Estrogen mediates inflammatory role of mast cells in endometriosis pathophysiology.

Endometriosis is an estrogen dependent, chronic inflammatory disease characterized by the growth of endometrial lining outside of the uterus. Mast cells have emerged as key players in regulating not only allergic responses but also other mechanisms such as angiogenesis, fibrosis, and pain. The influence of estrogen on mast cell function has also been recognized as a potential factor driving disease pathophysiology in number of allergic and chronic inflammatory conditions. However, precise information is lacking on the cross talk between endocrine and immune factors within the endometriotic lesions and whether that contributes to the involvement of mast cells with disease pathophysiology. In this study, we observed a significant increase in mast cell numbers within endometriotic lesions compared to matched eutopic endometrium from the same patients. Compared to eutopic endometrium, endometriotic lesions had significantly higher levels of stem cell factor (SCF), a potent growth factor critical for mast cell expansion, differentiation, and survival for tissue resident mast cells. Targeted mRNA Q-PCR array revealed that the endometriotic lesions harbour microenvironment (upregulation of CPA3, VCAM1, CCL2, CMA1, CCR1, and KITLG) that is conducive to mast cells recruitment and subsequent differentiation. To examine cross-talk of mast cells within the endometriotic lesion microenvironment, endometriotic epithelial cells (12Z) and endometrial stromal cells (hESC) incubated with mast cell-conditioned media showed significantly increased production of pro-inflammatory and chemokinetic cytokines. To further understand the impact of estrogen on mast cells in endometriosis, we induced endometriosis in C57BL/6 mice. Mature mast cells were significantly higher in peritoneal fluid of estrogen-treated mice compared to untreated mice within the sham operated groups. Mouse endometriotic lesion tissue revealed several genes (qRT-PCR) relevant in mast cell biology significantly upregulated in the estrogen treated, endometriosis-induced group compared to control endometrium. The endometriotic lesions from estrogen treated mice also had significantly higher density of Alcian blue stained mast cells compared to untreated lesions or control endometrium. Collectively, these findings suggest that endometriotic lesions provide a microenvironment necessary for recruitment and differentiation of mast cells. In turn, mast cells potentially release pro-inflammatory mediators that contribute to chronic pelvic pain and endometriosis disease progression.

Compassionate Care in the Age of Evidence-Based Practice: A Critical Discourse Analysis in the Context of Chronic Pain Care.

PURPOSE: Health professions education and practice have seen renewed calls to restore compassion to care. However, because of the ways evidence-based practice (EBP) has been implemented in health care, wherein research-based knowledge is privileged, the dominance of EBP may silence clinician and patient experience-based knowledge needed for compassionate care. This study explored what happens when the discourses of compassionate care and EBP interact in practice. METHOD: Chronic pain management in Canada was selected as the context for the study. Data collection involved compiling an archive of 458 chronic pain texts, including gray literature from 2009-2015 (non-peer-reviewed sources, e.g., guidelines), patient blog posts from 2013-2015, and transcripts of study interviews with 9 clinicians and postgraduate trainees from local pain clinics from 2015-2016. The archive was analyzed using an interpretive qualitative approach informed by critical discourse analysis. RESULTS: Four manifestations of the discourse of compassionate care were identified: curing the pain itself, returning to function, alleviating suffering, and validating the patient experience. These discourses produced particular subject positions, activities, practices, and privileged forms of knowledge. They operated in response, partnership, apology, and resistance, respectively, to the dominant discourse of EBP. These relationships were mediated by other prevalent discourses in the system: patient safety, patient-centered care, professional liability, interprofessional collaboration, and efficiency. CONCLUSIONS: Medical education efforts to foster compassion in health professionals and systems need to acknowledge the complex web of discourses-which carry with them their own expectations, material effects, and roles-and support people in navigating this web.

Binge Eating, Loss of Control over Eating, Emotional Eating, and Night Eating After Bariatric Surgery: Results from the Toronto Bari-PSYCH Cohort Study.

OBJECTIVES: We explored the severity of binge eating, loss of control over eating, emotional eating, and night eating before bariatric surgery and annually for 3 years following surgery. We also assessed the impact of post-operative eating psychopathology on weight outcomes. METHODS: Eight hundred forty-four patients participated in this prospective cohort study. Demographic factors, self-report measures of eating pathology (BES, NEQ, EES, EDE-Q), and weights (kg) were collected pre-surgery and annually for 3 years after surgery. RESULTS: The severity of problematic eating behaviors decreased after surgery and remained lower than baseline throughout follow-up. An increase was noted in binge eating scores (change in mean score ± SD = 0.85 ± 4.71; p = 0.002), emotional eating scores (2.00 ± 13.63; p = 0.033), and loss of control eating scores (1.11 ± 7.01; p < 0.001) after the first post-operative year that continued to the third post-operative year. There was also an increase in night eating scores between 2 and 3 years post-surgery (2.52 ± 8.00; p = 0.01). Higher 1-year post-operative binge eating scores were a significant predictor of lower 2-year % total weight loss (ß = - 0.39, confidence interval (CI) - 1.23, - 0.16, p = 0.012). CONCLUSIONS: The severity of problematic eating behaviors decrease after bariatric surgery, but increase significantly between the first and third post-operative years. Binge Eating Scale score at 1 year post-surgery was the only significant predictor of reduced percent total weight loss at 2 years. Additional prospective studies with adequate power are required to assess the progression of these eating pathologies beyond 3 years and their impact on weight outcomes beyond 2 years.

