin, Leticia; Gopal, Radha; Avery, Lyndsay; Davis, Marci; Cleveland, Hillary; Oury, Tim D; Rangel-Moreno, Javier; Khader, Shabaana A

    2013-11-01

    IL-10 production during intracellular bacterial infections is generally thought to be detrimental because of its role in suppressing protective T-helper cell 1 (Th1) responses. Francisella tularensis is a facultative intracellular bacterium that activates both Th1 and Th17 protective immune responses. Herein, we report that IL-10-deficient mice (Il10(-/-)), despite having increased Th1 and Th17 responses, exhibit increased mortality after pulmonary infection with F. tularensis live vaccine strain. We demonstrate that the increased mortality observed in Il10(-/-)-infected mice is due to exacerbated IL-17 production that causes increased neutrophil recruitment and associated lung pathology. Thus, although IL-17 is required for protective immunity against pulmonary infection with F. tularensis live vaccine strain, its production is tightly regulated by IL-10 to generate efficient induction of protective immunity without mediating pathology. These data suggest a critical role for IL-10 in maintaining the delicate balance between host immunity and pathology during pulmonary infection with F. tularensis live vaccine strain. Copyright © 2013 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  10. [Risk of certain obstetric pathologies in women employed in working conditions non-complying with the current legal status on work load and working conditions appropriate for pregnant women].

    PubMed

    Makowiec-Dabrowska, Teresa; Hanke, Wojciech; Sobala, Wojciech; Radwan-Włodarczyk, Zyta; Koszada-Włodarczyk, Wiesława

    2003-01-01

    The aim of the study was to define the incidence of prematurity and small-for-gestational age (SGA) infants in occupationally involved pregnant women, and to find out how far working conditions departing from binding regulations contribute to the risk of the development of these pathologies. The study was carried out on a representative sample of 3050 women employed for longer than one week during pregnancy in the Łódź district. An interview conducted with the subjects few days after delivery was the source of information about working conditions. The obtained information was compared with the real situation in about 10% of randomly selected workposts. A high level of consistence was observed. The study revealed that almost 60% of women work in conditions, which do not comply with the Labor Code provisions setting working conditions permissible for pregnant women. In the study group, 4.68% of prematurity and 6.15% of SGA were recorded. A 66% excess in the risk of delivering SGA infants in case of at least one factor not complying with regulations was revealed. The excess was growing with the increased number of departures from regulations and continuation of employment during pregnancy. It was estimated that the number of SGA cases would decrease by 28% if the working conditions would have met the requirements. A prolonged time of work, local vibration for > 4h/shift, forced work pace, excessive effort and forced body position during the work performance contributed mostly to the risk of pathology. Interestingly, the risk of premature delivery was lower by about 40% in women working in unsatisfactory conditions, which is attributed to termination of work immediately after the occurrence of pregnancy-threatening symptoms. Only those women whose pregnancy was not threatened with pathology could continue their work. The study revealed a quite large number of workplaces not complying with regulations on working conditions permissible for pregnant women. Therefore, studies in this area should be continued by physicians attending pregnant women, under programs aimed at preventing prematurity, and they should be expanded to include the detection of SGA during gestation and the implementation of relevant prophylactics.

  11. N-glycosylation by N-acetylglucosaminyltransferase V enhances the interaction of CD147/basigin with integrin β1 and promotes HCC metastasis.

    PubMed

    Cui, Jian; Huang, Wan; Wu, Bo; Jin, Jin; Jing, Lin; Shi, Wen-Pu; Liu, Zhen-Yu; Yuan, Lin; Luo, Dan; Li, Ling; Chen, Zhi-Nan; Jiang, Jian-Li

    2018-05-01

    While the importance of protein N-glycosylation in cancer cell migration is well appreciated, the precise mechanisms by which N-acetylglucosaminyltransferase V (GnT-V) regulates cancer processes remain largely unknown. In the current study, we report that GnT-V-mediated N-glycosylation of CD147/basigin, a tumor-associated glycoprotein that carries β1,6-N-acetylglucosamine (β1,6-GlcNAc) glycans, is upregulated during TGF-β1-induced epithelial-to-mesenchymal transition (EMT), which correlates with tumor metastasis in patients with hepatocellular carcinoma (HCC). Interruption of β1,6-GlcNAc glycan modification of CD147/basigin decreased matrix metalloproteinase (MMP) expression in HCC cell lines and affected the interaction of CD147/basigin with integrin β1. These results reveal that β1,6-branched glycans modulate the biological function of CD147/basigin in HCC metastasis. Moreover, we showed that the PI3K/Akt pathway regulates GnT-V expression and that inhibition of GnT-V-mediated N-glycosylation suppressed PI3K signaling. In summary, β1,6-branched N-glycosylation affects the biological function of CD147/basigin and these findings provide a novel approach for the development of therapeutic strategies targeting metastasis. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. © 2018 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

  12. [Effect of Cordyceps sinensis on the expression of HIF-1α and NGAL in rats with renal ischemia-reperfusion injury].

