Exploiting sweet relief for preeclampsia by targeting autophagy-lysosomal machinery and proteinopathy.

The etiology of preeclampsia (PE), a severe complication of pregnancy with several clinical manifestations and a high incidence of maternal and fetal morbidity and mortality, remains unclear. This issue is a major hurdle for effective treatment strategies. We recently demonstrated that PE exhibits an Alzheimer-like etiology of impaired autophagy and proteinopathy in the placenta.

Hypertensive disorders of pregnancy and subsequent risk of Alzheimer's disease and other dementias.

Introduction: Women with hypertensive disorders of pregnancy (HDP) have an increased risk of cardiovascular disease. Whether HDP is also associated with later-life dementia has not been fully explored.

Methods: Using the Utah Population Database, we performed an 80-year retrospective cohort study of 59,668 parous women.

Clinical impact of severe acute kidney injury on post-operative and brain injury outcomes in preterm infants following surgical necrotizing enterocolitis.

Background: To evaluate post-operative outcomes and white matter injury (WMI) using brain MRI at term equivalent in neonates with and without severe acute kidney injury (AKI) following surgical necrotizing enterocolitis (NEC).

Methods: A retrospective cohort study comparing neonates with severe (Stage 2/3) other (no AKI/Stage 1) AKI using KDIGO classification with multivariable models assessing this association in the context of multiple systemic comorbidities.

Results: Of 103 neonates with surgical NEC, 60 (58%) had severe AKI.

Evaluating systemic changes to support clinical and translational health research.

In evaluation research, "programs" are often conceptualized as clearly bounded, narrow in scope, focused on specific outcomes, using a well-defined linear causal model, and hence, suitable for standard evaluation methods. The evaluation work reported here was carried out in a more challenging context, where large, complex, interwoven systems were targets for change as a means to influence a diffuse array of outcomes. Our evaluation of an NIH-funded program to improve statewide infrastructure for clinical and translational health research ("Advance-CTR") used qualitative data provided by investigators who used the program's services, were funded awardees, or were members of an internal advisory committee (leadership representatives from partnering institutions).

Protein Network Analysis of Whole Exome Sequencing of Severe Preeclampsia.

Preeclampsia is a hypertensive disorder of pregnancy, which complicates up to 15% of US deliveries. It is an idiopathic disorder associated with several different phenotypes. We sought to determine if the genetic architecture of preeclampsia can be described by clusters of patients with variants in genes in shared protein interaction networks.

A core of differentially methylated CpG loci in gMDSCs isolated from neonatal and adult sources.

Background: Myeloid-derived suppressor cells (MDSCs), which include monocytic (mMDSCs) and granulocytic (gMDSCs) cells, are an immunosuppressive, heterogeneous population of cells upregulated in cancer and other pathologic conditions, in addition to normal conditions of stress. The origin of MDSCs is debated, and the regulatory pattern responsible for gMDSC differentiation remains unknown. Since DNA methylation (DNAm) contributes to lineage differentiation, we have investigated whether it contributes to the acquisition of the gMDSC phenotype.

Protein interaction networks define the genetic architecture of preterm birth.

The likely genetic architecture of complex diseases is that subgroups of patients share variants in genes in specific networks sufficient to express a shared phenotype. We combined high throughput sequencing with advanced bioinformatic approaches to identify such subgroups of patients with variants in shared networks. We performed targeted sequencing of patients with 2 or 3 generations of preterm birth on genes, gene sets and haplotype blocks that were highly associated with preterm birth.

Effects of Pharmacologic Treatment for Neonatal Abstinence Syndrome on DNA Methylation and Neurobehavior: A Prospective Cohort Study.

Objective: To determine whether pharmacologic treatment for neonatal abstinence syndrome (NAS) is associated with changes in DNA methylation (DNAm) of the mu-opioid receptor gene (OPRM1) and improvements in neonatal neurobehavior.

Study Design: Buccal swabs were collected from 37 neonates before and after morphine treatment for NAS. Genomic DNA was extracted, and DNAm was examined at 4 cytosine-phosphate-guanine (CpG) sites within the OPRM1 gene.

NEOage clocks - epigenetic clocks to estimate post-menstrual and postnatal age in preterm infants.

