A flow cell simulating a subsurface rock fracture for investigations of groundwater-derived biofilms

Laboratory scale continuous-flow-through chambers (flow cells) facilitate the observation of microbes in a controlled, fully hydrated environment, although these systems often do not simulate the environmental conditions under which microorganisms are found. We developed a flow cell that mimics a subsurface groundwater-saturated rock fracture and isamenable to confocal laser scanning microscopy while allowing for the simple removal of the attached biomass. This flow cell was used to investigate the effect of toluene, a representative contaminant for non-aqueous phase liquids, on groundwater-derived biofilms. Reduced average biofilm biomass and thickness, and diminished diversity of amplifiable 16S rRNA sequences were observed for biofilms that developed in the presence of toluene, compared to the biofilms grown in the absence of toluene. The flow cell also allowed the detection of fluorescent protein-labelled cells

Altered glycosylation of glycodelin in endometrial carcinoma

Glycodelin is a major glycoprotein expressed in reproductive tissues, like secretory and decidualized endometrium. It has several reproduction related functions that are dependent on specific glycosylation, but it has also been found to drive differentiation of endometrial carcinoma cells toward a less malignant phenotype. Here we aimed to elucidate whether the glycosylation and function of glycodelin is altered in endometrial carcinoma as compared with a normal endometrium. We carried out glycan structure analysis of glycodelin expressed in HEC-1B human endometrial carcinoma cells (HEC-1B Gd) by mass spectrometry glycomics strategies. Glycans of HEC-1B Gd were found to comprise a typical mixture of high-mannose, hybrid, and complex-type N-glycans, often containing undecorated LacNAc (Gal beta 1-4GlcNAc) antennae. However, several differences, as compared with previously reported glycan structures of normal human decidualized endometrium-derived glycodelin isoform, glycodelin-A (GdA), were also found. These included a lower level of sialylation and more abundant poly-LacNAc antennae, some of which are fucosylated. This allowed us to select lectins that showed different binding to these classes of glycodelin. Despite the differences in glycosylation between HEC-1B Gd and GdA, both showed similar inhibitory activity on trophoblast cell invasion and peripheral blood mononuclear cell proliferation. For the detection of cancer associated glycodelin, we established a novel in situ proximity-ligation based histochemical staining method using a specific glycodelin antibody and UEAI lectin. We found that the UEAI reactive glycodelin was abundant in endometrial carcinoma, but virtually absent in normal endometrial tissue even when glycodelin was strongly expressed. In conclusion, we established a histochemical staining method for the detection of endometrial carcinoma-associated glycodelin and showed that this specific glycodelin is exclusively expressed in cancer, not in normal endometrium. Similar methods can be used for studies of other glycoproteins. Glycodelin is a major endometrial glycoprotein. The authors analyzed glycan structures of endometrial carcinoma associated glycodelin and established a novel glycodelin-glycoform specific histochemical staining method. With this, they showed that glycodelin is differentially glycosylated in endometrial carcinoma tissue, as compared to normal endometrium, representing a neoantigen with potential clinical applications.Peer reviewe

Decidual glycodelin-A polarizes human monocytes into a decidual macrophage-like phenotype through Siglec-7

Decidual macrophages constitute 20-30% of the total leukocytes in the uterus of pregnant women, regulating the maternal immune tolerance and placenta development. Abnormal number or activities of decidual macrophages (dMs) are associated with fetal loss and pregnancy complications, such as preeclampsia. Monocytes differentiate into dMs in a decidua-specific microenvironment. Despite their important roles in pregnancy, the exact factors that regulate the differentiation into dMs remain unclear. Glycodelin-A (PAEP, hereafter referred to as GdA) is a glycoprotein that is abundantly present in the decidua, and plays an important role in fetomaternal defense and placental development. It modulates the differentiation and activity of several immune cell types residing in the decidua. In this study, we demonstrated that GdA induces the differentiation of human monocytes into dM-like phenotypes in terms of transcriptome, cell surface marker expression, secretome, and regulation of trophoblast and endothelial cell functions. We found that Sialic acid-binding Ig-like lectin 7 (Siglec-7) mediates the binding and biological actions of GdA in a sialic acid-dependent manner. We, therefore, suggest that GdA, induces the polarization of monocytes into dMs to regulate fetomatemal tolerance and placental development.Peer reviewe

