Partner behavioral responses to pain mediate the relationship between partner pain cognitions and pain outcomes in women with provoked vestibulodynia.

Partner behavioral responses to pain can have a significant impact on patient pain and depression, but little is known about why partners respond in specific ways. Using a cognitive-behavioral model, the present study examined whether partner cognitions were associated with partner behavioral responses, which prior work has found to predict patient pain and depressive symptoms. Participants were 354 women with provoked vestibulodynia and their partners. Partner pain-related cognitions were assessed using the partner versions of the Pain Catastrophizing Scale and Extended Attributional Style Questionnaire, whereas their behavioral responses to pain were assessed with the Multidimensional Pain Inventory. Patient pain was measured using a numeric rating scale, and depressive symptoms were assessed using the Beck Depression Inventory–II. Path analysis was used to examine the proposed model. Partner catastrophizing and negative attributions were associated with negative partner responses, which were associated with higher patient pain. It was also found that partner pain catastrophizing was associated with solicitous partner responses, which in turn were associated with higher patient pain and depressive symptoms. The effect of partner cognitions on patient outcomes was partially mediated by partner behavioral responses. Findings highlight the importance of assessing partner cognitions, both in research and as a target for intervention. Perspective The present study presents a cognitive-behavioral model to partially explain how significant others' thoughts about pain have an effect on patient pain and depressive symptoms. Findings may inform cognitive-behavioral therapy for couples coping with PVD.

Provoked vestibulodynia : mediators of the associations between partner responses, pain, and sexual satisfaction.

Provoked vestibulodynia (PVD) is a chronic, recurrent vulvo-vaginal pain condition affecting 12% of the general population, and is associated with sexual dysfunction, psychological distress, and reduced quality of life. There is growing interest in the role of interpersonal variables in PVD, which have been widely neglected. In a sample of 175 couples, the present study examined the mediating roles of partner and participant catastrophizing and self-efficacy in the association between solicitous partner responses and pain intensity, and that of dyadic adjustment in the association between solicitous and negative partner responses and sexual satisfaction. Couples completed measures of partner responses, catastrophizing, self-efficacy, dyadic adjustment, and depression. Women also completed measures of pain, sexual satisfaction, and sexual function. Controlling for depression and solicitousness perceived by the other member of the couple, catastrophizing and self-efficacy partially mediated the association between higher solicitous responses and higher pain during intercourse, accounting for 26 and 25% of the variance in this association for participant and partner-perceived responses, respectively. For both participant and partners, only pain catastrophizing was a unique mediator. Controlling for depression, sexual function and partner-perceived responses, dyadic adjustment partially mediated the association between higher participant-perceived solicitous responses and higher sexual satisfaction, and between higher participant-perceived negative responses and lower sexual satisfaction, accounting for 26% of the variance in each association. The current findings suggest that catastrophizing and dyadic adjustment may constitute a route by which partner responses exacerbate pain and increase or decrease sexual satisfaction in PVD couples.

Harmful or helpful : perceived solicitous and facilitative partner responses are differentially associated with pain and sexual satisfaction in women with provoked vestibulodynia.

Introduction.  Provoked vestibulodynia (PVD) is a highly prevalent vulvovaginal pain condition that negatively affects women's emotional, sexual, and relationship well-being. Recent studies have investigated the role of interpersonal variables, including partner responses. Aim.  We examined whether solicitous and facilitative partner responses were differentially associated with vulvovaginal pain and sexual satisfaction in women with PVD by examining each predictor while controlling for the other. Methods.  One hundred twenty-one women (M age = 30.60, SD = 10.53) with PVD or self-reported symptoms of PVD completed the solicitous subscale of the spouse response scale of the Multidimensional Pain Inventory, and the facilitative subscale of the Spouse Response Inventory. Participants also completed measures of pain, sexual function, sexual satisfaction, trait anxiety, and avoidance of pain and sexual behaviors (referred to as “avoidance”). Main Outcome Measures.  Dependent measures were the (i) Pain Rating Index of the McGill Pain Questionnaire with reference to pain during vaginal intercourse and (ii) Global Measure of Sexual Satisfaction Scale. Results.  Controlling for trait anxiety and avoidance, higher solicitous partner responses were associated with higher vulvovaginal pain intensity (β = 0.20, P = 0.03), and higher facilitative partner responses were associated with lower pain intensity (β = −0.20, P = 0.04). Controlling for sexual function, trait anxiety, and avoidance, higher facilitative partner responses were associated with higher sexual satisfaction (β = 0.15, P = 0.05). Conclusions.  Findings suggest that facilitative partner responses may aid in alleviating vulvovaginal pain and improving sexual satisfaction, whereas solicitous partner responses may contribute to greater pain.