    PubMed

    Yu, Honglei; Zhou, Qiaoling; Huang, Renfa; Yuan, Mingxia; Ao, Xiang; Yang, Jinghua

    2012-01-01

    To observe the level of urinary neutrophil gelatinase-associated lipocalin (NGAL), the expression of hypoxia inducible factor-1α (HIF-1α) and NGAL in rat kidney after renal ischemia and reperfusion (I/R), before and after the treatment with Cordyceps Sinensis (C. sinensis), and to explore the mechanism of C. sinensis against I/R injury. A total of 45 healthy male Sprague-Dawley rats were randomly divided into a sham group, a renal I/R model group, and a C. sinensis group (15 in each group).The rats in the sham group and the renal I/R model group were intragastrically administered saline (2 mL/d), and rats in the treatment group were intragastricabby administered of C. sinensis [5.0 g/(kg.d)]. The rats were sacrificed at 24, 48, and 72 h, respectively after the reperfusion and urinary N-acetyl-β-D-glucosaminidase (NAG) level was measured, renal function in rats was detected, and the pathological changes were observed with HE staining. We determined the urinary NGAL levels in the rats by ELISA, the expression of HIF-1α mRNA by RT-PCR, and the expressions of HIF-1α and NGAL proteins by confocal immunofluorescence. Compared with the sham group, the levels of BUN, SCr, levels of NAG and NGAL in urine were increased in the I/R group and the C. sinensis group, reached a peak at 24 h after the reperfusion and slowly declined at 48 and 72 h. Glomerular and tubulointerstitial areas in the sham group did not show any pathological change. Induced pathological changes included tubular cell necrosis, focal areas of proximal tubular dilation, distal tubular casts, effacement and loss of proximal tubule brush border, etc. Compared with the sham group, the expression of HIF-1α and NGAL in the kidney tissues of the I/R group and the C. sinensis group increased. C. sinensis can lower the level of NAG and NGAL in the urine and the expression of NGAL protein in the kidney tissues. It up-regulated the expression of HIF-1α mRNA and protein in the kidney tissues whilst attenuated the pathological changes. Renal I/R injury in rats can lead to pathological changes in renal tubular epithelial cells and renal interstitial damage, which are consistent with the pathological features of acute kidney injury (AKI).The level of urinary NAGL increases after the I/R, and positively correlates with the level of urinary NAG and pathological changes, suggesting that urinary NGAL may serve as a urinary biomarker for specific detection of tubular injury in AKI. C. sinensis can attenuate the renal I/ R-induced AKI. Its mechanism may be associated with up-regulating the expression of HIF-1α and down-regulating the expression of NGAL in the kidney tissues.

  13. The effect of natural and synthetic fatty acids on membrane structure, microdomain organization, cellular functions and human health.

    PubMed

    Ibarguren, Maitane; López, David J; Escribá, Pablo V

    2014-06-01

    This review deals with the effects of synthetic and natural fatty acids on the biophysical properties of membranes, and on their implication on cell function. Natural fatty acids are constituents of more complex lipids, like triacylglycerides or phospholipids, which are used by cells to store and obtain energy, as well as for structural purposes. Accordingly, natural and synthetic fatty acids may modify the structure of the lipid membrane, altering its microdomain organization and other physical properties, and provoking changes in cell signaling. Therefore, by modulating fatty acids it is possible to regulate the structure of the membrane, influencing the cell processes that are reliant on this structure and potentially reverting pathological cell dysfunctions that may provoke cancer, diabetes, hypertension, Alzheimer's and Parkinson's disease. The so-called Membrane Lipid Therapy offers a strategy to regulate the membrane composition through drug administration, potentially reverting pathological processes by re-adapting cell membrane structure. Certain fatty acids and their synthetic derivatives are described here that may potentially be used in such therapies, where the cell membrane itself can be considered as a target to combat disease. This article is part of a Special Issue entitled: Membrane Structure and Function: Relevance in the Cell's Physiology, Pathology and Therapy. Copyright © 2013 Elsevier B.V. All rights reserved.

  14. Mechanisms of Severe Acute Respiratory Syndrome Coronavirus-Induced Acute Lung Injury

    PubMed Central

    Gralinski, Lisa E.; Bankhead, Armand; Jeng, Sophia; Menachery, Vineet D.; Proll, Sean; Belisle, Sarah E.; Matzke, Melissa; Webb-Robertson, Bobbie-Jo M.; Luna, Maria L.; Shukla, Anil K.; Ferris, Martin T.; Bolles, Meagan; Chang, Jean; Aicher, Lauri; Waters, Katrina M.; Smith, Richard D.; Metz, Thomas O.; Law, G. Lynn; Katze, Michael G.; McWeeney, Shannon; Baric, Ralph S.

    2013-01-01

    ABSTRACT Systems biology offers considerable promise in uncovering novel pathways by which viruses and other microbial pathogens interact with host signaling and expression networks to mediate disease severity. In this study, we have developed an unbiased modeling approach to identify new pathways and network connections mediating acute lung injury, using severe acute respiratory syndrome coronavirus (SARS-CoV) as a model pathogen. We utilized a time course of matched virologic, pathological, and transcriptomic data within a novel methodological framework that can detect pathway enrichment among key highly connected network genes. This unbiased approach produced a high-priority list of 4 genes in one pathway out of over 3,500 genes that were differentially expressed following SARS-CoV infection. With these data, we predicted that the urokinase and other wound repair pathways would regulate lethal versus sublethal disease following SARS-CoV infection in mice. We validated the importance of the urokinase pathway for SARS-CoV disease severity using genetically defined knockout mice, proteomic correlates of pathway activation, and pathological disease severity. The results of these studies demonstrate that a fine balance exists between host coagulation and fibrinolysin pathways regulating pathological disease outcomes, including diffuse alveolar damage and acute lung injury, following infection with highly pathogenic respiratory viruses, such as SARS-CoV. PMID:23919993