Myocardial Fibrosis and Cardiac Decompensation in Aortic Stenosis

OBJECTIVES: Cardiac magnetic resonance (CMR) was used to investigate the extracellular compartment and myocardial fibrosis in patients with aortic stenosis, as well as their association with other measures of left ventricular decompensation and mortality. BACKGROUND: Progressive myocardial fibrosis drives the transition from hypertrophy to heart failure in aortic stenosis. Diffuse fibrosis is associated with extracellular volume expansion that is detectable by T1 mapping, whereas late gadolinium enhancement (LGE) detects replacement fibrosis. METHODS: In a prospective observational cohort study, 203 subjects (166 with aortic stenosis [69 years; 69% male]; 37 healthy volunteers [68 years; 65% male]) underwent comprehensive phenotypic characterization with clinical imaging and biomarker evaluation. On CMR, we quantified the total extracellular volume of the myocardium indexed to body surface area (iECV). The iECV upper limit of normal from the control group (22.5 ml/m(2)) was used to define extracellular compartment expansion. Areas of replacement mid-wall LGE were also identified. All-cause mortality was determined during 2.9 ± 0.8 years of follow up. RESULTS: iECV demonstrated a good correlation with diffuse histological fibrosis on myocardial biopsies (r = 0.87; p < 0.001; n = 11) and was increased in patients with aortic stenosis (23.6 ± 7.2 ml/m(2) vs. 16.1 ± 3.2 ml/m(2) in control subjects; p < 0.001). iECV was used together with LGE to categorize patients with normal myocardium (iECV <22.5 ml/m(2); 51% of patients), extracellular expansion (iECV ≥22.5 ml/m(2); 22%), and replacement fibrosis (presence of mid-wall LGE, 27%). There was evidence of increasing hypertrophy, myocardial injury, diastolic dysfunction, and longitudinal systolic dysfunction consistent with progressive left ventricular decompensation (all p < 0.05) across these groups. Moreover, this categorization was of prognostic value with stepwise increases in unadjusted all-cause mortality (8 deaths/1,000 patient-years vs. 36 deaths/1,000 patient-years vs. 71 deaths/1,000 patient-years, respectively; p = 0.009). CONCLUSIONS: CMR detects ventricular decompensation in aortic stenosis through the identification of myocardial extracellular expansion and replacement fibrosis. This holds major promise in tracking myocardial health in valve disease and for optimizing the timing of valve replacement. (The Role of Myocardial Fibrosis in Patients With Aortic Stenosis; NCT01755936)

Adverse prognosis associated with asymmetric myocardial thickening in aortic stenosis

Aims: Asymmetric wall thickening has been described in patients with aortic stenosis. However, it remains poorly characterized and its prognostic implications are unclear. We hypothesized this pattern of adaptation is associated with advanced remodelling, left ventricular decompenzation, and a poor prognosis. Methods and results: In a prospective observational cohort study, 166 patients with aortic stenosis (age 69, 69% males, mean aortic valve area 1.0 ± 0.4 cm2) and 37 age and sex-matched healthy volunteers underwent phenotypic characterization with comprehensive clinical, imaging, and biomarker evaluation. Asymmetric wall thickening on both echocardiography and cardiovascular magnetic resonance was defined as regional wall thickening ≥ 13 mm and > 1.5-fold the thickness of the opposing myocardial segment. Although no control subject had asymmetric wall thickening, it was observed in 26% (n = 43) of patients with aortic stenosis using magnetic resonance and 17% (n = 29) using echocardiography. Despite similar demographics, co-morbidities, valve narrowing, myocardial hypertrophy, and fibrosis, patients with asymmetric wall thickening had increased cardiac troponin I and brain natriuretic peptide concentrations (both P < 0.001). Over 28 [22, 33] months of follow-up, asymmetric wall thickening was an independent predictor of aortic valve replacement (AVR) or death whether detected by magnetic resonance [hazard ratio (HR) = 2.15; 95% confidence interval (CI) 1.29-3.59; P = 0.003] or echocardiography (HR = 1.79; 95% CI 1.08-3.69; P = 0.021). Conclusion: Asymmetric wall thickening is common in aortic stenosis and is associated with increased myocardial injury, left ventricular decompenzation, and adverse events. Its presence may help identify patients likely to proceed quickly towards AVR. Clinical Trial Registration: https://clinicaltrials.gov/show/NCT01755936: NCT01755936

