Vascular architecture of the human uterine cervix, as assessed in light and scanning electron microscopy

Objectives. The aim of this study was to visualize and describe the vasculature of the human uterine cervix.Materials and Methods. The material for this study was obtained from women (age between 20 to 45 years) during autopsy. The material was collected not later than 24 hours post-mortem. This study was performed using uteri from cadavers of menstruating nulliparas (33 uteri) and menstruating multiparas (27 uteri). Collected uteri were perfused via the afferent vessels with Mercox resin (for corrosion-casting and SEM assessment) or acrylic paint solution (light microscopy assessment). The research protocol was approved by the Jagiellonian University Ethics Committee (registry KBET/121/8/2007).Results. In all cases bilateral cervical branches (1-4), originating from the uterine artery, were found. Both in the vaginal and supravaginal parts of the cervix, four distinct vascular zones were found. In the pericanalar zone ran small veins, responsible for draining the mucosal capillaries. Both in the muscular layer, as well as in the pericanalar zone, arterioles and venules passed close to each other, often adjoining.Conclusions. This study does not confirm the existence of a single “cervicovaginal” artery, but shows that the vascular supply of the cervix comes from several vessels. It also introduces the idea of two systems, responsible for draining blood from the mucosal capillaries. Neither assessment in light microscopy nor in SEM has revealed any differences between multiparas and nulliparas, as to the vascular architecture of the cervix

Stated preferences for attributes of a CYP2C19 pharmacogenetic test among the general population presented with a hypothetical acute coronary syndrome scenario

Background: Pharmacogenetic (PGx) testing identifies pharmacotherapeutic risks to permit personalized therapy. Identifying the genetic profile of patients with acute coronary syndrome (ACS) who are considered for therapy with clopidogrel (P2Y12 receptor blockers) and acetylsalicylic acid (ASA) contributes to the treatment paradigm. Patient preferences would inform a collaborative framework and by extension inform healthcare policy formulation. Purpose: To quantify stated preferences (willingness to pay) for attributes of a novel point-of-care PGx (CYP2C19) test using a discrete choice experiment (DCE) from the general public in Ontario, Canada, and to identify starting point bias of the cost attribute. Methods: A web survey was created and included a questionnaire, decision board, and a DCE. DCE choice sets include the following attributes (levels): sample collection (blood, finger prick, and cheek swab), turnaround time for results (1 hr, 3 days, and 1 week), and cost in additional insurance premiums. The presence of starting point bias (cost attribute levels of $0,$1, $5 or$0, $2,$10) in the estimation of willingness to pay (WTP) was tested. Results: Estimates for turnaround time and cost attributes were statistically significant. Coefficients related to the starting point bias were also significant. Approximately 67% of survey participants chose the PGx test compared to status quo treatment options. WTP for a 1 hr turnaround time compared to a 1-week turnaround time was $10.77 (95% CI 9.58-12.25). Conclusion: This translational study shows preference for a point of care PGx test

Bi-Directional Effect of Cholecystokinin Receptor-2 Overexpression on Stress-Triggered Fear Memory and Anxiety in the Mouse

Fear, an emotional response of animals to environmental stress/threats, plays an important role in initiating and driving adaptive response, by which the homeostasis in the body is maintained. Overwhelming/uncontrollable fear, however, represents a core symptom of anxiety disorders, and may disturb the homeostasis. Because to recall or imagine certain cue(s) of stress/threats is a compulsory inducer for the expression of anxiety, it is generally believed that the pathogenesis of anxiety is associated with higher attention (acquisition) selectively to stress or mal-enhanced fear memory, despite that the actual relationship between fear memory and anxiety is not yet really established. In this study, inducible forebrain-specific cholecystokinin receptor-2 transgenic (IF-CCKR-2 tg) mice, different stress paradigms, batteries of behavioral tests, and biochemical assays were used to evaluate how different CCKergic activities drive fear behavior and hormonal reaction in response to stresses with different intensities. We found that in IF-CCKR-2 tg mice, contextual fear was impaired following 1 trial of footshock, while overall fear behavior was enhanced following 36 trials of footshock, compared to their littermate controls. In contrast to a standard Yerkes-Dodson (inverted-U shaped) stress-fear relationship in control mice, a linearized stress-fear curve was observed in CCKR-2 tg mice following gradient stresses. Moreover, compared to 1 trial, 36 trials of footshock in these transgenic mice enhanced anxiety-like behavior in other behavioral tests, impaired spatial and recognition memories, and prolonged the activation of adrenocorticotropic hormone (ACTH) and glucocorticoids (CORT) following new acute stress. Taken together, these results indicate that stress may trigger two distinctive neurobehavioral systems, depending on both of the intensity of stress and the CCKergic tone in the brain. A “threshold theory” for this two-behavior system has been suggested

Resolving the neural circuits of anxiety

Although anxiety disorders represent a major societal problem demanding new therapeutic targets, these efforts have languished in the absence of a mechanistic understanding of this subjective emotional state. While it is impossible to know with certainty the subjective experience of a rodent, rodent models hold promise in dissecting well-conserved limbic circuits. The application of modern approaches in neuroscience has already begun to unmask the neural circuit intricacies underlying anxiety by allowing direct examination of hypotheses drawn from existing psychological concepts. This information points toward an updated conceptual model for what neural circuit perturbations could give rise to pathological anxiety and thereby provides a roadmap for future therapeutic development.National Institute of Diabetes and Digestive and Kidney Diseases (U.S.) (NIH Director’s New Innovator Award DP2-DK-102256-01)National Institute of Mental Health (U.S.) (NIH) R01-MH102441-01)JPB Foundatio