Reproductive and developmental effects of phthalate diesters in females.

Phthalate diesters, widely used in flexible plastics and consumer products, have become prevalent contaminants in the environment. Human exposure is ubiquitous and higher phthalate metabolite concentrations documented in patients using medications with phthalate-containing slow release capsules raises concerns for potential health effects. Furthermore, animal studies suggest that phthalate exposure can modulate circulating hormone concentrations and thus may be able to adversely affect reproductive physiology and the development of estrogen sensitive target tissues. Therefore, we conducted a systematic review of the epidemiological and experimental animal literature examining the relationship between phthalate exposure and adverse female reproductive health outcomes. The epidemiological literature is sparse for most outcomes studied and plagued by small sample size, methodological weaknesses, and thus fails to support a conclusion of an adverse effect of phthalate exposure. Despite a paucity of experimental animal studies for several phthalates, we conclude that there is sufficient evidence to suggest that phthalates are reproductive toxicants. However, we note that the concentrations needed to induce adverse health effects are high compared to the concentrations measured in contemporary human biomonitoring studies. We propose that the current patchwork of studies, potential for additive effects and evidence of adverse effects of phthalate exposure in subsequent generations and at lower concentrations than in the parental generation support the need for further study

Yosemite Sam and Bugs Bunny

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The Link between Environmental Toxicant Exposure and Endometriosis Re-Examined

Endometriosis is widely acknowledged to be an estrogen dependent disease or unknown etiology. Recognition that environmental toxicants can bind with and activate the estrogen receptor, dysregulate steroid metabolism and, in some cases, act as anti-androgenic substances (phthalate esters) has led to proposal that exposure to environmental toxicants are associated with increased risk of endometriosis. Since our last review of the subject in 2008, the literature has expanded with several epidemiological and biomonitoring studies suggesting a potential association, whereas others have been unable to demonstrate a link between exposure and enhanced risk. Therefore, we carried out a systematic review and critical appraisal of the literature published over the past decade (2009–2019). The majority of studies found dealt with exposure to polychlorinated biphenyls (PCBs), dioxins, dioxin-like and non-dioxin-like compounds, bisphenol A and phthalate esters. Several studies suggest a potential association between exposure to environmental toxicants; however, important weaknesses in study design, methodology, and analysis together with many contradictory studies weaken confidence in these associations. Consequently, we conclude that despite a growing literature, evidence for an association between exposure to environmental toxicants and risk of endometriosis remains weak

Phytoestrogens in Human Pregnancy

Background. The hormonal milieu associated with pregnancy has become a focus of interest owing to potential links with the developmental origins of health and disease. Phytoestrogens are hormonally active plant-derived chemicals that may have an impact on human reproductive processes. However, developmental exposure to phytoestrogens has not been well characterized and thus our objective was to quantify phytoestrogen exposure during pregnancy and lactation. Methods. Women in the second trimester of pregnancy entered the study during counseling for prenatal genetic information. Women who had an indication for a genetic amniocentesis on the basis of late maternal age were approached for inclusion. They completed an environmental questionnaire; a sample of amniotic fluid was collected for karyotype, blood was collected from women during pregnancy and at birth, from the umbilical cord and breast milk. Samples were tested for the presence of daidzein and genistein by GC Mass Spectroscopy. Findings. Phytoestrogens are commonly found in pregnant women's serum and amniotic fluid during pregnancy. There is a sex difference in the concentrations with higher levels in amniotic fluid containing female fetuses. This difference was not present in maternal serum. Soy ingestion increases amniotic fluid phytoestrogen concentrations in female and male fetuses. The presence and concentrations of phytoestrogens did not differ in relation to common pregnancy complications or preexisting infertility

microRNA and Overcoming the Challenges of Their Use in the Diagnosis of Endometriosis

Endometriosis is a common estrogen dependent and inflammatory disease affecting approximately 176 million women worldwide. Currently, the time between onset of symptoms and a definitive diagnosis has been reported by several international studies to range from 6 to 12 years. Presently, laparoscopic surgery followed by histopathological confirmation of lesions remains the gold standard for diagnosis. In part because of cost and invasiveness, current trends favor reduced laparoscopic surgeries in preference of the non-surgical diagnosis of endometriosis. However, the search for a clinical marker or markers of endometriosis that provide equal or similar sensitivity and specificity to laparoscopy has remained elusive. Thus, the search for a diagnostic test for the diagnosis of endometriosis continues to be a high priority research and clinical issue. Recent studies have reported favorable results with microRNA; however, lack of replication and absence of validation suggest that circulating miRNA may not be reliable for clinical use. Use of different screening platforms together with divergent methods may account for some of the lack or reproducibility in the literature. Herein we critically assess the recent literature and explore sources for discrepant findings. We suggest that prospective studies using validated reference miRNA to normalize results together with improved study design may yet reveal a suitable diagnostic marker or panel of markers for the diagnosis of endometriosis