Epigenetic clocks based on DNA methylation (DNAm) can accurately predict chronological age and are thought to capture biological aging. A variety of epigenetic clocks have been developed for different tissue types and age ranges, but none have focused on postnatal age prediction for preterm infants. Epigenetic estimators of biological age might be especially informative in epidemiologic studies of neonates since DNAm is highly dynamic during the neonatal period and this is a key developmental window.

Novel blood test for early biomarkers of preeclampsia and Alzheimer's disease.

A non-invasive and sensitive blood test has long been a goal for early stage disease diagnosis and treatment for Alzheimer's disease (AD) and other proteinopathy diseases. We previously reported that preeclampsia (PE), a severe pregnancy complication, is another proteinopathy disorder with impaired autophagy. We hypothesized that induced autophagy deficiency would promote accumulation of pathologic protein aggregates.

An E-Textile Respiration Sensing System for NICU Monitoring: Design and Validation.

The world is witnessing a rising number of preterm infants who are at significant risk of medical conditions. These infants require continuous care in Neonatal Intensive Care Units (NICU). Medical parameters are continuously monitored in premature infants in the NICU using a set of wired, sticky electrodes attached to the body.

Improving the quality and quantity of clinical and translational research statewide: An application of group concept mapping.

Introduction: Advance Clinical and Translational Research (Advance-CTR) serves as a central hub to support and educate clinical and translational researchers in Rhode Island. Understanding barriers to clinical research in the state is the key to setting project aims and priorities.

Methods: We implemented a Group Concept Mapping exercise to characterize the views of researchers and administrators regarding how to increase the quality and quantity of clinical and translational research in their settings.

Advance-CTR: Statewide Infrastructure to Improve Health in Rhode Island through Clinical and Translational Research.

The universities, hospitals, government agencies, and community organizations in Rhode Island (RI) are well-positioned to bridge gaps between basic and clinical science. RI's manageable size, population demographics, and organizational structure present opportunities to test and implement impactful, transformative clinical and translational research. However, the state's resources had not been optimally coordinated to develop a multi-institutional, clinical and translational research infrastructure to improve clinical practice effectiveness and impact health care in RI.

The Effects of Delayed Cord Clamping on 12-Month Brain Myelin Content and Neurodevelopment: A Randomized Controlled Trial.

Objective: This study aimed to determine if delayed cord clamping (DCC) affected brain myelin water volume fraction (VFm) and neurodevelopment in term infants.

Study Design: This was a single-blinded randomized controlled trial of healthy pregnant women with term singleton fetuses randomized at birth to either immediate cord clamping (ICC) (≤ 20 seconds) or DCC (≥ 5 minutes). Follow-up at 12 months of age consisted of blood work for serum iron indices and lead levels, a nonsedated magnetic resonance imaging (MRI), followed within the week by neurodevelopmental testing.

Proteinarium: Multi-sample protein-protein interaction analysis and visualization tool.

We posit the likely architecture of complex diseases is that subgroups of patients share variants in genes in specific networks which are sufficient to give rise to a shared phenotype. We developed Proteinarium, a multi-sample protein-protein interaction (PPI) tool, to identify clusters of patients with shared gene networks. Proteinarium converts user defined seed genes to protein symbols and maps them onto the STRING interactome.

DNA methylation in children with prenatal methamphetamine exposure and environmental adversity.

Background: Methamphetamine (MA) use during pregnancy is a significant public health concern in the United States and affects long-term brain and behavioral development in children. We hypothesized that prenatal MA exposure would be related to greater DNA methylation of HSD11B2 and postnatal environmental stress.

Methods: The Infant Development, Environment, and Lifestyle Study (IDEAL), a longitudinal study of prenatal MA exposure enrolled mother-infant dyads in California, Hawaii, Iowa, and Oklahoma.

Placental extracellular vesicles and pre-eclampsia.

Pre-eclampsia is a hypertensive disease of pregnancy characterized by new-onset hypertension, with either proteinuria and/or organ dysfunction. Pre-eclampsia is a leading cause of maternal morbidity and mortality; however, the underlying cellular and molecular mechanisms are not well understood. There is consensus that the underlying mechanism(s) resulting in pre-eclampsia is centered around abnormal placentation, inadequate spiral-artery remodeling, and deficiency in trophoblast invasion, resulting in impaired maternal blood flow to the placenta and a release of signals and/or inflammatory mediators into maternal circulation triggering the systemic manifestations of pre-eclampsia.