  15. Gambling experiences, problems, research and policy: gambling in Germany.

    PubMed

    Ludwig, Monika; Kräplin, Anja; Braun, Barbara; Kraus, Ludwig

    2013-09-01

    The objective of this paper is to present an overview of gambling in Germany, including historical development, legislative and economic changes as well as treatment options and their effectiveness. The available scientific literature and research reports on gambling in Germany were reviewed to obtain relevant information on history, commercialization, legislation, treatment and research agenda. Gambling in Germany is characterized by compromises between protective and economic efforts. At present, gambling is illegal in Germany, and provision is subject to the state monopoly. Mere gaming machines (specific slot machines) are not classified as gambling activity, permitting commercial providers. In recent years, implementing regulations for state gambling and gaming machines have been changed. Concerning the treatment of pathological gambling, various options exist; treatment costs have been covered by health and pension insurance since 2001. Information on the effectiveness of treatment in Germany is limited. Similarly, the number of peer-reviewed publications on gambling is small. German gambling legislation was subject to major changes in the past years. Based on the available body of research (longitudinal), studies on risk and protective factors and the aetiology of pathological gambling are needed. The effectiveness of pathological gambling treatment in Germany and the impact of gambling regulations on gambling behaviour also need to be investigated. © 2012 The Authors, Addiction © 2012 Society for the Study of Addiction.

  16. Development of a Metaconceptual Awareness and Regulation Scale

    ERIC Educational Resources Information Center

    Kirbulut, Zubeyde Demet; Uzuntiryaki-Kondakci, Esen; Beeth, Michael Edward

    2016-01-01

    This study aimed to develop the Metaconceptual Awareness and Regulation Scale (MARS) -- a self-report instrument for measuring the extent to which students realise, monitor, and evaluate their ideas. MARS consists of 10 items scored on a six-point Likert scale for two factors: metaconceptual awareness and metaconceptual regulation. A pilot study…

  17. Assessing Preschool Teachers' Practices to Promote Self-Regulated Learning

    ERIC Educational Resources Information Center

    Adagideli, Fahretdin Hasan; Saraç, Seda; Ader, Engin

    2015-01-01

    Recent research reveals that in preschool years, through pedagogical interventions, preschool teachers can and should promote self-regulated learning. The main aim of this study is to develop a self-report instrument to assess preschool teachers' practices to promote self-regulated learning. A pool of 50 items was recruited through literature…

  18. The Relationship between EFL Learners' Self-Regulation and Their Listening Comprehension

    ERIC Educational Resources Information Center

    Fatemi, Mohammad Ali; Alishahi, Maral; Khorasani, Maryam Noori; Seifi, Monir

    2014-01-01

    Self-regulated EFL students can comprehend better what they listen. The present study sought to investigate the relationship between EFL learners' listening comprehension and their self-regulation. To achieve the goals of this study, 103 intermediate EFL learners were selected in Torbat-e- Heydarieh, Iran. Two instruments were employed and the…

  19. 18 CFR 12.41 - Monitoring instruments.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Monitoring instruments. 12.41 Section 12.41 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT SAFETY OF WATER POWER PROJECTS AND PROJECT WORKS...

  20. 18 CFR 12.41 - Monitoring instruments.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Monitoring instruments. 12.41 Section 12.41 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY REGULATIONS UNDER THE FEDERAL POWER ACT SAFETY OF WATER POWER PROJECTS AND PROJECT WORKS...

  1. 15 CFR 301.7 - Final disposition of an application.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... (Continued) INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.7 Final disposition of an application... not been advised of the port of entry of the instrument, or if entry has not been made when the...

  2. 15 CFR 301.7 - Final disposition of an application.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... (Continued) INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.7 Final disposition of an application... not been advised of the port of entry of the instrument, or if entry has not been made when the...

  3. 15 CFR 301.7 - Final disposition of an application.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... (Continued) INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.7 Final disposition of an application... not been advised of the port of entry of the instrument, or if entry has not been made when the...

  4. 15 CFR 301.7 - Final disposition of an application.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... (Continued) INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.7 Final disposition of an application... not been advised of the port of entry of the instrument, or if entry has not been made when the...

  5. 15 CFR 301.7 - Final disposition of an application.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... (Continued) INTERNATIONAL TRADE ADMINISTRATION, DEPARTMENT OF COMMERCE MISCELLANEOUS REGULATIONS INSTRUMENTS AND APPARATUS FOR EDUCATIONAL AND SCIENTIFIC INSTITUTIONS § 301.7 Final disposition of an application... not been advised of the port of entry of the instrument, or if entry has not been made when the...

  6. 75 FR 57375 - Establishment of Class E Airspace; Toledo, WA

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-09-21

    ... System (GPS) Standard Instrument Approach Procedure (SIAP) at Ed Carlson Memorial Field-South Lewis County Airport. This will improve the safety and management of Instrument Flight Rules (IFR) operations... is necessary for the safety and management of IFR operations. The FAA has determined this regulation...

  7. 17 CFR 1.28 - Appraisal of instruments purchased with customer funds.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... purchased with customer funds. 1.28 Section 1.28 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION GENERAL REGULATIONS UNDER THE COMMODITY EXCHANGE ACT Customers' Money, Securities, and Property § 1.28 Appraisal of instruments purchased with customer funds. Futures commission merchants who...

