Fetal Epigenetic Reprogramming: Evaluating the Role of Exposure to Maternal Dietary Metabolites and Bisphenols

The Developmental Origins of Health and Disease (DOHaD) paradigm correlates a suboptimal intrauterine environment to increased risk of chronic disease. This association is well accepted, and recent work indicates that environmentally induced changes in cellular function and disease etiology are mediated by changes in the epigenetic profile. For the purpose of this dissertation, epigenetics is defined as the study of mitotically and/or meiotically heritable changes in gene expression that cannot be explained by changes in DNA sequence. While we are beginning to understand the outcomes associated with prenatal exposure to components like the maternal diet and bisphenol-A (BPA), few studies in humans assess the epigenetic impact of these exposures. In order to accurately discern the association between maternal exposure and epigenetic reprogramming, studies are needed that evaluate prenatal exposure to both bisphenols and maternal diet during early pregnancy. Additionally, more research is needed that establishes epigenetic signatures of exposure in peripheral tissues. We utilized the Michigan Mother-Infant Pairs (MMIP) cohort to assess (Aim 1) the association of prenatal exposure to bisphenols BPA, BPF, and BPS and infant cord blood leukocyte DNA methylation, (Aim 2) maternal one-carbon metabolites across pregnancy and in association with DNA methylation in infant cord blood leukocytes, (Aim 3a) DNA methylation at candidate genes across three tissue types and their association with bisphenol exposure, and (Aim 3b) the association between prenatal bisphenol exposure and placental DNA methylation. Cutting edge techniques of microarray technology to profile DNA methylation at >850,000 CpG sites in both infant cord blood and placenta, untargeted metabolomics, and pyrosequencing were combined to answer our research questions. Aim 1 results suggest that prenatal exposure to BPA, as measured in maternal urine between 8-14 weeks of gestation, was significantly associated with differential DNA methylation at 38 CpG sites and three differentially methylated regions. Gene-set analysis of BPA-associated CpG sites revealed enrichment for pathways associated with the nervous system, immune response, and neuroinflammation. Aim 2 results suggest that maternal third trimester and cord blood one-carbon metabolite S-adenosylhomocysteine (SAH) were significantly correlated with a shift in the global distribution of DNA methylation in infant cord blood leukocytes. This aim also provides evidence of patterns of one-carbon metabolites within time points and across pregnancy. Aim 3a results suggest that candidate gene DNA methylation and tissue-specific associations with prenatal bisphenol exposure do significantly differ at some but not all genes tested across cord blood, cord tissue, and placenta from the same individuals. For example, mixed effect regression revealed that placental tissue DNA methylation was significantly associated with bisphenol exposure at three out of four genes, as compared to one in cord blood and none in cord tissue. These data may inform selection of surrogate tissues for environmental epigenetic studies. Lastly, Aim 3b exploratory analysis of epigenome-wide placental DNA methylation suggests prenatal exposure to bisphenols may be associated with alternations in pathways related to inflammation, vascularization, and preeclampsia. This dissertation contributes to the burgeoning field of epigenomics and helps to establish a foundation in our understanding of maternal exposures and their influences on epigenetic programming. Advances in epigenome-wide association studies will ultimately enable researchers, clinicians, and policymakers to target risk factors (e.g. environmental and nutritional exposures that perturb the methylome and downstream birth outcomes) and to better understand a portion of the elements underlying the developmental origins of health and disease.PHDNutritional SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/166148/1/cmccab_1.pd

Evaluation of the 'Connecting Residents in Scotland's Care Homes' Programme

This report details the findings from the ‘Connecting Residents in Scotland’s Care Homes’ (hereafter CRSCH) programme evaluation. The evaluation was commissioned by the Scottish Government Technology Enabled Care programme in conjunction with the Digital Health and Care Innovation Centre (DHI). The project looked to evaluate the programme from the perspectives of all stakeholders, including residents, care staff, managers, family and friends of residents, and policymakers. Our goal was to find how far the programme is meeting its goals, the issues influencing its effectiveness, and the individual and organisational factors that will influence its continued scale up and sustainability over the longer term. The evaluation was conducted between December 2021 and July 2022 by a research team from the Faculty of Social Sciences and the Stirling Management School at the University of Stirling

Executive Summary: Evaluation of the ‘Connecting Residents in Scotland’s Care Homes’ Programme