Imaging myocardial carcinoid with T2-STIR CMR

We used T2-STIR (Short Tau Inversion Recovery) cardiovascular magnetic resonance to demonstrate carcinoid tumor metastases to the heart and liver in a 64-year-old woman with a biopsy-proven ileal carcinoid tumor who was referred because of an abnormal echocardiogram

Radio Astronomy

Contains reports on sixteen research projects.National Science Foundation (Grant AST81-21416)National Science Foundation (Grant AST80-22864)National Aeronautics and Space Administration (Contract S-10665-C)National Aeronautics and Space Administration (Contract NAGW373)National Science Foundation (Grant AST79-19553)National Oceanic and Atmospheric Administration (Grant 04-8-M01-1)National Aeronautics and Space Administration (Grant NAG5-10)National Aeronautics and Space Administration (Contract NAS5-22929)Defense Advanced Research Projects Agency (Contract MDA 903-82-K-0521)Intelsat (Contract Intel-188)Joint Services Electronics Program (Contract DAAG29-80-C-0104)Lockheed Missiles and Space Company (Contract LS90B4860F

Assessing the impact of a primary care electronic medical record system in three Kenyan rural health centers

Objective: Efficient, effective health care requires rapid availability of patient information. We designed, implemented, and assessed the impact of a primary care electronic medical record (EMR) in three rural Kenyan health centers. Method: Local clinicians identified data required for primary care and public health reporting. We designed paper encounter forms to capture these data in adult medicine, pediatric, and antenatal clinics. Encounter form data were hand-entered into a new primary care module in an existing EMR serving onsite clinics serving patients infected with the human immunodeficiency virus (HIV). Before subsequent visits, Summary Reports were printed containing selected patient data with reminders for needed HIV care. We assessed effects on patient flow and provider work with time-motion studies before implementation and two years later, and we surveyed providers' satisfaction with the EMR. Results: Between September 2008 and December 2011, 72 635 primary care patients were registered and 114 480 encounter forms were completed. During 2011, 32 193 unique patients visited primary care clinics, and encounter forms were completed for all visits. Of 1031 (3.2%) who were HIV-infected, 85% received HIV care. Patient clinic time increased from 37 to 81 min/visit after EMR implementation in one health center and 56 to 106 min/visit in the other. However, outpatient visits to both health centers increased by 85%. Three-quarters of increased time was spent waiting. Despite nearly doubling visits, there was no change in clinical officers' work patterns, but the nurses' and the clerks' patient care time decreased after EMR implementation. Providers were generally satisfied with the EMR but desired additional training. Conclusions: We successfully implemented a primary care EMR in three rural Kenyan health centers. Patient waiting time was dramatically lengthened while the nurses' and the clerks' patient care time decreased. Long-term use of EMRs in such settings will require changes in culture and workflow

Non-invasive prenatal assessment of trisomy 21 by multiplexed maternal plasma DNA sequencing: large scale validity study

Objectives To validate the clinical efficacy and practical feasibility of massively parallel maternal plasma DNA sequencing to screen for fetal trisomy 21 among high risk pregnancies clinically indicated for amniocentesis or chorionic villus sampling