Estrogen- and Progesterone (P4)-Mediated Epigenetic Modifications of Endometrial Stromal Cells (EnSCs) and/or Mesenchymal Stem/Stromal Cells (MSCs) in the Etiopathogenesis of Endometriosis

Endometriosis is a common chronic inflammatory condition in which endometrial tissue appears outside the uterine cavity. Because ectopic endometriosis cells express both estrogen and progesterone (P4) receptors, they grow and undergo cyclic proliferation and breakdown similar to the endometrium. This debilitating gynecological disease affects up to 15% of reproductive aged women. Despite many years of research, the etiopathogenesis of endometrial lesions remains unclear. Retrograde transport of the viable menstrual endometrial cells with retained ability for attachment within the pelvic cavity, proliferation, differentiation and subsequent invasion into the surrounding tissue constitutes the rationale for widely accepted implantation theory. Accordingly, the most abundant cells in the endometrium are endometrial stromal cells (EnSCs). These cells constitute a particular population with clonogenic activity that resembles properties of mesenchymal stem/stromal cells (MSCs). Thus, a significant role of stem cell-based dysfunction in formation of the initial endometrial lesions is suspected. There is increasing evidence that the role of epigenetic mechanisms and processes in endometriosis have been underestimated. The importance of excess estrogen exposure and P4 resistance in epigenetic homeostasis failure in the endometrial/endometriotic tissue are crucial. Epigenetic alterations regarding transcription factors of estrogen and P4 signaling pathways in MSCs are robust in endometriotic tissue. Thus, perspectives for the future may include MSCs and EnSCs as the targets of epigenetic therapies in the prevention and treatment of endometriosis. Here, we reviewed the current known changes in the epigenetic background of EnSCs and MSCs due to estrogen/P4 imbalances in the context of etiopathogenesis of endometriosis

Phenotypic Heterogeneity in Dementia: A Challenge for Epidemiology and Biomarker Studies

Dementia can result from a number of distinct diseases with differing etiology and pathophysiology. Even within the same disease, there is considerable phenotypic heterogeneity with varying symptoms and disease trajectories. Dementia diagnosis is thus very complex, time-consuming, and expensive and can only be made definitively post-mortem with histopathological confirmation. These inherent difficulties combined with the overlap of some symptoms and even neuropathological features, present a challenging problem for research in the field. This has likely hampered progress in epidemiological studies of risk factors and preventative interventions, as well as genetic and biomarker research. Resource limitations in large epidemiologically studies mean that limited diagnostic criteria are often used, which can result in phenotypically heterogeneous disease states being grouped together, potentially resulting in misclassification bias. When biomarkers are identified for etiologically heterogeneous diseases, they will have low specificity for any utility in clinical practice, even if their sensitivity is high. We highlight several challenges in in the field which must be addressed for the success of future genetic and biomarker studies, and may be key to the development of the most effective treatments. As a step toward achieving this goal, defining the dementia as a biological construct based on the presence of specific pathological features, rather than clinical symptoms, will enable more precise predictive models. It has the potential to lead to the discovery of novel genetic variants, as well as the identification of individuals at heightened risk of the disease, even prior to the appearance of clinical symptoms

The current status of blood epigenetic biomarkers for dementia

Dementia is an overarching term which describes a group of symptoms that result in long-term decline in cognitive functioning that is significant enough to affect daily function. It is caused by a number of different diseases, the most common of which is Alzheimer’s disease. Currently, there are no definitive biomarkers for preclinical or diagnostic use, or which differentiate between underlying disease types. The purpose of this review is to highlight several important areas of research on blood-based biomarkers of dementia, with a specific focus on epigenetic biomarkers. A systematic search of the literature identified 77 studies that compared blood DNA methylation between individuals with dementia and controls and 45 studies that measured microRNA. Very few studies were identified that focused on histone modifications. There were many promising findings from studies in the field of blood-based epigenetic biomarkers of dementia, however, a lack of consistency in study design, technologies, and platforms used for the biomarker measurement, as well as statistical analysis methods, have hampered progress. To date, there are very few findings that have been independently replicated across more than one study, indicating a preponderance of false-positive findings and the field has likely been plagued by positive publication bias. Here, we highlight and discuss several of the limitations of existing studies and provide recommendations for how these could be overcome in future research. A robust framework should be followed to enable development of the most valid and reproducible biomarkers with the strongest clinical utility. Defining a series of biomarkers that may be complimentary to each other could permit a stronger multifactorial biomarker to be developed that would allow for not only accurate dementia diagnosis but preclinical detection.</p

