Neuroanatomic Correlates of Female Sexual Dysfunction in Multiple Sclerosis

OBJECTIVE: This study intended to determine associations between alterations of female sexual arousal as well as vaginal lubrication and the site of cerebral multiple sclerosis (MS) lesions. METHODS: In 44 women with MS (mean age: 36.5 ± 9.9 years), we assessed their medical history and evaluated sexual function using the Female Sexual Function Index scores for arousal and vaginal lubrication. We determined potential confounding factors of sexual dysfunction: age; disease duration; physical disability; depression; bladder or urinary dysfunction; and total volume of cerebral lesions. Arousal and lubrication scores were correlated with one another and with potential confounding factors. Cerebral MS lesions were recorded on imaging scans. A voxel-based lesion symptom mapping (VLSM) analysis adjusted for confounding variables was performed correlating cerebral sites of MS lesions with arousal and lubrication scores. RESULTS: Decreased arousal scores correlated with decreased lubrication scores; decreased lubrication scores were associated with bladder or urinary symptoms. Arousal and lubrication scores were not associated with any other variables. Multivariate VLSM analysis, including arousal and lubrication scores as covariables of interest, showed right occipital lesions associated with impaired arousal and left insular lesions associated with decreased lubrication. Impaired lubrication remained associated with left insular lesions after adjustment for bladder or urinary dysfunction. INTERPRETATION: Our data indicate that impaired female sexual arousal is associated with MS lesions in the occipital region, integrating visual information and modulating attention toward visual input. Impaired lubrication correlated with lesions in the left insular region, contributing to mapping and generating visceral arousal states

Family medicine in post-communist Europe needs a boost. Exploring the position of family medicine in healthcare systems of Central and Eastern Europe and Russia

<p>Abstract</p> <p>Background</p> <p>The countries of Central and Eastern Europe have experienced a lot of changes at the end of the 20th century, including changes in the health care systems and especially in primary care. The aim of this paper is to systematically assess the position of family medicine in these countries, using the same methodology within all the countries.</p> <p>Methods</p> <p>A key informants survey in 11 Central and Eastern European countries and Russia using a questionnaire developed on the basis of systematic literature review.</p> <p>Results</p> <p>Formally, family medicine is accepted as a specialty in all the countries, although the levels of its implementation vary across the countries and the differences are important. In most countries, solo practice is the most predominant organisational form of family medicine. Family medicine is just one of many medical specialties (e.g. paediatrics and gynaecology) in primary health care. Full introduction of family medicine was successful only in Estonia.</p> <p>Conclusions</p> <p>Some of the unification of the systems may have been the result of the EU request for adequate training that has pushed the policies towards higher standards of training for family medicine. The initial enthusiasm of implementing family medicine has decreased because there was no initiative that would support this movement. Internal and external stimuli might be needed to continue transition process.</p

Coordination in climbing: effect of skill, practice and constraints manipulation

BACKGROUND: Climbing is a physical activity and sport involving many subdisciplines. Minimization of prolonged pauses, use of a relatively simple path through a route and smooth transitions between movements broadly define skilled coordination in climbing. OBJECTIVES: To provide an overview of the constraints on skilled coordination in climbing and to explore future directions in this emerging field. METHODS: A systematic literature review was conducted in 2014 and retrieved studies reporting perceptual and movement data during climbing tasks. To be eligible for the qualitative synthesis, studies were required to report perceptual or movement data during climbing tasks graded for difficulty. RESULTS: Qualitative synthesis of 42 studies was carried out, showing that skilled coordination in climbing is underpinned by superior perception of climbing opportunities; optimization of spatial-temporal features pertaining to body-to-wall coordination, the climb trajectory and hand-to-hold surface contact; and minimization of exploratory behaviour. Improvements in skilled coordination due to practice are related to task novelty and the difficulty of the climbing route relative to the individual's ability level. CONCLUSION: Perceptual and motor adaptations that improve skilled coordination are highly significant for improving the climbing ability level. Elite climbers exhibit advantages in detection and use of climbing opportunities when visually inspecting a route from the ground and when physically moving though a route. However, the need to provide clear guidelines on how to improve climbing skill arises from uncertainties regarding the impacts of different practice interventions on learning and transfer

Identifying Ligand Binding Conformations of the β2-Adrenergic Receptor by Using Its Agonists as Computational Probes

