Levels of soluble fms-like tyrosine kinase one in first trimester and outcomes of pregnancy: a systematic review

Angiogenic factors are involved in formation of new blood vessels required for placental development and function; and critical for fetal growth and development. Soluble fms-like tyrosine kinase 1(sFlt-1) is an anti-angiogenic protein that inhibits formation of new blood vessels resulting in potential pregnancy complications. The objective of this study was to undertake a systematic review to assess levels of sFlt-1 in early pregnancy and association with adverse pregnancy outcomes. PubMed and Medline databases and reference lists were searched up to July 2010. Inclusion criteria were pregnant women, blood sample taken during first trimester and assessment/reporting of sFlt-1 concentrations and subsequent pregnancy complications. Twelve relevant studies were identified of 71 to 668 women. No pooling of results was undertaken due to variation in sFlt-1 concentrations (range, 166-6,349 pg/ml amongst controls), samples used (serum, plasma), different summary statistics (mean, median, odds ratio) and outcome definitions applied. Levels of sFlt-1 were generally higher among women who developed preeclampsia (11 studies) or gestational hypertension (two studies), but not significantly different to normotensive women in most studies. There was no consistent pattern in association between sFlt-1 concentrations and fetal growth restriction (4 studies); and levels were non-significantly higher for women with postpartum bleeding (1 study) and significantly lower for stillbirths (1 study).This review found no clear evidence of an association between sFlt-1 levels in first trimester and adverse pregnancy outcomes. However, findings were affected by methodological, biological and testing variations between studies; highlighting the need for consistent testing of new biomarkers and reporting of outcome measures

The effect of cross-contamination in the sequential interfacial polymerization on the RO performance of polyamide bilayer membranes

International audienceIn this study, hexafluoroalcohol-containing polyamide layer (HFAPA) was prepared on top of a conventional polyamide under-layer (REFPA) via sequential interfacial polymerization (SIP) to improve RO separation behavior, and the performance of the resulting bilayer membrane was thoroughly optimized by investigating the effect of cross-contamination in the SIP process. When several coupons of the polyamide bilayer membrane were prepared by SIP of MPD(aq), TMC(hx) and hexafluoroalcohol-containing diamine (HFAMDA)(aq) in the manner of subsequent membrane dipping, unreacted MPD monomer (mostly captured in the porous PSF support) carried over from the 1st interfacial reaction dissolved and accumulated in the 2nd aqueous solution as verified by UV spectroscopic analysis. The MPD contaminant then participated in the 2nd interfacial reaction, forming copolyamide with HFAMDA monomer onto the REFPA. Depending on the amount of MPD contaminant accumulated in the 2nd aqueous solution, the composition of the resulting co-polyamide in the top-layer varied, causing a significant variation of RO performance; the flux was gradually decreased with the increase of MPD contaminants while the salt rejection slightly increased (from 1st coupon toward 4th coupon). This result indicated that a trace amount of MPD contaminant may be necessary to maximize RO separation behavior. Through in-depth performance evaluation of polyamide bilayer membranes prepared by adding various known-amount of MPD into 2nd HFAMDA solution, and also by applying a frame process (2nd amine solution was applied only top surface of membrane) to eliminate uncontrollable MPD contamination, we have successfully demonstrated consistent RO performance, and identified an optimum material composition to provide superior separation performance. The bilayer membrane prepared by adding 1.2 mol% of MPD to the total amount of HFAMDA in the 2nd aqueous solution showed 99.8% NaCl rejection with the water flux of 45 LMH under the cross-flow filtration performed with 2000 ppm NaCl solution at 400 psi, 25 °C

Angiopoietin 1 and 2 serum concentrations in first trimester of pregnancy as biomarkers of adverse pregnancy outcomes

Objective: To assess Ang-1, Ang-2 and the Ang-1/Ang-2 ratio levels in the first trimester of pregnancy, their association with adverse pregnancy outcomes; and their predictive accuracy. Study Design: This cohort study measured serum Ang-1 and Ang-2 levels in 4,785 women with singleton pregnancies attending first trimester screening in New South Wales, Australia. Multivariate logistic regression models were used to assess the association and predictive accuracy of serum biomarkers with subsequent adverse pregnancy outcomes (small for gestational age, preterm birth, preeclampsia, miscarriage >10 weeks and stillbirth). Results: Median (interquartile range) levels for Ang-1, Ang-2 and the Ang-1/Ang-2 ratio for the total population were 19.6 ng/ml (13.6-26.4), 15.5 ng/ml (10.3-22.7) and 1.21 (0.83-1.73), respectively. Maternal age, weight, country of birth and socio-economic status significantly affected Ang-1, Ang-2 and the Ang-1/Ang-2 ratio levels. After adjusting for maternal and clinical risk factors, women with low Ang-2 levels (90th centile) had increased risk of developing most adverse pregnancy outcomes. Compared to the Ang-1/Ang-2 ratio alone, maternal and clinical risk factors had better predictive accuracy for most adverse pregnancy outcomes. The exception was miscarriage [Ang-1/Ang-2 ratio area under ROC curve (AUC) =0.70; maternal risk factors AUC =0.58]. Overall, adding the Ang-1/Ang-2 ratio to maternal risk factors did not improve the ability of the models to predict adverse pregnancy outcomes. Conclusions: Our findings suggest that the Ang-1/Ang-2 ratio in first trimester is associated with most adverse pregnancy outcomes, but do not predict outcomes any better than clinical and maternal risk factor information.Australian National Health and Medical Research Council (NHMRC) Project Grant (#632653)