  8. 17 CFR 1.26 - Deposit of instruments purchased with customer funds.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... purchased with customer funds. 1.26 Section 1.26 Commodity and Securities Exchanges COMMODITY FUTURES TRADING COMMISSION GENERAL REGULATIONS UNDER THE COMMODITY EXCHANGE ACT Customers' Money, Securities, and Property § 1.26 Deposit of instruments purchased with customer funds. (a) Each futures commission merchant...

  9. 40 CFR 63.1023 - Instrument and sensory monitoring for leaks.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... leaks. 63.1023 Section 63.1023 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... (CONTINUED) National Emission Standards for Equipment Leaks-Control Level 2 Standards § 63.1023 Instrument and sensory monitoring for leaks. (a) Monitoring for leaks. The owner or operator of a regulated...

  10. 76 FR 1063 - Modifications of Debt Instruments

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-01-07

    ... modified instrument received in an exchange will be classified as debt for Federal income tax purposes... properly classified as debt for Federal income tax purposes. Effective/Applicability Date The regulations... right that is not debt for federal income tax purposes. Paragraph (g) of this section contains examples...

  11. 21 CFR 876.1075 - Gastroenterology-urology biopsy instrument.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... biopsy instrument, gastro-urology biopsy needle and needle set, and nonelectric biopsy forceps. This... regulations. (b) Classification. (1) Class II (performance standards). (2) Class I for the biopsy forceps cover and the non-electric biopsy forceps. The devices subject to this paragraph (b)(2) are exempt from...

  12. 21 CFR 876.1075 - Gastroenterology-urology biopsy instrument.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... biopsy instrument, gastro-urology biopsy needle and needle set, and nonelectric biopsy forceps. This... regulations. (b) Classification. (1) Class II (performance standards). (2) Class I for the biopsy forceps cover and the non-electric biopsy forceps. The devices subject to this paragraph (b)(2) are exempt from...

  13. 21 CFR 876.1075 - Gastroenterology-urology biopsy instrument.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... biopsy instrument, gastro-urology biopsy needle and needle set, and nonelectric biopsy forceps. This... regulations. (b) Classification. (1) Class II (performance standards). (2) Class I for the biopsy forceps cover and the non-electric biopsy forceps. The devices subject to this paragraph (b)(2) are exempt from...

  14. 40 CFR 205.174 - Remedial orders.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... not in compliance with the regulations of this subpart. Potential orders are stop sale orders, orders... Noise Emission Test Procedures Appendix I-1 to Subparts D and E—Test Procedure for Street and off-road Motorcycles (a) Instrumentation. Proper usage of all test instrumentation is essential to obtain valid...

  15. 40 CFR 205.174 - Remedial orders.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... not in compliance with the regulations of this subpart. Potential orders are stop sale orders, orders... Noise Emission Test Procedures Appendix I-1 to Subparts D and E—Test Procedure for Street and off-road Motorcycles (a) Instrumentation. Proper usage of all test instrumentation is essential to obtain valid...

  16. 40 CFR 205.174 - Remedial orders.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... not in compliance with the regulations of this subpart. Potential orders are stop sale orders, orders... Noise Emission Test Procedures Appendix I-1 to Subparts D and E—Test Procedure for Street and off-road Motorcycles (a) Instrumentation. Proper usage of all test instrumentation is essential to obtain valid...

  17. 40 CFR 144.70 - Wording of the instruments.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 22 2010-07-01 2010-07-01 false Wording of the instruments. 144.70 Section 144.70 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) WATER PROGRAMS... the draft is payable pursuant to regulations issued under authority of the Safe Drinking Water Act...

  18. Artificial intelligence programming with LabVIEW: genetic algorithms for instrumentation control and optimization.

    PubMed

    Moore, J H

    1995-06-01

    A genetic algorithm for instrumentation control and optimization was developed using the LabVIEW graphical programming environment. The usefulness of this methodology for the optimization of a closed loop control instrument is demonstrated with minimal complexity and the programming is presented in detail to facilitate its adaptation to other LabVIEW applications. Closed loop control instruments have variety of applications in the biomedical sciences including the regulation of physiological processes such as blood pressure. The program presented here should provide a useful starting point for those wishing to incorporate genetic algorithm approaches to LabVIEW mediated optimization of closed loop control instruments.

  19. Adding the third dimension on adaptive optics retina imager thanks to full-field optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Blavier, Marie; Blanco, Leonardo; Glanc, Marie; Pouplard, Florence; Tick, Sarah; Maksimovic, Ivan; Mugnier, Laurent; Chènegros, Guillaume; Rousset, Gérard; Lacombe, François; Pâques, Michel; Le Gargasson, Jean-François; Sahel, José-Alain

    2009-02-01

    Retinal pathologies, like ARMD or glaucoma, need to be early detected, requiring imaging instruments with resolution at a cellular scale. However, in vivo retinal cells studies and early diagnoses are severely limited by the lack of resolution on eye-fundus images from classical ophthalmologic instruments. We built a 2D retina imager using Adaptive Optics to improve lateral resolution. This imager is currently used in clinical environment. We are currently developing a time domain full-field optical coherence tomograph. The first step was to conceive the images reconstruction algorithms and validation was realized on non-biological samples. Ex vivo retina are currently being imaged. The final step will consist in coupling both setups to acquire high resolution retina cross-sections.

  20. FHF2 isoforms differentially regulate Nav1.6 mediated resurgent sodium currents in dorsal root ganglion neurons

    PubMed Central

    Barbosa, Cindy; Xiao, Yucheng; Johnson, Andrew J.; Xie, Wenrui; Strong, Judith A.; Zhang, Jun-Ming; Cummins, Theodore R.

