Endometriosis is a chronic, painful disease without a cure. Due largely to chronic pain, endometriosis can lead to significant physical, mental, relationship, and financial burdens. Within the conventional single provider model of care—in which the patient is primarily taken care of by her physician and complementary strategies based on psychology, nutrition, pain medicine, pelvic physical therapy, and so on may not be readily available in a coordinated manner—most women with endometriosis live with unresolved pain and the consequences of that pain. We therefore propose that there is an urgent need to search for alternative models of care. In the current paper, we discuss our experiences with an model of care in which we adopt a long-term, patient-focused, and multidisciplinary chronic care model for women with endometriosis. Our objective is to improve long-term clinical outcomes for women with endometriosis. For geographical areas and healthcare systems in which it is feasible, we propose consideration of this multidisciplinary model of care as an alternative to the single provider model and offer guidance for those considering establishment of such a program. We also initiate a conversation about which clinical outcomes pertaining to endometriosis are important and should be tracked to assess the efficacy and value of multidisciplinary and other endometriosis healthcare models.
BACKGROUND Neurotrophins of the nerve growth factor family are soluble polypeptides that are best known for their role in nerve growth, survival and differentiation in the central nervous system. A growing body of literature shows that neurotrophins and their receptors are also expressed throughout the reproductive tract. OBJECTIVE AND RATIONALE Neurotrophins are key regulatory proteins in reproductive physiology during development and throughout adult life. Of the neurotrophins, the literature describing the expression and function of brain-derived neurotrophic factor (BDNF) and its high-affinity receptor, neurotrophin receptor kinase-2 (NTRK2), has been expanding rapidly. We therefore conducted a systematic inductive qualitative review of the literature to better define the role of the BDNF in the reproductive tract. We postulate that BDNF and NTRK2 are central regulatory proteins throughout the reproductive system. SEARCH METHODS An electronic search of Medline (PubMed) and Web of Science for articles relating to BDNF and the reproductive system was carried out between January 2018 and February 2019. OUTCOMES In the ovary, BDNF expression and levels have been linked with follicle organisation during ovarian development, follicle recruitment and growth and oocyte maturation. In the endometrium, BDNF is involved in cell proliferation and neurogenesis. In contrast, literature describing the role of BDNF in other reproductive tissues is sparse and BDNF-NTRK2 signalling in the male reproductive tract has been largely overlooked. Whilst estradiol appears to be the primary regulator of BDNF expression, we also identified reports describing binding sites for glucocorticoid and myocyte enhancer factor-2, a calcium-response element through activation of an N-methyl-D-aspartate (NMDA) receptor, and aryl hydrocarbon receptor nuclear transporter protein-4 (ARNT) response elements in promoter regions of the BDNF gene. Expression is also regulated by multiple microRNAs and post-translational processing of precursor proteins and intracellular shuttling. BDNF-NTRK2 signalling is modulated through tissue specific receptor expression of either the full-length or truncated NTRK2 receptor; however, the functional importance remains to be elucidated. Dysregulation of BDNF expression and circulating concentrations have been implicated in several reproductive disorders including premature ovarian failure, endometriosis, pre-eclampsia, intra-uterine growth restriction (IUGR) and several reproductive cancers. WIDER IMPLICATIONS We conclude that BDNF and its receptors are key regulatory proteins central to gonadal development, ovarian regulation and uterine physiology, as well as embryo and placenta development. Furthermore, dysregulation of BDNF-NTRK2 in reproductive diseases suggests their potential role as candidate clinical markers of disease and potential therapeutic targets.
Currently, a blood test for the diagnosis of endometriosis, a common estrogen-dependent gynecological disease, does not exist. Recent studies suggest that circulating concentrations of brain-derived neurotrophic factor (BDNF) have potential for the diagnosis of endometriosis. However, at present, BDNF can only be measured by ELISA, which requires a clinic visit, a routine blood sample, and laboratory testing. Therefore, we developed a point-of-care device (EndoChip) for use with small blood volumes that can be collected through a finger prick. Specifically, the presented device is a polymer-based chip with a nanoporous, wrinkled gold film acting as the electrode/sensing layer, allowing for the electrochemical detection of BDNF in plasma. Increasing concentrations of BDNF (0.1-2.0 ng/mL) induced significant differences in redox current. The biosensor produces a signal readout in a matter of seconds, and is ideal for realizing multiplexing. Blood samples were collected from women ( n = 20) with chronic pelvic pain undergoing a diagnostic laparoscopy. Plasma BDNF concentrations measured by commercial ELISA were positively correlated ( r = 0.8033; p < 0.001) with results from the EndoChip. Our results demonstrate a quick and reliable method for point-of-care quantification of circulating concentrations of BDNF and a promising diagnostic tool for endometriosis.
Background Postpartum depression (PPD) is a highly prevalent mental health problem that affects parental health with implications for child health in infancy, childhood, adolescence and beyond. The primary aim of this study was to critically appraise available systematic reviews describing interventions for PPD. The secondary aim was to evaluate the methodological quality of the included systematic reviews and their conclusions. Methods An electronic database search of MEDLINE, Embase, and the Cochrane Library from 2000 to 2020 was conducted to identify systematic reviews that examined an intervention for PPD. A Measurement Tool to Assess Systematic Reviews was utilized to independently score each included systematic review which was then critically appraised to better define the most effective therapeutic options for PPD. Results Of the 842 studies identified, 83 met the a priori criteria for inclusion. Based on the systematic reviews with the highest methodological quality, we found that use of antidepressants and telemedicine were the most effective treatments for PPD. Symptoms of PPD were also improved by traditional herbal medicine and aromatherapy. Current evidence for physical exercise and cognitive behavioural therapy in treating PPD remains equivocal. A significant, but weak relationship between AMSTAR score and journal impact factor was observed (p = 0.03, r = 0.24; 95% CI, 0.02 to 0.43) whilst no relationship was found between the number of total citations (p = 0.27, r = 0.12; 95% CI, − 0.09 to 0.34), or source of funding (p = 0.19). Conclusion Overall the systematic reviews on interventions for PPD are of low-moderate quality and are not improving over time. Antidepressants and telemedicine were the most effective therapeutic interventions for PPD treatment.
Long non-coding RNA, miRNA and proteins in exosomes isolated from the serum and peritoneal fluid of women with endometriosis are differentially expressed compared to controls. Experimental evidence demonstrates that exosome content modulates migration, invasion, angiogenesis and inflammation, central processes in endometriosis. It is suggested that exosomes and their content are important regulators in the pathophysiology of endometriosis.
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