A Survey of Healthcare Practitioners on Myofascial Pain Criteria.

OBJECTIVES: The goal of this study was to assess agreement on signs and symptoms of myofascial pain for chiropractors, physicians, and registered massage therapists. METHODS: 337 healthcare practitioners participated in the survey. The questionnaire probed clinician agreement with the chosen signs and symptoms using a 7-point agreement scale (1 = absolutely agree, 7 = absolutely disagree). Agreement was assessed using intraclass correlation within chiropractor, physician, and registered massage therapist groups and across all groups. Descriptive statistics, including mean response values, were used to assess which signs or symptoms were most often associated with myofascial pain. RESULTS: There was poor agreement within chiropractors, physicians, and registered massage therapists on the criteria that represent myofascial pain syndrome. Physicians and massage therapists were in agreement on 4 items and disagreed on 2 items. Chiropractors were in agreement on a different set of signs and symptoms relative to physicians and registered massage therapists, and they expressed neutrality on most statements in the questionnaire. Registered massage therapists were in most agreement amongst each other as a group (intraclass correlation coefficient [ICC] = 0.80) relative to chiropractors (ICC = 0.59) and physicians (ICC = 0.51). DISCUSSION: Our results suggest that there is a lack of agreement within and between healthcare practitioner groups on the signs and symptoms that define myofascial pain syndrome. We suggest the demonstrated variability in diagnostic knowledge be remedied through the establishment and universal use of official validated criteria. Future research should focus on developing criteria specific to myofascial pain syndrome. Finally, knowledge translation strategies may be implemented to increase clinician knowledge of available criteria.

A balancing act: RNA binding protein HuR/TTP axis in endometriosis patients.

Endometriosis, a major reproductive pathology affecting 8-10% of women is characterized by chronic inflammation and immune dysfunction. Human antigen R (HuR) and Tristetraprolin (TTP) are RNA binding proteins that competitively bind to cytokines involved in inflammation including: tumor necrosis factor alpha (TNF-α), granulocyte macrophage colony stimulating factor (GM-CSF), interleukin 6 (IL-6) among others, and stabilize and destabilize them, respectively. The aim of this study was to examine RNA binding protein (RNABP) HuR/TTP axis in endometriosis patients compared to menstrual stage matched healthy fertile controls in hopes of better understanding their contribution to the pathogenesis of endometriosis. Additionally, using a targeted in vitro siRNA approach, we examined whether knock-down of TTP can play a functional role on other RNABPs that competitively bind to inflammatory targets of TTP in both endometriotic and endometrial epithelial cell lines. Our results suggest that RNABPs TTP and HuR are dysregulated in endometriotic lesions compared to matched eutopic patient samples as well endometrium from healthy controls. Silencing of TTP in endometriotic and endometrial epithelial cells revealed differential response to inflammatory cytokines and other RNABPs. Our results suggest potential involvement of HuR/TTP RNA binding protein axis in regulation of inflammation in endometriosis.

Generating level-dependent models of cervical and thoracic spinal cord injury: Exploring the interplay of neuroanatomy, physiology, and function.

The majority of spinal cord injuries (SCI) occur at the cervical level, which results in significant impairment. Neurologic level and severity of injury are primary endpoints in clinical trials; however, how level-specific damages relate to behavioural performance in cervical injury is incompletely understood. We hypothesized that ascending level of injury leads to worsening forelimb performance, and correlates with loss of neural tissue and muscle-specific neuron pools. A direct comparison of multiple models was made with injury realized at the C5, C6, C7 and T7 vertebral levels using clip compression with sham-operated controls. Animals were assessed for 10weeks post-injury with numerous (40) outcome measures, including: classic behavioural tests, CatWalk, non-invasive MRI, electrophysiology, histologic lesion morphometry, neuron counts, and motor compartment quantification, and multivariate statistics on the total dataset. Histologic staining and T1-weighted MR imaging revealed similar structural changes and distinct tissue loss with cystic cavitation across all injuries. Forelimb tests, including grip strength, F-WARP motor scale, Inclined Plane, and forelimb ladder walk, exhibited stratification between all groups and marked impairment with C5 and C6 injuries. Classic hindlimb tests including BBB, hindlimb ladder walk, bladder recovery, and mortality were not different between cervical and thoracic injuries. CatWalk multivariate gait analysis showed reciprocal and progressive changes forelimb and hindlimb function with ascending level of injury. Electrophysiology revealed poor forelimb axonal conduction in cervical C5 and C6 groups alone. The cervical enlargement (C5-T2) showed progressive ventral horn atrophy and loss of specific motor neuron populations with ascending injury. Multivariate statistics revealed a robust dataset, rank-order contribution of outcomes, and allowed prediction of injury level with single-level discrimination using forelimb performance and neuron counts. Level-dependent models were generated using clip-compression SCI, with marked and reliable differences in forelimb performance and specific neuron pool loss.