Recently available G-protein coupled receptor (GPCR) structures and biophysical studies suggest that the difference between the effects of various agonists and antagonists cannot be explained by single structures alone, but rather that the conformational ensembles of the proteins need to be considered. Here we use an elastic network model-guided molecular dynamics simulation protocol to generate an ensemble of conformers of a prototypical GPCR, β2-adrenergic receptor (β2AR). The resulting conformers are clustered into groups based on the conformations of the ligand binding site, and distinct conformers from each group are assessed for their binding to known agonists of β2AR. We show that the select ligands bind preferentially to different predicted conformers of β2AR, and identify a role of β2AR extracellular region as an allosteric binding site for larger drugs such as salmeterol. Thus, drugs and ligands can be used as "computational probes" to systematically identify protein conformers with likely biological significance. © 2012 Isin et al

P-rex1 cooperates with PDGFRβ to drive cellular migration in 3D microenvironments

Expression of the Rac-guanine nucleotide exchange factor (RacGEF), P-Rex1 is a key determinant of progression to metastasis in a number of human cancers. In accordance with this proposed role in cancer cell invasion and metastasis, we find that ectopic expression of P-Rex1 in an immortalised human fibroblast cell line is sufficient to drive multiple migratory and invasive phenotypes. The invasive phenotype is greatly enhanced by the presence of a gradient of serum or platelet-derived growth factor, and is dependent upon the expression of functional PDGF receptor β. Consistently, the invasiveness of WM852 melanoma cells, which endogenously express P-Rex1 and PDGFRβ, is opposed by siRNA of either of these proteins. Furthermore, the current model of P-Rex1 activation is advanced through demonstration of P-Rex1 and PDGFRβ as components of the same macromolecular complex. These data suggest that P-Rex1 has an influence on physiological migratory processes, such as invasion of cancer cells, both through effects upon classical Rac1-driven motility and a novel association with RTK signalling complexes

Individual-environment interactions in swimming: The smallest unit for analysing the emergence of coordination dynamics in performance?

Displacement in competitive swimming is highly dependent on fluid characteristics, since athletes use these properties to propel themselves. It is essential for sport scientists and practitioners to clearly identify the interactions that emerge between each individual swimmer and properties of an aquatic environment. Traditionally, the two protagonists in these interactions have been studied separately. Determining the impact of each swimmer’s movements on fluid flow, and vice versa, is a major challenge. Classic biomechanical research approaches have focused on swimmers’ actions, decomposing stroke characteristics for analysis, without exploring perturbations to fluid flows. Conversely, fluid mechanics research has sought to record fluid behaviours, isolated from the constraints of competitive swimming environments (e.g. analyses in two-dimensions, fluid flows passively studied on mannequins or robot effectors). With improvements in technology, however, recent investigations have focused on the emergent circular couplings between swimmers’ movements and fluid dynamics. Here, we provide insights into concepts and tools that can explain these on-going dynamical interactions in competitive swimming within the theoretical framework of ecological dynamics

Pleosporales

One hundred and five generic types of Pleosporales are described and illustrated. A brief introduction and detailed history with short notes on morphology, molecular phylogeny as well as a general conclusion of each genus are provided. For those genera where the type or a representative specimen is unavailable, a brief note is given. Altogether 174 genera of Pleosporales are treated. Phaeotrichaceae as well as Kriegeriella, Zeuctomorpha and Muroia are excluded from Pleosporales. Based on the multigene phylogenetic analysis, the suborder Massarineae is emended to accommodate five families, viz. Lentitheciaceae, Massarinaceae, Montagnulaceae, Morosphaeriaceae and Trematosphaeriaceae

A snapshot of the organization and provision of primary care in Turkey

Contains fulltext : 96599.pdf (publisher's version ) (Open Access)BACKGROUND: This WHO study aimed to support Turkey in its efforts to strengthen the primary care (PC) system by implementing the WHO Primary Care Evaluation Tool (PCET). This article provides an overview of the organization and provision of primary care in Turkey. METHODS: The WHO Primary Care Evaluation Tool was implemented in two provinces (Bolu and Eskisehir) in Turkey in 2007/08. The Tool consists of three parts: a national questionnaire concerning the organisation and financing of primary care; a questionnaire for family doctors; and a questionnaire for patients who visit a family health centre. RESULTS: Primary care has just recently become an official health policy priority with the introduction of a family medicine scheme. Although the supply of family doctors (FDs) has improved, they are geographically uneven distributed, and nationwide shortages of primary care staff remain. Coordination of care could be improved and quality control mechanisms were lacking. However, patients were very satisfied with the treatment by FDs. CONCLUSIONS: The study provides an overview of the current state of PC in Turkey for two provinces with newly introduced family medicine, by using a structured approach to evaluate the essential functions of PC, including governance, financing, resource generation, as well as the characteristics of a "good" service delivery system (as being accessible, comprehensive, coordinated and continuous)