This report details the findings from the ‘Connecting Residents in Scotland’s Care Homes’ (hereafter CRSCH) programme evaluation. The evaluation was commissioned by the Scottish Government Technology Enabled Care programme in conjunction with the Digital Health and Care Innovation Centre (DHI). The project sought to evaluate the programme from the perspectives of all stakeholders, including residents, care staff, managers, family and friends of residents, and policymakers. The evaluation goal was to identify how far the programme is meeting its objectives, the issues influencing its effectiveness and the individual and organisational factors that will influence its continued scale up and sustainability over the longer term

Towards an Evaluation Framework for Inclusive Technological Innovation in Social and Health Care Services

With the COVID-19 pandemic came an influx of digital technologies introduced into the care home sector. Many care homes were not ready for digital changes, and subsequently, the inclusivity of these innovations was variable. We develop a holistic evaluation framework to assess the inclusivity of service innovations, including the well-being of care home residents and employees. We adopt a mixed methods approach using the ‘non-adoption, abandonment, and challenges to scale-up, spread, and sustainability - complexity assessment toolkit’ (NASSS-CAT) to evaluate the introduction of tablet computers into care homes across Scotland and assess the inclusivity of the innovation. The paper offers a theoretical synthesis by indicating how the seven dimensions of the NASSS-CAT can evaluate the six stages of the ladder of inclusive innovation. Results specify how the care home sector could be more inclusive of its residents and staff by co-creating innovation, developing staff training, and supporting the well-being/activities coordinators

Towards an Evaluation Framework for Inclusive Technological Innovation in Social and Health Care Services

With the COVID-19 pandemic came an influx of digital technologies introduced into the care home sector. Many care homes were not ready for digital changes, and subsequently, the inclusivity of these innovations was variable. We develop a holistic evaluation framework to assess the inclusivity of service innovations, including the well-being of care home residents and employees. We adopt a mixed methods approach using the ‘non-adoption, abandonment, and challenges to scale-up, spread, and sustainability - complexity assessment toolkit’ (NASSS-CAT) to evaluate the introduction of tablet computers into care homes across Scotland and assess the inclusivity of the innovation. The paper offers a theoretical synthesis by indicating how the seven dimensions of the NASSS-CAT can evaluate the six stages of the ladder of inclusive innovation. Results specify how the care home sector could be more inclusive of its residents and staff by co-creating innovation, developing staff training, and supporting the well-being/activities coordinators

Effectiveness of appropriately trained nurses in preoperative assessment: randomised controlled equivalence/non-inferiority trial

Objective To determine whether preoperative assessments carried out by appropriately trained nurses are inferior in quality to those carried out by preregistration house officers. Design Randomised controlled equivalence/non-inferiority trial. Setting Four NHS hospitals in three trusts. Three of the four were teaching hospitals. Participants All patients attending for assessment before general anaesthesia for general, vascular, urological, or breast surgery between April 1998 and March 1999. Intervention Assessment by one of three appropriately trained nurses or by one of several preregistration house officers. Main outcome measures History taken, physical examination, and investigations ordered. Measures evaluated by a specialist registrar in anaesthetics and placed in four categories: correct, overassessment, underassessment not affecting management, and underassessment possibly affecting management (primary outcome). Results 1907 patients were randomised, and 1874 completed the study; 926 were assessed by house officers and 948 by nurses. Overall 121/948 (13%) assessments carried out by nurses were judged to have possibly affected management compared with 138/926 (15%) of those performed by house officers. Nurses were judged to be non-inferior to house officers in assessment, although there was variation among them in terms of the quality of history taking. The house officers ordered considerably more unnecessary tests than the nurses (218/926 (24%) v 129/948 (14%). Conclusions There is no reason to inhibit the development of nurse led preoperative assessment provided that the nurses involved receive adequate training. However, house officers will continue to require experience in preoperative assessment

