Phenylalanine transfer across the isolated perfused human placenta: an experimental and modeling investigation.

Membrane transporters are considered essential for placental amino acid transfer, but the contribution of other factors, such as blood flow and metabolism, is poorly defined. In this study we combine experimental and modeling approaches to understand the determinants of [(14)C]phenylalanine transfer across the isolated perfused human placenta. Transfer of [(14)C]phenylalanine across the isolated perfused human placenta was determined at different maternal and fetal flow rates.

Sildenafil Therapy Normalizes the Aberrant Metabolomic Profile in the Comt(-/-) Mouse Model of Preeclampsia/Fetal Growth Restriction.

Preeclampsia (PE) and fetal growth restriction (FGR) are serious complications of pregnancy, associated with greatly increased risk of maternal and perinatal morbidity and mortality. These complications are difficult to diagnose and no curative treatments are available. We hypothesized that the metabolomic signature of two models of disease, catechol-O-methyl transferase (COMT(-/-)) and endothelial nitric oxide synthase (Nos3(-/-)) knockout mice, would be significantly different from control C57BL/6J mice.

Loss-of-function mutations in TNFAIP3 leading to A20 haploinsufficiency cause an early-onset autoinflammatory disease.

Systemic autoinflammatory diseases are driven by abnormal activation of innate immunity. Herein we describe a new disease caused by high-penetrance heterozygous germline mutations in TNFAIP3, which encodes the NF-κB regulatory protein A20, in six unrelated families with early-onset systemic inflammation. The disorder resembles Behçet's disease, which is typically considered a polygenic disorder with onset in early adulthood.

Molecular diagnosis: Implications for ophthalmology.

The effort to subdivide diseases and to individualize therapies based on characteristics of the patient has been labeled precision medicine. Jameson and Longo define precision medicine as "treatments targeted to the needs of individual patients on the basis of genetic, biomarker, phenotypic or psychosocial characteristics that distinguish a given patient from other patients with similar clinical presentations" (Jameson and Longo, 2015). We illustrate how molecular diagnosis can be applied to orbital inflammatory disease to achieve the goals of precision medicine.

GRANULOMATOSIS WITH POLYANGIITIS (GPA) PRESENTING WITH FROSTED BRANCH ANGIITIS.

Purpose: To report a case of frosted branch angiitis in a patient with granulomatosis with polyangiitis.

Methods: Clinical case report. Imaging was obtained with pseudo-color scanning laser ophthalmoscope photographs, fluorescein angiography, spectral domain optical coherence tomography, and B-scan ultrasound.

The impact of a human IGF-II analog ([Leu27]IGF-II) on fetal growth in a mouse model of fetal growth restriction.

Enhancing placental insulin-like growth factor (IGF) availability appears to be an attractive strategy for improving outcomes in fetal growth restriction (FGR). Our approach was the novel use of [Leu(27)]IGF-II, a human IGF-II analog that binds the IGF-II clearance receptor IGF-IIR in fetal growth-restricted (FGR) mice. We hypothesized that the impact of [Leu(27)]IGF-II infusion in C57BL/6J (wild-type) and endothelial nitric oxide synthase knockout (eNOS(-/-); FGR) mice would be to enhance fetal growth and investigated this from mid- to late gestation; 1 mg·kg(-1)·day(-1) [Leu(27)]IGF-II was delivered via a subcutaneous miniosmotic pump from E12.

Perceived discrimination predicts increased support for political rights and life satisfaction mediated by ethnic identity: A longitudinal analysis.

Objectives: The aim of the current research is to test predictions derived from the rejection-identification model and research on collective action using cross-sectional (Study 1) and longitudinal (Study 2) methods. Specifically, an integration of these 2 literatures suggests that recognition of discrimination can have simultaneous positive relationships with well-being and engagement in collective action via the formation of a strong ingroup identity.

Method: We test these predictions in 2 studies using data from a large national probability sample of Māori (the indigenous peoples of New Zealand), collected as part of the New Zealand Attitudes and Values Study (Ns for Study 1 and 2 were 1,981 and 1,373, respectively).

Implications of Coronary Artery Calcium Testing Among Statin Candidates According to American College of Cardiology/American Heart Association Cholesterol Management Guidelines: MESA (Multi-Ethnic Study of Atherosclerosis).

Background: The American College of Cardiology (ACC)/American Heart Association (AHA) cholesterol management guidelines have significantly broadened the scope of candidates eligible for statin therapy.