Evaluation of first trimester serum soluble endothelial cell-specific tyrosine kinase receptor in normal and affected pregnancies

Aims: To assess soluble endothelial cell-specific tyrosine kinase receptor (sTie-2) levels in the first trimester of pregnancy and its association with adverse pregnancy outcomes; and examine the predictive accuracy. Study Design: In this nested case-control study, serum sTie-2 levels were measured in 2,616 women with singleton pregnancies attending first trimester screening in New South Wales, Australia. Multivariate logistic regression models were used to assess the association and predictive accuracy of serum sTie-2 with subsequent adverse pregnancy outcomes. Results: Median (interquartile range) sTie-2 for the total population was 19.6 ng/ml (13.6-26.4). Maternal age, weight, and smoking status significantly affected sTie-2 levels. There was no difference in serum sTie-2 between unaffected and women with adverse pregnancy outcomes. After adjusting maternal and clinical risk factors, low sTie-2 (<25th centile) was associated with preeclampsia (Adjusted odds ratio: 1.61; 95%CI: 1.01-2.57), however, the accuracy of sTie-2 in predicting preeclampsia was not different from chance (AUC=0.54; P=0.08) and does not add valuable predictive information to maternal and clinical risk factors. Conclusions: Our findings suggest that low sTie-2 levels are associated with preeclampsia, however, it does not add valuable information to clinical and maternal risk factor information in predicting preeclampsia or any other adverse pregnancy outcomes.NHMR

Distinct Nav1.7-dependent pain sensations require different sets of sensory and sympathetic neurons

Human acute and inflammatory pain requires the expression of voltage-gated sodium channel Nav1.7 but its significance for neuropathic pain is unknown. Here we show that Nav1.7 expression in different sets of mouse sensory and sympathetic neurons underlies distinct types of pain sensation. Ablating Nav1.7 gene (SCN9A) expression in all sensory neurons using Advillin-Cre abolishes mechanical pain, inflammatory pain and reflex withdrawal responses to heat. In contrast, heat-evoked pain is retained when SCN9A is deleted only in Nav1.8-positive nociceptors. Surprisingly, responses to the hotplate test, as well as neuropathic pain, are unaffected when SCN9A is deleted in all sensory neurons. However, deleting SCN9A in both sensory and sympathetic neurons abolishes these pain sensations and recapitulates the pain-free phenotype seen in humans with SCN9A loss-of-function mutations. These observations demonstrate an important role for Nav1.7 in sympathetic neurons in neuropathic pain, and provide possible insights into the mechanisms that underlie gain-of-function Nav1.7-dependent pain conditions

Liquid biopsy for non-invasive monitoring of patients with kidney transplants

The current tools for diagnosing and monitoring native kidney diseases as well as allograft rejection in transplant patients are suboptimal. Creatinine and proteinuria are non-specific and poorly sensitive markers of injury. Tissue biopsies are invasive and carry potential complications. In this article, we overview the different techniques of liquid biopsy and discuss their potential to improve patients’ kidney health. Several diagnostic, predictive, and prognostic biomarkers have been identified with the ability to detect and monitor the activity of native kidney diseases as well as early and chronic allograft rejection, such as donor-derived cell-free DNA, exosomes, messenger RNA/microsomal RNA, proteomics, and so on. While the results are encouraging, additional research is still needed as no biomarker appears to be perfect for a routine application in clinical practice. Despite promising advancements in biomarkers, the most important issue is the lack of standardized pre-analytical criteria. Large validation studies and uniformed standard operating procedures are required to move the findings from bench to bedside. Establishing consortia such as the Liquid Biopsy Consortium for Kidney Diseases can help expedite the research process, allow large studies to establish standardized procedures, and improve the management and outcomes of kidney diseases and of kidney transplant recipients

Intelligent pointing increases the fraction of cloud-free CO2 and CH4 observations from space