The Ursinus Weekly, October 1, 1956

Fall Y retreat to be held at Fernbrook, Oct. 12-14 • Men\u27s council has opening session • Two new teachers join UC faculty • Deltas, Phi Psi give opening social affair • Pre-med society to have meeting on Oct. 9 • Class of 1960 arrives on campus • UC music groups plan Fall program • Curtain Club makes plans for frosh reception • APO invites interested students to first meeting • Sophs after frosh as customs begin • Philadelphia Orchestra releases schedule • Chemical society to hold meeting Oct. 8 • Forum, Oct. 10, to feature debate on candidates • WSGA to discuss two frosh affairs • Editorial: Das Wiedersehen • Senior and frosh: A comparison • How\u27s that, again? • Alpha Sig holds banquet • It went that a way • Ursinus Chess Club to hold first meeting Tuesday • Book review: Two flights by Lindbergh • Confident Bruin booters await opener with Drew U., Oct. 10th • Belles boast vets; Open with G\u27burg • Thirteen veterans return; Bruins upset in Susquehanna opener 26-13 • Art museum opens porcelain exhibithttps://digitalcommons.ursinus.edu/weekly/1411/thumbnail.jp

Reduction in Recurrent Cardiovascular Events with Prasugrel Compared with Clopidogrel in Patients with Acute Coronary Syndromes from the TRITON-TIMI 38 Trial

Aims: In the TRITON-TIMI 38 trial, greater platelet inhibition with prasugrel reduced the first occurrence of the primary endpoint (cardiovascular death, MI, or stroke) compared with clopidogrel in patients with an acute coronary syndrome (ACS) undergoing planned percutaneous coronary intervention. We hypothesized that prasugrel would reduce not only first events but also recurrent primary endpoint events and therefore total events compared with clopidogrel. Methods and results: Poisson regression analysis was performed to compare the number of occurrences of the primary endpoint between prasugrel and clopidogrel in TRITON-TIMI 38. Landmark analytic methods were used to evaluate the risk of a recurrent primary endpoint event following an initial non-fatal endpoint event. Among patients with an initial non-fatal event, second events were significantly reduced with prasugrel compared to clopidogrel (10.8 vs. 15.4%, HR 0.65, 95% CI 0.46–0.92; P = 0.016), as was CV death following the non-fatal event (3.7 vs. 7.1%, HR 0.46, 95% CI 0.25–0.82; P = 0.008). Overall there was a reduction of 195 total primary efficacy events with prasugrel vs. clopidogrel (rate ratio 0.79, 95% CI 0.71–0.87; P < 0.001). Recurrent bleeding events occurred infrequently (TIMI major non-CABG bleeds: four with prasugrel and two with clopidogrel). Study drug discontinuation was frequent following the initial major bleeding event (42% of patients discontinued study drug). Conclusion: While standard statistical analytic techniques for clinical trials censor patients who experience a component of the primary composite endpoint, total cardiovascular events remain important to both patients and clinicians. Prasugrel, a more potent anti-platelet agent, reduced both first and subsequent cardiovascular events compared with clopidogrel in patients with ACS

The Ursinus Weekly, March 4, 1957

Forum on student government scheduled for 8:00 tonight • March 15 date for annual show by students, faculty • Girls to discuss May Day on Wed. • Motion pictures viewed by Chemical Society • Chi Alpha schedules talk on integration • Curtain Club presents The Valiant, Feb. 26 • UC grad completes basic • Mary Jo Turtzo to represent UC in Glamour contest • Cub & Key Society requests outlines from junior men • 1957 Campus Chest fund drive • Annual drive begins today, closes on Friday, March 15 • YM-YW to sponsor music seminar; Begins Wednesday • YM-YW sponsor events for frosh • Local Rotarians set up scholarship to Ursinus • Frosh to present dance, The Golden nugget, Sat. • US foreign policy to be IRC program tonight • Editorial: Life for our organizations; It goes without saying • Letters to the editor • Obituary for a timid intellectual • Play review: The Valiant • He who hesitates • Ursinus five loses to Drexel, PMC; End with second worst slate, 0-16 • Belles top E. Stroudsburg; Win over William & Mary on weekend trip south • Padula emerges 4-year M. Atlantic champ; Wins second outstanding athlete award • Matmen gain first place tie with win over Drexel, 19-13 • Inside report on winless Bruinshttps://digitalcommons.ursinus.edu/weekly/1423/thumbnail.jp

The Lantern Vol. 27, No. 1, December 1958

• Thoughts • The Fifth Year • Grouse Shooting • Light • On Selfishness • A Christmas Prayer • Modern Magnificat • Pauses • Termination • Cynthilia • My Petticoat Princess • ?? • Stormhttps://digitalcommons.ursinus.edu/lantern/1076/thumbnail.jp