Care Works: Come Home for Care

Essential to executing the mission and vision of an academic medical center (AMC) is attracting and retaining the highest quality employees. As demonstrated by VCU’s commitment to the Great Place Initiative, the University has recognized that employees in today’s highly competitive environment demand competitive salary and benefit packages. Research has shown that access to high quality, on-site healthcare services provides significant benefits to both employees and employers, such as increased productivity and reduced wellness costs[1]. Yet, a query of de-identified patient records indicated that only a small percentage of VCU employees (~18%) utilized the health services provided by VCU Health System in 2016. VCU’s peer-institutions, other distinguished AMCs, and industry employers have implemented a variety of programs such as concierge services, expedited appointments, on-campus clinics, and lower copays to remain competitive and responsive to their employees. In light of the depth of these programs, Team CareWorks completed a comparative review of health and wellness related employee-specific benefits to determine how VCU might enhance its benefits through initiatives such as on-site medical clinics, prioritized appointments, telehealth, and on-site pharmacies. Informed by the comparative analysis, Team CareWorks will provide recommendations that VCU can use to: capitalize on the integrated relationship with VCU Health to enrich the health and wellness of its outstanding assets (the employees); and provide enhanced benefits to employees by making VCU Health more easily accessible and more appealing as a Medical Home. [1]Berry, Leonard, Ann M. Mirabito, & William B. Baun. “What\u27s the Hard Return on Employee Wellness Programs?” (2010). Harvard Business Review, December 2010.. Available at SSRN: https://ssrn.com/abstract=206487

454-Pyrosequencing: A Molecular Battiscope for Freshwater Viral Ecology

Viruses, the most abundant biological entities on the planet, are capable of infecting organisms from all three branches of life, although the majority infect bacteria where the greatest degree of cellular diversity lies. However, the characterization and assessment of viral diversity in natural environments is only beginning to become a possibility. Through the development of a novel technique for the harvest of viral DNA and the application of 454 pyrosequencing, a snapshot of the diversity of the DNA viruses harvested from a standing pond on a cattle farm has been obtained. A high abundance of viral genotypes (785) were present within the virome. The absolute numbers of lambdoid and Shiga toxin (Stx) encoding phages detected suggested that the depth of sequencing had enabled recovery of only ca. 8% of the total virus population, numbers that agreed within less than an order of magnitude with predictions made by rarefaction analysis. The most abundant viral genotypes in the pond were bacteriophages (93.7%). The predominant viral genotypes infecting higher life forms found in association with the farm were pathogens that cause disease in cattle and humans, e.g. members of the Herpesviridae. The techniques and analysis described here provide a fresh approach to the monitoring of viral populations in the aquatic environment, with the potential to become integral to the development of risk analysis tools for monitoring the dissemination of viral agents of animal, plant and human diseases

Current endometriosis care and opportunities for improvement

Endometriosis is a chronic disease associated with debilitating pain that affects many people assigned female at birth, from menarche through menopause, not just causing pain and infertility but also negatively impacting quality of life, participation in daily activities, productivity, and income. It is associated with increased incidence of obstetric and neonatal complications, anxiety, other chronic diseases, and substantial healthcare costs. Despite the profound negative impact of endometriosis on quality of life, current treatment options remain suboptimal and many patients express dissatisfaction with current care. The prevailing acute-care, single-provider model in which the provider works in relative isolation and thus with limited diagnostic and therapeutic strategies readily available proves inadequate for treating endometriosis. Patients would benefit from earlier diagnosis and referral to a center capable of providing a comprehensive and multimodal management plan that utilizes a chronic care model. Often this can only be achieved through multidisciplinary teams of providers with expertise in endometriosis. The authors acknowledge that many low- and middle-income countries do not have the resources to support such centers but could still benefit from any breakthroughs in treatment they bring about. Researchers need to agree on standardized core outcome measures, relevant to patients with endometriosis and the healthcare system as a whole. Only through increased societal and healthcare provider education and recognition of endometriosis as a chronic disease can we achieve better treatment outcomes

Calculating metalation in cells reveals CobW acquires Co(II) for vitamin B12 biosynthesis while related proteins prefer Zn(II)

Protein metal-occupancy (metalation) in vivo has been elusive. To address this challenge, the available free energies of metals have recently been determined from the responses of metal sensors. Here, we use these free energy values to develop a metalation-calculator which accounts for inter-metal competition and changing metal-availabilities inside cells. We use the calculator to understand the function and mechanism of GTPase CobW, a predicted CoII-chaperone for vitamin B12. Upon binding nucleotide (GTP) and MgII, CobW assembles a high-affinity site that can obtain CoII or ZnII from the intracellular milieu. In idealised cells with sensors at the mid-points of their responses, competition within the cytosol enables CoII to outcompete ZnII for binding CobW. Thus, CoII is the cognate metal. However, after growth in different [CoII], CoII-occupancy ranges from 10 to 97% which matches CobW-dependent B12 synthesis. The calculator also reveals that related GTPases with comparable ZnII affinities to CobW, preferentially acquire ZnII due to their relatively weaker CoII affinities. The calculator is made available here for use with other proteins