For most CO2 and CH4 satellites, only a small percentage (∼10%) of observations yield successful retrievals, with the remaining ∼90% rejected, primarily due to the effects of clouds. Discarding this large fraction of data is an inefficient strategy worth reconsidering due to the costs involved in developing, launching and operating the satellites to make these observations. However, if real-time cloud data are available together with pointing capability, cloud data can guide the instrument pointing in an “intelligent pointing” strategy for cloud avoidance. In this work, multiple intelligent pointing simulations were conducted, demonstrating the significant advantages of this approach for satellites in a highly elliptical orbit (HEO), from which nearly the whole Earth disk can be observed. Multiple factors are shown to contribute to intelligent pointing efficiency such as the size and shape (or aspect ratio) of the field of view (FOV). For the current baseline orbit and Imaging Fourier Transform Spectrometer (IFTS) observing characteristics for the proposed Arctic Observing Mission (AOM), the monthly fraction of cloud-free observations is roughly a factor of 2 (ranging from ∼1.5–2.5) more than obtained with standard pointing (in which cloud information is not used). A similar efficiency is expected in a geostationary orbit (GEO) with an IFTS, however, for a dispersive instrument in HEO or GEO, the gain is more modest. This result is primarily attributed to the ∼1:1 aspect ratio of the IFTS FOV, since it is more efficient for cloud avoidance and scanning irregularly-shaped land masses than the long and narrow slit projection of a typical dispersive spectrometer. These results have implications for the design of future CO2 or CH4 monitoring satellites and constellation architectures, as well as other fields of satellite earth observation in which clouds significantly impact observations

Localizing Chemotherapeutic Drug Release Through the Use of Polymer-Based Surgical Sealants to Treat Stage III Colorectal Cancer

Gemstone Team TUMORCurrent cancer treatments, such as systemic chemotherapy, induce several complications that affect the entire body; localizing chemotherapy to the tumor site has the potential to minimize harmful side effects. Solution blow spinning (SBS) offers the possibility of incorporating chemotherapy drugs into a polymer solution through the use of a compressed airbrush. This would allow for direct deposit of a polymer mat after surgically removing the tumor. Sutures, in combination with polymer sealants, could be used to prevent complications after surgery. This study focuses on stage IIIA colorectal cancer because cancer cells have not spread distantly yet, and treatment typically involves surgery followed by chemotherapy. Three key aims were addressed in this study to assess polymer-drug combinations’ compatibility with SBS, observe drug release patterns, and evaluate the effect of drug incorporation on polymer adhesion to intestinal tissue. Our results suggested that the polymer-drug combination of poly(L-lactide-co-ε-caprolactone) (PLCL) and capecitabine shows promise as an adhesive surgical sealant with a drug release pattern that is complementary to a typical resection healing timeline

Localizing Chemotherapeutic Drug Release to Treat Stage III Colorectal Cancer

These studies focused on the incorporation of chemotherapeutic drugs into biodegradable polymers, specifically poly(lactide-co-caprolactone) (PLCL), as a localized form of cancer treatment. In conjunction with the surgical resection of a tumor, this polymer can be used to deposit drugs directly at the site and minimize the risks posed by systemic chemotherapy. The methodology focused on Stage IIIA colorectal cancer due to its high recurrence rate and the common use of surgery as a form of treatment. In our experiments, data was collected to compare the various physical, chemical, and mechanical properties between PLCL fiber mats loaded with Capecitabine in order to evaluate the most ideal drug release pattern. Results found that the combinations we had tested thus far had shown a delayed release, meaning at least a week passed before initial drug dissociation from the polymer. Current results suggest a possible relationship between molecular weight and the delay period length, which has implications in future research. Different polymers will also be studied to assess the chemical impact on the release patterns we found in our data.The Do Good Institute, The Great Foundation, LaunchUMD donors, Gemstone Honors College, Kofinas La

Multiomics Longitudinal Modeling of Preeclamptic Pregnancies

Preeclampsia is a complex disease of pregnancy whose physiopathology remains unclear and that poses a threat to both mothers and infants. Specific complex changes in women\u27s physiology precede a diagnosis of preeclampsia. Understanding multiple aspects of such a complex changes at different levels of biology, can be enabled by simultaneous application of multiple assays. We developed prediction models for preeclampsia risk by analyzing six omics datasets from a longitudinal cohort of pregnant women. A machine learning-based multiomics model had high accuracy (area under the receiver operating characteristics curve (AUC) of 0.94, 95% confidence intervals (CI):[0.90, 0.99]). A prediction model using only ten urine metabolites provided an accuracy of the whole metabolomic dataset and was validated using an independent cohort of 16 women (AUC= 0.87, 95% CI:[0.76, 0.99]). Integration with clinical variables further improved prediction accuracy of the urine metabolome model (AUC= 0.90, 95% CI:[0.80, 0.99], urine metabolome, validated). We identified several biological pathways to be associated with preeclampsia. The findings derived from models were integrated with immune system cytometry data, confirming known physiological alterations associated with preeclampsia and suggesting novel associations between the immune and proteomic dynamics. While further validation in larger populations is necessary, these encouraging results will serve as a basis for a simple, early diagnostic test for preeclampsia