Woman and partner-perceived partner responses predict pain and sexual satisfaction in vestibulodynia couples

Introduction.  Provoked vestibulodynia (PVD) is a highly prevalent vulvovaginal pain condition that results in significant sexual dysfunction, psychological distress, and reduced quality of life. Although some intra-individual psychological factors have been associated with PVD, studies to date have neglected the interpersonal context of this condition. Aim.  We examined whether partner responses to women's pain experience—from the perspective of both the woman and her partner—are associated with pain intensity, sexual function, and sexual satisfaction. Methods.  One hundred ninety-one couples (M age for women = 33.28, standard deviation [SD] = 12.07, M age for men = 35.79, SD = 12.44) in which the woman suffered from PVD completed the spouse response scale of the Multidimensional Pain Inventory, assessing perceptions of partners' responses to the pain. Women with PVD also completed measures of pain, sexual function, sexual satisfaction, depression, and dyadic adjustment. Main Outcome Measures.  Dependent measures were women's responses to: (i) a horizontal analog scale assessing the intensity of their pain during intercourse; (ii) the Female Sexual Function Index; and (iii) the Global Measure of Sexual Satisfaction Scale. Results.  Controlling for depression, higher solicitous partner responses were associated with higher levels of women's vulvovaginal pain intensity. This association was significant for partner-perceived responses (β = 0.29, P < 0.001) and for woman-perceived partner responses (β = 0.16, P = 0.04). After controlling for sexual function and dyadic adjustment, woman-perceived greater solicitous partner responses (β = 0.16, P = 0.02) predicted greater sexual satisfaction. Partner-perceived responses did not predict women's sexual satisfaction. Partner responses were not associated with women's sexual function. Conclusions.  Findings support the integration of dyadic processes in the conceptualization and treatment of PVD by suggesting that partner responses to pain affect pain intensity and sexual satisfaction in affected women.

Relationship satisfaction moderates the associations between male partner responses and depression in women with vulvodynia : a dyadic daily experience study.

This article may not exactly replicate the final version published in the journal. It is not the copy of record. / Cet article ne constitue pas la version officielle, et peut différer de la version publiée dans la revue.

Investigation du rôle de Myo9b dans la migration des interneurones GABAergiques corticaux

Les encéphalopathies épileptogènes sont des maladies graves de l’enfance associant une épilepsie, souvent réfractaire, et un retard de développement. Les mécanismes sous-tendant ces maladies sont peu connus. Cependant, nous postulons que ces épilepsies puissent être causées par une dysfonction du réseau inhibiteur. En effet, des défauts de migration ou de maturation des interneurones GABAergiques (INs) corticaux induisent l’épilepsie, tant chez l’humain que chez la souris. Dans le but d’étudier les causes génétiques des encéphalopathies épileptogènes sporadiques inexpliquées, le laboratoire de la Dre Rossignol a procédé au séquençage d’exome entier d’une cohorte d’enfants atteints. Cela a permis d’identifier, chez un patient, une nouvelle mutation de novo, possiblement pathogène, dans le gène MYO9b. MYO9b est impliqué dans la migration de cellules immunitaires et cancéreuses et est exprimée durant le développement cérébral. Nous émettons l’hypothèse voulant que MYO9b puisse être importante pour la migration des INs corticaux. Les résultats présentés dans ce mémoire démontrent que Myo9b est exprimé dès le stade embryonnaire par les progéniteurs des INs corticaux et que son expression se restreint aux INs dans le cortex mature. De plus, nous démontrons que la répression ex vivo de Myo9b sélectivement dans les INs au sein de tranches corticales organotypiques embryonnaires mène à des défauts morphologiques majeurs de ces cellules en migration. En effet, ces cellules présentent une morphologie multipolaire et des neurites rostraux plus longs et plus complexes. Ces changements morphologiques pourraient avoir un impact majeur sur la migration des INs et ainsi perturber le développement des réseaux inhibiteurs.

Electron energy loss spectroscopy assessment of cationic migration in La2/3Ca1/3MnO3 thin films

Màster en Nanociència i Nanotecnologia curs 2006-2007. Directors: Francesca Peiró i Martínez and Jordi Arbiol i Cobos

Molecular mechanisms controlling the precision of chemokine guided cell migration