Objectives: This study evaluated the implications of the absence of coronary artery calcium (CAC) in reclassifying patients from a risk stratum in which statins are recommended to one in which they are not.

Methods: MESA (Multi-Ethnic Study of Atherosclerosis) is a longitudinal study of 6,814 men and women 45 to 84 years of age without clinical atherosclerotic cardiovascular disease (ASCVD) risk at enrollment.

Antibiotic susceptibility and molecular mechanisms of macrolide resistance in streptococci isolated from adult cystic fibrosis patients.

The cystic fibrosis (CF) airways are colonized by polymicrobial communities with high bacterial load and are influenced by frequent antibiotic exposures. This community includes diverse streptococci, some of which have been directly or indirectly associated with pulmonary exacerbations. As many streptococci are naturally competent, horizontal transfer of antibiotic-resistant determinants coupled with frequent and/or chronic antibiotic exposure may contribute to high resistance rates.

Metabolic syndrome and incident peripheral artery disease - the Multi-Ethnic Study of Atherosclerosis.

Objective: We evaluated whether metabolic syndrome (MetS) is associated with an increased incidence of lower extremity peripheral artery disease (PAD) in community dwelling people free of clinical cardiovascular disease at baseline. We assessed whether higher levels of inflammatory biomarkers may mediate the association of MetS with incident PAD.

Methods: MetS was defined at baseline as the presence of three or more of the following components: elevated waist circumference, triglycerides ≥150 mg/dL, reduced high-density lipoprotein (HDL) cholesterol, blood pressure ≥130/85 mm Hg or taking blood pressure medication, and fasting glucose ≥100 mg/dL and <126 mg/dL.

Regulation of constitutive and alternative mRNA splicing across the human transcriptome by PRPF8 is determined by 5' splice site strength.

Background: Sequential assembly of the human spliceosome on RNA transcripts regulates splicing across the human transcriptome. The core spliceosome component PRPF8 is essential for spliceosome assembly through its participation in ribonucleoprotein (RNP) complexes for splice-site recognition, branch-point formation and catalysis. PRPF8 deficiency is linked to human diseases like retinitis pigmentosa or myeloid neoplasia, but its genome-wide effects on constitutive and alternative splicing remain unclear.

Can Antihypertensive Treatment Restore the Risk of Cardiovascular Disease to Ideal Levels?: The Coronary Artery Risk Development in Young Adults (CARDIA) Study and the Multi-Ethnic Study of Atherosclerosis (MESA).

Background: It is unclear whether antihypertensive treatment can restore cardiovascular disease risk to the risk level of persons with ideal blood pressure (BP) levels.

Methods And Results: Data from the Multi-Ethnic Study of Atherosclerosis (MESA) and the Coronary Artery Risk Development in Young Adults (CARDIA) study were analyzed. Outcomes were compared among participants without or with antihypertensive treatment at 3 BP levels: <120/<80 mm Hg, systolic BP 120 to 139 mm Hg or diastolic BP 80 to 89 mm Hg (120 to 129/≤80 mm Hg for participants with diabetes), and systolic BP ≥140 or diastolic BP ≥90 mm Hg (systolic BP ≥130 or diastolic BP ≥80 mm Hg for participants with diabetes).

Clinical determinants of early parasitological response to ACTs in African patients with uncomplicated falciparum malaria: a literature review and meta-analysis of individual patient data.

Background: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses a major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to artemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African countries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs).

Utility of Nontraditional Risk Markers in Individuals Ineligible for Statin Therapy According to the 2013 American College of Cardiology/American Heart Association Cholesterol Guidelines.

Background: In the general population, the majority of cardiovascular events occur in people at the low to moderate end of population risk distribution. The 2013 American College of Cardiology/American Heart Association guideline on the treatment of blood cholesterol recommends consideration of statin therapy for adults with an estimated 10-year atherosclerotic cardiovascular disease (ASCVD) risk ≥7.5% based on traditional risk factors.

Why Wealthier People Think People Are Wealthier, and Why It Matters: From Social Sampling to Attitudes to Redistribution.

The present studies provide evidence that social-sampling processes lead wealthier people to oppose redistribution policies. In samples of American Internet users, wealthier participants reported higher levels of wealth in their social circles (Studies 1a and 1b). This was associated, in turn, with estimates of higher mean wealth in the wider U.

Orbital pseudotumor can be a localized form of granulomatosis with polyangiitis as revealed by gene expression profiling.