    2017-01-01

    Nav1.6 and Nav1.6 mediated resurgent currents have been implicated in several pain pathologies. However, our knowledge of how fast resurgent currents are modulated in neurons is limited. Our study explored the potential regulation of Nav1.6 mediated resurgent currents by isoforms of Fibroblast growth Factor Homologous factor 2 (FHF2) in an effort to address the gap in our knowledge. FHF2 isoforms colocalize with Nav1.6 in peripheral sensory neurons. Cell line studies suggest that these proteins differentially regulate inactivation. In particular, FHF2A mediates long-term inactivation, a mechanism proposed to compete with the open-channel blocker mechanism that mediates resurgent currents. On the other hand, FHF2B lacks the ability to mediate long-term inactivation and may delay inactivation favoring open-channel block. Based on these observations, we hypothesized that FHF2A limits resurgent currents, whereas, FHF2B enhances resurgent currents. Overall our results suggest that FHF2A negatively regulates fast resurgent current by enhancing long-term inactivation and delaying recovery. In contrast FHF2B positively regulated resurgent current and did not alter long-term inactivation. Chimeric constructs of FHF2A and Navβ4 (likely the endogenous open channel blocker in sensory neurons) exhibited differential effects on resurgent currents suggesting that specific regions within FHF2A and Navβ4 have important regulatory functions. Our data also indicate FHFAs and FHF2B isoform expression are differentially regulated in a radicular pain model and that associated neuronal hyperexcitability is substantially attenuated by a FHFA peptide. As such, these findings suggest that FHF2A and FHF2B regulate resurgent current in sensory neurons and may contribute to hyperexcitability associated with some pain pathologies. PMID:27999940

  1. Substance P acting via the neurokinin-1 receptor regulates adverse myocardial remodeling in a rat model of hypertension

    PubMed Central

    Dehlin, Heather M.; Manteufel, Edward J.; Monroe, Andrew L.; Reimer, Michael H.; Levick, Scott P.

    2013-01-01

    Background Substance P is a sensory nerve neuropeptide located near coronary vessels in the heart. Therefore, substance P may be one of the first mediators released in the heart in response to hypertension, and can contribute to adverse myocardial remodeling via interactions with the neurokinin-1 receptor. We asked: 1) whether substance P promoted cardiac hypertrophy, including the expression of fetal genes known to be re-expressed during pathological hypertrophy; and 2) the extent to which substance P regulated collagen production and fibrosis. Methods and Results Spontaneously hypertensive rats (SHR) were treated with the neurokinin-1 receptor antagonist L732138 (5 mg/kg/d) from 8 to 24 weeks of age. Age-matched WKY served as controls. The gene encoding substance P, TAC1, was up-regulated as blood pressure increased in SHR. Fetal gene expression by cardiomyocytes was increased in SHR and was prevented by L732138. Cardiac fibrosis also occurred in the SHR and was prevented by L732138. Endothelin-1 was up-regulated in the SHR and this was prevented by L732138. In isolated cardiac fibroblasts, substance P transiently up-regulated several genes related to cell-cell adhesion, cell-matrix adhesion, and extracellular matrix regulation, however, no changes in fibroblast function were observed. Conclusions Substance P activation of the neurokinin-1 receptor induced expression of fetal genes related to pathological hypertrophy in the hypertensive heart. Additionally, activation of the neurokinin-1 receptor was critical to the development of cardiac fibrosis. Since no functional changes were induced in isolated cardiac fibroblasts by substance P, we conclude that substance P mediates fibrosis via up-regulation of endothelin-1. PMID:23962787

  2. The nature of catecholamine-containing neurons in the enteric nervous system in relationship with organogenesis, normal human anatomy and neurodegeneration.