By the end of the first day of embryonic development, zebrafish primordial germ cells (PGCs) arrive at the site where the gonad develops. In our study we investigated the mechanisms controlling the precision of primordial germ cell arrival at their target. We found that in contrast with our expectations which were based on findings in Drosophila and mouse, the endoderm does not constitute a preferred migration substrate for the PGCs. Rather, endoderm derivatives are important for later stages of organogenesis keeping the PGC clusters separated. It would be interesting to investigate the precise mechanism by which endoderm controls germ cell position in the gonad. In their migration towards the gonad, zebrafish germ cells follow the gradient of chemokine SDF-1a, which they detect using the receptor CXCR4b that is expressed on their membrane. Here we show that the C-terminal region of CXCR4b is responsible for down-regulation of receptor activity as well as for receptor internalization. We demonstrate that receptor molecules unable to internalize are less potent in guiding germ cells to the site where the gonad develops, thereby implicating chemokine receptor internalization in facilitating precision of migration during chemotaxis in vivo. We demonstrate that while CXCR4b activity positively regulates the duration of the active migration phases, the down-regulation of CXCR4b signalling by internalization limits the duration of this phase. This way, receptor signalling contributes to the persistence of germ cell migration, whereas receptor down-regulation enables the cells to stop and correct their migration path close to the target where germ cells encounter the highest chemokine signal. Chemokine receptors are involved in directing cell migration in different processes such as lymphocyte trafficking, cancer and in the development of the vascular system. The C-terminal domain of many chemokine receptors was shown to be essential for controlling receptor signalling and internalization. It would therefore be important to determine whether the role for receptor internalization in vivo as described here (allowing periodical corrections to the migration route) and the mechanisms involved (reducing the level of signalling) apply for those other events, too.

Migration and Spatial Development

This is an empirical study with theoretical interpretation and elaboration simultaneously on the migration process and the related spatial development in contemporary China. In so doing, there is always a combination of series of studies of the modernization of the migrants themselves with accumulation of forms of capital and changes of lebenswelt (life world) as well as the regions of their origins by the effective use of the gained resources from outgoing migration and remigration. With great efforts made to put the issues together for analysis, the author has taken three approaches to the study based on the political and economic institutional arrangements, the field work data and the elaboration of respective findings. First, as the analytical parts of the institutional changes, which have gone through the whole research, many of the policies from state level to townships involved in the migration, remigration and spatial development have been interpreted with Chinese political and cultural insight. The making of these, as the means of understanding the contexts of macro level and micro level cases is served as key linkages between scholarly imagination and social reality. Indeed most of the discussions made to explain the phenomena such as the sudden upsurge of migration flows, the emergence of three generations, the strong and weak trends of remigration as well as the related spatial development planning, etc are mainly due to the domination, at least the impact of governments decision-making in spite of growing market functioning in often operative manners. Secondly, case studies of the effects of migration and remigration are carried out between the years of 1995 and 2005 in the costal urban regions as designations and the interior rural regions as origins. Conducted mainly by the author, the cases drawn in the research focus on the process of migration with an accumulation of forms of capital away from home and the effective use of the resources flowing back to home areas. As a result, ways of accumulation and utilization of the economic, social and cultural capital are described and interpreted in terms of the development and modernization of both the migrants themselves and the regions where they come out from or move to in the future. Thirdly, in accordance with the findings generated from the cases, the author proposes in the final chapter an important argumentation as conclusion that the duel social-economic structure will inevitably be broken up and reformulated with flows of migrants and forms of capital they possess as types of future spatial development that will be put into practice. With scenarios and all the other conclusions worked out in the end, the research concludes that the pluralistic spatial development in the condition of constant space flows between regions can be a decisive line of thinking in the process of urbanization, industrialization and modernization in the long run in the future. Since this is an exploratory study of the past and present, the author has left some space open for academic debates and put forward suggestions on the inclusion of future research before implementing policies necessary for migration associated spatial practice and development.