Biopsies and ANCA testing for limited forms of granulomatosis with polyangiitis (GPA) are frequently non-diagnostic. We characterized gene expression in GPA and other causes of orbital inflammation. We tested the hypothesis that a sub-set of patients with non-specific orbital inflammation (NSOI, also known as pseudotumor) mimics a limited form of GPA.

Placental Features of Late-Onset Adverse Pregnancy Outcome.

Objective: Currently, no investigations reliably identify placental dysfunction in late pregnancy. To facilitate the development of such investigations we aimed to identify placental features that differ between normal and adverse outcome in late pregnancy in a group of pregnancies with reduced fetal movement.

Methods: Following third trimester presentation with reduced fetal movement (N = 100), placental structure ex vivo was measured.

Putative Effect of Aquifer Recharge on the Abundance and Taxonomic Composition of Endemic Microbial Communities.

Drought events and the overexploitation of freshwater resources have led to the increased need to manage groundwater reserves. Aquifer storage and recovery (ASR), whereby artificial water is injected into aquifers for storage, is one of the proposed methods by which freshwater supplies can be increased. Microbial clogging following injection, however, is a major issue.

Is the association of hypertension with cardiovascular events stronger among the lean and normal weight than among the overweight and obese? The multi-ethnic study of atherosclerosis.

Previous studies that suggest the association of hypertension with cardiovascular disease (CVD) events is stronger in the lean/normal weight than in the obese have either included smokers, diabetics, or cancer patients, or did not account for central obesity. This study examines the interaction of adiposity with hypertension on CVD events using body mass index (BMI)-based definitions of overweight and obesity, as well as waist circumference (WC) to assess adiposity. In the Multi-Ethnic Study of Atherosclerosis, we classified 3657 nonsmoking men and women, free of baseline clinical CVD, diabetes mellitus and cancer, into 7 BMI-WC combinations defined by ethnicity-specific BMI (normal, overweight, class 1 obese, and class 2/3 obese) and ethnicity- and sex-specific WC categories (optimal or nonoptimal).

From Pre-Clinical Studies to Clinical Trials: Generation of Novel Therapies for Pregnancy Complications.

Complications of pregnancy represent a significant disease burden, with both immediate and lasting consequences for mother and baby. Two key pregnancy complications, fetal growth restriction (FGR) and preeclampsia (PE), together affect around 10%-15% of all pregnancies worldwide. Despite this high incidence, there are currently no therapies available to treat these pregnancy disorders.

Coronary Plaque Burden at Coronary CT Angiography in Asymptomatic Men and Women.

Purpose To assess the relationship between total, calcified, and noncalcified coronary plaque burdens throughout the entire coronary vasculature at coronary computed tomographic (CT) angiography in relationship to cardiovascular risk factors in asymptomatic individuals with low-to-moderate risk. Materials and Methods This HIPAA-compliant study had institutional review board approval, and written informed consent was obtained. Two hundred two subjects were recruited to an ongoing prospective study designed to evaluate the effect of HMG-CoA reductase inhibitors on atherosclerosis.

Recursive splicing in long vertebrate genes.

It is generally believed that splicing removes introns as single units from precursor messenger RNA transcripts. However, some long Drosophila melanogaster introns contain a cryptic site, known as a recursive splice site (RS-site), that enables a multi-step process of intron removal termed recursive splicing. The extent to which recursive splicing occurs in other species and its mechanistic basis have not been examined.

Abnormal Myocardial Function Is Related to Myocardial Steatosis and Diffuse Myocardial Fibrosis in HIV-Infected Adults.

Background: Impaired cardiac function persists in the era of effective human immunodeficiency virus (HIV) therapy, although the etiology is unclear. We used magnetic resonance imaging (MRI) to measure intramyocardial lipid levels and fibrosis as possible contributors to HIV-associated myocardial dysfunction.

Methods: A cross-sectional study of 95 HIV-infected and 30 matched-healthy adults, without known cardiovascular disease (CVD) was completed.

Regional differences in the psychological recovery of Christchurch residents following the 2010/2011 earthquakes: a longitudinal study.

We examined changes in psychological distress experienced by residents of Christchurch following two catastrophic earthquakes in late 2010 and early 2011, using data from the New Zealand Attitudes and Values Study (NZAVS), a national probability panel study of New Zealand adults. Analyses focused on the 267 participants (172 women, 95 men) who were living in central Christchurch in 2009 (i.e.