    PubMed

    Natale, G; Ryskalin, L; Busceti, C L; Biagioni, F; Fornai, F

    2017-09-01

    The gastrointestinal tract is provided with extrinsic and intrinsic innervation. The extrinsic innervation includes the classic vagal parasympathetic and sympathetic components, with afferent sensitive and efferent secretomotor fibers. The intrinsic innervations is represented by the enteric nervous system (ENS), which is recognized as a complex neural network controlling a variety of cell populations, including smooth muscle cells, mucosal secretory cells, endocrine cells, microvasculature, immune and inflammatory cells. This is finalized to regulate gastrointestinal secretion, absorption and motility. In particular, this network is organized in several plexuses each one providing quite autonomous control of gastrointestinal functions (hence the definition of "second brain"). The similarity between ENS and CNS is further substantiated by the presence of local sensitive pseudo- unipolar ganglionic neurons with both peripheral and central branching which terminate in the enteric wall. A large variety of neurons and neurotransmitters takes part in the ENS. However, the nature of these neurons and their role in the regulation of gastrointestinal functions is debatable. In particular, the available literature reporting the specific nature of catecholamine- containing neurons provides conflicting evidence. This is critical both for understanding the specific role of each catecholamine in the gut and, mostly, to characterize specifically the enteric neuropathology occurring in a variety of diseases. An emphasis is posed on neurodegenerative disorders, such as Parkinson's disease, which is associated with the loss of catecholamine neurons. In this respect, the recognition of the nature of such neurons within the ENS would contribute to elucidate the pathological mechanisms which produce both CNS and ENS degeneration and to achieve more effective therapeutic approaches. Despite a great emphasis is posed on the role of noradrenaline to regulate enteric activities only a few reports are available on the anatomy and physiology of enteric dopamine neurons. Remarkably, this review limits the presence of enteric noradrenaline (and adrenaline) only within extrinsic sympathetic nerve terminals. This is based on careful morphological studies showing that the only catecholamine-containing neurons within ENS would be dopaminergic. This means that enteric pathology of catecholamine neurons should be conceived as axon pathology for noradrenaline neurons and whole cell pathology for dopamine neurons which would be the sole catecholamine cell within intrinsic circuitries affecting gut motility and secretions.The gastrointestinal tract is provided with extrinsic and intrinsic innervation. The extrinsic innervation includes the classic vagal parasympathetic and sympathetic components, with afferent sensitive and efferent secretomotor fibers. The intrinsic innervations is represented by the enteric nervous system (ENS), which is recognized as a complex neural network  controlling a variety of cell populations, including smooth muscle cells, mucosal secretory cells, endocrine cells, microvasculature, immune and inflammatory cells. This is finalized to regulate gastrointestinal secretion, absorption and motility. In particular, this network is organized in several plexuses each one providing quite autonomous control of gastrointestinal functions (hence the definition of "second brain"). The similarity between ENS and CNS is further substantiated by the presence of local sensitive pseudounipolar ganglionic neurons with both peripheral and central branching which terminate in the enteric wall. A large variety of neurons and neurotransmitters takes part in the ENS. However, the nature of these neurons and their role in the regulation of gastrointestinal functions is debatable. In particular, the available literature reporting the specific nature of catecholamine-containing neurons provides conflicting evidence. This is critical both for understanding the specific role of each catecholamine in the gut and, mostly, to characterize specifically the enteric neuropathology occurring in a variety of diseases. An emphasis is posed on neurodegenerative disorders, such as including Parkinson's disease, which is associated with the loss of catecholamine neurons. In this respect, the recognition of the nature of such neurons within the ENS would contribute to elucidate the pathological mechanisms which produce both CNS and ENS degeneration and to achieve more effective therapeutic approaches. Despite a great emphasis is posed on the role of noradrenaline to regulate enteric activities only a few reports are available on the anatomy and physiology of enteric dopamine neurons. Remarkably, this review limits the presence of enteric noradrenaline (and adrenaline) only within extrinsic sympathetic nerve terminals. This is based on careful morphological studies showing that the only catecholamine-containing neurons within ENS would be dopaminergic. This means that enteric pathology of catecholamine neurons should be conceived as axon pathology for noradrenaline neurons and whole cell pathology for dopamine neurons which would be the sole catecholamine cell within intrinsic circuitries affecting gut motility and secretions.

  3. Hospital-acquired gangrenous mucormycosis.

    PubMed Central

    Patterson, J. E.; Barden, G. E.; Bia, F. J.

    1986-01-01

    A post-operative diabetic patient who had been treated for Serratia marcescens bacterial sepsis developed recurrent thrombosis of the left femoral artery following intra-arterial instrumentation. Pathological examination of arterial thrombus ultimately demonstrated invasive mucormycosis of the femoral artery and cultures of this material grew Rhizopus oryzae. The occurrence of cutaneous and subcutaneous mucormycosis is reviewed, as well as recently recognized nosocomial risk factors for mucormycosis, such as elasticized bandages and wound dressings. Images FIG. 1 FIG. 2 FIG. 3 PMID:3765666

  4. Speech-Language Pathology production regarding voice in popular singing.

    PubMed

    Drumond, Lorena Badaró; Vieira, Naymme Barbosa; Oliveira, Domingos Sávio Ferreira de

    2011-12-01

    To present a literature review about the Brazilian scientific production in Speech-Language Pathology and Audiology regarding voice in popular singing in the last decade, as for number of publications, musical styles studied, focus of the researches, and instruments used for data collection. Cross-sectional descriptive study carried out in two stages: search in databases and publications encompassing the last decade of researches in this area in Brazil, and reading of the material obtained for posterior categorization. The databases LILACS and SciELO, the Databasis of Dissertations and Theses organized by CAPES, the online version of Acta ORL, and the online version of OPUS were searched, using the following uniterms: voice, professional voice, singing voice, dysphonia, voice disorders, voice training, music, dysodia. Articles published between the years 2000 and 2010 were selected. The researches found were classified and categorized after reading their abstracts and, when necessary, the whole study. Twenty researches within the proposed theme were selected, all of which were descriptive, involving several musical styles. Twelve studies focused on the evaluation of the popular singer's voice, and the most frequently used data collection instrument was the auditory-perceptual evaluation. The results of the publications found corroborate the objectives proposed by the authors and the different methodologies. The number of studies published is still restricted when compared to the diversity of musical genres and the uniqueness of popular singer.

  5. Live volumetric (4D) visualization and guidance of in vivo human ophthalmic surgery with intraoperative optical coherence tomography

    PubMed Central

    Carrasco-Zevallos, O. M.; Keller, B.; Viehland, C.; Shen, L.; Waterman, G.; Todorich, B.; Shieh, C.; Hahn, P.; Farsiu, S.; Kuo, A. N.; Toth, C. A.; Izatt, J. A.