Untersuchungen zur Rolle von Isoformen katalytischer Untereinheiten der PKA

ZUSAMMENFASSUNG: Proteinkinasen übernehmen zentrale Aufgaben in der Signaltransduktion höherer Zellen. Dabei ist die cAMP-abhängige Proteinkinase (PKA) bezüglich ihrer Struktur und Funktion eine der am besten charakterisierten Proteinkinasen. Trotzdem ist wenig über direkte Interaktionspartner der katalytischen Untereinheiten (PKA-C) bekannt. In einem Split-Ubiquitin basiertem Yeast Two Hybrid- (Y2H-)System wurden potenzielle Interaktionspartner der PKA-C identifiziert. Als Bait wurden sowohl die humane Hauptisoform Cα (hCα) als auch die Proteinkinase X (PrKX) eingesetzt. Nach der Bestätigung der Funktionalität der PKA-C-Baitproteine, dem Nachweis der Expression und der Interaktion mit dem bekannten Interaktionspartner PKI wurde ein Y2H-Screen gegen eine Mausembryo-cDNA-Expressionsbibliothek durchgeführt. Von 2*10^6 Klonen wurden 76 Kolonien isoliert, die ein mit PrKX interagierendes Preyprotein exprimierten. Über die Sequenzierung der enthaltenen Prey-Vektoren wurden 25 unterschiedliche, potenzielle Interaktionspartner identifiziert. Für hCα wurden über 2*10^6 S. cerevisiae-Kolonien untersucht, von denen 1.959 positiv waren (1.663 unter erhöhter Stringenz). Über die Sequenzierung von ca. 10% der Klone (168) konnten Sequenzen für 67 verschiedene, potenzielle Interaktionspartner der hCα identifiziert werden. 15 der Preyproteine wurden in beiden Screens identifiziert. Die PKA-C-spezifische Wechselwirkung der insgesamt 77 Preyproteine wurde im Bait Dependency Test gegen largeT, ein Protein ohne Bezug zum PKA-System, untersucht. Aus den PKA-C-spezifischen Bindern wurden die löslichen Preyproteine AMY-1, Bax72-192, Fabp3, Gng11, MiF, Nm23-M1, Nm23-M2, Sssca1 und VASP256-375 für die weitere in vitro-Validierung ausgewählt. Die Interaktion von FLAG-Strep-Strep-hCα (FSS-hCα) mit den über Strep-Tactin aus der rekombinanten Expression in E. coli gereinigten One-STrEP-HA-Proteinen (SSHA-Proteine) wurde über Koimmunpräzipitation für SSHA-Fabp3, -Nm23-M1, -Nm23-M2, -Sssca1 und -VASP256-375 bestätigt. In SPR-Untersuchungen, für die hCα kovalent an die Oberfläche eines CM5-Sensorchips gekoppelt wurde, wurden die ATP/Mg2+-Abhängigkeit der Bindungen sowie differentielle Effekte der ATP-kompetitiven Inhibitoren H89 und HA-1077 untersucht. Freie hCα, die vor der Injektion zu den SSHA-Proteinen gegeben wurde, kompetierte im Gegensatz zu FSS-PrKX die Bindung an die hCα-Oberfläche. Erste kinetische Analysen lieferten Gleichgewichtsdissoziationskonstanten im µM- (SSHA-Fabp3, -Sssca1), nM- (SSHA-Nm23-M1, –M2) bzw. pM- (SSHA-VASP256-375) Bereich. In funktionellen Analysen konnte eine Phosphorylierung von SSHA-Sssca1 und VASP256-375 durch hCα und FSS-PrKX im Autoradiogramm nachgewiesen werden. SSHA-VASP256-375 zeigte zudem eine starke Inhibition von hCα im Mobility Shift-Assay. Dieser inhibitorische Effekt sowie die hohe Affinität konnten jedoch auf eine Kombination aus der Linkersequenz des Vektors und dem N-Terminus von VASP256-375 zurückgeführt werden. Über die Wechselwirkungen der hier identifizierten Interaktionspartner Fabp3, Nm23-M1 und Nm23-M2 mit hCα können in Folgeuntersuchungen neue PKA-Funktionen insbesondere im Herzen sowie während der Zellmigration aufgedeckt werden. Sssca1 stellt dagegen ein neues, näher zu charakterisierendes PKA-Substrat dar.

ADAM: A Decentralized Parallel Computer Architecture Featuring Fast Thread and Data Migration and a Uniform Hardware Abstraction

The furious pace of Moore's Law is driving computer architecture into a realm where the the speed of light is the dominant factor in system latencies. The number of clock cycles to span a chip are increasing, while the number of bits that can be accessed within a clock cycle is decreasing. Hence, it is becoming more difficult to hide latency. One alternative solution is to reduce latency by migrating threads and data, but the overhead of existing implementations has previously made migration an unserviceable solution so far. I present an architecture, implementation, and mechanisms that reduces the overhead of migration to the point where migration is a viable supplement to other latency hiding mechanisms, such as multithreading. The architecture is abstract, and presents programmers with a simple, uniform fine-grained multithreaded parallel programming model with implicit memory management. In other words, the spatial nature and implementation details (such as the number of processors) of a parallel machine are entirely hidden from the programmer. Compiler writers are encouraged to devise programming languages for the machine that guide a programmer to express their ideas in terms of objects, since objects exhibit an inherent physical locality of data and code. The machine implementation can then leverage this locality to automatically distribute data and threads across the physical machine by using a set of high performance migration mechanisms. An implementation of this architecture could migrate a null thread in 66 cycles -- over a factor of 1000 improvement over previous work. Performance also scales well; the time required to move a typical thread is only 4 to 5 times that of a null thread. Data migration performance is similar, and scales linearly with data block size. Since the performance of the migration mechanism is on par with that of an L2 cache, the implementation simulated in my work has no data caches and relies instead on multithreading and the migration mechanism to hide and reduce access latencies.