Experiences of adults with adult-onset type 1 diabetes: a cross-sectional study

Background Type 1 diabetes (T1D) is a chronic, autoimmune disease where the pancreas does not produce enough insulin. T1D requires ongoing management across the lifespan through insulin regulation, monitoring of blood glucose levels, and adherence to strict diet and exercise plans. The most recent National Diabetes Services Scheme Australian Diabetes Map indicates that 129 210 Australians currently have T1D. Traditionally considered a childhood disease, more than half of all T1D diagnoses actually occur in adults aged &gt;20 years. The aim of this study was to examine the experiences of individuals living with adult-onset T1D in relation to their diagnosis experience, access to health care, and post-diagnostic wellbeing. Methods An exploratory, cross-sectional study was undertaken. Participants completed an online survey delivered via Qualtrics detailing their experiences with adult-onset T1D. The survey contained four domains: (1) demographic information; (2) diagnosis experience; (3) access to care; and (4) post-diagnostic wellbeing, including the Hospital Anxiety and Depression Scale (HADS); and the Diabetes Distress Scale (T1-DDS). Data analysis was conducted using STATA SE (v16). Descriptive statistics (means, counts) were used to describe continuous data, and frequencies and odds ratios were used to describe categorical data. Results One hundred and twenty adults (mean age 49 years; 78% female) with adult-onset T1D (mean age at diagnosis 37 years) completed the survey. The most common symptoms prior to diagnosis were excess thirst, fatigue, frequent urination, and unintended weight loss. Half (50%) the sample received their T1D diagnosis from a general practitioner (GP). Several participants reported being misdiagnosed by their GP initially, representing an unadjusted odds ratio of 3.1 (95% CI 1.5, 6.2). Nearly half of all participants presented with anxiety (mean 7 (s.d. 4)) on the HADS, and most reported moderate levels of diabetes-related distress according to the T1-DDS. Conclusions These findings provide a starting point to understanding the experiences of adults living with adult-onset T1D and can be used to raise awareness of their challenges and needs. These exploratory findings can also be used to inform a larger, population-based study.</jats:p

Phenotypic Heterogeneity in Dementia: A Challenge for Epidemiology and Biomarker Studies

Dementia can result from a number of distinct diseases with differing etiology and pathophysiology. Even within the same disease, there is considerable phenotypic heterogeneity with varying symptoms and disease trajectories. Dementia diagnosis is thus very complex, time-consuming, and expensive and can only be made definitively post-mortem with histopathological confirmation. These inherent difficulties combined with the overlap of some symptoms and even neuropathological features, present a challenging problem for research in the field. This has likely hampered progress in epidemiological studies of risk factors and preventative interventions, as well as genetic and biomarker research. Resource limitations in large epidemiologically studies mean that limited diagnostic criteria are often used, which can result in phenotypically heterogeneous disease states being grouped together, potentially resulting in misclassification bias. When biomarkers are identified for etiologically heterogeneous diseases, they will have low specificity for any utility in clinical practice, even if their sensitivity is high. We highlight several challenges in in the field which must be addressed for the success of future genetic and biomarker studies, and may be key to the development of the most effective treatments. As a step toward achieving this goal, defining the dementia as a biological construct based on the presence of specific pathological features, rather than clinical symptoms, will enable more precise predictive models. It has the potential to lead to the discovery of novel genetic variants, as well as the identification of individuals at heightened risk of the disease, even prior to the appearance of clinical symptoms

Alcohol in human milk

This chapter overviews current scientific evidence on the impact of maternal alcohol consumption on human milk composition and breastfeeding, including observational, experimental, and animal studies in the field. Specifically, the chapter includes four sections summarizing: (1) factors that influence the variability of alcohol in human milk; (2) current recommendations on the collection, storage, and management of human milk with regard to alcohol use; (3) methodological and analytical approaches, challenges, and recommendations; and (4) research gaps and recommendations for future research in the field. Taken together, this review highlights an emerging body of evidence on maternal alcohol consumption and its impact on human milk composition and processing. Moreover, significant knowledge gaps are identified across all areas reviewed, underscoring important directions for future research in the field

Public involvement in global genomics research:A scoping review

Public involvement in research occurs when the public, patients, or research participants are actively contributing to the research process. Public involvement has been acknowledged as a key priority for prominent human genomics research initiatives in many different countries. However, to date, there has been no detailed analysis or review of the features, methods, and impacts of public involvement occurring in human genomics research projects worldwide. Here, we review the reported public involvement in 96 human genomics projects (initiatives), based on a database of initiatives hosted by the Global Alliance for Genomics and Health, according to information reported on public domain websites. To conduct the scoping review, we applied a structured categorization of criteria to all information extracted from the search. We found that only a third of all initiatives reported public involvement in any capacity (32/96, 33%). In those reporting public involvement, we found considerable variation in both the methods and tasks of involvement. Some noteworthy initiatives reported diverse and comprehensive ways of involving the public, occurring through different stages of the research project cycle. Three notable initiatives reported a total of eight distinct impacts as a result of involving people. Our findings suggest there would be intrinsic value in having more public involvement occur in human genomics research worldwide. We also suggest that more systematic ways of reporting and evaluating involvement would be highly beneficial, to help develop best practices