    2016-01-01

    Minimally-invasive microsurgery has resulted in improved outcomes for patients. However, operating through a microscope limits depth perception and fixes the visual perspective, which result in a steep learning curve to achieve microsurgical proficiency. We introduce a surgical imaging system employing four-dimensional (live volumetric imaging through time) microscope-integrated optical coherence tomography (4D MIOCT) capable of imaging at up to 10 volumes per second to visualize human microsurgery. A custom stereoscopic heads-up display provides real-time interactive volumetric feedback to the surgeon. We report that 4D MIOCT enhanced suturing accuracy and control of instrument positioning in mock surgical trials involving 17 ophthalmic surgeons. Additionally, 4D MIOCT imaging was performed in 48 human eye surgeries and was demonstrated to successfully visualize the pathology of interest in concordance with preoperative diagnosis in 93% of retinal surgeries and the surgical site of interest in 100% of anterior segment surgeries. In vivo 4D MIOCT imaging revealed sub-surface pathologic structures and instrument-induced lesions that were invisible through the operating microscope during standard surgical maneuvers. In select cases, 4D MIOCT guidance was necessary to resolve such lesions and prevent post-operative complications. Our novel surgical visualization platform achieves surgeon-interactive 4D visualization of live surgery which could expand the surgeon’s capabilities. PMID:27538478

  6. Live volumetric (4D) visualization and guidance of in vivo human ophthalmic surgery with intraoperative optical coherence tomography

    NASA Astrophysics Data System (ADS)

    Carrasco-Zevallos, O. M.; Keller, B.; Viehland, C.; Shen, L.; Waterman, G.; Todorich, B.; Shieh, C.; Hahn, P.; Farsiu, S.; Kuo, A. N.; Toth, C. A.; Izatt, J. A.

    2016-08-01

    Minimally-invasive microsurgery has resulted in improved outcomes for patients. However, operating through a microscope limits depth perception and fixes the visual perspective, which result in a steep learning curve to achieve microsurgical proficiency. We introduce a surgical imaging system employing four-dimensional (live volumetric imaging through time) microscope-integrated optical coherence tomography (4D MIOCT) capable of imaging at up to 10 volumes per second to visualize human microsurgery. A custom stereoscopic heads-up display provides real-time interactive volumetric feedback to the surgeon. We report that 4D MIOCT enhanced suturing accuracy and control of instrument positioning in mock surgical trials involving 17 ophthalmic surgeons. Additionally, 4D MIOCT imaging was performed in 48 human eye surgeries and was demonstrated to successfully visualize the pathology of interest in concordance with preoperative diagnosis in 93% of retinal surgeries and the surgical site of interest in 100% of anterior segment surgeries. In vivo 4D MIOCT imaging revealed sub-surface pathologic structures and instrument-induced lesions that were invisible through the operating microscope during standard surgical maneuvers. In select cases, 4D MIOCT guidance was necessary to resolve such lesions and prevent post-operative complications. Our novel surgical visualization platform achieves surgeon-interactive 4D visualization of live surgery which could expand the surgeon’s capabilities.

  7. Role of Regulators of G Protein Signaling Proteins in Bone Physiology and Pathophysiology.

    PubMed

    Jules, Joel; Yang, Shuying; Chen, Wei; Li, Yi-Ping

    2015-01-01

    Regulators of G protein signaling (RGS) proteins enhance the intrinsic GTPase activity of α subunits of the heterotrimeric G protein complex of G protein-coupled receptors (GPCRs) and thereby inactivate signal transduction initiated by GPCRs. The RGS family consists of nearly 37 members with a conserved RGS homology domain which is critical for their GTPase accelerating activity. RGS proteins are expressed in most tissues, including heart, lung, brain, kidney, and bone and play essential roles in many physiological and pathological processes. In skeletal development and bone homeostasis as well as in many bone disorders, RGS proteins control the functions of various GPCRs, including the parathyroid hormone receptor type 1 and calcium-sensing receptor and also regulate various critical signaling pathways, such as Wnt and calcium oscillations. This chapter will discuss the current findings on the roles of RGS proteins in regulating signaling of key GPCRs in skeletal development and bone homeostasis. We also will examine the current updates of RGS proteins' regulation of calcium oscillations in bone physiology and highlight the roles of RGS proteins in selected bone pathological disorders. Despite the recent advances in bone and mineral research, RGS proteins remain understudied in the skeletal system. Further understanding of the roles of RGS proteins in bone should not only provide great insights into the molecular basis of various bone diseases but also generate great therapeutic drug targets for many bone diseases. © 2015 Elsevier Inc. All rights reserved.

  8. 48 CFR 304.7001 - Numbering acquisitions.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Numbering acquisitions. 304.7001 Section 304.7001 Federal Acquisition Regulations System HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATIVE MATTERS Acquisition Instrument Identification Numbering System 304.7001 Numbering acquisitions. (a...

  9. A New Pathogenesis of Albuminuria: Role of Transcytosis.

    PubMed

    He, Fang-Fang; Gong, Yi; Li, Zhen-Qiong; Wu, Liang; Jiang, Hua-Jun; Su, Hua; Zhang, Chun; Wang, Yu-Mei

    2018-06-15

    Transcytosis is an important intracellular transport process by which multicellular organisms selectively move cargoes from apical to basolateral membranes without disrupting cellular homeostasis. In kidney, macromolecular components in the serum, such as albumin, low-density lipoprotein and immunoglobulins, pass through the glomerular filtration barrier (GFB) and proximal tubular cells (PTCs) by transcytosis. Protein transcytosis plays a vital role in the pathology of albuminuria, which causes progressive destruction of the GFB structure and function. However, the pathophysiological consequences of protein transcytosis in the kidney remain largely unknown. This article summarizes recent researches on the regulation of albumin transcytosis across the GFB and PTCs in both physiological and pathological conditions. Understanding the mechanism of albumin transcytosis may reveal potential therapeutic targets for prevention or alleviation of the pathological consequences of albuminuria. © 2018 The Author(s). Published by S. Karger AG, Basel.

  10. The role of hydrogen sulfide in aging and age-related pathologies.

    PubMed

    Perridon, Bernard W; Leuvenink, Henri G D; Hillebrands, Jan-Luuk; van Goor, Harry; Bos, Eelke M

    2016-09-27

    When humans grow older, they experience inevitable and progressive loss of physiological function, ultimately leading to death. Research on aging largely focuses on the identification of mechanisms involved in the aging process. Several proposed aging theories were recently combined as the 'hallmarks of aging'. These hallmarks describe (patho-)physiological processes that together, when disrupted, determine the aging phenotype. Sustaining evidence shows a potential role for hydrogen sulfide (H 2 S) in the regulation of aging. Nowadays, H 2 S is acknowledged as an endogenously produced signaling molecule with various (patho-) physiological effects. H 2 S is involved in several diseases including pathologies related to aging. In this review, the known, assumed and hypothetical effects of hydrogen sulfide on the aging process will be discussed by reviewing its actions on the hallmarks of aging and on several age-related pathologies.

  11. Interleukin-22: immunobiology and pathology

    PubMed Central

    Dudakov, Jarrod A.; Hanash, Alan M.; van den Brink, Marcel R.M.

    2015-01-01

    Interleukin-22 (IL-22) is a recently described IL-10 family cytokine that is produced by T-helper (Th)-17 cells, γδ T cells, NKT cells and newly described innate lymphoid cells (ILCs). Knowledge of IL-22 biology has rapidly evolved since its discovery in 2000, and a role for IL-22 has been identified in numerous tissues including the intestines, lung, liver, kidney, thymus, pancreas and skin. IL-22 primarily targets non-hematopoietic epithelial and stromal cells where it can promote proliferation and play a role in tissue regeneration. In addition, IL-22 regulates host defense at barrier surfaces. However, IL-22 has also been linked to several conditions involving inflammatory tissue pathology. In this review, we will assess the current understanding of this cytokine, including its physiologic and pathologic effects on epithelial cell function. PMID:25706098

  12. 76 FR 61258 - Revision of Class E Airspace; Allakaket, AK

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-04

    ... Allakaket, AK, to accommodate the amendment of one Standard Instrument Approach Procedure at the Allakaket Airport. The FAA is taking this action to enhance safety and management of Instrument Flight Rules (IFR... Regulations, part 51, subject to the annual revision of FAA Order 7400.9 and publication of conforming...

  13. 76 FR 60714 - Revision of Class E Airspace; Northway, AK

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-30

    ... Northway, AK, to accommodate the amendment of one Standard Instrument Approach Procedure at the Northway Airport. The FAA is taking this action to enhance safety and management of Instrument Flight Rules (IFR... incorporation by reference action under title 1, Code of Federal Regulations, part 51, subject to the annual...

  14. 76 FR 65944 - Establishment of Class E Airspace; Tatitlek, AK

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-25

    ... at Tatitlek, AK, to accommodate the creation of one standard instrument approach procedure at the Tatitlek Airport. The FAA is taking this action to enhance safety and management of Instrument Flight Rules... Regulations, part 51, subject to the annual revision of FAA Order 7400.9 and publication of conforming...

  15. 40 CFR 65.104 - Instrument and sensory monitoring for leaks.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... leaks. 65.104 Section 65.104 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR PROGRAMS (CONTINUED) CONSOLIDATED FEDERAL AIR RULE Equipment Leaks § 65.104 Instrument and sensory monitoring for leaks. (a) Monitoring for leaks. The owner or operator of a regulated source subject to this...

  16. 40 CFR 63.1004 - Instrument and sensory monitoring for leaks.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... leaks. 63.1004 Section 63.1004 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY (CONTINUED) AIR... (CONTINUED) National Emission Standards for Equipment Leaks-Control Level 1 § 63.1004 Instrument and sensory monitoring for leaks. (a) Monitoring for leaks. The owner or operator of a regulated source subject to this...

  17. 75 FR 49427 - Application of Section 108(i) to Partnerships and S Corporations

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-13

    ... reacquisitions of applicable debt instruments after December 31, 2008, and before January 1, 2011. The regulations affect partnerships and S corporations with respect to reacquisitions of applicable debt... deferred section 752 amount with respect to an applicable debt instrument. An agency may not conduct or...

  18. 78 FR 67298 - Establishment of Class E Airspace; Ennis, MT

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-12

    ... instrument approach procedures at Ennis-Big Sky Airport. This improves the safety and management of...) standard instrument approach procedures at the airport. This action is necessary for the safety and management of IFR operations. The FAA has determined this regulation only involves an established body of...

  19. 31 CFR 545.410 - Acquisition of instruments including bankers acceptances.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Acquisition of instruments including bankers acceptances. 545.410 Section 545.410 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY TALIBAN (AFGHANISTAN...

  20. 31 CFR 596.307 - Monetary instruments.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 31 Money and Finance:Treasury 3 2012-07-01 2012-07-01 false Monetary instruments. 596.307 Section 596.307 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF... includes coin or currency of the United States or of any other country, travelers' checks, personal checks...

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